bluuebunny/crossref_metadata_2025 huggingface dataset:
Podoplanin Expression Independently and Jointly with Oral Epithelial Dysplasia Grade Acts as a Potential Biomarker of Malignant Transformation in Oral Leukoplakia
Authors: Monteiro Luís , do Amaral Barbas , Delgado Leonor , Garcês Fernanda , Salazar Filomena , Pacheco José Júlio , Lopes Carlos , Warnakulasuriya Saman
Published: April 2022

Our aim was to evaluate the expression of biomarkers, CD44v6, CD147, EGFR, p53, p63, p73, p16, and podoplanin in oral leukoplakias (OL) and to assess their potential for prediction of malignant transformation (MT). We analyzed the expression of CD44v6, CD147, EGFR, p53, p63, p73, p16, and podoplanin by immunohistochemistry in 52 OL, comprised of 41 low-grade (LG) dysplasia and 11 high-grade (HG) cases. Twelve healthy normal tissues (NT) were also included. Univariate and multivariate analysis were performed to evaluate any association with MT. Variable expression among the studied markers was observed, with a significant increase of high expression from NT to LG and HG cases in CD44v6 (p = 0.002), P53 (p = 0.002), P73 (p = 0.043), and podoplanin (p < 0.001). In multivariate analysis, cases with high podoplanin score showed a significant increased risk of MT (HR of 10.148 (95% CI of 1.503–68.532; p = 0.017). Furthermore, podoplanin combined with binary dysplasia grade obtained a HR of 10.238 (95% CI of 2.06–50.889; p = 0.004). To conclude, CD44v6, p53, p73, and podoplanin showed an increasing expression along the natural history of oral carcinogenesis. Podoplanin expression independently or combined with dysplasia grade could be useful predictive markers of MT in OL.
New Insight in Histamine Functions
Authors: Sgambellone Silvia , Marri Silvia , Masini Emanuela , Lucarini Laura
Published: April 2022

The first properties of histamine (HA) that were elucidated were vasodilation and contraction of smooth muscles in the gut after stimulating gastric acid secretion and constriction of the bronchial area during anaphylaxis [...]
Aloperine: A Potent Modulator of Crucial Biological Mechanisms in Multiple Diseases
Authors: Tahir Muhammad , Ali Sakhawat , Zhang Wenting , Lv Boqiang , Qiu Wenge , Wang Juan
Published: April 2022

Aloperine is an alkaloid found in the seeds and leaves of the medicinal plant Sophora alopecuroides L. It has been used as herbal medicine in China for centuries due to its potent anti-inflammatory, antioxidant, antibacterial, and antiviral properties. Recently, aloperine has been widely investigated for its therapeutic activities. Aloperine is proven to be an effective therapeutic agent against many human pathological conditions, including cancer, viral diseases, and cardiovascular and inflammatory disorders. Aloperine is reported to exert therapeutic effects through triggering various biological processes, including cell cycle arrest, apoptosis, autophagy, suppressing cell migration, and invasion. It has also been found to be associated with the modulation of various signaling pathways in different diseases. In this review, we summarize the most recent knowledge on the modulatory effects of aloperine on various critical biological processes and signaling mechanisms, including the PI3K, Akt, NF-κB, Ras, and Nrf2 pathways. These data demonstrate that aloperine is a promising therapeutic candidate. Being a potent modulator of signaling mechanisms, aloperine can be employed in clinical settings to treat various human disorders in the future.
Potent and Broad-Spectrum Bactericidal Activity of a Nanotechnologically Manipulated Novel Pyrazole
Authors: Alfei Silvana , Caviglia Debora , Zorzoli Alessia , Marimpietri Danilo , Spallarossa Andrea , Lusardi Matteo , Zuccari Guendalina , Schito Anna Maria
Published: April 2022

The antimicrobial potency of the pyrazole nucleus is widely reported these days, and pyrazole derivatives represent excellent candidates for meeting the worldwide need for new antimicrobial compounds against multidrug-resistant (MDR) bacteria. Consequently, 3-(4-chlorophenyl)-5-(4-nitrophenylamino)-1H-pyrazole-4-carbonitrile (CR232), recently reported as a weak antiproliferative agent, was considered to this end. To overcome the CR232 water solubility issue and allow for the determination of reliable minimum inhibitory concentration values (MICs), we initially prepared water-soluble and clinically applicable CR232-loaded nanoparticles (CR232-G5K NPs), as previously reported. Here, CR232-G5K NPs have been tested on several clinically isolates of Gram-positive and Gram-negative species, including MDR strains. While for CR232 MICs ≥ 128 µg/mL (376.8 µM) were obtained, very low MICs (0.36–2.89 µM) were observed for CR232-G5K NPs against all of the considered isolates, including colistin-resistant isolates of MDR Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemases (KPCs)-producing K. pneumoniae (0.72 µM). Additionally, in time–kill experiments, CR232-G5K NPs displayed a rapid bactericidal activity with no significant regrowth after 24 h on all isolates tested, regardless of their difficult-to-treat resistance. Conjecturing a clinical use of CR232-G5K NPs, cytotoxicity experiments on human keratinocytes were performed, determining very favorable selectivity indices. Collectively, due to its physicochemical and biological properties, CR232-G5K NPs could represent a new potent weapon to treat infections sustained by broad spectrum MDR bacteria.
Phosphatidylethanolamine Deficiency and Triglyceride Overload in Perilesional Cortex Contribute to Non-Goal-Directed Hyperactivity after Traumatic Brain Injury in Mice
Authors: Hahnefeld Lisa , Vogel Alexandra , Gurke Robert , Geisslinger Gerd , Schäfer Michael K. E. , Tegeder Irmgard
Published: April 2022

Traumatic brain injury (TBI) is often complicated by long-lasting disabilities, including headache, fatigue, insomnia, hyperactivity, and cognitive deficits. In a previous study in mice, we showed that persistent non-goal-directed hyperactivity is a characteristic post-TBI behavior that was associated with low levels of endocannabinoids in the perilesional cortex. We now analyzed lipidome patterns in the brain and plasma in TBI versus sham mice in association with key behavioral parameters and endocannabinoids. Lipidome profiles in the plasma and subcortical ipsilateral and contralateral brain were astonishingly equal in sham and TBI mice, but the ipsilateral perilesional cortex revealed a strong increase in neutral lipids represented by 30 species of triacylglycerols (TGs) of different chain lengths and saturation. The accumulation of TG was localized predominantly to perilesional border cells as revealed by Oil Red O staining. In addition, hexosylceramides (HexCer) and phosphatidylethanolamines (PE and ether-linked PE-O) were reduced. They are precursors of gangliosides and endocannabinoids, respectively. High TG, low HexCer, and low PE/PE-O showed a linear association with non-goal-directed nighttime hyperactivity but not with the loss of avoidance memory. The analyses suggest that TG overload and HexCer and PE deficiencies contributed to behavioral dimensions of post-TBI psychopathology.
Post-Bariatric Hypoglycemia Is Associated with Endothelial Dysfunction and Increased Oxidative Stress
Authors: Lupoli Roberta , Calcaterra Ilenia , Annunziata Giuseppe , Tenore Giancarlo , Rainone Carmen , Schiavo Luigi , Capaldo Brunella , Di Minno Matteo Nicola Dario
Published: April 2022

Post-bariatric hypoglycemia (PBH) is a potentially serious complication that may occur after bariatric surgery. Recurrent hypoglycemia may exert detrimental effects on vascular function. The aim of the present study was to evaluate endothelial function and oxygen reactive compounds in patients who experience PBH compared with controls. We performed a cross-sectional study on subjects with PBH (HYPO) and those without (NO-HYPO), detected by seven-day continuous glucose monitoring (CGM) performed at least twelve months after bariatric surgery. We enrolled 28 post-bariatric subjects (17.9% males, mean age 40.6 ± 10.7 years), with 18 in the HYPO group and 10 in the NO-HYPO group. In the two groups, we measured brachial artery flow-mediated dilation (FMD), oxidized low-density lipoproteins (oxLDL) and reactive oxygen metabolites (D-ROMs). The HYPO group had significantly lower FMD values than the NO-HYPO group (3.8% ± 3.0 vs. 10.5% ± 2.0, p < 0.001). A significant correlation was found between FMD and the time spent in hypoglycemia (rho = −0.648, p < 0.001), the number of hypoglycemic events (rho = −0.664, p < 0.001) and the mean glucose nadir (rho = 0.532, p = 0.004). The HYPO group showed significantly higher levels of D-ROMs (416.2 ± 88.7 UCARR vs. 305.5 ± 56.3 UCARR, p < 0.001) and oxLDLs (770.5 ± 49.7 µEq/L vs. 725.1 ± 51.6 µEq/L, p = 0.035) compared to the NO-HYPO group. In the multiple linear regression analysis, hypoglycemia independently predicted FMD values (β = −0.781, p < 0.001), D-ROMs (β = 0.548, p = 0.023) and oxLDL levels (β = 0.409, p = 0.031). PBH is associated with impaired endothelial function accompanied by increased oxidative stress.
Expression of the Costimulatory Molecule B7-H4 in the Decidua and Placental Tissues in Patients with Placental Abruption
Authors: Bączkowska Monika , Dutsch-Wicherek Magdalena Maria , Przytuła Ewa , Faryna Jan , Wojtyła Cezary , Ali Mohamed , Knafel Anna , Ciebiera Michał
Published: April 2022

B7 homolog 4 protein (B7-H4), a member of the B7 family, is a immunomodulatory membrane protein. The aim of the study was to evaluate the expression of this protein in the decidua and placental tissues in case of placental abruption (PA) compared to cases of retained placental tissue (RPT) and controls. Tissue samples were obtained from 47 patients with PA, 60 patients with RPT, and 41 healthy controls. The samples were stained for B7-H4 expression, analyzed by an expert pathologist, and a semi-quantitative scale was applied. A statistical analysis revealed that the expression of B7-H4 was significantly higher in the decidua in PA samples compared to samples from patients with RPT (p-value < 0.001) and healthy controls (p-value < 0.001). The expression of B7-H4 in the placental chorionic villus was significantly higher in PA samples in relation to samples from healthy controls (p-value < 0.001) but not in relation to RPT samples (p-value = 0.0853). This finding suggests that B7-H4 might play an important role in mechanisms restoring reproductive tract homeostasis. Further research is necessary in regard to the role of B7-H4 in PA.
miR-195-5p Regulates Tight Junctions Expression via Claudin-2 Downregulation in Ulcerative Colitis
Authors: Scalavino Viviana , Piccinno Emanuele , Lacalamita Antonio , Tafaro Angela , Armentano Raffaele , Giannelli Gianluigi , Serino Grazia
Published: April 2022

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with an increased intestinal permeability. Several studies have shown that microRNAs (miRNAs) are involved in the IBD pathogenesis. Here, we aimed to functionally characterize the role of miRNAs in the regulation of intestinal permeability and barrier function. We identified 18 dysregulated miRNAs in intestinal epithelial cells (IECs) from the ulcerative colitis (UC) mice model and control mice. Among them, down-regulated miR-195-5p targeted claudin-2 (CLDN2) and was involved in impaired barrier function. CLDN2 expression levels were increased in UC mice models and negatively correlated with miR-195-5p expression. We demonstrated that gain-of-function of miR-195-5p in colonic epithelial cell lines decreased the CLDN2 levels. This modulation, in turn, downregulated claudin-1 (CLDN1) expression at protein level but not that of occludin. Our data support a previously unreported role of miR-195-5p in intestinal tight junctions’ regulation and suggest a potential pharmacological target for new therapeutic approaches in IBD.
Experimental Models for Testing the Efficacy of Pharmacological Treatments for Neonatal Hypoxic-Ischemic Encephalopathy
Authors: Landucci Elisa , Pellegrini-Giampietro Domenico E. , Facchinetti Fabrizio
Published: April 2022

Representing an important cause of long–term disability, term neonatal hypoxic-ischemic encephalopathy (HIE) urgently needs further research aimed at repurposing existing drug as well as developing new therapeutics. Since various experimental in vitro and in vivo models of HIE have been developed with distinct characteristics, it becomes important to select the appropriate preclinical screening cascade for testing the efficacy of novel pharmacological treatments. As therapeutic hypothermia is already a routine therapy for neonatal encephalopathy, it is essential that hypothermia be administered to the experimental model selected to allow translational testing of novel or repurposed drugs on top of the standard of care. Moreover, a translational approach requires that therapeutic interventions must be initiated after the induction of the insult, and the time window for intervention should be evaluated to translate to real world clinical practice. Hippocampal organotypic slice cultures, in particular, are an invaluable intermediate between simpler cell lines and in vivo models, as they largely maintain structural complexity of the original tissue and can be subjected to transient oxygen–glucose deprivation (OGD) and subsequent reoxygenation to simulate ischemic neuronal injury and reperfusion. Progressing to in vivo models, generally, rodent (mouse and rat) models could offer more flexibility and be more cost-effective for testing the efficacy of pharmacological agents with a dose–response approach. Large animal models, including piglets, sheep, and non-human primates, may be utilized as a third step for more focused and accurate translational studies, including also pharmacokinetic and safety pharmacology assessments. Thus, a preclinical proof of concept of efficacy of an emerging pharmacological treatment should be obtained firstly in vitro, including organotypic models, and, subsequently, in at least two different animal models, also in combination with hypothermia, before initiating clinical trials.
Dual-Functional Antioxidant and Antiamyloid Cerium Oxide Nanoparticles Fabricated by Controlled Synthesis in Water-Alcohol Solutions
Authors: Siposova Katarina , Huntosova Veronika , Garcarova Ivana , Shlapa Yuliia , Timashkov Illia , Belous Anatolii , Musatov Andrey
Published: April 2022

Oxidative stress is known to be associated with a number of degenerative diseases. A better knowledge of the interplay between oxidative stress and amyloidogenesis is crucial for the understanding of both, aging and age-related neurodegenerative diseases. Cerium dioxide nanoparticles (CeO2 NPs, nanoceria) due to their remarkable properties are perspective nanomaterials in the study of the processes accompanying oxidative-stress-related diseases, including amyloid-related pathologies. In the present work, we analyze the effects of CeO2 NPs of different sizes and Ce4+/Ce3+ ratios on the fibrillogenesis of insulin, SOD-like enzymatic activity, oxidative stress, biocompatibility, and cell metabolic activity. CeO2 NPs (marked as Ce1–Ce5) with controlled physical–chemical parameters, such as different sizes and various Ce4+/Ce3+ ratios, are synthesized by precipitation in water–alcohol solutions. All synthesized NPs are monodispersed and exhibit good stability in aqueous suspensions. ThT and ANS fluorescence assays and AFM are applied to monitor the insulin amyloid aggregation and antiamyloid aggregation activity of CeO2 NPs. The analyzed Ce1–Ce5 nanoparticles strongly inhibit the formation of insulin amyloid aggregates in vitro. The bioactivity is analyzed using SOD and MTT assays, Western blot, fluorescence microscopy, and flow cytometry. The antioxidative effects and bioactivity of nanoparticles are size- or valence-dependent. CeO2 NPs show great potential benefits for studying the interplay between oxidative stress and amyloid-related diseases, and can be used for verification of the role of oxidative stress in amyloid-related diseases.
Bio-Inspired Propulsion: Towards Understanding the Role of Pectoral Fin Kinematics in Manta-like Swimming
Authors: Menzer Alec , Gong Yuchen , Fish Frank E. , Dong Haibo
Published: April 2022

Through computational fluid dynamics (CFD) simulations of a model manta ray body, the hydrodynamic role of manta-like bioinspired flapping is investigated. The manta ray model motion is reconstructed from synchronized high-resolution videos of manta ray swimming. Rotation angles of the model skeletal joints are altered to scale the pitching and bending, resulting in eight models with different pectoral fin pitching and bending ratios. Simulations are performed using an in-house developed immersed boundary method-based numerical solver. Pectoral fin pitching ratio (PR) is found to have significant implications in the thrust and efficiency of the manta model. This occurs due to more optimal vortex formation and shedding caused by the lower pitching ratio. Leading edge vortexes (LEVs) formed on the bottom of the fin, a characteristic of the higher PR cases, produced parasitic low pressure that hinders thrust force. Lowering the PR reduces the influence of this vortex while another LEV that forms on the top surface of the fin strengthens it. A moderately high bending ratio (BR) can slightly reduce power consumption. Finally, by combining a moderately high BR = 0.83 with PR = 0.67, further performance improvements can be made. This enhanced understanding of manta-inspired propulsive mechanics fills a gap in our understanding of the manta-like mobuliform locomotion. This motivates a new generation of manta-inspired robots that can mimic the high speed and efficiency of their biological counterpart.
Mycelium-Based Composite Graded Materials: Assessing the Effects of Time and Substrate Mixture on Mechanical Properties
Authors: Ghazvinian Ali , Gürsoy Benay
Published: April 2022

Mycelium-based composites (MBC) are biodegradable, lightweight, and regenerative materials. Mycelium is the vegetative root of fungi through which they decompose organic matter. The proper treatment of the decomposition process results in MBC. MBC have been used in different industries to substitute common materials to address several challenges such as limited resources and large landfill waste after the lifecycle. One of the industries which started using this material is the architecture, engineering, and construction (AEC) industry. Therefore, scholars have made several efforts to introduce this material to the building industry. The cultivation process of MBC includes multiple parameters that affect the material properties of the outcome. In this paper, as a part of a larger research on defining a framework to use MBC as a structural material in the building industry, we defined different grades of MBC to address various functions. Furthermore, we tested the role of substrate mixture and the cultivation time on the mechanical behavior of the material. Our tests show a direct relationship between the density of the substrate and the mechanical strength. At the same time, there is a reverse relation between the cultivation time and the material mechanical performance.
The Structure of Bilirubin Oxidase from Bacillus pumilus Reveals a Unique Disulfide Bond for Site-Specific Direct Electron Transfer
Authors: Gihaz Shalev , Herzallh Nidaa Shrara , Cohen Yifat , Bachar Oren , Fishman Ayelet , Yehezkeli Omer
Published: April 2022

Efficient oxygen-reducing biocatalysts are essential for the development of biofuel cells or photo-bioelectrochemical applications. Bilirubin oxidase (BOD) is a promising biocatalyst for oxygen reduction processes at neutral pH and low overpotentials. BOD has been extensively investigated over the last few decades. While the enzyme’s internal electron transfer process and methods to establish electrical communication with electrodes have been elucidated, a crystal structure of BOD from bacterial origin has never been determined. Here we present the first crystal structure of BOD from Bacillus pumilus (BpBOD) at 3.5 Å resolution. Overall, BpBOD shows high homology with the fungal enzymes; however, it holds a unique surface-exposed disulfide bond between Cys229 and Cys322 residues. We present methodologies to orient the T1 site towards the electrode by coupling the reduced disulfide bond with maleimide moiety on the electrodes. The developed configurations were further investigated and revealed improved direct electron transfer rates with the electrodes. The work presented here may contribute to the construction of rationally designed bioanodes or biocathode configurations that are based on redox-active enzymes.
Neuropsychiatric Disorders in Pediatric Long COVID-19: A Case Series
Authors: Savino Rosa , Polito Anna N. , Arcidiacono Giulia , Poliseno Mariacristina , Lo Caputo Sergio
Published: April 2022

Few data are available regarding the incidence and the evolution of neuropsychiatric manifestations in children with a history of COVID-19. We herein report five consequent cases of pediatric patients with psychiatric and neurological symptoms of long COVID-19. All patients, mainly males, reported asymptomatic-to-mild COVID-19 and underwent home self-isolation. Abnormal movements, anxiety, and emotional dysregulation were the most recurrent symptoms observed from a few weeks to months after the resolution of the acute infection. A later onset was observed in younger patients. Blood tests and brain imaging resulted in negative results in all subjects; pharmacological and cognitive behavioral therapy was set. A multifactorial etiology could be hypothesized in these cases, as a result of a complex interplay between systemic and brain inflammation and environmental stress in vulnerable individuals. Longer follow-up is required to observe the evolution of neuropsychiatric manifestation in the present cohort and other young patients with previous SARS-CoV-2 infection.
The Effect of APOE ɛ4 on the Functional Connectivity in Frontoparietal Network in Hypertensive Patients
Authors: Wang Dandan , Xu Chang , Wang Wenxiao , Lu Hui , Zhang Junying , Liang Furu , Li Xin
Published: April 2022

Allele 4 of the apolipoprotein E gene (APOE ε4) and hypertension are considered risk factors for Alzheimer’s Disease (AD). The detection of differences in cognitive function and brain networks between hypertensive patients who are APOE ε4 carriers and non-carriers may help in understanding how hypertension and risk genes cumulatively impair brain function, which could provide critical insights into the genetic mechanism by which hypertension serves as a potential risk factor for cognitive decline and even AD. Using behavioral data from 233 elderly hypertensive patients and neuroimaging data from 38 of them from Beijing, China; the study aimed to assess the effects of APOE ε4 on cognition and to explore related changes in functional connectivity. Cognitively, the patients with APOE ε4 showed decreased executive function, memory and language. In the MRI sub-cohort, the frontoparietal networks in the APOE ε4 carrier group exhibited an altered pattern, mainly in the left precentral regions, inferior frontal lobe and angular gyrus. More importantly, the decline of cognitive function was correlated with abnormal FC in the left precentral regions in APOE ε4 carriers. APOE ε4 aggravated the dysfunction in frontal and parietal regions in hypertensive patients. This highlights the importance of brain protection in hypertensive patients, especially those with a genetic risk of AD.
Does Insomnia Increase the Risk of Suicide in Hospitalized Patients with Major Depressive Disorder? A Nationwide Inpatient Analysis from 2006 to 2015
Authors: Mansuri Zeeshan , Reddy Abhishek , Vadukapuram Ramu , Thootkur Mounica , Trivedi Chintan
Published: April 2022

Introduction. Insomnia is an important symptom associated with major depressive disorder (MDD). In addition, it is one of the risk factors for suicide. Studies have shown the relationship be-tween insomnia and suicidal behavior in patients with MDD. However, this association has not been evaluated in a large sample of hospitalized patients. Objectives. To evaluate the suicidal be-havior in MDD patients with insomnia compared to those without insomnia. Methods. From the National Inpatient Sample (NIS 2006–2015) database using the ICD-9 code, patients’ data were obtained with the primary diagnosis of MDD and comorbid diagnosis of insomnia disorders (MDD+I). These patients were compared with MDD patients without insomnia disorders (MDD–I) by performing a 1:2 match for the primary diagnosis code. Suicidal ideation/attempt da-ta were compared between the groups by multivariate logistic regression analysis. Results. After the diagnostic code matching, 139061 patients were included in the MDD+I group and 276496 patients in the MDD–I group. MDD+I patients were older (47 years vs. 45 years, p < 0.001) com-pared to the MDD–I group. The rate of suicidal ideation/attempt was 56.0% in the MDD+I group and 42.0% in the MDD–I group (p < 0.001). After adjusting for age, sex, race, borderline personal-ity disorders, anxiety disorders, and substance use disorders, ‘insomnia’ was associated with 1.71 times higher odds of suicidal behavior among MDD patients admitted to the hospital. (Odds ratio: 1.71, 95% confidence interval 1.60–1.82, p < 0.001). Conclusions. Insomnia among MDD patients is significantly associated with the risk of suicide. MDD patients with insomnia need to be closely monitored for suicidal behavior.
Experimental Research on the Properties and Formulation of Fly Ash Based Geopolymer Grouting Material
Authors: Zeng Qingwei , Gao Peiwei , Li Kuan , Dong Guoqing , Jin Guanglai , Sun Xuewei , Zhao Jingwei , Chen Lifeng
Published: April 2022

This paper experimentally investigated the effects of varying contents of Na2O in a modified sodium silicate, sodium silicate moduli (Ms), and contents of granulated blast furnace slag (GBFS) on the compressive strength and drying shrinkage of fly ash (FA)-based geopolymer grouting materials at different ages. X-ray diffraction (XRD), mercury intrusion porosimetry (MIP), and scanning electron microscopy–energy dispersive X-ray spectroscopy (SEM–EDS) were used to study the influences of different amounts of GBFS on the microstructure and product compositions of FA-based geopolymer grouting materials. The results show that the content of Na2O in modified sodium silicate, Ms, and the content of GBFS play a significant role in compressive strength and drying shrinkage of FA-based geopolymer grouting materials. In addition, the influence of Ms as well as the content of GBFS on the compressive strength and drying shrinkage of FA-based geopolymer grouting materials was deeply affected by curing age. The micro-performance tests and analysis clearly showed that incorporating 30 wt% GBFS can decrease the proportion of pores with large pore sizes, improve pore size distribution, and enhance the solubility of FA and further promote the formation of C-A-S-H gel within FA-based geopolymer grouting materials.
The Impacts of Greenery Systems on Indoor Thermal Environments in Transition Seasons: An Experimental Investigation
Authors: Hao Xiaoli , Liu Liping , Tan Hang , Lin Yaolin , Hu Jinhua , Yin Wei
Published: April 2022

The impacts of greenery systems (GSs) on microclimate conditions and building energy performance have been frequently investigated using experiments and simulations during the past decades, especially in summer and winter. However, few studies have focused on the performance of GSs in transition seasons. The ambient weather conditions vary with great fluctuations during transition seasons, which may result in severe oscillations in indoor environments. To investigate the impacts of GSs on indoor environments, an experiment was conducted using a contrastive test platform, which consisted of two experimental rooms, one equipped with a GS and the other without, from 1 April 2019 to 31 May 2019 in Hunan, China. Both rooms were free-running. The experimental results showed that the GS had the ability to reduce the oscillations in the indoor environment. The oscillations in indoor dry-bulb temperature (DBT) and relative humidity (RH) were reduced by 39.3% and 28.8%, respectively. The maximum daily DBT and RH ranges were, respectively, cut down by 3.5 °C and 12.4%. The maximum reductions in external and internal surface temperatures were 29.5 °C and 9.4 °C, respectively, for the GS, while the average reductions were 1.6~4.1 °C and 0.2~1.3 °C, respectively, depending on the orientation of the surfaces. The operative temperature (OT) during the daytime on sunny days was also lowered by the GS. The differences in OT between the two rooms ranged from −1.8 °C to 8.2 °C, with an average of 1.0 °C. The GS can improve the indoor thermal comfort during transition seasons. The thermal dissatisfaction was decreased by 7.9%. This lengthened the thermal comfort time by 15% across the whole day and by 28% during the daytime. This indicates reductions in air-conditioning system operating times, leading to energy savings.
A Consistent Protocol Reveals a Large Heterogeneity in the Biological Effectiveness of Proton and Carbon-Ion Beams for Various Sarcoma and Normal-Tissue-Derived Cell Lines
Authors: Yagi Masashi , Takahashi Yutaka , Minami Kazumasa , Matsuura Taeko , Nam Jin-Min , Onodera Yasuhito , Akagi Takashi , Maeda Takuya , Okimoto Tomoaki , Shirato Hiroki , Ogawa Kazuhiko
Published: April 2022

This study investigated variations in the relative biological effectiveness (RBE) values among various sarcoma and normal-tissue-derived cell lines (normal cell line) in proton beam and carbon-ion irradiations. We used a consistent protocol that specified the timing of irradiation after plating cells and detailed the colony formation assay. We examined the cell type dependence of RBE for proton beam and carbon-ion irradiations using four human sarcoma cell lines (MG63 osteosarcoma, HT1080 fibrosarcoma, SW872 liposarcoma, and SW1353 chondrosarcoma) and three normal cell lines (HDF human dermal fibroblast, hTERT-HME1 mammary gland, and NuLi-1 bronchus epithelium). The cells were irradiated with gamma rays, proton beams at the center of the spread-out Bragg peak, or carbon-ion beams at 54.4 keV/μm linear energy transfer. In all sarcoma and normal cell lines, the average RBE values in proton beam and carbon-ion irradiations were 1.08 ± 0.11 and 2.08 ± 0.36, which were consistent with the values of 1.1 and 2.13 used in current treatment planning systems, respectively. Up to 34% difference in the RBE of the proton beam was observed between MG63 and HT1080. Similarly, a 32% difference in the RBE of the carbon-ion beam was observed between SW872 and the other sarcoma cell lines. In proton beam irradiation, normal cell lines had less variation in RBE values (within 10%), whereas in carbon-ion irradiation, RBE values differed by up to 48% between hTERT-HME1 and NuLi-1. Our results suggest that specific dose evaluations for tumor and normal tissues are necessary for treatment planning in both proton and carbon-ion therapies.
Baseline Electrocardiographic and Echocardiographic Assessment May Help Predict Survival in Lung Cancer Patients—A Prospective Cardio-Oncology Study
Authors: Mędrek Sabina , Szmit Sebastian
Published: April 2022

Cardiovascular disease and cancer coexist and lead to exertional dyspnea. The aim of the study was to determine the prognostic significance of cardiac comorbidities, ECG and baseline echocardiography in lung cancer patients with varying degrees of reduced performance status. This prospective study included 104 patients with histopathologically confirmed lung cancer, pre-qualified for systemic treatment due to metastatic or locally advanced malignancy but not eligible for thoracic surgery. The patients underwent a comprehensive cardio-oncological evaluation. Overall survival negative predictors included low ECOG 2 (Eastern Cooperative Oncology Group) performance status, stage IV (bone or liver/adrenal metastases in particular), pleural effusion, the use of analgesics and among cardiac factors, two ECG parameters: atrial fibrillation (HR = 2.39) and heart rate >90/min (HR = 1.67). Among echocardiographic parameters, RVSP > 39 mmHg was a negative predictor (HR = 2.01), while RVSP < 21 mmHg and RV free wall strain < −30% were positive predictors (HR = 0.36 and HR = 0.56, respectively), whereas RV GLS < −25.5% had a borderline significance (HR = 0.59; p = 0.05). Logistical regression analysis showed ECOG = 2 significantly correlated with the following echocardiographic parameters: increasing RVSP, RV GLS, RV free wall strain and decreasing ACT, FAC (p < 0.05). Selected echocardiographic parameters may be helpful in predicting poor performance in lung cancer patients and, supplemented with ECG evaluation, broaden the possibilities of prognostic evaluation.
Influence of Esophageal Endoscopic Submucosal Dissection on the Changes of Energy Metabolism during the Perioperative Period
Authors: Kudo Sae , Chinda Daisuke , Shimoyama Tadashi , Yasuda Kohei , Akitaya Kazuki , Arai Tetsu , Miyazawa Kuniaki , Hayamizu Shiro , Yanagimachi Miyuki , Tsukamoto Toshiaki , Kaizuka Masatoshi , Sawada Yohei , Tatsuta Tetsuya , Hasui Keisuke , Kikuchi Hidezumi , Hiraga Hiroto , Sakuraba Hirotake , Mikami Tatsuya , Fukuda Shinsaku
Published: April 2022

Esophageal endoscopic submucosal dissection (ESD) is considered to be more complex than gastric ESD. This study aimed to assess the physical invasiveness of esophageal ESD during perioperative periods by measuring resting energy expenditure (REE). The factors affecting REE that could be used to identify patients requiring perioperative management were also investigated. Overall, 75 patients who had undergone esophageal ESD were prospectively enrolled. REE, body weight, and basal energy expenditure were measured on the day of and the day following ESD. The mean REE/body weight was 20.2 kcal/kg/day on the day of ESD and significantly increased to 23.0 kcal/kg/day one day after ESD. The stress factor on the day after ESD was 1.11. White blood cell, neutrophil, and C-reactive protein levels increased on the day after ESD and correlated with the changes in REE. Among the factors including age, body mass index, total resection area, operation time, and sarcopenia, only the total resection area was associated with changes in REE. In conclusion, energy metabolism increases during the perioperative period for esophageal ESD. The increase in the stress factor for esophageal ESD was higher than that in gastric and colorectal ESD. Furthermore, patients with large resection areas require greater attention in perioperative management.
Meta-Analysis of Randomized Controlled Trials on Yoga, Psychosocial, and Mindfulness-Based Interventions for Cancer-Related Fatigue: What Intervention Characteristics Are Related to Higher Efficacy?
Authors: Haussmann Alexander , Schmidt Martina , Illmann Mona , Schröter Marleen , Hielscher Thomas , Cramer Holger , Maatouk Imad , Horneber Markus , Steindorf Karen
Published: April 2022

Cancer-related fatigue (CRF) is a burdensome sequela of cancer treatments. Besides exercise, recommended therapies for CRF include yoga, psychosocial, and mindfulness-based interventions. However, interventions conducted vary widely, and not all show a significant effect. This meta-analysis aimed to explore intervention characteristics related to greater reductions in CRF. We included randomized controlled trials published before October 2021. Standardized mean differences were used to assess intervention efficacy for CRF and multimodel inference to explore intervention characteristics associated with higher efficacy. For the meta-analysis, we included 70 interventions (24 yoga interventions, 31 psychosocial interventions, and 15 mindfulness-based interventions) with 6387 participants. The results showed a significant effect of yoga, psychosocial, and mindfulness-based interventions on CRF but with high heterogeneity between studies. For yoga and mindfulness-based interventions, no particular intervention characteristic was identified to be advantageous for reducing CRF. Regarding psychosocial interventions, a group setting and work on cognition were related to higher intervention effects on CRF. The results of this meta-analysis suggest options to maximize the intervention effects of psychosocial interventions for CRF. The effects of yoga and mindfulness-based interventions for CRF appear to be independent of their design, although the limited number of studies points to the need for further research.
Azacitidine Plus Venetoclax for the Treatment of Relapsed and Newly Diagnosed Acute Myeloid Leukemia Patients
Authors: Garciaz Sylvain , Hospital Marie-Anne , Alary Anne-Sophie , Saillard Colombe , Hicheri Yosr , Mohty Bilal , Rey Jérôme , D’Incan Evelyne , Charbonnier Aude , Villetard Ferdinand , Maisano Valerio , Lombardi Laura , Ittel Antoine , Mozziconacci Marie-Joelle , Gelsi-Boyer Véronique , Vey Norbert
Published: April 2022

Venetoclax (VEN) belongs the BH3-mimetic class that selectively targets BCL-2, activating apoptosis. The combination of VEN and azacitidine (AZA) has changed the paradigm of treatment of newly diagnosed (ND) acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. There is scarce evidence for the use of VEN–AZA for relapsed or refractory (R/R) AML. We compared the outcome of 39 R/R AML and 38 ND AML patients treated between 01/20 and 12/21. The median age was 69 (22–86) and 73 (61–81) in the R/R and ND groups, respectively. Adverse cytogenetics were found in 36% of patients in the R/R group and 59% of patients in the ND group. Overall response rate was 37% in R/R AML, including 13% CR, 8% CRi, 3% PR and 13% MLFS, and 58% in the ND AML, including 32% CR, 13% CRi and 13% MLFS. Adverse cytogenetics was associated with treatment failure in the R/R group (Relative Risk = 0.13, p = 0.005). Median overall survival (OS) was 5.9 months in the R/R group and 9.4 months in the ND group. Median OS was 2.2 months in the adverse cytogenetics group versus 8.7 months in the intermediate cytogenetics group in the R/R group (p = 0.02). Median leukemia-free survival was not different between the two groups (9.4 months and 10.3 months), indicating that VEN–AZA can be an efficient salvage treatment for selected R/R AML patients. In conclusion, VEN–AZA is a promising treatment for ND AML and for selected R/R AML patients.
The Effect of Hyperthermia and Radiotherapy Sequence on Cancer Cell Death and the Immune Phenotype of Breast Cancer Cells
Authors: Sengedorj Azzaya , Hader Michael , Heger Lukas , Frey Benjamin , Dudziak Diana , Fietkau Rainer , Ott Oliver J. , Scheidegger Stephan , Barba Sergio Mingo , Gaipl Udo S. , Rückert Michael
Published: April 2022

Hyperthermia (HT) is an accepted treatment for recurrent breast cancer which locally heats the tumor to 39–44 °C, and it is a very potent sensitizer for radiotherapy (RT) and chemotherapy. However, currently little is known about how HT with a distinct temperature, and particularly, how the sequence of HT and RT changes the immune phenotype of breast cancer cells. Therefore, human MDA-MB-231 and MCF-7 breast cancer cells were treated with HT of different temperatures (39, 41 and 44 °C), alone and in combination with RT (2 × 5 Gy) in different sequences, with either RT or HT first, followed by the other. Tumor cell death forms and the expression of immune checkpoint molecules (ICMs) were analyzed by multicolor flow cytometry. Human monocyte-derived dendritic cells (moDCs) were differentiated and co-cultured with the treated cancer cells. In both cell lines, RT was the main stressor for cell death induction, with apoptosis being the prominent cell death form in MCF-7 cells and both apoptosis and necrosis in MDA-MB-231 cells. Here, the sequence of the combined treatments, either RT or HT, did not have a significant impact on the final outcome. The expression of all of the three examined immune suppressive ICMs, namely PD-L1, PD-L2 and HVEM, was significantly increased on MCF-7 cells 120 h after the treatment of RT with HT of any temperature. Of special interest for MDA-MB-231 cells is that only combinations of RT with HT of both 41 and 44 °C induced a significantly increased expression of PD-L2 at all examined time points (24, 48, 72, and 120 h). Generally, high dynamics of ICM expression can be observed after combined RT and HT treatments. There was no significant difference between the different sequences of treatments (either HT + RT or RT + HT) in case of the upregulation of ICMs. Furthermore, the co-culture of moDCs with tumor cells of any treatment had no impact on the expression of activation markers. We conclude that the sequence of HT and RT does not strongly affect the immune phenotype of breast cancer cells. However, when HT is combined with RT, it results in an increased expression of distinct immune suppressive ICMs that should be considered by including immune checkpoint inhibitors in multimodal tumor treatments with RT and HT. Further, combined RT and HT affects the immune system in the effector phase rather than in the priming phase.
A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer
Authors: Peinado-Serrano Javier , Quintanal-Villalonga Álvaro , Muñoz-Galvan Sandra , Verdugo-Sivianes Eva M. , Mateos Juan C. , Ortiz-Gordillo María J. , Carnero Amancio
Published: April 2022

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, generating an enormous economic and social impact that has not stopped growing in recent years. Cancer treatment for this neoplasm usually includes surgery, chemotherapy, molecular targeted treatments, and ionizing radiation. The prognosis in terms of overall survival (OS) and the disparate therapeutic responses among patients can be explained, to a great extent, by the existence of widely heterogeneous molecular profiles. The main objective of this study was to identify prognostic and predictive gene signatures of response to cancer treatment involving radiotherapy, which could help in making therapeutic decisions in patients with NSCLC. To achieve this, we took as a reference the differential gene expression pattern among commercial cell lines, differentiated by their response profile to ionizing radiation (radiosensitive versus radioresistant lines), and extrapolated these results to a cohort of 107 patients with NSCLC who had received radiotherapy (among other therapies). We obtained a six-gene signature (APOBEC3B, GOLM1, FAM117A, KCNQ1OT1, PCDHB2, and USP43) with the ability to predict overall survival and progression-free survival (PFS), which could translate into a prediction of the response to the cancer treatment received. Patients who had an unfavorable prognostic signature had a median OS of 24.13 months versus 71.47 months for those with a favorable signature, and the median PFS was 12.65 months versus 47.11 months, respectively. We also carried out a univariate analysis of multiple clinical and pathological variables and a bivariate analysis by Cox regression without any factors that substantially modified the HR value of the proposed gene signature.
Optical Genome Mapping as a Diagnostic Tool in Pediatric Acute Myeloid Leukemia
Authors: Suttorp Julia , Lühmann Jonathan Lukas , Behrens Yvonne Lisa , Göhring Gudrun , Steinemann Doris , Reinhardt Dirk , Neuhoff Nils von , Schneider Markus
Published: April 2022

Pediatric AML is characterized by numerous genetic aberrations (chromosomal translocations, deletions, insertions) impacting its classification for risk of treatment failure. Aberrations are described by classical cytogenetic procedures (karyotyping, FISH), which harbor limitations (low resolution, need for cell cultivation, cost-intensiveness, experienced staff required). Optical Genome Mapping (OGM) is an emerging chip-based DNA technique combining high resolution (~500 bp) with a relatively short turnaround time. Twenty-four pediatric patients with AML, bi-lineage leukemia, and mixed-phenotype acute leukemia were analyzed by OGM, and the results were compared with cytogenetics. Results were discrepant in 17/24 (70%) cases, including 32 previously unknown alterations called by OGM only. One newly detected deletion and two translocations were validated by primer walking, breakpoint-spanning PCR, and DNA sequencing. As an added benefit, in two cases, OGM identified a new minimal residual disease (MRD) marker. Comparing impact on risk stratification in de novo AML, 19/20 (95%) cases had concordant results while only OGM unraveled another high-risk aberration. Thus, OGM considerably expands the methodological spectrum to optimize the diagnosis of pediatric AML via the identification of new aberrations. Results will contribute to a better understanding of leukemogenesis in pediatric AML. In addition, aberrations identified by OGM may provide markers for MRD monitoring.
High-Performance of Electrocatalytic CO2 Reduction on Defective Graphene-Supported Cu4S2 Cluster
Authors: Zhang Qiyan , Li Yawei , Zhu Haiyan , Suo Bingbing
Published: April 2022

Electrochemical CO2 reduction reaction (CO2RR) to high-value chemicals is one of the most splendid approaches to mitigating environmental threats and energy shortage. In this study, the catalytic performance of CO2RR on defective graphene-supported Cu4S2 clusters as well as isolated Cu4Xn (X = O, S, Se; n = 2, 4) was systematically investigated based on density functional theory (DFT) computations. Calculation results revealed that the most thermodynamically feasible product is CH3OH among the C1 products on Cu4X2 clusters, in which the Cu4S2 cluster has the best activity concerning CH3OH synthesis with a limiting potential of −0.48 V. When the Cu4S2 cluster was further supported on defective graphene, the strong interaction between cluster and substrate could greatly improve the performance via tuning the electronic structure and improving the stability of the Cu4S2 cluster. The calculated free energy diagram indicated that it is also more energetically preferable for CH3OH production with a low limiting potential of −0.35 V. Besides, the defective graphene support has a significant ability to suppress the competing reactions, such as the hydrogen evolution reaction (HER) and CO and HCOOH production. Geometric structures, limiting potentials, and reduction pathways were also discussed to gain insight into the reaction mechanism and to find the minimum-energy pathway for C1 products. We hope this work will provide theoretical reference for designing and developing advanced supported Cu-based electrocatalysts for CO2 reduction.
Regional Development of Glioblastoma: The Anatomical Conundrum of Cancer Biology and Its Surgical Implication
Authors: De Luca Ciro , Virtuoso Assunta , Papa Michele , Certo Francesco , Barbagallo Giuseppe Maria Vincenzo , Altieri Roberto
Published: April 2022

Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion. Thus, glioma etiology remains largely unknown. In this review, we analyze the anatomical and biological basis of gliomagenesis considering neural stem cells, the spatiotemporal diversity of astrocytes, microglia, neurons and glutamate transporters, extracellular matrix and the peritumoral environment. The precise understanding of subpopulations constituting GBM, particularly astrocytes, is not limited to glioma stem cells (GSC) and could help in the understanding of tumor pathophysiology. The anatomical fingerprint is essential for non-invasive assessment of patients’ prognosis and correct surgical/radiotherapy planning.