bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Daily Temperatures over Andhra Pradesh, India, Using Artificial Neural Networks
Authors: Satyanarayana Gubbala Ch. , Sambasivarao Velivelli , Yasaswini Peddi , Ali Meer M.
Published: September 2023

In the recent past, Andhra Pradesh (AP) has experienced increasing trends in surface air mean temperature (SAT at a height of 2 m) because of climate change. In this paper, we attempt to estimate the SAT using the GFDL-ESM2G (Geophysical Fluid Dynamics Laboratory Earth System Model version 2G), available from the Coupled Model Intercomparison Project Phase-5 (CMIP5). This model has a mismatch with the India Meteorological Department (IMD)’s observations during April and May, which are the most heat-prone months in the state. Hence, in addition to the SAT from the model, the present paper considers other parameters, such as mean sea level pressure, surface winds, surface relative humidity, and surface solar radiation downwards, that have influenced the SAT. Since all five meteorological parameters from the GFDL-ESM2G model influence the IMD’s SAT, an artificial neural network (ANN) technique has been used to predict the SAT using the above five meteorological parameters as predictors (input) and the IMD’s SAT as the predictand (output). The model was developed using 1981–2020 data with different time lags, and results were tested for 2021 and 2022 in addition to the random testing conducted for 1981–2020. The statistical parameters between the IMD observations and the ANN estimations using GFDL-ESM2G predictions as input confirm that the SAT can be estimated accurately as described in the analysis section. The analysis conducted for different regions of AP reveals that the diurnal variations of SAT in the IMD observations and the ANN predictions over three regions (North, Central, and South AP) and overall AP compare well, with root mean square error varying between 0.97 °C and 1.33 °C. Thus, the SAT predictions provided in the GFDL-ESM2G model simulations could be improved statistically by using the ANN technique over the AP region.
Calibration of DustTrak and Low-Cost Sensors and Their Application for Assessment of Inhalation Exposures to Traffic-Related PM2.5 and PM1 in Ho Chi Minh City
Authors: Chi Nguyen Doan Thien , Ngan Tran Anh , Cong-Thanh Tran , Huy Duong Huu , Lung Shih-Chun Candice , Hien To Thi
Published: September 2023

The in-traffic microenvironment can enhance personal exposure to fine particulate matter (PM). With this study, we aimed to calibrate a DustTrak instrument (DustTrak 8533 DRX Aerosol Monitor, TSI Incorporated, Shoreview, MN, USA) and low-cost sensors (AS-LUNG-P sensors) and then assess inhalation exposure to PM2.5 and PM1 for different commuters in central areas of Ho Chi Minh City (HCM). The DustTrak instrument and low-cost sensors were calibrated using a gravimetric method under side-by-side conditions. Relationships between the DustTrak signals and PM concentrations measured by the gravimetric method were identified using simple linear regression models for PM2.5 (R2 = 0.998, p-value < 0.05) and PM1 (R2 = 0.989, p-value < 0.05). Meanwhile, PM concentrations determined by the AS-LUNG-P sensors and the gravimetric method were correlated using two-segmented linear regressions. To obtain the corresponding two-segment regression equations, the response of the AS-LUNG-P sensors was compared with the corrected DustTrak data. The coefficient of variation (CV) evaluated for all sensors was smaller than 10%, indicating that the data were applicable for particle assessment. For inhalation exposure assessment, the results showed that commuters using open transport modes, such as bikes, motorbikes, and walking, were exposed to more PM than those using closed transport modes (e.g., cars). Specifically, the bicyclists had the highest inhaled doses of PM among the open transport groups. PM exposure levels in the morning were higher than in the afternoon. Additionally, exposure levels to PM concentrations rapidly increased when passing through intersections of major roads and moderately decreased when using surgical facemasks.
Optimization of Vibrating Mesh Nebulizer Air Inlet Structure for Pulmonary Drug Delivery
Authors: Liu Yu , Chen Xiaole , Li Zhengqi , Yang Huizhen , Wang Jianwei
Published: September 2023

The vibrating mesh nebulizer (VMN) has gained popularity for its compactness and noiselessness. This study investigates the impact of different air inlet structures on the deposition fraction (DF) of droplets generated by VMNs in an idealized mouth–throat (MT) airway model. Three homemade VMNs with semi-circular inlet, symmetrical four-inlet, and multiple-orifice inlet structures were evaluated through simulations and experiments. The changes in droplet DF of 0.9% w/v concentration of nebulized sodium chloride (NaCl) droplets as a function of inertial parameters were acquired under different inhalation flow conditions. Additionally, flow field distributions in models with different inlet structures were analyzed at a steady inspiratory flow rate of 15 L/min. The results indicate that optimizing the VMN’s air inlet structure significantly enhances droplet delivery efficiency. The multiple–orifice inlet structure outperformed the other designs, directing the airflow from the inlet position to the center of the mouthpiece and then into the oral cavity, achieving a DF of up to 20% at an inhalation flow rate of 15 L/min. The region of high airflow velocity between the mouthpiece and oral cavity proved to be a favorable VMN inlet optimization, reducing direct droplet–wall collisions and improving delivery efficiency. These findings offer insights for VMN design and optimization to enhance pulmonary drug delivery effectiveness and therapeutic outcomes.
Research Advances on Nitrogen-Doped Carbon Materials in COx Hydrogenation
Authors: Deng Chao , Xu Lujing , Hu Kehao , Chen Xixi , Gao Ruxing , Zhang Leiyu , Wang Lei , Zhang Chundong
Published: September 2023

The excessive consumption of fossil fuels has resulted in massive carbon emissions and serious ecological and environmental crises. Therefore, achieving the efficient utilization of waste carbon sources is considered as an important pathway to addressing the aforementioned issues in the context of carbon neutrality. Developing and designing suitable catalyst materials has become the key to converting COx into valuable platform chemicals and value-added liquid fuels (e.g., CO, CH4, CH3OH, and C2+ hydrocarbons). A moderate interaction between nitrogen-doped carbon materials and active metals is more favorable for the progress of the COx hydrogenation reaction compared to traditional metal oxide carriers. In this work, we comprehensively summarize the synthesis methods of N-doped carbon materials and the relevant research progress in the field of COx hydrogenation. In addition, a general assessment of carbon-based catalysts for COx hydrogenation reactions, concerning the support and metal properties, the activity and product selectivity, and their interactions is systematically discussed. Finally, this review discusses the roles of N-doped carbon materials, the current challenges, and future development directions.
Genomic Landscape of Multidrug Resistance and Virulence in Enterococcus faecalis IRMC827A from a Long-Term Patient
Authors: Borgio J. Francis , AlJindan Reem , Alghourab Lujeen H. , Alquwaie Rahaf , Aldahhan Razan , Alhur Norah F. , AlEraky Doaa M. , Mahmoud Nehal , Almandil Noor B. , AbdulAzeez Sayed
Published: September 2023

We report on a highly virulent, multidrug-resistant strain of Enterococcus faecalis IRMC827A that was found colonizing a long-term male patient at a tertiary hospital in Khobar, Saudi Arabia. The E. faecalis IRMC827A strain carries several antimicrobial drug resistance genes and harbours mobile genetic elements such as Tn6009, which is an integrative conjugative element that can transfer resistance genes between bacteria and ISS1N via an insertion sequence. Whole-genome-sequencing-based antimicrobial susceptibility testing on strains from faecal samples revealed that the isolate E. faecalis IRMC827A is highly resistant to a variety of antibiotics, including tetracycline, doxycycline, minocycline, dalfopristin, virginiamycin, pristinamycin, chloramphenicol, streptomycin, clindamycin, lincomycin, trimethoprim, nalidixic acid and ciprofloxacin. The isolate IRMC827A carries several virulence factors that are significantly associated with adherence, biofilm formation, sortase-assembled pili, manganese uptake, antiphagocytosis, and spreading factor of multidrug resistance. The isolate also encompasses two mutations (G2576T and G2505A) in the 23S rRNA gene associated with linezolid resistance and three more mutations (gyrA p.S83Y, gyrA p.D759N and parC p.S80I) of the antimicrobial resistance phenotype. The findings through next-generation sequencing on the resistome, mobilome and virulome of the isolate in the study highlight the significance of monitoring multidrug-resistant E. faecalis colonization and infection in hospitalized patients. As multidrug-resistant E. faecalis is a serious pathogen, it is particularly difficult to treat and can cause fatal infections. It is important to have quick and accurate diagnostic tests for multidrug-resistant E. faecalis, to track the spread of multidrug-resistant E. faecalis in healthcare settings, and to improve targeted interventions to stop its spread. Further research is necessary to develop novel antibiotics and treatment strategies for multidrug-resistant E. faecalis infections.
Metagenomic Analysis of the Composition of Microbial Consortia Involved in Spruce Degradation over Time in Białowieża Natural Forest
Authors: Janusz Grzegorz , Mazur Andrzej , Pawlik Anna , Kołodyńska Dorota , Jaroszewicz Bogdan , Marzec-Grządziel Anna , Koper Piotr
Published: September 2023

Deadwood plays an important role in forest ecology; its degradation and, therefore, carbon assimilation is carried out by fungi and bacteria. To quantify the abundance and distribution of microbial taxa inhabiting dead spruce logs fallen over a span of 50 years and the soil beneath, we used taxonomic profiling with NGS sequencing of hypervariable DNA fragments of ITS1 and 16S V3-V4, respectively. The analysis of sequencing data revealed a high level of diversity in microbial communities participating in the degradation of spruce logs. Differences in the relative abundance of microbial taxa between the samples of the wood that died in 1974 and 2014, and of the soil in its immediate vicinity, were visible, especially at the genus level. Based on the Lefse analysis significantly higher numbers of classified bacterial taxa were observed in the wood and soil samples from 2014 (wood: 1974-18 and 2014-28 taxa; soil: 1974-8 and 2014-41 taxa) while the number of classified fungal taxa was significantly higher in the wood and soil samples from 1974 (wood: 1974-17 and 2014-9 taxa; soil: 1974-57 and 2014-28 taxa). Most of the bacterial and fungal amplicon sequence variants (ASVs) unique to wood were found in the samples from 1974, while those unique to soil were detected in the samples from 2014. The ATR-FTIR method supported by CHN analysis revealed physicochemical changes in deadwood induced by the activity of fungal and bacterial organisms.
Activation of σ1-Receptors by R-Ketamine May Enhance the Antidepressant Effect of S-Ketamine
Authors: Kalkman Hans O.
Published: September 2023

Ketamine is a racemic mixture composed of two enantiomers, S-ketamine and R-ketamine. In preclinical studies, both enantiomers have exhibited antidepressant effects, but these effects are attributed to distinct pharmacological activities. The S-enantiomer acts as an NMDA-channel blocker and as an opioid μ-receptor agonist, whereas the R-enantiomer binds to σ1-receptors and is believed to act as an agonist. As racemate, ketamine potentially triggers four biochemical pathways involving the AGC-kinases, PKA, Akt (PKB), PKC and RSK that ultimately lead to inhibitory phosphorylation of GSK3β in microglia. In patients with major depressive disorder, S-ketamine administered as a nasal spray has shown clear antidepressant activity. However, when compared to intravenously infused racemic ketamine, the response rate, duration of action and anti-suicidal activity of S-ketamine appear to be less pronounced. The σ1-protein interacts with μ-opioid and TrkB-receptors, whereas in preclinical experiments σ1-agonists reduce μ-receptor desensitization and improve TrkB signal transduction. TrkB activation occurs as a response to NMDA blockade. So, the σ1-activity of R-ketamine may not only enhance two pathways via which S-ketamine produces an antidepressant response, but it furthermore provides an antidepressant activity in its own right. These two factors could explain the apparently superior antidepressant effect observed with racemic ketamine compared to S-ketamine alone.
Predictors of Nocturnal Hypoxemic Burden in Patients Undergoing Elective Coronary Artery Bypass Grafting Surgery
Authors: Tafelmeier Maria , Blagoeva Verka-Georgieva , Trum Maximilian , Hegner Philipp , Floerchinger Bernhard , Camboni Daniele , Creutzenberg Marcus , Zeman Florian , Schmid Christof , Maier Lars Siegfried , Wagner Stefan , Linz Dominik , Baumert Mathias , Arzt Michael
Published: September 2023

Background: Nocturnal hypoxemia has been linked to increased cardiovascular morbidity and mortality. Several common diseases, such as sleep-disordered breathing (SDB), heart failure (HF), obesity, and pulmonary disease, coincide with an elevated nocturnal hypoxemic burden with and without repetitive desaturations. Research question: This study aimed to evaluate the association of relevant common diseases with distinctive metrics of nocturnal hypoxemic burden with and without repetitive desaturations in patients undergoing coronary artery bypass grafting surgery. Study design and methods: In this subanalysis of the prospective observational study, CONSIDER-AF (NCT02877745) portable SDB monitoring was performed on 429 patients with severe coronary artery disease the night before cardiac surgery. Pulse oximetry was used to determine nocturnal hypoxemic burden, as defined by total recording time spent with oxygen saturation levels < 90% (T90). T90 was further characterized as T90 due to intermittent hypoxemia (T90desaturation) and T90 due to nonspecific and noncyclic SpO2-drifts (T90non-specific). Results: Multivariable linear regression analysis identified SDB (apnea–hypopnea-index ≥ 15/h; B [95% CI]: 6.5 [0.4; 12.5], p = 0.036), obesity (8.2 [2.5; 13.9], p = 0.005), and mild-to-moderate chronic obstructive pulmonary disease (COPD, 16.7 [8.5; 25.0], p < 0.001) as significant predictors of an increased nocturnal hypoxemic burden. Diseases such as SDB, obesity and HF were significantly associated with elevated T90desaturation. In contrast, obesity and mild-to-moderate COPD were significant modulators of T90non-specific. Interpretation: SDB and leading causes for SDB, such as obesity and HF, are associated with an increased nocturnal hypoxemic burden with repetitive desaturations. Potential causes for hypoventilation syndromes, such as obesity and mild-to-moderate COPD, are linked to an increased hypoxemic burden without repetitive desaturations. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02877745.
The Role of M1 and M2 Myocardial Macrophages in Promoting Proliferation and Healing via Activating Epithelial-to-Mesenchymal Transition
Authors: Kang Shaowei , Wang Bin , Xie Yanan , Cao Xu , Wang Mei
Published: September 2023

(1) Background: The activation of sequential processes for the formation of permanent fibrotic tissue following myocardial infarction (MI) is pivotal for optimal healing of heart tissue. M1 and M2 macrophages are known to play essential roles in wound healing by the activation of cardiac fibroblasts after an episode of MI. However, the molecular and cellular mechanisms mediated by these macrophages in cellular proliferation, fibrosis, and wound healing remain unclear. (2) Methods: In the present study, we aimed to explore the mechanisms by which M1 and M2 macrophages contribute to cellular proliferation, fibrosis, and wound healing. Using both in vivo and cellular models, we examined the remodeling effects of M1 and M2 macrophages on infarcted cardiac fibroblasts and their role in promoting cardiac healing post-MI. (3) Results: Our findings indicate that M1 macrophages induce a proliferative effect on infarcted cardiac fibroblasts by exerting an anti-apoptotic effect, thereby preventing cell death. Moreover, M1 macrophages were found to activate the mechanism of epithelial-to-mesenchymal transition (EMT), resulting in wound healing and inducing the fibrotic process. The present findings suggest that M1 macrophages play a crucial role in promoting cardiac remodeling post-MI, as they activate the EMT pathway and contribute to increased collagen production and fibrotic changes. (4) Conclusions: The present study provides insights into molecular and cellular mechanisms mediated by M1 and M2 macrophages in cellular proliferation, fibrosis, and wound healing post-MI. Our findings highlight the critical role of M1 macrophages in promoting cardiac remodeling by activating the EMT pathway. Understanding these mechanisms can potentially result in the development of targeted therapies aimed at enhancing the healing process and improving outcomes following MI.
Application of Machine Learning to Predict COVID-19 Spread via an Optimized BPSO Model
Authors: Alkhammash Eman H. , Assiri Sara Ahmad , Nemenqani Dalal M. , Althaqafi Raad M. M. , Hadjouni Myriam , Saeed Faisal , Elshewey Ahmed M.
Published: September 2023

During the pandemic of the coronavirus disease (COVID-19), statistics showed that the number of affected cases differed from one country to another and also from one city to another. Therefore, in this paper, we provide an enhanced model for predicting COVID-19 samples in different regions of Saudi Arabia (high-altitude and sea-level areas). The model is developed using several stages and was successfully trained and tested using two datasets that were collected from Taif city (high-altitude area) and Jeddah city (sea-level area) in Saudi Arabia. Binary particle swarm optimization (BPSO) is used in this study for making feature selections using three different machine learning models, i.e., the random forest model, gradient boosting model, and naive Bayes model. A number of predicting evaluation metrics including accuracy, training score, testing score, F-measure, recall, precision, and receiver operating characteristic (ROC) curve were calculated to verify the performance of the three machine learning models on these datasets. The experimental results demonstrated that the gradient boosting model gives better results than the random forest and naive Bayes models with an accuracy of 94.6% using the Taif city dataset. For the dataset of Jeddah city, the results demonstrated that the random forest model outperforms the gradient boosting and naive Bayes models with an accuracy of 95.5%. The dataset of Jeddah city achieved better results than the dataset of Taif city in Saudi Arabia using the enhanced model for the term of accuracy.
Blink Reflex Examination in Patients with Amyotrophic Lateral Sclerosis Compared to Diseases Affecting the Peripheral Nervous System and Healthy Controls
Authors: Rostás Róbert , Fekete István , Horváth László , Fekete Klára
Published: September 2023

Amyotrophic lateral sclerosis (ALS) is a fatal form of neuromuscular disease. The aim of this study was to assess changes in the blink reflex (BR) parameters as a valid and easy-to-use tool in ALS patients. We assessed the BR test in patients with a definitive diagnosis of ALS, healthy volunteers, and patients with diseases affecting the peripheral nervous system. The BR was studied in 29 patients who met the Awaji criteria. Latencies were compared with our healthy controls (N = 50) and other diseases of the peripheral nervous system (N = 61). The ALS Functional Rating Scale—Revised (ALSFRS-R) was used to evaluate functional status. Significantly prolonged R2i and R2c latencies were found in the ALS group compared with the healthy control group (p < 0.001). The latencies of R1, R2i, R2c were all increased in the bulbar subtype compared to the limb-onset subtype (p < 0.05). According to our results, BR examination might be a promising tool to monitor the course of the disease or serve as a prognostic biomarker in patients with ALS, but it should be assessed in further studies. The abnormalities detected through BR might help perform earlier interventions in ALS patients and might be useful in other diseases affecting the peripheral nervous system.
Exploring Pragmatic Deficits in Relation to Theory of Mind and Executive Functions: Evidence from Individuals with Right Hemisphere Stroke
Authors: Tsolakopoulos Dimitrios , Kasselimis Dimitrios , Laskaris Nikolaos , Angelopoulou Georgia , Papageorgiou Georgios , Velonakis Georgios , Varkanitsa Maria , Tountopoulou Argyro , Vassilopoulou Sofia , Goutsos Dionysis , Potagas Constantin
Published: September 2023

Research investigating pragmatic deficits in individuals with right hemisphere damage focuses on identifying the potential mechanisms responsible for the nature of these impairments. Nonetheless, the presumed shared cognitive mechanisms that could account for these deficits have not yet been established through data-based evidence from lesion studies. This study aimed to examine the co-occurrence of pragmatic language deficits, Theory of Mind impairments, and executive functions while also exploring their associations with brain lesion sites. Twenty-five patients suffering from unilateral right hemisphere stroke and thirty-seven healthy participants were recruited for this study. The two groups were tested in pragmatics, Theory of Mind, and executive function tasks. Structural imaging data were also obtained for the identification of the lesion sites. The findings of this study suggest a potential convergence among the three aforementioned cognitive mechanisms. Moreover, we postulate a hypothesis for a neural circuitry for communication impairments observed in individuals with right hemisphere damage.
Age-Specific Effects of Visual Feature Binding
Authors: Werrmann Michelle , Niedeggen Michael
Published: September 2023

Temporary binding of visual features enables objects to be stored and maintained in the visual working memory as a singular structure, irrespective of its inherent complexity. Although working memory capacity is reduced in aging, previous behavioral studies suggest that binding is preserved. Using event-related brain potentials (ERPs), we tested whether stimulus encoding is different in younger (N = 26, mean age = 28.5) and older (N = 22; mean age = 67.4) participants in a change detection task. The processing costs of binding were defined by the difference between feature-alone (color or shape) and feature-binding (color–shape) conditions. The behavioral data revealed that discrimination ability was reduced in the feature-binding condition, and that this effect was more attenuated in older participants. A corresponding ERP effect was not found in early components related to visual feature detection and processing (posterior N1 and frontal P2). However, the late positive complex (LPC) was more often expressed in the feature-binding condition, and the increase in amplitude was more pronounced in older participants. The LPC can be related to attentional allocation processes which might support the maintenance of the more complex stimulus representation in the binding task. However, the selective neural overactivation in the encoding phase observed in older participants does not prevent swap errors in the subsequent retrieval phase.
The Effects of Cognitive Control on the Subcomponents of Language Control in Spoken and Written Productions
Authors: Yang Tingting , Lin Weihao , Zheng Guorui , Wang Ruiming
Published: September 2023

Aims: The present study aimed to investigate whether and how the subcomponents of language control during spoken and written productions were modulated by cognitive control. Method: In the current study, unbalanced Chinese–English bilinguals were recruited from a convenience sample at a university to complete the cued language naming task in spoken production and written production, which measured the local language control (as indexed by language switch costs) and the global language control (as indexed by language mixing costs and reversed language dominance effect). In addition, all the participants performed the Simon task, which measured their general inhibitory control ability by calculating the Simon effect, and performed the AX-CPT task to measure their reactive/proactive control preference by calculating their BSI score. All the data were collected using E-prime 2.0 and analyzed in R. Linear mixed-effect model analyses were conducted to reveal the similarities and differences between spoken production and written production for the first-step analysis. Then, the Simon effect and BSI scores were inserted into the mixed-effect models of the switch costs and mixing costs in spoken production and written production, respectively, to explore whether cognitive control can predict the subcomponents of bilingual control. Results: The results showed similar symmetrical switch costs in spoken and written modalities. In contrast, there was a reversed language dominance effect (in the mixed language context) and asymmetrical mixing costs in spoken production but neither in written production. Furthermore, we found that the Simon effect significantly negatively predicted the L2 mixing costs in spoken production, whereas the BSI score significantly negatively predicted both the L1 and L2 mixing costs in written production. Conclusion: The findings indicated that, for unbalanced bilinguals, local language control is shared between two modalities, while global language control is modality-independent between spoken production and written production. More importantly, the findings also suggested that global language control in spoken production relies more on the individuals’ general inhibitory control, while in written production, it relies more on their cognitive control strategy. Global language control in spoken and written productions separately engages specific aspects of cognitive control, which may account for different forms of processing in global language control between speaking and writing.
Identifying Critical Factors and Trends Leading to Fatal Accidents in Small-Scale Construction Sites in Korea
Authors: Hwang Jong-Moon , Won Jeong-Hun , Jeong Hyeon-Ji , Shin Seung-Hyeon
Published: September 2023

Small-scale construction sites in South Korea account for about 91.5% of all construction workplaces and contribute to 72.3% of the total accidents and fatalities. Safety measures at these sites are often underestimated, and proper safety education is lacking. In particular, the fatality rate is about 4.43 times higher compared to medium-/large-scale construction sites. In this study, a systematic analysis was conducted to examine the causes and trends of industrial accidents in small-scale construction sites to address these issues. This study analyzed industrial accidents in small-scale construction sites using statistical analysis, LDA topic modeling, and network analysis based on data from the Korea Occupational Safety and Health Agency (KOSHA) from 2018 to 2022. The analysis revealed that the most critical cause of accidents in small-scale construction sites is ‘Scaffolding and working platforms’, with accidents primarily involving ‘Fall’. Furthermore, various risk factors and accident trends were identified in apartment construction, new building projects, and mobile scaffolding usage. This study systematically analyzed the causes and trends of industrial accidents at small-scale construction sites, providing important evidence to enhance safety management and preventive measures. The results are expected to play a crucial role in establishing a safety culture at construction sites and ensuring the wellbeing of construction workers.
Effect on the Thermal Properties of Building Mortars with Microencapsulated Phase Change Materials for Radiant Floors
Authors: Li Guo , Xu Guoqiang , Tao Zhiyi
Published: September 2023

The use of slag silicate cement mortar as a thermal mass layer for radiant floor heating systems holds significant potential for active thermal energy storage systems in buildings. The main objective of this article is to experimentally test the thermal performance of slag silicate cement mortar thermal storage blocks after the addition of phase change materials. The present study focuses on investigating the thermal performance of thermal storage blocks made of slag silicate cement mortar that incorporates a microencapsulated phase change material (mPCM). The mPCM consists of particles of paraffin-coated resin, which are uniformly distributed in the mortar. The analysis revealed that the introduction of mPCM particles into the mortar decreases the bulk density by approximately 9.4% for every 5% increase in mPCM particles ranging from 0% to 20%. The results obtained utilizing the Hot Disk characterization method demonstrate that the mPCM particles significantly affect the thermal properties of the mortar. Particularly, the thermal conductivity and thermal diffusion coefficient of the SSC30 mortar with a 17.31 wt.% mass of mPCM particles decreased by 59% and 69%, respectively. The results of this study provide a basis for the application of RFHS end-use thermal storage layers.
MET in Non-Small-Cell Lung Cancer (NSCLC): Cross ‘a Long and Winding Road’ Looking for a Target
Authors: Spitaleri Gianluca , Trillo Aliaga Pamela , Attili Ilaria , Del Signore Ester , Corvaja Carla , Corti Chiara , Uliano Jacopo , Passaro Antonio , de Marinis Filippo
Published: September 2023

Non-Small-Cell Lung Cancer (NSCLC) can harbour different MET alterations, such as MET overexpression (MET OE), MET gene amplification (MET AMP), or MET gene mutations. Retrospective studies of surgical series of patients with MET-dysregulated NSCLC have shown worse clinical outcomes irrespective of the type of specific MET gene alteration. On the other hand, earlier attempts failed to identify the ‘druggable’ molecular gene driver until the discovery of MET exon 14 skipping mutations (METex14). METex14 are rare and amount to around 3% of all NSCLCs. Patients with METex14 NSCLC attain modest results when they are treated with immune checkpoint inhibitors (ICIs). New selective MET inhibitors (MET-Is) showed a long-lasting clinical benefit in patients with METex14 NSCLC and modest activity in patients with MET AMP NSCLC. Ongoing clinical trials are investigating new small molecule tyrosine kinase inhibitors, bispecific antibodies, or antibodies drug conjugate (ADCs). This review focuses on the prognostic role of MET, the summary of pivotal clinical trials of selective MET-Is with a focus on resistance mechanisms. The last section is addressed to future developments and challenges.
Immunotherapy-Related Oral Adverse Effects: Immediate Sequelae, Chronicity and Secondary Cancer
Authors: Elad Sharon , Yarom Noam , Zadik Yehuda
Published: September 2023

(1) Background: Immunotherapy-related adverse effects (irAEs) have been reported to manifest in oral tissues, mainly as lichenoid and non-lichenoid lesions and salivary gland dysfunction; however, the characterization of oral irAEs and their clinical impact is limited. (2) Methods: This is a retrospective clinical chart review of 14 patients with oral irAEs, describing the impact of the oral irAEs in terms of the immediate effect, treatment, chronicity of the irAEs and the development of oral cancer. (3) Results: Common symptoms were pain and dry mouth, causing no-to-severe pain and/or dry mouth sensation. The immediate sequala ranged from sensitivity to certain foods up to elimination of oral intake. Treatment included conventional palliation techniques with or without systemic steroids. Discontinuation of the immunotherapy agents was required in 6 patients. Innovative treatment modalities included photobiomodulation for oral mucosal pain relief, and salivary gland intraductal irrigations for relief of salivary gland hypofunction. Late sequala included the development of proliferative leukoplakia and oral cancer. (4) Conclusions: Patients treated with immunotherapy may develop debilitating oral irAEs. They should be followed for oral involvement so treatment may be initiated when the symptoms are mild to avoid discontinuation of the immunotherapy. Patients that develop oral lichenoid lesions should receive long-term follow-up, as they may have higher risk for oral cancer.
Hypermethylation of DNA Methylation Markers in Non-Cirrhotic Hepatocellular Carcinoma
Authors: Fu Siyu , Deger Teoman , Boers Ruben G. , Boers Joachim B. , Doukas Michael , Gribnau Joost , Wilting Saskia M. , Debes José D. , Boonstra Andre
Published: September 2023

Aberrant DNA methylation changes have been reported to be associated with carcinogenesis in cirrhotic HCC, but DNA methylation patterns for these non-cirrhotic HCC cases were not examined. Therefore, we sought to investigate DNA methylation changes on non-cirrhotic HCC using reported promising DNA methylation markers (DMMs), including HOXA1, CLEC11A, AK055957, and TSPYL5, on 146 liver tissues using quantitative methylation-specific PCR and methylated DNA sequencing. We observed a high frequency of aberrant methylation changes in the four DMMs through both techniques in non-cirrhotic HCC compared to cirrhosis, hepatitis, and benign lesions (p < 0.05), suggesting that hypermethylation of these DMMs is specific to non-cirrhotic HCC development. Also, the combination of the four DMMs exhibited 78% sensitivity at 80% specificity with an AUC of 0.85 in discriminating non-cirrhotic HCC from hepatitis and benign lesions. In addition, HOXA1 showed a higher aberrant methylation percentage in non-cirrhotic HCC compared to cirrhotic HCC (43.3% versus 13.3%, p = 0.039), which was confirmed using multivariate linear regression (p < 0.05). In summary, we identified aberrant hypermethylation changes in HOXA1, CLEC11A, AK055957, and TSPYL5 in non-cirrhotic HCC tissues compared to cirrhosis, hepatitis, and benign lesions, providing information that could be used as potentially detectable biomarkers for these unusual HCC cases in clinical practice.
Could Immune Checkpoint Disorders and EBV Reactivation Be Connected in the Development of Hematological Malignancies in Immunodeficient Patients?
Authors: Mertowska Paulina , Mertowski Sebastian , Smolak Konrad , Kita Gabriela , Guz Katarzyna , Kita Aleksandra , Pasiarski Marcin , Smok-Kalwat Jolanta , Góźdź Stanisław , Grywalska Ewelina
Published: September 2023

Primary immunodeficiencies (PIDs) and secondary immunodeficiencies (SIDs) are characterized by compromised immune function, rendering individuals susceptible to infections and potentially influencing cancer development. Epstein–Barr virus (EBV), a widespread herpesvirus, has been linked to cancer, particularly in those with weakened immune systems. This study aims to compare selected immune parameters, focusing on immune checkpoint molecules (PD-1/PD-L1, CTLA-4/CD86, CD200R/CD200), and EBV reactivation in patients with chronic lymphocytic leukemia (CLL, a representative of SIDs) and common variable immunodeficiency (CVID, a representative of PIDs). We performed a correlation analysis involving patients diagnosed with CLL, CVID, and a healthy control group. EBV reactivation was assessed using specific antibody serology and viral load quantification. Peripheral blood morphology, biochemistry, and immunophenotyping were performed, with emphasis on T and B lymphocytes expressing immune checkpoints and their serum concentrations. Our findings revealed elevated EBV reactivation markers in both CLL and CVID patients compared with healthy controls, indicating increased viral activity in immunodeficient individuals. Furthermore, immune checkpoint expression analysis demonstrated significantly altered percentages of T and B lymphocytes expressing PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200 in CLL and CVID patients. This suggests a potential interplay between immune checkpoint dysregulation and EBV reactivation in the context of immunodeficiency. In conclusion, our study underscores the intricate relationship between immune dysfunction, EBV reactivation, and immune checkpoint modulation in the context of immunodeficiency-associated cancers. The altered expression of immune checkpoints, along with heightened EBV reactivation, suggests a potential mechanism for immune evasion and tumor progression. These findings provide insights into the complex interactions that contribute to cancer development in immunocompromised individuals, shedding light on potential therapeutic targets for improved management and treatment outcomes. Further investigations are warranted to elucidate the underlying mechanisms and to explore potential interventions to mitigate cancer risk in these patient populations.
Holmium-166 Transarterial Radioembolization for the Treatment of Intrahepatic Cholangiocarcinoma: A Case Series
Authors: Vermeulen Sim , De Keukeleire Katrien , Dorny Nicole , Colle Isabelle , Van Den Bossche Bert , Nuttens Victor , Ooms Dirk , De Bondt Pieter , De Winter Olivier
Published: September 2023

Background: Transarterial radioembolization (TARE) is used to treat primary and secondary malignancies in the liver that are not amenable to curative resection. Accumulating evidence demonstrates the efficacy and safety of TARE with yttrium-90 (90Y), which is the most widely used radionuclide for TARE, and later with holmium-166 (166Ho) for various indications. However, the safety and efficacy of 166Ho TARE in patients with intrahepatic cholangiocarcinoma (ICC) remains to be studied. Methods: This was a retrospective case series study of seven consecutive patients with ICC who were treated with 166-Ho-TARE in our center. We recorded the clinical parameters and outcomes of the TARE procedures, the tumor response according to mRECIST, subsequent treatments, and adverse events. Results: Three out of the seven patients had a partial or complete response. Two patients had stable disease after the first TARE procedure, and two of the patients (one with a complete response, and one with stable disease) were alive at the time of analysis. No serious adverse events related to the procedure were recorded. Conclusions: This is the first case series reporting the safety and tumor response outcomes of 166Ho-TARE for ICC. The treatment demonstrated its versatility, allowing for reaching a high tumor dose, which is important for improving tumor response and treating patients in a palliative setting, where safety and the preservation of quality of life are paramount.
What Is Most Important to Family Caregivers When Helping Patients Make Treatment-Related Decisions: Findings from a National Survey
Authors: Bechthold Avery C. , Azuero Andres , Puga Frank , Ejem Deborah B. , Kent Erin E. , Ornstein Katherine A. , Ladores Sigrid L. , Wilson Christina M. , Knoepke Christopher E. , Miller-Sonet Ellen , Odom J. Nicholas
Published: September 2023

Prioritizing patient values—who/what matters most—is central to palliative care and critical to treatment decision making. Yet which factors are most important to family caregivers in these decisions remains understudied. Using data from a U.S. national survey of cancer caregivers (N = 1661), we examined differences in factors considered very important by caregivers when partnering with patients in cancer treatment decision making by cancer stage and caregiver sociodemographics. Fifteen factors were rated on a 4-point Likert-scale from ‘very unimportant’ to ‘very important.’ Descriptive statistics were used to characterize caregiver factors and tabulate proportions of importance for each. Generalized linear mixed effect modeling was used to examine the importance of factors by cancer stage, and chi-square analyses were performed to determine associations between caregiver sociodemographics and the five most commonly endorsed factors: quality of life (69%), physical well-being (68%), length of life (66%), emotional well-being (63%), and opinions/feelings of oncology team (59%). Significant associations (all p’s < 0.05) of small magnitude were found between the most endorsed factors and caregiver age, race, gender, and ethnicity, most especially ‘opinions/feelings of the oncology team’. Future work is needed to determine the best timing and approach for eliciting and effectively incorporating caregiver values and preferences into shared treatment decision making.
Differential Gene Expression of Checkpoint Markers and Cancer Markers in Mouse Models of Spontaneous Chronic Colitis
Authors: Ephraim Ramya , Fraser Sarah , Devereaux Jeannie , Stavely Rhian , Feehan Jack , Eri Rajaraman , Nurgali Kulmira , Apostolopoulos Vasso
Published: September 2023

The presence of checkpoint markers in cancer cells aids in immune escape. The identification of checkpoint markers and early cancer markers is of utmost importance to gain clarity regarding the relationship between colitis and progressive inflammation leading to cancer. Herein, the gene expression levels of checkpoint makers, cancer-related pathways, and cancer genes in colon tissues of mouse models of chronic colitis (Winnie and Winnie-Prolapse mice) using next-generation sequencing are determined. Winnie mice are a result of a Muc2 missense mutation. The identification of such genes and their subsequent expression and role at the protein level would enable novel markers for the early diagnosis of cancer in IBD patients. The differentially expressed genes in the colonic transcriptome were analysed based on the Kyoto Encyclopedia of Genes and Genomes pathway. The expression of several oncogenes is associated with the severity of IBD, with Winnie-Prolapse mice expressing a large number of key genes associated with development of cancer. This research presents a number of new targets to evaluate for the development of biomarkers and therapeutics.
CCl4-TMEDA-CuCl—A Novel Convenient Catalytic System for Dimerization of Terminal Acetylenes in Mild Conditions
Authors: Muzalevskiy Vasiliy M. , Shastin Alexey V. , Tirkasheva Sarvinoz I. , Ziyadullaev Odiljon E. , Parmanov Askar B. , Nenajdenko Valentine G.
Published: September 2023

A novel catalytic system for homocoupling terminal acetylenes was elaborated based on CuCl as a catalyst (10 mol%), TMEDA as a base and CCl4 as an oxidant. The influence of the solvent, base, amount of catalyst and CCl4 on the reaction was investigated. Methanol was found to be the solvent of choice. The broad synthetic scope of the reaction was demonstrated. Diynes with various substituents were prepared in up to 92% yields. The possible reaction mechanism is discussed.
Prominent COF, g-C3N4, and Their Heterojunction Materials for Selective Photocatalytic CO2 Reduction
Authors: Bika Panagiota , Papailias Ilias , Giannakopoulou Tatiana , Tampaxis Christos , Steriotis Theodore A. , Trapalis Christos , Dallas Panagiotis
Published: September 2023

New heterojunction materials (HJs) were synthesized in-situ by molecularly bonding the monomers of a triazine-based covalent organic framework (bulk COF) on the template of exfoliated carbon nitride (g-C3N4). The photocatalysts reduced carbon dioxide to carbon monoxide in aqueous dispersions under UV irradiation. The g-C3N4 showed production of 6.50 μmol CO g−1 h−1 and the bulk COF of 2.77 μmol CO g−1 h−1. The CO yield was evaluated in sustainability photoreduction cycles and their CO2 uptake capacity and isosteric heat of adsorption were estimated. All the heterojunction photocatalysts obtained ameliorated CO production rates compared to the bulk COF. Finally, the influence of the Pt co-catalyst on the photocatalytic activities was determined without the addition of any sacrificial agent, and the COF:g-C3N4 heterojunction with the ratio of 1:10 was proven to be a photocatalytic system with an optimum and selective, CO yield of 7.56 μmol g−1 h−1.
Regulation of Microglial Signaling by Lyn and SHIP-1 in the Steady-State Adult Mouse Brain
Authors: Chu Erskine , Mychasiuk Richelle , Tsantikos Evelyn , Raftery April L. , L’Estrange-Stranieri Elan , Dill Larissa K. , Semple Bridgette D. , Hibbs Margaret L.
Published: September 2023

Chronic neuroinflammation and glial activation are associated with the development of many neurodegenerative diseases and neuropsychological disorders. Recent evidence suggests that the protein tyrosine kinase Lyn and the lipid phosphatase SH2 domain-containing inositol 5′ phosphatase-1 (SHIP-1) regulate neuroimmunological responses, but their homeostatic roles remain unclear. The current study investigated the roles of Lyn and SHIP-1 in microglial responses in the steady-state adult mouse brain. Young adult Lyn−/− and SHIP-1−/− mice underwent a series of neurobehavior tests and postmortem brain analyses. The microglial phenotype and activation state were examined by immunofluorescence and flow cytometry, and neuroimmune responses were assessed using gene expression analysis. Lyn−/− mice had an unaltered behavioral phenotype, neuroimmune response, and microglial phenotype, while SHIP-1−/− mice demonstrated reduced explorative activity and exhibited microglia with elevated activation markers but reduced granularity. In addition, expression of several neuroinflammatory genes was increased in SHIP-1−/− mice. In response to LPS stimulation ex vivo, the microglia from both Lyn−/− and SHIP-1−/− showed evidence of hyper-activity with augmented TNF-α production. Together, these findings demonstrate that both Lyn and SHIP-1 have the propensity to control microglial responses, but only SHIP-1 regulates neuroinflammation and microglial activation in the steady-state adult brain, while Lyn activity appears dispensable for maintaining brain homeostasis.
The Present and Future of Optic Pathway Glioma Therapy
Authors: Dal Bello Simone , Martinuzzi Deborah , Tereshko Yan , Veritti Daniele , Sarao Valentina , Gigli Gian Luigi , Lanzetta Paolo , Valente Mariarosaria
Published: September 2023

Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas, which are aggressive cancers associated with a poor outcome. Our review aims to explore the established standards of care for both types of tumors, highlight the emerging therapeutic strategies for OPG treatment, and propose potential alternative therapies that, while originally studied in a broader glioma context, may hold promise for OPGs pending further investigation. These potential therapies encompass immunotherapy approaches, molecular-targeted therapy, modulation of the tumor microenvironment, nanotechnologies, magnetic hyperthermia therapy, cyberKnife, cannabinoids, and the ketogenic diet. Restoring visual function is a significant challenge in cases where optic nerve damage has occurred due to the tumor or its therapeutic interventions. Numerous approaches, particularly those involving stem cells, are currently being investigated as potential facilitators of visual recovery in these patients.