bluuebunny/crossref_metadata_2025 huggingface dataset:
Facemask Usage Among People With Primary Ciliary Dyskinesia During the COVID-19 Pandemic: A Participatory Project
Authors: Pedersen Eva S. L. , Collaud Eugenie N. R. , Mozun Rebeca , Dexter Katie , Kruljac Catherine , Silberschmidt Hansruedi , Lucas Jane S. ,   COVID-PCD patient advisory group
Published: January 2022

Objectives: Primary ciliary dyskinesia (PCD) is a rare genetic disease that causes recurrent respiratory infections. People with PCD may be at high risk of severe COVID-19 and protection against SARS-CoV-2 is therefore important. We studied facemask usage and problems reported in relation with their use among people with PCD.

Methods: We used data from COVID-PCD, an international observational cohort study. A questionnaire was e-mailed to participants in October 2020 that asked about facemask usage.

Results: In total, 282 participants from 27 countries were included (Median age 32 years; 63% female). In total, 252 (89%) wore facemasks everywhere in public, 13 (5%) wore facemasks in most places, and 17 (6%) did not wear facemasks in public. Half of the participants reported that it was uncomfortable to wear facemasks because of runny nose, cough, or difficulty breathing. Participants less often wore facemasks when there was no national requirement.

Conclusion: Most people with PCD wore facemasks despite frequent respiratory problems related to their use. Facemask usage was most frequent in countries with a national requirement emphasizing the importance of nationwide policies mandating facemasks.
Convex Neural Networks Based Reinforcement Learning for Load Frequency Control under Denial of Service Attacks
Authors: Zeng Fancheng , Qi Guanqiu , Zhu Zhiqin , Sun Jian , Hu Gang , Haner Matthew
Published: January 2022

With the increase in the complexity and informatization of power grids, new challenges, such as access to a large number of distributed energy sources and cyber attacks on power grid control systems, are brought to load-frequency control. As load-frequency control methods, both aggregated distributed energy sources (ADES) and artificial intelligence techniques provide flexible solution strategies to mitigate the frequency deviation of power grids. This paper proposes a load-frequency control strategy of ADES-based reinforcement learning under the consideration of reducing the impact of denial of service (DoS) attacks. Reinforcement learning is used to evaluate the pros and cons of the proposed frequency control strategy. The entire evaluation process is realized by the approximation of convex neural networks. Convex neural networks are used to convert the nonlinear optimization problems of reinforcement learning for long-term performance into the corresponding convex optimization problems. Thus, the local optimum is avoided, the optimization process of the strategy utility function is accelerated, and the response ability of controllers is improved. The stability of power grids and the convergence of convex neural networks under the proposed frequency control strategy are studied by constructing Lyapunov functions to obtain the sufficient conditions for the steady states of ADES and the weight convergence of actor–critic networks. The article uses the IEEE14, IEEE57, and IEEE118 bus testing systems to verify the proposed strategy. Our experimental results confirm that the proposed frequency control strategy can effectively reduce the frequency deviation of power grids under DoS attacks.
Sertoli, Leydig, and Spermatogonial Cells’ Specific Gene and Protein Expressions as Dog Testes Evolve from Immature into Mature States
Authors: Kasimanickam Vanmathy R. , Kasimanickam Ramanathan K.
Published: January 2022

Sertoli, Leydig, and spermatogonial cells proliferate and differentiate from birth to puberty and then stay stable in adulthood. We hypothesized that expressions of spermatogenesis-associated genes are not enhanced with a mere increase of these cells’ numbers. To accept this postulation, we investigated the abundances of Sertoli cell-specific FSHR and AMH, Leydig cell-specific LHR and INSL3, and spermatogonia-specific THY1 and CDH1 markers in immature and mature canine testis. Four biological replicates of immature and mature testes were processed, and RT-PCR was performed to elucidate the cells’ specific markers. The data were analyzed by ANOVA, using the 2−∆∆Ct method to ascertain differences in mRNA expressions. In addition, Western blot and IHC were performed. Gene expressions of all the studied cells’ specific markers were down-regulated (p < 0.05) in adult testis compared with immature testis. Western blot and immunohistochemistry showed the presence of these proteins in the testis. Protein expressions were greater in immature testis compared with mature testis (p < 0.05). Despite the obvious expansion of these cells’ numbers from immature to adult testis, the cells’ specific markers were not enriched in mature testis compared with immature dog testis. The results support the postulation that the gene expressions do not directly correlate with the increase of the cell numbers during post-natal development but changes in gene expressions show functional significance.
Process of Introduction of Australian Braford Cattle to South America: Configuration of Population Structure and Genetic Diversity Evolution
Authors: González Araceli Rocío Marisel , Navas González Francisco Javier , Crudeli Gustavo Ángel , Delgado Bermejo Juan Vicente , Camacho Vallejo María Esperanza , Quirino Celia Raquel
Published: January 2022

This study analyzes the evolution of the population structure and genetic diversity of Braford cattle in South America from 1949 to 2019 to suggest effective strategies for breeding in the future. The percentage of bulls historically increased. The average generational interval decreased to 11.78 years for the current population. Average inbreeding (F) and coancestry (C) are low and show a historically increasing trend (0.001% to 0.002%, respectively). The degree of nonrandom mating (α) increased from −0.0001 to 0.0001 denoting a change in the trend to mate similar individuals. The average relatedness coefficient (ΔR) increased in the current period from 0.002% to 0.004%. A single ancestor explained 4.55% to 7.22% of the population’s gene pool. While the effective population size based on the individual inbreeding rate (NeFi) was 462.963, when based on the individual coancestry rate (NeCi), it was 420.168. Genetic diversity loss is small and mainly ascribed to bottlenecks (0.12%) and to unequal contributions of the founders (0.02%). Even if adequate levels of diversity can be found, practices that consider the overuse of individual bulls (conditioned by nature or not), could lead to a long-term reduction in diversity. The present results permit tailoring genetic management strategies that are perfectly adapted to the needs that the population demands internationally.
Experimental Study to Replicate Wood Fuel Conversion in a Downdraft Gasifier: Features and Mechanism of Single Particle Combustion in an Inert Channel
Authors: Svishchev Denis
Published: January 2022

Downdraft gasification is a promising process of energy conversion of wood biomass. There are such fuel conversion conditions that differ favorably from conventional conditions. In such conditions, there is no pyrolysis zone in the fuel bed, which precedes the oxidation zone. Fuel is supplied into the oxidizing zone without charring, where it reacts with the intensive cold air flow from tuyeres. The study aims to replicate the conversion of particles in a gasifier close to tuyeres. For this purpose, the individual particles are burned in the muffle furnace space and the quartz channel replicating presence of other bed particles at a first approximation. In the experiment, the furnace temperature was varied, as well as the velocity of air supplied to the particle. Two-stage and single-stage mechanisms of particle combustion were identified. A two-stage process is observed in the range of tuyere velocities below 20 m s−1. The two-stage mechanism is characterized by a stage of devolatilization and volatiles combustion, followed by a stage of char residue combustion. The stages are predominantly separate from each other, and their degree of overlapping is low, amounting to 24%. At the tuyere velocities above 125 m s−1 combustion of particles is realized primarily as a single-stage process. The intensive air flow reaches the fuel particle surface and initiates combustion of the surface char layer. In this case, the stages of devolatilization and char residue combustion run concurrently for the most part. In the single-stage mechanism, the degree of stage overlapping is significantly higher and amounts to 60–95%. For the two-stage combustion mechanism, the effect of cyclic movement of the flame across the particle surface is evident. The number of cycles can reach eight. This effect is due to the change of conversion stages. At air velocity above 95 m s−1, fragmentation of fuel particles commences. A layer of char formed at an initial stage of burning heats up in the intensive air flow and is separated from the particle surface. The heated walls of the quartz channel contribute to the intensification of particle combustion. This effect is probably due to the swirling of the flame between the wall and the particle surface.
Estimating Weibull Parameters Using Mabchour’s Method (MMab) for Wind Power at RAWA City, Iraq
Authors: Altmimi Amani I. , Al-Swaiedi Safaa J. , Abdullah Oday Ibraheem
Published: January 2022

Wind power is one of the most important sources of renewable energy. In this research paper, we developed an approach to select the optimum site among four different locations in Iraq (Talafar, Nasiriyah, Baghdad and RAWA) according to wind power density. Based on the optimization process, it was found that the RAWA city is the optimal site. We adopted Mabchour’s Method (MMab) to estimate the Weibull distribution parameters (c, k) for RAWA city at two heights (10 m and 50 m) for the period (2017–2019). It was found that the Mabchour technique (MMab) produced accurate results with minimum consumed time and effort. This was because the values of k and c were close to each other. Additionally, the coefficient values of the results of the Weibull measurements were very close to the average wind speeds that we measured. The values of the correlation coefficients between the Weibull scale parameters and the form were calculated and were equal to R2 = 0.9971. The minimum value of the coefficient of variation (COV) for turbulence intensity was found to be 26% in July 2018, when the wind speeds reached their maximum. The highest error of wind power density between measured data (PM) and Weibull distribution (PW) was found to be 4.48%, at a height of 50 m.
Research on Pre-Seismic Feature Recognition of Spatial Electric Field Data Recorded by CSES
Authors: Li Zhong , Li Jinwen , Huang Jianping , Yin Huichao , Jia Juan
Published: January 2022

In order to study the abnormal disturbance of the space ionosphere caused by strong earthquakes, the methods of SGF + WTA and EMD + ER are proposed and compared. The methods are applied to the 7.7 magnitude earthquake that occurred on the southern coast of Cuba on 29 January 2020 based on the electric field ultra-low frequency waveform data recorded by the ZH-1 electromagnetic satellite. Analyzing the electric field waveform data of the six orbits in and around the epicenter within five days before the earthquake and revisiting the orbit within two months, the significant information about the changes in the ionospheric electric field before the earthquake is obtained. The results demonstrate that: (1) in terms of time, large anomalies appeared before the earthquake on 16 January, and some orbital perturbations lasted until 2 February; (2) in terms of location, the disturbance changes are mainly concentrated over the central earthquake zone, and there are few conjugate zones; (3) in terms of amplitude, during the five days before the impending earthquake, most of the orbital disturbances exceeded the threshold of the background value while some of the orbital disturbances were less than the threshold; (4) in terms of morphology, the fluctuation that did not exceed the threshold appeared in the south of the earthquake area while a few appeared in the north. At the same time, the analysis method proposed in this paper is able to effectively extract the characteristics of electric field signal, clearly describe the abnormal signal change information before the earthquake, and provide a new method reference for the study of spatial electric field waveform data.
Assessing the Impacts of Human Activities on Air Quality during the COVID-19 Pandemic through Case Analysis
Authors: Chi Xin , Hua Jie , Hua Shuyang , Ren Xiao , Yang Shuanghe
Published: January 2022

COVID-19 is the latest of many pandemic affecting the world in the past few decades, and it has had a significant impact on the global environment. Some research has analysed the effects of the pandemic on air quality; however, very few studies have employed relationship analytics. In order to analyse the potential relationship between pandemic-related information and air quality data from a more holistic and detailed point of view, we propose a methodology based on pure data analysis. Three types of data were collected, namely air quality index, pandemic-related events, and number of COVID cases. Data were collected from five cities—Wuhan, New York, Seoul, Melbourne, and Singapore—to further analyse the response of air quality index to COVID events, thus revealing how human activity influences air quality from a pandemic perspective. The results show that a potential connection does exist in most cases and provide more evidence showing that air pollution declined during the pandemic. However, the strength of this relationship may also be related to other factors, such as geography, politics, population density, and measures imposed by local authorities, etc. This study provides another perspective to assist stakeholders in improving environmental decision making.
Small Hero with Great Powers: Vaccinia Virus E3 Protein and Evasion of the Type I IFN Response
Authors: Szczerba Mateusz , Subramanian Sambhavi , Trainor Kelly , McCaughan Megan , Kibler Karen V. , Jacobs Bertram L.
Published: January 2022

Poxviridae have developed a plethora of strategies to evade innate and adaptive immunity. In this review, we focused on the vaccinia virus E3 protein, encoded by the E3L gene. E3 is present within the Chordopoxvirinae subfamily (with the exception of the avipoxviruses and molluscum contagiosum virus) and displays pleiotropic effects on the innate immune system. Initial studies identified E3 as a double-stranded RNA (dsRNA)-binding protein (through its C terminus), able to inhibit the activation of protein kinase dependent on RNA (PKR) and the 2′5′-oligoadenylate synthetase (OAS)/RNase L pathway, rendering E3 a protein counteracting the type I interferon (IFN) system. In recent years, N-terminal mutants of E3 unable to bind to Z-form nucleic acids have been shown to induce the cellular death pathway necroptosis. This pathway was dependent on host IFN-inducible Z-DNA-binding protein 1 (ZBP1); full-length E3 is able to inhibit ZBP1-mediated necroptosis. Binding to what was identified as Z-RNA has emerged as a novel mechanism of counteracting the type I IFN system and has broadened our understanding of innate immunity against viral infections. This article gives an overview of the studies leading to our understanding of the vaccinia virus E3 protein function and its involvement in viral pathogenesis. Furthermore, a short summary of other viral systems is provided.
Tau mRNA Metabolism in Neurodegenerative Diseases: A Tangle Journey
Authors: da Costa Paulo J. , Hamdane Malika , Buée Luc , Martin Franck
Published: January 2022

Tau proteins are known to be mainly involved in regulation of microtubule dynamics. Besides this function, which is critical for axonal transport and signal transduction, tau proteins also have other roles in neurons. Moreover, tau proteins are turned into aggregates and consequently trigger many neurodegenerative diseases termed tauopathies, of which Alzheimer’s disease (AD) is the figurehead. Such pathological aggregation processes are critical for the onset of these diseases. Among the various causes of tau protein pathogenicity, abnormal tau mRNA metabolism, expression and dysregulation of tau post-translational modifications are critical steps. Moreover, the relevance of tau function to general mRNA metabolism has been highlighted recently in tauopathies. In this review, we mainly focus on how mRNA metabolism impacts the onset and development of tauopathies. Thus, we intend to portray how mRNA metabolism of, or mediated by, tau is associated with neurodegenerative diseases.
A Sensitive Aptasensor Using Biotin-Streptavidin System for Patulin Detection in Apple Juice
Authors: Tang Xiaoqian , Zhang Qi , Isabel Pividori Maria , Zhang Zhaowei , Marty Jean-Louis , Catanante Gaëlle
Published: January 2022

Patulin contamination in fruits, vegetables, and their products is considered a serious health risk factor for food safety and human health. Thus, a rapid, simple detection method for patulin is becoming important, which could provide a tool for routine screening and food surveys. The objective of this study was to develop a sensitive aptamer-based lateral flow assay (FLA) using Streptavidin functionalized gold nanoparticles for sensitive patulin detection. An excellent dynamic range for patulin detection was obtained (2.7~139.8 ng/mL in the buffer and 7.07~359.5 ng/mL in the sample) with no affinity for other mycotoxins such as zearalenone (ZEN), ochratoxin A (OTA), aflatoxin B1 (AFB1), citrinin or tenuazonic acid (TEA). The limit of detection was 0.19 ng/mL in the buffer and 0.36 ng/mL in the real sample. The recoveries were 83.3% to 107.1%, with a satisfactory RSD value from 6.5% to 7.5%. Hence the established LFA could be used as a rapid, simple, on-site screening tool for PAT determination in apple juice.
Oxidative and Nitrosative Stress in Major Depressive Disorder: A Case Control Study
Authors: Somani Aditya , Singh Abhishek Kumar , Gupta Bandna , Nagarkoti Sheela , Dalal Pronob Kumar , Dikshit Madhu
Published: January 2022

Introduction: The role of increased oxidative stress and alterations to the nitric oxide (NO) pathway have been implicated in major depressive disorder (MDD). The two pathways interact closely with each other but have not been studied simultaneously in MDD. This study aimed to assess and compare the levels of oxidative and nitrosative stress in the neutrophils (PMNs) of drug-naive MDD patients and their first-degree relatives. Methods: 29 drug-naive MDD patients and 27 healthy first-degree relatives and healthy controls aged 18–45 years were included in this study. An assessment of the levels of reactive oxygen species (ROS), nitrites, neuronal NO synthase (nNOS), and myeloperoxidase in PMNs, and cortisol in serum was carried out. Results: Compared to healthy controls, the generation of free radicals, myeloperoxidase activity, and nNOS mRNA expression in PMNs, and cortisol level in serum were significantly higher in drug-naive depression patients. Indeed, increased levels of myeloperoxidase and serum cortisol were also noted in first-degree relatives. The total nitrite content in the PMNs and plasma however was significantly lower in both patients and first-degree relatives. Interestingly, a positive correlation was established in the ROS levels in the PMNs, plasma and neutrophil nitrite, and the serum cortisol level between MDD patients and their first-degree relatives. Conclusion: The results of this study contribute towards a better understanding of the familial association of depressive disorder, and demonstrate for the first time that neutrophil ROS/RNS, plasma nitrite, and serum cortisol levels are positively correlated between MDD patients and their first-degree relatives. However, further studies in larger, more diverse samples are needed to extend these pathways as potential biomarkers to identify persons at high risk for psychopathology at an early stage.
Pre-Service Teachers Learning to Teach English to Very Young Learners in Macau: Do Beliefs Trump Practice?
Authors: Reynolds Barry Lee , Ha Xuan Van , Ding Chen , Zhang Xiaofang , Liu Sylvia , Ma Xiaoyan
Published: January 2022

The global importance of English and therefore the teaching of the English language has made the English language curriculum an integral part of all levels of teacher education, including early childhood education. The purpose of this study was to first explore the beliefs about the teaching of English to very young learners held by pre-service pre-primary teachers in Macau and then to see whether these beliefs were reflected in their microteaching. Qualitative content analysis performed on the written reflections and transcriptions of the microteaching videos of 75 pre-service pre-primary teachers found that their beliefs about classroom practices, lesson planning, and English as a foreign language (EFL) learners and learning were the most predominant beliefs exhibited in their reflections and were evidenced in their microteaching. Less predominant, but still salient, were their beliefs about the goals of language learning, assessment, teaching, pedagogical knowledge, and content. No observable practices were found regarding the pre-service teachers’ beliefs about the role of teaching, learning to teach, microteaching, the self, the subject, hearsay, self-assessment, and schooling. The current study found that with only limited exposure to EFL teaching methodology from a single course, the pre-service pre-primary teachers were able to implement some of their beliefs about several important aspects of teaching English to very young learners.
Comprehensive Evaluation of Vocal Outcomes and Quality of Life after Total Laryngectomy and Voice Restoration with J-Flap and Tracheoesophageal Puncture
Authors: Tsao Chung-Kan , Marchi Filippo , Kang Chung-Jan , Sampieri Claudio , Lu Yi-An , Huang Shiang-Fu , Chen Yu-Ting , Giordano Giorgio , Peretti Giorgio , Parrinello Giampiero , Iandelli Andrea , Fang Tuan-Jen
Published: January 2022

Background: Tracheoesophageal puncture with a voice prosthesis is the gold standard for speech rehabilitation in patients that receive a laryngopharyngectomy. However, a novel surgical technique, using a tubularized anterolateral tight flap, named “J-flap,” has been demonstrated to produce adequate voice restoration. We aimed to compare the outcomes and the quality of life of patients who underwent voice rehabilitation with both techniques. Methods: We enrolled patients that underwent laryngopharyngectomy and voice restoration surgery. The control group received a tracheoesophageal puncture with a voice prosthesis, while the study group received J-flap reconstruction. A total of 20 patients received voice prosthesis rehabilitation, while 18 received J-flap reconstruction. Speech and vocal outcomes and quality of life metrics were collected. Results: The objective phonatory performances and the acoustic voice analysis did not outline a significant difference. Speech pathologists judged the consonant pronunciation in the J-flap group as less accurate (p < 0.001). The voice handicap index revealed a moderate impairment for the J-flap group (p < 0.001). Quality of life scores were higher for the voice prosthesis group. Conclusion: Voice prostheses and J-flaps share similar objective phonatory outcomes. Quality of life was more impaired in the J-flap group. In our view, these two techniques possess complementary characteristics in clinical practice, taking into account health care system regulations and patients’ social background.
Platelet Count and Survival after Cancer
Authors: Giannakeas Vasily , Kotsopoulos Joanne , Brooks Jennifer D. , Cheung Matthew C. , Rosella Laura , Lipscombe Lorraine , Akbari Mohammad R. , Austin Peter C. , Narod Steven A.
Published: January 2022

Thrombocytosis is associated with cancer progression and death for many cancer types. It is unclear if platelet count is also associated with cancer survival. We conducted a cohort study of 112,231 adults in Ontario with a diagnosis of cancer between January 2007 and December 2016. We included patients who had a complete blood count (CBC) completed in the 30 days prior to their cancer diagnosis. Subjects were assigned to one of three categories according to platelet count: low (≤25th percentile), medium (>25 to <75th percentile), and high (≥75th percentile). Study subjects were followed from the date of their cancer diagnosis for cancer-specific death. Of the 112,231 eligible cancer patients in the cohort study, 40,329 (35.9%) died from their cancer in the follow-up period. Relative to those with a medium platelet count, the rate of cancer-specific death was higher among individuals with a high platelet count (HR 1.52; 95%CI 1.48–1.55) and was lower among individuals with a low platelet count (HR 0.91; 95%CI 0.88–0.93). A high platelet count was associated with poor survival for many cancer types. Platelet count could potentially be used as a risk stratification measure for cancer patients.
Recent Advanced in the Treatment of Advanced SCC Tumors
Authors: Basset-Seguin Nicole , Maubec Eve
Published: January 2022

Squamous cell carcinoma (SCC) is the second most frequent form of skin cancer after basal cell carcinoma. While most SCC can be treated by surgery or radiotherapy, some progress into an advanced form and are no longer suitable for these treatments. Guidelines and staging systems have help to define these advanced SCC (aSCC), for which prognosis was very poor until recently. Platin-based chemotherapy was traditionally used, but few prospective trials and no treatment regimen was recommended. Furthermore, toxicity in elderly patients limited its use. The development of immunotherapy has improved the prognosis of these difficult-to-treat aSCC. In this review, we define high risk and aSCC and explored current treatment strategies for these tumors.
Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges
Authors: Wu Bocheng , Sodji Quaovi H. , Oyelere Adegboyega K.
Published: January 2022

Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chronic inflammatory diseases and cancers. We also recognized the value of the re-evaluation of the disease-specific roles of multiple pathways implicated in the pathophysiology of chronic inflammatory diseases and cancers—as well as the application of data from single-cell RNA sequencing in the success of future drug discovery endeavors.
Safety and Efficacy of 177Lutetium-PSMA-617 Radioligand Therapy Shortly after Failing 223Radium-Dichloride
Authors: Baumgarten Justus , Groener Daniel , Nguyen Ngoc Christina , Mader Nicolai , Chaurasia Maximilian , Davis Karen , Wichert Jennifer , Chun Felix K. H. , Tselis Nikolaos , Happel Christian , Grünwald Frank , Sabet Amir
Published: January 2022

Bone-seeking 223Radium-dichloride (223Ra) is an established treatment prolonging survival and reducing morbidity in selected patients with metastatic castration-resistant prostate cancer (mCRPC) with skeletal involvement. Radioligand therapy with 177Lutetium-PSMA-617 (177Lu-PSMA-617) has been increasingly implemented in patients with mCRPC failing conventional treatment options. In this study, the safety and efficacy of 177Lu-PSMA-617 in patients with progressive bone involvement under treatment with 223Ra was assessed. Twenty-eight men (median age 73 years, range 63–89 years) with progressive mCRPC, who started 177Lu-PSMA-617 within 8 weeks after the last 223Ra administration, received a median of 4 (IQR 3–6) and a total of 120 cycles of 223Ra and a median of 4 (IQR 2–7) cycles 177Lu-PSMA-617 with a mean treatment activity of 6.5 ± 1.2 GBq per cycle, reaching a mean cumulative activity of 30.7 ± 23.4 GBq. A PSA response (≥50% PSA decline 12 weeks after the first 177Lu-PSMA-617 cycle) was observed in 18/28 (64.3%) patients and imaging-based partial remission (PR) was observed in 11/28 (39.3%) patients. Median imaging-based progression-free survival (PFS) was 10 (95% CI, 6–14) months and median overall survival (OS) was 18 (95% CI, 14–22) months. Patients with low bone tumor burden (2–20 lesions) had a significantly longer OS (28 vs. 14 months, p < 0.045) compared to patients with a high tumor burden (>20 lesions). Grade ≥ 3 hematological toxicity was observed in six patients after their last treatment cycle with anemia, leukopenia and thrombocytopenia in 5/28 (17.9%), 4/28 (14.3%) and 6/28 (21.4%) patients, respectively. In progressive bone-metastatic mCRPC patients, prompt initiation of 177Lu-PSMA-617 after failing 223Ra is effective with an acceptable toxicity profile.
Alternative Splicing, Epigenetic Modifications and Cancer: A Dangerous Triangle, or a Hopeful One?
Authors: Gimeno-Valiente Francisco , López-Rodas Gerardo , Castillo Josefa , Franco Luis
Published: January 2022

The alteration of epigenetic modifications often causes cancer onset and development. In a similar way, aberrant alternative splicing may result in oncogenic products. These issues have often been individually reviewed, but there is a growing body of evidence for the interconnection of both causes of cancer. Actually, aberrant splicing may result from abnormal epigenetic signalization and epigenetic factors may be altered by alternative splicing. In this way, the interrelation between epigenetic marks and alternative splicing form the base of a triangle, while cancer may be placed at the vertex. The present review centers on the interconnections at the triangle base, i.e., between alternative splicing and epigenetic modifications, which may result in neoplastic transformations. The effects of different epigenetic factors, including DNA and histone modifications, the binding of non-coding RNAs and the alterations of chromatin organization on alternative splicing resulting in cancer are first considered. Other less-frequently considered questions, such as the epigenetic regulation of the splicing machinery, the aberrant splicing of epigenetic writers, readers and erasers, etc., are next reviewed in their connection with cancer. The knowledge of the above-mentioned relationships has allowed increasing the collection of biomarkers potentially useful as cancer diagnostic and/or prognostic tools. Finally, taking into account on one hand that epigenetic changes are reversible, and some epigenetic drugs already exist and, on the other hand, that drugs intended for reversing aberrations in alternative splicing, therapeutic possibilities for breaking the mentioned cancer-related triangle are discussed.
Development of Preclinical Ultrasound Imaging Techniques to Identify and Image Sentinel Lymph Nodes in a Cancerous Animal Model
Authors: Bacou Marion , Rajasekaran Vidya , Thomson Adrian , Sjöstrand Sandra , Kaczmarek Katarzyna , Ochocka-Fox Anna Maria , Gerrard Adam D. , Moug Susan , Jansson Tomas , Mulvana Helen , Moran Carmel M. , Farrington Susan M.
Published: January 2022

Lymph nodes (LNs) are believed to be the first organs targeted by colorectal cancer cells detached from a primary solid tumor because of their role in draining interstitial fluids. Better detection and assessment of these organs have the potential to help clinicians in stratification and designing optimal design of oncological treatments for each patient. Whilst highly valuable for the detection of primary tumors, CT and MRI remain limited for the characterization of LNs. B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) can improve the detection of LNs and could provide critical complementary information to MRI and CT scans; however, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines advise that further evidence is required before US or CEUS can be recommended for clinical use. Moreover, knowledge of the lymphatic system and LNs is relatively limited, especially in preclinical models. In this pilot study, we have created a mouse model of metastatic cancer and utilized 3D high-frequency ultrasound to assess the volume, shape, and absence of hilum, along with CEUS to assess the flow dynamics of tumor-free and tumor-bearing LNs in vivo. The aforementioned parameters were used to create a scoring system to predict the likelihood of a disease-involved LN before establishing post-mortem diagnosis with histopathology. Preliminary results suggest that a sum score of parameters may provide a more accurate diagnosis than the LN size, the single parameter currently used to predict the involvement of an LN in disease.
High-Definition Ultrasound Characterization of Squamous Carcinoma of the Tongue: A Descriptive Observational Study
Authors: Di Stasio Dario , Montella Marco , Romano Antonio , Colella Giuseppe , Serpico Rosario , Lucchese Alberta
Published: January 2022

High-definition ultrasonography is a diagnostic tool that uses sound echoes to produce images of tissues and organs. In the head and neck region, ultrasounds have been used to diagnose different types of lesions. The intraoral approach was shown to be a real-time, non-invasive way to characterize oral lesions. The tongue is the most often examined region because of its accessibility. This observational study aimed to describe the qualitative characteristics of tongue squamous cell carcinoma images obtained with high-definition intraoral ultrasound by comparing them with the corresponding histopathological sample. Twenty patients were enrolled in this study. The scans of the lesions were carried out with an 18 MHz linear ultrasound probe following the long axis of the lesion. For each lesion, five frames were selected, on which descriptive analysis was performed. A histological sample was taken and then compared to the ultrasonographic acquisition. The sonographic appearance of the tissue layers has a good correlation between ultrasound and histological morphology, and it was easy to distinguish the tumor from the homogenous composition of the tongue tissues. Furthermore, a correlation between the structure by section and pattern of tumor margin features by ultrasound was obtained. Intraoral ultrasonography appears to be a promising technique in the non-invasive characterization of tongue squamous cell carcinoma. Further studies will be needed to improve the technique in terms of ergonomics and repeatability.
Characteristics and Outcome of Elderly Patients (>55 Years) with Acute Lymphoblastic Leukemia
Authors: Wenge Daniela V. , Wethmar Klaus , Klar Corinna A. , Kolve Hedwig , Sauer Tim , Angenendt Linus , Evers Georg , Call Simon , Kerkhoff Andrea , Khandanpour Cyrus , Kessler Torsten , Mesters Rolf , Schliemann Christoph , Mikesch Jan-Henrik , Reicherts Christian , Brüggemann Monika , Berdel Wolfgang E. , Lenz Georg , Stelljes Matthias
Published: January 2022

Prognosis of elderly ALL patients remains dismal. Here, we retrospectively analyzed the course of 93 patients > 55 years with B-precursor (n = 88) or T-ALL (n = 5), who received age-adapted, pediatric-inspired chemotherapy regimens at our center between May 2003 and October 2020. The median age at diagnosis was 65.7 years, and surviving patients had a median follow-up of 3.7 years. CR after induction therapy was documented in 76.5%, while the rate of treatment-related death within 100 days was 6.4%. The OS of the entire cohort at 1 and 3 year(s) was 75.2% (95% CI: 66.4–84.0%) and 47.3% (95% CI: 36.8–57.7%), respectively, while the EFS at 1 and 3 years(s) was 59.0% (95% CI: 48.9–69.0%) and 32.9% (95% CI: 23.0–42.8%), respectively. At 3 years, the cumulative incidence (CI) of relapse was 48.3% (95% CI: 38.9–59.9%), and the CI rate of death in CR was 17.3% (95% CI: 10.9–27.5%). Older age and an ECOG > 2 represented risk factors for inferior OS, while BCR::ABL1 status, immunophenotype, and intensity of chemotherapy did not significantly affect OS. We conclude that intensive treatment is feasible in selected elderly ALL patients, but high rates of relapse and death in CR underline the need for novel therapeutic strategies.
Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts
Authors: Soma Emi , Yamayoshi Asako , Toda Yuki , Mishima Yuji , Hosogi Shigekuni , Ashihara Eishi
Published: January 2022

Nucleic acid medicines have been developed as new therapeutic agents against various diseases; however, targeted delivery of these reagents into cancer cells, particularly hematologic cancer cells, via systemic administration is limited by the lack of efficient and cell-specific delivery systems. We previously demonstrated that monoclonal antibody (mAb)-oligonucleotide complexes targeting exosomal microRNAs with linear oligo-D-arginine (Arg) linkers were transferred into solid cancer cells and inhibited exosomal miRNA functions. In this study, we developed exosome-capturing anti-CD63 mAb-conjugated small interfering RNAs (siRNAs) with branched Arg linkers and investigated their effects on multiple myeloma (MM) cells. Anti-CD63 mAb-conjugated siRNAs were successfully incorporated into MM cells. The incorporation of exosomes was inhibited by endocytosis inhibitors. We also conducted a functional analysis of anti-CD63 mAb-conjugated siRNAs. Ab-conjugated luciferase+ (luc+) siRNAs significantly decreased the luminescence intensity in OPM-2-luc+ cells. Moreover, treatment with anti-CD63 mAb-conjugated with MYC and CTNNB1 siRNAs decreased the mRNA transcript levels of MYC and CTNNB1 to 52.5% and 55.3%, respectively, in OPM-2 cells. In conclusion, exosome-capturing Ab-conjugated siRNAs with branched Arg linkers can be effectively delivered into MM cells via uptake of exosomes by parental cells. This technology has the potential to lead to a breakthrough in drug delivery systems for hematologic cancers.
Genetic Landscape of Multistep Hepatocarcinogenesis
Authors: Takeda Haruhiko , Takai Atsushi , Eso Yuji , Takahashi Ken , Marusawa Hiroyuki , Seno Hiroshi
Published: January 2022

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Although several targeted therapy agents are available for advanced HCC, their antitumor efficacy remains limited. As the complex genetic landscape of HCC would compromise the antitumor efficacy of targeted therapy, a deeper understanding of the genetic landscape of hepatocarcinogenesis is necessary. Recent comprehensive genetic analyses have revealed the driver genes of HCC, which accumulate during the multistage process of hepatocarcinogenesis, facilitating HCC genetic heterogeneity. In addition, as early genetic changes may represent key therapeutic targets, the genetic landscapes of early HCC and precancerous liver tissues have been characterized in recent years, in parallel with the advancement of next-generation sequencing analysis. In this review article, we first summarize the landscape of the liver cancer genome and its intratumor heterogeneity. We then introduce recent insight on early genetic alterations in hepatocarcinogenesis, especially those in early HCC and noncancerous liver tissues. Finally, we summarize the multistep accumulation of genetic aberrations throughout cancer progression and discuss the future perspective towards the clinical application of this genetic information.
Adrenal Mass Characterization in the Era of Quantitative Imaging: State of the Art
Authors: Barat Maxime , Cottereau Anne-Ségolène , Gaujoux Sébastien , Tenenbaum Florence , Sibony Mathilde , Bertherat Jérôme , Libé Rossella , Gaillard Martin , Jouinot Anne , Assié Guillaume , Hoeffel Christine , Soyer Philippe , Dohan Anthony
Published: January 2022

Detection and characterization of adrenal lesions have evolved during the past two decades. Although the role of imaging in adrenal lesions associated with hormonal secretion is usually straightforward, characterization of non-functioning adrenal lesions may be challenging to confidently identify those that need to be resected. Although many adrenal lesions can be readily diagnosed when they display typical imaging features, the diagnosis may be challenging for atypical lesions. Computed tomography (CT) remains the cornerstone of adrenal imaging, but other morphological or functional modalities can be used in combination to reach a diagnosis and avoid useless biopsy or surgery. Early- and delayed-phase contrast-enhanced CT images are essential for diagnosing lipid-poor adenoma. Ongoing studies are evaluating the capabilities of dual-energy CT to provide valid virtual non-contrast attenuation and iodine density measurements from contrast-enhanced examinations. Adrenal lesions with attenuation values between 10 and 30 Hounsfield units (HU) on unenhanced CT can be characterized by MRI when iodinated contrast material injection cannot be performed. 18F-FDG PET/CT helps differentiate between atypical benign and malignant adrenal lesions, with the adrenal-to-liver maximum standardized uptake value ratio being the most discriminative variable. Recent studies evaluating the capabilities of radiomics and artificial intelligence have shown encouraging results.
The Fairy Chemical Imidazole-4-carboxamide Inhibits the Expression of Axl, PD-L1, and PD-L2 and Improves Response to Cisplatin in Melanoma
Authors: Inoue Chisa , Yasuma Taro , D’Alessandro-Gabazza Corina N. , Toda Masaaki , Fridman D’Alessandro Valeria , Inoue Ryo , Fujimoto Hajime , Kobori Hajime , Tharavecharak Suphachai , Takeshita Atsuro , Nishihama Kota , Okano Yuko , Wu Jing , Kobayashi Tetsu , Yano Yutaka , Kawagishi Hirokazu , Gabazza Esteban C.
Published: January 2022

The leading cause of death worldwide is cancer. Many reports have proved the beneficial effect of mushrooms in cancer. However, the precise mechanism is not completely clear. In the present study, we focused on the medicinal properties of biomolecules released by fairy ring-forming mushrooms. Fairy chemicals generally stimulate or inhibit the growth of surrounding vegetation. In the present study, we evaluated whether fairy chemicals (2-azahypoxanthine, 2-aza-8-oxohypoxanthine, and imidazole-4-carboxamide) exert anticancer activity by decreasing the expression of Axl and immune checkpoint molecules in melanoma cells. We used B16F10 melanoma cell lines and a melanoma xenograft model in the experiments. Treatment of melanoma xenograft with cisplatin combined with imidazole-4-carboxamide significantly decreased the tumor volume compared to untreated mice or mice treated cisplatin alone. In addition, mice treated with cisplatin and imidazole-4-carboxamide showed increased peritumoral infiltration of T cells compared to mice treated with cisplatin alone. In vitro studies showed that all fairy chemicals, including imidazole-4-carboxamide, inhibit the expression of immune checkpoint molecules and Axl compared to controls. Imidazole-4-carboxamide also significantly blocks the cisplatin-induced upregulation of PD-L1. These observations point to the fairy chemical imidazole-4-carboxamide as a promising coadjuvant therapy with cisplatin in patients with cancer.
Post-Discharge Effects and Parents’ Opinions of Intranasal Fentanyl with Oral Midazolam Sedation in Pediatric Dental Patients: A Cross-Sectional Study
Authors: Alhaidari Roaa I. , AlSarheed Maha A.
Published: January 2022

The aim of this study was to evaluate the post-discharge effects of oral midazolam with intranasal fentanyl sedation in pediatric patients who had dental treatment and to evaluate parents’ preference regarding sedation visits. Methods: A total of 32 uncooperative healthy pediatric patients aged 3–6 years old who met the inclusion criteria were included. In the first visit, one group received oral midazolam (0.7 mg/kg) with intranasal fentanyl (1 μg/kg) sedation (M/F) and the other group received oral midazolam with intranasal placebo (M), and in the second visit each group received the other type of sedation in a cross-over type. In this cross-sectional study, a post-discharge phone-call questionnaire was carried out 24 h after both sedation visits with the parents to evaluate the children’s behavior, function, balance, eating pattern, sleeping pattern, vomiting incidents, and any possible side effects, as well as parents’ satisfaction and preference. The Wilcoxon signed-rank test was used to analyze the categorical variables, and the Chi-square test was performed to analyze the parents’ preference. Result: A total of 32 parents responded to the phone-call questionnaire after 64 sedation visits. All of them were mothers. There was no statistically significant difference between the two groups with respect to recovery to normal function and balance, behavior, incidents of fever, vomiting, sleep disturbance, oversleeping, and adverse behavioral changes (p > 0.05). Children required a significantly longer amount of time until the first meal after M/F sedation (p = 0.04). No significant difference was found between parents’ preferences regarding the sedation visits (p > 0.05). Conclusion: Intranasal fentanyl added to oral midazolam sedation could have an effect on post-discharge adverse behavioral changes, prolonged sleeping, and prolonged recovery time. Children sedated with midazolam/fentanyl required a longer amount of time until the first meal. Vomiting and fever occurred similarly in both sedation regimens with a low incidence. There was no difference in parents’ preferences regarding the two sedation regimens.
The Effect of Corrective Feedback in Basic Cognitive Tasks: A Study in Early Childhood
Authors: Moret-Tatay Carmen , Vaquer-Cardona Enrique , Bernabé-Valero Gloria , Blasco-Magraner José Salvador , Sáiz-Mauleón Begoña , Jorques-Infante María José , Iborra-Marmolejo Isabel , Beneyto-Arrojo María José
Published: January 2022

The aim of this study was to examine the effect of trial-by-trial corrective feedback in a go-no-go task for children. A sample of 40 preschool students, divided into 4- and 5-year-olds, participated in the study, as well as a group of 20 university students. All the groups performed the task in a counterbalanced design of blocks with and without corrective feedback. Reaction time and accuracy rate were measured as dependent variables. Moreover, reaction time was also analyzed through an ex-Gaussian fit. Children were slightly more accurate and slower under the presence of corrective feedback, suggesting a more conservative pattern. University students were faster, but corrective feedback did not reach the statistical level. Regarding reaction time components, a reduction of the distribution tails, depicted by the τ parameter, was found for both groups under the corrective feedback condition. This suggests that parameterization of reaction time can be considered as a strategy for a more detailed analysis to examine the effect of corrective feedback, even at early ages. In this way, corrective feedback depicted beneficial effects in the τ parameter at early ages, suggesting its use in basic cognitive tasks based on go-no-go but not for older groups.