bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of Sorafenib and Lenvatinib in Patients Who Underwent Surgery or Whole-Brain Radiotherapy for Brain Metastasis of Hepatocellular Carcinoma
Authors: Perng Pang-Shuo , Lai Yu-Hsuan , Lee Po-Hsuan , Huang Chi-Chen , Hsu Hao-Hsiang , Lee Jung-Shun
Published: March 2022

Surgery or whole-brain radiotherapy (WBRT) for the management of brain metastasis of hepatocellular carcinoma (HCC) is associated with improved survival. However, the efficacy of multi-tyrosine kinase inhibitors (TKIs) and possible bleeding complications have not been studied in these patients. Therefore, this study aimed at investigating TKI safety and efficacy in these patients. We retrospectively reviewed 39 patients who underwent surgery or WBRT for brain metastasis of HCC. Intracranial tumor bleeding rates were compared between patients who did and did not receive TKIs. Survival outcomes were analyzed using the log-rank and Cox regression tests. A total of 22 and 7 patients received sorafenib and lenvatinib, respectively. The intracranial tumor bleeding rates were 61.5% and 70% in patients who did and did not receive TKIs, respectively (p > 0.99). Survival analysis revealed craniotomy (adjusted odds ratio [AOR]: 0.45, p = 0.04), a higher Karnofsky Performance Score (AOR: 0.97, p < 0.01), and TKI use (AOR: 0.26, p < 0.01) were positive prognostic factors for overall survival. TKIs were associated with better survival outcomes in patients who underwent surgery or WBRT for brain metastasis of HCC and did not increase intracranial bleeding. Therefore, TKIs are efficacious and safe for treating brain metastasis of HCC.
Prognostic Factors for Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis
Authors: Maglietta Giuseppe , Diodati Francesca , Puntoni Matteo , Lazzarelli Silvia , Marcomini Barbara , Patrizi Laura , Caminiti Caterina
Published: March 2022

Evidence shows that a substantial proportion of patients with COVID-19 experiences long-term consequences of the disease, but the predisposing factors are poorly understood. We conducted a systematic review and meta-analysis to identify factors present during COVID-19 hospitalization associated with an increased risk of exhibiting new or persisting symptoms (Post-COVID-19 Syndrome, PCS). MedLine and WebOfScience were last searched on 30 September 2021. We included English language clinical trials and observational studies investigating prognostic factors for PCS in adults previously hospitalized for COVID-19, reporting at least one individual prospective follow-up of minimum 12 weeks. Two authors independently assessed risk of bias, which was judged generally moderate. Risk factors were included in the analysis if their association with PCS was investigated by at least two studies. To summarize the prognostic effect of each factor (or group of factors), odds ratios were estimated using raw data. Overall, 20 articles met the inclusion criteria, involving 13,340 patients. Associations were statistically significant for two factors: female sex with any symptoms (OR 1.52; 95% CI 1.27–1.82), with mental health symptoms (OR 1.67, 95% CI 1.21–2.29) and with fatigue (OR 1.54, 95% CI 1.32–1.79); acute disease severity with respiratory symptoms (OR 1.66, 95% CI 1.03–2.68). The I² statistics tests were calculated to quantify the degree of study heterogeneity. This is the first meta-analysis measuring the association between factors present during COVID-19 hospitalization and long-term sequelae. The role of female sex and acute disease severity as independent prognostic factors must be confirmed in robust longitudinal studies with longer follow-up. Identifying populations at greatest risk for PCS can enable the development of targeted prevention and management strategies. Systematic review registration: PROSPERO CRD42021253467.
Glycaemic Variability and Hyperglycaemia as Prognostic Markers of Major Cardiovascular Events in Diabetic Patients Hospitalised in Cardiology Intensive Care Unit for Acute Heart Failure
Authors: Gerbaud Edouard , Bouchard de La Poterie Ambroise , Baudinet Thomas , Montaudon Michel , Beauvieux Marie-Christine , Lemaître Anne-Iris , Cetran Laura , Seguy Benjamin , Picard François , Vélayoudom Fritz-Line , Ouattara Alexandre , Kabore Rémi , Coste Pierre , Domingues-Dos-Santos Pierre , Catargi Bogdan
Published: March 2022

(1) Background: Hyperglycaemia and hypoglycaemia are both emerging risk factors for cardiovascular disease. Nevertheless, the potential effect of glycaemic variability (GV) on mid-term major cardiovascular events (MACE) in diabetic patients presenting with acute heart failure (AHF) remains unclear. This study investigates the prognostic value of GV in diabetic patients presenting with acute heart failure (AHF). (2) Methods: this was an observational study including consecutive patients with diabetes and AHF between January 2015 and November 2016. GV was calculated using standard deviation of glycaemia values during initial hospitalisation in the intensive cardiac care unit. MACE, including recurrent AHF, new-onset myocardial infarction, ischaemic stroke and cardiac death, were recorded. The predictive effects of GV on patient outcomes were analysed with respect to baseline characteristics and cardiac status. (3) Results: In total, 392 patients with diabetes and AHF were enrolled. During follow-up (median (interquartile range) 29 (6–51) months), MACE occurred in 227 patients (57.9%). In total, 92 patients died of cardiac causes (23.5%), 107 were hospitalised for heart failure (27.3%), 19 had new-onset myocardial infarction (4.8%) and 9 (2.3%) had an ischaemic stroke. Multivariable logistic regression analysis showed that GV > 50 mg/dL (2.70 mmol/L), age > 75 years, reduced left ventricular ejection fraction (LVEF < 30%) and female gender were independent predictors of MACE: hazard ratios (HR) of 3.16 (2.25–4.43; p < 0.001), 1.54 (1.14–2.08; p = 0.005), 1.47 (1.06–2.07; p = 0.02) and 1.43 (1.05–1.94; p = 0.03), respectively. (4) Conclusions: among other well-known factors of HF, a GV cut-off value of >50 mg/dL was the strongest independent predictive factor for mid-term MACE in patients with diabetes and AHF.
Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?
Authors: Akirov Amit , Shimon Ilan , Fleseriu Maria , Dotan Idit , Manisterski Yossi , Aviran-Barak Nirit , Nadler Varda , Alboim Sandra , Shochat Tzipora , Tsvetov Gloria , Hirsch Dania
Published: March 2022

Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing’s disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Methods: Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. Results: The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, p = NS) and Cushingoid features (27.5% vs. 20.0%, p = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2 × ULN vs. 1.3 ± 0.8 × ULN, respectively, p = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. Conclusions: While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study.
Investigating Cancerous Exosomes’ Effects on CD8+ T-Cell IL-2 Production in a 3D Unidirectional Flow Bioreactor Using 3D Printed, RGD-Functionalized PLLA Scaffolds
Authors: Karami Daniel , Srivastava Akhil , Ramesh Rajagopal , Sikavitsas Vassilios I.
Published: March 2022

Exosomes from cancer cells are implicated in cancer progression and metastasis, carrying immunosuppressive factors that limit the antitumor abilities of immune cells. The development of a real-time, 3D cell/scaffold construct flow perfusion system has been explored as a novel tool in the study of T-cells and exosomes from cancer cells. Exosomes from human lung cancer (H1299 and A549) cells were co-cultured in a unidirectional flow bioreactor with CD8+ T-cells immobilized onto 3D-printed RGD-functionalized poly(L-lactic) acid (PLLA) scaffolds and assessed for IL-2 production. The IL-2 production was investigated for a wide range of T-cell to exosome ratios. With the successful incorporation of the RGD binding motif onto the PLLA surface at controllable densities, CD8+ T-cells were successfully attached onto 2D disks and 3D printed porous PLLA scaffolds. T-cell attachment increased with increasing RGD surface density. The diameter of the attached T-cells was 7.2 ± 0.2 µm for RGD densities below 0.5 nmoles/mm2 but dropped to 5.1 ± 0.3 µm when the RGD density was 2 nmoles/mm2 due to overcrowding. The higher the number of cancer exosomes, the less the IL-2 production by the surface-attached T-cells. In 2D disks, the IL-2 production was silenced for T-cell to exosome ratios higher than 1:10 in static conditions. IL-2 production silencing in static 3D porous scaffolds required ratios higher than 1:20. The incorporation of flow resulted in moderate to significant T-cell detachment. The portions of T-cells retained on the 3D scaffolds after exposure for 4 h to 0.15 or 1.5 mL/min of perfusion flow were 89 ± 11% and 30 ± 8%, respectively. On 3D scaffolds and in the presence of flow at 0.15 ml/min, both H1299 and A549 cancerous exosomes significantly suppressed IL-2 production for T-cell to exosome ratios of 1:1000. The much higher level of exosomes needed to silence the IL-2 production from T-cells cultured under unidirectional flow, compared to static conditions, denotes the importance of the culturing conditions and the hydrodynamic environment, on the interactions between CD8+ T-cells and cancer exosomes.
Multi-Modality Microscopy Image Style Augmentation for Nuclei Segmentation
Authors: Liu Ye , Wagner Sophia J. , Peng Tingying
Published: March 2022

Annotating microscopy images for nuclei segmentation by medical experts is laborious and time-consuming. To leverage the few existing annotations, also across multiple modalities, we propose a novel microscopy-style augmentation technique based on a generative adversarial network (GAN). Unlike other style transfer methods, it can not only deal with different cell assay types and lighting conditions, but also with different imaging modalities, such as bright-field and fluorescence microscopy. Using disentangled representations for content and style, we can preserve the structure of the original image while altering its style during augmentation. We evaluate our data augmentation on the 2018 Data Science Bowl dataset consisting of various cell assays, lighting conditions, and imaging modalities. With our style augmentation, the segmentation accuracy of the two top-ranked Mask R-CNN-based nuclei segmentation algorithms in the competition increases significantly. Thus, our augmentation technique renders the downstream task more robust to the test data heterogeneity and helps counteract class imbalance without resampling of minority classes.
Assessment of Biological Activities of Fungal Endophytes Derived Bioactive Compounds Isolated from Amoora rohituka
Authors: Verma Ashish , Gupta Priyamvada , Rai Nilesh , Tiwari Rajan Kumar , Kumar Ajay , Salvi Prafull , Kamble Swapnil C. , Singh Santosh Kumar , Gautam Vibhav
Published: March 2022

Fungal endophytes have remarkable potential to produce bioactive compounds with numerous pharmacological significance that are used in various disease management and human welfare. In the current study, a total of eight fungal endophytes were isolated from the leaf tissue of Amoora rohituka, and out of which ethyl acetate (EA) extract of Penicillium oxalicum was found to exhibit potential antioxidant activity against DPPH, nitric oxide, superoxide anion and hydroxyl free radicals with EC50 values of 178.30 ± 1.446, 75.79 ± 0.692, 169.28 ± 0.402 and 126.12 ± 0.636 µg/mL, respectively. The significant antioxidant activity of EA extract of P. oxalicum is validated through highest phenolic and flavonoid content, and the presence of unique bioactive components observed through high-performance thin layer chromatography (HPTLC) fingerprinting. Moreover, EA extract of P. oxalicum also displayed substantial anti-proliferative activity with IC50 values of 56.81 ± 0.617, 37.24 ± 1.26 and 260.627 ± 5.415 µg/mL against three cancer cells HuT-78, MDA-MB-231 and MCF-7, respectively. Furthermore, comparative HPTLC fingerprint analysis and antioxidant activity of P. oxalicum revealed that fungal endophyte P. oxalicum produces bioactive compounds in a host-dependent manner. Therefore, the present study signifies that fungal endophyte P. oxalicum associated with the leaf of A. rohituka could be a potential source of bioactive compounds with antioxidant and anticancer activity.
Mycotherapy: Potential of Fungal Bioactives for the Treatment of Mental Health Disorders and Morbidities of Chronic Pain
Authors: Meade Elaine , Hehir Sarah , Rowan Neil , Garvey Mary
Published: March 2022

Mushrooms have been used as traditional medicine for millennia, fungi are the main natural source of psychedelic compounds. There is now increasing interest in using fungal active compounds such as psychedelics for alleviating symptoms of mental health disorders including major depressive disorder, anxiety, and addiction. The anxiolytic, antidepressant and anti-addictive effect of these compounds has raised awareness stimulating neuropharmacological investigations. Micro-dosing or acute dosing with psychedelics including Lysergic acid diethylamide (LSD) and psilocybin may offer patients treatment options which are unmet by current therapeutic options. Studies suggest that either dosing regimen produces a rapid and long-lasting effect on the patient post administration with a good safety profile. Psychedelics can also modulate immune systems including pro-inflammatory cytokines suggesting a potential in the treatment of auto-immune and other chronic pain conditions. This literature review aims to explore recent evidence relating to the application of fungal bioactives in treating chronic mental health and chronic pain morbidities.
How Do Fungi Survive in the Sea and Respond to Climate Change?
Authors: Jones E. B. Gareth , Ramakrishna Sundari , Vikineswary Sabaratnam , Das Diptosh , Bahkali Ali H. , Guo Sheng-Yu , Pang Ka-Lai
Published: March 2022

With the over 2000 marine fungi and fungal-like organisms documented so far, some have adapted fully to life in the sea, while some have the ability to tolerate environmental conditions in the marine milieu. These organisms have evolved various mechanisms for growth in the marine environment, especially against salinity gradients. This review highlights the response of marine fungi, fungal-like organisms and terrestrial fungi (for comparison) towards salinity variations in terms of their growth, spore germination, sporulation, physiology, and genetic adaptability. Marine, freshwater and terrestrial fungi and fungal-like organisms vary greatly in their response to salinity. Generally, terrestrial and freshwater fungi grow, germinate and sporulate better at lower salinities, while marine fungi do so over a wide range of salinities. Zoosporic fungal-like organisms are more sensitive to salinity than true fungi, especially Ascomycota and Basidiomycota. Labyrinthulomycota and marine Oomycota are more salinity tolerant than saprolegniaceous organisms in terms of growth and reproduction. Wide adaptability to saline conditions in marine or marine-related habitats requires mechanisms for maintaining accumulation of ions in the vacuoles, the exclusion of high levels of sodium chloride, the maintenance of turgor in the mycelium, optimal growth at alkaline pH, a broad temperature growth range from polar to tropical waters, and growth at depths and often under anoxic conditions, and these properties may allow marine fungi to positively respond to the challenges that climate change will bring. Other related topics will also be discussed in this article, such as the effect of salinity on secondary metabolite production by marine fungi, their evolution in the sea, and marine endophytes.
SterylAcetyl Hydrolase 1 (BbSay1) Links Lipid Homeostasis to Conidiogenesis and Virulence in the Entomopathogenic Fungus Beauveria bassiana
Authors: Peng Yue-Jin , Zhang Hao , Feng Ming-Guang , Ying Sheng-Hua
Published: March 2022

Beauveria bassiana, as a well-studied entomopathogenic fungus, has a great potential for the biological control of insect pests. Lipid metabolism has been linked to the life cycle of B. bassiana; however, the underlying mechanisms remain unknown. In this study, a homolog of yeast steryl acetyl hydrolase 1 (Say1) was functionally characterized. The loss of B. bassianaSAY1 (BbSAY1) impaired the lipid homeostasis in conidia, with a significant reduction in oleic acid content. The ΔBbsay1 mutant strain displayed anelevated accumulation of lipid bodies and aweakened membrane permeability. As for phenotypic aspects, gene loss resulted in significant defects in germination, conidiation, and virulence. Our findings highlight that Say1, involved in lipid homeostasis, contributes to the cytomembrane integrity, development, and virulence in B. bassiana.
Current Status, Issues and Future Prospects of Personalized Medicine for Each Disease
Authors: Yamamoto Yuichi , Kanayama Norihiro , Nakayama Yusuke , Matsushima Nobuko
Published: March 2022

In recent years, with the advancement of next-generation sequencing (NGS) technology, gene panel tests have been approved in the field of cancer diseases, and approaches to prescribe optimal molecular target drugs to patients are being developed. In the field of rare diseases, whole-genome and whole-exome analysis has been used to identify the causative genes of undiagnosed diseases and to diagnose patients’ diseases, and further progress in personalized medicine is expected. In order to promote personalized medicine in the future, we investigated the current status and progress of personalized medicine in disease areas other than cancer and rare diseases, where personalized medicine is most advanced. We selected rheumatoid arthritis and psoriasis as the inflammatory disease, in addition to Alzheimer’s disease. These diseases have high unmet needs for personalized medicine from the viewpoints of disease mechanisms, diagnostic biomarkers, therapeutic drugs with diagnostic markers and treatment satisfaction. In rheumatoid arthritis and psoriasis, there are many therapeutic options; however, diagnostic methods have not been developed to select the best treatment for each patient. In addition, there are few effective therapeutic agents in Alzheimer’s disease, although clinical trials of many candidate drugs have been conducted. In rheumatoid arthritis and psoriasis, further elucidation of the disease mechanism is desired to enable the selection of appropriate therapeutic agents according to the patient profile. In the case of Alzheimer’s disease, progress in preventive medicine is desired through the establishment of an early diagnosis method as well as the research and development of innovative therapeutic agents. To this end, we hope for further research and development of diagnostic markers and new drugs through progress in comprehensive data analysis such as comprehensive genomic and transcriptomic information. Furthermore, new types of markers such as miRNAs and the gut microbiome are desired to be utilized in clinical diagnostics.
Next-Generation Sequencing in Lung Cancer Patients: A Comparative Approach in NSCLC and SCLC Mutational Landscapes
Authors: Pop-Bica Cecilia , Ciocan Cristina Alexandra , Braicu Cornelia , Haranguș Antonia , Simon Marioara , Nutu Andreea , Pop Laura Ancuta , Slaby Ondrej , Atanasov Atanas G. , Pirlog Radu , Al Hajjar Nadim , Berindan-Neagoe Ioana
Published: March 2022

Background: Lung cancer remains one of the most diagnosed malignancies, being the second most diagnosed cancer, while still being the leading cause of cancer-related deaths. Late diagnosis remains a problem, alongside the high mutational burden encountered in lung cancer. Methods: We assessed the genetic profile of cancer genes in lung cancer using The Cancer Genome Atlas (TCGA) datasets for mutations and validated the results in a separate cohort of 32 lung cancer patients using tumor tissue and whole blood samples for next-generation sequencing (NGS) experiments. Another separate cohort of 32 patients was analyzed to validate some of the molecular alterations depicted in the NGS experiment. Results: In the TCGA analysis, we identified the most commonly mutated genes in each lung cancer dataset, with differences among the three histotypes analyzed. NGS analysis revealed TP53, CSF1R, PIK3CA, FLT3, ERBB4, and KDR as being the genes most frequently mutated. We validated the c.1621A>C mutation in KIT. The correlation analysis indicated negative correlation between adenocarcinoma and altered PIK3CA (r = −0.50918; p = 0.0029). TCGA survival analysis indicated that NRAS and IDH2 (LUAD), STK11 and TP53 (LUSC), and T53 (SCLC) alterations are correlated with the survival of patients. Conclusions: The study revealed differences in the mutational landscape of lung cancer histotypes.
Influence of Senior Executives Characteristics on Corporate Environmental Disclosures: A Bibliometric Analysis
Authors: Arslan Hafiz Muhammad , Chengang Ye , Bilal  , Siddique Muhammad , Yahya Yusra
Published: March 2022

This study aims to synthesize the literature on the top management team (TMT) characteristics influence on environmental disclosures of public organizations and identify recent trends, key themes, influential journals, and authors. Our study recruited 88 research articles on the relationship of TMT characteristics and environmental disclosures from 54 academic journals published from 2010 to 2021 for bibliometric analysis. Our study has identified three influential streams: (1) Role of Politically connections of TMT, good governance in environmental disclosures; (2) Significance of environmental disclosures and performance; and (3) institutional investors and environmental disclosures. Thematic map classifies the TMT characteristics and environmental disclosures relationship themes into four categories: Niche theme (e.g., financial expertise, CFO characteristics, CEO tenure, and board backgrounds); motor themes (e.g., environmental sustainability and climate change); emerging/declining themes (e.g., Environmental disclosure, managerial ownership, and CEO tenure); and basic/transversal themes (e.g., CEO characteristics, upper echelon theory, corporate governance). This study assists academicians, policymakers, managers, and consultants in the corporate sector to understand the role of different dimensions of TMT characteristics regarding environmental disclosures. Our study concludes with important practical implications and future research directions.
Wearable Sensors for Vital Signs Measurement: A Survey
Authors: Lv Zhihan , Li Yuxi
Published: March 2022

With the outbreak of coronavirus disease-2019 (COVID-19) worldwide, developments in the medical field have aroused concerns within society. As science and technology develop, wearable medical sensors have become the main means of medical data acquisition. To analyze the intelligent development status of wearable medical sensors, the current work classifies and prospects the application status and functions of wireless communication wearable medical sensors, based on human physiological data acquisition in the medical field. By understanding its working principles, data acquisition modes and action modes, the work chiefly analyzes the application of wearable medical sensors in vascular infarction, respiratory intensity, body temperature, blood oxygen concentration, and sleep detection, and reflects the key role of wearable medical sensors in human physiological data acquisition. Further exploration and prospecting are made by investigating the improvement of information security performance of wearable medical sensors, the improvement of biological adaptability and biodegradability of new materials, and the integration of wearable medical sensors and intelligence-assisted rehabilitation. The research expects to provide a reference for the intelligent development of wearable medical sensors and real-time monitoring of human health in the follow-up medical field.
Optimization of Production–Living–Ecological Space in National Key Poverty-Stricken City of Southwest China
Authors: Wang Di , Fu Jingying , Jiang Dong
Published: March 2022

Trade-offs and conflicts among different sectors of production, living, and ecology have become important issues in regional sustainable development planning due to both the versatility and limitation of land resources, especially in poverty-stricken mountainous areas. This study builds an optimization model to assist policymakers in simulating land demand and allocation in the future. The model takes socioeconomic and demographic development into consideration and couples local planning policy with land use data from the perspective of system integration. The model was employed for a case study of Zhaotong city to optimize production–living–ecological (PLE) space. The results show that the model provides a feasible method to explore the sustainable development pattern of territorial space, especially in distressed regions.
Liquid Biopsy in Diagnosis and Prognosis of High-Grade Gliomas; State-of-the-Art and Literature Review
Authors: Bonosi Lapo , Ferini Gianluca , Giammalva Giuseppe Roberto , Benigno Umberto Emanuele , Porzio Massimiliano , Giovannini Evier Andrea , Musso Sofia , Gerardi Rosa Maria , Brunasso Lara , Costanzo Roberta , Paolini Federica , Graziano Francesca , Scalia Gianluca , Umana Giuseppe Emmanuele , Di Bonaventura Rina , Sturiale Carmelo Lucio , Iacopino Domenico Gerardo , Maugeri Rosario
Published: March 2022

Gliomas, particularly high-grade gliomas, represent the most common and aggressive tumors of the CNS and are still burdened by high mortality and a very poor prognosis, regardless of the type of therapy. Their diagnosis and monitoring rely on imaging techniques and direct biopsy of the pathological tissue; however, both procedures have inherent limitations. To address these limitations, liquid biopsies have been proposed in this field. They could represent an innovative tool that could help clinicians in the early diagnosis, monitoring, and prognosis of these tumors. Furthermore, the rapid development of next-generation sequencing (NGS) technologies has led to a significant reduction in sequencing cost, with improved accuracy, providing a molecular profile of cancer and leading to better survival results and less disease burden. This paper focuses on the current clinical application of liquid biopsy in the early diagnosis and prognosis of cancer, introduces NGS-related methods, reviews recent progress, and summarizes challenges and future perspectives.
Elasto-Dynamic Modeling of an Over-Constrained Parallel Kinematic Machine Using a Beam Model
Authors: Chanal Hélène , Guichard Aurélie , Blaysat Benoît , Caro Stéphane
Published: March 2022

This article deals with the development of a simple model to evaluate the first natural frequencies of over-constrained parallel kinematic machines (PKMs). The simplest elasto-dynamic models are based on multi-body approaches. However, these approaches require an expression of the Jacobian matrices that may be difficult to obtain for complex PKMs. Therefore, this paper focuses on the determination of the global mass and stiffness matrices of an over-constrained PKM in stationary configurations without the use of Jacobian matrices. The PKM legs are modeled by beams. Because the legs are connected to a moving platform and the mechanism is over-constrained, constraint equations between the parameters that model the deformation of each leg are determined according to screw theory. The first natural frequencies and associated modes can then be determined. It should be noted that the proposed method can be easily used at the conceptual design stage of PKMs. The Tripteor X7 machine is used as an illustrative example and is characterized experimentally.
Comprehensive Comparison of Two Fault Tolerant Axial Field Modular Flux-Switching Permanent Magnet Machines with Different Stator and Rotor Pole-Pairs Combinations
Authors: Tu Yixiang , Lin Mingyao , Lin Keman , Kong Yong , Xu Da
Published: March 2022

This paper gives a comprehensive comparison among two fault-tolerant axial field modular flux-switching (AFFSPM) machines with different stator modular segments (U- and E-core) and stator-slots/pole-pairs combinations. The topologies of two AFFSPM machines are introduced, each with two feasible stator slots and rotor pole-pairs combinations with high winding factors based on the slot-conductor back-EMF star vectors theory. Then, the static performance including the air-gap flux density, flux linkage, back-electromagnetic force (back-EMF), and electromagnetic torque are analyzed and compared. Moreover, the fault-tolerant capability is then investigated by the torque performance under one- and two-phase open-circuit conditions in which the corresponding fault-tolerant control strategies are applied. The predicted results confirm that the 6-stator slot/11-rotor-pole-pair E-core AFFSPM machine exhibits the best performance of the four candidates.
Optimization Design and Performance Analysis of a Reverse-Salient Permanent Magnet Synchronous Motor
Authors: Zhao Xiaokun , Kou Baoquan , Huang Changchuang , Zhang Lu
Published: March 2022

The reverse-salient permanent magnet synchronous motor (RSPMSM) is a competitive candidate for electric vehicles due to its high torque density and high efficiency. This paper proposes an optimized RSPMSM by adopting a segmented permanent magnet structure. First, the structure, electromagnetic torque, and current control laws of the RSPMSM are introduced in detail. Second, the optimization design method of the RSPMSM is proposed by taking the torque and constant-power speed range as optimized objectives, with the saliency ratio as a constraint. The optimized model of the RSPMSM is determined using the genetic algorithm (GA). Further performance analysis and comparisons are made between the initial motor and the optimized motor. Finally, a prototype is manufactured, and the performance of the RSPMSM is verified through the finite element method (FEM) and experiments.
Exact Solution of Nonlinear Behaviors of Imperfect Bioinspired Helicoidal Composite Beams Resting on Elastic Foundations
Authors: Almitani Khalid H. , Mohamed Nazira , Alazwari Mashhour A. , Mohamed Salwa A. , Eltaher Mohamed A.
Published: March 2022

This paper presents exact solutions for the nonlinear bending problem, the buckling loads, and postbuckling configurations of a perfect and an imperfect bioinspired helicoidal composite beam with a linear rotation angle. The beam is embedded on an elastic medium, which is modeled by two elastic foundation parameters. The nonlinear integro-differential governing equation of the system is derived based on the Euler–Bernoulli beam hypothesis, von Kármán nonlinear strain, and initial curvature. The Laplace transform and its inversion are directly applied to solve the nonlinear integro-differential governing equations. The nonlinear bending deflections under point and uniform loads are derived. Closed-form formulas of critical buckling loads, as well as nonlinear postbuckling responses of perfect and imperfect beams are deduced in detail. The proposed model is validated with previous works. In the numerical results section, the effects of the rotation angle, amplitude of initial imperfection, elastic foundation constants, and boundary conditions on the nonlinear bending, critical buckling loads, and postbuckling configurations are discussed. The proposed model can be utilized in the analysis of bio-inspired beam structures that are used in many energy-absorption applications.
A Novel Spatial–Temporal Radial Trefftz Collocation Method for 3D Transient Wave Propagation Analysis with Specified Sound Source Excitation
Authors: Chen Lin , Xu Wenzhi , Fu Zhuojia
Published: March 2022

In this paper, a novel semi-analytical collocation solver, the spatial–temporal radial Trefftz collocation method (STRTCM) is proposed to solve 3D transient wave equations with specified sound source excitations. Unlike the traditional time discretization strategies, the proposed numerical scheme introduces the spatial–temporal radial Trefftz functions (STRTFs) as the basis functions for the spatial and temporal discretization of the transient wave equations. The STRTFs are constructed in the spatial–temporal domain, which is a combination of 3D Euclidean space and time into a 4D manifold. Moreover, since the initial and boundary conditions are imposed on the spatial–temporal domain boundaries, the original transient wave propagation problem can be converted to an inverse boundary value problem. To deal with the specified time-dependent sound source excitations, the composite multiple reciprocity technique is extended from the spatial domain to the spatial–temporal domain, which transforms the original problem with a source term into a high-order problem without a source term. By deriving the related STRTFs for the considered high-order problem, the proposed scheme only requires the node discretization on the spatial–temporal domain boundaries. The efficiency of the proposed method is numerically verified by four benchmark examples under 3D transient wave equations with specified time-dependent sound source excitation.
Exact Analytical H-BER for Ad Hoc XOR H-Map Detector for Two Differentially Modulated BPSK Sources in H-MAC Channel
Authors: Lukac Jozef , Sykora Jan
Published: March 2022

In the article, we present an ad hoc (AH) detector for two differentially encoded BPSK sources in the Hierarchical MAC (H-MAC), i.e., for the case when the receiver sees the superposition of non-orthogonal signals from individual sources. (Prefix “H-” means Hierarchical, it emphasizes that the entity is related to the many-to-one principle.) The AH detector decodes the XOR H-map of the two BPSK streams—in other words, it decides whether the transmitted symbols from the two sources are the same or opposite. The BER of the detection in H-MAC is denoted as H-BER. The H-BER is compared with the other two differential detectors, with the coherent (Coh) detector, and with an approximate coherent (ApC) detector. The exact analytical H-BER formula is derived for the ad hoc and coherent detectors. The proposed ad hoc detector is very simple for evaluation, does not require the estimation of subchannel phases, does not depend on noise variance, and it is uniformly only roughly 3.5 dB worse than the coherent one.
Effect of a Vaccination against the Dengue Fever Epidemic in an Age Structure Population: From the Perspective of the Local and Global Stability Analysis
Authors: Chamnan Anusit , Pongsumpun Puntani , Tang I-Ming , Wongvanich Napasool
Published: March 2022

The effect of vaccination on the dengue fever epidemic described by an age structured modified SIR (Susceptible-Infected-Retired) model is studied using standard stability analysis. The chimeric yellow fever dengue tetravalent dengue vaccine (CYD-TDV™) is a vaccine recently developed to control this epidemic in several Southeast Asian countries. The dengue vaccination program requires a total of three injections, 6 months apart at 0, 6, and 12 months. The ages of the recipients are nine years and above. In this paper, we analyze the mathematical dynamics SIR transmission model of the epidemic. The stability of the model is established using Routh–Hurwitz criteria to see if a Hopf Bifurcation occurs and see when the equilibrium states are local asymptotically stable or global asymptotically stable. We have determined the efficiency of CYD-TDV by simulating the optimal numerical solution for each age range for this model. The numerical results showed the optimal age for vaccination and significantly reduced the severity and severity of the disease.
A Galerkin/POD Reduced-Order Model from Eigenfunctions of Non-Converged Time Evolution Solutions in a Convection Problem
Authors: Cortés Jesús , Herrero Henar , Pla Francisco
Published: March 2022

A Galerkin/POD reduced-order model from eigenfunctions of non-converged time evolution transitory states in a problem of Rayleigh–Bénard is presented. The problem is modeled in a rectangular box with the incompressible momentum equations coupled with an energy equation depending on the Rayleigh number R as a bifurcation parameter. From the numerical solution and stability analysis of the system for a single value of the bifurcation parameter, the whole bifurcation diagram in an interval of values of R is obtained. Three different bifurcation points and four types of solutions are obtained with small errors. The computing time is drastically reduced with this methodology.
Mitigating Benzodiazepine Dependence and the Risk of Drug-Induced QTc Prolongation in the Treatment of Gastroparesis: A Case Report
Authors: Tranchina Karley , Matlock Derek , Hernandez Carlos , Turgeon Jacques , Bingham Jennifer M.
Published: March 2022

Patients are often faced with challenges when it comes to safe therapeutic options. An 89-year-old female with a history of arrhythmias and refractory gastroparesis complained of adverse drug events from her benzodiazepine. While performing a comprehensive medication review and a medication safety review using an advanced clinical decision support system, the pharmacist successfully tapered off the benzodiazepine to a safer alternative antidepressant indicated for the treatment of gastroparesis. Special attention was given to selecting drugs with less QT prolongation risk, based on her age, current drug regimen, previous medical history, and presence of polypharmacy.
Hemorrhagic Colitis Caused by Everolimus in a Patient with Nonfunctional Pancreatic Neuroendocrine Neoplasms: A Case Report
Authors: Arakawa Noriyuki , Irisawa Atsushi , Ishida Kazuyuki , Tsunoda Takuya , Yamaguchi Yoshiko , Yamabe Akane , Eizuka Makoto , Tokioka Shunzo , Wakabayashi Hiroto
Published: March 2022

A 60-year-old woman was diagnosed with nonfunctional pancreatic neuroendocrine neoplasm with multiple liver metastases and was administered everolimus. Due to persistent epigastric pain and diarrhea, a colonoscopy was performed on the 14th day after the start of everolimus administration, which revealed small bleeding ulcers in the ileocecal region, transverse colon, and rectum. These adverse effects were attributed to the everolimus; it was immediately discontinued, and the patient’s clinical symptoms and imaging findings improved. We concurred that the administration of calcium channel blockers resulted in the inhibition of everolimus metabolism and the disease onset. The everolimus was discontinued. There was no subsequent recurrence of hemorrhagic colitis.
Kinesiophobia in People with Multiple Sclerosis and Its Relationship with Physical Activity, Pain and Acceptance of Disease
Authors: Wasiuk-Zowada Dagmara , Brzęk Anna , Krzystanek Ewa , Knapik Andrzej
Published: March 2022

Background and Objectives: Multiple sclerosis (MS) is the most common chronic demyelinating disease. Factors that reduce the occurrence of symptoms include physical activity (PA). However, the data indicate that PA levels among people with MS are lower than those of healthy peers. The cause may be kinesiophobia. The aim of the study was to determine the level of kinesiophobia among people with MS and its relationship with age, disease duration, functional status, PA, and degree of acceptance of the disease. Materials and Methods: Eighty people aged 35–69 were examined: 60 women (75%) and 20 men (25%). The Expanded Disability Status Scale (EDSS) was used to determine the level of disability (median: 3.50; min–max: 1–6). The research questionnaire consisted of a metric section, Visual Analogue Scale (VAS) for pain, Tampa Scale of Kinesiophobia (TSK), Acceptance of Illness Scale (AIS), and Modified Baecke Questionnaire for Older Adults for physical activity. Results: Of the respondents, 52.50% were characterized by a high level of kinesiophobia (>37 points). Correlation analysis: TSK and PA showed the following: r = −0.363 (p = 0.001). Regression explains kinesiophobia in 44% (R2 = 0.4364; p < 0.0000). The predictors of TSK were as follows: disability level: p < 0.01, ß = 0.33; disease acceptance: p < 0.01, ß = −0.34; PA: p < 0.05, ß < −0.05. Conclusions: The problem of kinesiophobia is significant in MS patients, and its predictors are the functional status of the patients, low degree of acceptance of the disease, and low level of physical activity. The age and duration of the disease do not determine the problem of fear of movement.
A Review of Recent Developments of Pervaporation Membranes for Ethylene Glycol Purification
Authors: Rostovtseva Valeriia , Faykov Ilya , Pulyalina Alexandra
Published: March 2022

Ethylene glycol (EG) is an essential reagent in the chemical industry including polyester and antifreeze manufacture. In view of the constantly expanding field of EG applications, the search for and implementation of novel economical and environmentally friendly technologies for the separation of organic and aqueous–organic solutions remain an issue. Pervaporation is currently known to significantly reduce the energy and resource consumption of a manufacturer when obtaining high-purity components using automatic, easily scalable, and compact equipment. This review provides an overview of the current research and advances in the pervaporation of EG-containing mixtures (water/EG and methanol/EG), as well as a detailed analysis of the relationship of pervaporation performance with the membrane structure and properties of membrane materials. It is discussed that a controlled change in the structure and transport properties of a membrane is possible using modification methods such as treatment with organic solvents, introduction of nonvolatile additives, polymer blending, crosslinking, and heat treatment. The use of various modifiers is also described, and a particularly positive effect of membrane modification on the separation selectivity is highlighted. Among various polymers, hydrophilic PVA-based membranes stand out for optimal transport properties that they offer for EG dehydrating. Fabricating of TFC membranes with a microporous support layer appears to be a viable approach to the development of productivity without selectivity loss. Special attention is given to the recovery of methanol from EG, including extensive studies of the separation performance of polymer membranes. Membranes based on a CS/PVP blend with inorganic modifiers are specifically promising for methanol removal. With regard to polymer wettability properties, it is worth mentioning that membranes based on hydrophobic polymers (e.g., SPEEK, PBI/PEI, PEC, PPO) are capable of exhibiting much higher selectivity due to diffusion limitations.
Dysfunction of EAAT3 Aggravates LPS-Induced Post-Operative Cognitive Dysfunction
Authors: Wang Xiao-Yan , Liu Wen-Gang , Hou Ai-Sheng , Song Yu-Xiang , Ma Yu-Long , Wu Xiao-Dong , Cao Jiang-Bei , Mi Wei-Dong
Published: March 2022

Numerous results have revealed an association between inhibited function of excitatory amino acid transporter 3 (EAAT3) and several neurodegenerative diseases. This was also corroborated by our previous studies which showed that the EAAT3 function was intimately linked to learning and memory. With this premise, we examined the role of EAAT3 in post-operative cognitive dysfunction (POCD) and explored the potential benefit of riluzole in countering POCD in the present study. We first established a recombinant adeno-associated-viral (rAAV)-mediated shRNA to knockdown SLC1A1/EAAT3 expression in the hippocampus of adult male mice. The mice then received an intracerebroventricular microinjection of 2 μg lipopolysaccharide (LPS) to construct the POCD model. In addition, for old male mice, 4 mg/kg of riluzole was intraperitoneally injected for three consecutive days, with the last injection administered 2 h before the LPS microinjection. Cognitive function was assessed using the Morris water maze 24 h following the LPS microinjection. Animal behavioral tests, as well as pathological and biochemical assays, were performed to clarify the role of EAAT3 function in POCD and evaluate the effect of activating the EAAT3 function by riluzole. In the present study, we established a mouse model with hippocampal SLC1A1/EAAT3 knockdown and found that hippocampal SLC1A1/EAAT3 knockdown aggravated LPS-induced learning and memory deficits in adult male mice. Meanwhile, LPS significantly inhibited the expression of EAAT3 membrane protein and the phosphorylation level of GluA1 protein in the hippocampus of adult male mice. Moreover, riluzole pretreatment significantly increased the expression of hippocampal EAAT3 membrane protein and also ameliorated LPS-induced cognitive impairment in elderly male mice. Taken together, our results demonstrated that the dysfunction of EAAT3 is an important risk factor for POCD susceptibility and therefore, it may become a promising target for POCD treatment.