bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Different Copy Number Variations of the CLCN2 Gene in Chinese Cattle and Their Association with Growth Traits
Authors: Tang Jia , Shen Xuemei , Yang Yu , Yang Haiyan , Qi Ao , Yang Shuling , Qu Kaixing , Lan Xianyong , Huang Bizhi , Chen Hong
Published: December 2021

Copy number variation (CNV) can affect gene function and even individual phenotypic traits by changing the transcription and translation level of related genes, and it also plays an important role in species evolution. Chloride voltage-gated channel 2 (CLCN2) encodes a voltage-gated chloride channel (CLC-2), which has a wide organ distribution and is ubiquitously expressed. Based on previous studies, we hypothesize that CLCN2 could be a candidate gene involved in cell volume regulation, transepithelial transport and cell proliferation. This study aimed to explore CNVs in the CLCN2 gene and investigate its association with growth traits in four Chinese cattle breeds (Yunling cattle, Xianan cattle, Qinchuan cattle and Pinan cattle). We identified there are two copy number variation regions (CNV1: 3600 bp, including exon 2–11; CNV2: 4800 bp, including exon 21–22) of the CLCN2 gene. The statistical analysis showed that the CNV1 mutation in the YL cattle population was significantly associated with cannon circumference (p < 0.01). The CNV2 mutation in the XN cattle population had a significant effect on body slanting length, chest girth and body weight (p < 0.05). In the YL cattle, the association analysis of CLCN2 gene CNV1 and CNV2 combination with cannon circumference was significant (p < 0.01). Our results provide evidence that CNV1 and CNV2 in CLCN2 are associated with growth traits in two different cattle populations and could be used as candidate markers for cattle molecular breeding.
Soft Pneumatic Fingertip Actuator Incorporating a Dual Air Chamber to Generate Multi-Mode Simultaneous Tactile Feedback
Authors: Hashem Mohammad Shadman , Joolee Joolekha Bibi , Hassan Waseem , Jeon Seokhee
Published: December 2021

A complete set of diverse haptic feedbacks is essential for a highly realistic and immersive virtual environment. In this sense, a multi-mode haptic interface that simultaneously generates multiple kinds of haptic signals is highly desirable. In this paper, we propose a new silicone-made pneumatically controlled fingertip actuator to render pressure and vibrotactile feedback concurrently to offer a realistic and effective haptic sensation. A new silicone-based stacked dual-layer air chamber was designed. The volume of the chambers is controlled by pneumatic valves with compressed air tanks. The top/upper air chamber renders vibration feedback, whereas the bottom/lower air chamber renders pressure feedback. The proposed silicone-made fingertip actuator is designed so that it can be easily worn at the fingertips. To demonstrate the potential of the system, a virtual environment for rendering three different types of haptic textures was implemented. Extensive performance evaluation and user studies were carried out to demonstrate the proposed actuator’s effectiveness compared to an actuator with single vibrotactile feedback.
Phase Formation and the Electrical Properties of YSZ/rGO Composite Ceramics Sintered Using Silicon Carbide Powder Bed
Authors: Glukharev Artem , Glumov Oleg , Smirnov Ivan , Boltynjuk Evgeniy , Kurapova Olga , Konakov Vladimir
Published: December 2021

Fully stabilized zirconia/graphene composites are very promising advanced structural materials having mixed ion–electron conductivity for energy storage and energy conversion applications. The existing methods of the composite manufacturing have a number of disadvantages that limit their practical use. Thus, the search for new sintering methods is an actively developing area. In this work, we report for the first time the application of the SiC powder bed sintering technique for fully stabilized zirconia (YSZ) composite fabrication. The reduced graphene oxide (rGO) was used as a graphene derivative. As a result, well-formed ceramics with high density and crystallinity, the maximal microhardness of 13 GPa and the values of the ionic conductivity up to 10−2 S/cm at 650 °C was obtained. The effects of the sintering conditions and rGO concentration on the microstructure and conductivities of ceramics are discussed in detail. The suggested powder bed sintering technique in a layered graphite/SiC/graphite powder bed allowed well-formed dense YSZ/rGO ceramics fabrication and can become a suitable alternative to existing methods for various oxide ceramic matrix composite fabrication: both conventional sintering and non-equilibrium (SPS, flash sintering) approaches.
Assessing the Relevance of Opinions in Uncertainty and Info-Incompleteness Conditions
Authors: Iovane Gerardo , Landi Riccardo Emanuele , Rapuano Antonio , Amatore Riccardo
Published: December 2021

Researchers are interested in defining decision support systems that can act in contexts characterized by uncertainty and info-incompleteness. The present study proposes a learning model for assessing the relevance of probability, plausibility, credibility, and possibility opinions in the conditions above. The solution consists of an Artificial Neural Network acquiring input features related to the considered set of opinions and other relevant attributes. The model provides the weights for minimizing the error between the expected outcome and the ground truth concerning a given phenomenon of interest. A custom loss function was defined to minimize the Mean Best Price Error (MBPE), while the evaluation of football players’ was chosen as a case study for testing the model. A custom dataset was constructed by scraping the Transfermarkt, Football Manager, and FIFA21 information sources and by computing a sentiment score through BERT, obtaining a total of 398 occurrences, of which 85% were employed for training the proposed model. The results show that the probability opinion represents the best choice in conditions of info-completeness, predicting the best price with 0.86 MBPE (0.61% of normalized error), while an arbitrary set composed of plausibility, credibility, and possibility opinions was considered for deciding successfully in info-incompleteness, achieving a confidence score of 2.47±0.188 MBPE (1.89±0.15% of normalized error). The proposed solution provided high performance in predicting the transfer cost of a football player in conditions of both info-completeness and info-incompleteness, revealing the significance of extending the feature space to opinions concerning the quantity to predict. Furthermore, the assumptions of the theoretical background were confirmed, as well as the observations found in the state of the art regarding football player evaluation.
Chaotic Features of Decomposed Time Series from Tidal River Water Level
Authors: Lee Myungjin , Kim Hung Soo , Kwak Jaewon , Kim Jongsung , Kim Soojun
Published: December 2021

This study assessed the characteristics of water-level time series of a tidal river by decomposing it into tide, wave, rainfall-runoff, and noise components. Especially, the analysis for chaotic behavior of each component was done by estimating the correlation dimension with phase-space reconstruction of time series and by using a close returns plot (CRP). Among the time series, the tide component showed chaotic characteristics to have a correlation dimension of 1.3. It was found out that the water level has stochastic characteristics showing the increasing trend of the correlation exponent in the embedding dimension. Other components also showed the stochastic characteristics. Then, the CRP was used to examine the characteristics of each component. The tide component showed the chaotic characteristics in its CRP. The CRP of water level showed an aperiodic characteristic which slightly strayed away from its periodicity, and this might be related to the tide component. This study showed that a low water level is mainly affected by a chaotic tide component through entropy information. Even though the water level did not show chaotic characteristics in the correlation dimension, it showed stochastic chaos characteristics in the CRP. Other components showed stochastic characteristics in the CRP. It was confirmed that the water level showed chaotic characteristics when it was not affected by rainfall and stochastic characteristics deviating from the bounded trajectory when water level rises due to rainfall. Therefore, we have shown that the water level related to the chaotic tide component can also have chaotic properties because water level is influenced by chaotic tide and rainfall shock, thus it showed stochastic chaos characteristics.
Enhanced Image Captioning with Color Recognition Using Deep Learning Methods
Authors: Chang Yeong-Hwa , Chen Yen-Jen , Huang Ren-Hung , Yu Yi-Ting
Published: December 2021

Automatically describing the content of an image is an interesting and challenging task in artificial intelligence. In this paper, an enhanced image captioning model—including object detection, color analysis, and image captioning—is proposed to automatically generate the textual descriptions of images. In an encoder–decoder model for image captioning, VGG16 is used as an encoder and an LSTM (long short-term memory) network with attention is used as a decoder. In addition, Mask R-CNN with OpenCV is used for object detection and color analysis. The integration of the image caption and color recognition is then performed to provide better descriptive details of images. Moreover, the generated textual sentence is converted into speech. The validation results illustrate that the proposed method can provide more accurate description of images.
Attitudes toward Applying Facial Recognition Technology for Red-Light Running by E-Bikers: A Case Study in Fuzhou, China
Authors: Yang Yanqun , Yin Danni , Easa Said M. , Liu Jiang
Published: December 2021

The application of facial recognition technology (FRT) can effectively reduce the red-light running behavior of e-bikers. However, the privacy issues involved in FRT have also attracted widespread attention from society. This research aims to explore the public and traffic police’s attitudes toward FRT to optimize the use and implementation of FRT. A structured questionnaire survey of 270 people and 94 traffic police in Fuzhou, China, was used. In the research, we use several methods to analyze the investigation data, including Mann–Whitney U test, Kruskal–Wallis test, and multiple correspondence analysis. The survey results indicate that the application of FRT has a significant effect on reducing red-light running behavior. The public’s educational level and driving license status are the most influential factors related to their attitudes to FRT (p < 0.001). Public members with these attributes show more supportive attitudes to FRT and more concerns about privacy invasion. There are significant differences between the public and traffic police in attitudes toward FRT (p < 0.001). Compared with the public, traffic police officers showed more supportive attitudes to FRT. This research contributes to promoting the application of FRT legitimately and alleviating people’s concerns about the technology.
Evaluation of the Influence between Local Meteorology and Air Quality in Beijing Using Generalized Additive Models
Authors: Hou Kun , Xu Xia
Published: December 2021

Previous studies have confirmed the inextricable connection between meteorological factors and air pollutants. This study presents the complex nonlinear relationship between meteorological variables and four major air pollutants under high-concentration air pollution in Beijing. The generalized additive model combined with marginal effects is used for quantitative analysis. After controlling the confounding factors such as long-term trends, seasonality and spatio-temporal deviation, the final fitting results exhibit that temperature, relative humidity and visibility are the most significant meteorological variables associating with PM2.5 concentration, and the marginal effect reaches 80%, −23% and 270%, respectively. Temperature and relative humidity are the most significant variables for SO2, and the marginal effect reaches 15% and 7%. The most significant variables for O3 are temperature and solar radiation, with marginal effect of up to 70% and 8%. Atmospheric pressure and temperature results in a positive effect on CO, and the marginal effect can reach 18% and 80%. All these indicate that local meteorological variables are a significant driving factor for air quality in Beijing. Other variables, such as wind speed, visibility, and precipitation, display some influence on air pollutants, but have less explanatory power in the model. Overall, our study provides a better understanding of the relationship between local meteorological variables and air quality, as well as an insight into how climate change affects air quality.
Urban Canyon in the CBD of Rio de Janeiro (Brazil): Thermal Profile of Avenida Rio Branco during Summer
Authors: Lemos Lidiane de Oliveira , Júnior Antonio Carlos Oscar , Mendonça Francisco
Published: December 2021

This study aims to evaluate the thermal field of the central business district (CBD) of Rio de Janeiro during summer from land surface temperature (LST) and the thermal characteristics of the urban canopy layer (UCL) of the urban canyon in Avenida Rio Branco. In order to conduct this evaluation, two methods were employed: (1) TIRS Landsat-8 sensor for data selection and processing (latest generation, 2011–2020); (2) a field survey using nine sampling points—seven along two mobile transects, one fixed point, and one vertical measurement point, which required the use of an RPA (remotely piloted aircraft). Three categories of analysis were established for the field survey based on the prevailing synoptic situations: stability, instability, and post-instability. The CBD is characterized by extensive areas with surface heat islands, in which temperatures were higher than 38.9 °C; the areas with milder LSTs were Campo do Santana, Avenida Rio Branco, and one of the mixed-use zones (Praça Mauá). With respect to Rio Branco Avenue, the LST niches of lowest elevation were derived through building shadowing; however, due to the nature of the data, the orbital data diverged from the observation data of the 10 field-study days. In situ data revealed that the characteristics urban morphology of Avenida Rio Branco, by contrast with the LST result, is susceptible to the formation of atmospheric heat islands, presenting heat islands of very strong magnitude (over 6.1 °C) in atmospheric stability, strong magnitude (4.1–6.0 °C) in atmospheric instability, and moderate magnitude (2.1–4.0 °C) in post-atmospheric instability. Despite the synoptic situation, thermal cores were concentrated at 1 p.m. The intersection between Avenida Rio Branco, Rua do Ouvidor, and Praça Mauá stored most of the solar energy received during the day due to the greater sky obstruction caused by the verticalization. Finally, vertical analysis demonstrated the formation of a thermal inversion on the night of the highest mean air temperature (29.5 °C), probably due to the roughness and number of buildings in the urban canyon.
Impact of Indoor-Outdoor Temperature Difference on Building Ventilation and Pollutant Dispersion within Urban Communities
Authors: Hu Yun , Wu Yihui , Wang Qun , Hang Jian , Li Qingman , Liang Jie , Ling Hong , Zhang Xuelin
Published: December 2021

Mechanical ventilation consumes a huge amount of global energy. Natural ventilation is a crucial solution for reducing energy consumption and enhancing the capacity of atmospheric self-purification. This paper evaluates the impacts of indoor-outdoor temperature differences on building ventilation and indoor-outdoor air pollutant dispersion in urban areas. The Computational Fluid Dynamics (CFD) method is employed to simulate the flow fields in the street canyon and indoor environment. Ventilation conditions of single-side ventilation mode and cross-ventilation mode are investigated. Air change rate, normalized concentration of traffic-related air pollutant (CO), intake fraction and exposure concentration are calculated to for ventilation efficiency investigation and exposure assessment. The results show that cross ventilation increases the air change rate for residential buildings under isothermal conditions. With the indoor-outdoor temperature difference, heating could increase the air change rate of the single-side ventilation mode but restrain the capability of the cross-ventilation mode in part of the floors. Heavier polluted areas appear in the upstream areas of single-side ventilation modes, and the pollutant can diffuse to middle-upper floors in cross-ventilation modes. Cross ventilation mitigates the environmental health stress for the indoor environment when indoor-outdoor temperature difference exits and the personal intake fraction is decreased by about 66% compared to the single-side ventilation. Moreover, the existence of indoor-outdoor temperature differences can clearly decrease the risk of indoor personal exposure under both two natural ventilation modes. The study numerically investigates the building ventilation and pollutant dispersion in the urban community with natural ventilation. The method and the results are helpful references for optimizing the building ventilation plan and improving indoor air quality.
Pilot Studies of the Unique Highland Palsa Mire in Western Sayan (Tuva Republic, Russian Federation)
Authors: Kirpotin Sergey N. , Kvasnikova Zoia N. , Potapova Sophia A. , Volkova Irina I. , Volkov Igor V. , Pyak Andrei I. , Byzaakay Arisiya A. , Kolesnichenko Larisa G. , Lushchaeva Inna V. , Khovalyg Aldynay O. , Kuzhevskaia Irina V. , Chursin Vladislav V. , Peregon Anna M.
Published: December 2021

In contrast to the well-studied West Siberian sector of frozen bogs in the Russian Arctic, the frozen mound bogs (so-called “palsas”) on the highlands of Southern Siberia have not yet been studied, but they are suspected to be even more sensitive to ongoing climate change. This article provides the pilot study on palsa mire Kara-Sug in the highland areas of Western Sayan mountain system, Tuva Republic. The study focuses on the current state of palsa mire and surrounding landscapes, providing wide range of ecological characteristics while describing ongoing transformations of natural landscapes under a changing climate. The study used a variety of field and laboratory methods: the integrated landscape-ecological approach, the study of peat deposits, geobotanical analysis, and modern analysis of the chemical composition of water, peat, and soils. The study shows that highland palsa mires are distinguished by their compactness and high variety of cryogenic landforms leading to high floristic and ecosystem diversity compared with lowland palsa mires. This information brings new insights and contributes to a better understanding of extrazonal highland palsa mires, which remain a “white spot” in the global environmental sciences.
Medical Decision Making for Cardiac MRI with CFD “Detection of Severe Stenosis Using a 5D Model of the Descending Aorta”
Authors: Sakly Houneida , Said Mourad , Tagina Moncef
Published: December 2021

The aim of this study is to develop a reliable 5D (x, y, z, time, flow dimension) model for medical decision making. Sophisticated techniques for the assessment of serious stenosis were developed using time-dependent instantaneous pressure gradients through the aorta (flow rate, Reynolds number, velocity, etc.). A 74 cardiac MRI scan and 3057 scans were performed on a 10-year-old patient with congenital valve and valvular aortic stenosis on sensitive MRI and coarctation (operated and then dilated) in the sense of shone syndrome. The occlusion rate was estimated to be 80.5%. The stenosis area was approximately 15 mm long and 10 mm high. The fluid solver (NS) exhibited a significant shear stress of −3.735 × 10−5 Pa within the first 10 iterations. There was a significant drop in the flux mass of −0.0050 (kg/s), as well as high blood turbulence in vortex field lines and low geometry Reynolds cells. The fifth dimension was used for negative velocity prediction (−81.4 cm/s). The discoveries of the 5D aortic simulation are convincing based on the evaluation of its physical and biomedical features.
Evaluation of Fixational Behavior throughout Life
Authors: Altemir Irene , Alejandre Adrian , Fanlo-Zarazaga Alvaro , Ortín Marta , Pérez Teresa , Masiá Belén , Pueyo Victoria
Published: December 2021

Background: To quantify development of gaze stability throughout life during short and long fixational tasks using eye tracking technology. Methods: Two hundred and fifty-nine participants aged between 5 months and 77 years were recruited along the study. All participants underwent a complete ophthalmological assessment. Fixational behavior during long and short fixational tasks was analyzed using a DIVE (Device for an Integral Visual Examination), a digital test assisted with eye tracking technology. The participants were divided into ten groups according to their age. Group 1, 0–2 years; group 2, 2–5 years; group 3, 5–10 years; group 4, 10–20 years; group 5, 20–30 years; group 6, 30–40 years; group 7, 40–50 years; group 8, 50–60 years; group 9, 60–70 years; and group 10, over 70 years. Results: Gaze stability, assessed by logBCEA (log-transformed bivariate contour ellipse area), improved with age from 5 months to 30 years (1.27 vs. 0.57 deg2 for long fixational task, 0.73 vs. −0.04 deg2 for short fixational task), while fixations tend to be longer (1.95 vs. 2.80 msec for long fixational tasks and 0.80 vs. 1.71 msec for short fixational tasks). All fixational outcomes worsened progressively from the fifth decade of life. Log-transformed bivariate contour ellipse area (0.79, 0.83, 0.91, 1.42 deg2 for long fixational task and 0.01, 0.18, 0.28, 0.44 deg2 for short fixational task, for group 7, 8, 9, and 10 respectively). Stimuli features may influence oculomotor performance, with smaller stimuli providing prolonged fixations. Conclusions: Fixational behavior can be accurately assessed from 5 months of age using a DIVE. We report normative data of gaze stability and duration of fixations for every age group. Currently available technology may increase the accuracy of our visual assessments at any age.
Putting the Pieces Together: Mental Construction of Semantically Congruent and Incongruent Scenes in Dementia
Authors: Wilson Nikki-Anne , Ahmed Rebekah M. , Piguet Olivier , Irish Muireann
Published: December 2021

Scene construction refers to the process by which humans generate richly detailed and spatially cohesive scenes in the mind’s eye. The cognitive processes that underwrite this capacity remain unclear, particularly when the envisaged scene calls for the integration of various types of contextual information. Here, we explored social and non-social forms of scene construction in Alzheimer’s disease (AD; n = 11) and the behavioural variant of frontotemporal dementia (bvFTD; n = 15) relative to healthy older control participants (n = 16) using a novel adaptation of the scene construction task. Participants mentally constructed detailed scenes in response to scene–object cues that varied in terms of their sociality (social; non-social) and congruence (congruent; incongruent). A significant group × sociality × congruence interaction was found whereby performance on the incongruent social scene condition was significantly disrupted in both patient groups relative to controls. Moreover, bvFTD patients produced significantly less contextual detail in social relative to non-social incongruent scenes. Construction of social and non-social incongruent scenes in the patient groups combined was significantly associated with independent measures of semantic processing and visuospatial memory. Our findings demonstrate the influence of schema-incongruency on scene construction performance and reinforce the importance of episodic–semantic interactions during novel event construction.
Olfaction as a Marker for Psychiatric and Neurological Diseases
Authors: El-Hage Wissam
Published: December 2021

Olfaction is one of the oldest senses among the five human senses [...]
Addressing Dual Disorders in a Medium-Term Admission Unit
Authors: Arnau Francisco , Benito Ana , Villar Mariano , Ortega María , López-Peláez Lucía , Haro Gonzalo
Published: December 2021

Due to the significant functional repercussions suffered by patients with dual disorder, we must evaluate which ones can benefit from intensive rehabilitative therapies in medium-stay psychiatric units. This was a retrospective study of patient medical records which intended to analyze sociodemographic and clinical variables and parameters related to the hospitalization and discharge of patients admitted to the Medium-Stay Unit (MSU) at the Castellón Provincial Hospital Consortium over 2 years (2017 and 2018), according to the presence or absence of dual disorders in these patients. Patients with a dual disorder represented 55.2% of the hospitalized patients. A higher proportion of them were male, were relatively younger, and had an earlier onset of mental illness, fewer associated medical pathologies, and shorter hospital admission times to the Short-Term Hospitalization Unit than those who did not present a dual disorder. A diagnosis on the schizophrenia spectrum with cannabis use or polyconsumption was the most common diagnosis; 98.2% of all the patients responded adequately to admission to the MSU. This work highlighted the need for higher doses of depot paliperidone in patients with dual disorders.
Personalizing Dual-Target Cortical Stimulation with Bayesian Parameter Optimization Successfully Treats Central Post-Stroke Pain: A Case Report
Authors: Dastin-van Rijn Evan M. , König Seth D. , Carlson Danielle , Goel Vasudha , Grande Andrew , Nixdorf Donald R. , Benish Sarah , Widge Alik S. , Nahas Ziad , Park Michael C. , Netoff Tay I. , Herman Alexander B. , Darrow David P.
Published: December 2021

Central pain disorders, such as central post-stroke pain, remain clinically challenging to treat, despite many decades of pharmacological advances and the evolution of neuromodulation. For treatment refractory cases, previous studies have highlighted some benefits of cortical stimulation. Recent advances in new targets for pain and the optimization of neuromodulation encouraged our group to develop a dual cortical target approach paired with Bayesian optimization to provide a personalized treatment. Here, we present a case report of a woman who developed left-sided facial pain after multiple thalamic strokes. All previous pharmacologic and interventional treatments failed to mitigate the pain, leaving her incapacitated due to pain and medication side effects. She subsequently underwent a single burr hole for placement of motor cortex (M1) and dorsolateral prefrontal cortex (dlPFC) paddles for stimulation with externalization. By using Bayesian optimization to find optimal stimulation parameters and stimulation sites, we were able to reduce pain from an 8.5/10 to a 0/10 during a 5-day inpatient stay, with pain staying at or below a 2/10 one-month post-procedure. We found optimal treatment to be simultaneous stimulation of M1 and dlPFC without any evidence of seizure induction. In addition, we found no worsening in cognitive performance during a working memory task with dlPFC stimulation. This personalized approach using Bayesian optimization may provide a new foundation for treating central pain and other functional disorders through systematic evaluation of stimulation parameters.
Secondary Impact of COVID-19 Pandemic on People with Parkinson’s Disease—Results of a Polish Online Survey
Authors: Krzysztoń Karolina , Mielańczuk-Lubecka Beata , Stolarski Jakub , Poznańska Anna , Kępczyńska Katarzyna , Zdrowowicz Agata , Domitrz Izabela , Kochanowski Jan
Published: December 2021

The COVID-19 pandemic causes increased mental stress and decreased mobility, which may affect people with Parkinson’s disease (PD). The study aimed to investigate the secondary impact of the COVID-19 pandemic on the level of activity, quality of life (QoL) and PD-related symptoms. The respondents completed an online survey in Polish in the period from December, 2020 to June, 2021. The questionnaire was completed by 47 participants aged 43 to 90 years (mean 72.1 ± 1.3 years). A total of 94% reported reduced contact with family and friends. Over 90% remained active during the pandemic. However, 55% of people with PD showed subjectively lower level of activity then before the pandemic. Moreover, 36% of the respondents felt afraid to visit a doctor and reported problems with access to medication. Subjective QoL reduction was reported by 80%, and 83% declared worsening of PD symptoms. The post pandemic deterioration of motor symptoms in people with PD did not affect their QoL. However, the deterioration of contacts and feelings of isolation had a significant impact on the decline in quality of life (p = 0.022 and p = 0.009, respectively) and the presence of anxiety (p = 0.035 and p = 0.007, respectively). These results may indicate than greater importance of social and mental factors than fitness and health-related factors in the QoL self-assessment of the people with PD.
Insights into Dyslexia Genetics Research from the Last Two Decades
Authors: Erbeli Florina , Rice Marianne , Paracchini Silvia
Published: December 2021

Dyslexia, a specific reading disability, is a common (up to 10% of children) and highly heritable (~70%) neurodevelopmental disorder. Behavioral and molecular genetic approaches are aimed towards dissecting its significant genetic component. In the proposed review, we will summarize advances in twin and molecular genetic research from the past 20 years. First, we will briefly outline the clinical and educational presentation and epidemiology of dyslexia. Next, we will summarize results from twin studies, followed by molecular genetic research (e.g., genome-wide association studies (GWASs)). In particular, we will highlight converging key insights from genetic research. (1) Dyslexia is a highly polygenic neurodevelopmental disorder with a complex genetic architecture. (2) Dyslexia categories share a large proportion of genetics with continuously distributed measures of reading skills, with shared genetic risks also seen across development. (3) Dyslexia genetic risks are shared with those implicated in many other neurodevelopmental disorders (e.g., developmental language disorder and dyscalculia). Finally, we will discuss the implications and future directions. As the diversity of genetic studies continues to increase through international collaborate efforts, we will highlight the challenges in advances of genetics discoveries in this field.
Sex-Based Clinical Outcome in Advanced NSCLC Patients Undergoing PD-1/PD-L1 Inhibitor Therapy—A Retrospective Bi-Centric Cohort Study
Authors: Lang David , Brauner Anna , Huemer Florian , Rinnerthaler Gabriel , Horner Andreas , Wass Romana , Brehm Elmar , Kaiser Bernhard , Greil Richard , Lamprecht Bernd
Published: December 2021

Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy (n = 228) or ICI-CHT combination treatment (n = 80) for advanced NSCLC. Kaplan–Meier analyses were used to calculate progression-free (PFS) and overall survival (OS), influencing variables were evaluated using Cox-regression analyses. No significant sex differences for PFS/OS could be detected in either cohort. Men receiving ICI monotherapy had a statistically significant independent impact on PFS by Eastern Cooperative Oncology Group performance status (ECOG) ≥2 (hazard ratio (HR) 1.90, 95% confidence interval (CI): 1.10–3.29, p = 0.021), higher C-reactive protein (CRP; HR 1.06, 95%CI: 1.00–1.11, p = 0.037) and negative programmed death-ligand 1 (PD-L1) status (HR 2.04, 95%CI: 1.32–3.15, p = 0.001), and on OS by CRP (HR 1.09, 95%CI: 1.03–1.14, p = 0.002). In men on ICI-CHT combinations, multivariate analyses (MVA) revealed squamous histology (HR 4.00, 95%CI: 1.41–11.2, p = 0.009) significant for PFS; and ECOG ≥ 2 (HR 5.58, 95%CI: 1.88–16.5, p = 0.002) and CRP (HR 1.19, 95%CI: 1.06–1.32, p = 0.002) for OS. Among women undergoing ICI monotherapy, no variable proved significant for PFS, while ECOG ≥ 2 had a significant interaction with OS (HR 1.90, 95%CI 1.04–3.46, p = 0.037). Women treated with ICI-CHT had significant MVA findings for CRP with both PFS (HR 1.09, 95%CI: 1.02–1.16, p = 0.007) and OS (HR 1.11, 95%CI: 1.03–1.19, p = 0.004). Although men and women responded similarly to both ICI mono- and ICI-CHT treatment, predictors of response differed by sex.
Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions
Authors: Lamas Nuno Jorge , Martel Arnaud , Nahon-Estève Sacha , Goffinet Samantha , Macocco Adam , Bertolotto Corine , Lassalle Sandra , Hofman Paul
Published: December 2021

Uveal melanoma (UM) is the most common malignant intraocular tumour in the adult population. It is a rare cancer with an incidence of nearly five cases per million inhabitants per year, which develops from the uncontrolled proliferation of melanocytes in the choroid (≈90%), ciliary body (≈6%) or iris (≈4%). Patients initially present either with symptoms like blurred vision or photopsia, or without symptoms, with the tumour being detected in routine eye exams. Over the course of the disease, metastases, which are initially dormant, develop in nearly 50% of patients, preferentially in the liver. Despite decades of intensive research, the only approach proven to mildly control disease spread are early treatments directed to ablate liver metastases, such as surgical excision or chemoembolization. However, most patients have a limited life expectancy once metastases are detected, since there are limited therapeutic approaches for the metastatic disease, including immunotherapy, which unlike in cutaneous melanoma, has been mostly ineffective for UM patients. Therefore, in order to offer the best care possible to these patients, there is an urgent need to find robust models that can accurately predict the prognosis of UM, as well as therapeutic strategies that effectively block and/or limit the spread of the metastatic disease. Here, we initially summarized the current knowledge about UM by compiling the most relevant epidemiological, clinical, pathological and molecular data. Then, we revisited the most important prognostic factors currently used for the evaluation and follow-up of primary UM cases. Afterwards, we addressed emerging prognostic biomarkers in UM, by comprehensively reviewing gene signatures, immunohistochemistry-based markers and proteomic markers resulting from research studies conducted over the past three years. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues of research in UM.
The Increasing Prognostic and Predictive Roles of the Tumor Primary Chemosensitivity Assessed by CA-125 Elimination Rate Constant K (KELIM) in Ovarian Cancer: A Narrative Review
Authors: Lauby Ambroise , Colomban Olivier , Corbaux Pauline , Peron Julien , Van Wagensveld Lilian , Gertych Witold , Bakrin Naoual , Descargues Pierre , Lopez Jonathan , Kepenekian Vahan , Glehen Olivier , Philip Charles Andre , Devouassoux-Shisheboran Mojgan , Tod Michel , Freyer Gilles , You Benoit
Published: December 2021

Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate because 75% of patients are diagnosed with advanced stage III–IV disease. About 50% of patients are now treated with neoadjuvant chemotherapy followed by interval debulking surgery (IDS). In that context, there is a need for accurate predictors of tumor primary chemosensitivity, as it may impact the feasibility of subsequent IDS. Across seven studies with more than 12,000 patients, including six large randomized clinical trials and a national cancer registry, along with a mega-analysis database with 5842 patients, the modeled CA-125 ELIMination rate constant K (KELIM), the calculation of which is based on the longitudinal kinetics during the first three cycles of platinum-based chemotherapy, was shown to be a reproducible indicator of tumor intrinsic chemosensitivity. Indeed, KELIM is strongly associated with the likelihood of complete IDS, subsequent platinum-free interval, progression-free survival, and overall survival, along with the efficacy of maintenance treatment with bevacizumab or veliparib. As a consequence, KELIM might be used to guide more subtly the medical and surgical treatments in a first-line setting. Moreover, it could be used to identify the patients with poorly chemosensitive disease, who will be the best candidates for innovative treatments meant to reverse the chemoresistance, such as cell cycle inhibitors or immunotherapy.
Nelfinavir Induces Cytotoxicity towards High-Grade Serous Ovarian Cancer Cells, Involving Induction of the Unfolded Protein Response, Modulation of Protein Synthesis, DNA Damage, Lysosomal Impairment, and Potentiation of Toxicity Caused by Proteasome Inhibition
Authors: Subeha Mahbuba R. , Goyeneche Alicia A. , Bustamante Prisca , Lisio Michael A. , Burnier Julia V. , Telleria Carlos M.
Published: December 2021

High-grade serous ovarian cancer (HGSOC) is a significant cause of mortality among women worldwide. Traditional treatment consists of platinum-based therapy; however, rapid development of platinum resistance contributes to lower life expectancy, warranting newer therapies to supplement the current platinum-based protocol. Repurposing market-available drugs as cancer therapeutics is a cost- and time-effective way to avail new therapies to drug-resistant patients. The anti-HIV agent nelfinavir (NFV) has shown promising toxicity against various cancers; however, its role against HGSOC is unknown. Here, we studied the effect of NFV against HGSOC cells obtained from patients along disease progression and carrying different sensitivities to platinum. NFV triggered, independently of platinum sensitivity, a dose-dependent reduction in the HGSOC cell number and viability, and a parallel increase in hypo-diploid DNA content. Moreover, a dose-dependent reduction in clonogenic survival of cells escaping the acute toxicity was indicative of long-term residual damage. In addition, dose- and time-dependent phosphorylation of H2AX indicated NFV-mediated DNA damage, which was associated with decreased survival and proliferation signals driven by the AKT and ERK pathways. NFV also mediated a dose-dependent increase in endoplasmic reticulum stress-related molecules associated with long-term inhibition of protein synthesis and concurrent cell death; such events were accompanied by a proapoptotic environment, signaled by increased phospho-eIF2α, ATF4, and CHOP, increased Bax/Bcl-2 ratio, and cleaved executer caspase-7. Finally, we show that NFV potentiates the short-term cell cycle arrest and long-term toxicity caused by the proteasome inhibitor bortezomib. Overall, our in vitro study demonstrates that NFV can therapeutically target HGSOC cells of differential platinum sensitivities via several mechanisms, suggesting its prospective repurposing benefit considering its good safety profile.
Automatic Segmentation of Metastatic Breast Cancer Lesions on 18F-FDG PET/CT Longitudinal Acquisitions for Treatment Response Assessment
Authors: Moreau Noémie , Rousseau Caroline , Fourcade Constance , Santini Gianmarco , Brennan Aislinn , Ferrer Ludovic , Lacombe Marie , Guillerminet Camille , Colombié Mathilde , Jézéquel Pascal , Campone Mario , Normand Nicolas , Rubeaux Mathieu
Published: December 2021

Metastatic breast cancer patients receive lifelong medication and are regularly monitored for disease progression. The aim of this work was to (1) propose networks to segment breast cancer metastatic lesions on longitudinal whole-body PET/CT and (2) extract imaging biomarkers from the segmentations and evaluate their potential to determine treatment response. Baseline and follow-up PET/CT images of 60 patients from the EPICUREseinmeta study were used to train two deep-learning models to segment breast cancer metastatic lesions: One for baseline images and one for follow-up images. From the automatic segmentations, four imaging biomarkers were computed and evaluated: SULpeak, Total Lesion Glycolysis (TLG), PET Bone Index (PBI) and PET Liver Index (PLI). The first network obtained a mean Dice score of 0.66 on baseline acquisitions. The second network obtained a mean Dice score of 0.58 on follow-up acquisitions. SULpeak, with a 32% decrease between baseline and follow-up, was the biomarker best able to assess patients’ response (sensitivity 87%, specificity 87%), followed by TLG (43% decrease, sensitivity 73%, specificity 81%) and PBI (8% decrease, sensitivity 69%, specificity 69%). Our networks constitute promising tools for the automatic segmentation of lesions in patients with metastatic breast cancer allowing treatment response assessment with several biomarkers.
Lifestyle and Hepatocellular Carcinoma What Is the Evidence and Prevention Recommendations
Authors: Zelber-Sagi Shira , Noureddin Mazen , Shibolet Oren
Published: December 2021

The increasing burden of hepatocellular carcinoma (HCC) emphasizes the unmet need for primary prevention. Lifestyle measures appear to be important modifiable risk factors for HCC regardless of its etiology. Lifestyle patterns, as a whole and each component separately, are related to HCC risk. Dietary composition is important beyond obesity. Consumption of n-3 polyunsaturated fatty acids, as well as fish and poultry, are inversely associated with HCC, while red meat, saturated fat, and cholesterol are related to increased risk. Sugar consumption is associated with HCC risk, while fiber and vegetable intake is protective. Data from multiple studies clearly show a beneficial effect for physical activity in reducing the risk of HCC. However, the duration, mode and intensity of physical activity needed are yet to be determined. There is evidence that smoking can lead to liver fibrosis and liver cancer and has a synergistic effect with alcohol drinking. On the other hand, an excessive amount of alcohol by itself has been associated with increased risk of HCC directly (carcinogenic effect) or indirectly (liver fibrosis and cirrhosis progression. Large-scale intervention studies testing the effect of comprehensive lifestyle interventions on HCC prevention among diverse cohorts of liver disease patients are greatly warranted.
Catalytic and Biological Activity of Silver and Gold Complexes Stabilized by NHC with Hydroxy Derivatives on Nitrogen Atoms
Authors: Sirignano Marco , Mariconda Annaluisa , Vigliotta Giovanni , Ceramella Jessica , Iacopetta Domenico , Sinicropi Maria Stefania , Longo Pasquale
Published: December 2021

In this paper is reported the synthesis of N,N′ hydroxy derivative of NHC silver (3a–4a) and gold(I) (3b–4b) complexes of general formula [M(NHC)2]+ [MX2]−. All compounds were characterized by spectroscopic and analytic techniques. The complexes turned out to be effective in both catalytic and biological applications. They catalyzed the coupling of aldehyde, piperidine, and phenylacetylene in A3-reaction to produce propargylamines and showed antimicrobial activity. In fact, minimal inhibition concentration (MIC) tests with Gram-positive and Gram-negative bacteria demonstrated that the silver compounds are selective toward E. coli, whereas the gold analogues are active against S. aureus. Moreover, the N,N′ hydroxy derivative of NHC silver complexes 3a and 4a exhibited good anticancer activity on the HeLA cancer cells (3a-IC50 = 12.2 ± 0.1 µM, 4a-IC50 = 11.9 ± 1.2 µM), whereas gold complex 4b displayed good anticancer activity towards the MCF-7 cells (IC50 = 12.2 ± 1.2 µM).
Synthesis and Characterisation of Cobalt Ferrite Coatings for Oxygen Evolution Reaction
Authors: Kubisztal Julian , Kubisztal Marian
Published: December 2021

In this paper, two novel procedures based on powder sedimentation, thermal treatment, and galvanostatic deposition were proposed for the preparation of porous cobalt ferrite (CoFe2O4) coatings with a metallic and organic binder for use as catalysts in the oxygen evolution reaction (OER). The electrochemical properties of the obtained electrode materials were determined as well, using both dc and ac methods. It was found that cobalt ferrite coatings show excellent electrocatalytic properties towards the oxygen evolution reaction (OER) with overpotential measured at a current density of 10 mAcm−2 from 287 to 295 mV and a Tafel slope of 35–45 mVdec−1. It was shown that the increase in the apparent activity of the CoFe2O4 coatings with an organic binder results mainly from a large electrochemically active area. Incorporation of the nickel binder between the CoFe2O4 particles causes an increase in both the conductivity and the electrochemically active area. The Tafel slopes indicate that the same rate-determining step controls the OER for all obtained coatings. Furthermore, it was shown that the CoFe2O4 electrodes exhibit no significant activity decrease after 28 h of oxygen evolution. The proposed coating preparation procedures open a new path to develop high-performance OER electrocatalysts.
Evaluation of Kinetic Pseudo-Order in the Photocatalytic Degradation of Ofloxacin
Authors: Rytwo Giora , Zelkind Arye Lev
Published: December 2021

Ofloxacin is a highly efficient and widely used antibiotic drug. It is classified as a refractory pollutant due to its poor biodegradability. Consequently, it is commonly found in water sources, requiring efficient methods for its removal. Advanced oxidation processes (AOPs) offer efficient alternatives since those yield complete degradation not achieved in adsorption or membrane processes. Previous studies suggest ofloxacin degradation follows a pseudo-first or -second order processes, whereas for full removal of refractory pollutants—lower pseudo-orders are required. Monitoring the actual “pseudo-order” degradation kinetics of ofloxacin is needed to evaluate any proposed AOP process. This study presents a simple procedure to evaluate pseudo-orders of AOPs. Photolysis of 20 μM ofloxacin solutions follow pseudo-zero order kinetics, with half-life times (t1/2) of approx. 60 min. TiO2 heterogenous catalysts have been shown to have no influence at low concentrations (0.2 mg L−1), but a significant reduction of half-life time (t1/2 = 20 min) and increase in pseudo-order (0.8) is measured at 2.0 mg L−1. Similar results are obtained with homogenous catalysis by 2.0 mg L−1 H2O2. The combination of H2O2 and TiO2 catalysts shows additional reduction in half-time life with increase in the pseudo-order to 1.2. The conclusions are (1) heterogenous and homogenous photocatalysis can effectively degrade ofloxacin, (2) combined photocatalysis yields higher pseudo-order, being less prone to achieve full removal, and (3) analysis of specific pseudo-orders in AOPs of refractory pollutants helps to further elucidate the efficiency of the processes.