bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Bevacizumab Combined with Pemetrexed in the Treatment of Recurrent and Metastatic Cervical Cancer
Authors: He Ying , Wang Jing , Xie Shuangshuang , Xue Qianlong
Published: May 2022

Background

To investigate the efficacy and safety of bevacizumab combined with pemetrexed in the treatment of recurrent and metastatic cervical cancer.

Methods

Clinical data of 65 patients with recurrent and metastatic cervical cancer who were admitted to our hospital were collected for retrospective analysis. All patients were administered with bevacizumab combined with pemetrexed for 4–6 cycles (21 days as 1 cycle). The short-term clinical efficacy and adverse reactions were compared between the two groups. In addition, the survival status of patients was followed up and recorded.

Results

At least 4 cycles of chemotherapy were given to the 65 patients. There were 0 cases of complete response (CR), 14 cases of partial response (PR), 36 cases of stable disease (SD) and 15 cases of progressive disease (PD). The objective response rate (ORR) and the disease control rate (DCR) were 21.5% (14/65) and 76.9% (50/65), respectively. DCR was superior in patients with squamous cell carcinoma to that in those with adenocarcinoma (p = 0.039), but no statistically significant difference was found in ORR. Patients with extra-pelvic metastatic lesions had a better efficacy than those with intra-pelvic metastatic lesions, but the difference was not statistically significant (p > 0.05). The post-treatment adverse reactions mainly involved fatigue, nausea and vomiting, bleeding, leukopenia, anemia, thrombocytopenia, transaminase elevation, hypertension, proteinuria and neurotoxicity, most of which were grade I–II that ameliorated after symptomatic therapy. Grade III adverse reactions mainly included pain in 5 cases (7.7%), leukopenia in 17 cases (26.2%), anemia in 22 cases (33.8%), thrombocytopenia in 6 cases (9.2%), hypertension in 5 cases (7.7%) and neurotoxicity in 7 cases (10.8%). The follow-up results manifested that median overall survival (OS) and median progression-free survival (PFS) were 10.6 months and 6.6 months, respectively.

Conclusion

Bevacizumab combined with pemetrexed exhibits certain efficacy in the treatment of recurrent and metastatic cervical cancer, with tolerable adverse reactions. Therefore, this therapeutic option deserves clinical popularization and application.
Removal of Aflatoxins Using Agro-Waste-Based Materials and Current Characterization Techniques Used for Biosorption Assessment
Authors: Vázquez-Durán Alma , Nava-Ramírez María de Jesús , Téllez-Isaías Guillermo , Méndez-Albores Abraham
Published: May 2022

Aflatoxins are the most hazardous fungal-generated secondary metabolites produced by toxigenic Aspergillus species. These toxins are frequently detected in food and feed and impose either acute or chronic effects in humans and animals, causing great public concern. Because of the adverse effects of aflatoxins, many physical, chemical, and biological decontamination approaches have been developed. However, the most commonly used procedure is the addition of adsorbent materials into aflatoxin-contaminated diets to reduce toxin absorption and distribution to blood and target organs. In recent times, sorption technology with agro-waste-based materials has appeared as a promising alternative over conventional binding agents with the benefits of low cost, higher rentability, feasibility, and exceptional efficiencies. This review is mainly focused on discussing the most important agro-waste-based materials able to adsorb aflatoxins such as pomaces, seeds, stems, hulls, peels, leaves, berries, lignins, fibers, weeds, and various horticultural byproducts. Further data of the in vitro, in vivo, and in silico efficacy of these biomaterials to adsorb and then desorb aflatoxins are given. Besides, an overview of the main characterization techniques used to elucidate the most important physical and chemical mechanisms involved in the biosorption is presented. Finally, conclusions and future research necessities are also outlined.
Talent Management in the Banking Sector: A Systematic Literature Review
Authors: Theodorsson Unnar , Gudlaugsson Thorhallur , Gudmundsdottir Svala
Published: May 2022

This paper conducts a systematic literature review and relates to how talent management (TM) and recruitment strategies are applied in the financial sector, and specifically in the banking sector. The goals of this paper are to provide a comprehensive analysis of TM research in the financial sector, identify and debate major research topics, and suggest future research possibilities. The study examines publications that were published between 2000 and 2021, which were obtained from the databases Web of Science and Scopus. According to the findings, academics are becoming more interested in TM in the banking sector, which appears to be linked to the severe scarcity of skilled people who possess required talents. The findings are relevant to both academia and the banking sector, as the paper provides data relating to what has already been researched in academia, while also highlighting the need for more research into how TM is understood, valued and implemented. Consequently, this paper paves the way for academics to conduct empirical research on TM and recruitment tactics in the banking sector and the financial sector as a whole. This paper is structured according to the PRISMA requirements for systematic literature reviews.
Ectopic Expression of Kenaf (Hibiscus cannabinus L.) HcWRKY50 Improves Plants’ Tolerance to Drought Stress and Regulates ABA Signaling in Arabidopsis
Authors: Niu Xiaoping , Chen Meixia , She Zeyuan , Aslam Mohammad , Qi Jianmin , Qin Yuan
Published: May 2022

Kenaf (Hibiscus cannabinus L.) is an environmentally friendly, multipurpose fiber crop suitable for osmotic stress tolerance studies. However, the mechanisms of tolerance remain largely unknown. Here, we identified a stress-responsive HcWRKY50 gene from kenaf (Hibiscus cannabinus L.) and studied its function and tolerance under drought stress. HcWRKY50 is a nuclear-localized protein. The overexpression of HcWRKY50 in Arabidopsis showed higher drought tolerance, exhibiting increased root length and lateral root number, and reduced stomatal density compared with the control lines. The seed germination and seedling growth of HcWRKY50 transgenic plants showed less sensitivity to ABA but they became more sensitive to ABA in their stomatal aperture. Furthermore, qRT-PCR analysis revealed that HcWRKY50 regulated ABA signaling by promoting the expression of several key ABA-responsive and stress-responsive genes such as RD29B and COR47 in transgenic lines. Taken together, this study demonstrated that the kenaf transcription factor HcWRKY50 regulates seed germination and seedling growth and improves drought stress tolerance via an ABA signaling pathway.
Estimating Leaf Water Content through Low-Cost LiDAR
Authors: Hama Akira , Matsumoto Yutaro , Matsuoka Nobuhiro
Published: May 2022

In recent years, rapid development has been achieved in technologies and sensors related to autonomous driving and assistive technologies. In this study, low-cost light detection and ranging (LiDAR) was used to estimate leaf water content (LWC) by measuring LiDAR reflectance instead of morphological measurement (e.g., plant size), which is the conventional method. Experimental results suggest that reflection intensity can be corrected using the body temperature of LiDAR, when using reflection intensity observed by LiDAR. Comparisons of corrected LiDAR observation data and changes in reflectance attributed to leaf drying suggest that the reflectance increases with leaf drying in the 905 nm band observed with a hyperspectral camera. The LWC is estimated with an R2 of 0.950, RMSE of 6.78%, and MAPE of 18.6% using LiDAR reflectance. Although the 905 nm wavelength used by LiDAR is not the main water absorption band, the reflectance is closely related to the leaf structure; therefore, it is believed that the reflectance changes with structural changes accompanying drying, which allows for the indirect estimation of LWC. This can help utilize the reflectance of the 905 nm single-wavelength LiDAR, which, to the best of our knowledge has not been used in plant observations for estimating LWC.
Optimizing Irrigation and Nitrogen Management to Increase Yield and Nitrogen Recovery Efficiency in Double-Cropping Rice
Authors: Zhu Haijun , Zhang Ting , Zhang Chunlan , He Xiaoe , Shi Ailong , Tan Weijian , Yi Zhenxie , Wang Xuehua
Published: May 2022

Water and nitrogen are the key factors affecting the yield and nitrogen recovery efficiency of double-cropping rice, but information about optimizing nitrogen fertilizer and irrigation management to achieve high yield is still limited. The purpose was to study the effects of different nitrogen application rates (D1, D2, D3, D4 (0, 112.5, 150.0, and 187.5 kg ha−1 for early-season rice and 0, 135, 180, and 225 kg ha−1 for late-season rice)) and irrigation conditions (G1, Alternate wetting and drying irrigation, G2, flooding irrigation) on rice yield and nitrogen recovery efficiency. Field experiments were carried out in the early and late seasons of the subtropical environment in Heshan County, Hunan Province, China in 2018 and 2019. The results showed that the yield was increased by the comprehensive action of reasonable irrigation mode and nitrogen management. Under G1D4 and G1D3 treatments, the maximum grain yield of early-season rice was 7.42 t ha−1, which was 0.8~35.9% higher than other treatments, and that of late-season rice was 8.20 t ha−1, which was 13.3~67.0% higher than other treatments. The increase of yield in G1D4 and G1D3 treatments was due to the increase in dry matter accumulation, effective Panicles number, and Spikelets per panicle, whose increase was due to an increase in photosynthesis and nitrate reductase activity. Compared with other treatments, late-season rice G1D3 treatment achieved a higher yield with less nitrogen fertilizer, while early-season rice G1D4 treatment achieved the highest yield, but the nitrogen recovery efficiency decreased. We should focus on more effective nitrogen fertilizer and irrigation management to further improve the yield potential of double-cropping rice.
Cybernetic Hive Minds: A Review
Authors: Chowdhury Anirban , Ramadas Rithvik
Published: May 2022

Insect swarms and migratory birds are known to exhibit something known as a hive mind, collective consciousness, and herd mentality, among others. This has inspired a whole new stream of robotics known as swarm intelligence, where small-sized robots perform tasks in coordination. The social media and smartphone revolution have helped people collectively work together and organize in their day-to-day jobs or activism. This revolution has also led to the massive spread of disinformation amplified during the COVID-19 pandemic by alt-right Neo Nazi Cults like QAnon and their counterparts from across the globe, causing increases in the spread of infection and deaths. This paper presents the case for a theoretical cybernetic hive mind to explain how existing cults like QAnon weaponize group think and carry out crimes using social media-based alternate reality games. We also showcase a framework on how cybernetic hive minds have come into existence and how the hive mind might evolve in the future. We also discuss the implications of these hive minds for the future of free will and how different malfeasant entities have utilized these technologies to cause problems and inflict harm by various forms of cyber-crimes and predict how these crimes can evolve in the future.
Experimental Cyclic Heat Stress on Intestinal Permeability, Bone Mineralization, Leukocyte Proportions and Meat Quality in Broiler Chickens
Authors: Rocchi Alessandro , Ruff Jared , Maynard Clay J. , Forga Aaron J. , Señas-Cuesta Roberto , Greene Elizabeth S. , Latorre Juan D. , Vuong Christine N. , Graham Brittany D. , Hernandez-Velasco Xochitl , Tellez Guillermo , Petrone-Garcia Victor M. , Laverty Lauren , Hargis Billy M. , Erf Gisela F. , Owens Casey M. , Tellez-Isaias Guillermo
Published: May 2022

The goal of this research was to assess cyclic heat stress on gut permeability, bone mineralization, and meat quality in chickens. Two separate trials were directed. 320 day-of-hatch Cobb 500 male chicks were randomly assigned to four thermoneutral (TN) and four cyclic heat stress (HS) chambers with two pens each, providing eight replicates per treatment in each trial (n = 20 chicks/replicate). Environmental conditions in the TN group were established to simulate commercial production settings. Heat stress chickens were exposed to cyclic HS at 35 °C for 12 h/day from days 7–42. Performance parameters, intestinal permeability, bone parameters, meat quality, and leukocyte proportions were estimated. There was a significant (p < 0.05) reduction in body weight (BW), BW gain, and feed intake, but the feed conversion ratio increased in chickens under cyclic HS. Moreover, HS chickens had a significantly higher gut permeability, monocyte and basophil levels, but less bone mineralization than TN chickens. Nevertheless, the TN group had significant increases in breast yield, woody breast, and white striping in breast fillets compared to HS. These results present an alternative model to our previously published continuous HS model to better reflect commercial conditions to evaluate commercially available nutraceuticals or products with claims of reducing the severity of heat stress.
Capsaicin Potently Blocks Salmonella typhimurium Invasion of Vero Cells
Authors: Ayariga Joseph A. , Abugri Daniel A. , Amrutha Balagopal , Villafane Robert
Published: May 2022

Salmonella typhimurium (S. typhimurium) is one of the major food and waterborne bacteria that causes several health outbreaks in the world. Although there are few antibiotics against this bacterium, some of these drugs are challenged with resistance and toxicity. To mitigate this challenge, our group explored the ethnomedicinal/herbalism knowledge about a certain spice used in Northern Ghana in West Africa against bacterial and viral infection. This plant is Capsicum chinense (C. chinense). The plant is one of the commonest food spices consumed across the world. The seed of the plant contains both capsaicin and dihydrocapsaicin. Apart from capsaicin and dihydrocapsaicin, other major capsaicinoids in C. chinense include nordihydrocapsaicin, homodihydrocapsaicin, and homocapsaicin. In this pilot work, we investigated the antibacterial activity of pure capsaicin and capsaicin extract obtained from C. chinense against S. typhimurium in vitro. Capsaicin extract showed potent inhibition of S. typhimurium growth at concentrations as low as 100 ng/mL, whereas pure capsaicin comparatively showed poorer inhibition of bacteria growth at such a concentration. Interestingly, both capsaicin extract and pure capsaicin were found to potently block a S. typhimurium invasion of the Vero cell in vitro. Taken together, we believed that capsaicin might work synergistically with dihydrocapsaicin or the other capsaicinoids to inhibit S. typhimurium growth, whereas individually, capsaicin or dihydrocapsaicin could potently block the bacteria entry and invasion of Vero cells.
A Differential Phase-Modulated Interferometer with Rotational Error Compensation for Precision Displacement Measurement
Authors: Yan Liping , Yan Yucen , Chen Benyong , Lou Yingtian
Published: May 2022

In this paper, a differential phase-modulated interferometer (DPMI) is proposed to compensate for the rotational error for precision displacement measurement. In DPMI, a reference interferometer sharing the same reference arm with the measurement interferometer is constructed. Using the two interferometers to differentially measure the displacement, the unbalanced environmental disturbance on the measurement can be minimized. An integrated 2 × 2 array photodetector (APD) is adopted in DPMI. Based on APD with differential wavefront sensing (DWS) technology, the rotation angle can be detected and compensated. Therefore, precision displacement without rotational error and unbalanced environmental disturbance can be achieved. Three confirmatory experiments were performed, and the experimental results show that the maximum displacement drift is reduced from 902.9 nm to 16.3 nm in 100 min stability test, the standard deviations between the pitch and yaw angles obtained by DPMI and Renishaw interferometer are 1.68 × 10−5° and 1.86 × 10−5°, respectively, and the maximum deviation between the measurement result of DPMI and the stage positioning before and after angle compensation is reduced from 5.207 μm to about 0.719 μm.
Selection of Production Reliability Indicators for Project Simulation Model
Authors: Pusztai László Péter , Nagy Lajos , Budai István
Published: May 2022

Due to technological enhancements, traditional, qualitative decision-making methods are usually replaced by data-driven decision-making even in smaller companies. Process simulation is one of these solutions, which can help companies avoid costly failures as well as evaluate positive or negative effects. The reason for this paper is twofold: first, authors conducted a Quality Function Deployment analysis to find the most vital reliability indicators in the field of production scheduling. The importance was acquired from the meta-analysis of papers published in major journals. The authors found 3 indicators to be the most important: mean time between failure (MTBF), mean repair time and mean downtime. The second part of the research is for the implementation of these indicators to the stochastic environment: possible means of application are proposed, confirming the finding with a case study in which 100 products must be produced. The database created from the simulation is analyzed in terms of major production KPIs, such as production quantity, total process time and efficiency of the production. The results of the study show that calculating with reliability issues in production during the negotiation of a production deadline supports business excellence.
IoT Intrusion Detection Using Machine Learning with a Novel High Performing Feature Selection Method
Authors: Albulayhi Khalid , Abu Al-Haija Qasem , Alsuhibany Suliman A. , Jillepalli Ananth A. , Ashrafuzzaman Mohammad , Sheldon Frederick T.
Published: May 2022

The Internet of Things (IoT) ecosystem has experienced significant growth in data traffic and consequently high dimensionality. Intrusion Detection Systems (IDSs) are essential self-protective tools against various cyber-attacks. However, IoT IDS systems face significant challenges due to functional and physical diversity. These IoT characteristics make exploiting all features and attributes for IDS self-protection difficult and unrealistic. This paper proposes and implements a novel feature selection and extraction approach (i.e., our method) for anomaly-based IDS. The approach begins with using two entropy-based approaches (i.e., information gain (IG) and gain ratio (GR)) to select and extract relevant features in various ratios. Then, mathematical set theory (union and intersection) is used to extract the best features. The model framework is trained and tested on the IoT intrusion dataset 2020 (IoTID20) and NSL-KDD dataset using four machine learning algorithms: Bagging, Multilayer Perception, J48, and IBk. Our approach has resulted in 11 and 28 relevant features (out of 86) using the intersection and union, respectively, on IoTID20 and resulted 15 and 25 relevant features (out of 41) using the intersection and union, respectively, on NSL-KDD. We have further compared our approach with other state-of-the-art studies. The comparison reveals that our model is superior and competent, scoring a very high 99.98% classification accuracy.
Estimation of Blast-Induced Peak Particle Velocity through the Improved Weighted Random Forest Technique
Authors: He Biao , Lai Sai Hin , Mohammed Ahmed Salih , Sabri Mohanad Muayad Sabri , Ulrikh Dmitrii Vladimirovich
Published: May 2022

Blasting is one of the primary aspects of the mining operations, and its environmental effects interfere with the safety of lives and property. Therefore, it is essential to accurately estimate the environmental impact of blasting, i.e., peak particle velocity (PPV). In this study, a regular random forest (RF) model was developed using 102 blasting samples that were collected from an open granite mine. The model inputs included six parameters, while the output is PPV. Then, to improve the performance of the regular RF model, five techniques, i.e., refined weights based on the accuracy of decision trees and the optimization of three metaheuristic algorithms, were proposed to enhance the predictive capability of the regular RF model. The results showed that all refined weighted RF models have better performance than the regular RF model. In particular, the refined weighted RF model using the whale optimization algorithm (WOA) showed the best performance. Moreover, the sensitivity analysis results revealed that the powder factor (PF) has the most significant impact on the prediction of the PPV in this project case, which means that the magnitude of the PPV can be managed by controlling the size of the PF.
Weather Radar Echo Extrapolation Method Based on Deep Learning
Authors: Zhang Fugui , Lai Can , Chen Wanjun
Published: May 2022

In order to forecast some high intensity and rapidly changing phenomena, such as thunderstorms, heavy rain, and hail within 2 h, and reduce the influence brought by destructive weathers, this paper proposes a weather radar echo extrapolation method based on deep learning. The proposed method includes the design and combination of the data preprocessing, convolutional long short-term memory (Conv-LSTM) neuron and encoder–decoder model. We collect eleven thousand weather radar echo data in high spatiotemporal resolution, these data are then preprocessed before they enter the neural network for training to improve the data’s quality and make the training better. Next, the neuron integrates the structure and the advantages of convolutional neural network (CNN) and long short-term memory (LSTM), called Conv-LSTM, is applied to solve the problem that the full-connection LSTM (FC-LSTM) cannot extract the spatial information of input data. This operation replaced the full-connection structure in the input-to-state and state-to-state parts so that the Conv-LSTM can extract the information from other dimensions. Meanwhile, the encoder–decoder model is adopted due to the size difference of the input and output data to combine with the Conv-LSTM neuron. In the neural network training, mean square error (MSE) loss function weighted according to the rate of rainfall is added. Finally, the matrix “point-to-point” test method, including the probability of detection (POD), critical success index (CSI), false alarm ratio (FAR) and spatial test method contiguous rain areas (CRA), is used to examine the radar echo extrapolation’s results. Under the threshold of 30 dBZ, at the time of 1 h, we achieved 0.60 (POD), 0.42 (CSI) and 0.51 (FAR), compared with 0.42, 0.28 and 0.58 for the CTREC algorithm, and 0.30, 0.24 and 0.71 for the TITAN algorithm. Meanwhile, at the time of 1 h, we achieved 1.35 (total MSE ) compared with 3.26 for the CTREC algorithm and 3.05 for the TITAN algorithm. The results demonstrate that the radar echo extrapolation method based on deep learning is obviously more accurate and stable than traditional radar echo extrapolation methods in near weather forecasting.
3D Modeling of the Crystalline Lens Complex under Pseudoexfoliation
Authors: Jud Leonor , Castro André P. G. , Ruben Rui B. , Feijóo Bernardo , Ribeiro Filomena J. , Fernandes Paulo R.
Published: May 2022

Pseudoexfoliation, one of the most frequent crystalline lens complex disorders, is prevalent in up to 30% of individuals older than 60 years old. This disease can lead to severe conditions, such as subluxation or dislocation of the lens, due to the weakening of the zonules. The goal for the present study was to understand the relevant biomechanical features that can lead to the worsening of an individual’s visual capacity under pseudoexfoliation. To this end, finite element models based on a 62-year-old lens complex were developed, composed by the capsular bag, cortex, nucleus, anterior, equatorial, and posterior zonular fibers. Healthy and pseudoexfoliative conditions were simulated, varying the location of the zonulopathy (inferior/superior) and the degenerated layer. The accommodative capacity of the models with inferior dialysis of the zonular fibers was, on average, 4.7% greater than for the cases with superior dialysis. If the three sets of zonules were disrupted, this discrepancy increased to 14.9%. The present work provides relevant data to be further analyzed in clinical scenarios, as these models (and their future extension to a wider age range) can help in identifying the most influential regions for the reduction of the visual capacity of the lens.
Endothelin and the Cardiovascular System: The Long Journey and Where We Are Going
Authors: Haryono Andreas , Ramadhiani Risa , Ryanto Gusty Rizky Teguh , Emoto Noriaki
Published: May 2022

Endothelin was first discovered more than 30 years ago as a potent vasoconstrictor. In subsequent years, three isoforms, two canonical receptors, and two converting enzymes were identified, and their basic functions were elucidated by numerous preclinical and clinical studies. Over the years, the endothelin system has been found to be critical in the pathogenesis of several cardiovascular diseases, including hypertension, pulmonary arterial hypertension, heart failure, and coronary artery disease. In this review, we summarize the current knowledge on endothelin and its role in cardiovascular diseases. Furthermore, we discuss how endothelin-targeting therapies, such as endothelin receptor antagonists, have been employed to treat cardiovascular diseases with varying degrees of success. Lastly, we provide a glimpse of what could be in store for endothelin-targeting treatment options for cardiovascular diseases in the future.
A High Throughput Lipidomics Method Using Scheduled Multiple Reaction Monitoring
Authors: Bhaskar Akash Kumar , Naushin Salwa , Ray Arjun , Singh Praveen , Raj Anurag , Pradhan Shalini , Adlakha Khushboo , Siddiqua Towfida Jahan , Malakar Dipankar , Dash Debasis , Sengupta Shantanu
Published: May 2022

Lipid compositions of cells, tissues, and bio-fluids are complex, with varying concentrations and structural diversity making their identification challenging. Newer methods for comprehensive analysis of lipids are thus necessary. Herein, we propose a targeted-mass spectrometry based lipidomics screening method using a combination of variable retention time window and relative dwell time weightage. Using this method, we identified more than 1000 lipid species within 24-min. The limit of detection varied from the femtomolar to the nanomolar range. About 883 lipid species were detected with a coefficient of variance <30%. We used this method to identify plasma lipids altered due to vitamin B12 deficiency and found a total of 18 lipid species to be altered. Some of the lipid species with ω-6 fatty acid chains were found to be significantly increased while ω-3 decreased in vitamin B12 deficient samples. This method enables rapid screening of a large number of lipid species in a single experiment and would substantially advance our understanding of the role of lipids in biological processes.
Recent Progress in Green Conversion of Biomass Alcohol to Chemicals via Aerobic Oxidation
Authors: Zhang Yifei , Cao Changhai , Li Gao
Published: May 2022

The aerobic oxidation of biomass transformations into valuable chemical products via a green catalytic process is one of the most important protocols because of its low reaction temperature and high productivity rate. Recently, the introduction of small-sized Cu and Au nanoparticles (e.g., 1–3 nm) upon the surface of oxides can provide more catalytic active sites and then enhance the catalytic activity of aerobic oxidations significantly. The introduction of these metal nanoparticles is a kind of perfect catalyst for enhancing the efficiency of the activation of oxygen molecules and the separation of photo-generated holes and electrons during the photo-oxidation reactions. In this account, we summarize recent progress of the aerobic oxidation of biomass alcohol toward the production of highly valuable chemicals over supported catalysts of metal nanoparticles (NPs), including methanol conversion into methyl formate via photo-oxidation over CuOx/TiO2 nanocomposites, biomass ethanol transformation with biomass furfural to produce hydrocarbons biofuels over Au/NiO catalysts, and glucose oxidation to gluconic acid using Au/activated carbon (Au/AC) as catalysts. Furthermore, at the atomic level, to understand the structure-property correlations, insights into molecular activations of oxygen and biomass, and the investigation of active catalytic sites on photo/catalysts will be detailed and discussed. Finally, future studies are needed to achieve more exciting progress in the fundamental revealing of the catalytic reaction mechanisms and conversion pathway and the future perspective in industrial applications.
Therapeutic Targeting of Rab GTPases: Relevance for Alzheimer’s Disease
Authors: Jordan Kate L. , Koss David J. , Outeiro Tiago F. , Giorgini Flaviano
Published: May 2022

Rab GTPases (Rabs) are small proteins that play crucial roles in vesicle transport and membrane trafficking. Owing to their widespread functions in several steps of vesicle trafficking, Rabs have been implicated in the pathogenesis of several disorders, including cancer, diabetes, and multiple neurodegenerative diseases. As treatments for neurodegenerative conditions are currently rather limited, the identification and validation of novel therapeutic targets, such as Rabs, is of great importance. This review summarises proof-of-concept studies, demonstrating that modulation of Rab GTPases in the context of Alzheimer’s disease (AD) can ameliorate disease-related phenotypes, and provides an overview of the current state of the art for the pharmacological targeting of Rabs. Finally, we also discuss the barriers and challenges of therapeutically targeting these small proteins in humans, especially in the context of AD.
Brain-Derived Neurotropic Factor in Neurodegenerative Disorders
Authors: Ibrahim Abdallah Mohammad , Chauhan Lalita , Bhardwaj Aditi , Sharma Anjali , Fayaz Faizana , Kumar Bhumika , Alhashmi Mohamed , AlHajri Noora , Alam Md Sabir , Pottoo Faheem Hyder
Published: May 2022

Globally, neurodegenerative diseases cause a significant degree of disability and distress. Brain-derived neurotrophic factor (BDNF), primarily found in the brain, has a substantial role in the development and maintenance of various nerve roles and is associated with the family of neurotrophins, including neuronal growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). BDNF has affinity with tropomyosin receptor kinase B (TrKB), which is found in the brain in large amounts and is expressed in several cells. Several studies have shown that decrease in BDNF causes an imbalance in neuronal functioning and survival. Moreover, BDNF has several important roles, such as improving synaptic plasticity and contributing to long-lasting memory formation. BDNF has been linked to the pathology of the most common neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. This review aims to describe recent efforts to understand the connection between the level of BDNF and neurodegenerative diseases. Several studies have shown that a high level of BDNF is associated with a lower risk for developing a neurodegenerative disease.
Targeting of Mevalonate-Isoprenoid Pathway in Acute Myeloid Leukemia Cells by Bisphosphonate Drugs
Authors: Chiarella Emanuela , Nisticò Clelia , Di Vito Anna , Morrone Helen Linda , Mesuraca Maria
Published: May 2022

Metabolic reprogramming represents a hallmark of tumorigenesis to sustain survival in harsh conditions, rapid growth and metastasis in order to resist to cancer therapies. These metabolic alterations involve glucose metabolism, known as the Warburg effect, increased glutaminolysis and enhanced amino acid and lipid metabolism, especially the cholesterol biosynthesis pathway known as the mevalonate pathway and these are upregulated in several cancer types, including acute myeloid leukemia (AML). In particular, it was demonstrated that the mevalonate pathway has a pivotal role in cellular transformation. Therefore, targeting this biochemical process with drugs such as statins represents a promising therapeutic strategy to be combined with other anticancer treatments. In the last decade, several studies have revealed that amino-bisphosphonates (BP), primarily used for bone fragility disorders, also exhibit potential anti-cancer activity in leukemic cells, as well as in patients with symptomatic multiple myeloma. Indeed, these compounds inhibit the farnesyl pyrophosphate synthase, a key enzyme in the mevalonate pathway, reducing isoprenoid formation of farnesyl pyrophosphate and geranylgeranyl pyrophosphate. This, in turn, inhibits the prenylation of small Guanosine Triphosphate-binding proteins, such as Ras, Rho, Rac, Rab, which are essential for regulating cell survival membrane ruffling and trafficking, interfering with cancer key signaling events involved in clonal expansion and maturation block of progenitor cells in myeloid hematological malignancies. Thus, in this review, we discuss the recent advancements about bisphosphonates’ effects, especially zoledronate, analyzing the biochemical mechanisms and anti-tumor effects on AML model systems. Future studies will be oriented to investigate the clinical relevance and significance of BP treatment in AML, representing an attractive therapeutic strategy that could be integrated into chemotherapy.
Role of Cytokines and Chemokines in Angiogenesis in a Tumor Context
Authors: GEINDREAU Mannon , BRUCHARD Mélanie , VEGRAN Frédérique
Published: May 2022

During carcinogenesis, tumors set various mechanisms to help support their development. Angiogenesis is a crucial process for cancer development as it drives the creation of blood vessels within the tumor. These newly formed blood vessels insure the supply of oxygen and nutrients to the tumor, helping its growth. The main factors that regulate angiogenesis are the five members of the vascular endothelial growth factor (VEGF) family. Angiogenesis is a hallmark of cancer and has been the target of new therapies this past few years. However, angiogenesis is a complex phenomenon with many redundancy pathways that ensure its maintenance. In this review, we will first describe the consecutive steps forming angiogenesis, as well as its classical regulators. We will then discuss how the cytokines and chemokines present in the tumor microenvironment can induce or block angiogenesis. Finally, we will focus on the therapeutic arsenal targeting angiogenesis in cancer and the challenges they have to overcome.
Effect of Treatment in a Specialized Pediatric Hemato-Oncology Setting on 5-Year Survival in Acute Lymphoblastic Leukemia: A Quasi-Experimental Study
Authors: van der Linde Margrietha , van Leeuwen Nikki , Eijkenaar Frank , Rijneveld Anita W. , Pieters Rob , Karim-Kos Henrike E.
Published: May 2022

Survival rates of adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) are inferior to those of pediatric ALL patients. In part, this may be caused by differences in treatment setting. Generally, children are treated in specialized pediatric hemato-oncology settings, whereas AYAs are treated in adult hemato-oncology settings. Since 2005, adult treatment protocols have included pediatric-inspired chemotherapy, which has been the standard of care for AYAs from 2008 onwards. This study aims to assess whether, despite protocols in both settings having become more similar, there remains an effect of treatment in specialized pediatric hemato-oncology settings on 5-year survival for ALL patients in the Netherlands. We used nationwide registry data (2004–2013) on 472 ALL patients aged between 10 and 30 years old. A fuzzy regression discontinuity design was applied to estimate the treatment effect using two-stage least squares regression with the treatment threshold at 17 years and 7 months of age, adjusting for sex, age at diagnosis, and immunophenotype. We found a risk difference of 0.419 (p = 0.092; 95% CI = −0.0686; 0.907), meaning a 41.9 percentage point greater probability of surviving five years after diagnosis for ALL patients treated in specialized pediatric hemato-oncology settings. Our results suggest that ALL patients around the threshold could benefit from increased collaboration between pediatric and adult hemato-oncology in terms of survival.
Exercise Adherence in Men with Prostate Cancer Undergoing Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis
Authors: Toohey Kellie , Hunter Maddison , Paterson Catherine , Mortazavi Reza , Singh Benjamin
Published: May 2022

Androgen deprivation therapy (ADT) for prostate cancer treatment is associated with adverse physiological changes; however, exercise can improve outcomes. This systematic review and meta-analysis aimed to determine exercise intervention adherence and its effects on physiological outcomes in men diagnosed with prostate cancer undergoing ADT. Uniquely, this review incorporated a meta-aggregation of qualitative data, providing perspectives from the men’s experiences. A systematic review and meta-analysis were completed following PRISMA guidelines. Databases (CINAHL, Cochrane, PubMed) were searched for studies using “prostate cancer”, “exercise intervention”, and “androgen deprivation therapy”. Quantitative randomised controlled trials describing adherence to exercise interventions were selected, with qualitative articles selected based on descriptions of experiences around participation. Subgroup meta-analyses of adherence, exercise mode, and intervention duration were completed for quality of life, aerobic fitness, fatigue, and strength. In total, 644 articles were identified, with 29 (n = 23 quantitative; n = 6 qualitative) articles from 25 studies included. Exercise had no effects (p < 0.05) on quality of life and fatigue. Significant effects (all p < 0.05) were observed for aerobic fitness, and upper- and lower-body strength. Adherence to exercise-based interventions was 80.38%, with improvements observed in aerobic fitness and strength. Subgroup analysis revealed exercise adherence impacted fatigue and strength, with greater improvements observed in programs >12-weeks.
P720R USP8 Mutation Is Associated with a Better Responsiveness to Pasireotide in ACTH-Secreting PitNETs
Authors: Treppiedi Donatella , Marra Giusy , Di Muro Genesio , Esposito Emanuela , Barbieri Anna Maria , Catalano Rosa , Mangili Federica , Bravi Francesca , Locatelli Marco , Lania Andrea Gerardo , Ferrante Emanuele , Indirli Rita , Nozza Emma , Arlati Federico , Spada Anna , Arosio Maura , Mantovani Giovanna , Peverelli Erika
Published: May 2022

Somatic mutations in the ubiquitin specific peptidase 8 (USP8) gene have been associated with higher levels of somatostatin (SS) receptor subtype 5 (SSTR5) in adrenocorticotroph hormone (ACTH)-secreting pituitary neuroendocrine tumors (PitNETs). However, a correlation between the USP8 mutational status and favourable responses to pasireotide, the somatostatin multi-receptor ligand acting especially on SSTR5, has not been investigated yet. Here, we studied the impact of USP8 mutations on pasireotide responsiveness in human and murine corticotroph tumor cells. SSTR5 upregulation was observed in USP8 wild-type primary tumor cells transfected with S718del USP8 mutant. However, cell transfection with S718del USP8 and C40-USP8 mutants in in vitro sensitive cultures from USP8 wild-type tumors abolished their ability to respond to pasireotide and did not confer pasireotide responsiveness to the in vitro resistant culture. Pasireotide failed to reduce ACTH secretion in primary cells from one S718P USP8-mutated tumor but exerted a strong antisecretory effect in primary cells from one P720R USP8-mutated tumor. In agreement, AtT-20 cells transfection with USP8 mutants led to SSTR5 expression increase but pasireotide could reduce ACTH production and cyclin E expression in P720R USP8 overexpressing cells, only. In situ Proximity Ligation Assay and immunoflurescence experiments revealed that P720R USP8 mutant is still able to bind 14-3-3 proteins in AtT-20 cells, without affecting SSTR5 localization. In conclusion, P720R USP8 mutation might be considered as a molecular predictor of favourable response to pasireotide in corticotroph tumor cells.
SMER28 Attenuates PI3K/mTOR Signaling by Direct Inhibition of PI3K p110 Delta
Authors: Kirchenwitz Marco , Stahnke Stephanie , Prettin Silvia , Borowiak Malgorzata , Menke Laura , Sieben Christian , Birchmeier Carmen , Rottner Klemens , Stradal Theresia E. B. , Steffen Anika
Published: May 2022

SMER28 (Small molecule enhancer of Rapamycin 28) is an autophagy-inducing compound functioning by a hitherto unknown mechanism. Here, we confirm its autophagy-inducing effect by assessing classical autophagy-related parameters. Interestingly, we also discovered several additional effects of SMER28, including growth retardation and reduced G1 to S phase progression. Most strikingly, SMER28 treatment led to a complete arrest of receptor tyrosine kinase signaling, and, consequently, growth factor-induced cell scattering and dorsal ruffle formation. This coincided with a dramatic reduction in phosphorylation patterns of PI3K downstream effectors. Consistently, SMER28 directly inhibited PI3Kδ and to a lesser extent p110γ. The biological relevance of our observations was underscored by SMER28 interfering with InlB-mediated host cell entry of Listeria monocytogenes, which requires signaling through the prominent receptor tyrosine kinase c-Met. This effect was signaling-specific, since entry of unrelated, gram-negative Salmonella Typhimurium was not inhibited. Lastly, in B cell lymphoma cells, which predominantly depend on tonic signaling through PI3Kδ, apoptosis upon SMER28 treatment is profound in comparison to non-hematopoietic cells. This indicates SMER28 as a possible drug candidate for the treatment of diseases that derive from aberrant PI3Kδ activity.
Induced CAR-Macrophages as a Novel Therapeutic Cell Type for Cancer Immune Cell Therapies
Authors: Su Siyu , Lei Anhua , Wang Xudong , Lu Hengxing , Wang Shuhang , Yang Yuqi , Li Ning , Zhang Yi , Zhang Jin
Published: May 2022

The Chimeric antigen receptor (CAR)-T cell therapy has made inroads in treating hematological malignancies. Nonetheless, there are still multiple hurdles in CAR-T cell therapy for solid tumors. Primary CAR-expressing macrophage cells (CAR-Ms) and induced pluripotent stem cells (iPSCs)-derived CAR-expressing macrophage cells (CAR-iMacs) have emerged as attractive alternatives in our quest for an efficient and inexpensive approach for tumor immune cell therapy. In this review, we list the current state of development of human CAR-macrophages and provide an overview of the crucial functions of human CAR-macrophages in the field of tumor immune cell therapy.
Genotoxicity Associated with 131I and 99mTc Exposure in Nuclear Medicine Staff: A Physical and Biological Monitoring Study
Authors: Miszczyk Justyna , Gałaś Aleksander , Panek Agnieszka , Kowalska Aldona , Kostkiewicz Magdalena , Borkowska Eliza , Brudecki Kamil
Published: May 2022

Nuclear medicine staff are constantly exposed to low doses of ionizing radiation. This study investigated the level of genotoxic effects in hospital employees exposed to routinely used 131I and 99mTc in comparison with a control group. The study compared the results of physical and biological monitoring in peripheral blood lymphocytes. The effects of confounding factors, such as smoking status and physical activity, were also considered. Physical dosimetry monitoring revealed differences in the individual annual effective dose as measured by finger ring dosimeter and whole-body dosimeter between the 131I- and 99mTc-exposed groups. The DNA damage studies revealed differences between the groups in terms of excess premature chromosome condensation (PCC) fragments and tail DNA. Physical activity and smoking status differentiated the investigated groups. When assessed by the level of physical activity, the highest mean values of tail DNA were observed for the 99mTc group. When assessed by work-related physical effort, excess PCC fragments were significantly higher in the 131I group than in the control group. In the investigated groups, the tail DNA values were significantly different between non-smokers and past or current smokers, but excess PCC fragments did not significantly differ by smoking status. It is important to measure exposure to low doses of ionizing radiation and assess the potential risk from this exposure. Such investigations support the need to continue epidemiological and experimental studies to improve our understanding of the mechanisms of the health effects of radionuclides and to develop predictive models of the behavior of these complex systems in response to low-dose radiation.
Structures and Bonding in Hexacarbonyl Diiron Polyenes: Cycloheptatriene and 1,3,5-Cyclooctatriene
Authors: Zhang Min , Liang Guangchao
Published: May 2022

Structural preferences of (1,3,5-cyclooctatriene) hexacarbonyl diiron [(C8H10)Fe2(CO)6] and cycloheptatriene hexacarbonyl diiron [(C7H8)Fe2(CO)6] were explored using density functional theory (DFT) computations. DFT computations together with experimental results demonstrated that structure with the [η3, (η1, η2)] mode is the preferred structure in (C8H10)Fe2(CO)6, and the [η3,η3] mode is preferred in (C7H8)Fe2(CO)6. For (C8H10)Fe2(CO)6, the conversion between the structures with [η3, (η1, η2)] mode and the [η3, η3] mode is prevented by the relatively high activation barrier. (C8H10)Fe2(CO)6 is indicated as a fluxional molecule with a Gibbs free energy of activation of 8.5 kcal/mol for its ring flicking process, and an excellent linear correlation (R2 = 0.9909) for the DFT simulated 1H-NMR spectra was obtained. Results provided here will develop the understanding on the structures of other polyene analogs.
Use of Visual Pedagogy to Help Children with ASDs Facing the First Dental Examination: A Randomized Controlled Trial
Authors: Cirio Silvia , Salerno Claudia , Mbanefo Stefania , Oberti Luca , Paniura Lujbicca , Campus Guglielmo , Cagetti Maria Grazia
Published: May 2022

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders that don’t have a direct effect on oral health, but severe difficulties in oral hygiene and dental procedures expose people with ASDs to an increased risk of oral diseases. This RCT aimed to evaluate which pedagogical tool was the best to prepare children with ASDs for their first dental examination, either video or photo aids. Two different criteria were used to evaluate their efficacy: the achieved steps into which the procedure was divided (n = 8), and the level of cooperation according to the Frankl Behavioral Scale. One hundred-thirteen subjects were randomly assigned to the two groups and 84 subjects completed the trial (Video group n = 41; Photo group n = 43). A predictive model for the achievement of the Preliminary (1–4) or Dental (4–8) steps was performed using a multivariate logistic regression procedure. Children in the Video group achieved more steps, but the comparison between groups was statistically significant only for the Preliminary steps (p = 0.04). The percentage of subjects judged as cooperating was similar in the two groups. The results of this study underline that behavioural intervention should be used as an effective strategy to prepare subjects with ASDs for a dental examination.