bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Different Output Powers of Blue Diode Laser along with Curcumin and Riboflavin against Streptococcus mutans around Orthodontic Brackets: An In Vitro Study
Authors: Pordel Edris , Ghasemi Trife , Afrasiabi Shima , Benedicenti Stefano , Signore Antonio , Chiniforush Nasim
Published: August 2023

Objectives: The aim of the present study was to determine the effects of antimicrobial photodynamic therapy (aPDT) using the blue diode laser (BDL) with different output powers and the photosensitizers riboflavin and curcumin on reducing the number of Streptococcus mutans around orthodontic brackets. Materials and methods: A total of 36 orthodontic brackets were contaminated with S. mutans and randomly assigned to 12 groups as follows: control, riboflavin alone, riboflavin + BDL with an output power of 200, 300, 400, or 500 mW, and curcumin alone, curcumin + BDL with an output power of 200, 300, 400, or 500 mW, and 0.2% chlorhexidine (CHX-positive control). Orthodontic brackets were irradiated with a BDL (wavelength 445 nm) at a power density of 0.4–1.0 W/cm2 for 30 s. All orthodontic brackets were examined under a stereomicroscope at 10× magnification. Mean colony-forming units (CFUs)/mL were measured before and after treatment. A one-way analysis of variance with Tukey’s post hoc test was performed to compare CFU/mL between groups. Results: CHX and curcumin plus BDL with an output power of 500 mW had the highest reduction in S. mutans colony numbers (p < 0.001). The curcumin groups were more effective than the riboflavin groups. Riboflavin alone and riboflavin + BDL with an output power of 200 mW showed no significant difference from the control group (p = 0.99 and 0.74, respectively). Conclusion: Our results suggest that aPDT using curcumin as a photosensitizer plus BDL with an output power of 500 mW and a power density of 1.0 W/cm2 at a wavelength of 445 nm can effectively reduce colonies of S. mutans around stainless steel brackets.
Machine Learning-Based Virtual Screening and Molecular Simulation Approaches Identified Novel Potential Inhibitors for Cancer Therapy
Authors: Shahab Muhammad , Zheng Guojun , Khan Abbas , Wei Dongqing , Novikov Alexander S.
Published: August 2023

Cyclin-dependent kinase 2 (CDK2) is a promising target for cancer treatment, developing new effective CDK2 inhibitors is of great significance in anticancer therapy. The involvement of CDK2 in tumorigenesis has been debated, but recent evidence suggests that specifically inhibiting CDK2 could be beneficial in treating certain tumors. This approach remains attractive in the development of anticancer drugs. Several small-molecule inhibitors targeting CDK2 have reached clinical trials, but a selective inhibitor for CDK2 is yet to be discovered. In this study, we conducted machine learning-based drug designing to search for a drug candidate for CDK2. Machine learning models, including k-NN, SVM, RF, and GNB, were created to detect active and inactive inhibitors for a CDK2 drug target. The models were assessed using 10-fold cross-validation to ensure their accuracy and reliability. These methods are highly suitable for classifying compounds as either active or inactive through the virtual screening of extensive compound libraries. Subsequently, machine learning techniques were employed to analyze the test dataset obtained from the zinc database. A total of 25 compounds with 98% accuracy were predicted as active against CDK2. These compounds were docked into CDK2’s active site. Finally, three compounds were selected based on good docking score, and, along with a reference compound, underwent MD simulation. The Gaussian naïve Bayes model yielded superior results compared to other models. The top three hits exhibited enhanced stability and compactness compared to the reference compound. In conclusion, our study provides valuable insights for identifying and refining lead compounds as CDK2 inhibitors.
A Smartphone-Based sEMG Signal Analysis System for Human Action Recognition
Authors: Yu Shixin , Zhan Hang , Lian Xingwang , Low Sze Shin , Xu Yifei , Li Jiangyong , Zhang Yan , Sun Xiaojun , Liu Jingjing
Published: August 2023

In lower-limb rehabilitation, human action recognition (HAR) technology can be introduced to analyze the surface electromyography (sEMG) signal generated by movements, which can provide an objective and accurate evaluation of the patient’s action. To balance the long cycle required for rehabilitation and the inconvenient factors brought by wearing sEMG devices, a portable sEMG signal acquisition device was developed that can be used under daily scenarios. Additionally, a mobile application was developed to meet the demand for real-time monitoring and analysis of sEMG signals. This application can monitor data in real time and has functions such as plotting, filtering, storage, and action capture and recognition. To build the dataset required for the recognition model, six lower-limb motions were developed for rehabilitation (kick, toe off, heel off, toe off and heel up, step back and kick, and full gait). The sEMG segment and action label were combined for training a convolutional neural network (CNN) to achieve high-precision recognition performance for human lower-limb actions (with a maximum accuracy of 97.96% and recognition accuracy for all actions reaching over 97%). The results show that the smartphone-based sEMG analysis system proposed in this paper can provide reliable information for the clinical evaluation of lower-limb rehabilitation.
From Enzymatic Dopamine Biosensors to OECT Biosensors of Dopamine
Authors: Ravariu Cristian
Published: August 2023

Neurotransmitters are an important category of substances used inside the nervous system, whose detection with biosensors has been seriously addressed in the last decades. Dopamine, a neurotransmitter from the catecholamine family, was recently discovered to have implications for cardiac arrest or muscle contractions. In addition to having many other neuro-psychiatric implications, dopamine can be detected in blood, urine, and sweat. This review highlights the importance of biosensors as influential tools for dopamine recognition. The first part of this article is related to an introduction to biosensors for neurotransmitters, with a focus on dopamine. The regular methods in their detection are expensive and require high expertise personnel. A major direction of evolution of these biosensors has expanded with the integration of active biological materials suitable for molecular recognition near electronic devices. Secondly, for dopamine in particular, the miniaturized biosensors offer excellent sensitivity and specificity and offer cheaper detection than conventional spectrometry, while their linear detection ranges from the last years fall exactly on the clinical intervals. Thirdly, the applications of novel nanomaterials and biomaterials to these biosensors are discussed. Older generations, metabolism-based or enzymatic biosensors, could not detect concentrations below the micro-molar range. But new generations of biosensors combine aptamer receptors and organic electrochemical transistors, OECTs, as transducers. They have pushed the detection limit to the pico-molar and even femto-molar ranges, which fully correspond to the usual ranges of clinical detection of human dopamine in body humors that cover 0.1 ÷ 10 nM. In addition, if ten years ago the use of natural dopamine receptors on cell membranes seemed impossible for biosensors, the actual technology allows co-integrate transistors and vesicles with natural receptors of dopamine, like G protein-coupled receptors. The technology is still complicated, but the uni-molecular detection selectivity is promising.
SAM-Support-Based Electrochemical Sensor for Aβ Biomarker Detection of Alzheimer’s Disease
Authors: Le Phan Gia , Le Hien T. Ngoc , Kim Hee-Eun , Cho Sungbo
Published: August 2023

Alzheimer’s disease has taken the spotlight as a neurodegenerative disease which has caused crucial issues to both society and the economy. Specifically, aging populations in developed countries face an increasingly serious problem due to the increasing budget for patient care and an inadequate labor force, and therefore a solution is urgently needed. Recently, diverse techniques for the detection of Alzheimer’s biomarkers have been researched and developed to support early diagnosis and treatment. Among them, electrochemical biosensors and electrode modification proved their effectiveness in the detection of the Aβ biomarker at appropriately low concentrations for practice and point-of-care application. This review discusses the production and detection ability of amyloid beta, an Alzheimer’s biomarker, by electrochemical biosensors with SAM support for antibody conjugation. In addition, future perspectives on SAM for the improvement of electrochemical biosensors are also proposed and discussed.
Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS)—Does it Really Exist?
Authors: Freua Fernando , Mahler João Vitor , Lima Pedro Lucas Grangeiro de Sá Barreto , Neville Iuri Santana , Portella Leonardo Barreira , Marussi Victor Hugo Rocha , Lancellotti Carmen Lucia Penteado , Nobrega Paulo Ribeiro , Silva Guilherme Diogo
Published: August 2023

Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS) is a rare variant of the CLIPPERS spectrum with less than ten reports published so far. There is ongoing discussion regarding whether SLIPPERS is a disease entity on its own or just an acronym encompassing many underlying diagnoses, such as sarcoidosis, vasculitis and anti-glial fibrillary acidic protein (GFAP)-associated disease. A 40-year-old woman presented with episodes of language and attention impairment. Magnetic resonance imaging (MRI) revealed T2/FLAIR hyperintense lesions in the subcortical white matter associated with a micronodular, curvilinear perivascular contrast-enhancement. Alternative diagnoses were excluded. There was a remarkable response to steroids. A relapse occurred after six years, and the biopsy showed perivascular T-cell lymphocytic infiltrate, without granulomas, vasculitis, or neoplasia. There was complete resolution of the relapse after steroids. This case represents the longest reported follow-up of a patient diagnosed with SLIPPERS, and brain biopsy after 6 years did not suggest alternative diagnoses. This report contributes to the discussion regarding the possibility that exclusive supratentorial CLIPPERS-like pathology might be an isolated disease entity, but more biopsy-proven cases with a longer follow-up are needed to support this hypothesis. Recently, GFAP astrocytopathy has been characterized and might correspond to a significant number of cases previously diagnosed as CLIPPERS or SLIPPERS.
The Impact Mechanism of Consumer’s Initial Visit to an Automobile 4S Store on Test Drive Intention: Product Aesthetics, Space Image, Service Quality, and Brand Image
Authors: Jiang Qianling , Deng Liyuan , Yang Chun
Published: August 2023

[Purpose/Significance] Under the influence of various factors such as the pandemic, oil prices, and economic conditions, the global automotive industry has entered a period of downturn. Therefore, how to activate market potential and increase consumers’ willingness to purchase cars has become an important research topic. Unlike many other products, test drives play a significant role in the car-buying process. [Method/Procedure] This study employs a questionnaire survey to explore how consumer perceptions of product aesthetics, space quality, and service quality during their initial visit to an automobile 4S store influence their test drive intention through two dimensions of brand image: symbolic and experiential. A structural equation model is used to establish a test drive intention impact model incorporating these dimensions. [Results/Conclusions] The study found that brand image, both symbolic and experiential, plays a significant mediating role in enhancing potential consumers’ test drive intentions. Space image had the most significant impact on brand image. Although product aesthetics did not directly affect brand image experientially, they remained an important factor in enhancing brand image symbolically. [Contribution/Value] The results of this study can provide insights for automotive brand managers, automobile 4S store designers, and others aiming to promote the sustainable development of automotive consumption.
What Sustains Mask-Wearing Behavior among Elders in a Rural Community in the Post-COVID-19 Era: An Exploratory Mixed-Methods Study
Authors: Lertsakulbunlue Sethapong , Kittisarapong Pinyada , Pikulkaew Sirikorn , Pusayapaibul Pree , Tangtongsoonthorn Apisit , Wichaiboon Chanunpisut , Amornchatchawankul Fasai , Marsook Suranuch , Mahaisawariya Supakrit , Subwongcharoen Nattasit , Petcharat Phitchayut , Luksanasup Bannawit , Lortharaprasert Thakornphong , Tieantanyatip Bavorn , Kantiwong Anupong , Jongcherdchootrakul Kanlaya
Published: August 2023

The current study investigates the factors influencing face-mask-wearing practices among elderly individuals in rural Thailand. A mixed-methods approach was employed, involving qualitative interviews with 15 elderly participants and a subsequent survey of 201 elders. Seven subthemes were identified, including the perceived benefits of mask-wearing, the perceived threat of COVID-19, mask-wearing enhancing attractiveness and self-confidence, social norms, misconceptions about COVID-19 prevention tools, perceived barriers to mask-wearing, and resources to afford face masks. The developed themes, codes, and quotes were utilized for creating a questionnaire. The survey revealed the adherence of 81.1% of the participants to mask-wearing. Structural equation modeling (SEM) analysis demonstrated that motivation, comprising (1) the perceived threat of COVID-19, (2) alternative threats aside from COVID-19, and (3) the perceived benefits of a face mask strongly affected mask-wearing practices (β = 0.68, p < 0.001) and the willingness to wear a face mask (β = 0.61, p < 0.001). Social norms had a negative direct effect on the perceived barrier (β = −0.48, p < 0.001) and a positive direct effect on mask-wearing practices (β = 0.25, p = 0.001). This study highlights that motivation and social norms play pivotal roles in sustaining mask-wearing behavior among rural elderly populations. Encouraging local cooperative actions through community rules could initiate behavioral changes within the community. These findings contribute to the understanding of factors influencing mask-wearing and provide insights into designing effective interventions to promote mask-wearing among elderly individuals in rural areas.
Enhancing Zero-Energy Building Operations for ESG: Accurate Solar Power Prediction through Automatic Machine Learning
Authors: Lee Sanghoon , Park Sangmin , Kang Byeongkwan , Choi Myeong-in , Jang Hyeonwoo , Shmilovitz Doron , Park Sehyun
Published: August 2023

Solar power systems, such as photovoltaic (PV) systems, have become a necessary feature of zero-energy buildings because efficient building design and construction materials alone are not sufficient to meet the building’s energy consumption needs. However, solar power generation is subject to fluctuations based on weather conditions, and these fluctuations are higher than other renewable energy sources. This phenomenon has emphasized the importance of predicting solar power generation through weather forecasting. In this paper, an Automatic Machine Learning (AML)-based method is proposed to create multiple prediction models based on solar power generation and weather data. Then, the best model to predict daily solar power generation is selected from these models. The solar power generation data used in this study was obtained from an actual solar system installed in a zero-energy building, while the weather data was obtained from open data provided by the Korea Meteorological Administration. In addition, To verify the validity of the proposed method, an ideal data model with high accuracy but difficult to apply to the actual system and a comparison model with a relatively low accuracy but suitable for application to the actual system were created. The performance was compared with the model created by the proposed method. Based on the validation process, the proposed approach shows 5–10% higher prediction accuracies compared to the comparison model.
Multi-Level Numerical Modelling and Analysis of Tile Vaults
Authors: López López David , Mendes Nuno , Oliveira Daniel V. , Calderón Valdiviezo Lucrecia J. , Domènech-Rodríguez Marta
Published: August 2023

The complex structural behaviour of masonry, with its brittle response in tension, frictional response in shear, and anisotropy, makes it challenging to model accurately. Tile vaults, with their unique features such as different binders and bricks placed flat, have distinctive structural performance, and determining the most suitable assessment method is still a subject of debate in both academic and professional circles. This paper presents a study on the structural analysis of tile vaults, aiming at evaluating different numerical approaches for this type of structure. The examination of these approaches and their effectiveness in capturing the structural behaviour of tile vaults intends to offer valuable insights to researchers and professionals in this field. Experimental research was initially carried out in order to provide data for the calibration of the structural models. Two full-scale vaults were tested. Furthermore, several material characterization tests were also performed. The numerical assessment was carried out through limit analysis and non-linear static analysis with numerical models based on the Finite Element Method (FEM). Two FEM models were prepared using different modelling approaches for masonry, namely the macro-modelling and the simplified micro-modelling approaches. The results of the limit analysis presented a load capacity significantly lower than the ultimate load obtained from the experimental tests. The calibrated FEM models presented good results in comparison to the experimental results, namely in terms of damage pattern and load capacity.
Pancreatic Cancer: From Genetic Mechanisms to Translational Challenges
Authors: Pastorino Lorenza , Ghiorzo Paola , Bruno William
Published: August 2023

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive malignancies in industrialized countries, is predicted to become the second leading cause of cancer deaths by 2040 [...]
Mitochondrial Metabolism: A New Dimension of Personalized Oncology
Authors: Behnam Babak , Taghizadeh-Hesary Farzad
Published: August 2023

Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells’ mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironments, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The tumors’ responses to anticancer treatments vary, ranging from a complete response to even cancer progression during treatment. Therefore, personalized cancer treatment is of crucial importance. So far, personalized cancer treatment has been based on genomic analysis. Evidence shows that tumors with high mitochondrial content are more resistant to treatment. This paper illustrates how mitochondrial metabolism can participate in cancer resistance to chemotherapy, immunotherapy, and radiotherapy. Pretreatment evaluation of mitochondrial metabolism can provide additional information to genomic analysis and can help to improve personalized oncological treatments. This article outlines the importance of mitochondrial metabolism in cancer biology and personalized treatments.
Intake of the Total, Classes, and Subclasses of (Poly)Phenols and Risk of Prostate Cancer: A Prospective Analysis of the EPIC Study
Authors: Almanza-Aguilera Enrique , Guiñón-Fort Daniel , Perez-Cornago Aurora , Martínez-Huélamo Miriam , Andrés-Lacueva Cristina , Tjønneland Anne , Eriksen Anne Kirstine , Katzke Verena , Bajracharya Rashmita , Schulze Matthias B. , Masala Giovanna , Oliverio Andreina , Tumino Rosario , Manfredi Luca , Lasheras Cristina , Crous-Bou Marta , Sánchez Maria-José , Amiano Pilar , Colorado-Yohar Sandra M. , Guevara Marcela , Sonestedt Emily , Bjartell Anders , Thysell Elin , Weiderpass Elisabete , Aune Dagfinn , Aglago Elom K. , Travis Ruth C. , Zamora-Ros Raul
Published: August 2023

Existing epidemiological evidence regarding the potential role of (poly)phenol intake in prostate cancer (PCa) risk is scarce and, in the case of flavonoids, it has been suggested that their intake may increase PCa risk. We investigated the associations between the intake of the total and individual classes and subclasses of (poly)phenols and the risk of PCa, including clinically relevant subtypes. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort included 131,425 adult men from seven European countries. (Poly)phenol intake at baseline was assessed by combining validated center/country-specific dietary questionnaires and the Phenol-Explorer database. Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). In total, 6939 incident PCa cases (including 3501 low-grade and 710 high-grade, 2446 localized and 1268 advanced, and 914 fatal Pca cases) were identified during a mean follow-up of 14 years. No associations were observed between the total intake of (poly)phenols and the risk of PCa, either overall (HRlog2 = 0.99, 95% CI 0.94–1.04) or according to PCa subtype. Null associations were also found between all classes (phenolic acids, flavonoids, lignans, and stilbenes) and subclasses of (poly)phenol intake and the risk of PCa, overall and according to PCa subtype. The results of the current large prospective cohort study do not support any association between (poly)phenol intake and PCa incidence.
Malignancy Associated with Low-Risk HPV6 and HPV11: A Systematic Review and Implications for Cancer Prevention
Authors: Silva Leandro Lima da , Teles Amanda Mara , Santos Joana M. O. , Souza de Andrade Marcelo , Medeiros Rui , Faustino-Rocha Ana I. , Oliveira Paula A. , dos Santos Ana Paula Azevedo , Ferreira Lopes Fernanda , Braz Geraldo , Brito Haissa O. , Costa Rui M. Gil da
Published: August 2023

High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0–5.5% for penile and 0–87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV.
Metabolic Alterations Caused by Simultaneous Loss of HK2 and PKM2 Leads to Photoreceptor Dysfunction and Degeneration
Authors: Weh Eric , Goswami Moloy , Chaudhury Sraboni , Fernando Roshini , Miller Nick , Hager Heather , Sheskey Sarah , Sharma Vikram , Wubben Thomas J. , Besirli Cagri G.
Published: August 2023

HK2 and PKM2 are two main regulators of aerobic glycolysis. Photoreceptors (PRs) use aerobic glycolysis to produce the biomass necessary for the daily renewal of their outer segments. Previous work has shown that HK2 and PKM2 are important for the normal function and long-term survival of PRs but are dispensable for PR maturation, and their individual loss has opposing effects on PR survival during acute nutrient deprivation. We generated double conditional (dcKO) mice lacking HK2 and PKM2 expression in rod PRs. Western blotting, immunofluorescence, optical coherence tomography, and electroretinography were used to characterize the phenotype of dcKO animals. Targeted and stable isotope tracing metabolomics, qRT-PCR, and retinal oxygen consumption were performed. We show that dcKO animals displayed early shortening of PR inner/outer segments, followed by loss of PRs with aging, much more rapidly than either knockout alone without functional loss as measured by ERG. Significant alterations to central glucose metabolism were observed without any apparent changes to mitochondrial function, prior to PR degeneration. Finally, PR survival following experimental retinal detachment was unchanged in dcKO animals as compared to wild-type animals. These data suggest that HK2 and PKM2 have differing roles in promoting PR neuroprotection and identifying them has important implications for developing therapeutic options for combating PR loss during retinal disease.
Mass Cytometry as a Tool for Investigating Senescence in Multiple Model Systems
Authors: Abdul-Aziz Amina , Devine Raymond D. , Lyberger Justin M. , Chang Hsiaochi , Kovacs Amy , Lerma James R. , Rogers Andrew M. , Byrd John C. , Hertlein Erin , Behbehani Gregory K.
Published: August 2023

Cellular senescence is a durable cell cycle arrest as a result of the finite proliferative capacity of cells. Senescence responds to both intrinsic and extrinsic cellular stresses, such as aging, mitochondrial dysfunction, irradiation, and chemotherapy. Here, we report on the use of mass cytometry (MC) to analyze multiple model systems and demonstrate MC as a platform for senescence analysis at the single-cell level. We demonstrate changes to p16 expression, cell cycling fraction, and histone tail modifications in several established senescent model systems and using isolated human T cells. In bone marrow mesenchymal stromal cells (BMSCs), we show increased p16 expression with subsequent passage as well as a reduction in cycling cells and open chromatin marks. In WI-38 cells, we demonstrate increased p16 expression with both culture-induced senescence and oxidative stress-induced senescence (OSIS). We also use Wanderlust, a trajectory analysis tool, to demonstrate how p16 expression changes with histone tail modifications and cell cycle proteins. Finally, we demonstrate that repetitive stimulation of human T cells with CD3/CD28 beads induces an exhausted phenotype with increased p16 expression. This p16-expressing population exhibited higher expression of exhaustion markers such as EOMES and TOX. This work demonstrates that MC is a useful platform for studying senescence at a single-cell protein level, and is capable of measuring multiple markers of senescence at once with high confidence, thereby improving our understanding of senescent pathways.
Glucocorticoid Receptor Regulates and Interacts with LEDGF/p75 to Promote Docetaxel Resistance in Prostate Cancer Cells
Authors: Sanchez-Hernandez Evelyn S. , Ochoa Pedro T. , Suzuki Tise , Ortiz-Hernandez Greisha L. , Unternaehrer Juli J. , Alkashgari Hossam R. , Diaz Osterman Carlos J. , Martinez Shannalee R. , Chen Zhong , Kremsky Isaac , Wang Charles , Casiano Carlos A.
Published: August 2023

Patients with advanced prostate cancer (PCa) invariably develop resistance to anti-androgen therapy and taxane-based chemotherapy. Glucocorticoid receptor (GR) has been implicated in PCa therapy resistance; however, the mechanisms underlying GR-mediated chemoresistance remain unclear. Lens epithelium-derived growth factor p75 (LEDGF/p75, also known as PSIP1 and DFS70) is a glucocorticoid-induced transcription co-activator implicated in cancer chemoresistance. We investigated the contribution of the GR–LEDGF/p75 axis to docetaxel (DTX)-resistance in PCa cells. GR silencing in DTX-sensitive and -resistant PCa cells decreased LEDGF/p75 expression, and GR upregulation in enzalutamide-resistant cells correlated with increased LEDGF/p75 expression. ChIP-sequencing revealed GR binding sites in the LEDGF/p75 promoter. STRING protein–protein interaction analysis indicated that GR and LEDGF/p75 belong to the same transcriptional network, and immunochemical studies demonstrated their co-immunoprecipitation and co-localization in DTX-resistant cells. The GR modulators exicorilant and relacorilant increased the sensitivity of chemoresistant PCa cells to DTX-induced cell death, and this effect was more pronounced upon LEDGF/p75 silencing. RNA-sequencing of DTX-resistant cells with GR or LEDGF/p75 knockdown revealed a transcriptomic overlap targeting signaling pathways associated with cell survival and proliferation, cancer, and therapy resistance. These studies implicate the GR–LEDGF/p75 axis in PCa therapy resistance and provide a pre-clinical rationale for developing novel therapeutic strategies for advanced PCa.
Chronic Inflammation, Oxidative Stress and Metabolic Plasticity: Three Players Driving the Pro-Tumorigenic Microenvironment in Malignant Mesothelioma
Authors: Fiorilla Irene , Martinotti Simona , Todesco Alberto Maria , Bonsignore Gregorio , Cavaletto Maria , Patrone Mauro , Ranzato Elia , Audrito Valentina
Published: August 2023

Malignant pleural mesothelioma (MPM) is a lethal and rare cancer, even if its incidence has continuously increased all over the world. Asbestos exposure leads to the development of mesothelioma through multiple mechanisms, including chronic inflammation, oxidative stress with reactive oxygen species (ROS) generation, and persistent aberrant signaling. Together, these processes, over the years, force normal mesothelial cells’ transformation. Chronic inflammation supported by “frustrated” macrophages exposed to asbestos fibers is also boosted by the release of pro-inflammatory cytokines, chemokines, growth factors, damage-associated molecular proteins (DAMPs), and the generation of ROS. In addition, the hypoxic microenvironment influences MPM and immune cells’ features, leading to a significant rewiring of metabolism and phenotypic plasticity, thereby supporting tumor aggressiveness and modulating infiltrating immune cell responses. This review provides an overview of the complex tumor–host interactions within the MPM tumor microenvironment at different levels, i.e., soluble factors, metabolic crosstalk, and oxidative stress, and explains how these players supporting tumor transformation and progression may become potential and novel therapeutic targets in MPM.
Autoimmune Limbic Encephalitis in Patients with Hematologic Malignancies after Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide
Authors: Heo Bu Yeon , Lee Myung-Won , Choi Suyoung , Jung Yunju , Pham Thi Thuy Duong , Jang Yunseon , Park Jung-Hyun , Kang Sora , Koh Jeong Suk , Jo Deog-Yeon , Kwon Jaeyul , Song Ik-Chan
Published: August 2023

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with post-transplant cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflammatory biomarkers, and reconstitution of various T cell populations. Of 35 patients, 4 developed LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.
Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity
Authors: Chang Chia-Chi , Jiang Shih-Sheng , Tsai Fang-Yu , Hsu Pei-Ju , Hsieh Chen-Chan , Wang Li-Tzu , Yen Men-Luh , Yen B. Linju
Published: August 2023

Three-dimensional (3D) in vitro spheroid/organoid culture increasingly appears to better mimic physiological states than standard 2D systems. The biological consequence of 3D spheroids, however, differs for different cell types: for pluripotent embryonic stem cells (ESCs), differentiation and loss of stemness occur, while the converse is true for somatic and cancer cells. Despite such diverse consequences, there are likely conserved mechanisms governing 3D spheroid formation across cell types that are unknown but could be efficiently targeted for translational application. To elucidate such processes, we performed transcriptome analysis with functional validation on 2D- and 3D-cultured mouse ESCs, mesenchymal stromal/stem cells (MSCs), and cancer cells. At both the transcriptomic and functional levels, 3D spheroid formation resulted in commitment towards known cell-specific functional outcomes. Surprisingly in all cell types, downregulation of the cholesterol synthesis pathway was found during 3D spheroid formation, with modulation concomitantly affecting 3D spheroid formation and cell-specific consequences; similar results were seen with human cell types. Furthermore, improved antioxidant capacity after 3D spheroid formation across cell types was further enhanced with modulation of the pathway. These findings demonstrate the profound cell-specific consequences and the translational value of understanding conserved mechanisms across diverse cell types after 3D spheroid formation.
Nicotinic Acetylcholine Receptor Dysfunction in Addiction and in Some Neurodegenerative and Neuropsychiatric Diseases
Authors: Vallés Ana Sofía , Barrantes Francisco J.
Published: August 2023

The cholinergic system plays an essential role in brain development, physiology, and pathophysiology. Herein, we review how specific alterations in this system, through genetic mutations or abnormal receptor function, can lead to aberrant neural circuitry that triggers disease. The review focuses on the nicotinic acetylcholine receptor (nAChR) and its role in addiction and in neurodegenerative and neuropsychiatric diseases and epilepsy. Cholinergic dysfunction is associated with inflammatory processes mainly through the involvement of α7 nAChRs expressed in brain and in peripheral immune cells. Evidence suggests that these neuroinflammatory processes trigger and aggravate pathological states. We discuss the preclinical evidence demonstrating the therapeutic potential of nAChR ligands in Alzheimer disease, Parkinson disease, schizophrenia spectrum disorders, and in autosomal dominant sleep-related hypermotor epilepsy. PubMed and Google Scholar bibliographic databases were searched with the keywords indicated below.
New SDS-Based Polyelectrolyte Multicore Nanocarriers for Paclitaxel Delivery—Synthesis, Characterization, and Activity against Breast Cancer Cells
Authors: Szwed Marzena , Michlewska Sylwia , Kania Katarzyna , Szczęch Marta , Marczak Agnieszka , Szczepanowicz Krzysztof
Published: August 2023

The low distribution of hydrophobic anticancer drugs in patients is one of the biggest limitations during conventional chemotherapy. SDS-based polyelectrolyte multicore nanocarriers (NCs) prepared according to the layer by layer (LbL) procedure can release paclitaxel (PTX), and selectively kill cancer cells. Our main objective was to verify the antitumor properties of PTX-loaded NCs and to examine whether the drug encapsulated in these NCs retained its cytotoxic properties. The cytotoxicity of the prepared nanosystems was tested on MCF-7 and MDA-MB-231 tumour cells and the non-cancerous HMEC-1 cell line in vitro. Confocal microscopy, spectrophotometry, spectrofluorimetry, flow cytometry, and RT PCR techniques were used to define the typical hallmarks of apoptosis. It was demonstrated that PTX encapsulated in the tested NCs exhibited similar cytotoxicity to the free drug, especially in the triple negative breast cancer model. Moreover, SDS/PLL/PTX and SDS/PLL/PGA/PTX significantly reduced DNA synthesis. In addition, PTX-loaded NCs triggered apoptosis and upregulated the transcription of Bax, AIF, cytochrome-c, and caspase-3 mRNA. Our data demonstrate that these novel polyelectrolyte multicore NCs coated with PLL or PLL/PGA are good candidates for delivering PTX. Our discoveries have prominent implications for the possible choice of newly synthesized, SDS-based polyelectrolyte multicore NCs in different anticancer therapeutic applications.
Recent Advances in Dynamic DNA Nanodevice
Authors: Fan Qin , Yang Linzi , Chao Jie
Published: August 2023

DNA nanotechnology has been widely used to fabricate precise nanometer-scale machines. In particular, dynamic DNA nanodevices have demonstrated their ability to mimic molecular motions and fluctuations in bion-anomic systems. The elaborately designed DNA nanomachines can conduct a variety of motions and functions with the input of specific commands. A dynamic DNA nanodevice with excellent rigidity and unprecedented processability allows for structural transformation or predictable behavior, showing great potential in tackling single-molecule sensing, drug delivery, molecular systems, and so on. Here, we first briefly introduce the development history of DNA nanotechnology. The driving energy of dynamic DNA nanomachines is also discussed with representative examples. The motor pattern of DNA nanomachines is classified into four parts including translational motion, shear motion, 360° rotation, and complex motion. This review aims to provide an overview of the latest reports on the dynamic DNA nanomachine and give a perspective on their future opportunities.
Enhanced Fluorescence in a Lens-Less Fiber-Optic Sensor for C-Reactive Protein Detection
Authors: Esteso Victoria , Lombardi Pietro , Chiavaioli Francesco , Majumder Prosenjit , Colautti Maja , Howitz Steffen , Cecchi Paolo , Baldini Francesco , Giannetti Ambra , Toninelli Costanza
Published: August 2023

In today’s medicine, the celerity of the bio-assays analysis is crucial for the timely selection of the appropriate therapy and hence its effectiveness, especially in case of diseases characterized by the late onset of symptoms. In this paper, a lens-less fiber optics-based fluorescence sensor designed for the measurement of labeled bio-assays is presented and its potential for the early diagnosis of sepsis via C-reactive protein (CRP) detection is demonstrated. The sensor performance results from the combination of two key elements: a planar antenna that redirects fluorescence the marker emission and an automated fiber-based optical system for multi-spot analysis. First, the working principle of the device is demonstrated with a well-established antibody–antigen format (immunoglobulin IgG/anti-IgG assay), reporting more than one order of magnitude enhanced limit of detection (LOD) and limit of quantification (LOQ) for the planar antenna with respect to a standard glass substrate. The prototype is then tested against a sample mimicking a realistic case, prepared with commercially available human serum, showing a LOD and LOQ in the clinical range of interest (0.0015 μg/mL and 0.005 μg/mL, respectively) for the investigation of the sepsis biomarker CRP. These results validate the developed prototype as a simple and easy-to-operate device, compatible with standardized micro-well arrays, and potentially suitable for POC applications.
Real-Time Monitoring of Cement Paste Carbonation with In Situ Optical Fiber Sensors
Authors: da Silva Pedro M. , Mendes João P. , Coelho Luís C. C. , de Almeida José M. M. M.
Published: August 2023

Reinforced concrete structures are prevalent in infrastructure and are of significant economic and social importance to humanity. However, they are prone to decay from cement paste carbonation. pH sensors have been developed to monitor cement paste carbonation, but their adoption by the industry remains limited. This work introduces two new methods for monitoring cement paste carbonation in real time that have been validated through the accelerated carbonation of cement paste samples. Both configurations depart from traditional pH monitoring. In the first configuration, the carbonation depth of a cement paste sample is measured using two CO2 optical fiber sensors. One sensor is positioned on the surface of the sample, while the other is embedded in the middle. As the carbonation depth progresses and reaches the embedded CO2 sensor, the combined response of the sensors changes. In the second configuration, a multimode fiber is embedded within the paste, and its carbonation is monitored by observing the increase in reflected light intensity (1.6–18%) resulting from the formation of CaCO3. Its applicability in naturally occurring carbonation is tested at concentrations of 3.2% CO2, and the influence of water is positively evaluated; thus, this setup is suitable for real-world testing and applications.
The Most Valuable Predictive Factors for Bronchopulmonary Dysplasia in Very Preterm Infants
Authors: Chen Wenwen , Zhang Zhenhai , Xu Liping , Chen Chao
Published: August 2023

Introduction: It is urgent to make a rapid screening of infants at the highest risk for bronchopulmonary dysplasia (BPD) via some succinct postnatal biomarkers, such as Ureaplasma Urealyticum (UU) infection and chest radiograph images. Methods: A retrospective study was performed. Moderate to severe BPD or death was set as the main outcome. The association between putative variables and the main outcome were assessed by bivariate analyses and logistic regression. Results: A total of 134 infants were enrolled. Bivariate analyses showed the gestational age, birth weight, appearances of diffuse opacities or grid shadows/interstitial opacities or mass opacities or cystic lucencies on chest radiographic images, a ductal diameter ≥1.5 mm and whether UU infection was associated with BPD. After adjustment by logistic regression, the risk of BPD with gestational age, sex and specific chest-radiographic manifestations remained significant. Conclusions: Chest radiograph images (appearance of diffuse opacities or grid shadows/interstitial opacities or mass opacities or cystic lucencies) could provide a quick prediction of developing BPD in clinical practice, in addition to gestational age and sex. UU infection was not an independent risk factor for BPD.
An Unusual Case of Neonatal Hypotonia and Femur Fracture: Neuromuscular Variant of Glycogen Storage Disease Type IV
Authors: Bezirganoglu Handan , Adanur Saglam Kubra
Published: August 2023

Glycogen storage disease type IV (GSD IV) (OMIM #232500) is an autosomal recessive disorder caused by deficiency of the glycogen-branching enzyme. Here, we report a patient presenting with prematurity and severe hypotonia resulting from a complicated pregnancy with polyhydramnios. During her stay in the neonatal unit, the infant remained dependent on a ventilator, and her movements were mostly absent, except for occasional small movements of her fingers. A spontaneous fracture of femur shaft occurred in the postnatal fourth week. Whole-exome sequencing of DNA from the patient revealed a homozygous missense variant in the GBE1 gene (c.1693C>T, p.Arg565Trp). The variation detected in the index case was also confirmed by Sanger sequencing in the patient and respective parents. This study showed that the neuromuscular subtypes of GSD-IV should be considered as a possible differential diagnosis in severe neonatal hypotonia cases.
Pediatric Trauma and Trauma Team Activation in a Swiss Pediatric Emergency Department: An Observational Cohort Study
Authors: Herren Anouk , Palmer Cameron S. , Landolt Markus A. , Lehner Markus , Neuhaus Thomas J. , Simma Leopold
Published: August 2023

Background. Trauma is one of the most common causes of death in childhood, but data on severely injured Swiss children are absent from existing national registries. Our aim was to analyze trauma activations and the profiles of critically injured children at a tertiary, non-academic Swiss pediatric emergency department (PED). In the absence of a national pediatric trauma database, this information may help to guide the design of infrastructure, processes within organizations, training, and policies. Methods. A retrospective analysis of pediatric trauma patients in a prospective resuscitation database over a 2-year period. Critically injured trauma patients under the age of 16 years were included. Patients were described with established triage and injury severity scales. Statistical evaluation included logistic regression analysis. Results. A total of 82 patients matched one or more of the study inclusion criteria. The most frequent age group was 12–15 years, and 27% were female. Trauma team activation (TTA) occurred with 49 patients (59.8%). Falls were the most frequent mechanism of injury, both overall and for major trauma. Road-traffic-related injuries had the highest relative risk of major trauma. In the multivariate analysis, patients receiving medicalized transport were more likely to trigger a TTA, but there was no association between TTA and age, gender, or Injury Severity Score (ISS). Nineteen patients (23.2%) sustained major trauma with an ISS > 15. Injuries of Abbreviated Injury Scale severity 3 or greater were most frequent to the head, followed by abdomen, chest, and extremities. The overall mortality rate in the cohort was 2.4%. Conclusions: Major trauma presentations only comprise a small proportion of the total patient load in the PED, and trauma team activation does not correlate with injury severity. Low exposure to high-acuity patients highlights the importance of deliberate learning and simulation for all professionals in the PED. Our findings indicate that high priority should be given to training in the management of severely injured children in the PED. The leading major trauma mechanisms were preventable, which should prompt further efforts in injury prevention.