bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase 1b Adaptive Androgen Deprivation Therapy Trial in Metastatic Castration Sensitive Prostate Cancer
Authors: Zhang Jingsong , Gallaher Jill , Cunningham Jessica J. , Choi Jung W. , Ionescu Filip , Chatwal Monica S. , Jain Rohit , Kim Youngchul , Wang Liang , Brown Joel S. , Anderson Alexander R. , Gatenby Robert A.
Published: October 2022

Background: We hypothesize that cancer survival can be improved through adapting treatment strategies to cancer evolutionary dynamics and conducted a phase 1b study in metastatic castration sensitive prostate cancer (mCSPC). Methods: Men with asymptomatic mCSPC were enrolled and proceeded with a treatment break after achieving > 75% PSA decline with LHRH analog plus an NHA. ADT was restarted at the time of PSA or radiographic progression and held again after achieving >50% PSA decline. This on-off cycling of ADT continued until on treatment imaging progression. Results: At data cut off in August 2022, only 2 of the 16 evaluable patients were off study due to imaging progression at 28 months from first dose of LHRH analog for mCSPC. Two additional patients showed PSA progression at 12.4 and 20.5 months and remain on trial. Since none of the 16 patients developed imaging progression at 12 months, the study succeeded in its primary objective of feasibility. The secondary endpoints of median time to PSA progression and median time to radiographic progression have not been reached at a median follow up of 26 months. Conclusions: It is feasible to use an individual’s PSA response and testosterone levels to guide intermittent ADT in mCSPC.
Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma IDH Wildtype
Authors: Kashani Elham , Vassella Erik
Published: October 2022

Serine/Threonine protein phosphatase 2A (PP2A) is a heterotrimeric (or occasionally, heterodimeric) phosphatase with pleiotropic functions and ubiquitous expression. Despite the fact that they all contribute to protein dephosphorylation, multiple PP2A complexes exist which differ considerably by their subcellular localization and their substrate specificity, suggesting diverse PP2A functions. PP2A complex formation is tightly regulated by means of gene expression regulation by transcription factors, microRNAs, and post-translational modifications. Furthermore, a constant competition between PP2A regulatory subunits is taking place dynamically and depending on the spatiotemporal circumstance; many of the integral subunits can outcompete the rest, subjecting them to proteolysis. PP2A modulation is especially important in the context of brain tumors due to its ability to modulate distinct glioma-promoting signal transduction pathways, such as PI3K/Akt, Wnt, Ras, NF-κb, etc. Furthermore, PP2A is also implicated in DNA repair and survival pathways that are activated upon treatment of glioma cells with chemo-radiation. Depending on the cancer cell type, preclinical studies have shown some promise in utilising PP2A activator or PP2A inhibitors to overcome therapy resistance. This review has a special focus on “glioblastoma, IDH wild-type” (GBM) tumors, for which the therapy options have limited efficacy, and tumor relapse is inevitable.
Oligometastatic Disease: When Stage IV Breast Cancer Could Be “Cured”
Authors: Gion Maria , Saavedra Cristina , Perez-Garcia Jose , Cortes Javier
Published: October 2022

Although metastatic breast cancer remains an incurable disease, there are patients with a limited number of metastatic lesions that, in addition to systemic therapy, can be treated with “radical therapy” and sometimes reach the status of no long-term evidence of disease. Whether or not these patients can be considered cured is still a matter of debate. Unfortunately, the definition of the oligometastatic disease remains unclear, and it can occur with multiple different presentations. The absence of remarkable biomarkers, the difficulty in designing the appropriate clinical trials, and the failure to offer this group of patients radical approaches in advanced-stage clinical trials are just some of the current problems that we face in treating patients with oligometastatic breast cancer. Although most of the data come from retrospective studies and do not use the same definition of “oligometastatic disease,” here we review the main studies exploring the role of surgery or radiotherapy in patients with the oligometastatic disease and the different results. Some, but not all, studies have shown an increase in survival when surgery and/or radiotherapy were performed for oligometastatic disease. However, better clinical trial designs are needed to confirm the role of “aggressive” approaches for patients with breast cancer and oligometastatic disease.
Diagnosis and Management of Porocarcinoma
Authors: Miyamoto Kodai , Yanagi Teruki , Maeda Takuya , Ujiie Hideyuki
Published: October 2022

Eccrine porocarcinoma, also known as porocarcinoma (PC) and malignant eccrine poroma, is very rare and is known to arise from the cutaneous intraepidermal ducts of the sweat glands. Its etiology is not well understood; however, some studies suggest that PC tumors originate from benign eccrine poroma. Recently, several gene alterations have been reported in PC that can reveal mechanisms of the oncogenic process. Since the clinical and histopathological findings of PC are variable, PC is difficult to diagnose precisely, especially when the histology resembles that of cutaneous squamous cell carcinoma or poroma. Immunohistochemical staining with carcinoembryonic antigen and epithelial membrane antigen may help to distinguish PC from other tumors. The standard treatment for local PC is wide local excision. The prognosis of patients with metastatic PC is poor, with mortality rates of approximately 60–70%. The efficacy of radiation and chemotherapy for metastatic PC is limited; however, immunotherapy with pembrolizumab, a programmed cell death protein 1 inhibitor, could be a promising treatment. This review focuses on the history, pathogenesis, pathological features, diagnosis, and treatment of eccrine porocarcinoma.
Geostatistical Modeling and Heterogeneity Analysis of Tumor Molecular Landscape
Authors: Hajihosseini Morteza , Amini Payam , Voicu Dan , Dinu Irina , Pyne Saumyadipta
Published: October 2022

Intratumor heterogeneity (ITH) is associated with therapeutic resistance and poor prognosis in cancer patients, and attributed to genetic, epigenetic, and microenvironmental factors. We developed a new computational platform, GATHER, for geostatistical modeling of single cell RNA-seq data to synthesize high-resolution and continuous gene expression landscapes of a given tumor sample. Such landscapes allow GATHER to map the enriched regions of pathways of interest in the tumor space and identify genes that have spatial differential expressions at locations representing specific phenotypic contexts using measures based on optimal transport. GATHER provides new applications of spatial entropy measures for quantification and objective characterization of ITH. It includes new tools for insightful visualization of spatial transcriptomic phenomena. We illustrate the capabilities of GATHER using real data from breast cancer tumor to study hallmarks of cancer in the phenotypic contexts defined by cancer associated fibroblasts.
LGL Clonal Expansion and Unexplained Cytopenia: Two Clues Don’t Make an Evidence
Authors: Calabretto Giulia , Attardi Enrico , Gurnari Carmelo , Semenzato Gianpietro , Voso Maria Teresa , Zambello Renato
Published: October 2022

Clonal expansions of large granular lymphocytes (LGL) have been reported in a wide spectrum of conditions, with LGL leukemia (LGLL) being the most extreme. However, the boundaries between LGLL and LGL clones are often subtle, and both conditions can be detected in several clinical scenarios, particularly in patients with cytopenias. The intricate overlap of LGL clonal expansion with other disease entities characterized by unexplained cytopenias makes their classification challenging. Indeed, precisely assigning whether cytopenias might be related to inadequate hematopoiesis (i.e., LGL as a marginal finding) rather than immune-mediated mechanisms (i.e., LGLL) is far from being an easy task. As LGL clones acquire different pathogenetic roles and relevance according to their diverse clinical settings, their detection in the landscape of bone marrow failures and myeloid neoplasms has recently raised growing clinical interest. In this regard, the current availability of different diagnostic techniques, including next generation sequencing, shed light on the relationship between LGL clones and cytopenias, paving the way towards a better disease classification for precision medicine treatments. Herein, we discuss the clinical relevance of LGL clones in the diagnostic algorithm to be followed in patients presenting with cytopenias, offering a foundation for rational management approaches.
Bridging the Scientific Gaps to Identify Effective Treatments in Adrenocortical Cancer
Authors: Michael Nicholas , Nilubol Naris
Published: October 2022

Adrenocortical cancer (ACC) typically presents in advanced stages of disease and has a dismal prognosis. One of the foremost reasons for this is the lack of available systemic therapies, with mitotane remaining the backbone of treatment since its discovery in the 1960s, despite underwhelming efficacy. Surgery remains the only potentially curative option, but about half of patients will recur post-operatively, often with metastatic disease. Other local treatment options have been attempted but are only used practically on a case-by-case basis. Over the past few decades there have been significant advances in understanding the molecular background of ACC, but this has not yet translated to better treatment options. Attempts at novel treatment strategies have not provided significant clinical benefit. This paper reviews our current treatment options and molecular understanding of ACC and the reasons why a successful treatment has remained elusive. Additionally, we discuss the knowledge gaps that need to be overcome to bring us closer to successful treatment and ways to bridge them.
Evaluation of the Heat Shock Protein 90 Inhibitor Ganetespib as a Sensitizer to Hyperthermia-Based Cancer Treatments
Authors: Scutigliani Enzo M. , Liang Yongxin , IJff Marloes , Rodermond Hans , Mei Xionge , Korver Miriam P. , Orie Vaneesha S. , Hoebe Ron A. , Picavet Daisy I. , Oei Arlene , Kanaar Roland , Krawczyk Przemek M.
Published: October 2022

Hyperthermia is being used as a radio- and chemotherapy sensitizer for a growing range of tumor subtypes in the clinic. Its potential is limited, however, by the ability of cancer cells to activate a protective mechanism known as the heat stress response (HSR). The HSR is marked by the rapid overexpression of molecular chaperones, and recent advances in drug development make their inhibition an attractive option to improve the efficacy of hyperthermia-based therapies. Our previous in vitro work showed that a single, short co-treatment with a HSR (HSP90) inhibitor ganetespib prolongs and potentiates the effects of hyperthermia on DNA repair, enhances hyperthermic sensitization to radio- and chemotherapeutic agents, and reduces thermotolerance. In the current study, we first validated these results using an extended panel of cell lines and more robust methodology. Next, we examined the effects of hyperthermia and ganetespib on global proteome changes. Finally, we evaluated the potential of ganetespib to boost the efficacy of thermo-chemotherapy and thermo-radiotherapy in a xenograft murine model of cervix cancer. Our results revealed new insights into the effects of HSR inhibition on cellular responses to heat and show that ganetespib could be employed to increase the efficacy of hyperthermia when combined with radiation.
HDACi: The Columbus’ Egg in Improving Cancer Treatment and Reducing Neurotoxicity?
Authors: Squarzoni Angelica , Scuteri Arianna , Cavaletti Guido
Published: October 2022

Histone deacetylases (HDACs) are a group of enzymes that modify gene expression through the lysine acetylation of both histone and non-histone proteins, leading to a broad range of effects on various biological pathways. New insights on this topic broadened the knowledge on their biological activity and even more questions arose from those discoveries. The action of HDACs is versatile in biological pathways and, for this reason, inhibitors of HDACs (HDACis) have been proposed as a way to interfere with HDACs’ involvement in tumorigenesis. In 2006, the first HDACi was approved by FDA for the treatment of cutaneous T-cell lymphoma; however, more selective HDACis were recently approved. In this review, we will consider new information on HDACs’ expression and their regulation for the treatment of central and peripheral nervous system diseases.
The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development
Authors: Tornesello Maria Lina , Cerasuolo Andrea , Starita Noemy , Tornesello Anna Lucia , Bonelli Patrizia , Tuccillo Franca Maria , Buonaguro Luigi , Isaguliants Maria G. , Buonaguro Franco M.
Published: October 2022

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is universally enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein–Barr virus (EBV) LMP1, Kaposi’s sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) Tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate on recent findings on virus–telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer-causing viruses.
Microwave-Assisted Biodiesel Production Using UiO-66 MOF Derived Nanocatalyst: Process Optimization Using Response Surface Methodology
Authors: Gouda Shiva Prasad , H. Anal Jasha Momo , Kumar Puneet , Dhakshinamoorthy Amarajothi , Rashid Umer , Rokhum Samuel Lalthazuala
Published: October 2022

The present work is on the transesterification of soybean oil to biodiesel under microwave irradiation using a biomass and MOF−derived CaO−ZrO2 heterogeneous catalyst. The optimisation of different parameters was processed by adopting a central composite design for a response−surface methodology (RSM). The experimental data were fitted to a quadratic equation employing multiple regressions and investigated by analysis of variance (ANOVA). The catalyst was exhaustively characterised by XRD, TGA, FTIR BET, SEM, TEM, CO2 TPD and XPS. In addition, the synthesized biodiesel was characterized by 1H and 13C NMR, GCMS. The physicochemical properties of the biodiesel were also reported and compared with the ASTM standards. The maximum yield that was obtained after optimization using RSM was 97.22 ± 0.4% with reaction time of 66.2 min, at reaction temperature of 73.2 °C, catalyst loading of 6.5 wt.%, and methanol−to−oil ratio of 9.7 wt.%.
A Systematic Review on Solar Heterogeneous Photocatalytic Water Disinfection: Advances over Time, Operation Trends, and Prospects
Authors: Silerio-Vázquez Felipe de J. , Núñez-Núñez Cynthia M. , Proal-Nájera José B. , Alarcón-Herrera María T.
Published: October 2022

Access to drinking water is a human right recognized by the United Nations. It is estimated that more than 2.1 billion people lack access to drinking water with an adequate microbiological quality, which is associated to 80% of all diseases, as well as with millions of deaths caused by infections, especially in children. Water disinfection technologies need a continuous improvement approach to meet the growing demand caused by population growth and climate change. Heterogeneous photocatalysis with semiconductors, which is an advanced oxidation process, has been proposed as a sustainable technology for water disinfection, as it does not need addition of any chemical substance and it can make use of solar light. Nevertheless, the technology has not been deployed industrially and commercially yet, mainly because of the lack of efficient reactor designs to treat large volumes of water, as most research focus on lab-scale experimentation. Additionally, very few applications are often tested employing actual sunlight. The present work provide a perspective on the operation trends and advances of solar heterogeneous photocatalytic reactors for water disinfection by systematically analyzing pertaining literature that made actual use of sunlight, with only 60 reports found out of the initially 1044 papers detected. These reports were discussed in terms of reactor employed, photocatalyst used, microorganism type, overall disinfection efficiency, and location. General prospects for the progression of the technology are provided as well.
Towards the Standardization of Intestinal In Vitro Advanced Barrier Model for Nanoparticles Uptake and Crossing: The SiO2 Case Study
Authors: Vincentini Olimpia , Prota Valentina , Cecchetti Serena , Bertuccini Lucia , Tinari Antonella , Iosi Francesca , De Angelis Isabella
Published: October 2022

Increasing interest is being addressed to the development of a reliable, reproducible and relevant in vitro model of intestinal barrier, mainly for engineered nanomaterials hazard and risk assessment, in order to meet regulatory and scientific demands. Starting from the consolidated Caco-2 cell model, widely used for determining translocation of drugs and chemicals, the establishment of an advanced intestinal barrier model with different level of complexity is important for overcoming Caco-2 monoculture limitations. For this purpose, a tri-culture model, consisting of two human intestinal epithelial cells (Caco-2 and HT29-MTX) and a human lymphocyte B cell (Raji B), was developed by several research groups to mimic the in vivo intestinal epithelium, furnishing appropriate tools for nanotoxicological studies. However, tri-culture model shows high levels of variability in ENM uptake/translocation studies. With the aim of implementing the standardization and optimization of this tri-culture for ENM translocation studies, the present paper intends to identify and discuss such relevant parameters involved in model establishment as: tri-culture condition set-up, barrier integrity evaluation, mucus characterization, M-cell induction. SiO2 fluorescent nanoparticles were used to compare the different models. Although a low level of SiO2 translocation is reported for all the different culture conditions. a relevant role of mucus and M-cells in NPs uptake/translocation has been highlighted.
The Role of Crosstalk between Adipose Cells and Myocytes in the Pathogenesis of Sarcopenic Obesity in the Elderly
Authors: Zamboni Mauro , Mazzali Gloria , Brunelli Anna , Saatchi Tanaz , Urbani Silvia , Giani Anna , Rossi Andrea P. , Zoico Elena , Fantin Francesco
Published: October 2022

As a result of aging, body composition changes, with a decline in muscle mass and an increase in adipose tissue (AT), which reallocates from subcutaneous to visceral depots and stores ectopically in the liver, heart and muscles. Furthermore, with aging, muscle and AT, both of which have recognized endocrine activity, become dysfunctional and contribute, in the case of positive energy balance, to the development of sarcopenic obesity (SO). SO is defined as the co-existence of excess adiposity and low muscle mass and function, and its prevalence increases with age. SO is strongly associated with greater morbidity and mortality. The pathogenesis of SO is complex and multifactorial. This review focuses mainly on the role of crosstalk between age-related dysfunctional adipose and muscle cells as one of the mechanisms leading to SO. A better understanding of this mechanisms may be useful for development of prevention strategies and treatments aimed at reducing the occurrence of SO.
Diabetic Macular Edema: Current Understanding, Molecular Mechanisms and Therapeutic Implications
Authors: Zhang Jingfa , Zhang Jingxiang , Zhang Chaoyang , Zhang Jingting , Gu Limin , Luo Dawei , Qiu Qinghua
Published: October 2022

Diabetic retinopathy (DR), with increasing incidence, is the major cause of vision loss and blindness worldwide in working-age adults. Diabetic macular edema (DME) remains the main cause of vision impairment in diabetic patients, with its pathogenesis still not completely elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of DR and DME. Currently, intravitreal injection of anti-VEGF agents remains as the first-line therapy in DME treatment due to the superior anatomic and functional outcomes. However, some patients do not respond satisfactorily to anti-VEGF injections. More than 30% patients still exist with persistent DME even after regular intravitreal injection for at least 4 injections within 24 weeks, suggesting other pathogenic factors, beyond VEGF, might contribute to the pathogenesis of DME. Recent advances showed nearly all the retinal cells are involved in DR and DME, including breakdown of blood-retinal barrier (BRB), drainage dysfunction of Müller glia and retinal pigment epithelium (RPE), involvement of inflammation, oxidative stress, and neurodegeneration, all complicating the pathogenesis of DME. The profound understanding of the changes in proteomics and metabolomics helps improve the elucidation of the pathogenesis of DR and DME and leads to the identification of novel targets, biomarkers and potential therapeutic strategies for DME treatment. The present review aimed to summarize the current understanding of DME, the involved molecular mechanisms, and the changes in proteomics and metabolomics, thus to propose the potential therapeutic recommendations for personalized treatment of DME.
Cross-Talk and Subset Control of Microglia and Associated Myeloid Cells in Neurological Disorders
Authors: Mills Jatia , Ladner Liliana , Soliman Eman , Leonard John , Morton Paul D. , Theus Michelle H.
Published: October 2022

Neurological disorders are highly prevalent and often lead to chronic debilitating disease. Neuroinflammation is a major driver across the spectrum of disorders, and microglia are key mediators of this response, gaining wide acceptance as a druggable cell target. Moreover, clinical providers have limited ability to objectively quantify patient-specific changes in microglia status, which can be a predictor of illness and recovery. This necessitates the development of diagnostic biomarkers and imaging techniques to monitor microglia-mediated neuroinflammation in coordination with neurological outcomes. New insights into the polarization status of microglia have shed light on the regulation of disease progression and helped identify a modifiable target for therapeutics. Thus, the detection and monitoring of microglia activation through the inclusion of diagnostic biomarkers and imaging techniques will provide clinical tools to aid our understanding of the neurologic sequelae and improve long-term clinical care for patients. Recent achievements demonstrated by pre-clinical studies, using novel depletion and cell-targeted approaches as well as single-cell RNAseq, underscore the mechanistic players that coordinate microglial activation status and offer a future avenue for therapeutic intervention.
Osteoprotegerin (OPG) Upregulation Activates Breast Stromal Fibroblasts and Enhances Their Pro-Carcinogenic Effects through the STAT3/IL-6 Signaling
Authors: Al-Nasrallah Huda K. , Al-Ansari Mysoon M. , Aboussekhra Abdelilah
Published: October 2022

Breast carcinomas are composed of cancer cells surrounded by various types of non-cancer cells such as fibroblasts. While active cancer-associated fibroblasts (CAFs) support tumor initiation and progression, quiescent breast stromal fibroblasts (BSFs) inhibit these effects through various cytokines such as osteoprotegerin (OPG). We showed here that OPG is upregulated in CAFs as compared to their adjacent normal tumor counterpart fibroblasts. Interestingly, breast cancer cells can upregulate OPG in BSFs in an IL-6-dependent manner through the IL-6/STAT3 pathway. When upregulated by ectopic expression, OPG activated BSFs through the NF-κB/STAT3/AUF1 signaling pathway and promoted their paracrine pro-carcinogenic effects in an IL-6-dependent manner. In addition, this increase in the OPG level enhanced the potential of BSFs to promote the growth of humanized orthotopic tumors in mice. However, specific OPG knock-down suppressed active CAFs and their paracrine pro-carcinogenic effects. Similar effects were observed when CAF cells were exposed to the pure recombinant OPG (rOPG) protein. Together, these findings show the importance of OPG in the activation of stromal fibroblasts and the possible use of rOPG or inhibitors of the endogenous protein to target CAFs as precision cancer therapeutics.
Osteoporosis and Alveolar Bone Health in Periodontitis Niche: A Predisposing Factors-Centered Review
Authors: Zhu Li , Zhou Chenchen , Chen Shuo , Huang Danyuan , Jiang Yukun , Lan Yuanchen , Zou Shujuan , Li Yuyu
Published: October 2022

Periodontitis is a periodontal inflammatory condition that results from disrupted periodontal host–microbe homeostasis, manifested by the destruction of tooth-supporting structures, especially inflammatory alveolar bone loss. Osteoporosis is characterized by systemic deterioration of bone mass and microarchitecture. The roles of many systemic factors have been identified in the pathogenesis of osteoporosis, including endocrine change, metabolic disorders, health-impaired behaviors and mental stress. The prevalence rate of osteoporotic fracture is in sustained elevation in the past decades. Recent studies suggest that individuals with concomitant osteoporosis are more vulnerable to periodontal impairment. Current reviews of worse periodontal status in the context of osteoporosis are limited, mainly centering on the impacts of menopausal and diabetic osteoporosis on periodontitis. Herein, this review article makes an effort to provide a comprehensive view of the relationship between osteoporosis and periodontitis, with a focus on clarifying how those risk factors in osteoporotic populations modify the alveolar bone homeostasis in the periodontitis niche.
The Primary Cilium and Neuronal Migration
Authors: Stoufflet Julie , Caillé Isabelle
Published: October 2022

The primary cilium (PC) is a microtubule-based tiny sensory organelle emanating from the centrosome and protruding from the surface of most eukaryotic cells, including neurons. The extremely severe phenotypes of ciliopathies have suggested their paramount importance for multiple developmental events, including brain formation. Neuronal migration is an essential step of neural development, with all neurons traveling from their site of birth to their site of integration. Neurons perform a unique type of cellular migration called cyclic saltatory migration, where their soma periodically jumps along with the stereotyped movement of their centrosome. We will review here how the role of the PC on cell motility was first described in non-neuronal cells as a guide pointing to the direction of migration. We will see then how these findings are extended to neuronal migration. In neurons, the PC appears to regulate the rhythm of cyclic saltatory neuronal migration in multiple systems. Finally, we will review recent findings starting to elucidate how extracellular cues sensed by the PC could be intracellularly transduced to regulate the machinery of neuronal migration. The PC of migrating neurons was unexpectedly discovered to display a rhythmic extracellular emergence during each cycle of migration, with this transient exposure to the external environment associated with periodic transduction of cyclic adenosine monophosphate (cAMP) signaling at the centrosome. The PC in migrating neurons thus uniquely appears as a beat maker, regulating the tempo of cyclic saltatory migration.
Modification of Hinge/Transmembrane and Signal Transduction Domains Improves the Expression and Signaling Threshold of GXMR-CAR Specific to Cryptococcus spp.
Authors: dos Santos Matheus Henrique , Machado Michele Procópio , Kumaresan Pappanaicken R. , da Silva Thiago Aparecido
Published: October 2022

Chimeric antigen receptors (CARs) redirect T cells to recognize a specific target. CAR components play a pivotal role in antigen specificity, structure stability, expression on cell surface, and induction of cellular activation, which together determine the success of CAR T-cell therapy. CAR products targeting B-cell lymphoma encouraged the development of new CAR applications beyond cancer. For example, our group developed a CAR to specifically target glucuronoxylomannan (GXM) in the capsule of Cryptococcus species, called GXMR-CAR or GXMR-IgG4-28ζ. Cryptococcus are fungi that cause the life-threatening disease cryptococcosis, and GXMR-IgG4-28ζ redirected T cells to target yeast and titan cell forms of Cryptococcus spp. Here, we replaced the IgG4-hinge and CD28-transmembrane domains from GXMR-CAR with a CD8α molecule as the hinge/transmembrane and used CD28 or 4-1BB molecules as co-stimulatory domains, creating GXMR-8-28ζ and GXMR-8-BBζ, respectively. Jurkat cells expressing GXMR-CAR containing CD8α as the hinge/transmembrane improved the CAR expression and induced a tonic signaling. GXMR-8-28ζ and GXMR-8-BBζ induced high levels of IL-2 and up-regulation of CD69 expression in the presence of reference strains of C. neoformans and C. gattii. Moreover, GXMR-8-28ζ and GXMR-8-BBζ showed increased strength in response to incubation with clinical isolates of Cryptococcuss spp., and 4-1BB co-stimulatory domain triggered a more pronounced cellular activation. Dasatinib, a tyrosine kinase inhibitor, attenuated the GXMR-CAR signaling cascade’s engagement in the presence or absence of its ligand. This study optimized novel second-generation GXMR-CARs containing the CD8-hinge/transmembrane domain that improved CAR expression, antigen recognition, and signal strength in T-cell activation.
Characterization of Thermal Barrier Coatings Using an Active Thermography Approach
Authors: Curà Francesca , Sesana Raffaella , Corsaro Luca , Mantoan Riccardo
Published: October 2022

The aim of this paper is to define and set up an experimental procedure, based on active thermography, for the characterization of coatings for industrial applications. This procedure is intended to be a fast and reliable method, alternative to the consolidated one described in International Standards. In more detail, a classical active thermographic set up, and not a dedicated apparatus, was used for that aim, and data processing techniques referred to the analytical approach described in Standards. The active thermography procedure provided the measurement of the surface temperature of specimens undergoing a thermal excitation, applied by means of a laser pulse (Pulsed Technique). Temperature data processing, according to and adapting the Standard procedures, allowed to obtain thermal conductivity and diffusivity information. In particular, two coating processes (Atmospheric and Suspension Plasma Spray) applied to the same base material, Inconel 601, and the same coating material were investigated. These results were compared in terms of thermal properties variation with respect to base and coated materials, and in terms of different coating processes (APS and SPS). Obtained results were also compared to those available in literature.
An Approach to the Simultaneous Determination of a Panel of Five Biomarkers for the Early Detection of Brain Cancer Using the Stochastic Method
Authors: Cioates Negut Catalina , Stefan-van Staden Raluca-Ioana , Sfirloaga Paula
Published: October 2022

The simultaneous determination of heregulin-α and HER 1–4 plays an important role in brain cancer diagnosis and treatment. To date, only enzyme-linked immunosorbent assay (ELISA) or a semiquantitative colorimetric method have been used for the assay of these biomarkers; these methods are quite expensive and can only determine one biomarker in a run. Four 3D stochastic microsensors based on multi-walled carbon nanotubes enriched with gold nanoparticles and modified with inulin were designed for the simultaneous determination of heregulin-α and HER 1–4 in tumor brain tissue and whole blood samples. For the simultaneous measurement of HRG-α and HER 1–4, all sensors demonstrated low limits of determination (as fg mL−1 magnitude order), high sensitivities, and wide concentration ranges. From biological samples, high recovery values of more than 96% of analytes were obtained. The proposed sensor can detect HER 1–4 and heregulin-α in whole blood and tumor tissue samples at the same time.
Studies on the Interaction of Rose Bengal with the Human Serum Albumin Protein under Spectroscopic and Docking Simulations Aspects in the Characterization of Binding Sites
Authors: Yoguim Maurício I. , Grandini Giulia S. , Bertozo Luiza de C. , Caracelli Ignez , Ximenes Valdecir F. , de Souza Aguinaldo R.
Published: October 2022

Rose Bengal (RB) is a xanthene dye used as a sensitizer to convert triplet (3O2) to singlet oxygen (1O2). This photophysical property makes it one of the most used dyes in photodynamic therapy. Thus, understanding its interaction with biomacromolecules can provide helpful information about its mode of action and application. The protein chosen for this study was human serum albumin (HSA), which has nine binding sites for fatty acids (FA), and at least three sites for interactions of drugs (DS). The complexation of HSA with RB caused a maximum bathochromic shift in its absorption. From this displacement and the application of the Benesi–Hildebrand model, the ligand–protein association constant (3.90 ± 0.08 × 105 M−1) was obtained. Applying the Job’s Plot method resulted in a 6:1 (ligand-protein) stoichiometry. The determination of preferred binding sites was performed by measuring the association constant in the presence of drugs for which their binding sites in HSA are already well established, such as warfarin (DS1), ibuprofen (DS2 and FA6), digitoxin (DS3), diazepam (DS2), and diflunisal (DS2 and FA6). From these studies, it was found that RB is able to bind at DS1, DS3, and FA6 sites but not at DS2. Subsequently, molecular docking studies using the 2BX8 and 2BXE crystallographic structures were performed and corroborated the experimental results. The lowest energy poses were −52.13, −58.79, and −67.55 kcal mol−1 at DS1, DS3, and FA6, respectively. Conversely, DS2 was the lower affinity binding site. In conclusion, HSA has a high affinity for RB, being able to bind up to six dye molecules.
A Sensitive Co-MOF/CNTs/SiO2 Composite Based Electrode for Determination of Gallic Acid
Authors: Zhu Luyi , Zhou Qinan , Shao Wenqing , Wei Zhenbo , Wang Jun
Published: October 2022

A novel Co-based organic frameworks/carbon nanotubes/silicon dioxide (Co-MOF/CNTs/SiO2)-modified Au electrode was fabricated and taken as a platform for gallic acid (GA) detection. The composite combined the advantages of Co-MOF, CNTs and SiO2, and higher electrochemical response of Co-MOF/CNTs/SiO2-modified electrode indicated that the composite material exhibited satisfied the catalytic activity towards GA. Moreover, the electrochemical oxidation process of GA was deeply investigated on the surface of electrode based on computational investigations. Hirshfeld charges and condensed Fukui functions of each atom in GA were calculated. Besides, the catalysis of Co-MOF to GA was further investigated based on density functional theory. The quantitative determination of GA was carried out and showed a linear range between 0.05–200 μM, with low limit of detection. The sensitivity value of the self-assembled electrochemical sensor was calculated to be 593.33 μA cm−2 mM−1, and the selectivity, reproducibility and stability of the gallic acid sensor were also confirmed in the study.
Children with Low Handgrip Strength: A Narrative Review of Possible Exercise Strategies to Improve Its Development
Authors: Abe Takashi , Thiebaud Robert S. , Ozaki Hayao , Yamasaki Sakiya , Loenneke Jeremy P.
Published: October 2022

Background: Handgrip strength (HGS) is a predictor of health in both children and adults. Evidence suggests that without a possible strategy, children with low HGS may become adults with low HGS. However, little is known about what strategies are effective for children with low HGS to achieve a higher baseline level in adulthood. This narrative review aimed to investigate whether physical exercise interventions could improve HGS in children. Methods: The relevant databases/search engine was searched using keywords related to the main topics discussed throughout this review. Results: Our findings suggest that it may not be possible to improve HGS over that observed from normal development with physical education or traditional resistance-training programs. However, if the training program includes exercises that directly stimulate the forearm/hand muscle groups to grip, it may be possible to obtain changes in HGS that exceed the changes due to normal developmental growth. Conclusion: Although there are associations between HGS and markers of health, no research could be identified that examined whether increasing HGS would lead to an improvement in health. If an increase in HGS really does represent an improvement in long-term health, then gripping exercise may need to be included into physical activity programs during the growth/development phase.
Radiographic Features of COVID-19 in Children—A Systematic Review
Authors: Bergin Niamh , Moore Niamh , Doyle Shauna , England Andrew , McEntee Mark F.
Published: October 2022

INTRODUCTION: The SARS-CoV-19 (COVID-19) pandemic has become a global problem but has affected the paediatric population less so than in adults. The clinical picture in paediatrics can be different to adults but nonetheless both groups have been subject to frequent imaging. The overall aim of this study was to comprehensively summarise the findings of the available literature describing the chest radiograph (CXR) findings of paediatric patients with confirmed COVID-19. The COVID-19 landscape is rapidly changing, new information is being constantly brought to light, it is therefore important to appraise clinicians and the wider scientific community on the radiographic features of COVID-19 in children. METHODS: Four databases, which included, PubMed; Medline; CINAHL; ScienceDirect were searched from the 30 November 2020 to the 5 March 2021. The review was conducted using the “Preferred Reporting Items for Systematic Reviews and Meta-Analysis, PRISMA” guidelines. Studies were included for (1) publications with full text available, (2) patients with confirmed COVID-19 diagnoses, (3) CXR imaging features of COVID-19 were reported, (4) the age of patients was 0–18 years, (5) studies were limited to human subjects and (6) a language restriction of English was placed on the search. Quality assessment of included articles used the National of Health Quality Assessment Tool for Case Series Studies. RESULTS: Eight studies met our criteria for inclusion in the review. All eight studies documented the number of CXRs obtained, along with the number of abnormal CXRs. Seven out of the eight studies noted greater than 50% of the CXRs taken were abnormal. Opacification was the number one feature that was recorded in all eight studies, followed by pleural effusion which was seen in six studies. Consolidation and peri-bronchial thickening features were both evident in four studies. Opacification was sub-divided into common types of opacities i.e., consolidation, ground glass opacities, interstitial, alveolar and hazy. Consolidation was reported in half of the studies followed by ground glass opacities and interstitial opacities which was seen in three out of the eight studies. CONCLUSION: This systematic review provides insight into the common COVID-19 features that are seen on CXRs in paediatric patients. Opacification was the most common feature reported, with consolidation, ground glass and interstitial opacities the top three opacifications seen. Peri-bronchial thickening is reported. in the paediatric population but this differs from the adult population and was not reported as a common radiographic finding typically seen in adults. ADVANCES IN KNOWLEDGE: This systematic review highlights the CXR appearances of paediatric patients with confirmed SARS-CoV-19, to gain insight into the disease pathophysiology and provide a comprehensive summary of the features for clinicians aiding optimal management.
First Aid Training for Children in Kindergarten: A Pilot Randomized Control Study
Authors: Tse Eleana , Plakitsi Katerina , Voulgaris Spyridon , Alexiou George A.
Published: October 2022

First aid is a fundamental skill for every human of every age, so training in first aid is necessary at a variety of levels. First aid training in schools is essential, but to date, only short reports have been published on the effectiveness of first aid training in kindergarten. We conducted a pilot randomized controlled study on the impact of first aid training on children in kindergarten. We randomly selected 24 children aged 4–5 years from one kindergarten, who were allocated to either a training group (14 children) or a control group (10 children). The training program consisted of three lessons. An eleven-question questionnaire was administered to the children in the training group one day before, one day after, and two and six months after the training, and once to the those in the control group. Before the training, no significant difference was detected in the score on the questionnaire between the two groups. After the lessons, the children in the training group scored significantly higher on the questionnaire than before the lessons, and than the children in the control group. At two and six months after the training, the scores of the children in the training group had decreased but remained higher than before the training and higher that those of the control group. These preliminary results indicate that kindergarten children may benefit from first aid training, but further studies are needed to verify these observations and to explore ways of maintaining the knowledge acquired in training.
Built-Up Closed-Rib Steel Orthotropic Bridge Decks
Authors: Natsheh Sufian H. , Menzemer Craig C.
Published: October 2022

A new built-up closed-rib section is proposed that may improve the installation, performance, and durability of orthotropic steel bridge decks. The rib is composed of two partial or whole standard hot-rolled steel sections which are connected by a steel plate. The concept is used to design a built-up closed-rib replacement for the Benjamin Franklin Bridge deck. In addition, section performance was compared with the actual bulb section as well as a typical trapezoidal section through finite element simulations. The analyses indicate that the built-up section has smaller stress concentration values as compared with the other sections, and hence, improved fatigue resistance is expected. Finally, it is concluded that the built-up rib has potential to be considered in future orthotropic steel deck designs.
Effect of the Addition of Shellac Self-Healing and Discoloration Microcapsules on the Performance of Coatings Applied on Ebiara Solid Board
Authors: Qin Yanzhao , Yan Xiaoxing
Published: October 2022

Self-made shellac microcapsules and discoloration microcapsules in different proportions were added to water-based coatings and the influence of different proportions of self-healing discoloration microcapsules on the coating performance for Ebiara solid boards was discussed. Through a three-factor, two-level orthogonal experiment, the effects of the content of the addition of discoloration microcapsules, shellac microcapsules, and microcapsules on the performance of the coating were explored; the most influential factor of microcapsules was the shellac microcapsule content. Through the coating repair experiment, after 5 days of repair, the coating without adding shellac microcapsules does not display the repair effect. When the shellac microcapsules and discoloration microcapsules were added simultaneously, the width of the coating decreased by 3–6 μm after 5 days of repair, displaying a good repair effect. The shellac microcapsules have a great influence on the surface roughness of coatings. After adding the shellac and discoloration microcapsules, the hardness of the coating was not significantly affected. It was found that there was no chemical reaction between the coating and microcapsules. The best comprehensive performance was obtained by adding 15.0% shellac microcapsules in primer and 20.0% discoloration microcapsules in topcoat. The results provided a reference for multifunctional wood coatings.
A Response to the COVID-19 Pandemic: Experience of the University of Botswana
Authors: Bolaane Benjamin , Moalosi Richie , Rapitsenyane Yaone , Kgwadi Monageng , Kommula Venkata , Gandure Jerekias
Published: October 2022

The outbreak of COVID-19 presented many challenges to the global community. The scientific community developed vaccines to mitigate the virus spread and morbidity. Higher Education institutions shifted their research and development activities toward developing COVID-19 interventions. The University of Botswana set up a multi-disciplinary design team that responded to society’s COVID-19 needs. An agile methodology and co-creation process to design medical assistive devices was adopted for the study. These methods are human-centred, participatory, and have the added advantage of developing impactful, value-added, and acceptable products. This paper reports on the experiences of developing assistive breathing devices in response to the COVID-19 crisis. Experience gained from the study has enabled universities to continue to build local capacity in research and development to respond effectively and efficiently to future pandemics and any pressing societal challenge.
A Promising Crystalline KCl: Electrolyte Material for Studying the Electrochemical Properties of Cerium on Liquid Indium Electrodes
Authors: Xu Minghui , Zhao Yan , Ji Yuanpeng , Dong Yunfa , Leng Huaqian , Li Xiaowei , He Weidong , Qiao Liang
Published: October 2022

Potassium chloride crystals are good conductors in the UV to mid-infrared broadband and can be widely used as materials for high-power CO2 lasers. However, the most important use of potassium chloride crystals has been overlooked; their stable chemistry and wide electrochemical window allow them to form molten eutectic salts with other chlorides for the dry reprocessing of spent fuel. The aim of this work is to investigate the electrochemical properties of the actinide substitute cerium metal on liquid indium media in order to provide basic data for further realization of lanthanides (Ln)/actinides (An) separation. In this paper, we investigated the electrochemical behavior of 3LiCl-2KCl-CeCl3 melt at liquid metal media indium (In) electrode using various transient electrochemical analysis methods, such as cyclic voltammetry, square wave voltammetry and open circuit potential technique. The quasi-equilibrium potentials of Ce3+ at different temperatures on the liquid metal In electrode were determined. On the redox process, the reaction kinetics of the oxidation–reduction process in the 3LiCl-2KCl-CeCl3 system is studied. It was determined that the reduction of Ce3+ at the liquid metal In electrode is an irreversible single-step process with three electron transfers. The relationship between the diffusion coefficient and the reduction process of Ce3+ ions on liquid metal indium electrodes at different temperatures was determined. The expression for the diffusion coefficient and temperature of Ce3+ at the liquid metal indium electrode is: lnD = 1.43 − 7974.69/T.