bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimycotoxin Analysis in Oat, Rice, Almond and Soy Beverages by Liquid Chromatography-Tandem Mass Spectrometry
Authors: Juan Cristina , Mañes Jordi , Juan-García Ana , Moltó Juan Carlos
Published: April 2022

This study developed and validated an analytical methodology for the determination of aflatoxins, enniatins, beauvericin, zearalenone, ochratoxin-A, alternariols, HT-2 and T-2 toxin in soy, oat, rice and almond beverages, based on solid phase extraction columns (SPE) and analyzed by liquid chromatography coupled to mass spectrometry in tandem. C18 SPE was successfully applied, obtaining recoveries that range from 72 ± 12% (ochratoxin-A) to 99 ± 4% (ENA1) at high level (L1) and 65 ± 8% (T-2) to 128 ± 9% (alternariol monomethyl ether) at low levels (L3). The methodology was validated according to Commission Decision 2002/657/EC, with limits of quantification ranging from 0.3 (AFs in oat beverages) to 18 ng/mL (HT-2 in rice beverage). The analysis of 56 beverage samples purchased from Valencia (Spain) showed at least one mycotoxin occurring in 95% of samples, including carcinogenic aflatoxins, and oat beverage was the most contaminated. This is a newest validated methodology for the quantification of sixty mycotoxins in oat, rice, almond and soy beverages.
Hyperspectral Image Classification with Imbalanced Data Based on Semi-Supervised Learning
Authors: Zheng Xiaorou , Jia Jianxin , Chen Jinsong , Guo Shanxin , Sun Luyi , Zhou Chan , Wang Yawei
Published: April 2022

Hyperspectral remote sensing image classification has been widely employed for numerous applications, such as environmental monitoring, agriculture, and mineralogy. During such classification, the number of training samples in each class often varies significantly. This imbalance in the dataset is often not identified because most classifiers are designed under a balanced dataset assumption, which can distort the minority classes or even treat them as noise. This may lead to biased and inaccurate classification results. This issue can be alleviated by applying preprocessing techniques that enable a uniform distribution of the imbalanced data for further classification. However, it is difficult to add new natural features to a training model by artificial combination of samples by using existing preprocessing techniques. For minority classes with sparse samples, the addition of sufficient natural features can effectively alleviate bias and improve the generalization. For such an imbalanced problem, semi-supervised learning is a creative solution that utilizes the rich natural features of unlabeled data, which can be collected at a low cost in the remote sensing classification. In this paper, we propose a novel semi-supervised learning-based preprocessing solution called NearPseudo. In NearPseudo, pseudo-labels are created by the initialization classifier and added to minority classes with the corresponding unlabeled samples. Simultaneously, to increase reliability and reduce the misclassification cost of pseudo-labels, we created a feedback mechanism based on a consistency check to effectively select the unlabeled data and its pseudo-labels. Experiments were conducted on a state-of-the-art representative hyperspectral dataset to verify the proposed method. The experimental results demonstrate that NearPseudo can achieve better classification accuracy than other common processing methods. Furthermore, it can be flexibly applied to most typical classifiers to improve their classification accuracy. With the intervention of NearPseudo, the accuracy of random forest, k-nearest neighbors, logistic regression, and classification and regression tree increased by 1.8%, 4.0%, 6.4%, and 3.7%, respectively. This study addresses research a gap to solve the imbalanced data-based limitations in hyperspectral image classification.
Energy Evolution Analysis of Coal Fracture Damage Process Based on Digital Image Processing
Authors: Wu Zhonghu , Li Liping , Lou Yili , Wang Wentao
Published: April 2022

Coal rocks often contain calcite, which has a significant effect on the mechanical properties of coal and the energy evolution during rupture damage. In this study, the meso-scale of rock is considered, and the spatial distribution of the internal structure of coal is characterized by digital image technology. Uniaxial compression tests were conducted using RFPA on coal rocks containing calcite veins with diverse dip angles. The research results show that the different azimuth angles of the calcite veins change the internal stress distribution of the coal, resulting in higher coal compressive strength at low dip angles (0°, 15° and 30°). Under high dip angles (45°, 60°, 75° and 90°), coal has lower compressive strength. The fracture mode of coal is significantly affected by calcite. At low dip angle, the fracture mode of coal and rock is complex, which are inclined Z-type (0°), V-type (15°) and inverted V-type (30°), respectively. At high dip angle, the fracture mode of coal and rock is single, which is type I failure mode. The destruction process of coal rocks is influenced by calcite veins. Under low dip angle, the internal stress distribution of coal is relatively uniform, the weak cementation between matrix and calcite vein in coal is not easy to be damaged, the stress required for coal failure is large and the input energy, accumulated elastic energy and impact energy index are large. Under high dip angle, the internal stress distribution of coal is uneven, the weak cementitious material between matrix and calcite vein in coal is easy to be damaged and the input energy, accumulated elastic energy and impact energy index are small.
Recoil Control of Deepwater-Drilling Riser with Optimal Guaranteed Cost H∞ Control
Authors: Sun Yue-Ting , Zhao Yan-Dong , Zhang Bao-Lin , Zhang Wei , Su Hao
Published: April 2022

In deepwater-drilling engineering, it is necessary to disconnect the bottom equipment of the lower marine-riser package from the blowout preventer when encountering multi-hazard environmental factors. In order to reduce the impact of recoil on the drilling platform after the sudden disconnection of the riser, in this paper, an optimal guaranteed cost H∞ recoil control problem is considered for the drilling riser. First, a three-element mass-damper-spring deepwater-drilling riser model subject to fluid discharge and heave motion of offshore platform is given. Then, an optimal guaranteed cost H∞ controller (OGCHC) is designed to suppress the recoil response of the drilling riser, and the sufficient conditions for the asymptotic stability of the closed-loop system are derived. Third, it is found through simulation results that the designed OGCHC can reduce the recoil response effectively. In order to further analyze the advantages of the OGCHC, the performance indices of the riser without active-recoil control and with optimal control (OC) and OGCHC are compared. It is shown that the average response amplitudes of three mass blocks of the riser are almost the same, while the control cost by the OGCHC is less than that by the OC. Further, under the designed recoil control, no riser compression occurs, thereby ensuring the safety of the riser system.
Robot-Agnostic Interaction Controllers Based on ROS
Authors: Storiale Federica , Ferrentino Enrico , Chiacchio Pasquale
Published: April 2022

In robotized industrial scenarios, the need for efficiency and flexibility is increasing, especially when tasks must be executed in dangerous environments and/or require the simultaneous manipulation of dangerous/fragile objects by multiple heterogeneous robots. However, the underlying hardware and software architecture is typically characterized by constraints imposed by the robots’ manufacturers, which complicates their integration and deployment. This work aims to demonstrate that widely used algorithms for robotics, such as interaction control, can be made independent of the hardware architecture, abstraction level, and functionality provided by the low-level proprietary controllers. As a consequence, a robot-independent control framework can be devised, which reduces the time and effort needed to configure the robotic system and adapt it to changing requirements. Robot-agnostic interaction controllers are implemented on top of the Robot Operating System (ROS) and made freely available to the robotic community. Experiments were performed on the Universal Robots UR10 research robot, the Comau Smart-Six industrial robot, and their digital twins, so as to demonstrate that the proposed control algorithms can be easily deployed on different hardware and simulators without reprogramming.
Typhoon Quantitative Precipitation Forecasts by the 2.5 km CReSS Model in Taiwan: Examples and Role of Topography
Authors: Wang Chung-Chieh , Paul Sahana , Huang Shin-Yi , Wang Yi-Wen , Tsuboki Kazuhisa , Lee Dong-In , Lee Ji-Sun
Published: April 2022

In this study, 24 h quantitative precipitation forecasts (QPFs) in Taiwan at the ranges of day 1 (0–24 h), day 2 (24–48 h), and day 3 (48–72 h) by a cloud-resolving model are examined using categorical statistics, targeted mainly for the most-rainy 24 h from 10 typhoon cases between 2010 and 2015, following two earlier studies that evaluated the overall performance for all the typhoons that hit Taiwan from 2010 to 2012 and through 2015. In the selected examples with a peak amount of 322 to 1110 mm, the QPFs by the model (with a grid size of 2.5 km) are shown to be of very high quality for two typhoons (Soulik and Soudelor), and fairly good quality for three cases (Fanapi, Megi, and Fung-Wong) up to day 3 and for four others (Saola, Kong-Rey, Nanmadol, and Tembin) within day 2, respectively. The results are more variable for the one remaining case of Matmo, also impressive on day 1 but degraded at longer ranges. Overall, the quality of the QPFs ranges from excellent to satisfactory for all the typhoons studied as the threat score can achieve 0.2 at thresholds fairly close to the observed peak amount in some typhoons, or at least about half of it in most others. Since the majority of the typhoons produced the greatest rainfall amounts over the mountains in Taiwan due to the topographic effect, in agreement with many previous studies, the QPF skills by the model, often extending into high thresholds, as demonstrated, suggest that heavy rainfall from typhoons in Taiwan is generally of high predictability if and when the model has an adequate resolution.
Impact of Global Climate Change on the Distribution Range and Niche Dynamics of Eleutherodactylus planirostrish in China
Authors: Mu Chaosheng , Guo Xuecheng , Chen Youhua
Published: April 2022

Species distribution models (SDMs) have become indispensable tools in risk assessment and conservation decision-making for invasive species. Eleutherodactylus planirostris has a strong dispersal ability, and the main route of introduction to new regions is likely transport via seedlings. This species is understood as one of the foremost successful invasive amphibian species with direct or indirect negative impacts in multiple regions. In this study, we used MaxEnt to assess suitable areas for this species under current and future climates globally and in China. We considered seven climatic variables, three timepoints (current, 2050, and 2070), and three CO2 emission scenarios. Annual mean temperature, precipitation of the driest month, and annual precipitation were the most important variables predicting E. planirostris occurrence. This species has a much larger suitable habitat area in China than reflected by the current distribution, so the species is likely to spread from the Pearl River Delta to surrounding areas. Under future warming, its invasive range will expand northward in China. In conclusion, this study assessed the risk of invasion of this species and made recommendations for management and prevention.
The Self-Organization of Marine Microbial Networks under Evolutionary and Ecological Processes: Observations and Modeling
Authors: Liu Zhenghua , Wang Jianjun , Meng Delong , Li Liangzhi , Liu Xueduan , Gu Yabing , Yan Qingyun , Jiang Chengying , Yin Huaqun
Published: April 2022

Evolutionary and ecological processes are primary drivers of ecological network constrictions. However, the ways that these processes underpin self-organization and modularity in networks are poorly understood. Here, we performed network analyses to explore the evolutionary and ecological effects on global marine microbial co-occurrence networks across multiple network levels, including those of nodes, motifs, modules and whole networks. We found that both direct and indirect species interactions were evolutionarily and ecologically constrained across at least four network levels. Compared to ecological processes, evolutionary processes generally showed stronger long-lasting effects on indirect interactions and dominated the network assembly of particle-associated communities in spatially homogeneous environments. Regarding the large network path distance, the contributions of either processes to species interactions generally decrease and almost disappear when network path distance is larger than six. Accordingly, we developed a novel mathematical model based on scale-free networks by considering the joint effects of evolutionary and ecological processes. We simulated the self-organization of microbial co-occurrence networks and found that long-lasting effects increased network stability via decreasing link gain or loss. Overall, these results revealed that evolutionary and ecological processes played key roles in the self-organization and modularization of microbial co-occurrence networks.
Mutational Effect of Some Major COVID-19 Variants on Binding of the S Protein to ACE2
Authors: Li Zhendong , Zhang John Z. H.
Published: April 2022

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has many variants that accelerated the spread of the virus. In this study, we investigated the quantitative effect of some major mutants of the spike protein of SARS-CoV-2 binding to the human angiotensin-converting enzyme 2 (ACE2). These mutations are directly related to the Variant of Concern (VOC) including Alpha, Beta, Gamma, Delta and Omicron. Our calculations show that five major mutations (N501Y, E484K, L452R, T478K and K417N), first reported in Alpha, Beta, Gamma and Delta variants, all increase the binding of the S protein to ACE2 (except K417N), consistent with the experimental findings. We also studied an additional eight mutations of the Omicron variant that are located on the interface of the receptor binding domain (RDB) and have not been reported in other VOCs. Our study showed that most of these mutations (except Y505H and G446S) enhance the binding of the S protein to ACE2. The computational predictions helped explain why the Omicron variant quickly became dominant worldwide. Finally, comparison of several different computational methods for binding free energy calculation of these mutants was made. The alanine scanning method used in the current calculation helped to elucidate the residue-specific interactions responsible for the enhanced binding affinities of the mutants. The results show that the ASGB (alanine scanning with generalized Born) method is an efficient and reliable method for these binding free energy calculations due to mutations.
Hepatic Steatosis Is Associated with High White Blood Cell and Platelet Counts
Authors: Chao Yu-Lin , Wu Pei-Yu , Huang Jiun-Chi , Chiu Yi-Wen , Lee Jia-Jung , Chen Szu-Chia , Chang Jer-Ming , Hwang Shang-Jyh , Chen Hung-Chun
Published: April 2022

The incidence of hepatic steatosis is increasing globally, and it is important to identify those at risk to prevent comorbidities. Complete blood count is a simple, convenient, and inexpensive laboratory examination which can be used to obtain white blood cell (WBC) and platelet counts. The aims of this study were to investigate the relationships between WBC and platelet counts with hepatic steatosis, and whether WBC and platelet counts were associated with the severity of hepatic steatosis. We enrolled 1969 participants residing in southern Taiwan who took part in a health survey from June 2016 to September 2018 in this cross-sectional study. None of the participants were heavy alcohol users or had a history of hepatitis B or C. We collected laboratory data, and the severity of hepatic steatosis was determined by abdominal ultrasound. The overall prevalence rate of hepatic steatosis was 42.0%. There were significant trends of stepwise increases in WBC count (p < 0.001) corresponding to the severity of hepatic steatosis. After multivariable linear regression analysis, hepatic steatosis was significantly associated with high WBC count (coefficient β, 0.209; 95% confidence interval (CI), 0.055 to 0.364; p = 0.008) and high platelet count (coefficient β, 12.213; 95% CI, 6.092 to 18.334; p < 0.001); also, higher WBC counts corresponded with the severity of hepatic steatosis.
Circulating miRNA Correlates with Lipid Profile and Disease Activity in Psoriatic Arthritis, Rheumatoid Arthritis, and Ankylosing Spondylitis Patients
Authors: Bonek Krzysztof , Kuca Warnawin Ewa , Kornatka Anna , Plebańczyk Magdalena , Burakowski Tomasz , Maśliński Włodzimierz , Wisłowska Małgorzata , Głuszko Piotr , Ciechomska Marzena
Published: April 2022

This study aimed to investigate the associations of microRNA (miRs) signatures with cytokines, serum lipids, and disease activity in patients with psoriatic arthritis (PsA), ankylosing spondylitis (AS), and rheumatoid arthritis (RA). In total, 65 patients (PsA n = 25, AS n = 25, RA n = 15) and 25 healthy controls (HC) were enrolled into the study. The expression of miR-223-5p, miR-92b-3p, miR-485-3p, miR-10b-5p, let-7d-5p, miR-26a-2-3p, miR-146b-3p, and cytokines levels were measured in sera. DIANA-mirPath analysis was used to predict pathways targeted by the dysregulated miRs. Disease activity scores were calculated. Lipid profile, uric acid, glucose level, and C-reactive protein (CRP) concentrations were determined in the blood. Based on lipid profiles, the PsA group had hypertriglyceridaemia, and RA patients revealed mixed dyslipidaemia, while in AS, no specific changes were found. miR expression analysis revealed upregulation of miR-26a-2-3p and miR-10b-5p in PsA, miR-485-3p in AS, and let-7d-5p in RA. Several correlations between disease activity indexes, metabolites levels, and expression of miRs were observed in PsA, RA, and AS patients. Finally, in ROC analysis, miR-26a-2-3p/miR-485-3p, and let-7d-5p/miR-146b-3p tandems revealed high sensitivity and specificity in distinguishing between PsA, AS, and RA. Our study illustrates the superiority of miR expressions in distinguishing between RA, PsA, and AS. In PsA, a unique regulatory pathway exists through miR-26a-2-3p, miR-223-5p, miR-10b-5p, and miR-92b-3p that converges proatherogenic metabolism and disease activity.
Emerging Methods of Monitoring Volatile Organic Compounds for Detection of Plant Pests and Disease
Authors: MacDougall Samantha , Bayansal Fatih , Ahmadi Ali
Published: April 2022

Each year, unwanted plant pests and diseases, such as Hendel or potato soft rot, cause damage to crops and ecosystems all over the world. To continue to feed the growing population and protect the global ecosystems, the surveillance and management of the spread of these pests and diseases are crucial. Traditional methods of detection are often expensive, bulky and require expertise and training. Therefore, inexpensive, portable, and user-friendly methods are required. These include the use of different gas-sensing technologies to exploit volatile organic compounds released by plants under stress. These methods often meet these requirements, although they come with their own set of advantages and disadvantages, including the sheer number of variables that affect the profile of volatile organic compounds released, such as sensitivity to environmental factors and availability of soil nutrients or water, and sensor drift. Furthermore, most of these methods lack research on their use under field conditions. More research is needed to overcome these disadvantages and further understand the feasibility of the use of these methods under field conditions. This paper focuses on applications of different gas-sensing technologies from over the past decade to detect plant pests and diseases more efficiently.
Rapid Detection of Deoxynivalenol in Dry Pasta Using a Label-Free Immunosensor
Authors: Malvano Francesca , Pilloton Roberto , Rubino Alfredo , Albanese Donatella
Published: April 2022

This work focused on the development and optimization of an impedimetric label-free immunosensor for detecting deoxynivalenol (DON). A monoclonal antibody for DON detection was immobilized on a modified gold electrode with a cysteamine layer and polyamidoamine (PAMAM) dendrimers. Cyclic voltammetry and electrochemical impedance spectroscopy techniques were used to monitor the layer-by-layer development of the immunosensor design, while electrochemical impedance spectroscopy and differential pulse voltammetry were employed to investigate the antigen/antibody interaction. The PAMAM dendrimers, allowing to immobilize a large number of monoclonal antibodies, permitted reaching, through the DPV technique, a high sensitivity and a low limit of detection equal to 1 ppb. The evaluation of the possible reuse of the immunosensors highlighted a decrease in the analytical performances of the regenerated immunosensors. After evaluating the matrix effect, the developed immunosensor was used to quantify DON in pasta samples spiked with a known mycotoxin concentration. Taking into consideration the DON extraction procedure used for the pasta samples and the matrix effect related to the sample, the proposed immunosensor showed a limit of detection of 50 ppb, which is lower than the maximum residual limit imposed by European Regulation for DON in dry pasta (750 ppb).
A Multilayer Perception for Estimating the Overall Risk of Residential Projects in the Conceptual Stage
Authors: Badawy Mohamed , Alqahtani Fahad K. , Sherif Mohamed
Published: April 2022

The ability to foresee hazards early plays a critical role in estimating the entire cost of a project. Although several studies have established models to predict the total cost of a project at a conceptual stage, there remains a research vacuum in measuring the overall risk at this stage. Using artificial neural networks, this research provides a strategy for estimating the overall risk in residential projects at the conceptual stage. There are eight important components in the suggested paradigm. The model was created using data from 149 projects. In the first hidden layer in the model, there are five neurons, and in the second hidden layer, there are three neurons. The suggested model’s mean absolute error rate was 11.7%. In the conceptual stage of residential projects, the number of floors, the type of interior finishes, and the implementation of risk management processes are the significant aspects that influence the overall risk. The proposed model assists project managers in precisely estimating the project’s overall risk, which leads to a more accurate estimation of the contract’s entire worth at the conceptual stage, allowing the stakeholders to decide whether or not to proceed with the project.
A Simplified Thermal Comfort Calculation Method of Radiant Floor Cooling Technology for Office Buildings in Northern China
Authors: Wang Xiaolong , Mu Tian , Zhang Lili , Zhang Wenke , Zhang Linhua
Published: April 2022

The increasing application of floor heating technology promotes the development of floor radiant cooling technology (abbreviated as FRC technology). Many office buildings in northern China try to use FRC technology to cool in summer, but thermal comfort is the key problem restricting the promotion of this technology. The thermal comfort problems of an office room with floor radiant cooling were studied in this paper by the methods of numerical simulation, control variable, and data fitting, and the experimental results were verified in multiple ways. It was found that, for an office room using floor radiant cooling, the effect of the floor surface temperature on thermal comfort was about 16%, while the effect of indoor air temperature was about 84%, and relative humidity had little effect on thermal comfort. A simplified thermal comfort calculation model was proposed, which could be used as an indicator to adjust the floor surface and indoor air temperature, or could be used to calculate the PMV-PPD value. The findings have guiding significance for the design and control of FRC technology.
History and Updates of the GROINSS-V Studies
Authors: Wagner Marise M. , van der Zee Ate G. J. , Oonk Maaike H. M.
Published: April 2022

Surgical management of vulvar cancer is associated with high morbidity rates. The main aim of the GROINSS-V studies is reducing treatment-related morbidity by finding safe alternative treatment options in early-stage vulvar cancer patients. This article reviews the history, results, and updates of the GROINSS-V studies. The first GROINSS-V study was a multicenter observational study (from 2000 to 2006), which investigated the safety and clinical applicability of the sentinel lymph node procedure in patients with early-stage vulvar cancer. GROINSS-V-I showed that omitting inguinofemoral lymphadenectomy was safe in early-stage vulvar cancer patients with a negative sentinel lymph node, with an impressive reduction in treatment-related morbidity. GROINSS-V-II, a prospective multicenter phase II single-arm treatment trial (from 2005 to 2016) investigated whether radiotherapy could be a safe alternative for inguinofemoral lymphadenectomy in patients with a metastatic sentinel lymph node. This study showed that radiotherapy in patients with sentinel lymph node micrometastases (≤2 mm) was safe in terms of groin recurrence rate and with less treatment-related morbidity. These results, published in August 2021, should be implemented in (inter)national treatment guidelines for vulvar cancer. GROINSS-V-III recently started including patients. This study investigates the effectiveness and safety of chemoradiation in patients with a macrometastasis (>2 mm) in the sentinel lymph node.
Correction: Bar-Sela et al. Cannabis Consumption Used by Cancer Patients during Immunotherapy Correlates with Poor Clinical Outcome. Cancers 2020, 12, 2447
Authors: Bar-Sela Gil , Cohen Idan , Campisi-Pinto Salvatore , Lewitus Gil M. , Oz-Ari Lanuel , Jehassi Ayellet , Peer Avivit , Turgeman Ilit , Vernicova Olga , Berman Paula , Wollner Mira , Moskovitz Mor , Meiri David
Published: April 2022

In the original article [...]
Valganciclovir as Add-on to Second-Line Therapy in Patients with Recurrent Glioblastoma
Authors: Pantalone Mattia Russel , Rahbar Afsar , Söderberg-Naucler Cecilia , Stragliotto Giuseppe
Published: April 2022

Glioblastoma invariably recurs despite aggressive and multimodal first-line treatment and no standardized second-line therapy exists. We previously reported that treatment with the antiviral drug valganciclovir as an add-on to standard therapy significantly prolonged overall survival in 102 patients with newly diagnosed glioblastoma compared to contemporary controls. Here we present the results of retrospective survival analyses including patients with glioblastoma that initiated valganciclovir therapy after recurrence. Twenty-nine patients with recurrent glioblastoma received valganciclovir as an add-on to second-line therapy at Karolinska University Hospital. Contemporary controls were 109 patients with glioblastoma who received similar second-line therapy at our institution. We retrospectively analyzed survival data of these patients. Patients with recurrent glioblastoma who received valganciclovir had longer median overall survival after recurrence than controls (12.1 vs. 7.4 months, respectively, p = 0.0028). The drug was well tolerated. Both patients who underwent re-operation and patients that were not re-operated after recurrence benefitted significantly from valganciclovir therapy. Valganciclovir prolonged survival after recurrence both in patients with an unmethylated and methylated MGMT promoter gene. Valganciclovir was safe to use and prolonged median survival after recurrence for patients with recurrent glioblastoma, re-operated or not after recurrence, and with methylated or unmethylated MGMT promoter gene.
Physical Activity and Long-Term Risk of Breast Cancer, Associations with Time in Life and Body Composition in the Prospective Malmö Diet and Cancer Study
Authors: Boraka Öykü , Klintman Marie , Rosendahl Ann H.
Published: April 2022

Being physically active as part of everyday life reduces breast cancer risk. Less is known whether the benefits of an active lifestyle differ depending on the timing of physical activity in life or anthropometric characteristics. The aim of this study was to bring further insights to the association of physical activity in relation to menopausal status and body composition with breast cancer risk by making use of a prospective Swedish cohort (Malmö Diet and Cancer Study) with long-term follow-up. Physical activity information of 15,983 participants for the past 12 months prior to study entry was assessed according to metabolic equivalent task (MET)-hours/week to integrate duration and intensity of reported activities. During 23.2 years median follow-up, 1302 invasive breast cancers occurred. Women reporting a high physical activity at study baseline, corresponding to >1 h daily walking/week (≥28.5 MET-h/week), had a 23% lower long-term breast cancer risk (HRadj = 0.77, 95% CI 0.66–0.90) than those reporting low physical activity, being most pronounced among perimenopausal and postmenopausal women, and women with waist circumference, body fat percentage, or BMI in the upper-normal and overweight range. For premenopausal women or women having obesity or the largest body composition, high physical activity alone did not modify the breast cancer risk, suggesting additional preventive measures indicated in these groups to reduce the long-term risk of breast cancer.
The Role of Fast-Cycling Atypical RHO GTPases in Cancer
Authors: Aspenström Pontus
Published: April 2022

The RHO GTPases comprise a subfamily within the RAS superfamily of small GTP-hydrolyzing enzymes and have primarily been ascribed roles in regulation of cytoskeletal dynamics in eukaryotic cells. An oncogenic role for the RHO GTPases has been disregarded, as no activating point mutations were found for genes encoding RHO GTPases. Instead, dysregulated expression of RHO GTPases and their regulators have been identified in cancer, often in the context of increased tumor cell migration and invasion. In the new landscape of cancer genomics, activating point mutations in members of the RHO GTPases have been identified, in particular in RAC1, RHOA, and CDC42, which has suggested that RHO GTPases can indeed serve as oncogenes in certain cancer types. This review describes the current knowledge of these cancer-associated mutant RHO GTPases, with a focus on how their altered kinetics can contribute to cancer progression.
A Mutated Prostatic Acid Phosphatase (PAP) Peptide-Based Vaccine Induces PAP-Specific CD8+ T Cells with Ex Vivo Cytotoxic Capacities in HHDII/DR1 Transgenic Mice
Authors: Vu Pauline Le , Vadakekolathu Jayakumar , Idri Sarra , Nicholls Holly , Cavaignac Manon , Reeder Stephen , Khan Masood A. , Christensen Dennis , Pockley Alan Graham , McArdle Stéphanie E.
Published: April 2022

Background: Current treatments for castrate (hormone)-resistant prostate cancer (CRPC) remain limited and are not curative, with a median survival from diagnosis of 23 months. The PAP-specific Sipuleucel-T vaccine, which was approved by the FDA in 2010, increases the Overall Survival (OS) by 4 months, but is extremely expensive. We have previously shown that a 15 amino accid (AA) PAP sequence-derived peptide could induce strong immune responses and delay the growth of murine TRAMP-C1 prostate tumors. We have now substituted one amino acid and elongated the sequence to include epitopes predicted to bind to several additional HLA haplotypes. Herein, we present the immunological properties of this 42mer-mutated PAP-derived sequence (MutPAP42mer). Methods: The presence of PAP-135-143 epitope-specific CD8+ T cells in the blood of patients with prostate cancer (PCa) was assessed by flow cytometry using Dextramer™ technology. HHDII/DR1 transgenic mice were immunized with mutated and non-mutated PAP-derived 42mer peptides in the presence of CAF®09 or CpG ODN1826 (TLR-9 agonist) adjuvants. Vaccine-induced immune responses were measured by assessing the proportion and functionality of splenic PAP-specific T cells in vitro. Results: PAP-135-143 epitope-specific CD8+ T cells were detected in the blood of patients with PCa and stimulation of PBMCs from patients with PCa with mutPAP42mer enhanced their capacity to kill human LNCaP PCa target cells expressing PAP. The MutPAP42mer peptide was significantly more immunogenic in HHDII/DR1 mice than the wild type sequence, and immunogenicity was further enhanced when combined with the CAF®09 adjuvant. The vaccine induced secretory (IFNγ and TNFα) and cytotoxic CD8+ T cells and effector memory splenic T cells. Conclusions: The periphery of patients with PCa exhibits immune responsiveness to the MutPAP42mer peptide and immunization of mice induces/expands T cell-driven, wild-type PAP immunity, and therefore, has the potential to drive protective anti-tumor immunity in patients with PCa.
Surgical Outcomes of Laparoscopic Pelvic Lymph Node Debulking during Staging Aortic Lymphadenectomy in Locally Advanced Cervical Cancer: A Multicenter Study
Authors: Díaz-Feijoó Berta , Acosta Úrsula , Torné Aureli , Gil-Ibáñez Blanca , Hernández Alicia , Domingo Santiago , Bradbury Melissa , Gil-Moreno Antonio
Published: April 2022

Background: Few studies have evaluated laparoscopic pelvic lymph node (PLN) debulking during staging aortic lymphadenectomy in locally advanced cervical cancer (LACC). It allows us to know the lymph node status and facilitates the action of chemoradiotherapy (CRT) by reducing tumor burden. We evaluated its feasibility and compared the perioperative morbidity and the time to CRT with a control group. Methods: This was a multicenter retrospective study of patients with LACC FIGO stage IIIC1r who were recipients of CRT. We compared two cohorts: group 1, which consisted of 164 patients with surgical staging by laparoscopic aortic lymphadenectomy and PLN debulking, and group 2, which consisted of 111 patients with aortic lymphadenectomy alone. Results: Excision of the bulky nodes was possible in all patients in group 1 except for one. Surgery lasted a median of 82 min longer in group 1 but there was no greater intraoperative bleeding or increased hospital stay. There were no significant differences in intraoperative or postoperative complications between the groups. A significantly shorter time from surgery to the start of RT was observed in group 1. Conclusions: It is feasible to perform laparoscopic PLN debulking in the same procedure as the staging aortic lymphadenectomy in LACC without increasing surgical or postoperative complications and without delaying the start of CRT compared to single aortic lymphadenectomy.
Modified Body Mass Index as a Novel Nutritional and Prognostic Marker in Patients with Cardiac Amyloidosis
Authors: Dongiglio Francesca , Palmiero Giuseppe , Monda Emanuele , Rubino Marta , Verrillo Federica , Caiazza Martina , Cirillo Annapaola , Fusco Adelaide , Vetrano Erica , Lioncino Michele , Diana Gaetano , Di Fraia Francesco , Cerciello Giuseppe , Manganelli Fiore , Vriz Olga , Limongelli Giuseppe
Published: April 2022

The nutritional assessment is gaining clinical relevance since cardiac cachexia and malnutrition are emerging as novel markers of functional status and prognosis in many cardiovascular disorders, including cardiac amyloidosis (CA). This study aimed to evaluate the prognostic role of different nutritional indices for cardiovascular mortality in patients with CA and subgroups. Fifty CA patients (26 AL and 24 ATTR wild-type) were retrospectively analyzed. All patients underwent a comprehensive clinical and laboratory evaluation. Conventional body mass index (cBMI), modified BMI (mBMI), new BMI (nBMI) and prognostic nutritional index (PNI) were analyzed. Multivariate regression analysis was performed to identify the association between nutritional and other clinical-laboratory parameters with cardiovascular death. Compared to ATTRwt patients, those with AL showed lower mBMI values. No significant difference was observed for the other nutritional indices. During a median follow-up of 11.2 months, a lower mBMI quartile was associated with worse survival, in both groups. In multivariate analysis, mBMI emerged as an independent predictor for cardiovascular death. This study showed that mBMI is a novel index of malnutrition and an independent risk factor for cardiovascular mortality in patients with CA in both AL and ATTRwt form.
Whole-Genome Sequence and Comparative Analysis of Trichoderma asperellum ND-1 Reveal Its Unique Enzymatic System for Efficient Biomass Degradation
Authors: Zheng Fengzhen , Han Tianshuo , Basit Abdul , Liu Junquan , Miao Ting , Jiang Wei
Published: April 2022

The lignocellulosic enzymes of Trichoderma asperellum have been intensely investigated toward efficient conversion of biomass into high-value chemicals/industrial products. However, lack of genome data is a remarkable hurdle for hydrolase systems studies. The secretory enzymes of newly isolated T. asperellum ND-1 during lignocellulose degradation are currently poorly known. Herein, a high-quality genomic sequence of ND-1, obtained by both Illumina HiSeq 2000 sequencing platforms and PacBio single-molecule real-time, has an assembly size of 35.75 Mb comprising 10,541 predicted genes. Secretome analysis showed that 895 proteins were detected, with 211 proteins associated with carbohydrate-active enzymes (CAZymes) responsible for biomass hydrolysis. Additionally, T. asperellum ND-1, T. atroviride IMI 206040, and T. virens Gv-298 shared 801 orthologues that were not identified in T. reesei QM6a, indicating that ND-1 may play critical roles in biological-control. In-depth analysis suggested that, compared with QM6a, the genome of ND-1 encoded a unique enzymatic system, especially hemicellulases and chitinases. Moreover, after comparative analysis of lignocellulase activities of ND-1 and other fungi, we found that ND-1 displayed higher hemicellulases (particularly xylanases) and comparable cellulases activities. Our analysis, combined with the whole-genome sequence information, offers a platform for designing advanced T. asperellum ND-1 strains for industrial utilizations, such as bioenergy production.
Isospecific Polymerization of Halide- and Amino-Substituted Styrenes Using a Bis(phenolate) Titanium Catalyst
Authors: Wang Qiyuan , Zhang Zhen , Jiang Yang , Zhang Yanfeng , Li Shihui , Cui Dongmei
Published: April 2022

Isospecific polymerization of polar styrenes is a challenge of polymer science. Particularly challenging are monomers bearing electron-withdrawing substituents or bulky substituents. Here, we report the coordination polymerization of halide- and amino-functionalized styrenes including para-fluorostyrene (pFS), para-chlorostyrene (pClS), para-bromostyrene (pBrS), and para-(N,N-diethylamino)styrene (DMAS) using 2,2′-sulfur-bridged bis(phenolate) titanium precursor (1). The combination of 1 and [Ph3C][B(C6F5)4] and AliBu3 provides crystalline poly(pFS)s with perfect isotacticity (mmmm > 95%) and high molecular weights (≤16.0 × 104 g mol−1). Upon activation with a large excess of DMAO, 1 reaches polymerization activity of 5.58 × 105 g molTi−1 h−1 producing isotactic poly(pFS)s featuring higher molecular weights (≤39.6 × 104 g mol−1). The distinguished performance of the 1/DMAO system has been extended to the polymerization of pClS and pBrS, both usually involve halogen abstraction during the polymerization, to produce isotactic and high molecular weight (Mn = 32.2 × 104 vs. 13.7 × 104 g mol−1) polymers in good activities (2.18 × 105 vs. 1.31 × 105 g molTi−1 h−1). Surprisingly, 1/DMAO is nearly inactive for DMAS polymerization, on contrary, the system 1/[Ph3C][B(C6F5)4]/AliBu3 displays isoselectivity (mmmm > 95%) albeit in a moderate activity.
CVD and COVID-19: Emerging Roles of Cardiac Fibroblasts and Myofibroblasts
Authors: Katwa Laxmansa C. , Mendoza Chelsea , Clements Madison
Published: April 2022

Cardiovascular disease (CVD) is the leading cause of death worldwide. Current data suggest that patients with cardiovascular diseases experience more serious complications with coronavirus disease-19 (COVID-19) than those without CVD. In addition, severe COVID-19 appears to cause acute cardiac injury, as well as long-term adverse remodeling of heart tissue. Cardiac fibroblasts and myofibroblasts, being crucial in response to injury, may play a pivotal role in both contributing to and healing COVID-19-induced cardiac injury. The role of cardiac myofibroblasts in cardiac fibrosis has been well-established in the literature for decades. However, with the emergence of the novel coronavirus SARS-CoV-2, new cardiac complications are arising. Bursts of inflammatory cytokines and upregulation of TGF-β1 and angiotensin (AngII) are common in severe COVID-19 patients. Cytokines, TGF-β1, and Ang II can induce cardiac fibroblast differentiation, potentially leading to fibrosis. This review details the key information concerning the role of cardiac myofibroblasts in CVD and COVID-19 complications. Additionally, new factors including controlling ACE2 expression and microRNA regulation are explored as promising treatments for both COVID-19 and CVD. Further understanding of this topic may provide insight into the long-term cardiac manifestations of the COVID-19 pandemic and ways to mitigate its negative effects.
Mechanical Cues, E-Cadherin Expression and Cell “Sociality” Are Crucial Crossroads in Determining Pancreatic Ductal Adenocarcinoma Cells Behavior
Authors: Bianchi Francesca , Sommariva Michele , Cornaghi Laura Brigida , Denti Luca , Nava Ambra , Arnaboldi Francesca , Moscheni Claudia , Gagliano Nicoletta
Published: April 2022

E-cadherin, an epithelial-to-mesenchymal transition (EMT) marker, is coupled to actin cytoskeleton and distributes cell forces acting on cells. Since YAP transduces mechanical signals involving actin cytoskeleton, we aimed to investigate the relationship between YAP and mechanical cues in pancreatic ductal adenocarcinoma (PDAC) cell lines, characterized by different EMT-related phenotypes, cultured in 2D monolayers and 3D spheroids. We observed that the YAP/p-YAP ratio was reduced in HPAC and MIA PaCa-2 cell lines and remained unchanged in BxPC-3 cells when cultured in a 3D setting. CTGF and CYR61 gene expression were down-regulated in all PDAC 3D compared to 2D cultures, without any significant effect following actin cytoskeleton inhibition by Cytochalasin B (CyB) treatment. Moreover, LATS1 mRNA, indicating the activation of the Hippo pathway, was not influenced by CyB and differed in all PDAC cell lines having different EMT-related phenotype but a similar pattern of CTGF and CYR61 expression. Although the role of YAP modulation in response to mechanical cues in cancer cells remains to be completely elucidated, our results suggest that cell arrangement and phenotype can determine variable outcomes to mechanical stimuli in PDAC cells. Moreover, it is possible to speculate that YAP and Hippo pathways may act as parallel and not exclusive inputs that, converging at some points, may impact cell behavior.
Comparative Proteomics Combined with Morphophysiological Analysis Revealed Chilling Response Patterns in Two Contrasting Maize Genotypes
Authors: Zou Jinpeng , Yang Liang , Li Yuhong , Piao Mingxin , Li Yaxing , Yao Nan , Zhang Xiaohong , Zhang Qian , Hu Guanghui , Yang Deguang , Zuo Zecheng
Published: April 2022

Maize yield is significantly influenced by low temperature, particularly chilling stress at the maize seedling stage. Various physiological approaches have been established to resist chilling stress; however, the detailed proteins change patterns underlying the maize chilling stress response at the seedling stage remain unknown, preventing the development of breeding-based methods to resist chilling stress in maize. Thus, we performed comprehensive physiological, comparative proteomics and specific phytohormone abscisic acid (ABA) assay on different maize inbred lines (tolerant-line KR701 and sensitive-line hei8834) at different seedling stages (the first leaf stage and third leaf stage) under chilling stress. The results revealed several signalling proteins and pathways in response to chilling stress at the maize seedling stage. Meanwhile, we found ABA pathway was important for chilling resistance of tolerant-line KR701 at the first leaf stage. Related chilling-responsive proteins were further catalogued and analysed, providing a resource for further investigation and maize breeding.
Towards Kinase Inhibitor Therapies for Fragile X Syndrome: Tweaking Twists in the Autism Spectrum Kinase Signaling Network
Authors: D’Incal Claudio , Broos Jitse , Torfs Thierry , Kooy R. Frank , Vanden Berghe Wim
Published: April 2022

Absence of the Fragile X Messenger Ribonucleoprotein 1 (FMRP) causes autism spectrum disorders and intellectual disability, commonly referred to as the Fragile X syndrome. FMRP is a negative regulator of protein translation and is essential for neuronal development and synapse formation. FMRP is a target for several post-translational modifications (PTMs) such as phosphorylation and methylation, which tightly regulate its cellular functions. Studies have indicated the involvement of FMRP in a multitude of cellular pathways, and an absence of FMRP was shown to affect several neurotransmitter receptors, for example, the GABA receptor and intracellular signaling molecules such as Akt, ERK, mTOR, and GSK3. Interestingly, many of these molecules function as protein kinases or phosphatases and thus are potentially amendable by pharmacological treatment. Several treatments acting on these kinase-phosphatase systems have been shown to be successful in preclinical models; however, they have failed to convincingly show any improvements in clinical trials. In this review, we highlight the different protein kinase and phosphatase studies that have been performed in the Fragile X syndrome. In our opinion, some of the paradoxical study conclusions are potentially due to the lack of insight into integrative kinase signaling networks in the disease. Quantitative proteome analyses have been performed in several models for the FXS to determine global molecular processes in FXS. However, only one phosphoproteomics study has been carried out in Fmr1 knock-out mouse embryonic fibroblasts, and it showed dysfunctional protein kinase and phosphatase signaling hubs in the brain. This suggests that the further use of phosphoproteomics approaches in Fragile X syndrome holds promise for identifying novel targets for kinase inhibitor therapies.