bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of a Rotary Transformer for Installations on Large Shafts
Authors: Toscani Nicola , Brunetti Massimo , Carmeli Maria Stefania , Castelli Dezza Francesco , Mauri Marco
Published: March 2022

Rotary transformers are adopted to transfer energy from primary to secondary in situations in which the two sides are in relative rotation. These devices are cylindrical transformers with two cores and the corresponding winding separated by an air gap. Their employment became quite convenient with the availability of power electronics, allowing the operation of electrical systems at relatively high frequencies. In particular, this paper proposes the design of a light and efficient transformer which can be used in applications involving large shafts. Moreover, a sliced arrangement for the magnetic core is proposed together with the experimental validation of this solution on a reduced-size prototype.
Geometric Design of a Face Gear Drive with Low Sliding Ratio
Authors: Sheng Wei , Zhao Jiang , Li Zhengminqing , Zhang Hong , Zhu Rupeng
Published: March 2022

A design method of low sliding ratio face gear drive is presented. The rack and gear meshing pair with a low sliding ratio is obtained by constructing the contact path. The face gear is then formed by this gear, and its tooth width characteristics are analyzed. Combined with the explicit solution of the meshing point of the tooth surface, a method to solve the sliding ratio of the proposed face gear pair is given, and the effects of relevant design parameters on the sliding ratio are analyzed. Moreover, the rationality of the tooth profile design is verified by 3D modeling and motion simulation. The proposed face gear pair has a lower sliding ratio, as well as larger tooth width, than those of traditional face gear drive (the pinion is involute spur gear) with the same basic parameters. The results of this study can provide points of reference for reducing friction and improving the mechanical efficiency of face gear drives.
Artificial Intelligence Applications on Restaging [18F]FDG PET/CT in Metastatic Colorectal Cancer: A Preliminary Report of Morpho-Functional Radiomics Classification for Prediction of Disease Outcome
Authors: Alongi Pierpaolo , Stefano Alessandro , Comelli Albert , Spataro Alessandro , Formica Giuseppe , Laudicella Riccardo , Lanzafame Helena , Panasiti Francesco , Longo Costanza , Midiri Federico , Benfante Viviana , La Grutta Ludovico , Burger Irene Andrea , Bartolotta Tommaso Vincenzo , Baldari Sergio , Lagalla Roberto , Midiri Massimo , Russo Giorgio
Published: March 2022

The aim of this study was to investigate the application of [18F]FDG PET/CT images-based textural features analysis to propose radiomics models able to early predict disease progression (PD) and survival outcome in metastatic colorectal cancer (MCC) patients after first adjuvant therapy. For this purpose, 52 MCC patients who underwent [18F]FDGPET/CT during the disease restaging process after the first adjuvant therapy were analyzed. Follow-up data were recorded for a minimum of 12 months after PET/CT. Radiomics features from each avid lesion in PET and low-dose CT images were extracted. A hybrid descriptive-inferential method and the discriminant analysis (DA) were used for feature selection and for predictive model implementation, respectively. The performance of the features in predicting PD was performed for per-lesion analysis, per-patient analysis, and liver lesions analysis. All lesions were again considered to assess the diagnostic performance of the features in discriminating liver lesions. In predicting PD in the whole group of patients, on PET features radiomics analysis, among per-lesion analysis, only the GLZLM_GLNU feature was selected, while three features were selected from PET/CT images data set. The same features resulted more accurately by associating CT features with PET features (AUROC 65.22%). In per-patient analysis, three features for stand-alone PET images and one feature (i.e., HUKurtosis) for the PET/CT data set were selected. Focusing on liver metastasis, in per-lesion analysis, the same analysis recognized one PET feature (GLZLM_GLNU) from PET images and three features from PET/CT data set. Similarly, in liver lesions per-patient analysis, we found three PET features and a PET/CT feature (HUKurtosis). In discrimination of liver metastasis from the rest of the other lesions, optimal results of stand-alone PET imaging were found for one feature (SUVbwmin; AUROC 88.91%) and two features for merged PET/CT features analysis (AUROC 95.33%). In conclusion, our machine learning model on restaging [18F]FDGPET/CT was demonstrated to be feasible and potentially useful in the predictive evaluation of disease progression in MCC.
Pollution Indexing and Health Risk Assessment of Heavy-Metals-Laden Indoor and Outdoor Dust in Elementary School Environments in Riyadh, Saudi Arabia
Authors: Alotaibi Modhi O. , Albedair Lamia A. , Alotaibi Nahaa M. , Elobeid Mudawi M. , Al-Swadi Hamed A. , Alasmary Zafer , Ahmad Munir
Published: March 2022

The prevalence of potentially toxic heavy metals (HMs)-bearing dust in the environment is posing serious health risks to humans. Therefore, the occurrence of HMs in indoor and outdoor dust samples of elementary school’s environment in Riyadh, Saudi Arabia, were reported, and associated potential human health risks were estimated in this study. Dust samples were collected from outdoor and indoor environments from eighteen elementary schools using a soft plastic brush. The mean concentrations of Cd, Co, Cu, Ni, Pb, and Zn in collected indoor dust samples were much higher (0.08, 3.45, 59.20, 15.20, 4.99, and 94.10 mg kg−1, respectively) than that of outdoor dust samples (0.07, 3.07, 42.20, 13.60, 4.57, and 62.40 mg kg−1, respectively), due to fans operation, opened windows, and resuspension of dust by children’s activities. The values of estimated enrichment factor revealed that both the outdoor and indoor dusts were moderately contaminated with Zn and Cu, while highly contaminated with Cd and Pb. However, the estimated potential ecological risks associated with HMs were lower. Health risks (non-carcinogenic and carcinogenic) calculations exhibited no potential risks of HMs in the schools’ dust toward children. However, health risks for children were determined in the following order: up to 6 years > 6–12 years > adults. Therefore, assessing the potential health risks posed by HM-contaminated dust in school environments is necessary to avoid any possible children’s health concerns.
Some Korovkin-Type Approximation Theorems Associated with a Certain Deferred Weighted Statistical Riemann-Integrable Sequence of Functions
Authors: Srivastava Hari Mohan , Jena Bidu Bhusan , Paikray Susanta Kumar
Published: March 2022

Here, in this article, we introduce and systematically investigate the ideas of deferred weighted statistical Riemann integrability and statistical deferred weighted Riemann summability for sequences of functions. We begin by proving an inclusion theorem that establishes a relation between these two potentially useful concepts. We also state and prove two Korovkin-type approximation theorems involving algebraic test functions by using our proposed concepts and methodologies. Furthermore, in order to demonstrate the usefulness of our findings, we consider an illustrative example involving a sequence of positive linear operators in conjunction with the familiar Bernstein polynomials. Finally, in the concluding section, we propose some directions for future research on this topic, which are based upon the core concept of statistical Lebesgue-measurable sequences of functions.
A Non-Standard Finite Difference Scheme for a Diffusive HIV-1 Infection Model with Immune Response and Intracellular Delay
Authors: Liu Xiao-Lan , Zhu Cheng-Cheng
Published: March 2022

In this paper, we propose and study a diffusive HIV infection model with infected cells delay, virus mature delay, abstract function incidence rate and a virus diffusion term. By introducing the reproductive numbers for viral infection R0 and for CTL immune response number R1, we show that R0 and R1 act as threshold parameter for the existence and stability of equilibria. If R0≤1, the infection-free equilibrium E0 is globally asymptotically stable, and the viruses are cleared; if R1≤11, the CTL-activated equilibrium E2 is globally asymptotically stable, and the infection is chronic with persistent CTL response. Next, we study the dynamic of the discreted system of our model by using non-standard finite difference scheme. We find that the global stability of the equilibria of the continuous model and the discrete model is not always consistent. That is, if R0≤1, or R1≤11, the global stability of the two kinds model is not consistent. Finally, numerical simulations are carried out to illustrate the theoretical results and show the effects of diffusion factors on the time-delay virus model.
Recent Advances in Bacterial Amelioration of Plant Drought and Salt Stress
Authors: Gamalero Elisa , Glick Bernard R.
Published: March 2022

The recent literature indicates that plant growth-promoting bacteria (PGPB) employ a range of mechanisms to augment a plant’s ability to ameliorate salt and drought stress. These mechanisms include synthesis of auxins, especially indoleacetic acid, which directly promotes plant growth; synthesis of antioxidant enzymes such as catalase, superoxide dismutase and peroxidase, which prevents the deleterious effects of reactive oxygen species; synthesis of small molecule osmolytes, e.g., trehalose and proline, which structures the water content within plant and bacterial cells and reduces plant turgor pressure; nitrogen fixation, which directly improves plant growth; synthesis of exopolysaccharides, which protects plant cells from water loss and stabilizes soil aggregates; synthesis of antibiotics, which protects stress-debilitated plants from soil pathogens; and synthesis of the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase, which lowers the level of ACC and ethylene in plants, thereby decreasing stress-induced plant senescence. Many of the reports of overcoming these plant stresses indicate that the most successful PGPB possess several of these mechanisms; however, the involvement of any particular mechanism in plant protection is nearly always inferred and not proven.
Functional Adaptation of Vocalization Revealed by Morphological and Histochemical Characteristics of Sonic Muscles in Blackmouth Croaker (Atrobucca nibe)
Authors: Lee Hung-Tai , Huang Bao-Quey , Liao Cheng-Hsin
Published: March 2022

Sound production in the blackmouth croaker (Atrobucca nibe) was characterized using acoustic, morphological, and histochemical methods. Their calls consisted of a train of two to seven pulses; the frequency ranged from 180 to 3000 Hz, with a dominant frequency of 326 ± 40 Hz. The duration of each call ranged from 80 to 360 ms. Male A. nibe possess a pair of bilaterally symmetric sonic muscles attached to the body wall adjacent to the swim bladder. The average diameter of the sonic muscle fibers was significantly shorter than that of the abdominal muscle fibers. Semithin sections of the sonic muscle fibers revealed a core-like structure (central core) and the radial arrangement of the sarcoplasmic reticulum and myofibrils. Numerous mitochondria were distributed within the central core and around the periphery of the fibers. Most of the fibers were identified as Type IIa on the basis of their myosin adenosine triphosphatase activities, but a few were identified as Type IIc fibers. All sonic muscle fibers exhibited strong oxidative enzyme activity and oxidative and anaerobic capabilities. The features suggest that the sonic muscles of A. nibe are morphologically and physiologically adapted for fast twitching and fatigue resistance, which support fish vocalization.
NAMPT Inhibitor and P73 Activator Represses P53 R175H Mutated HNSCC Cell Proliferation in a Synergistic Manner
Authors: Cai Bi-He , Bai Zhi-Yu , Lien Ching-Feng , Yu Si-Jie , Lu Rui-Yu , Wu Ming-Han , Wu Wei-Chen , Chen Chia-Chi , Hsu Yi-Chiang
Published: March 2022

The p53 family has the following three members: p53, p63 and p73. p53 is a tumor suppressor gene that frequently exhibits mutation in head and neck cancer. Most p53 mutants are loss-of-function (LoF) mutants, but some acquire some oncogenic function, such as gain of function (GoF). It is known that the aggregation of mutant p53 can induce p53 GoF. The p73 activators RETRA and NSC59984 have an anti-cancer effect in p53 mutation cells, but we found that p73 activators were not effective in all head and neck squamous cell carcinoma (HNSCC) cell lines, with different p53 mutants. A comparison of the gene expression profiles of several regulator(s) in mutant HNSCC cells with or without aggregation of p53 revealed that nicotinamide phosphoribosyltransferase (NAMPT) is a key regulator of mutant p53 aggregation. An NAMPT inhibitor, to reduce abnormal aggregation of mutant p53, used in combination with a p73 activator, was able to effectively repress growth in HNSCC cells with p53 GoF mutants. This study, therefore, suggests a potential combination therapy approach for HNSCC with a p53 GoF mutation.
The Effect of Heat Treatment of β-Tricalcium Phosphate-Containing Silica-Based Bioactive Aerogels on the Cellular Metabolism and Proliferation of MG63 Cells
Authors: Hegedűs Csaba , Czibulya Zsuzsanna , Tóth Ferenc , Dezső Balázs , Hegedűs Viktória , Boda Róbert , Horváth Dóra , Csík Attila , Fábián István , Tóth-Győri Enikő , Sajtos Zsófi , Lázár István
Published: March 2022

β-Tricalcium phosphate was combined with silica aerogel in composites prepared using the sol–gel technique and supercritical drying. The materials were used in this study to check their biological activity and bone regeneration potential with MG63 cell experiments. The composites were sintered in 100 °C steps in the range of 500–1000 °C. Their mechanical properties, porosities, and solubility were determined as a function of sintering temperature. Dissolution studies revealed that the released Ca-/P molar ratios appeared to be in the optimal range to support bone tissue induction. Cell viability, ALP activity, and type I collagen gene expression results all suggested that the sintering of the compound at approximately 700–800 °C as a scaffold could be more powerful in vivo to facilitate bone formation within a bone defect, compared to that documented previously by our research team. We did not observe any detrimental effect on cell viability. Both the alkaline phosphatase enzyme activity and the type I collagen gene expression were significantly higher compared with the control and the other aerogels heat-treated at different temperatures. The mesoporous silica-based aerogel composites containing β-tricalcium phosphate particles treated at temperatures lower than 1000 °C produced a positive effect on the osteoblastic activity of MG63 cells. An in vivo 6 month-long follow-up study of the mechanically strongest 1000 °C sample in rat calvaria experiments provided proof of a complete remodeling of the bone.
Structure of Some Green Tea Catechins and the Availability of Intracellular Copper Influence Their Ability to Cause Selective Oxidative DNA Damage in Malignant Cells
Authors: Farhan Mohd , Rizvi Asim , Ahmad Aamir , Aatif Mohammad , Alam Mir Waqas , Hadi Sheikh Mumtaz
Published: March 2022

The possible roles of elevated endogenous copper levels in malignant cells are becoming increasingly understood at a greater depth. Our laboratory has previously demonstrated that tea catechins have the ability to mobilize endogenous copper and undergo a Fenton-like reaction that can selectively damage cancer cells. In this communication, by using a diverse panel of malignant cell lines, we demonstrate that the ability of the catechin family [(−)-epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), (−)-epicatechin (EC), and (+)-catechin (C)] to induce apoptosis is dependent on their structure. We further confirm that reactive oxygen species (ROS) are the terminal effectors causing copper-mediated DNA damage. Our studies demonstrate the role of cellular copper transporters CTR1 and ATP7A in the survival dynamics of malignant cells post-EGCG exposure. The results, when considered together with our previous studies, highlight the critical role that copper dynamics and mobilization plays in cancer cells and paves the way for a better understanding of catechins as nutraceutical supplements for malignancies.
Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder
Authors: Marques Ana Rita , Santos João Xavier , Martiniano Hugo , Vilela Joana , Rasga Célia , Romão Luísa , Vicente Astrid Moura
Published: March 2022

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition with unclear etiology. Many genes have been associated with ASD risk, but the underlying mechanisms are still poorly understood. An important post-transcriptional regulatory mechanism that plays an essential role during neurodevelopment, the Nonsense-Mediated mRNA Decay (NMD) pathway, may contribute to ASD risk. In this study, we gathered a list of 46 NMD factors and regulators and investigated the role of genetic variants in these genes in ASD. By conducting a comprehensive search for Single Nucleotide Variants (SNVs) in NMD genes using Whole Exome Sequencing data from 1828 ASD patients, we identified 270 SNVs predicted to be damaging in 28.7% of the population. We also analyzed Copy Number Variants (CNVs) from two cohorts of ASD patients (N = 3570) and discovered 38 CNVs in 1% of cases. Importantly, we discovered 136 genetic variants (125 SNVs and 11 CNVs) in 258 ASD patients that were located within protein domains required for NMD. These gene variants are classified as damaging using in silico prediction tools, and therefore may interfere with proper NMD function in ASD. The discovery of NMD genes as candidates for ASD in large patient genomic datasets provides evidence supporting the involvement of the NMD pathway in ASD pathophysiology.
Novel Biomarkers of Inflammation for the Management of Diabetes: Immunoglobulin-Free Light Chains
Authors: Matsumori Akira
Published: March 2022

Virus infection, inflammation and genetic factors are important factors in the pathogenesis of diabetes mellitus. The nuclear factor-kappa B (NF-κB) is a family of transcription factors that bind the enhancer of the κ light chain gene of B cell immunoglobulin. NF-κB plays an essential role in the activation and development of B cells, and the activation of NF-κB is critical in the inflammation and development of diabetes mellitus. Recently, immunoglobulin-free light chain (FLC) λ was found to be increased in the sera of patients with diabetes mellitus, and the FLC λ and κ/λ ratios are more specific and sensitive markers for the diagnosis of diabetes relative to glycated hemoglobin A1c. Thus, FLCs may be promising biomarkers of inflammation that could relate to the activation of NF-κB. We suggest that NF-κB could be a target for an anti-inflammatory strategy in preventing and treating diabetes when FLCs are modified. FLCs could be a surrogate endpoint in the management of diabetes. In this review, the role of inflammation in the pathogenesis of diabetes, as well as the novel inflammatory biomarkers of FLCs for the management of diabetes, are discussed.
Applying Machine Learning with Localized Surface Plasmon Resonance Sensors to Detect SARS-CoV-2 Particles
Authors: Liang Jiawei , Zhang Wei , Qin Yu , Li Ying , Liu Gang Logan , Hu Wenjun
Published: March 2022

The sudden outbreak of COVID-19 rapidly developed into a global pandemic, which caused tens of millions of infections and millions of deaths. Although SARS-CoV-2 is known to cause COVID-19, effective approaches to detect SARS-CoV-2 using a convenient, rapid, accurate, and low-cost method are lacking. To date, most of the diagnostic methods for patients with early infections are limited to the detection of viral nucleic acids via polymerase chain reaction (PCR), or antigens, using an enzyme-linked immunosorbent assay or a chemiluminescence immunoassay. This study developed a novel method that uses localized surface plasmon resonance (LSPR) sensors, optical imaging, and artificial intelligence methods to directly detect the SARS-CoV-2 virus particles without any sample preparation. The virus concentration can be qualitatively and quantitatively detected in the range of 125.28 to 106 vp/mL through a few steps within 12 min with a limit of detection (LOD) of 100 vp/mL. The accuracy of the SARS-CoV-2 positive or negative assessment was found to be greater than 97%, and this was demonstrated by establishing a regression machine learning model for the virus concentration prediction (R2 > 0.95).
A Preliminary Report of Network Electroencephalographic Measures in Primary Progressive Apraxia of Speech and Aphasia
Authors: Utianski Rene L. , Botha Hugo , Caviness John N. , Worrell Gregory A. , Duffy Joseph R. , Clark Heather M. , Whitwell Jennifer L. , Josephs Keith A.
Published: March 2022

The objective of this study was to characterize network-level changes in nonfluent/agrammatic Primary Progressive Aphasia (agPPA) and Primary Progressive Apraxia of Speech (PPAOS) with graph theory (GT) measures derived from scalp electroencephalography (EEG) recordings. EEGs of 15 agPPA and 7 PPAOS patients were collected during relaxed wakefulness with eyes closed (21 electrodes, 10–20 positions, 256 Hz sampling rate, 1–200 Hz bandpass filter). Eight artifact-free, non-overlapping 1024-point epochs were selected. Via Brainwave software, GT weighted connectivity and minimum spanning tree (MST) measures were calculated for theta and upper and lower alpha frequency bands. Differences in GT and MST measures between agPPA and PPAOS were assessed with Wilcoxon rank-sum tests. Of greatest interest, Spearman correlations were computed between behavioral and network measures in all frequency bands across all patients. There were no statistically significant differences in GT or MST measures between agPPA and PPAOS. There were significant correlations between several network and behavioral variables. The correlations demonstrate a relationship between reduced global efficiency and clinical symptom severity (e.g., parkinsonism, AOS). This preliminary, exploratory study demonstrates potential for EEG GT measures to quantify network changes associated with degenerative speech–language disorders.
Effects of CPAP on Language Recovery in Post-Stroke Aphasia: A Review of Recent Literature
Authors: Mercer Eve , Sherfey Eleanor , Ogbu Candice , Riley Ellyn A.
Published: March 2022

Obstructive sleep apnea is highly prevalent in the post-stroke population, and has been shown to affect cognitive, neurological, and functional status. Continuous positive airway pressure (CPAP) treatment is one of the most effective interventions for obstructive sleep apnea, but compliance is often low due to confounding effects of co-occurring conditions, side effects of treatment titration procedures, and individual patient personality characteristics, perceptions, and social factors. Current research suggests that CPAP treatment for obstructive sleep apnea is not associated with significant risk and can subsequently improve post-stroke motor and neurocognitive function. However, effects of CPAP treatment on post-stroke speech and language recovery remain unclear. Post-stroke communication disorders (e.g., aphasia, dysarthria, and apraxia) are also highly prevalent in this population. Knowledge of the potential positive impact of CPAP on language recovery could contribute to patients’ motivation to comply with CPAP treatment and provide incentive for speech-language pathologists to refer patients to sleep medicine specialists. In this review of the literature, we examine the question of what effect CPAP treatment may have on post-stroke speech and language function and recovery, as well as summarize the current knowledge on cognitive, neurological, and functional effects. While this review of the literature found CPAP to have varying effects on different cognitive domains, there was not sufficient evidence to determine effects on language recovery. Further research is necessary to determine the potential effects of CPAP treatment on speech and language recovery among stroke patients.
Worry Modifies the Relationship between Locus Coeruleus Activity and Emotional Mnemonic Discrimination
Authors: Pagen Linda H. G. , Poser Benedikt A. , van Boxtel Martin P. J. , Priovoulos Nikos , van Hooren Roy W. E. , Verhey Frans R. J. , Jacobs Heidi I. L.
Published: March 2022

Background: The locus coeruleus (LC) plays a critical role in modulating emotional memory performance via widespread connections to the medial temporal lobe (MTL). Interestingly, both the LC and MTL are affected during aging. Therefore, we aimed to investigate whether worry during cognitive aging changes the relationship between memory performance and the neural activity patterns during an emotional memory task. Methods: Twenty-eight participants aged 60–83 years from the Maastricht Aging study conducted an emotional mnemonic discrimination task during a 7T fMRI-scan. We performed a robust multiple linear regression to examine the association between worry and mnemonic memory performance under different levels of arousal. Subsequently, we examined if worry modifies the relationship between neuronal activity and mnemonic memory performance. Results: We observed that under low arousal, only participants with low compared to high levels of worry benefitted from additional LC activity. Under high arousal, additional LC activity was associated with lower mnemonic memory performance. Conclusion: Our results suggest there might be an optimal involvement of the NA-system for optimal memory discrimination performance, as we observed that under low levels of worry and with lower levels of arousal, higher LC activity might be needed to achieve similar levels of optimal memory performance as achieved under higher arousal when LC activity remained lower.
Architectural Simulations on Spatio-Temporal Changes of Settlement Outdoor Thermal Environment in Guanzhong Area, China
Authors: Xin Kai , Zhao Jingyuan , Wang Tianhui , Gao Weijun , Zhang Qihui
Published: March 2022

This paper aims to provide data support for rural sustainable development through analyzing the spatio-temporal characteristics of the interactions of the outdoor thermal environment. The ordinary and representative rural settlements in the Guanzhong area were selected to analyze the dynamic process of the rural thermal environment through field measurements and numerical simulations. RMSE (root mean square error) and MAPE (mean absolute percentage) were used to verify the numerical simulation model, and physiological equivalent temperature (PET) was used to evaluate the outdoor thermal environment. Results show that the ENVI-met model reliably predicts the thermal environment of a rural settlement, as the air temperature and relative humidity values range of the RMSE and MAPE were 0.85–1.79 and 2.04–5.11%, respectively. Moreover, the air temperature rose by 3.08% and relative humidity dropped by 4.42% from 2003 to 2018 as the amount of artificial surfaces increased by 35.4% and the PET index gradually increased by 27.43% at daytime and 34.03% at nighttime. Furthermore, trees could improve the outdoor thermal environment significantly, mainly because the average air temperature decreased by 3.6% and relative humidity increased by 8%, and the PET index decreased by 12.4% and 13.1%, respectively, for daytime and nighttime. This case study is representative of rural settlements in the Guanzhong plain, and thus is an appeal to rural planners to pay attention to the thermal environment issues caused by increased artificial underlay surfaces and to focus on trees in rural areas.
Experimental Validation of the Model of Reverberation Time Prediction in a Room
Authors: Nowoświat Artur , Olechowska Marcelina
Published: March 2022

It is well known that the uncertainty of input data has a great influence on the accuracy of room acoustics simulations. The aforementioned accuracy is significantly influenced by the selection of the acoustic properties of room-delimiting materials. Moreover, simulation errors are attributed to the fact that rooms can be very irregular and sound diffusion can be uneven, and thus sound absorption can be unevenly distributed over the surfaces. Therefore, a very important element is the validation of the simulation model of interior acoustics, even when we use ready-made software dedicated to interior acoustics for the simulation. In the article, the reverberation room model simulated in the ODEON program was subjected to validation. The program is based on a hybrid method combining the ray and virtual source methods. For the validation, appropriate measurements of the reverberation time in that room were carried out. The validation was undertaken using the criterion of correct validation, consisting of comparing the value of the comparison error and the value of the validation uncertainty.
Taking Advantage of the Senescence-Promoting Effect of Olaparib after X-ray and Proton Irradiation Using the Senolytic Drug, ABT-263
Authors: Huart Camille , Fransolet Maude , Demazy Catherine , Le Calvé Benjamin , Lucas Stéphane , Michiels Carine , Wéra Anne-Catherine
Published: March 2022

Radiotherapy (RT) is a key component of cancer treatment. Although improvements have been made over the years, radioresistance remains a challenge. For this reason, a better understanding of cell fates in response to RT could improve therapeutic options to enhance cell death and reduce adverse effects. Here, we showed that combining RT (photons and protons) to noncytotoxic concentration of PARP inhibitor, Olaparib, induced a cell line-dependent senescence-like phenotype. The senescent cells were characterized by morphological changes, an increase in p21 mRNA expression as well as an increase in senescence-associated β-galactosidase activity. We demonstrated that these senescent cells could be specifically targeted by Navitoclax (ABT-263), a Bcl-2 family inhibitor. This senolytic drug led to significant cell death when combined with RT and Olaparib, while limited cytotoxicity was observed when used alone. These results demonstrate that a combination of RT with PARP inhibition and senolytics could be a promising therapeutic approach for cancer patients.
Polymerase Epsilon-Associated Ultramutagenesis in Cancer
Authors: Xing XuanXuan , Jin Ning , Wang Jing
Published: March 2022

With advances in next generation sequencing (NGS) technologies, efforts have been made to develop personalized medicine, targeting the specific genetic makeup of an individual. Somatic or germline DNA Polymerase epsilon (PolE) mutations cause ultramutated (>100 mutations/Mb) cancer. In contrast to mismatch repair-deficient hypermutated (>10 mutations/Mb) cancer, PolE-associated cancer is primarily microsatellite stable (MSS) In this article, we provide a comprehensive review of this PolE-associated ultramutated tumor. We describe its molecular characteristics, including the mutation sites and mutation signature of this type of tumor and the mechanism of its ultramutagenesis. We discuss its good clinical prognosis and elucidate the mechanism for enhanced immunogenicity with a high tumor mutation burden, increased neoantigen load, and enriched tumor-infiltrating lymphocytes. We also provide the rationale for immune checkpoint inhibitors in PolE-mutated tumors.
Tumor Immune Microenvironment in Lymphoma: Focus on Epigenetics
Authors: García-Domínguez Daniel J. , Hontecillas-Prieto Lourdes , Palazón-Carrión Natalia , Jiménez-Cortegana Carlos , Sánchez-Margalet Víctor , de la Cruz-Merino Luis
Published: March 2022

Lymphoma is a neoplasm arising from B or T lymphocytes or natural killer cells characterized by clonal lymphoproliferation. This tumor comprises a diverse and heterogeneous group of malignancies with distinct clinical, histopathological, and molecular characteristics. Despite advances in lymphoma treatment, clinical outcomes of patients with relapsed or refractory disease remain poor. Thus, a deeper understanding of molecular pathogenesis and tumor progression of lymphoma is required. Epigenetic alterations contribute to cancer initiation, progression, and drug resistance. In fact, over the past decade, dysregulation of epigenetic mechanisms has been identified in lymphomas, and the knowledge of the epigenetic aberrations has led to the emergence of the promising epigenetic therapy field in lymphoma tumors. However, epigenetic aberrations in lymphoma not only have been found in tumor cells, but also in cells from the tumor microenvironment, such as immune cells. Whereas the epigenetic dysregulation in lymphoma cells is being intensively investigated, there are limited studies regarding the epigenetic mechanisms that affect the functions of immune cells from the tumor microenvironment in lymphoma. Therefore, this review tries to provide a general overview of epigenetic alterations that affect both lymphoma cells and infiltrating immune cells within the tumor, as well as the epigenetic cross-talk between them.
Outcome of Children and Adolescents with Recurrent Classical Hodgkin Lymphoma: The Italian Experience
Authors: Garaventa Alberto , Parodi Stefano , Guerrini Giulia , Farruggia Piero , Sala Alessandra , Pillon Marta , Buffardi Salvatore , Rossi Francesca , Bianchi Maurizio , Zecca Marco , Vinti Luciana , Facchini Elena , Casini Tommaso , Bernasconi Sayla , Amoroso Loredana , D’Amico Salvatore , Provenzi Massimo , De Santis Raffaela , Sau Antonella , Muggeo Paola , Mura Rosa Maria , Haupt Riccardo , Mascarin Maurizio , Burnelli Roberta
Published: March 2022

The objective of this study was to identify prognostic factors for children and adolescents with relapsed or progressive classical Hodgkin’s lymphoma (cHL) to design salvage therapy tailored to them. We analyzed a homogeneous pediatric population, diagnosed with progressive/relapsed cHL previously enrolled in two subsequent protocols of the Italian Association of Pediatric Hematology and Oncology in the period 1996–2016. There were 272 eligible patients, 17.5% of treated patients with cHL. Overall survival (OS) and event-free survival (EFS) after a 10-year follow-up were 65.3% and 53.3%, respectively. Patients with progressive disease (PD), advanced stage at recurrence, and ≥5 involved sites showed a significantly worse OS. PD, advanced stage, and extra-nodal involvement at recurrence were significantly associated with a poorer EFS. Multivariable analysis identified three categories for OS based on the type of recurrence and number of localizations: PD and ≥5 sites: OS 34%; PD and <5 sites: OS 56.5%; relapses: OS 73.6%. Four categories were obtained for EFS based on the type of recurrence and stage: PD and stage 3–4: EFS 25.5%; PD and stage 1–2: EFS 43%; relapse and stage 3–4: EFS 55.4%; relapse and stage 1–2: EFS 72.1%. Patients with PD, in advanced stage, or with ≥5 involved sites had a very poor survival and they should be considered refractory to first- and second-line standard chemotherapy. Probably, they should be considered for more innovative approaches since the first progression. Conversely, patients who relapsed later with localized disease had a better prognosis, and they could be considered for a conservative approach.
Degradation of Ibuprofen by the Electro/Fe3+/Peroxydisulfate Process: Reactive Kinetics, Degradation Products and Mechanism
Authors: Qiu Na , Shen Chanchan , Liu Yongxia , Li Xiuqing , Jia Guangyin , Qin Jingping , Wang Xinglei
Published: March 2022

Ibuprofen (IBU), a nonsteroidal anti-inflammatory drug, is one of the most widely used and frequently detected pharmaceuticals and personal care products in water bodies. This study examined the IBU degradation in aquatic solutions via ferric ion activated peroxydisulfate (PDS) coupled with electro-oxidation (EC/Fe3+/PDS). The degradation mechanisms involved three synergistic reactions in the EC/Fe3+/PDS system, including: (1) the electro-oxidation; (2) SO4•− generated from the activation of PDS by ferrous ions formed via cathodic reduction; (3) SO4•− generated from the electron transfer reaction. The radical scavenging experiments indicated that SO4•− and •OH dominated the oxidation process. The effects of the applied current density, PDS concentration, Fe3+ dosage, initial IBU concentration and initial pH as well as inorganic anions and humic acid on the degradation efficiency, were studied, and the degradation process of IBU followed the pseudo-first-order kinetic model. About 99.37% of IBU was removed in 60 min ((Fe3+ concentration) = 2.0 mM, (PDS concentration) = 12 mM, (initial IBU concentration) = 30 mg/L, current density = 15 mA/cm2, initial pH = 3). Finally, seven intermediate compounds were identified and probable IBU degradation pathways in the EC/Fe3+/PDS system were speculated.
Molecular Characterization of Portuguese Patients with Hereditary Cerebellar Ataxia
Authors: Santos Mariana , Damásio Joana , Carmona Susana , Neto João Luís , Dehghani Nadia , Guedes Leonor Correia , Barbot Clara , Barros José , Brás José , Sequeiros Jorge , Guerreiro Rita
Published: March 2022

Hereditary cerebellar ataxia (HCA) comprises a clinical and genetic heterogeneous group of neurodegenerative disorders characterized by incoordination of movement, speech, and unsteady gait. In this study, we performed whole-exome sequencing (WES) in 19 families with HCA and presumed autosomal recessive (AR) inheritance, to identify the causal genes. A phenotypic classification was performed, considering the main clinical syndromes: spastic ataxia, ataxia and neuropathy, ataxia and oculomotor apraxia (AOA), ataxia and dystonia, and ataxia with cognitive impairment. The most frequent causal genes were associated with spastic ataxia (SACS and KIF1C) and with ataxia and neuropathy or AOA (PNKP). We also identified three families with autosomal dominant (AD) forms arising from de novo variants in KIF1A, CACNA1A, or ATP1A3, reinforcing the importance of differential diagnosis (AR vs. AD forms) in families with only one affected member. Moreover, 10 novel causal-variants were identified, and the detrimental effect of two splice-site variants confirmed through functional assays. Finally, by reviewing the molecular mechanisms, we speculated that regulation of cytoskeleton function might be impaired in spastic ataxia, whereas DNA repair is clearly associated with AOA. In conclusion, our study provided a genetic diagnosis for HCA families and proposed common molecular pathways underlying cerebellar neurodegeneration.
Iron Regulatory Protein 1 Inhibits Ferritin Translation Responding to OsHV-1 Infection in Ark Clams, Scapharca Broughtonii
Authors: Huang Bowen , Zhang Xiang , Liu Qin , Bai Changming , Li Chen , Wang Chongming , Xin Lusheng
Published: March 2022

Elemental iron is an indispensable prosthetic group of DNA replication relative enzymes. The upregulation of ferritin translation by iron regulatory proteins (IRP1) in host cells is a nutritional immune strategy to sequester available iron to pathogens. The efficient replication of Ostreid herpesvirus 1 (OsHV-1), a lethal dsDNA virus among bivalves, depends on available iron. OsHV-1 infection was found to trigger iron limitation in ark clams; however, it is still an enigma how OsHV-1 successfully conducted rapid replication, escaping host iron limitations. In this study, we identified the IRP1 protein (designated as SbIRP-1) in the ark clam (Scapharca broughtonii) and found it could bind to the iron-responsive element (IRE) of ferritin (SbFn) mRNA based on electrophoretic mobility shift assay (EMSA). Knockdown of SbIRP-1 expression (0.24 ± 1.82-fold of that in NC group, p < 0.01) by RNA interference resulted in the accumulation of SbFn in hemocytes (1.79 ± 0.01-fold, p < 0.01) post-24 h of enhanced RNA interference injection. During OsHV-1 infection, SbFn mRNA was significantly upregulated in hemocytes from 24 h to 60 h, while its protein level was significantly reduced from 24 h to 48 h, with the lowest value at 36 h post-infection (0.11 ± 0.01-fold, p < 0.01). Further analysis by RNA immunoprecipitation assays showed that OsHV-1 could enhance the binding of SbIRP-1 with the SbFn IRE, which was significantly increased (2.17 ± 0.25-fold, p < 0.01) at 36 h post-infection. Consistently, SbIRP-1 protein expression was significantly increased in hemocytes from 12 h to 48 h post OsHV-1 infection (p < 0.01). In conclusion, the results suggest that OsHV-1 infection could suppress post-transcriptional translation of SbFn through the regulation of SbIRP-1, which likely contributes to OsHV-1 evasion of SbFn-mediating host iron limitation.
Enantiopure Cyclometalated Rh(III) and Ir(III) Complexes Displaying Rigid Configuration at Metal Center: Design, Structures, Chiroptical Properties and Role of the Iodide Ligand
Authors: Groué Antoine , Tranchier Jean-Philippe , Gontard Geoffrey , Jean Marion , Vanthuyne Nicolas , Amouri Hani
Published: March 2022

Enantiopure N-heterocyclic carbene half-sandwich metal complexes of the general formula [Cp*M(C^C:)I] (M = Rh, Ir; C^C: = NI-NHC; NI-H = Naphthalimide; NHC = N-heterocyclic carbene) are reported. The rhodium compound was obtained as a single isomer displaying six membered metallacycle and was resolved on chiral column chromatography to the corresponding enantiomers (S)-[Cp*Rh(C^C:)I] (S)-2 and (R)-[Cp*Rh(C^C:)I] (R)-2. The iridium congener, however, furnishes a pair of regioisomers, which were resolved into (S)-[Cp*Ir(C^C:)I] (S)-3 and (R)-[Cp*Ir(C^C:)I] (R)-3 and (S)-[Cp*Ir(C^C:)I] (S)-4 and (R)-[Cp*Ir(C^C:)I] (R)-4. These regioisomers differ from each other, only by the size of the metallacycle; five-membered for 3 and six-membered for 4. The molecular structures of (S)-2 and (S)-4 are reported. Moreover, the chiroptical properties of these compounds are presented and discussed. These compounds display exceptional stable configurations at the metal center in solution with enantiomerization barrier ΔG≠ up to 124 kJ/mol. This is because the nature of the naphthalimide-NHC clamp ligand and the iodide ligand contribute to their configuration’s robustness. In contrast to related complexes reported in the literature, which are often labile in solution.
A Comparative Study of Aqueous and Non-Aqueous Solvents to Be Used in Low-Temperature Serial Molecular–Electronic Sensors
Authors: Zaitsev Dmitry , Egorov Ivan , Agafonov Vadim
Published: March 2022

This paper presents the experimental results of studying the samples of the electrochemical sensors of motion parameters on the base of Molecular Electronics Technology (MET). The sensors with microelectromechanical (MEMS) electrode assembly use electrolytes based on aqueous and non-aqueous solutions of potassium and lithium iodides. Electrolyte solutions contain impurities of ionic liquids and alcohols to achieve stable low-temperature operation and acceptable technical parameters of serial devices. The dependence of the general sensitivity and the shape of the amplitude-frequency characteristic on temperature have been studied. For the marginally acceptable samples, which had an acceptable temperature dependence of the conversion coefficient and low activation energies for the diffusion coefficient, the level of self-noise was found. The activation energy of the electrolyte diffusion coefficient was determined based on the analysis of the dependence of the background current on temperature. A conclusion was made regarding the possible prospects for using the studied solutions and components for operation in serial devices.
Exploring the Mechanisms Underlying the Effectiveness of Psychosocial Aftercare in Pediatric Chronic Pain Treatment: A Qualitative Approach
Authors: Dogan Meltem , Hartenstein-Pinter Almut , Lopez Lumbi Susanne , Blankenburg Markus , Frühwald Michael C. , Ahnert Rosemarie , Braun Sarah , Marschall Ursula , Zernikow Boris , Wager Julia
Published: March 2022

A newly developed specialized psychosocial aftercare program (PAC) for pediatric patients with chronic pain following an intensive interdisciplinary pain treatment (IIPT) was found to be significantly more effective than IIPT alone. This qualitative study aimed to gain further insight into the mechanisms and prerequisites for the effectiveness of this specialized aftercare program. We conducted structured telephone interviews with patients, parents, and health care professionals conducting PAC. A total of 16 interviews were conducted—seven interviews with parents, six interviews with patients, and three interviews with health care professionals—and transcribed verbatim. Data were analyzed using reflexive thematic analysis. Four major themes consisting of 20 subcategories were identified, namely (1) frame conditions, (2) person factors, (3) stabilization and (4) catalyst. The foundations of treatment success are frame conditions, such as flexibility or constancy, and person factors, such as respect or expertise. Based on these foundations, stabilization is achieved through security, mediation, orientation and support. Altogether, these components of PAC reveal their potential as catalysts for further improvement even after discharge from IIPT. Overall, patients and their families emphasized widespread personal relevance and acceptance of the PAC program. The findings of this study may be employed in the development of other aftercare programs or interventions involving families in the context of psychotherapeutic and psychosocial health care.
Prevalence, Trends, and Outcomes of Pulmonary Embolism Treated with Mechanical and Surgical Thrombectomy from a Nationwide Inpatient Sample
Authors: Raghupathy Shalini , Barigidad Achala Prashant , Doorgen Raydiene , Adak Shrestha , Malik Rohma Rafique , Parulekar Gaurav , Patel Jeet Janak , Lanka Santh Prakash , Varghese George Mohan , Rashid Mohammed , Patel Urvish , Patel Achint , Hsieh Ya-Ching
Published: March 2022

Pulmonary embolism (PE) is the third most common vascular disease in the US, a frequently underdiagnosed and potentially fatal condition where embolic material blocks one or more pulmonary arteries impairing blood flow. In this study, we aim to describe the prevalence, outcomes, and predictors of mortality of PE patients treated with mechanical (MT) and surgical thrombectomy (ST). This is a retrospective study using the Agency for Healthcare Research and Quality’s HCUP NIS data from 2010–2018. We used the ninth and tenth revisions of the International Classification of Diseases clinical modification codes (ICD-9-CM and ICD-10-CM) to identify patients admitted with a primary diagnosis of PE (ICD-10-CM codes I26.02, I26.09, I26.92, I26.93, I26.94, and I26.99; ICD-9-CM codes 415.11, 415.13, and 415.19). We extracted demographics, hospital-level, and patient-level characteristics, and defined the severity of comorbid conditions using Deyo modification of the Elixhauser Comorbidity Index. The primary outcomes of interest were the utilization trends of PE (treated with MT and ST); the secondary outcomes were mortality, discharge to facility, peri-procedural complications, and length of hospital (LOS) stay; the tertiary outcome was to identify the predictors of in-hospital mortality. From 2010–2018, there were 1,627,718 hospitalizations for PE, of which 6531 (0.39%) underwent MT and 3465 (0.21%) underwent ST. The utilization trend of MT increased from 336 (0.20%) in 2010 to 1655 (0.87%) in 2018; the utilization trend of ST was 260 (0.15%) in 2010 and 430 (0.23%) in 2018. The unadjusted in-hospital mortality for MT was 9.1% with the mean LOS being 7(±0.3) days; for ST, mortality was 13.9% with a mean LOS of 13(±0.4) days. The occurrences of periprocedural complications for MT and ST were as follows: invasive mechanical ventilation was 13.8% and 32%; cardiopulmonary bypass was 3.3% and 68.3%; pulmonary embolectomy surgery was 1.7%; and bleeding complications were 1.4% and 3.4%. Predictors associated with in-hospital mortality for MT were: increasing age (OR 1.2, 95% CI 1.0–1.3, p < 0.026), female sex (OR 1.9, 95% CI 1.2–2.8, p < 0.004), large hospitals (OR 2.2, 95% 1.4–3.5, p < 0.001), and teaching hospitals (OR 1.8, 95% CI 1.1–3.1, p < 0.023). The predictor of in-hospital mortality for ST was increasing age (OR 1.2, 95% CI 1.0–1.4, p < 0.046). The number of MT procedures performed has rapidly increased over the past decade. Further studies are warranted to determine their rise and therapeutic use.