bluuebunny/crossref_metadata_2025 huggingface dataset:
Impulse Signal Detection for Bearing Fault Diagnosis via Residual-Variational Mode Decomposition
Authors: Liu Yuhu , Chai Yi , Liu Bowen , Wang Yiming
Published: March 2021

A novel method named residual-variational mode decomposition (RVMD) is proposed in this study to extract bearing fault features accurately. RVMD can determine the number of modes and the balance parameter adaptively, and it has two stages. In the first stage, the signal is decomposed into a series of modes until the correlation coefficient between the raw signal and the decomposition results reaches the threshold. A redefined kurtosis, which can resist the interferences from aperiodic impulse efficiency, is applied to rebuild the ensemble kurtosis index. The mode that has the largest rebuild-ensemble kurtosis, and its neighbors, are kept. By putting the residual signal into the second stage, an iteration process is applied to determine the optimal parameters for variational mode decomposition (VMD). VMD is re-run with the optimal parameters, and the sub-mode filtered with the larger rebuild-ensemble kurtosis is examined by the envelope analysis technology to observe the fault feature. The effectiveness of RVMD is verified by the simulation signal and three experiment signals. Its superiority is shown by comparing it with some existing methods.
The Impact of Aerosols on Satellite Radiance Data Assimilation Using NCEP Global Data Assimilation System
Authors: Wei Shih-Wei , Lu Cheng-Hsuan (Sarah) , Liu Quanhua , Collard Andrew , Zhu Tong , Grogan Dustin , Li Xu , Wang Jun , Grumbine Robert , Bhattacharjee Partha S.
Published: March 2021

Aerosol radiative effects have been studied extensively by climate and weather research communities. However, aerosol impacts on radiance in the context of data assimilation (DA) have received little research attention. In this study, we investigated the aerosol impacts on the assimilation of satellite radiances by incorporating time-varying three-dimensional aerosol distributions into the radiance observation operator. A series of DA experiments was conducted for August 2017. We assessed the aerosol impacts on the simulated brightness temperatures (BTs), bias correction and quality control (QC) algorithms for the assimilated infrared sensors, and analyzed temperature fields. We found that taking the aerosols into account reduces simulated BT in thermal window channels (8 to 13 μm) by up to 4 K over dust-dominant regions. The cooler simulated BTs result in more positive first-guess departures, produce more negative biases, and alter the QC checks about 20%/40% of total/assimilated observations at the wavelength of 10.39 μm. As a result, assimilating aerosol-affected BTs produces a warmer analyzed lower atmosphere and sea surface temperature which have better agreement with measurements over the trans-Atlantic region.
Evaluation and Improvement of the Quality of Ground-Based Microwave Radiometer Clear-Sky Data
Authors: Li Qing , Wei Ming , Wang Zhenhui , Chu Yanli
Published: March 2021

To assess the quality of the retrieved products from ground-based microwave radiometers, the “clear-sky” Level-2 data (LV2) products (profiles of atmospheric temperature and humidity) filtered through a radiometer in Beijing during the 24 months from January 2010 to December 2011 were compared with radiosonde data. Evident differences were revealed. Therefore, this paper investigated an approach to calibrate the observed brightness temperatures by using the model-simulated brightness temperatures as a reference under clear-sky conditions. The simulation was completed with a radiative transfer model and National Centers for Environmental Prediction final analysis (NCEP FNL) data that are independent of the radiometer system. Then, the least-squares method was used to invert the calibrated brightness temperatures to the atmospheric temperature and humidity profiles. A comparison between the retrievals and radiosonde data showed that the calibration of the brightness temperature observations is necessary, and can improve the inversion of temperature and humidity profiles compared with the original LV2 products. Specifically, the consistency with radiosonde was clearly improved: the correlation coefficients are increased, especially, the correlation coefficient for water vapor density increased from 0.2 to 0.9 around the 3 km height; the bias decreased to nearly zero at each height; the RMSE (root of mean squared error) for temperature profile was decreased by more than 1 degree at most heights; the RMSE for water vapor density was decreased from greater than 4 g/m3 to less than 1.5 g/m3 at 1 km height; and the decrease at all other heights were also noticeable. In this paper, the evolution of a temperature inversion process is given as an example, using the high-temporal-resolution brightness temperature after quality control to obtain a temperature and humidity profile every two minutes. Therefore, the characteristics of temperature inversion that cannot be seen by conventional radiosonde data (twice daily) were obtained by radiometer. This greatly compensates for the limited temporal coverage of radiosonde data. The approach presented by this paper is a valuable reference for the reprocessing of the historical observations, which have been accumulated for years by less-calibrated radiometers.
Future Irrigation Water Requirements of the Main Crops Cultivated in the Niger River Basin
Authors: Abdoulaye Abdoulaye Oumarou , Lu Haishen , Zhu Yonghua , Hamoud Yousef Alhaj
Published: March 2021

Precise agricultural predictions of climate change effects on crop water productivity are essential to ensure food security and alleviate water scarcity. In this regard, the present study provides an overview of the future impacts of climate change on the irrigation of agricultural products such as rice, millet, maize, cassava, sorghum, and sugar cane. These crops are some of the most-consumed foodstuffs in countries of the Niger River basin. This study is realized throughout 2020 to 2080, and three Global Climate Models (GCMs) (CSIRO, MIROC5, and ECHAM. MPI-ESM-LR) have been used. The GCMs data have been provided by the IPCC5 database. The irrigation water requirement for each crop was calculated using Smith’s CROPWAT approach. The Penman–Monteith equation recommended by the FAO was used to calculate the potential evapotranspiration. The inter-annual results of the IWR, according to the set of models selected, illustrate that the largest quantities of water used for irrigation are generally observed between January and March, and the lowest quantities are the most often seen between July and September. The majority of models also illustrate a peak in the IWR between March and April. Sorghum and millet are the crops consuming the least amount of water for irrigation; followed by cassava, then rice and corn, and finally sugar cane. The most significant IWRs, which have been predicted, will be between 16.3 mm/day (MIROC5 model, RCP 4.5) and 45.9 mm/day (CSIRO model, RCP 4.5), particularly in Mali, Niger, Algeria, and rarely in Burkina-Faso (CSIRO model, RCP4.5 and 8.5). The lowest IWRs predicted by the models will be from 1.29 mm/day (MIROC5 model, RCP 4.5) to 33.4 mm/day (CSIRO model, RCP 4.5); they will be observed according to the models in Guinea, southern Mali, Ivory Coast, center and southern Nigeria, and Cameroon. However, models predict sugarcane to be the plant with the highest IWR, between 0.25 mm/day (Benin in 2020–2040) and 25.66 mm/day (Chad in 2060–2080). According to the models’ predictions, millet is the crop with the most IWR, between 0.20 mm/day (Benin from 2020 to 2060) and 19.37 mm/day (Chad in 2060–2080). With the results of this study, the countries belonging to the Niger River basin can put in place robust policies in the water resources and agriculture sectors, thus ensuring food security and high-quality production of staple crops, and avoiding water scarcity while facing the negative impacts of climate change.
Semiclassical Phase Analysis for a Trapped-Atom Sagnac Interferometer
Authors: Luo Zhe , Moan E. R. , Sackett C. A.
Published: March 2021

A Sagnac atom interferometer can be constructed using a Bose–Einstein condensate trapped in a cylindrically symmetric harmonic potential. Using the Bragg interaction with a set of laser beams, the atoms can be launched into circular orbits, with two counterpropagating interferometers allowing many sources of common-mode noise to be excluded. In a perfectly symmetric and harmonic potential, the interferometer output would depend only on the rotation rate of the apparatus. However, deviations from the ideal case can lead to spurious phase shifts. These phase shifts have been theoretically analyzed for anharmonic perturbations up to quartic in the confining potential, as well as angular deviations of the laser beams, timing deviations of the laser pulses, and motional excitations of the initial condensate. Analytical and numerical results show the leading effects of the perturbations to be second order. The scaling of the phase shifts with the number of orbits and the trap axial frequency ratio are determined. The results indicate that sensitive parameters should be controlled at the 10−5 level to accommodate a rotation sensing accuracy of 10−9 rad/s. The leading-order perturbations are suppressed in the case of perfect cylindrical symmetry, even in the presence of anharmonicity and other errors. An experimental measurement of one of the perturbation terms is presented.
A Weak Turnpike Property for Perturbed Dynamical Systems with a Lyapunov Function
Authors: Zaslavski Alexander J.
Published: March 2021

In this work, we obtain a weak version of the turnpike property of trajectories of perturbed discrete disperse dynamical systems, which have a prototype in mathematical economics.
Determination of Diffusion Coefficients of Lithium in Solid Electrolyte LiPON
Authors: Rudy Alexander , Mironenko Alexander , Naumov Victor , Novozhilova Alena , Skundin Alexander , Fedorov Ivan
Published: March 2021

A structural model of LiPON solid electrolyte, containing elements that simulate drift conductivity, diffusion conductivity, and leakage current was proposed. The dependence of the impedance of the structural model on frequency was calculated, and the parameters of the model at which the theoretical curve best approximates the experimental Nyquist diagrams were determined. Based on these data, the ion diffusion coefficient and conductivity of LiPON were calculated, which are D1 = 1.5 × 10−11 cm2/s and σ = 1.9 × 10−6 S/cm, respectively.
Hormonal (Im)Balance and Reproductive System’s Disorders in Transplant Recipients—A Review
Authors: Szypulska-Koziarska Dagmara , Misiakiewicz-Has Kamila , Wiszniewska Barbara
Published: March 2021

The rising need for treatment of end stage of organ failure results in an increased number of graft recipients yearly. The most commonly transplanted organs are kidney, heart, liver, bone marrow, lung and skin. The procedure of transplantation saves and prolongs the lives of chronically ill patients or at least improves the quality. However, following transplantation recipients must take immunosuppressive drugs on a daily basis. Usually, the immunosuppressive therapy comprises two or three drugs from different groups, as the mechanism of their action varies. Although the benefits of intake of immunosuppressants is undeniable, numerous side effects are associated with them. To different extents, they are neurotoxic, nephrotoxic and may influence the function of the reproductive system. Nowadays, when infertility is an urgent problem even among healthy pairs, transplant recipients face the problem of disturbance in the hypothalamic−pituitary axis. This review will provide an overview of the most common disturbances among the concentration of sex-related hormones in recipients of both sexes at different ages, including sexually immature children, adults of reproductive age as well as elderly women and men. We have also focused on the numerous side effects of immunosuppressive therapy regarding function and morphology of reproductive organs both in males and females. The current review also presents the regimen of immunosuppressive therapy and time since transplantation.
Microbially Mediated Chemical Ecology of Animals: A Review of Its Role in Conspecific Communication, Parasitism and Predation
Authors: Mazorra-Alonso Mónica , Tomás Gustavo , Soler Juan José
Published: March 2021

Microbial symbionts are nowadays considered of pivotal importance for animal life. Among the many processes where microorganisms are involved, an emerging research avenue focuses on their major role in driving the evolution of chemical communication in their hosts. Volatiles of bacterial origin may underlie chemical communication and the transfer of social information through signals, as well as inadvertent social information. We reviewed the role of microorganisms in animal communication between conspecifics, and, because the microbiome may cause beneficial as well as deleterious effects on their animal hosts, we also reviewed its role in determining the outcome of the interactions with parasites and predators. Finally, we paid special attention to the hypothetical role of predation and parasitism in driving the evolution of the animal microbiome. We highlighted the novelty of the theoretical framework derived from considering the microbiota of animals in scenarios of communication, parasitism, and predation. We aimed to encourage research in these areas, suggesting key predictions that need to be tested to better understand what is one of the main roles of bacteria in animal biology.
Effects on Lignin Redistribution in Eucalyptus globulus Fibres Pre-Treated by Steam Explosion: A Microscale Study to Cellulose Accessibility
Authors: Troncoso-Ortega Eduardo , Castillo Rosario del P. , Reyes-Contreras Pablo , Castaño-Rivera Patricia , Teixeira Mendonça Regis , Schiappacasse Nicolás , Parra Carolina
Published: March 2021

The objective of this study was to investigate structural changes and lignin redistribution in Eucalyptus globulus pre-treated by steam explosion under different degrees of severity (S0), in order to evaluate their effect on cellulose accessibility by enzymatic hydrolysis. Approximately 87.7% to 98.5% of original glucans were retained in the pre-treated material. Glucose yields after the enzymatic hydrolysis of pre-treated material improved from 19.4% to 85.1% when S0 was increased from 8.53 to 10.42. One of the main reasons for the increase in glucose yield was the redistribution of lignin as micro-particles were deposited on the surface and interior of the fibre cell wall. This information was confirmed by laser scanning confocal fluorescence and FT-IR imaging; these microscopic techniques show changes in the physical and chemical characteristics of pre-treated fibres. In addition, the results allowed the construction of an explanatory model for microscale understanding of the enzymatic accessibility mechanism in the pre-treated lignocellulose.
Dietary Iron Intake in Excess of Requirements Impairs Intestinal Copper Absorption in Sprague Dawley Rat Dams, Causing Copper Deficiency in Suckling Pups
Authors: Lee Jennifer K. , Ha Jung-Heun , Collins James F.
Published: March 2021

Physiologically relevant iron-copper interactions have been frequently documented. For example, excess enteral iron inhibits copper absorption in laboratory rodents and humans. Whether this also occurs during pregnancy and lactation, when iron supplementation is frequently recommended, is, however, unknown. Here, the hypothesis that high dietary iron will perturb copper homeostasis in pregnant and lactating dams and their pups was tested. We utilized a rat model of iron-deficiency/iron supplementation during pregnancy and lactation to assess this possibility. Rat dams were fed low-iron diets early in pregnancy, and then switched to one of 5 diets with normal (1×) to high iron (20×) until pups were 14 days old. Subsequently, copper and iron homeostasis, and intestinal copper absorption (by oral, intragastric gavage with 64Cu), were assessed. Copper depletion/deficiency occurred in the dams and pups as dietary iron increased, as evidenced by decrements in plasma ceruloplasmin (Cp) and superoxide dismutase 1 (SOD1) activity, depletion of hepatic copper, and liver iron loading. Intestinal copper transport and tissue 64Cu accumulation were lower in dams consuming excess iron, and tissue 64Cu was also low in suckling pups. In some cases, physiological disturbances were noted when dietary iron was only ~3-fold in excess, while for others, effects were observed when dietary iron was 10–20-fold in excess. Excess enteral iron thus antagonizes the absorption of dietary copper, causing copper depletion in dams and their suckling pups. Low milk copper is a likely explanation for copper depletion in the pups, but experimental proof of this awaits future experimentation.
Resting-State Functional Connectivity in Mathematical Expertise
Authors: Shim Miseon , Hwang Han-Jeong , Kuhl Ulrike , Jeon Hyeon-Ae
Published: March 2021

To what extent are different levels of expertise reflected in the functional connectivity of the brain? We addressed this question by using resting-state functional magnetic resonance imaging (fMRI) in mathematicians versus non-mathematicians. To this end, we investigated how the two groups of participants differ in the correlation of their spontaneous blood oxygen level-dependent fluctuations across the whole brain regions during resting state. Moreover, by using the classification algorithm in machine learning, we investigated whether the resting-state fMRI networks between mathematicians and non-mathematicians were distinguished depending on features of functional connectivity. We showed diverging involvement of the frontal–thalamic–temporal connections for mathematicians and the medial–frontal areas to precuneus and the lateral orbital gyrus to thalamus connections for non-mathematicians. Moreover, mathematicians who had higher scores in mathematical knowledge showed a weaker connection strength between the left and right caudate nucleus, demonstrating the connections’ characteristics related to mathematical expertise. Separate functional networks between the two groups were validated with a maximum classification accuracy of 91.19% using the distinct resting-state fMRI-based functional connectivity features. We suggest the advantageous role of preconfigured resting-state functional connectivity, as well as the neural efficiency for experts’ successful performance.
Not Only Mania or Depression: Mixed States/Mixed Features in Paediatric Bipolar Disorders
Authors: Janiri Delfina , Conte Eliana , De Luca Ilaria , Simone Maria Velia , Moccia Lorenzo , Simonetti Alessio , Mazza Marianna , Marconi Elisa , Monti Laura , Chieffo Daniela Pia Rosaria , Kotzalidis Georgios , Janiri Luigi , Sani Gabriele
Published: March 2021

Background: early onset is frequent in Bipolar Disorders (BDs), and it is characterised by the occurrence of mixed states (or mixed features). In this systematic review, we aimed to confirm and extend these observations by providing the prevalence rates of mixed states/features and data on associated clinical, pharmacological and psychopathological features. Methods: following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched from inception to 9 February 2021 for all studies investigating mixed states/mixed features in paediatric BD. Data were independently extracted by multiple observers. The prevalence rates of mixed states/features for each study were calculated. Results: eleven studies were included in our review, involving a total patient population of 1365 individuals. Overall, of the patients with paediatric age BD, 55.2% had mixed states/features (95% CI 40.1–70.3). Children with mixed states/features presented with high rates of comorbidities, in particular, with Attention Deficit Hyperactivity Disorder (ADHD). Evidences regarding the psychopathology and treatment response of mixed states/features are currently insufficient. Conclusions: our findings suggested that mixed states/features are extremely frequent in children and adolescents with BD and are characterised by high levels of comorbidity. Future investigations should focus on the relationship between mixed states/features and psychopathological dimensions as well as on the response to pharmacological treatment.
Chronic Alcohol Use Induces Molecular Genetic Changes in the Dorsomedial Thalamus of People with Alcohol-Related Disorders
Authors: Hade Andreas-Christian , Philips Mari-Anne , Reimann Ene , Jagomäe Toomas , Eskla Kattri-Liis , Traks Tanel , Prans Ele , Kõks Sulev , Vasar Eero , Väli Marika
Published: March 2021

The Mediodorsal (MD) thalamus that represents a fundamental subcortical relay has been underrepresented in the studies focusing on the molecular changes in the brains of subjects with alcohol use disorder (AUD). In the current study, MD thalamic regions from AUD subjects and controls were analyzed with Affymetrix Clariom S human microarray. Long-term alcohol use induced a significant (FDR ≤ 0.05) upregulation of 2802 transcripts and downregulation of 1893 genes in the MD thalamus of AUD subjects. A significant upregulation of GRIN1 (glutamate receptor NMDA type 1) and FTO (alpha-ketoglutarate dependent dioxygenase) was confirmed in western blot analysis. Immunohistochemical staining revealed similar heterogenous distribution of GRIN1 in the thalamic nuclei of both AUD and control subjects. The most prevalent functional categories of upregulated genes were related to glutamatergic and GABAergic neurotransmission, cellular metabolism, and neurodevelopment. The prevalent gene cluster among down-regulated genes was immune system mediators. Forty-two differentially expressed genes, including FTO, ADH1B, DRD2, CADM2, TCF4, GCKR, DPP6, MAPT and CHRH1, have been shown to have strong associations (FDR p < 10−8) with AUD or/and alcohol use phenotypes in recent GWA studies. Despite a small number of subjects, we were able to detect robust molecular changes in the mediodorsal thalamus caused by alcohol emphasizing the importance of deeper brain structures such as diencephalon, in the development of AUD-related dysregulation of neurocircuitry.
Neural Oscillation Associated with Contagious Itch in Patients with Atopic Dermatitis
Authors: Lee In-Seon , Kim Kyuseok , Park Hi-Joon , Lee Hyangsook , Jung Won-Mo , Kim Do-Won , Chae Younbyoung
Published: March 2021

Objective: Itch is an unpleasant sensation associated with an urge to scratch and is a major health care issue associated with atopic dermatitis (AD). Contagious itch, i.e., subjective feelings of itchiness induced by watching others’ scratching behavior, is common in patients with AD. Using electroencephalography, we examined alpha (8–13 Hz) oscillations in sensorimotor areas associated with the desire to scratch in patients with AD. Methods: Thirty-six patients with AD and 34 healthy controls (HCs) participated in this study. They evaluated their itch levels after watching short videos of a model scratching or tapping parts of his body. Neural oscillations were recorded from nine electrodes, including those placed over sensorimotor areas. Time–frequency analysis was used to compare mu rhythm suppression over the sensorimotor areas in response to these videos between patients with AD and HCs. Results: The behavioral test showed that the visual stimuli induced increased feelings of itchiness in patients with AD relative to HCs under the tapping and scratching conditions. The time–frequency analysis revealed that mu rhythm suppression in response to scratching images was significantly prominent in patients with AD, but not in HCs. Conclusion: Patients with AD exhibited increased susceptibility to contagious itch. This phenomenon might be related to enhanced mu rhythm suppression in sensorimotor areas of the brain in these patients. Our findings provide new insight into the neurophysiological basis of itch sensations in patients with AD.
Characteristics Associated with Depression Severity in 270 Juveniles in a Major Depressive Episode
Authors: Serra Giulia , Iannoni Maria Elena , Trasolini Monia , Maglio Gino , Frattini Camilla , Casini Maria Pia , Baldessarini Ross J. , Vicari Stefano
Published: March 2021

Introduction: Severe depression is prevalent in young persons and can lead to disability and elevated suicidal risk. Objectives: To identify clinical and demographic factors associated with the severity of depression in juveniles diagnosed with a major mood disorder, as a contribution to improving clinical treatment and reducing risk of suicide. Methods: We analyzed factors associated with depression severity in 270 juveniles (aged 6–18 years) in a major depressive episode, evaluated and treated at the Bambino Gesù Children’s Hospital of Rome. Depressive symptoms were rated with the revised Children’s Depression Rating Scale (CDRS-R) and manic symptoms with the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) Mania Rating Scale (K-SADS-MRS). Bivariate comparisons were followed by multivariable linear regression modeling. Results: Depression severity was greater among females than males (55.0 vs. 47.2), with the diagnosis of a major depressive disorder (MDD) vs. bipolar disorder (BD; 53.8 vs. 49.3), and tended to increase with age (slope = 1.14). Some symptoms typical of mania were associated with greater depression severity, including mood lability, hallucinations, delusions, and irritability, whereas less likely symptoms were hyperactivity, pressured speech, grandiosity, high energy, and distractibility. Factors independently and significantly associated with greater depression severity in multivariable linear regression modeling were: MDD vs. BD diagnosis, female sex, higher anxiety ratings, mood lability, and irritability. Conclusions: Severe depression was significantly associated with female sex, the presence of some manic or psychotic symptoms, and with apparent unipolar MDD. Manic/psychotic symptoms should be assessed carefully when evaluating a juvenile depressive episode and considered in treatment planning in an effort to balance risks of antidepressants and the potential value of mood-stabilizing and antimanic agents to decrease the severity of acute episodes and reduce suicidal risk.
Increased Visceral Adipose Tissue and Hyperinsulinemia Raise the Risk for Recurrence of Non-B Non-C Hepatocellular Carcinoma after Curative Treatment
Authors: Imai Kenji , Takai Koji , Miwa Takao , Maeda Toshihide , Hanai Tatsunori , Shiraki Makoto , Suetsugu Atsushi , Shimizu Masahito
Published: March 2021

We investigated the factors affecting recurrence-free survival in patients with non-B non-C hepatocellular carcinoma (HCC) who received curative treatment. Decision-tree analysis was performed in 72 curative cases of non-B non-C HCC to extract the risk factors for recurrence. The reliability of the extracted risk factors was evaluated using the Kaplan–Meier method and the Cox proportional hazards model. The decision-tree analysis extracted three factors—visceral adipose tissue (VAT) index (VATI; <71 and ≥71 cm2/m2), which was the cross-sectional areas of VAT on the computed tomographic image at the umbilical level, normalized by the square of the height, fasting immunoreactive insulin (FIRI; <5.5 and ≥5.5 µU/mL), and alpha-fetoprotein (AFP; <11 and ≥11 ng/mL). The Cox proportional hazards model showed that VATI (hazard ratio (HR): 2.556, 95% confidence interval (CI): 1.191–5.486, p = 0.016), FIRI (HR: 3.149, 95% CI: 1.156–8.575, p = 0.025), and AFP (HR: 3.362, 95% CI: 1.550–7.288, p = 0.002) were all independent risk factors for HCC recurrence. Non-B non-C HCC patients with a higher VATI (≥71 cm2/m2) or higher FIRI (≥5.5 µU/mL) and AFP (≥11 ng/mL) if VATI was <71 cm2/m2 are prone to recurrence after curative treatment.
Apoptosis-Inducing TNF Superfamily Ligands for Cancer Therapy
Authors: Diaz Arguello Olivia A. , Haisma Hidde J.
Published: March 2021

Cancer is a complex disease with apoptosis evasion as one of its hallmarks; therefore, apoptosis induction in transformed cells seems a promising approach as a cancer treatment. TNF apoptosis-inducing ligands, which are naturally present in the body and possess tumoricidal activity, are attractive candidates. The most studied proteins are TNF-α, FasL, and TNF-related apoptosis-inducing ligand (TRAIL). Over the years, different recombinant TNF family-derived apoptosis-inducing ligands and agonists have been designed. Their stability, specificity, and half-life have been improved because most of the TNF ligands have the disadvantages of having a short half-life and affinity to more than one receptor. Here, we review the outlook on apoptosis-inducing ligands as cancer treatments in diverse preclinical and clinical stages and summarize strategies of overcoming their natural limitations to improve their effectiveness.
Combination Assessment of Diffusion-Weighted Imaging and T2-Weighted Imaging Is Acceptable for the Differential Diagnosis of Lung Cancer from Benign Pulmonary Nodules and Masses
Authors: Usuda Katsuo , Ishikawa Masahito , Iwai Shun , Iijima Yoshihito , Motono Nozomu , Matoba Munetaka , Doai Mariko , Hirata Keiya , Uramoto Hidetaka
Published: March 2021

The purpose of this study is to determine whether the combination assessment of DWI and T2-weighted imaging (T2WI) improves the diagnostic ability for differential diagnosis of lung cancer from benign pulmonary nodules and masses (BPNMs). The optimal cut-off value (OCV) for differential diagnosis was set at 1.470 × 10−3 mm2/s for apparent diffusion coefficient (ADC), and at 2.45 for T2 contrast ratio (T2 CR). The ADC (1.24 ± 0.29 × 10−3 mm2/s) of lung cancer was significantly lower than that (1.69 ± 0.58 × 10−3 mm2/s) of BPNM. The T2 CR (2.01 ± 0.52) of lung cancer was significantly lower than that (2.74 ± 1.02) of BPNM. As using the OCV for ADC, the sensitivity was 83.9% (220/262), the specificity 63.4% (33/52), and the accuracy 80.6% (253/314). As using the OCV for T2 CR, the sensitivity was 89.7% (235/262), the specificity 61.5% (32/52), and the accuracy 85.0% (267/314). In 212 PNMs which were judged to be malignant by both DWI and T2WI, 203 PNMs (95.8%) were lung cancers. In 33 PNMs which were judged to be benign by both DWI and T2WI, 23 PNMs (69.7%) were BPNMs. The combined assessment of DWI and T2WI could judge PNMs more precisely and would be acceptable for differential diagnosis of PNMs.
Hot and Cold Tumors: Is Endoglin (CD105) a Potential Target for Vessel Normalization?
Authors: Ollauri-Ibáñez Claudia , Ayuso-Íñigo Blanca , Pericacho Miguel
Published: March 2021

Tumors are complex masses formed by malignant but also by normal cells. The interaction between these cells via cytokines, chemokines, growth factors, and enzymes that remodel the extracellular matrix (ECM) constitutes the tumor microenvironment (TME). This TME can be determinant in the prognosis and the response to some treatments such as immunotherapy. Depending on their TME, two types of tumors can be defined: hot tumors, characterized by an immunosupportive TME and a good response to immunotherapy; and cold tumors, which respond poorly to this therapy and are characterized by an immunosuppressive TME. A therapeutic strategy that has been shown to be useful for the conversion of cold tumors into hot tumors is vascular normalization. In this review we propose that endoglin (CD105) may be a useful target of this strategy since it is involved in the three main processes involved in the generation of the TME: angiogenesis, inflammation, and cancer-associated fibroblast (CAF) accumulation. Moreover, the analysis of endoglin expression in tumors, which is already used in the clinic to study the microvascular density and that is associated with worse prognosis, could be used to predict a patient’s response to immunotherapy.
Impact on All-Cause and Cardiovascular Mortality Rates of Coronary Artery Calcifications Detected during Organized, Low-Dose, Computed-Tomography Screening for Lung Cancer: Systematic Literature Review and Meta-Analysis
Authors: Gendarme Sébastien , Goussault Helene , Assié Jean-Baptiste , Taleb Cherifa , Chouaïd Christos , Landre Thierry
Published: March 2021

Although organized, low-dose, computed-tomography (CT) scan lung-cancer screening has been shown to lower all-cause and lung-cancer-specific mortality, the primary cause of death for subjects eligible for such screening remains cardiovascular (CV) mortality. This meta-analysis study was undertaken to evaluate the impact of screening-scan-detected coronary artery calcifications (CACs) on CV and all-cause mortality. We conducted a systematic review and meta-analysis of studies reporting CV mortality according to the Agatson CAC score for participants in a lung-cancer screening program of randomized clinical or cohort studies. PubMed, Embase, and Cochrane databases were screened in June 2020. Two authors independently selected articles and extracted data. Six studies, including 20,175 subjects, were retained. CV and all-cause mortality rates were higher for subjects with CAC scores >0, with respective relative risks of 2.02 [95% CI 1.23–3.32] and 2.29 [95% CI 1.00–5.21]. Both mortality rates were even higher for those with high CAC scores (>400 or >1000). CACs are more common in men than in women, with an odds ratio of 1.49 [95% CI 1.40–1.59]. The presence of CAC is associated with CV mortality with an RR of 2.05 [95% CI 1.20–3.57] in men and 2.37 [CI 95% 1.29–5.09] in women, respectively. Analysis of lung-cancer-screening scans for CACs is a tool able to predict CV mortality. Prospective studies within those programs are needed to assess the benefit of primary CV prevention based on CAC detection.
Immunmodulatory Treatment Strategies of Hepatocellular Carcinoma: From Checkpoint Inhibitors Now to an Integrated Approach in the Future
Authors: Ocker Matthias , Mayr Christian , Kiesslich Tobias , Stintzing Sebastian , Neureiter Daniel
Published: March 2021

Background: Hepatocellular carcinoma (HCC) still represents a human tumor entity with very limited therapeutic options, especially for advanced stages. Here, immune checkpoint modulating drugs alone or in combination with local ablative techniques could open a new and attractive therapeutic “door” to improve outcome and response rate for patients with HCC. Methods: Published data on HCC experimental to pre-(clinical) treatment strategies from standard of care to novel immunomodulatory concepts were summarized and discussed in detail. Results: Overall, our knowledge of the role of immune checkpoints in HCC is dramatically increased in the last years. Experimental and pre-clinical findings could be translated to phase 1 and 2 clinical trials and became standard of care. Local ablative techniques of HCC could improve the effectivity of immune checkpoint inhibitors in situ. Conclusions: This review demonstrates the importance of immunomodulatory treatment strategies of HCC, whereby the “best treatment code” of immune checkpoint drugs, combination with ablative techniques and of timing must be evaluated in coming clinical trials.
Which Is the Best Treatment in Recurrent Thymoma? A Systematic Review and Meta-Analysis
Authors: Chiappetta Marco , Grossi Ugo , Sperduti Isabella , Margaritora Stefano , Marulli Giuseppe , Fiorelli Alfonso , Sandri Alberto , Mizuno Tetsuya , Cusumano Giacomo , Hamaji Masatsugu , Cesario Alfredo , Lococo Filippo
Published: March 2021

Background: Optimal recurrent thymoma management remains arguable because of limited patient numbers, and relatively late and variable recurrence patterns. Given the absence of high-quality evidence and relatively small study cohorts, we performed a quantitative meta-analysis to determine the outcome of surgical and non-surgical approaches assessing the five-year overall survival (5y overall survival (OS)) in patients with recurrent thymoma. Methods: We performed a comprehensive literature search and analysis according to PRISMA guidelines of studies published from 1 January 1980 until 18 June 2020 from PubMed/MEDLINE, EMBASE, and Scopus. We included studies with the cohorts’ superior to 30 patients describing recurrent thymoma treatment, comparing surgical and non-surgical approaches reporting survival data. Results: Literature search revealed 3017 articles. Nine studies met all inclusion criteria and were selected for the meta-analysis. The recurrences were local/regional in 73–98% of cases and multiple in 49–72%. After treatment, 5y OS ranged from 48–77% and 10y OS from 37–51%. The quantitative meta-analysis showed a better outcome comparing surgical vs other treatments. Two studies showed statistically significant risk differences in the 5y OS favoring complete resection. After pooling results of seven studies using the random model, the combined 5y OS risk difference was 0.39, with lower and upper limits of 0.16 and 0.62, respectively (p = 0.001), and a moderate heterogeneity among studies (p = 0.098, I2 = 43.9%). Definitive conclusions could not be drawn regarding the prognostic impact of myasthenia gravis, histology, and patterns of relapse reported in literature. Conclusions: Surgical treatment after thymoma recurrence is associated with a significant better 5y OS; therefore, surgical resection should be preferred in all technically feasible cases.
Residual Disease in Glioma Recurrence: A Dangerous Liaison with Senescence
Authors: Putavet Diana A. , de Keizer Peter L. J.
Published: March 2021

With a dismally low median survival of less than two years after diagnosis, Glioblastoma (GBM) is the most lethal type of brain cancer. The standard-of-care of surgical resection, followed by DNA-damaging chemo-/radiotherapy, is often non-curative. In part, this is because individual cells close to the resection border remain alive and eventually undergo renewed proliferation. These residual, therapy-resistant cells lead to rapid recurrence, against which no effective treatment exists to date. Thus, new experimental approaches need to be developed against residual disease to prevent GBM survival and recurrence. Cellular senescence is an attractive area for the development of such new approaches. Senescence can occur in healthy cells when they are irreparably damaged. Senescent cells develop a chronic secretory phenotype that is generally considered pro-tumorigenic and pro-migratory. Age is a negative prognostic factor for GBM stage, and, with age, senescence steadily increases. Moreover, chemo-/radiotherapy can provide an additional increase in senescence close to the tumor. In light of this, we will review the importance of senescence in the tumor-supportive brain parenchyma, focusing on the invasion and growth of GBM in residual disease. We will propose a future direction on the application of anti-senescence therapies against recurrent GBM.
UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation
Authors: Nelson Ryan S. , Seligson Nathan D. , Bottiglieri Sal , Carballido Estrella , Cueto Alex Del , Imanirad Iman , Levine Richard , Parker Alexander S. , Swain Sandra M. , Tillman Emma M. , Hicks J. Kevin
Published: March 2021

Multi-gene assays often include UGT1A1 and, in certain instances, may report associated toxicity risks for irinotecan, belinostat, pazopanib, and nilotinib. However, guidance for incorporating UGT1A1 results into therapeutic decision-making is mostly lacking for these anticancer drugs. We summarized meta-analyses, genome-wide association studies, clinical trials, drug labels, and guidelines relating to the impact of UGT1A1 polymorphisms on irinotecan, belinostat, pazopanib, or nilotinib toxicities. For irinotecan, UGT1A1*28 was significantly associated with neutropenia and diarrhea, particularly with doses ≥ 180 mg/m2, supporting the use of UGT1A1 to guide irinotecan prescribing. The drug label for belinostat recommends a reduced starting dose of 750 mg/m2 for UGT1A1*28 homozygotes, though published studies supporting this recommendation are sparse. There was a correlation between UGT1A1 polymorphisms and pazopanib-induced hepatotoxicity, though further studies are needed to elucidate the role of UGT1A1-guided pazopanib dose adjustments. Limited studies have investigated the association between UGT1A1 polymorphisms and nilotinib-induced hepatotoxicity, with data currently insufficient for UGT1A1-guided nilotinib dose adjustments.
Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma
Authors: Radocha Jakub , van de Donk Niels W. C. J. , Weisel Katja
Published: March 2021

Multiple myeloma is the second most common hematologic malignancy. Current treatment strategies are mainly based on immunomodulatory drugs, proteasome inhibitors or combination of both. Novel agents added to these backbone treatments represent a promising strategy in treatment of newly diagnosed as well as relapsed and refractory multiple myeloma patients. In this respect, the incorporation of monoclonal antibodies into standard-of-care regimens markedly improved prognosis of myeloma patients during the last years. More specifically, monoclonal anti-CD38 antibodies, daratumumab and isatuximab, have been implemented into treatment strategies from first-line treatment to refractory disease. In addition, the monoclonal anti-SLAM-F7 antibody elotuzumab in combination with immunomodulatory drugs has improved the clinical outcomes of patients with relapsed/refractory disease. Belantamab mafodotin is the first approved antibody drug conjugate directed against B cell maturation antigen and is currently used as a monotherapy for patients with advanced disease. This review focuses on clinical efficacy and safety of monoclonal antibodies as well as antibody drug conjugates in multiple myeloma.
Flavonoids Alleviate Peripheral Neuropathy Induced by Anticancer Drugs
Authors: Siddiqui Manaal , Abdellatif Basma , Zhai Kevin , Liskova Alena , Kubatka Peter , Büsselberg Dietrich
Published: March 2021

Purpose: This study aimed to assess the potential of flavonoids in combating CIPN. Methods: PubMed and Google Scholar were used, and studies that investigated flavonoids in models of CIPN and models of neuropathic pain similar to CIPN were included. Only studies investigating peripheral mechanisms of CIPN were used. Results: Flavonoids inhibit several essential mechanisms of CIPN, such as proinflammatory cytokine release, astrocyte and microglial activation, oxidative stress, neuronal damage and apoptosis, mitochondrial damage, ectopic discharge, and ion channel activation. They decreased the severity of certain CIPN symptoms, such as thermal hyperalgesia and mechanical, tactile, and cold allodynia. Conclusions: Flavonoids hold immense promise in treating CIPN; thus, future research should investigate their effects in humans. Specifically, precise pharmacological mechanisms and side effects need to be elucidated in human models before clinical benefits can be achieved.
Catalytic Performance of CPM-200-In/Mg in the Cycloaddition of CO2 and Epoxides
Authors: Gu Yunjang , Choe Youngson , Park Dae-Won
Published: March 2021

Crystalline porous materials (CPM)-200-In and CPM-200-In/Mg metal-organic frameworks (MOFs) were synthesized by a solvothermal method and were characterized by using powder X-ray diffraction (PXRD), FT-IR, Brunauer–Emmett–Teller (BET), temperature programmed desorption (TPD), TGA, XPS, and SEM-EDS. They were used as heterogeneous catalysts for the cycloaddition of CO2 with epoxides and found to be highly efficient toward the cycloaddition reaction at moderate reaction conditions under solvent-free conditions. The catalyst was easily separated by a simple filtration and can be reused up to five consecutive times without any considerable decrease of its initial activity. CPM-200-In/Mg showed excellent catalytic performance in the cycloaddition reaction due to the synergistic role of the acidic sites and basic sites. A plausible reaction mechanism for the CPM-200-In/Mg MOF catalyzed cycloaddition reaction is proposed based on the experimental results and our previously reported DFT (Density Functional Theory) studies.
One-Pot Synthesis of 7, 7-Dimethyl-4-Phenyl-2-Thioxo-2,3,4,6,7, 8-Hexahydro-1H-Quinazoline-5-OnesUsing Zinc Ferrite Nanocatalyst and Its Bio Evaluation
Authors: Rao Tentu Nageswara , Krishnarao Nalla , Ahmed Faheem , Alomar Suliman Yousef , Albalawi Fadwa , Mani Panagal , Aljaafari Abdullah , Parvatamma Botsa , Arshi Nishat , Kumar Shalendra
Published: March 2021

A simple and highly efficient protocol for the synthesis of derivatives 7, 7-dimethyl-4-phenyl-2-thioxo-2, 3, 4, 6, 7, 8-hexahydro-1H-quinazoline-5-one from 5, 5-dimethyl cyclohexane-1, 3-dione (4a–4h) (dimedone) has been described. The aryl aldehydes were substituted with thiourea in the presence of synthesized zinc ferrite nanocatalyst, which increased the yield under reflux through condensation, followed by cyclization to give desired products. The other advantages are that it is eco-friendly and economically affordable for large-scale production. Structural validation and characterization of all the newly synthesized compounds were evaluated by spectral analysis (mass spectrometry, proton nuclear magnetic resonance (1HNMR), and Carbon-13 nuclear magnetic resonance(13CNMR)spectroscopies. The structure of antibacterial and antifungal assays was performed with the newly synthesized compounds. The antimicrobial activity of title compounds possessing electron-withdrawing groups such as (4e–4h) (Cl, Br, and cyano group) exhibited more active potential than the electron-donating groups, C6H5,4-C6H4, 3-OC2H5-4OH-C6H3, etc., (4a–4d) containing moiety.
Catalytic Epoxidation of 3-Carene and Limonene with Aqueous Hydrogen Peroxide, and Selective Synthesis of α-Pinene Epoxide from Turpentine
Authors: Fomenko Vladislav V. , Laev Sergey S. , Salakhutdinov Nariman F.
Published: March 2021

The epoxidation of turpentine (technical α-pinene), 3-carene, and limonene with aqueous hydrogen peroxide was studied in a new catalytic system employing manganese sulfate, salicylic acid, sodium bicarbonate, and acetonitrile, as a polar solvent. The proposed approach makes it possible to carry out a “chemical separation” of turpentine components, yielding valuable individual derivatives of monoterpenes without the need to isolate individual monoterpene reagents. Specific methods have been developed for the production of α-pinene epoxide, 3-carene epoxide, limonene diepoxide, as well as for two related compounds: 3-carene-5-one and 3-carene-2,5-dione.
Effect of Muscle Cell Preservation on Viability and Differentiation of Hamstring Tendon Graft In Vitro
Authors: Lee Jin Kyu , Jo Sungsin , Lee Young Lim , Weon Subin , Song Jun-Seob , Sung Il-Hoon , Kim Tae-Hwan
Published: March 2021

Muscle tissue is often removed during hamstring tendon graft preparation for anterior cruciate ligament (ACL) reconstruction. The purpose of the study was to test whether preservation of muscle remnants on a tendon graft is beneficial to the graft healing process following ACL reconstruction. Co-culturing of tendon-derived cells (TDCs) and muscle-derived cells (MDCs) was performed at various ratios, and their potential for cell viability and multilineage differentiation was compared to a single TDC cell group. Ligamentous and chondrogenic differentiation was most enhanced when a small population of MDCs was co-cultured with TDCs (6:2 co-culture group). Cell viability and osteogenic differentiation were proportionally enhanced with increasing MDC population size. MDCs co-cultured with TDCs possess both the ability to enhance cell viability and differentiate into other cell lineages.