bluuebunny/crossref_metadata_2025 huggingface dataset:
Lockdown due to COVID-19 in Spanish Children Up to 6 Years: Consequences on Diet, Lifestyle, Screen Viewing, and Sleep
Authors: Díaz-Rodríguez Mercedes , Carretero-Bravo Jesús , Pérez-Muñoz Celia , Deudero-Sánchez Mercedes
Published: June 2022

Objectives: To record how the habits of children under 6 years of age in Cadiz have changed during lockdown, in order to identify those that could be a handicap for the problem of overweight and obesity.

Methods: We developed a new questionnaire to analyse family living habits. The questionnaire was administered online to parents of children aged zero-six years. Eating habits, sedentary lifestyles, screen viewing, and sleep changes were evaluated.

Results: Changes were found in family living habits, as shown by the results of McNemar’s tests (p-value < 0.01 in all pairs except one, p-value = 0.097). A worsening of habits was also found to be more accentuated in families with low income, low educational level or small size of home. Some positive aspects associated with family meals and parental involvement were found.

Conclusions: The lockdown has showed a significant break in the main routines of the children that could affect their health and may add to the worsening of the already poor childhood obesity situation. The positive aspects found can be instrumental in improving the situation in future similar situations.
From Haphazard to a Sustainable Normothermic Regional Perfusion Service: A Blueprint for the Introduction of Novel Perfusion Technologies
Authors: Hunt Fiona , Johnston Chris J. C. , Coutts Lesley , Sherif Ahmed E. , Farwell Lynsey , Stutchfield Ben M. , Sewpaul Avi , Sutherland Andrew , Babu Benoy I. , Currie Ian S. , Oniscu Gabriel C.
Published: June 2022

Normothermic Regional Perfusion (NRP) has shown encouraging clinical results. However, translation from an experimental to routine procedure poses several challenges. Herein we describe a model that led to the implementation of NRP into standard clinical practice in our centre following an iterative process of refinement incorporating training, staffing and operative techniques. Using this approach we achieved a four-fold increase in trained surgical staff and a 6-fold increase in competent senior organ preservation practitioners in 12 months, covering 93% of the retrieval calls. We now routinely provide NRP throughout the UK and attended 186 NRP retrievals from which 225 kidneys, 26 pancreases and 61 livers have been transplanted, including 5 that were initially declined by all UK transplant centres. The 61 DCD(NRP) liver transplants undertaken exhibited no primary non-function or ischaemic cholangiopathy with up to 8 years of follow-up. This approach also enabled successful implementation of ex situ normothermic liver perfusion which together with NRP contributed 37.5% of liver transplant activity in 2021. Perfusion technologies (in situ and ex situ) are now supported by a team of Advanced Perfusion and Organ Preservation Specialists. The introduction of novel perfusion technologies into routine clinical practice presents significant challenges but can be greatly facilitated by developing a specific role of Advanced Perfusion and Organ Preservation Specialist supported by a robust education, training and recruitment programme.
Attitude Maneuver and Stability Control of Hyper-Agile Satellite Using Reconfigurable Control Moment Gyros
Authors: Qu Zhi , Zhang Gaofei , Meng Ziyang , Xu Kai , Xu Ruiqin , Di Jiaojiao
Published: June 2022

Addressing the problems of insurmountable unknown frictional disturbance and balancing the trade-off between high maneuverability and stability during attitude maneuver are important in low-cost miniaturized single control moment gyro clusters (SGCMGs) for hyper-agile satellite. This paper proposes a new concept of reconfigurable octagonal cone-type SGCMGs by considering practical engineering requirements of hyper-agile satellites. Firstly, the momentum characteristics of typical configurations are quantitatively explained, and the evaluation metrics for SGCMGs based on norm L∞ and norm L2 are defined, respectively. Secondly, a reconfiguration design of SGCMGs from octagonal cone-type into pyramid-type is proposed by analyzing the unknown disturbance mechanism based on SGCMGs. When the hyper-agile satellite is supported to perform fast attitude maneuvers, all units of SGCMGs can work together to output rough and large torque. On the other hand, when the maneuvering ends with stable pointing control, gimbles of one pyramid-type SGCMGs are locked down and fine torque is outputted using another pyramid-type SGCMGs. This will greatly reduce the difficulty of controller design and improve the satellite attitude performance indices. The superiority of the control strategy and selection of the proposed actuator is verified by experiments.
Fault-Tolerant Control for Hexacopter UAV Using Adaptive Algorithm with Severe Faults
Authors: Nguyen Ngoc Phi , Xuan Mung Nguyen , Ha Le Nhu Ngoc Thanh , Hong Sung Kyung
Published: June 2022

In this paper, a fault-tolerant control method is proposed for a hexacopter under uncertainties. The proposed method is based on adaptive-sliding-mode control (ASMC) and a control allocation scheme. First, a mathematical model of the hexacopter is employed with model uncertainties. Next, the control allocation strategy is combined with ASMC to handle actuator faults, which can distribute the virtual control signal to redundant actuators. A modified fault-tolerant control is proposed to overcome this virtual input saturation. Finally, the system stability is validated using the Lyapunov theory. The performance of the proposed method is compared with that of normal ASMC. The simulation results show that the suggested strategy can realize quicker compensation under faulty conditions.
Mars Exploration Using Sailplanes
Authors: Bouskela Adrien , Kling Alexandre , Schuler Tristan , Shkarayev Sergey , Kalita Himangshu , Thangavelautham Jekan
Published: June 2022

We present the preliminary design of sailplanes, used for Mars exploration. The sailplanes mitigate the weight and energy storage limitations traditionally associated with powered flight by instead exploiting atmospheric wind gradients for dynamic soaring, and slope/thermal updrafts for static soaring. Equations of motion for the sailplanes were combined with wind profiles from the Mars Regional Atmospheric Modeling System (MRAMS) for two representative sites: Jezero crater, Perseverance’s landing site, and over a section of the Valles Marineris canyon. Optimal flight trajectories were obtained from the constrained optimization problem, using the lift coefficient and the roll angle as control parameters. Numerical results for complete dynamic soaring cycles demonstrated that the total sailplane energy at the end of a soaring cycle increases by 6.8–11%. The absence of a propulsion system, allowing for a compact form factor, means the sailplanes can be packaged into CubeSats and deployed as secondary payloads at a relatively low cost; providing scientific data over locations inaccessible by current landers and rovers. Various sailplane deployment methods are considered, including rapid deployment during Entry, Descent, and Landing (EDL) of a Mars Science Laboratory-class (MSL) vehicle and slow deployment using a blimp.
Evaluation of Marine Fisheries Vulnerability in China and Its Spatial Effects: Evidence from Coastal Regions
Authors: Li Yutong , Ji Jianyue
Published: June 2022

Based on data from 10 coastal regions in China, this study establishes an evaluation index system for marine fisheries using the theoretical framework of the DPSR model. The entropy method is used to calculate the degree of marine fisheries vulnerability in each region of China from 2009 to 2018. The spatial Durbin model (SDM) is also used to analyze the influencing factors and spatial spillover effects of marine fisheries vulnerability from four perspectives of economic efficiency, industrial structure, environmental regulation, and ecological pollution. The results show significant positive direct effects between the economic efficiency, ecological pollution, and vulnerability of marine fisheries. At the same time, there are significant negative effects between the industrial structure, environmental regulation, and vulnerability of marine fisheries. In terms of spatial spillover effects, economic efficiency, environmental regulation, and ecological pollution show positive spatial spillover effects, while the industrial structure shows negative spatial spillover effects. These findings provide a theoretical basis for the sustainable development of marine fisheries in China.
Copy Number Variation (CNV): A New Genomic Insight in Horses
Authors: Laseca Nora , Molina Antonio , Valera Mercedes , Antonini Alicia , Demyda-Peyrás Sebastián
Published: June 2022

Copy number variations (CNVs) are a new-fangled source of genetic variation that can explain changes in the phenotypes in complex traits and diseases. In recent years, their study has increased in many livestock populations. However, the study and characterization of CNVs in equines is still very limited. Our study aimed to investigate the distribution pattern of CNVs, characterize CNV regions (CNVRs), and identify the biological pathways affected by CNVRs in the Pura Raza Española (PRE) breed. To achieve this, we analyzed high-density SNP genotyping data (670,804 markers) from a large cohort of 654 PRE horses. In total, we identified 19,902 CNV segments and 1007 CNV regions in the whole population. The length of the CNVs ranged from 1.024 kb to 4.55 Mb, while the percentage of the genome covered by CNVs was 4.4%. Interestingly, duplications were more abundant than deletions and mixed CNVRs. In addition, the distribution of CNVs across the chromosomes was not uniform, with ECA12 being the chromosome with the largest percentage of its genome covered (19.2%), while the highest numbers of CNVs were found in ECA20, ECA12, and ECA1. Our results showed that 71.4% of CNVRs contained genes involved in olfactory transduction, olfactory receptor activity, and immune response. Finally, 39.1% of the CNVs detected in our study were unique when compared with CNVRs identified in previous studies. To the best of our knowledge, this is the first attempt to reveal and characterize the CNV landscape in PRE horses, and it contributes to our knowledge of CNVs in equines, thus facilitating the understanding of genetic and phenotypic variations in the species. However, further research is still needed to confirm if the CNVs observed in the PRE are also linked to variations in the specific phenotypical differences in the breed.
Immunocyte Populations Observed from Birth to Weaning in Blood, Spleen and Mesenteric Lymph Nodes of Piglets
Authors: Harayama Tomoko , Tsukahara Takamitsu , Fukuta Kikuto , Oda Machi , Inoue Ryo
Published: June 2022

Susceptibility to pathogen infections and efficacy of vaccination highly depend on the immune status of the piglet. Here, we measured immunocytes in piglets from birth to weaning to elucidate how immunocyte populations change during development and are affected by weaning. Crossbred piglets were used. Suckling piglets were euthanized at 1, 7, 14, 21, 28 or 35 days old (3~4 piglets at each time point). In addition, seven piglets were weaned at 21 days old, with four being euthanized at 28 days old and the remaining at 35 days old. Piglet carcasses were dissected, and blood, mesenteric lymph nodes (MLN) and spleen were sampled. In total, seven antibodies were used to stain the immunocyte population. Dynamics of myeloid (CD3–SWC3+CD16+), natural killer (NK; CD3–SWC3–CD16+), killer T (CD3+CD8+), helper T (CD3+CD4+) and B (CD3–CD21+) cells were analyzed. Percentage of innate immunity cells such as myeloid cells declined (p < 0.05) from the first day after birth. In contrast, percentage of NK cells increased in piglets while they were still suckling. Killer T, helper T, and B cell populations increased around 2~3 weeks after birth. No significant differences in the populations of the evaluated cell types were observed between suckling and weaned piglets at least for 14 days post weaning.
Heteroaryl-Ethylenes as New Effective Agents for High Priority Gram-Positive and Gram-Negative Bacterial Clinical Isolates
Authors: Bivona Dalida Angela , Mirabile Alessia , Bonomo Carmelo , Bonacci Paolo Giuseppe , Stracquadanio Stefano , Marino Andrea , Campanile Floriana , Bonaccorso Carmela , Fortuna Cosimo Gianluca , Stefani Stefania , Musso Nicolò , Bongiorno Dafne
Published: June 2022

The World Health Organization has identified antimicrobial resistance as a public health emergency and developed a global priority pathogens list of antibiotic-resistant bacteria that can be summarized in the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales species), reminding us of their ability to escape the effect of antibacterial drugs. We previously tested new heteroaryl-ethylene compounds in order to define their spectrum of activity and antibacterial capability. Now, we focus our attention on PB4, a compound with promising MIC and MBC values in all conditions tested. In the present study, we evaluate the activity of PB4 on selected samples of ESKAPE isolates from nosocomial infections: 14 S. aureus, 6 E. faecalis, 7 E. faecium, 12 E. coli and 14 A. baumannii. Furthermore, an ATCC control strain was selected for all species tested. The MIC tests were performed according to the standard method. The PB4 MIC values were within very low ranges regardless of bacterial species and resistance profiles: from 0.12 to 2 mg/L for S. aureus, E. faecalis, E. faecium and A. baumannii. For E. coli, the MIC values obtained were slightly higher (4–64 mg/L) but still promising. The PB4 heteroaryl-ethylenic compound was able to counteract the bacterial growth of both high-priority Gram-positive and Gram-negative clinical strains. Our study contributes to the search for new molecules that can fight bacterial infections, in particular those caused by MDR bacteria in hospitals. In the future, it would be interesting to evaluate the activity of PB4 in animal models to test for its toxicity.
Revisiting the Frequency and Antimicrobial Resistance Patterns of Bacteria Implicated in Community Urinary Tract Infections
Authors: Silva Andreia , Costa Elisabeth , Freitas Américo , Almeida Adelaide
Published: June 2022

Urinary tract infections (UTIs) are one of the most common infectious diseases at the community level. The continue misuse of antimicrobials is leading to an increase in bacterial resistance, which is a worldwide problem. The objective of this work was to study the incidence and pattern of antimicrobial resistance of the main bacteria responsible for UTI in the community of central and northern Portugal, and establish an appropriate empirical treatment. The urine samples were collected in Avelab—Laboratório Médico de Análises Clínicas over a period of 5 years (2015–2019). The urine cultures were classified as positive when bacterial growth was equal to or higher than 105 CFU/mL, and only for these cases, an antimicrobial susceptibility test was performed. Of the 106,019 samples analyzed, 15,439 had a urinary infection. Urinary infections were more frequent in females (79.6%) than in males (20.4%), affecting more elderly patients (56.9%). Escherichia coli (70.1%) was the most frequent uropathogen, followed by Klebsiella pneumoniae (8.9%). The bacteria responsible for UTI varied according to the patient’s sex, with the greatest differences being observed for Enterococcus faecalis and Pseudomonas aeruginosa, these being more prevalent in men. In general, there was a growth in bacterial resistance as the age of the patients increased. The resistance of bacteria in male patients was, in most cases, statistically different (Chi-Square test, p < 0.05) from that observed for bacteria isolated from female patients, showing, in general, higher resistance in male patients. Although E. coli was the most responsible uropathogen for UTI, it was among the bacteria most susceptible to antibiotics. The isolates of K. pneumoniae, Proteus vulgaris and Enterobacter showed high resistance to the tested antimicrobials. The most common multidrug-resistant (MDR) bacteria implicated in UTI were K. pneumoniae (40.4%) and P. aeruginosa (34.7%), but E. coli, the most responsible bacteria for UTI, showed a MDR of 23.3%. When we compared our results with the results from 10 years ago for the same region, in general, an increase in bacterial resistance was observed. The results of this study confirmed that urinary tract infections are a very common illness, caused frequently by resistant uropathogens, for which the antibiotic resistance profile has varied over a short time, even within a specific region. This indicates that periodically monitoring the microbial resistance of each region is essential in order to select the best empirical antibiotic therapy against these infections, and prevent or decrease the resistance among uropathogenic strains.
Pain in Hemophilia: Unexplored Role of Oxidative Stress
Authors: Fouda Raghda , Argueta Donovan A. , Gupta Kalpna
Published: June 2022

Hemophilia is the most common X-linked bleeding diathesis caused by the genetic deficiency of coagulation factors VIII or IX. Despite treatment advances and improvements in clinical management to prevent bleeding, management of acute and chronic pain remains to be established. Repeated bleeding of the joints leads to arthropathy, causing pain in hemophilia. However, mechanisms underlying the pathogenesis of pain in hemophilia remain underexamined. Herein, we describe the novel perspectives on the role for oxidative stress in the periphery and the central nervous system that may contribute to pain in hemophilia. Specifically, we cross examine preclinical and clinical studies that address the contribution of oxidative stress in hemophilia and related diseases that affect synovial tissue to induce acute and potentially chronic pain. This understanding would help provide potential treatable targets using antioxidants to ameliorate pain in hemophilia.
Travel Time Prediction on Long-Distance Road Segments in Thailand
Authors: Chawuthai Rathachai , Ainthong Nachaphat , Intarawart Surasee , Boonyanaet Niracha , Sumalee Agachai
Published: June 2022

This study proposes a method by which to predict the travel time of vehicles on long-distance road segments in Thailand. We adopted the Self-Attention Long Short-Term Memory (SA-LSTM) model with a Butterworth low-pass filter to predict the travel time on each road segment using historical data from the Global Positioning System (GPS) tracking of trucks in Thailand. As a result, our prediction method gave a Mean Absolute Error (MAE) of 12.15 min per 100 km, whereas the MAE of the baseline was 27.12 min. As we can estimate the travel time of vehicles with a lower error, our method is an effective way to shape a data-driven smart city in terms of predictive mobility.
Numerical Assessment of Side-Wind Effects on a Bus in Urban Conditions
Authors: Szodrai Ferenc
Published: June 2022

The drag coefficient is usually considered to be a constant value, which allows us to calculate the aerodynamic losses. However, at lower speeds and wind, this value could be distorted. This also applies to buses in urban environments where due to traffic, the speed is relatively low. Since the schedule of the buses is fixed, based on the driving cycle, they travel at a nominal cruising speed. This makes it possible to examine the drag losses in a quasi-steady condition. To find the magnitude of this distortion in losses, a large-eddy simulation method was used with the help of commercially available software. Symmetrical and asymmetrical flows were induced into the digital wind tunnel to assess the distribution of the forces in the cruising direction and examine the flow patterns. It was discovered that the drag forces behave differently due to the low speeds, and calculations should be performed differently compared to high-speed drag evaluations.
Selection Methodology of Composite Material for Retractable Main Landing Gear Strut of a Lightweight Aircraft
Authors: Ahmad Muhammad Ayaz , Rafiq Hamza , Shah Syed Irtiza Ali , Khan Sabih Ahmad , Rizvi Syed Tauqeer ul Islam , Shams Taimur Ali
Published: June 2022

The design and development of high-strength and low-weight composite landing gear struts is still a challenge in today’s world. In this study, a selection methodology for fiber-reinforced composite material for retractable main landing gear struts for specified lightweight aircraft up to 1600 kg mass is proposed. Four different fiber-reinforced composite materials, two each from the glass-fiber and carbon-fiber families, including E-glass fiber/epoxy, S-glass fiber/epoxy, T300 carbon fiber/epoxy, and AS carbon fiber/epoxy, were considered for analysis. For the design and analysis of a main landing gear strut, maximum landing loads for one point and two point landing conditions were calculated using FAA FAR 23 airworthiness requirements. Materials were categorized based on their strength-to-weight ratio and the Tsai-Wu failure criterion. Landing gear struts meeting the Tsai-Wu failure criterion, and having a maximum strength-to-weight ratio, were then modeled for performance under a collision detection test. This research concludes that T300 carbon fibre/epoxy is a recommended material for the manufacture of landing gear struts for specified lightweight aircraft.
Complex Method of Airfield Pavement Condition Evaluation Based on APCI Index
Authors: Wesolowski Mariusz , Blacha Krzysztof , Iwanowski Pawel
Published: June 2022

Airfield infrastructure management should be effective. First of all, renovation works should be planned and carried out so that the equipment or resources, both financial and personal, are used optimally. The basis for planning funds should be knowledge about the actual pavement condition and, more importantly, the future pavement condition. The main goal of the paper is to present a complex method of technical condition assessment of airfield pavements made of cement and asphalt concrete, as well as natural pavements, which are part of the ground maneuvering field on each airfield. The authors propose a new method of assessing the technical condition of the pavement based on the Airfield Pavement Condition Index (APCI). Compared to existing methods, based mostly on the visual assessment of the pavement surface damages, the APCI method also includes the inventory of the repairs and diagnostic tests such as the assessment of the load capacity, evenness, anti-skid properties and the surface layer tensile bond strength. The presented mathematical models enable automation of pavement assessment process. That can lower costs and speed up whole evaluation.
Extended Chaotic-Map-Based User Authentication and Key Agreement for HIPAA Privacy/Security Regulations
Authors: Hsieh Yi-Pei , Lee Kuo-Chang , Lee Tian-Fu , Su Guo-Jun
Published: June 2022

Background: The US government has enacted the Health Insurance Portability and Accountability Act (HIPAA), in which patient control over electronic protected health information is a major issue of concern. The two main goals of the Act are the privacy and security regulations in the HIPAA and the availability and confidentiality of electronic protected health information. The most recent authenticated key-agreement schemes for HIPAA privacy/security have been developed using time-consuming modular exponential computations or scalar multiplications on elliptic curves to provide higher security. However, these authenticated key-agreement schemes either have a heavy computational cost or suffer from authorization problems. Methods: Recent studies have demonstrated that cryptosystems using chaotic-map operations are more efficient than those that use modular exponential computations and scalar multiplications on elliptic curves. Additionally, enhanced Chebyshev polynomials exhibit the semigroup property and the commutative property. Hence, this paper develops a secure and efficient certificate-based authenticated key-agreement scheme for HIPAA privacy/security regulations by using extended chaotic maps. Results and Conclusions: This work develops a user-authentication and key-agreement scheme that solves security problems that afflict related schemes. This proposed key-agreement scheme depends on a certificate-management center to enable doctors, patients and authentication servers to realize mutual authentication through certificates and thereby reduce the number of rounds of communications that are required. The proposed scheme not only provides more security functions, but also has a lower computational cost than related schemes.
Transcriptome Analysis and GC-MS Profiling of Key Fatty Acid Biosynthesis Genes in Akebia trifoliata (Thunb.) Koidz Seeds
Authors: Zhong Yicheng , Zhao Yunlei , Wang Yue , Niu Juan , Sun Zhimin , Chen Jianhua , Luan Mingbao
Published: June 2022

Akebia trifoliata (Thunb.) Koidz is an important Chinese medicinal and economic crop. Its seeds, which are rich in fatty acids, are usually discarded. As of now, A. trifoliata lipid biosynthesis pathways and genes have not been clearly described. In this work, we found that seed and fruit development of A. trifoliata were not synchronized, and that when the fruit was ripe, seed oil content was not at its highest. As seeds developed, linoleic and oleic acid content was found to decrease and increase, respectively. RNA sequencing yielded 108.45 GB of clean reads from 15 cDNA libraries, containing 8756 differentially expressed genes. We identified 65 unigenes associated with lipid biosynthesis, including fatty acid and triacylglycerol biosynthesis. The 65 unigenes were mapped to the A. trifoliata lipid synthesis pathway. There were 20 AtrFAD family members in A. trifoliata, which could be divided into four sub-groups with the highest number of AtrSADs. Our study revealed the dynamic changes in A. trifoliata seed oil content and composition during its growth period and provides large-scale and comprehensive transcriptome data of A. trifoliata seeds. These findings provide a basis for the improvement of A. trifoliata seed oil yield and quality.
A Novel Approach to Modeling and Forecasting Cancer Incidence and Mortality Rates through Web Queries and Automated Forecasting Algorithms: Evidence from Romania
Authors: Tudor Cristiana
Published: June 2022

Cancer remains a leading cause of worldwide mortality and is a growing, multifaceted global burden. As a result, cancer prevention and cancer mortality reduction are counted among the most pressing public health issues of the twenty-first century. In turn, accurate projections of cancer incidence and mortality rates are paramount for robust policymaking, aimed at creating efficient and inclusive public health systems and also for establishing a baseline to assess the impact of newly introduced public health measures. Within the European Union (EU), Romania consistently reports higher mortality from all types of cancer than the EU average, caused by an inefficient and underfinanced public health system and lower economic development that in turn have created the phenomenon of “oncotourism”. This paper aims to develop novel cancer incidence/cancer mortality models based on historical links between incidence and mortality occurrence as reflected in official statistics and population web-search habits. Subsequently, it employs estimates of the web query index to produce forecasts of cancer incidence and mortality rates in Romania. Various statistical and machine-learning models—the autoregressive integrated moving average model (ARIMA), the Exponential Smoothing State Space Model with Box-Cox Transformation, ARMA Errors, Trend, and Seasonal Components (TBATS), and a feed-forward neural network nonlinear autoregression model, or NNAR—are estimated through automated algorithms to assess in-sample fit and out-of-sample forecasting accuracy for web-query volume data. Forecasts are produced with the overperforming model in the out-of-sample context (i.e., NNAR) and fed into the novel incidence/mortality models. Results indicate a continuation of the increasing trends in cancer incidence and mortality in Romania by 2026, with projected levels for the age-standardized total cancer incidence of 313.8 and the age-standardized mortality rate of 233.8 representing an increase of 2%, and, respectively, 3% relative to the 2019 levels. Research findings thus indicate that, under the no-change hypothesis, cancer will remain a significant burden in Romania and highlight the need and urgency to improve the status quo in the Romanian public health system.
From SGAP-Model to SGAP-Score: A Simplified Predictive Tool for Post-Surgical Recurrence of Pheochromocytoma
Authors: Parasiliti-Caprino Mirko , Bioletto Fabio , Lopez Chiara , Bollati Martina , Maletta Francesca , Caputo Marina , Gasco Valentina , La Grotta Antonio , Limone Paolo , Borretta Giorgio , Volante Marco , Papotti Mauro , Pia Anna , Terzolo Massimo , Morino Mario , Pasini Barbara , Veglio Franco , Ghigo Ezio , Arvat Emanuela , Maccario Mauro
Published: June 2022

A reliable prediction of the recurrence risk of pheochromocytoma after radical surgery would be a key element for the tailoring/personalization of post-surgical follow-up. Recently, our group developed a multivariable continuous model that quantifies this risk based on genetic, histopathological, and clinical data. The aim of the present study was to simplify this tool to a discrete score for easier clinical use. Data from our previous study were retrieved, which encompassed 177 radically operated pheochromocytoma patients; supervised regression and machine-learning techniques were used for score development. After Cox regression, the variables independently associated with recurrence were tumor size, positive genetic testing, age, and PASS. In order to derive a simpler scoring system, continuous variables were dichotomized, using > 50 mm for tumor size, ≤ 35 years for age, and ≥ 3 for PASS as cut-points. A novel prognostic score was created on an 8-point scale by assigning 1 point for tumor size > 50 mm, 3 points for positive genetic testing, 1 point for age ≤ 35 years, and 3 points for PASS ≥ 3; its predictive performance, as assessed using Somers’ D, was equal to 0.577 and was significantly higher than the performance of any of the four dichotomized predictors alone. In conclusion, this simple scoring system may be of value as an easy-to-use tool to stratify recurrence risk and tailor post-surgical follow-up in radically operated pheochromocytoma patients.
The Intricate Epigenetic and Transcriptional Alterations in Pediatric High-Grade Gliomas: Targeting the Crosstalk as the Oncogenic Achilles’ Heel
Authors: Huchedé Paul , Leblond Pierre , Castets Marie
Published: June 2022

Pediatric high-grade gliomas (pHGGs) are a deadly and heterogenous subgroup of gliomas for which the development of innovative treatments is urgent. Advances in high-throughput molecular techniques have shed light on key epigenetic components of these diseases, such as K27M and G34R/V mutations on histone 3. However, modification of DNA compaction is not sufficient by itself to drive those tumors. Here, we review molecular specificities of pHGGs subcategories in the context of epigenomic rewiring caused by H3 mutations and the subsequent oncogenic interplay with transcriptional signaling pathways co-opted from developmental programs that ultimately leads to gliomagenesis. Understanding how transcriptional and epigenetic alterations synergize in each cellular context in these tumors could allow the identification of new Achilles’ heels, thereby highlighting new levers to improve their therapeutic management.
Widen the Applicability of a Convolutional Neural-Network-Assisted Glaucoma Detection Algorithm of Limited Training Images across Different Datasets
Authors: Ko Yu-Chieh , Chen Wei-Shiang , Chen Hung-Hsun , Hsu Tsui-Kang , Chen Ying-Chi , Liu Catherine Jui-Ling , Lu Henry Horng-Shing
Published: June 2022

Automated glaucoma detection using deep learning may increase the diagnostic rate of glaucoma to prevent blindness, but generalizable models are currently unavailable despite the use of huge training datasets. This study aims to evaluate the performance of a convolutional neural network (CNN) classifier trained with a limited number of high-quality fundus images in detecting glaucoma and methods to improve its performance across different datasets. A CNN classifier was constructed using EfficientNet B3 and 944 images collected from one medical center (core model) and externally validated using three datasets. The performance of the core model was compared with (1) the integrated model constructed by using all training images from the four datasets and (2) the dataset-specific model built by fine-tuning the core model with training images from the external datasets. The diagnostic accuracy of the core model was 95.62% but dropped to ranges of 52.5–80.0% on the external datasets. Dataset-specific models exhibited superior diagnostic performance on the external datasets compared to other models, with a diagnostic accuracy of 87.50–92.5%. The findings suggest that dataset-specific tuning of the core CNN classifier effectively improves its applicability across different datasets when increasing training images fails to achieve generalization.
Biomimicry Training to Promote Employee Engagement in Sustainability
Authors: McInerney Sarah J. , Niewiarowski Peter H.
Published: June 2022

Employees play a critical role in the success of corporate sustainability initiatives, yet sustained employee engagement is a constant challenge. The psychology literature states that to intrinsically motivate employees to engage in sustainability, there must be opportunity for employees to engage in practices that are directly relevant to their job duties. Traditional ad hoc initiatives such as Earth Week events, recycling challenges and so on, are not sufficient to derive this type of intrinsic motivation. Therefore, the goal of this study was to examine the psychological impact of a biomimicry sustainable innovation training program, to intrinsically motivate R&D employees to reconnect with nature and identify whether this promotes creative thinking and employee engagement. Due to COVID-19 restrictions, the current study conducted virtual workshops with R&D employees and demonstrated that biomimicry training was intrinsically motivating to employees and was valued as a practice that could be incorporated into R&D job duties. In conclusion, this study provides an adaptable procedural template for biomimicry training with a corporate audience. The results demonstrate a strong business case for organizations to experiment with biomimicry by illustrating its potential to create positive change across several business units beyond sustainable innovation to include human resources and sustainable marketing.
Investigation of the Serotonergic Activity and the Serotonin Content in Serum and Platelet, and the Possible Role of the Serotonin Transporter in Patients with Depression
Authors: Obermanns Jasmin , Flasbeck Vera , Steinmann Saskia , Juckel Georg , Emons Barbara
Published: June 2022

According to the monoamine hypothesis, the development of depression is associated with dysfunctions of the serotonergic system. Alterations in the serotonin transporter gene (5-HTTLPR), the serotonergic activity in the brain, and the content of serotonin (5-HT) have been related to depression and were examined separately by previous studies. This study investigates these parameters in 89 depressed patients and 89 healthy participants. We investigated the serotonergic activity measured by the loudness dependence of auditory evoked potentials (LDAEP). In addition to the examination of the serotonin content (serum and platelet), enzyme-linked immunosorbent assays (ELISA) were used and 5-HTTLPR genotypes were analyzed. We observed a lower serotonin content in patients compared to healthy participants. Further, we noticed a correlation between anxiety and depression-associated symptoms with serotonergic activity. Patients treated with SSRI/SNRI showed decreased contents of serum serotonin compared to patients without any psychotropic medication or other psychotropic medications. Since the serotonergic activity, peripheral serotonin content, and 5-HTTLPR were unrelated, the results suggest independent alterations of central and peripheral serotonergic systems in depression. In line with this finding, serotonergic activity was related to anxiety and depression symptoms. Furthermore, the applied medication seems to influence serum serotonin content in patients with depression.
Impact of Political, Social Safety, and Legal Risks and Host Country Attitude towards Foreigners on Project Performance of China Pakistan Economic Corridor (CPEC)
Authors: Rajput Amer , Maqsoom Ahsen , Shah Syed , Ullah Fahim , Munawar Hafiz , Rehman Muhammad , Albattah Mohammed
Published: June 2022

The China Pakistan Economic Corridor (CPEC) project was signed between China and Pakistan in the year 2013. This mega project connects the two countries to enhance their economic ties and give them access to international markets. The initial investment for the project was $46 billion with a tentative duration of fifteen years. Being an extensive project in terms of cost and duration, many factors and risks affect its performance. This study aims to investigate the effects of political (PR), social safety (SR), and legal risks (LR) on the project performance (PP) of the CPEC. It further investigates the significance of the host country’s attitude towards foreigners (HCA). A research framework consisting of PR, SR, and LR as independent variables, PP as the dependent variable, and HCA as moderator is formulated and tested in the current study. In this quantitative study, the Likert scale is used to measure the impact of the assessed risks. A questionnaire survey is used as a data collection tool to collect data and test the research framework and associated hypotheses. The partial least square structural equation modeling (PLS-SEM) is used to perform the empirical test for validation of the study, with a dataset of 99 responses. The empirical investigation finds a negative relationship between PR, SR, LR, and PP. It is concluded that PR, SR, and LR negatively influence the PP of CPEC. Furthermore, HCA negatively moderates the PR, LR, and PP of CPEC. In contrast, the value of SR and PP is positive in the presence of the positive HCA.
Blood-Derived Liquid Biopsies Using Foundation One® Liquid CDx for Children and Adolescents with High-Risk Malignancies: A Monocentric Experience
Authors: Cahn Fanny , Revon-Riviere Gabriel , Min Victoria , Rome Angélique , Filaine Pauline , Pelletier Annick , Abed Sylvie , Gentet Jean-Claude , Verschuur Arnauld , André Nicolas
Published: June 2022

Precision oncology requires tumor molecular profiling to identify actionable targets. Tumor biopsies are considered as the gold standard, but their indications are limited by the burden of procedures in children. Blood-derived liquid biopsy (LB) is a potential alternative that is not yet documented in real-world settings, especially in pediatric oncology. We performed a retrospective analysis of children and teenagers with a relapsing or refractory disease, upon whom LB was performed using the Foundation One® liquid CDx from 1 January 2020 to 31 December 2021 in a single center. Forty-five patients (27 boys) were included, with a median age of 9 years of age (range: 1.5–17 years old). Underlying malignancies were neuroblastoma (12 patients), bone sarcoma (12), soft tissue sarcoma (9), brain tumors (7), and miscellaneous tumors (5). Forty-three patients had metastatic disease. Six patients had more than one biopsy because of a failure in first LB. Median time to obtain results was 13 days. Overall, analysis was successful for 33/45 patients. Eight patients did not present any molecular abnormalities. Molecular alterations were identified in 25 samples with a mean of 2.1 alterations per sample. The most common alterations concerned TP53 (7 pts), EWS-FLI1 (5), ALK (3), MYC (3), and CREBBP (2). TMB was low in all cases. Six patients received treatment based on the results from LB analysis and all were treated off-trial. Three additional patients were included in early phase clinical trials. Mean duration of treatment was 85 days, with one patient with stable disease after eight months. Molecular profiling using Foundation One® Liquid CDx was feasible in pediatric patients with high-risk solid tumors and lead to identification of targetable mutations in a subset of patients.
Expansion of Liver Transplantation Criteria for Hepatocellular Carcinoma from Milan to UCSF in Australia and New Zealand and Justification for Metroticket 2.0
Authors: Barreto Savio G. , Strasser Simone I. , McCaughan Geoffrey W. , Fink Michael A. , Jones Robert , McCall John , Munn Stephen , Macdonald Graeme A. , Hodgkinson Peter , Jeffrey Gary P. , Jaques Bryon , Crawford Michael , Brooke-Smith Mark E. , Chen John W.
Published: June 2022

Background: Expansion in liver transplantation (LT) criteria for HCC from Milan to UCSF has not adversely impacted overall survival, prompting further expansion towards Metroticket 2.0 (MT2). In this study, we compared patient survival post-transplant before and after 2007 and long-term outcomes for LT within Milan versus UCSF criteria (to determine the true benefit of the expansion of criteria) and retrospectively validated the MT2 criteria. Methods: Retrospective analysis of ANZLITR (including all patients transplanted for HCC since July 1997). The entire cohort was divided based on criteria used at the time of listing, namely, Milan era (1997–2006) and the UCSF era (2007–July 2015). Results: The overall 5- and 10-year cumulative survival rates for the entire cohort of 691 patients were 78% and 69%, respectively. Patients transplanted in UCSF era had significantly higher 5- and 10-year survival rates than in the Milan era (80% vs. 73% and 72% vs. 65%, respectively; p = 0.016). In the UCSF era, the 5-year survival rate for patients transplanted within Milan criteria was significantly better than those transplanted outside Milan but within UCSF criteria (83% vs. 73%; p < 0.024). Patients transplanted within the MT2 criteria had a significantly better 5- and 10-year survival rate as compared to those outside the criteria (81% vs. 64% and 73% vs. 50%, respectively; p = 0.001). Conclusion: Overall survival following LT for HCC has significantly improved over time despite expanding criteria from Milan to UCSF. Patients fulfilling the MT2 criteria have a survival comparable to the UCSF cohort. Thus, expansion of criteria to MT2 is justifiable.
Basal Cell Carcinoma: Pathology, Current Clinical Treatment, and Potential Use of Lipid Nanoparticles
Authors: Łasińska Izabela , Zielińska Aleksandra , Mackiewicz Jacek , Souto Eliana B.
Published: June 2022

Skin cancer is the most common type of carcinoma diagnosed worldwide, with significant morbidity and mortality rates among Caucasians, in particular basal cell carcinoma (BCC). The main risk factors of BCC are well-identified, and there are many chemotherapeutic drugs available for its treatment. The effectiveness of therapeutic options is governed by several factors, including the location of the tumor, its size, and the presence of metastases (although rare for BCC). However, available treatments are based on non-targeted approaches, which encounter a significant risk of systemic toxicity in several organs. Site-specific chemotherapy for BCC has been proposed via the loading of anticancer drugs into nanoparticles. Among various types of nanoparticles, in this review, we focus on potential new regimens for the treatment of BCC using classical anticancer drugs loaded into novel lipid nanoparticles. To meet patient aesthetic expectations and enhance the effectiveness of basal cell carcinoma treatment, new therapeutic topical strategies are discussed, despite a limited number of reports available in the literature.
Parental Sleep, Distress, and Quality of Life in Childhood Acute Lymphoblastic Leukemia: A Longitudinal Report from Diagnosis up to Three Years Later
Authors: Rensen Niki , Steur Lindsay , Grootenhuis Martha , Twisk Jos , van Eijkelenburg Natasha , van der Sluis Inge , Dors Natasja , van den Bos Cor , Tissing Wim , Kaspers Gertjan , van Litsenburg Raphaële
Published: June 2022

This study assessed sleep, distress and quality of life (QoL) in parents of children with acute lymphoblastic leukemia (ALL) from diagnosis to three years after, and the impact of sleep and distress on QoL. Additionally, this study explored determinants of sleep and distress. Parents completed the MOS Sleep, Distress Thermometer for Parents and SF-12 at four-five months (T0), one year (T1), two years (T2), and three years (T3) after diagnosis. The course of outcomes and longitudinal impact of clinically relevant sleep problems (>1SD above reference’s mean) and clinical distress (score ≥ 4) on QoL Z-scores were assessed with linear mixed-models. Determinants of sleep and distress were assessed with multinomial mixed-models. Parents (81% mothers) of 139 patients (60% males; 76% medium-risk (MR)) participated. Distress and QoL gradually restored from T0 to T3. Sleep problems improved, but were still elevated at T3: 33% reported clinically relevant sleep problems, of which 48% in concurrence with distress. Over time, presence of sleep problems or distress led to lower mental QoL Z-scores (SD-score −0.2 and −0.5, respectively). Presence of both led to a cumulatively lower Z-score (SD-score −1.3). Parents in the latter group were more likely to report insufficient social support, parenting problems, a chronic illness, pain for their child, having a child with MR-ALL, and being closer to diagnosis. In conclusion, parental well-being improves over time, yet sleep problems persist. In combination with ongoing distress, they cumulatively affect QoL. Special attention should be given to parents who are vulnerable to worse outcomes.
Advances and Challenges in Biocatalysts Application for High Solid-Loading of Biomass for 2nd Generation Bio-Ethanol Production
Authors: Singhania Reeta , Patel Anil , Raj Tirath , Tsai Mei-Ling , Chen Chiu-Wen , Dong Cheng-Di
Published: June 2022

Growth in population and thereby increased industrialization to meet its requirement, has elevated significantly the demand for energy resources. Depletion of fossil fuel and environmental sustainability issues encouraged the exploration of alternative renewable eco-friendly fuel resources. Among major alternative fuels, bio-ethanol produced from lignocellulosic biomass is the most popular one. Lignocellulosic biomass is the most abundant renewable resource which is ubiquitous on our planet. All the plant biomass is lignocellulosic which is composed of cellulose, hemicellulose and lignin, intricately linked to each other. Filamentous fungi are known to secrete a plethora of biomass hydrolyzing enzymes. Mostly these enzymes are inducible, hence the fungi secrete them economically which causes challenges in their hyperproduction. Biomass’s complicated structure also throws challenges for which pre-treatments of biomass are necessary to make the biomass amorphous to be accessible for the enzymes to act on it. The enzymatic hydrolysis of biomass is the most sustainable way for fermentable sugar generation to convert into ethanol. To have sufficient ethanol concentration in the broth for efficient distillation, high solid loading >20% of biomass is desirable and is the crux of the whole technology. High solid loading offers several benefits including a high concentration of sugars in broth, low equipment sizing, saving cost on infrastructure, etc. Along with the benefits, several challenges also emerged simultaneously, like issues of mass transfer, low reaction rate due to water constrains in, high inhibitor concentration, non-productive binding of enzyme lignin, etc. This article will give an insight into the challenges for cellulase action on cellulosic biomass at a high solid loading of biomass and its probable solutions.