bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization and Applicability of a Bone Spheroid Model for the Evaluation of Cytocompatibility of Bone Substitutes
Authors: Brochado Ana Carolina Batista , Silva Daniela Costa , Silva Joice Correa da , Lowenstein Adam , Gameiro Vinicius Schott , Mavropoulos Elena , Mourão Carlos F. , Alves Gutemberg Gomes
Published: January 2023

In vitro cell-based tests are an important preclinical step for the safety assessment of biomaterials and drugs. Three-dimensional cell culture models (3D) may improve the limitations of the usual 2D models, as they better simulate a physiological environment. This work describes the characterization of a 3D spheroid model of MC3T3-E1 murine preosteoblasts for the testing of bone-substitute materials and investigates its adequacy to some of the most employed cell viability tests. The spheroids presented structural stability for 28 days in culture, with a regular spheroidal aspect, compact surface, and dense inner structure, with high potential for mineralization, but a time-dependent reduction in size. The use of colorimetric tests (MTT, XTT, and NRU) did not achieve satisfactory optical densities and did not correlate with cell density in the 3D model, as the aggregates remain strongly stained even after dye extraction steps. On the other hand, the LDH test achieved appropriate optical density and a high correlation with cell density (r2 = 0.77) and identified a dose–response for a well-known cytotoxic polymer (latex), while no toxicity was identified for biocompatible PLA wires. These results indicate that material testing with 3D bone cell models requires a careful choice of test methods and parameters.
RESEMBLE: A Real-Time Stack for Synchronized Mesh Mobile Bluetooth Low Energy Networks
Authors: Leonardi Luca , Lo Bello Lucia , Patti Gaetano
Published: January 2023

Bluetooth Low Energy (BLE) is a wireless technology for low-power, low-cost and lowcomplexity short-range communications. On top of the BLE stack, the Bluetooth Mesh profile can be adopted to handle large networks with mesh topologies. BLE is a promising candidate for the implemention of Industrial Wireless Sensor Networks (IWSNs), thanks to its wide diffusion (e.g., on smartphones and tablets) and the lower cost of the devices compared to other wireless industrial communication technologies. However, neither the BLE nor the Bluetooth Mesh specifications can provide real-time messages with bounded delays. To overcome this limitation, this work proposes RESEMBLE, a real-time stack developed on top of BLE that is able to realize low-cost IWSNs over mesh topologies. RESEMBLE offers support to both real-time and non-real-time communications on the same network. Moreover, RESEMBLE provides clock synchronization, thus allowing for Time Division Multiple Access (TDMA) transmissions. The clock synchronization provided by RESEMBLE can be also exploited by the upper layers’ industrial applications to implement timecoordinated actions.
A Survey on Toxic Volatile Organic Compounds (VOCs): Toxicological Profiles, Health Exposure Risks, and Regulatory Strategies for Mitigating Emissions from Stationary Sources in Taiwan
Authors: Tsai Wen-Tien
Published: January 2023

With the revision of the Air Pollution Control Act in Taiwan announced on 1 August 2018, several provisions or regulations have been added to strengthen the control of hazardous air pollutants (HAPs) from stationary sources. Therefore, this paper conducted a survey of sixty toxic volatile organic compounds (VOCs) designated as HAPs in Taiwan and also performed a comparison between some developed countries (i.e., the USA, Japan, and Korea) using the latest databases issued by the relevant agencies/organizations. Furthermore, these designated HAPs were reviewed by their carcinogenic classifications and occupational exposure limits. Finally, the regulatory measures for controlling the emissions of toxic VOCs from stationary sources in Taiwan were addressed to echo the public concerns about their human health risk. Except for trichloroacetic acid, the designated toxic VOCs in Taiwan are included in the list of HAPs in the USA. By comparison, the number of designated HAPs is obviously higher than those in Japan and Korea. Based on the carcinogen classification by the International Agency for Research on Cancer (IARC), the toxic VOCs as confirmed human carcinogens (Group 1) include benzene, benzidine, 1,3-butadiene, 1,2-dichloroproane, ethylene oxide, formaldehyde, 4,4-methylene bis(2-chloroaniline), trichloroethylene, and vinyl chloride. To achieve the purpose of protecting public health, the follow-up control actions of HAPs from stationary sources in Taiwan involved regulatory countermeasures, including the establishment of emission limits, reporting systems, reduction plans for potential high-risk areas or plants, the incentive of an air pollution fee levy, as well as an ambient air concentration monitoring network.
An Efficient EMS for BESS in Monopolar DC Networks with High Penetration of Renewable Generation: A Convex Approximation
Authors: Grisales-Noreña Luis Fernando , Montoya Oscar Danilo , Hernández Jesus C.
Published: January 2023

This research presents an efficient energy management system (EMS) for battery energy storage systems (BESS) connected to monopolar DC distribution networks which considers a high penetration of photovoltaic generation. The optimization model that expresses the EMS system with the BESS and renewable generation can be classified as a nonlinear programming (NLP) model. This study reformulates the NLP model as a recursive convex approximation (RCA) model. The proposed RCA model is developed by applying a linear approximation for the voltage magnitudes only at nodes that include constant power loads. The nodes with BESS and renewables are approximated through the relaxation of their voltage magnitude. Numerical results obtained in the monopolar version of a 33-bus system, which included three generators and three BESS, demonstrate the effectiveness of the RCA reformulation when compared to the solution of the exact NLP model via combinatorial optimization techniques. Additional simulations considering wind power and diesel generators allow one to verify the effectiveness of the proposed RCA in dealing with the efficient operation of distributed energy resources in monopolar DC networks via recursive convex programming.
Towards Ready-to-Use Iron-Crosslinked Alginate Beads as Mesenchymal Stem Cell Carriers
Authors: Baudequin Timothée , Wee Hazel , Cui Zhanfeng , Ye Hua
Published: January 2023

Micro-carriers, thanks to high surface/volume ratio, are widely studied as mesenchymal stem cell (MSCs) in vitro substrate for proliferation at clinical rate. In particular, Ca-alginate-based biomaterials (sodium alginate crosslinked with CaCl2) are commonly investigated. However, Ca-alginate shows low bioactivity and requires functionalization, increasing labor work and costs. In contrast, films of sodium alginate crosslinked with iron chloride (Fe-alginate) have shown good bioactivity with fibroblasts, but MSCs studies are lacking. We propose a first proof-of-concept study of Fe-alginate beads supporting MSCs proliferation without functionalization. Macro- and micro-carriers were prepared (extrusion and electrospray) and we report for the first time Fe-alginate electrospraying optimization. FTIR spectra, stability with various mannuronic acids/guluronic acids (M/G) ratios and size distribution were analyzed before performing cell culture. After confirming literature results on films with human MSCs, we showed that Macro-Fe-alginate beads offered a better environment for MSCs adhesion than Ca-alginate. We concluded that Fe-alginate beads showed great potential as ready-to-use carriers.
Impact of Frailty on Outcomes of First-Line Pembrolizumab Monotherapy in a Real-World Population with Advanced Non-Small Cell Lung Cancer
Authors: Jiménez Galán Rocío , Prado-Mel Elena , Alvarez de Sotomayor Maria , Martin Laila Abdel-Kader
Published: January 2023

ICIs have been able to improve overall survival in advanced-stage lung cancer. The benefit of this therapy is limited in patients with poor ECOG PS. However, this scale is imprecise and can be influenced by different factors, such as frailty. Cancer patients have a high risk of frailty independently of age. In this observational, single-center, retrospective study, we investigated the effect of frailty on the effectiveness of pembrolizumab in first-line use in a cohort of 101 patients with metastatic NSCLC. Frailty was determined using a frailty score system developed by Sakakida et al. Univariate and multivariate analysis was performed to determine the prognostic role of frailty on OS and PFS. Median OS was significantly higher in patients with low frailty compared with intermediate and high frailty (23.8 vs. 7.0 and 1.8 months, respectively; p < 0.001). Median PFS was also significantly higher in patients with low frailty compared with intermediate and high frailty (10.5 vs. 3.9 and 1.6 months; p < 0.001, respectively). Frailty was the only variable that showed significant differences in OS and PFS. Multivariate analysis confirms frailty as an independent predictor of OS and PFS. Frailty assessment could help to select which patients are candidates for ICIs in NSCLC.
Isolation, Characterization, and Biocompatibility of Bisporitin, a Ribotoxin-like Protein from White Button Mushroom (Agaricus bisporus)
Authors: Ragucci Sara , Hussain Hafiza Zumra Fatima , Bosso Andrea , Landi Nicola , Clemente Angela , Pedone Paolo Vincenzo , Pizzo Elio , Di Maro Antimo
Published: January 2023

White button mushroom (Agaricus bisporus (J.E. Lange) Imbach) is one of the widely consumed edible mushrooms. Indeed, A. bisporus fruiting bodies are a rich source of nutrients and bioactive molecules. In addition, several enzymes with biotechnological applications are found in A. bisporus (e.g., enzymes for lignocellulose degradation). Here, a novel ribotoxin-like protein (RL-P) from the edible mushroom A. bisporus was purified and characterized. This RL-P, named bisporitin, is a monomeric protein (17-kDa) exhibiting specific ribonucleolytic activity by releasing the α-fragment (hallmark of RL-Ps) when incubated with rabbit ribosomes. In addition, bisporitin shows magnesium-dependent endonuclease activity and displays a similar far-UV CD spectrum as ageritin, the prototype of RL-Ps, isolated from Cyclocybe aegerita fruiting bodies. Interestingly, bisporitin is the first member of RL-Ps to have noticeably lower thermal stability (Tm = 48.59 ± 0.98 °C) compared to RL-Ps isolated in other mushrooms (Tm > 70 °C). Finally, this protein is only partially hydrolyzed in an in vitro digestive system and does not produce adverse growing effects on eukaryotic cell lines. This evidence paves the way for future investigations on possible bioactivities of this RL-P in the digestive system.
Analysis of Antioxidant and Antiviral Effects of Olive (Olea europaea L.) Leaf Extracts and Pure Compound Using Cancer Cell Model
Authors: Pennisi Rosamaria , Ben Amor Ichrak , Gargouri Bochra , Attia Hamadi , Zaabi Rihab , Chira Ahlem Ben , Saoudi Mongi , Piperno Anna , Trischitta Paola , Tamburello Maria Pia , Sciortino Maria Teresa
Published: January 2023

The present study aims to assess the antioxidant and antiviral effectiveness of leaf extracts obtained from Olea europaea L. var. sativa and Olea europaea L. var. sylvestris. The total antioxidant activity was determined via both an ammonium phosphomolybdate assay and a nitric oxide radical inhibition assay. Both extracts showed reducing abilities in an in vitro system and in human HeLa cells. Indeed, after oxidative stress induction, we found that exposition to olive leaf extracts protects human HeLa cells from lipid peroxidation and increases the concentration of enzyme antioxidants such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase. Additionally, OESA treatment affects viral DNA accumulation more than OESY, probably due to the exclusive oleuropein content. In fact, subtoxic concentrations of oleuropein inhibit HSV-1 replication, stimulating the phosphorylation of PKR, c-FOS, and c-JUN proteins. These results provide new knowledge about the potential health benefits and mechanisms of action of oleuropein and oleuropein-rich extracts.
Multimodal Optical Monitoring of Auto- and Allografts of Skin on a Burn Wound
Authors: Turchin Ilya , Beschastnov Vladimir , Peretyagin Petr , Perekatova Valeriya , Kostyuk Alexey , Orlova Anna , Koloshein Nikita , Khilov Aleksandr , Sergeeva Ekaterina , Kirillin Mikhail , Ryabkov Maksim
Published: January 2023

The aim of the study was to investigate the dynamics of the state of allo- and autografts of skin on a wound using optical modalities: diffuse reflectance spectroscopy (DRS), optical coherence tomography (OCT), and laser Doppler flowmetry (LDF). A deep thermal burn was simulated in 24 rats covering 20% of the body surface. On day 3 after the injury, a fascial necrectomy of two 500 mm2 areas on the left and right sides of the midline of the animal body were excised. Allografts and autografts were placed in the centers of these areas. Optical measurements of grafts were performed on the 0, 3rd, 6th, 10th, and 13th days after transplantation. The allografts demonstrated a pronounced decrease in oxygenation, blood content, and perfusion compared to autografts on the 6th day; in the following days of observation, these values returned to the average values of autografts. Water content gradually decreased from the beginning to the end of observation. In conclusion, optical diagnostics revealed changes in the morphological microstructure, the rate of restoration of blood circulation, and oxygen exchange in the early stages, specific for the allo- and autograft.
Detecting Early Cognitive Decline in Alzheimer’s Disease with Brain Synaptic Structural and Functional Evaluation
Authors: Ribarič Samo
Published: January 2023

Early cognitive decline in patients with Alzheimer’s (AD) is associated with quantifiable structural and functional connectivity changes in the brain. AD dysregulation of Aβ and tau metabolism progressively disrupt normal synaptic function, leading to loss of synapses, decreased hippocampal synaptic density and early hippocampal atrophy. Advances in brain imaging techniques in living patients have enabled the transition from clinical signs and symptoms-based AD diagnosis to biomarkers-based diagnosis, with functional brain imaging techniques, quantitative EEG, and body fluids sampling. The hippocampus has a central role in semantic and episodic memory processing. This cognitive function is critically dependent on normal intrahippocampal connections and normal hippocampal functional connectivity with many cortical regions, including the perirhinal and the entorhinal cortex, parahippocampal cortex, association regions in the temporal and parietal lobes, and prefrontal cortex. Therefore, decreased hippocampal synaptic density is reflected in the altered functional connectivity of intrinsic brain networks (aka large-scale networks), including the parietal memory, default mode, and salience networks. This narrative review discusses recent critical issues related to detecting AD-associated early cognitive decline with brain synaptic structural and functional markers in high-risk or neuropsychologically diagnosed patients with subjective cognitive impairment or mild cognitive impairment.
Design and Prediction of Aptamers Assisted by In Silico Methods
Authors: Lee Su Jin , Cho Junmin , Lee Byung-Hoon , Hwang Donghwan , Park Jee-Woong
Published: January 2023

An aptamer is a single-stranded DNA or RNA that binds to a specific target with high binding affinity. Aptamers are developed through the process of systematic evolution of ligands by exponential enrichment (SELEX), which is repeated to increase the binding power and specificity. However, the SELEX process is time-consuming, and the characterization of aptamer candidates selected through it requires additional effort. Here, we describe in silico methods in order to suggest the most efficient way to develop aptamers and minimize the laborious effort required to screen and optimise aptamers. We investigated several methods for the estimation of aptamer-target molecule binding through conformational structure prediction, molecular docking, and molecular dynamic simulation. In addition, examples of machine learning and deep learning technologies used to predict the binding of targets and ligands in the development of new drugs are introduced. This review will be helpful in the development and application of in silico aptamer screening and characterization.
Urinary Oxidative Stress Biomarkers in the Diagnosis of Detrusor Overactivity in Female Patients with Stress Urinary Incontinence
Authors: Chen Wei-Hsin , Jiang Yuan-Hong , Kuo Hann-Chorng
Published: January 2023

Ninety-three women with urodynamic stress incontinence (USI) and a mean age of 60.8 ± 10.7 (36–83) years were retrospectively enrolled. According to their VUDS, 31 (33%) were grouped into USI and detrusor overactivity (DO), 28 (30.1%) were grouped into USI and hypersensitive bladder (HSB), and 34 (36.6%) were controls (USI and stable bladder). The USI and DO group had significantly increased 8-isoprostane (mean, 33.3 vs. 10.8 pg/mL) and 8-hydroxy-2-deoxyguanosine (8-OHdG; mean, 28.9 vs. 17.4 ng/mL) and decreased interleukin (IL)-2 (mean, 0.433 vs. 0.638 pg/mL), vascular endothelial growth factor (mean, 5.51 vs. 8.99 pg/mL), and nerve growth factor (mean, 0.175 vs. 0.235 pg/mL) levels compared to controls. Oxidative stress biomarkers were moderately diagnostic of DO from controls, especially 8-isoprostane (area under the curve (AUC) > 0.7). Voided volume was highly diagnostic of DO from either controls or non-DO patients (AUC 0.750 and 0.915, respectively). The proposed prediction model with voided volume, 8-OHdG, and 8-isoprostane (cutoff values 384 mL, 35 ng/mL, and 37 pg/mL, respectively) had an accuracy of 81.7% (sensitivity, 67.7%; specificity, 88.7%; positive predictive value, 75.0%; negative predictive value, 84.6%). Combined with voided volume, urinary oxidative stress biomarkers have the potential to be used to identify urodynamic DO in patients with USI.
Measurable Residual Disease and Clonal Evolution in Acute Myeloid Leukemia from Diagnosis to Post-Transplant Follow-Up: The Role of Next-Generation Sequencing
Authors: Sperotto Alessandra , Bochicchio Maria Teresa , Simonetti Giorgia , Buccisano Francesco , Peccatori Jacopo , Piemontese Simona , Calistri Elisabetta , Ciotti Giulia , Pierdomenico Elisabetta , De Marchi Roberta , Ciceri Fabio , Gottardi Michele
Published: January 2023

It has now been ascertained that acute myeloid leukemias—as in most type of cancers—are mixtures of various subclones, evolving by acquiring additional somatic mutations over the course of the disease. The complexity of leukemia clone architecture and the phenotypic and/or genotypic drifts that can occur during treatment explain why more than 50% of patients—in hematological remission—could relapse. Moreover, the complexity and heterogeneity of clone architecture represent a hindrance for monitoring measurable residual disease, as not all minimal residual disease monitoring methods are able to detect genetic mutations arising during treatment. Unlike with chemotherapy, which imparts a relatively short duration of selective pressure on acute myeloid leukemia clonal architecture, the immunological effect related to allogeneic hematopoietic stem cell transplant is prolonged over time and must be overcome for relapse to occur. This means that not all molecular abnormalities detected after transplant always imply inevitable relapse. Therefore, transplant represents a critical setting where a measurable residual disease-based strategy, performed during post-transplant follow-up by highly sensitive methods such as next-generation sequencing, could optimize and improve treatment outcome. The purpose of our review is to provide an overview of the role of next-generation sequencing in monitoring both measurable residual disease and clonal evolution in acute myeloid leukemia patients during the entire course of the disease, with special focus on the transplant phase.
Flow Control around the UAS-S45 Pitching Airfoil Using a Dynamically Morphing Leading Edge (DMLE): A Numerical Study
Authors: Bashir Musavir , Zonzini Nicola , Botez Ruxandra Mihaela , Ceruti Alessandro , Wong Tony
Published: January 2023

This paper investigates the effect of the Dynamically Morphing Leading Edge (DMLE) on the flow structure and the behavior of dynamic stall vortices around a pitching UAS-S45 airfoil with the objective of controlling the dynamic stall. An unsteady parametrization framework was developed to model the time-varying motion of the leading edge. This scheme was then integrated within the Ansys-Fluent numerical solver by developing a User-Defined-Function (UDF), with the aim to dynamically deflect the airfoil boundaries, and to control the dynamic mesh used to morph and to further adapt it. The dynamic and sliding mesh techniques were used to simulate the unsteady flow around the sinusoidally pitching UAS-S45 airfoil. While the γ−Reθ  turbulence model adequately captured the flow structures of dynamic airfoils associated with leading-edge vortex formations for a wide range of Reynolds numbers, two broader studies are here considered. Firstly, (i) an oscillating airfoil with the DMLE is investigated; the pitching-oscillation motion of an airfoil and its parameters are defined, such as the droop nose amplitude (AD) and the pitch angle at which the leading-edge morphing starts (MST). The effects of the AD and the MST on the aerodynamic performance was studied, and three different amplitude cases are considered. Secondly, (ii) the DMLE of an airfoil motion at stall angles of attack was investigated. In this case, the airfoil was set at stall angles of attack rather than oscillating it. This study will provide the transient lift and drag at different deflection frequencies of 0.5 Hz, 1 Hz, 2 Hz, 5 Hz, and 10 Hz. The results showed that the lift coefficient for the airfoil increased by 20.15%, while a 16.58% delay in the dynamic stall angle was obtained for an oscillating airfoil with DMLE with AD = 0.01 and MST = 14.75°, as compared to the reference airfoil. Similarly, the lift coefficients for two other cases, where AD = 0.05 and AD = 0.0075, increased by 10.67% and 11.46%, respectively, compared to the reference airfoil. Furthermore, it was shown that the downward deflection of the leading edge increased the stall angle of attack and the nose-down pitching moment. Finally, it was concluded that the new radius of curvature of the DMLE airfoil minimized the streamwise adverse pressure gradient and prevented significant flow separation by delaying the Dynamic Stall Vortex (DSV) occurrence.
The Adjustment of Complexity on Sarcasm Processing in Chinese: Evidence from Reading Time Indicators
Authors: Li Yutong , Shi Hanwen , Li Shan , Gao Lei , Gao Xiaolei
Published: January 2023

It is controversial whether sarcasm processing should go through literal meaning processing. There is also a lack of eye movement evidence for Chinese sarcasm processing. In this study, we used eye movement experiments to explore the processing differences between sarcastic and literal meaning in Chinese text and whether this was regulated by sentence complexity. We manipulated the variables of complexity and literality. We recorded 33 participants’ eye movements when they were reading Chinese text and the results were analyzed by a linear mixed model. We found that, in the early stage of processing, there was no difference between the processing time of the sarcastic meaning and the literal meaning of simple remarks, whereas for complex remarks, the time needed to process the sarcastic meaning was longer than that needed to process the literal meaning. In the later stage of processing, regardless of complexity, the processing time of the sarcastic meaning was longer than that of the literal meaning. These results suggest that sarcastic speech processing in Chinese is influenced by literal meaning, and the effect of literal meaning on sarcastic remarks is regulated by complexity. Sarcastic meaning was expressed differently in different stages of processing. These results support the hierarchical salience hypothesis of the serial modular model.
Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2
Authors: Sivananthan Siyamini , Lee Laura , Anderson Glenn , Csanyi Barbara , Williams Ruth , Gissen Paul
Published: January 2023

The introduction of intracerebroventricular (ICV) enzyme replacement therapy (ERT) for treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease has produced dramatic improvements in disease management. However, assessments of therapeutic effect for ICV ERT are limited to clinical observational measures, namely the CLN2 Clinical Rating Scale, a subjective measure of motor and language performance. There is a need for an objective biomarker to enable assessments of disease progression and response to treatment. To address this, we investigated whether the proportion of cells with abnormal storage inclusions on electron microscopic examination of peripheral blood buffy coats could act as a biomarker of disease activity in CLN2 disease. We conducted a prospective longitudinal analysis of six patients receiving ICV ERT. We demonstrated a substantial and continuing reduction in the proportion of abnormal cells over the course of treatment, whereas symptomatic scores revealed little or no change over time. Here, we proposed the use of the proportion of cells with abnormal storage as a biomarker of response to therapy in CLN2. In the future, as more tissue-specific biomarkers are developed, the buffy coats may form part of a panel of biomarkers in order to give a more holistic view of a complex disease.
Correlates of Taxane-Induced Neuropathy, an Electronic Health Record Based Observational Study
Authors: Dorand R. Dixon , Zheng Neil S. , Agarwal Rajiv , Carroll Robert J. , Rubinstein Samuel M. , Winkfield Karen M. , Wei Wei-Qi , Berlin Jordan , Shu Xiao-Ou
Published: January 2023

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common therapeutic complication affecting cancer patients’ quality-of-life. We evaluated clinical characteristics, demographics, and lifestyle factors in association with CIPN following taxane treatment. Methods: Data were extracted from the electronic health record of 3387 patients diagnosed with a primary cancer and receiving taxane (i.e., paclitaxel or docetaxel) at Vanderbilt University Medical Center. Neuropathy was assessed via a validated computer algorithm. Univariate and multivariate regression models were applied to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) of CIPN-associated factors. Results: Female sex (OR = 1.28, 95% CI = 1.01–1.62), high body-mass index (BMI) (OR = 1.31, 95% CI = 1.06–1.61 for overweight, and OR = 1.49, 95% CI = 1.21–1.83 for obesity), diabetes (OR = 1.66, 95% CI = 1.34–2.06), high mean taxane dose (OR = 1.05, 95% CI = 1.03–1.08 per 10 mg/m2), and more treatment cycles (1.12, 95% CI = 1.10–1.14) were positively associated with CIPN. Concurrent chemotherapy (OR = 0.74, 95% CI = 0.58–0.94) and concurrent radiotherapy (OR = 0.77, 95% CI = 0.59–1.00) were inversely associated with CIPN. Obesity and diabetes both had a stronger association with docetaxel CIPN compared to paclitaxel, although interaction was only significant for diabetes and taxane (p = 0.019). Increased BMI was associated with CIPN only among non-diabetic patients (OR:1.34 for overweight and 1.68 for obesity), while diabetes increased CIPN risk across all BMI strata (ORs were 2.65, 2.41, and 2.15 for normal weight, overweight, and obese, respectively) compared to normal-weight non-diabetic patients (p for interaction = 0.039). Conclusions: Female sex, obesity, and diabetes are significantly associated with taxine-induced CIPN. Further research is needed to identify clinical and pharmacologic strategies to prevent and mitigate CIPN in at-risk patient populations.
Anti-Invasive and Anti-Migratory Effects of Ononin on Human Osteosarcoma Cells by Limiting the MMP2/9 and EGFR-Erk1/2 Pathway
Authors: Gong Guowei , Ganesan Kumar , Xiong Qingping , Zheng Yuzhong
Published: January 2023

Osteosarcoma is a common malignancy of the bone. Due to its high metastatic properties, osteosarcoma becomes the leading cause of cancer death worldwide. Ononin is an isoflavone glycoside known to have various pharmacological properties, including antioxidant and anti-inflammatory activities. In the present study, we aimed to investigate the efficacy of ononin on osteosarcoma cell migration, invasion, and the underlying mechanisms. The in vitro anti-tumorigenic and anti-migratory properties of ononin were determined by MTT, colony formation, invasion, and migration in MG-63 and U2OS osteosarcoma cell lines. The results were compared with the standard chemotherapeutic drug, doxorubicin (DOX), as a positive control. The dose-dependent manners of ononin treatment increased the expression of apoptosis and inhibition of cell proliferation through the EGFR-Erk1/2 signaling pathways. Additionally, ononin significantly inhibited the invasion and migration of human osteosarcoma cells. For consistency, we used the MG-63-xenograft mice model to confirm the in vivo anti-tumorigenic and anti-migratory efficacy of ononin by inhibiting the protein expressions of EGFR-Erk1/2 and MMP2/9. According to the histological study, ononin had no adverse effect on the liver and kidney. Overall, our findings suggested that ononin could be a potentially effective agent against the development and metastasis of osteosarcoma.
Clinical and Immunologic Characteristics of Non-Hematologic Cancers in Patients with Inborn Errors of Immunity
Authors: Delavari Samaneh , Wang Yating , Moeini shad Tannaz , Pashangzadeh Salar , Nazari Farzad , Salami Fereshte , Abolhassani Hassan
Published: January 2023

Inborn errors of immunity (IEI) are a heterogeneous group of inherited disorders, and almost 500 genes associated with these disorders have been identified. Defects in IEI genes lead to diverse clinical manifestations including increased susceptibility to recurrent or prolonged infections, immune dysregulation phenotypes (such as severe atopy, allergy, autoimmunity, and uncontrolled inflammation, lymphoproliferation), as well as predisposition to malignancies. Although the majority of IEI patients present hematologic cancers, the characteristics of other types of cancers are not well described in these groups of patients. By investigating 5384 IEI patients registered in the Iranian national registry the clinical and immunologic phenotypes of patients with non-hematologic cancers were compared with other malignant and non-malignant patients. Solid tumors were reported <20% of malignant IEI patients (n = 27/144 patients) and appeared to be very heterogeneous by type and localization as well as molecular defects (mainly due to DNA repair defect resulted from ATM deficiency). The correlation between the type of malignancy and survival status was remarkable as patients with non-hematologic cancers survive higher than IEI patients with hematologic cancers. Our findings showed that different types of malignancy could be associated with specific entities of IEI. Therefore, the education of physicians about the risk of malignancies in IEI is required for personalized treatment and appropriate management of patients.
Systemic Oncological Treatments versus Supportive Care for Patients with Advanced Hepatobiliary Cancers: An Overview of Systematic Reviews
Authors: Bracchiglione Javier , Rodríguez-Grijalva Gerardo , Requeijo Carolina , Santero Marilina , Salazar Josefina , Salas-Gama Karla , Meade Adriana-Gabriela , Antequera Alba , Auladell-Rispau Ariadna , Quintana María Jesús , Solà Ivan , Urrútia Gerard , Acosta-Dighero Roberto , Bonfill Cosp Xavier
Published: January 2023

Background: The trade-off between systemic oncological treatments (SOTs) and UPSC in patients with primary advanced hepatobiliary cancers (HBCs) is not clear in terms of patient-centred outcomes beyond survival. This overview aims to assess the effectiveness of SOTs (chemotherapy, immunotherapy and targeted/biological therapies) versus UPSC in advanced HBCs. Methods: We searched for systematic reviews (SRs) in PubMed, EMBASE, the Cochrane Library, Epistemonikos and PROSPERO. Two authors assessed eligibility independently and performed data extraction. We estimated the quality of SRs and the overlap of primary studies, performed de novo meta-analyses and assessed the certainty of evidence for each outcome. Results: We included 18 SRs, most of which were of low quality and highly overlapped. For advanced hepatocellular carcinoma, SOTs showed better overall survival (HR = 0.62, 95% CI 0.55–0.77, high certainty for first-line therapy; HR = 0.85, 95% CI 0.79–0.92, moderate certainty for second-line therapy) with higher toxicity (RR = 1.18, 95% CI 0.87–1.60, very low certainty for first-line therapy; RR = 1.58, 95% CI 1.28–1.96, low certainty for second-line therapy). Survival was also better for SOTs in advanced gallbladder cancer. No outcomes beyond survival and toxicity could be meta-analysed. Conclusion: SOTs in advanced HBCs tend to improve survival at the expense of greater toxicity. Future research should inform other patient-important outcomes to guide clinical decision making.
Tumor Infiltrating Lymphocytes across Breast Cancer Subtypes: Current Issues for Biomarker Assessment
Authors: Valenza Carmine , Taurelli Salimbeni Beatrice , Santoro Celeste , Trapani Dario , Antonarelli Gabriele , Curigliano Giuseppe
Published: January 2023

Tumor-infiltrating lymphocytes (TILs) represent a surrogate biomarker of anti-tumor, lymphocyte-mediated immunity. In early, triple-negative breast cancer, TILs have level 1B of evidence to predict clinical outcomes. TILs represent a promising biomarker to select patients who can experience a better prognosis with de-intensified cancer treatments and derive larger benefits from immune checkpoint inhibitors. However, the assessment and the validation of TILs as a biomarker require a prospective and rigorous demonstration of its clinical validity and utility, provided reproducible analytical performance. With pending data about the prospective validation of TILs’ clinical validity to modulate treatments in early breast cancer, this review summarizes the most important current issues and future challenges related to the implementation of TILs assessments across all breast cancer subtypes and their potential integration into clinical practice.
Monitoring and Modulating Diet and Gut Microbes to Enhance Response and Reduce Toxicity to Cancer Treatment
Authors: Knisely Anne , Seo Yongwoo David , Wargo Jennifer A. , Chelvanambi Manoj
Published: January 2023

The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis. In this review, we discuss the scientific evidence on the role that gut microbes and diet play in response and toxicity to cancer treatment. We highlight studies across multiple cancer cohorts that have shown an association between particular gut microbiome signatures and an improved response to immune checkpoint blockade, chemotherapy, and adoptive cell therapies, as well as the role of particular microbes in driving treatment-related toxicity and how the microbiome can be modulated through strategies, such as fecal transplant. We also summarize the current literature that implicate high fiber and ketogenic diets in improved response rates to immunotherapy and chemotherapy, respectively. Finally, we discuss the relevance of these findings in the context of patient care, advocate for a holistic approach to cancer treatment, and comment on the next frontier of targeted gut and tumor microbiome modulation through novel therapeutics, dietary intervention, and precision-medicine approaches.
Recent Advances on Fine-Tuning Engineering Strategies of CeO2-Based Nanostructured Catalysts Exemplified by CO2 Hydrogenation Processes
Authors: Varvoutis Georgios , Lykaki Maria , Marnellos George E. , Konsolakis Michalis
Published: January 2023

Ceria-based oxides have been extensively involved in a wide range of catalytic applications due to their intriguing properties, related mostly to their superior redox features in conjunction with peculiar metal-support interaction phenomena. Most importantly, the fine-tuning of key interrelated factors, such as the size, morphology and electronic state of the catalyst’s counterparts, can exert a profound influence on the intrinsic characteristics and interfacial reactivity with pronounced implications in catalysis. The present review, while also elaborating our recent efforts in the field, aims to provide key fundamental and practical aspects in relation to the rational design and functionalization strategies of ceria-based catalysts, exemplified by the CO2 hydrogenation processes, namely, CO2 methanation and reverse water–gas shift (rWGS) reactions. Firstly, a description of the most prominent catalytically relevant features of cerium oxide is provided, focusing on reducibility and metal-support interaction phenomena, followed by a brief overview of the current status of ceria-based catalysts for various energy and environmental applications. Then, the main implications of fine-tuning engineering via either appropriate synthesis routes or aliovalent doping on key activity descriptors are thoroughly discussed and exemplified by state-of-the-art ceria-based catalysts for CO2 hydrogenation. It is clearly revealed that highly active and cost-efficient ceria-based catalytic materials can be obtained on the grounds of the proposed functionalization strategy, with comparable or even superior reactivity to that of noble metal catalysts for both the studied reactions. In a nutshell, it can be postulated that the dedicated fabrication of CeO2-based systems with augmented redox capabilities and, thus, oxygen vacancies abundance can greatly enhance the activation of gas-phase CO2 towards CO or CH4. Besides, the morphology-engineering of CeO2-based catalysts can notably affect the CO2 hydrogenation performance, by means of an optimum metal-ceria interphase based on the exposed facets, whereas doping and promotion strategies can effectively shift the reaction pathway towards the selective production of either CO or CH4. The conclusions derived from the present work can provide design and fine-tuning principles for cost-efficient, highly active and earth-abundant metal oxide systems, not only for the CO2 hydrogenation process but for various other energy and environmental applications.
Therapeutic Hypothermia after Cardiac Arrest Attenuates Hindlimb Paralysis and Damage of Spinal Motor Neurons and Astrocytes through Modulating Nrf2/HO-1 Signaling Pathway in Rats
Authors: Ahn Ji Hyeon , Lee Tae-Kyeong , Kim Dae Won , Shin Myoung Cheol , Cho Jun Hwi , Lee Jae-Chul , Tae Hyun-Jin , Park Joon Ha , Hong Seongkweon , Lee Choong-Hyun , Won Moo-Ho , Kim Yang Hee
Published: January 2023

Cardiac arrest (CA) and return of spontaneous circulation (ROSC), a global ischemia and reperfusion event, lead to neuronal damage and/or death in the spinal cord as well as the brain. Hypothermic therapy is reported to protect neurons from damage and improve hindlimb paralysis after resuscitation in a rat model of CA induced by asphyxia. In this study, we investigated roles of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the lumbar spinal cord protected by therapeutic hypothermia in a rat model of asphyxial CA. Male Sprague-Dawley rats were subjected to seven minutes of asphyxial CA (induced by injection of 2 mg/kg vecuronium bromide) and hypothermia (four hours of cooling, 33 ± 0.5 °C). Survival rate, hindlimb motor function, histopathology, western blotting, and immunohistochemistry were examined at 12, 24, and 48 h after CA/ROSC. The rats of the CA/ROSC and hypothermia-treated groups had an increased survival rate and showed an attenuated hindlimb paralysis and a mild damage/death of motor neurons located in the anterior horn of the lumbar spinal cord compared with those of the CA/ROSC and normothermia-treated groups. In the CA/ROSC and hypothermia-treated groups, expressions of cytoplasmic and nuclear Nrf2 and HO-1 were significantly higher in the anterior horn compared with those of the CA/ROSC and normothermia-treated groups, showing that cytoplasmic and nuclear Nrf2 was expressed in both motor neurons and astrocytes. Moreover, in the CA/ROSC and hypothermia-treated group, interleukin-1β (IL-1β, a pro-inflammatory cytokine) expressed in the motor neurons was significantly reduced, and astrocyte damage was apparently attenuated compared with those found in the CA/ROSC and normothermia group. Taken together, our results indicate that hypothermic therapy after CA/ROSC attenuates CA-induced hindlimb paralysis by protecting motor neurons in the lumbar spinal cord via activating the Nrf2/HO-1 signaling pathway and attenuating pro-inflammation and astrocyte damage (reactive astrogliosis).
Noncentrosymmetric Supramolecular Hydrogen-Bonded Assemblies Based on Achiral Pyrazine-Bridged Zinc(II) Coordination Polymers with Pyrazinedione Derivatives
Authors: Yoneda Ko , Kanazashi Ken , Kumagai Hitoshi , Ishikawa Ryuta , Kawata Satoshi
Published: January 2023

Reaction of M(OAc)2·xH2O (M, x = Zn, 2 and Co, 4), 1,4-dihydro-5,6-dicyano-2,3-pyrazinedione (H2CN2pyzdione), and pyrazine (pyz) affords two compounds of the same molecular formula {[M(H2O)6][M(CN2pyzdione)2(pyz)]·6H2O}n (M = Zn for 1 and Co for 2) in which discrete units of [M(H2O)6]2+ are linked to one-dimensional chains of [M(CN2pyzdione)2(pyz)]2– via multiple O–H···O hydrogen-bonding interactions and M2+-bound H2O molecules in [M(H2O)6]2+ also serve as linkers of hydrogen-bonded interstitial H2O molecules. Remarkably, 1 crystallizes in the monoclinic crystal system, the similar crystal system and unit cell parameters as 2, but with a space group distinct from 1 and 2, i.e., 1 is the noncentrosymmetric space group C2, whereas 2 is the centrosymmetric space group C2/m. This polar structure for 1 is induced by the presence of alternating arrangements of distinguishable two axial Zn–N bonds within [Zn(CN2pyzdione)2(pyz)]2– chains. Indeed, solid-state circular dichroism spectra of 1 exhibit significant Cotton effects, as evidenced by the polar space group C2. Moreover, these Cotton effects show clear temperature-dependence depending on contents of H2O molecules of 1.
Carbon Materials for Organophosphate Pesticide Sensing
Authors: Lazarević-Pašti Tamara
Published: January 2023

Organophosphates are mainly used as pesticides to protect crops from pests. Because organophosphate pesticides’ use has expanded dramatically worldwide, accurate monitoring of their concentrations in the environment and food has become of utmost importance. Once considered acutely toxic due to acetylcholinesterase inhibition, nowadays organophosphates are classified as extremely dangerous compounds, with a broad spectrum of toxicity types, by the World Health Organization. Having in mind their extensive use and diverse harmful effects, it is necessary to develop easy, rapid, and highly sensitive methods for organophosphate detection. Regardless of numerous conventional techniques for organophosphate detection, the construction of portable sensors is required to make routine analysis possible. Extensive literature on the different sensors for organophosphate detection is available. Many of them rely on the use of various carbon materials. There are many classes of carbon materials used in sensing element construction, as well as supporting materials. This review focuses on electrochemical and optical sensors based on carbon materials. Special attention is paid to the selectivity, sensitivity, stability, and reusability of reviewed sensors.
Iatrogenic Neonatal Esophageal Perforation: A European Multicentre Review on Management and Outcomes
Authors: Sorensen Eva , Yu Connie , Chuang Shu-Ling , Midrio Paola , Martinez Leopoldo , Nash Mathew , Jester Ingo , Saxena Amulya K.
Published: January 2023

Background: The aim of this multicenter retrospective study and literature review was to review management and outcomes of neonatal esophageal perforation (NEP). Methods: Protocol data were collected from four European Centers on gestational age, factors surrounding feeding tube insertion, management and outcomes. Results: The 5-year study period (2014–2018) identified eight neonates with median gestational age of 26 + 4 weeks (23 + 4–39) and median birth weight 636 g (511–3500). All patients had NEP from enterogastric tube insertions, with the perforation occurring at median 1st day of life (range 0–25). Seven/eight patients were ventilated (two/seven-high frequency oscillation). NEP became apparent on first tube placement (n = 1), first change (n = 5), and after multiple changes (n = 2). Site of perforation was known in six (distal n = 3, proximal n = 2 and middle n = 1). Diagnosis was established by respiratory distress (n = 4), respiratory distress and sepsis (n = 2) and post-insertion chest X-ray (n = 2). Management in all patients included antibiotics and parenteral nutrition with two/eight receiving steroids and ranitidine, one/eight steroids only and one/eight ranitidine only. One neonate had a gastrostomy inserted, while in another an enterogastric tube was orally successfully re-inserted. Two neonates developed pleural effusion and/or mediastinal abscess requiring chest tube. Three neonates had significant morbidities (related to prematurity) and there was one death 10 days post-perforation (related to prematurity complications). Conclusions: NEP during NGT insertion is rare even in premature infants after evaluating data from four tertiary centers and reviewing the literature. In this small cohort, conservative management seems to be safe. A larger sample size will be necessary to answer questions on efficacy of antibiotics, antacids and NGT re-insertion time frame in NEP.
Heterostructure Films of SiO2 and HfO2 for High-Power Laser Optics Prepared by Plasma-Enhanced Atomic Layer Deposition
Authors: Alam Shawon , Paul Pallabi , Beladiya Vivek , Schmitt Paul , Stenzel Olaf , Trost Marcus , Wilbrandt Steffen , Mühlig Christian , Schröder Sven , Matthäus Gabor , Nolte Stefan , Riese Sebastian , Otto Felix , Fritz Torsten , Gottwald Alexander , Szeghalmi Adriana
Published: January 2023

Absorption losses and laser-induced damage threshold (LIDT) are considered to be the major constraints for development of optical coatings for high-power laser optics. Such coatings require paramount properties, such as low losses due to optical absorption, high mechanical stability, and enhanced damage resistance, to withstand high-intensity laser pulses. In this work, heterostructures were developed by sub-nanometer thin films of SiO2 and HfO2 using the plasma-enhanced atomic layer deposition (PEALD) technique. Thin-film characterization techniques, such as spectroscopic ellipsometry, spectrophotometry, substrate curvature measurements, X-ray reflectivity, and Fourier transform infrared spectroscopy, were employed for extracting optical constants, residual stress, layer formation, and functional groups present in the heterostructures, respectively. These heterostructures demonstrate tunable refractive index, bandgap, and improved optical losses and LIDT properties. The films were incorporated into antireflection coatings (multilayer stacks and graded-index coatings) and the LIDT was determined at 355 nm wavelength by the R-on-1 method. Optical absorptions at the reported wavelengths were characterized using photothermal common-path interferometry and laser-induced deflection techniques.