bluuebunny/crossref_metadata_2025 huggingface dataset:
Ribociclib Induces Broad Chemotherapy Resistance and EGFR Dependency in ESR1 Wildtype and Mutant Breast Cancer
Authors: Mayayo-Peralta Isabel , Faggion Beatrice , Hoekman Liesbeth , Morris Ben , Lieftink Cor , Goldsbrough Isabella , Buluwela Lakjaya , Siefert Joseph C. , Post Harm , Altelaar Maarten , Beijersbergen Roderick , Ali Simak , Zwart Wilbert , Prekovic Stefan
Published: December 2021

While endocrine therapy is highly effective for the treatment of oestrogen receptor-α (ERα)-positive breast cancer, a significant number of patients will eventually experience disease progression and develop treatment-resistant, metastatic cancer. The majority of resistant tumours remain dependent on ERα-action, with activating ESR1 gene mutations occurring in 15–40% of advanced cancers. Therefore, there is an urgent need to discover novel effective therapies that can eradicate cancer cells with aberrant ERα and to understand the cellular response underlying their action. Here, we evaluate the response of MCF7-derived, CRISPR-Cas9-generated cell lines expressing mutant ERα (Y537S) to a large number of drugs. We report sensitivity to numerous clinically approved inhibitors, including CDK4/6 inhibitor ribociclib, which is a standard-of-care therapy in the treatment of metastatic ERα-positive breast cancer and currently under evaluation in the neoadjuvant setting. Ribociclib treatment induces senescence in both wildtype and mutant ERα breast cancer models and leads to a broad-range drug tolerance. Strikingly, viability of cells undergoing ribociclib-induced cellular senescence is maintained via engagement of EGFR signalling, which may be therapeutically exploited in both wildtype and mutant ERα-positive breast cancer. Our study highlights a wide-spread reduction in sensitivity to anti-cancer drugs accompanied with an acquired vulnerability to EGFR inhibitors following CDK4/6 inhibitor treatment.
Role of MicroRNAs in the Development and Progression of the Four Medulloblastoma Subgroups
Authors: Bevacqua Emilia , Farshchi Jasmin , Niklison-Chirou Maria Victoria , Tucci Paola
Published: December 2021

Medulloblastoma is the most frequent malignant brain tumour in children. Medulloblastoma originate during the embryonic stage. They are located in the cerebellum, which is the area of the central nervous system (CNS) responsible for controlling equilibrium and coordination of movements. In 2012, medulloblastoma were divided into four subgroups based on a genome-wide analysis of RNA expression. These subgroups are named Wingless, Sonic Hedgehog, Group 3 and Group 4. Each subgroup has a different cell of origin, prognosis, and response to therapies. Wingless and Sonic Hedgehog medulloblastoma are so named based on the main mutation originating these tumours. Group 3 and Group 4 have generic names because we do not know the key mutation driving these tumours. Gene expression at the post-transcriptional level is regulated by a group of small single-stranded non-coding RNAs. These microRNA (miRNAs or miRs) play a central role in several cellular functions such as cell differentiation and, therefore, any malfunction in this regulatory system leads to a variety of disorders such as cancer. The role of miRNAs in medulloblastoma is still a topic of intense clinical research; previous studies have mostly concentrated on the clinical entity of the single disease rather than in the four molecular subgroups. In this review, we summarize the latest discoveries on miRNAs in the four medulloblastoma subgroups.
Targeting KRAS in NSCLC: Old Failures and New Options for “Non-G12c” Patients
Authors: Jacobs Francesca , Cani Massimiliano , Malapelle Umberto , Novello Silvia , Napoli Valerio Maria , Bironzo Paolo
Published: December 2021

Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene mutations are among the most common driver alterations in non-small cell lung cancer (NSCLC). Despite their high frequency, valid treatment options are still lacking, mainly due to an intrinsic complexity of both the protein structure and the downstream pathway. The increasing knowledge about different mutation subtypes and co-mutations has paved the way to several promising therapeutic strategies. Despite the best results so far having been obtained in patients harbouring KRAS exon 2 p.G12C mutation, even the treatment landscape of non-p.G12C KRAS mutation positive patients is predicted to change soon. This review provides a comprehensive and critical overview of ongoing studies into NSCLC patients with KRAS mutations other than p.G12C and discusses future scenarios that will hopefully change the story of this disease.
Somatic and Abdominal Acupuncture for Pain Treatment in Adolescent Complex Regional Pain Syndrome (CRPS) of the Upper Limb: A Case Report
Authors: Marchetti Giuliano , Vittori Alessandro , Mascilini Ilaria , Francia Elisa , Insalaco Antonella , De Benedetti Fabrizio , Picardo Sergio Giuseppe
Published: December 2021

Complex regional pain syndrome (CRPS) is still poorly understood. It is a pain disorder in which pain is disproportionate to the initial stimulus. There is no specific therapy for CRPS, but it can be managed by a combination of treatments. We report a 13-year-old girl with CRPS of the upper limb treated with somatic and abdominal acupuncture. She described a severe, pulsating pain in the left wrist and hand, with hypersensitivity, allodynia, a marked reduction in strength, and swelling and sweating at the level of the fingers. Pain began three months previously, after a trauma to the left wrist. The diagnostic tests performed were negative. At the first visit we recommended oral tramadol. During the first two sessions we used somatic acupuncture. At the third session, the girl reported suffering intolerable pain in the affected limb during the previous sessions, so we decided to use abdominal acupuncture. After 8 sessions of abdominal acupuncture the pain completely disappeared. Acupuncture could be a potential alternative when conservative therapy with physical and medical treatment fails, but more often parents and adolescents prefer this therapy since other comorbidities are often present in pediatric populations and abdominal acupuncture could be a valuable alternative aid.
Human Microbiome in Children, at the Crossroad of Social Determinants of Health and Personalized Medicine
Authors: Sainz Talía , Pignataro Valeria , Bonifazi Donato , Ravera Simona , Mellado María José , Pérez-Martínez Antonio , Escudero Adela , Ceci Adriana , Calvo Cristina
Published: December 2021

The evolving field of microbiome research offers an excellent opportunity for biomarker identification, understanding drug metabolization disparities, and improving personalized medicine. However, the complexities of host–microbe ecological interactions hinder clinical transferability. Among other factors, the microbiome is deeply influenced by age and social determinants of health, including environmental factors such as diet and lifestyle conditions. In this article, the bidirectionality of social and host–microorganism interactions in health will be discussed. While the field of microbiome-related personalized medicine evolves, it is clear that social determinants of health should be mitigated. Furthermore, microbiome research exemplifies the need for specific pediatric investigation plans to improve children’s health.
A 3D Lead Iodide Hybrid Based on a 2D Perovskite Subnetwork
Authors: Ben Haj Salah Maroua , Tessier Justine , Mercier Nicolas , Allain Magali , Leblanc Antonin , Che Xiaoyang , Katan Claudine , Kepenekian Mikael
Published: December 2021

Lead halide perovskites have emerged as promising materials for various optoelectronic applications. For photovoltaics, the reference compound is the 3D perovskite (MA)PbI3 (MA+ = methylammonium). However, this material suffers from instabilities towards humidity or light. This makes the search of new stable 3D lead halide materials very relevant. A strategy is the use of intermediate size cations instead of MA, which are not suitable to form the 3D ABX3 perovskites or 2D perovskites. Here, we report on a novel 3D metal halide hybrid material based on the intermediate size cation hydroxypropylammonium (HPA+), (HPA)6(MA)Pb5I17. We will see that extending the carbon chain length from two CH2 units (in the hydroxylethylammonium cation, HEA+) to three (HPA+) precludes the formation of a perovskite network as found in the lead and iodide deficient perovskite (HEA,MA)1+xPbxI3−x. In (HPA)6(MA)Pb5I17 the 3D lead halide network results from a 2D perovskite subnetworks linked by a PbI6 octahedra sharing its faces. DFT calculations confirm the direct band gap and reveal the peculiar band structure of this 3D network. On one hand the valence band has a 1D nature involving the p orbitals of the halide. On the other, the conduction band possesses a clear 2D character involving hybridization between the p orbitals of the metal and the halide.
The Evolving Role of Immunotherapy in Stage III Non-Small Cell Lung Cancer
Authors: Perdrizet Kirstin , Cheema Parneet K.
Published: December 2021

The management of Stage III non-small cell lung cancer (NSCLC) is complex and requires multidisciplinary input. Since the publication of the PACIFIC trial (consolidative durvalumab post concurrent chemotherapy and radiation in Stage III disease) which showed improved survival for patients in the immunotherapy arm, there has been much interest in the use of immunotherapy in the Stage III setting. In this review, we explore the biologic and clinical rationale for the use of immunotherapy in Stage III NSCLC, present previously published and upcoming data in the neoadjuvant, adjuvant, and concurrent realms of Stage III management, and discuss unanswered questions and challenges moving forward.
A Prototypical Network-Based Approach for Low-Resource Font Typeface Feature Extraction and Utilization
Authors: Li Kangying , Batjargal Biligsaikhan , Maeda Akira
Published: December 2021

This paper introduces a framework for retrieving low-resource font typeface databases by handwritten input. A new deep learning model structure based on metric learning is proposed to extract the features of a character typeface and predict the category of handwrittten input queries. Rather than using sufficient training data, we aim to utilize ancient character font typefaces with only one sample per category. Our research aims to achieve decent retrieval performances over more than 600 categories of handwritten characters automatically. We consider utilizing generic handcrafted features to train a model to help the voting classifier make the final prediction. The proposed method is implemented on the ‘Shirakawa font oracle bone script’ dataset as an isolated ancient-character-recognition system based on free ordering and connective strokes. We evaluate the proposed model on several standard character and symbol datasets. The experimental results showed that the proposed method provides good performance in extracting the features of symbols or characters’ font images necessary to perform further retrieval tasks. The demo system has been released, and it requires only one sample for each character to predict the user input. The extracted features have a better effect in finding the highest-ranked relevant item in retrieval tasks and can also be utilized in various technical frameworks for ancient character recognition and can be applied to educational application development.
Potential Combination Drug Therapy to Prevent Redox Stress and Mitophagy Dysregulation in Retinal Müller Cells under High Glucose Conditions: Implications for Diabetic Retinopathy
Authors: Singh Lalit Pukhrambam , Devi Takhellambam S.
Published: December 2021

Chronic hyperglycemia-induced thioredoxin-interacting protein (TXNIP) expression, associated oxidative/nitrosative stress (ROS/RNS), and mitochondrial dysfunction play critical roles in the etiology of diabetic retinopathy (DR). However, there is no effective drug treatment to prevent or slow down the progression of DR. The purpose of this study is to examine if a combination drug treatment targeting TXNIP and the mitochondria-lysosome pathway prevents high glucose-induced mitochondrial stress and mitophagic flux in retinal Müller glial cells in culture, relevant to DR. We show that diabetes induces TXNIP expression, redox stress, and Müller glia activation (gliosis) in rat retinas when compared to non-diabetic rat retinas. Furthermore, high glucose (HG, 25 mM versus low glucose, LG 5.5 mM) also induces TXNIP expression and mitochondrial stress in a rat retinal Müller cell line, rMC1, in in vitro cultures. Additionally, we develop a mitochondria-targeted mCherry and EGFP probe tagged with two tandem COX8a mitochondrial target sequences (adenovirus-CMV-2×mt8a-CG) to examine mitophagic flux in rMC1. A triple drug combination treatment was applied using TXNIP-IN1 (which inhibits TXNIP interaction with thioredoxin), Mito-Tempo (mitochondrial anti-oxidant), and ML-SA1 (lysosome targeted activator of transient calcium channel MCOLN1/TRPML1 and of transcription factor TFEB) to study the mitochondrial–lysosomal axis dysregulation. We found that HG induces TXNIP expression, redox stress, and mitophagic flux in rMC1 versus LG. Treatment with the triple drug combination prevents mitophagic flux and restores transcription factor TFEB and PGC1α nuclear localization under HG, which is critical for lysosome biosynthesis and mitogenesis, respectively. Our results demonstrate that 2×mt8a-CG is a suitable probe for monitoring mitophagic flux, both in live and fixed cells in in vitro experiments, which may also be applicable to in vivo animal studies, and that the triple drug combination treatment has the potential for preventing retinal injury and disease progression in diabetes.
A Method for Class-Imbalance Learning in Android Malware Detection
Authors: Guan Jun , Jiang Xu , Mao Baolei
Published: December 2021

More and more Android application developers are adopting many different methods against reverse engineering, such as adding a shell, resulting in certain features that cannot be obtained through decompilation, which causes a serious sample imbalance in Android malware detection based on machine learning. Hence, the researchers have focused on how to solve class-imbalance to improve the performance of Android malware detection. However, the disadvantages of the existing class-imbalance learning are mainly the loss of valuable samples and the computational cost. In this paper, we propose a method of Class-Imbalance Learning (CIL), which first selects representative features, uses the clustering K-Means algorithm and under-sampling to retain the important samples of the majority class while reducing the number of samples of the majority class. After that, we use the Synthetic Minority Over-Sampling Technique (SMOTE) algorithm to generate minority class samples for data balance, and finally use the Random Forest (RF) algorithm to build a malware detection model. The result of experiments indicates that CIL effectively improves the performance of Android malware detection based on machine learning, especially for class imbalance. Compared with existing class-imbalance learning methods, CIL is also effective for the Machine Learning Repository from the University of California, Irvine (UCI) and has better performance in some data sets.
A Data-Driven Framework to Predict Lithium-Ion Battery Cell Imbalance for Real-Time Battery Management Systems
Authors: Li Chao , Pelegri Assimina
Published: December 2021

Models that can predict battery cells’ thermal and electrical behaviors are necessary for real-time battery management systems to regulate the imbalance within battery cells. This work introduces a Gaussian Process Regression (GPR)-based data-driven framework that succeeds the Multi-Scale Multi-Dimensional (MSMD) modeling structure. The framework can make highly accurate predictions at the same level as full-order full-distribution simulations based on MSMD. A pseudo-2D model is used to generate training data and is combined with a process that shifts computation burdens from real-time battery management systems to lab data preparation. The testing results highlight the reliability of the GPR-based data-driven framework in terms of accuracy and stability under various operational conditions.
Flow-Induced Vibrations of Single and Multiple Heated Circular Cylinders: A Review
Authors: Ali Ussama , Islam Md. , Janajreh Isam , Fatt Yap , Alam Md. Mahbub
Published: December 2021

This study is an effort to encapsulate the fundamentals and major findings in the area of fluid-solid interaction, particularly the flow-induced vibrations (FIV). Periodic flow separation and vortex shedding stretching downstream induce dynamic fluid forces on the bluff body and results in oscillatory motion of the body. The motion is generally referred to as flow-induced vibrations. FIV is a dynamic phenomenon as the motion, or the vibration of the body is subjected to the continuously changing fluid forces. Sometimes FIV is modeled as forced vibrations to mimic the vibration response due to the fluid forces. FIV is a deep concern of engineers for the design of modern heat exchangers, particularly the shell-and-tube type, as it is the major cause for the tube failures. Effect of important parameters such as Reynolds number, spacing ratio, damping coefficient, mass ratio and reduced velocity on the vibration characteristics (such as Strouhal number, vortex shedding, vibration frequency and amplitude, etc.) is summarized. Flow over a bluff body with wakes developed has been studied widely in the past decades. Several review articles are available in the literature on the area of vortex shedding and FIV. None of them, however, discusses the cases of FIV with heat transfer. In particular systems, FIV is often coupled to heat transfer, e.g., in nuclear power plants, FIV causes wear and tear to heat exchangers, which can eventually lead to catastrophic failure. As the circular shape is the most common shape for tubes and pipes encountered in practice, this review will only focus on the FIV of circular cylinders. In this attempt, FIV of single and multiple cylinders in staggered arrangement, including tandem and side-by-side arrangement is summarized for heated and unheated cylinder(s) in the one- and two-degree of freedom. The review also synthesizes the effect of fouling on heat transfer and flow characteristics. Finally, research prospects for heated circular cylinders are also stated.
Three-Dimensional CFD Simulations of Start-Up Processes of a Pump-Turbine Considering Governor Regulation
Authors: Yang Zhiyan , Cheng Yongguang , Liu Ke , Hou Xiaoxia , Zhang Xiaoxi , Wang Xi , Ding Jinghuan
Published: December 2021

The pumped-storage power station is an efficient stability regulator of the power grid. However, due to the instability of the pump-turbine in the S-shaped characteristic region, rotational speed fluctuation is easy to occur in the speed no-load condition, making synchronization with and connection to the grid difficult. To investigate the key factors of these difficult grid connections, the start-up processes of a practical pump-turbine under the lowest head condition were simulated by using the three-dimensional CFD method, in which the governor regulating equations with different regulating parameters were integrated successfully. The results show that the working points oscillate with the fluctuations of rotational speed, discharge, and torque, and different regulating parameters have a significant influence on the dynamic histories. In addition, the internal flow patterns, especially the backflows at the runner inlet, keep apparent values at the middle span (0.5 span) but have regular transitions near the shroud side (0.7–0.8 span). The faster the guide vanes adjust, the faster the backflows change, and the larger the macro parameters fluctuate. Overall, the instability of the start-up is the result of the periodical evolutions of backflows at the runner inlet, because the trend and period of the radial velocities at different inlet span locations are consistent with those of the discharge.
Cellulosic Butanol Biorefinery: Production of Biobutanol from High Solid Loadings of Sweet Sorghum Bagasse—Simultaneous Saccharification, Fermentation, and Product Recovery
Authors: Qureshi Nasib , Saha Badal , Liu Siqing , Ezeji Thaddeus , Nichols Nancy
Published: December 2021

Butanol was produced commercially from cornstarch and sugarcane molasses (renewable resources) until 1983, when production of these plants was forced to cease because of unfavorable economics of production caused in part by escalating prices of these feedstocks. During recent years, the focus of research has been on the use of economically available agricultural biomass and residues and cutting-edge science and technology to make butanol production a commercially viable process again. In this study, we produced butanol from sweet sorghum bagasse (SSB) by employing high concentrations of SSB solids and integrated process technology through which simultaneous saccharification, fermentation, and recovery (SSFR) were conducted as one unit operation. The concentrated SSB (16–22% dry wt. basis or 160–220 gL−1) was used to reduce reactor size and potentially reduce fixed and operational costs. Indeed, ABE productivity and yield of 0.21 gL−1h−1 and 0.39 were obtained, respectively, when 160 gL−1 SSB (16%, dry wt.) was used in the SSFR process. In nonintegrated systems, use of >90 gL−1 solid loading is improbable and has not been done until this study.
Complete Genome Sequences and Pathogenicity Analysis of Two Red Sea Bream Iridoviruses Isolated from Cultured Fish in Korea
Authors: Jeong Min-A , Jeong Ye-Jin , Kim Kwang-Il
Published: December 2021

In Korea, red sea bream iridovirus (RSIV), especially subtype II, has been the main causative agent of red sea bream iridoviral disease since the 1990s. Herein, we report two Korean RSIV isolates with different subtypes based on the major capsid protein and adenosine triphosphatase genes: 17SbTy (RSIV mixed subtype I/II) from Japanese seabass (Lateolabrax japonicus) and 17RbGs (RSIV subtype II) from rock bream (Oplegnathus fasciatus). The complete genome sequences of 17SbTy and 17RbGs were 112,360 and 112,235 bp long, respectively (115 and 114 open reading frames [ORFs], respectively). Based on nucleotide sequence homology with sequences of representative RSIVs, 69 of 115 ORFs of 17SbTy were most closely related to subtype II (98.48–100% identity), and 46 were closely related to subtype I (98.77–100% identity). In comparison with RSIVs, 17SbTy and 17RbGs carried two insertion/deletion mutations (ORFs 014R and 102R on the basis of 17SbTy) in regions encoding functional proteins (a DNA-binding protein and a myristoylated membrane protein). Notably, survival rates differed significantly between 17SbTy-infected and 17RbGs-infected rock breams, indicating that the genomic characteristics and/or adaptations to their respective original hosts might influence pathogenicity. Thus, this study provides complete genome sequences and insights into the pathogenicity of two newly identified RSIV isolates classified as a mixed subtype I/II and subtype II.
Characterization of Bioactive Phenolics and Antioxidant Capacity of Edible Bean Extracts of 50 Fabaceae Populations Grown in Thailand
Authors: Tungmunnithum Duangjai , Drouet Samantha , Lorenzo Jose Manuel , Hano Christophe
Published: December 2021

Fabaceae is the third largest family containing great variation among populations. However, previous studies mainly focus on single species, and phytochemicals at population level have never been reported. This work aims to complete this knowledge with 50 populations from throughout Thailand by (1) determining total phenolic (TPC), flavonoid (TFC), and anthocyanin (TAC) contents; and (2) investigating in vitro and cellular antioxidant potentials. Phytochemicals of 50 populations from different localities are differed, illustrating high heterogeneity occurring in polyphenols accumulations. Vigna unguiculata subsp. sesquipedalis populations showed low variability in TPC ranging from 628.3 to 717.3 mg/100 g DW gallic acid equivalent, whereas the high variability found in TFC and TAC range from 786.9 to 1536.1 mg/100 g DW quercetin equivalent, and 13.4 to 41.6 mg/100 g DW cyanidin equivalent. Red cultivar population #16 had the greatest TAC, but surprisingly the cream cultivars were relatively high in anthocyanins. HPLC quantification of genistein and daidzein showed great variations among populations. In vitro antioxidant results indicated that antioxidant capacity mediated by electron transfer. Cellular antioxidants ranged from 59.7% to 87.9% of ROS/RNS in yeast model. This study investigated at the population level contributing to better and frontier knowledge for nutraceutical/phytopharmaceutical sectors to seek potential raw plant material.
A Multi-Ingredient Formula Ameliorates Exercise-Induced Fatigue by Changing Metabolic Pathways and Increasing Antioxidant Capacity in Mice
Authors: Chen Hui , Ma Xuan , Cao Lixing , Zhao Shuang , Zhao Chong , Yin Shutao , Hu Hongbo
Published: December 2021

Multiple mechanisms are involved in exercise-induced fatigue, including energy depletion, metabolite accumulation, and oxidative stress, etc. The mechanistic findings provide a rationale for a multi-targeted approach to exercise-induced fatigue management. This study created a multi-ingredient formula mixed with valine, isoleucine, leucine, β-alanine, creatine, l-carnitine, quercetin, and betaine, based on the functional characteristics of these agents, and evaluated the preventive effect of this mechanism-based formula on exercise-induced fatigue. Results showed that the 7-d formula supplement significantly increased the running duration time of mice by 14% and the distance by 20% in an exhaustive treadmill test, indicating that the formula could delay fatigue appearance and improve exercise performance. Mechanistically, the formula enhanced fatty acid oxidation and spared liver glycogen by regulating the fat/glucose metabolism-related signaling pathways, including phospho-adenosine monophosphate-activated protein kinase α (p-AMPKα), phospho-acetyl CoA carboxylase (p-ACC), carnitine palmitoyl-transferase 1B (CPT1B), fatty acid translocase (CD36), and glucose transporter type 4 (GLUT4), and increased antioxidant capacity. The findings suggested that the formula tested in this study effectively ameliorated exercise-induced fatigue by targeting multi-signaling pathways, showing promise as a regimen to fight exercise-induced fatigue.
A Mixed Element Algorithm Based on the Modified L1 Crank–Nicolson Scheme for a Nonlinear Fourth-Order Fractional Diffusion-Wave Model
Authors: Wang Jinfeng , Yin Baoli , Liu Yang , Li Hong , Fang Zhichao
Published: December 2021

In this article, a new mixed finite element (MFE) algorithm is presented and developed to find the numerical solution of a two-dimensional nonlinear fourth-order Riemann–Liouville fractional diffusion-wave equation. By introducing two auxiliary variables and using a particular technique, a new coupled system with three equations is constructed. Compared to the previous space–time high-order model, the derived system is a lower coupled equation with lower time derivatives and second-order space derivatives, which can be approximated by using many time discrete schemes. Here, the second-order Crank–Nicolson scheme with the modified L1-formula is used to approximate the time direction, while the space direction is approximated by the new MFE method. Analyses of the stability and optimal L2 error estimates are performed and the feasibility is validated by the calculated data.
Enhancing Stem Cell Therapy for Cartilage Repair in Osteoarthritis—A Hydrogel Focused Approach
Authors: Liu Yisi , Wang Meng , Luo Yixuan , Liang Qianyi , Yu Yin , Chen Fei , Yao Jun
Published: December 2021

Stem cells hold tremendous promise for the treatment of cartilage repair in osteoarthritis. In addition to their multipotency, stem cells possess immunomodulatory effects that can alleviate inflammation and enhance cartilage repair. However, the widely clinical application of stem cell therapy to cartilage repair and osteoarthritis has proven difficult due to challenges in large-scale production, viability maintenance in pathological tissue site and limited therapeutic biological activity. This review aims to provide a perspective from hydrogel-focused approach to address few key challenges in stem cell-based therapy for cartilage repair and highlight recent progress in advanced hydrogels, particularly microgels and dynamic hydrogels systems for improving stem cell survival, retention and regulation of stem cell fate. Finally, progress in hydrogel-assisted gene delivery and genome editing approaches for the development of next generation of stem cell therapy for cartilage repair in osteoarthritis are highlighted.
Molecular Analysis Reveals a High Diversity of Anopheline Mosquitoes in Yanomami Lands and the Pantanal Region of Brazil
Authors: Silva-do-Nascimento Teresa Fernandes , Sánchez-Ribas Jordi , Oliveira Tatiane M. P. , Bourke Brian Patrick , Oliveira-Ferreira Joseli , Rosa-Freitas Maria Goreti , Lourenço-de-Oliveira Ricardo , Marinho-e-Silva Mariana , Neves Maycon Sebastião Alberto Santos , Conn Jan E. , Sallum Maria Anice Mureb
Published: December 2021

Identifying the species of the subfamily Anophelinae that are Plasmodium vectors is important to vector and malaria control. Despite the increase in cases, vector mosquitoes remain poorly known in Brazilian indigenous communities. This study explores Anophelinae mosquito diversity in the following areas: (1) a Yanomami reserve in the northwestern Amazon Brazil biome and (2) the Pantanal biome in southwestern Brazil. This is carried out by analyzing cytochrome c oxidase (COI) gene data using Refined Single Linkage (RESL), Assemble Species by Automatic Partitioning (ASAP), and tree-based multi-rate Poisson tree processes (mPTP) as species delimitation approaches. A total of 216 specimens collected from the Yanomami and Pantanal regions were sequenced and combined with 547 reference sequences for species delimitation analyses. The mPTP analysis for all sequences resulted in the delimitation of 45 species groups, while the ASAP analysis provided the partition of 48 groups. RESL analysis resulted in 63 operational taxonomic units (OTUs). This study expands our scant knowledge of anopheline species in the Yanomami and Pantanal regions. At least 18 species of Anophelinae mosquitoes were found in these study areas. Additional studies are now required to determine the species that transmit Plasmodium spp. in these regions.
Interocular Symmetry Analysis of Corneal Elevation Using the Fellow Eye as the Reference Surface and Machine Learning
Authors: Mehravaran Shiva , Dehzangi Iman , Rahman Md Mahmudur
Published: December 2021

Unilateral corneal indices and topography maps are routinely used in practice, however, although there is consensus that fellow-eye asymmetry can be clinically significant, symmetry studies are limited to local curvature and single-point thickness or elevation measures. To improve our current practices, there is a need to devise algorithms for generating symmetry colormaps, study and categorize their patterns, and develop reference ranges for new global discriminative indices for identifying abnormal corneas. In this work, we test the feasibility of using the fellow eye as the reference surface for studying elevation symmetry throughout the entire corneal surface using 9230 raw Pentacam files from a population-based cohort of 4613 middle-aged adults. The 140 × 140 matrix of anterior elevation data in these files were handled with Python to subtract matrices, create color-coded maps, and engineer features for machine learning. The most common pattern was a monochrome circle (“flat”) denoting excellent mirror symmetry. Other discernible patterns were named “tilt”, “cone”, and “four-leaf”. Clustering was done with different combinations of features and various algorithms using Waikato Environment for Knowledge Analysis (WEKA). Our proposed approach can identify cases that may appear normal in each eye individually but need further testing. This work will be enhanced by including data of posterior elevation, thickness, and common diagnostic indices.
Effect of Low Pressure and Low Oxygen Treatments on Fruit Quality and the In Vivo Growth of Penicillium digitatum and Penicillium italicum in Oranges
Authors: Archer John , Pristijono Penta , Vuong Quan V. , Palou Lluís , Golding John B.
Published: December 2021

Penicillium digitatum and P. italicum are the major postharvest pathogens in citrus. To reduce postharvest decay, the use of low-oxygen (0.9 kPa O2) (LO) or low-pressure (6.6 kPa) (LP) treatments were evaluated during the storage of navel oranges for four or eight days. The results showed that exposure to both LO and LP treatments reduced in vivo pathogen growth compared to the untreated (UTC) oranges, with LO being the most effective. The effects of LO and LP on fruit metabolism and quality were further assessed, and it was found that there was no effect on fruit ethylene production, respiration rate, TSS (total soluble solids), TA (titratable acidity) or fruit firmness. However, both LO and LP treatments did have an effect on juice ethanol concentration and fruit weight-loss. The effect of adding exogenous ethylene at either LP (1 µL/L) or atmospheric pressure (AP) (at either 0.1, 1 µL/L) was also evaluated, and results showed that the addition of ethylene at these concentrations had no effect on mould diameter at LP or AP. Therefore, both LO of 0.9 kPa O2 and LP of 6.6 kPa at 20 °C are potential non-chemical postharvest treatments to reduce mould development during storage with minimal effects on fruit quality.
QTL Analysis of the Content of Some Bioactive Compounds in Brassica rapa L. Grown under Light Culture Conditions
Authors: Egorova Ksenia V. , Sinyavina Nadezhda G. , Artemyeva Anna M. , Kocherina Natalia V. , Chesnokov Yuriy V.
Published: December 2021

The article presents the results of biochemical and QTL (Quantitative Trait Loci) analysis of dry matter content, nutrient and biologically active compounds: sugars, ascorbic acid, chlorophylls a and b, anthocyanins and carotenoids in populations of doubled haploid lines of leaf, root crops, and oilseeds of the Brassica rapa L. species grown in optimal light culture conditions, but with different photoperiod durations. The purpose of this study was to evaluate the effect of the photoperiod on the transition to bolting and the accumulation of biologically active substances, as well as how the localization and identification of chromosomal loci determined the content of certain phytochemicals. The influence of the length of daylight hours on the content of components of the biochemical composition was assessed. It was shown that growing under conditions of a 16 h photoperiod increased the content of dry matter, sugars, vitamin C, and anthocyanins. On the contrary, the content of photosynthetic pigments was higher under the conditions of a 12 h photoperiod. Valuable lines that can be sources of biologically active compounds were revealed. Based on the results of the obtained data, 102 QTLs were mapped, which determine the manifestation of the studied biochemical quality traits in the B. rapa doubled haploid lines under conditions of short and long daylight hours. Molecular markers genetically linked to the selected QTLs were determined. It was revealed that the identified loci controlling all the studied biochemical traits were mainly in the fifth, sixth, seventh, and ninth linkage groups, which correlated with the data obtained in the field and greenhouse. Most of the identified loci controlled several studied traits simultaneously. The identified QTLs and identified molecular markers are of interest for further study of the genetic control of the economically valuable traits determined by them and for the implementation of marker-assisted selection in B. rapa. The data obtained can be used in genetic and breeding work, including for the obtaining of new genotypes, lines and cultivars with a valuable biochemical composition, adapted for cultivation under specific photoperiodic conditions.
Satureja montana Essential Oil, Zein Nanoparticles and Their Combination as a Biocontrol Strategy to Reduce Bacterial Spot Disease on Tomato Plants
Authors: Oliveira-Pinto Paulo R. , Mariz-Ponte Nuno , Sousa Rose Marie O. F. , Torres Ana , Tavares Fernando , Ribeiro Artur , Cavaco-Paulo Artur , Fernandes-Ferreira Manuel , Santos Conceição
Published: December 2021

Tomato bacterial spot (Bs), caused by Xanthomonas spp., including X. euvesicatoria (Xeu) remains a major threat for tomato production. The emergence of copper resistance strains of Xeu calls urgently for eco-friendly phytosanitary treatments as sustainable green alternatives for disease control. Satureja spp. essential oil (EO) has antimicrobial activity against xanthomonads and combined with zein nanoparticles (ZNPs), might offer a viable option for field applications. This study aims to evaluate the effects of S. montana EO, of ZNPs, and their combination in a nanoformulation, on Xeu quantity, and how these compounds modulate molecular and physiological changes in the pathosystem. Uninfected and infected tomato plants (var. Oxheart) were treated with EO; ZNPs and nanoformulation (EO + ZNPs). Treatments reduced Xeu amount by a minimum of 1.6-fold (EO) and a maximum of 202-fold (ZNPs) and improved plants’ health. Nanoformulation and ZNPs increased plants’ phenolic content. ZNPs significantly increased GPX activity and reduced CAT activity. Overall treatments upregulated transcripts of the phenylpropanoid pathway in infected plants, while ZNPs and nanoformulation upregulated those transcripts in uninfected plants. Both sod and aao transcripts were downregulated by treatments in infected plants. These findings demonstrate that S. montana EO, ZNPs and their nanoformulation are suitable to integrate tomato bacterial spot management strategies, mainly due to their antimicrobial activity on Xeu, however further field studies clarifying the long-term action of these products are required. These results also support the prophylactic potential of ZNPs on tomato bacterial spot.
Experiences of Online COVID-19 Information Acquisition among Persons with Type 2 Diabetes and Varying eHealth Literacy
Authors: Sjöström Anna , Hajdarevic Senada , Hörnsten Åsa , Öberg Ulrika , Isaksson Ulf
Published: December 2021

During the COVID-19 pandemic, the Internet has been a major source of information for people to keep updated with news and guidelines. However, concerns have been raised about the ‘infodemic’, which includes the overabundance of online information and the spread of misleading information. Adequate eHealth literacy skills among world citizens have therefore been emphasized as vital during the pandemic. Persons with type 2 diabetes have been at increased risk of severe outcomes of COVID-19 disease. This study aimed to explore online COVID-19 information acquisition experiences among persons with type 2 diabetes and varying eHealth literacy. Fifty-eight participants filled out the eHealth Literacy Scale (eHEALS), along with a qualitative questionnaire with free-text questions. Additionally, 10 participants were interviewed. Thematic analysis was applied to identify patterns in participants’ experiences. Two domains were identified: perceived challenges with online information about COVID-19, and coping strategies to manage challenges. The perceived challenges were: being exposed to information overload, dealing with conflicting information, and being strongly emotionally affected. The related coping strategies were: protecting oneself, trusting authorities, taking command, and using common sense. These strategies often involved triangulation of the information obtained, including participants consulting their common sense, various sources, or family and friends. This paper highlights the crucial role of authorities in delivering online information, that according to health literacy principles, is easy to access, understand, and use. Furthermore, our results reinforce the importance of diabetes nurses, as well as healthcare professionals in general, in encouraging patients to share their Internet findings, promote information from reliable sources, and deliver tailored information that suits individual needs. Because our results underline the importance of social support in eHealth literacy and the assessment of online health information, the inclusion of family and friends needs to be increasingly considered in diabetes care. Due to the small homogenous sample, the results of this study cannot be generalized. However, the reader can assess the transferability to other situations and settings based on our contextual descriptions.
COVID-19 Vaccine Early Skepticism, Misinformation and Informational Needs among Essential Workers in the USA
Authors: Savoia Elena , Su Maxwell , Piltch-Loeb Rachael , Masterson Evelyn , Testa Marcia A.
Published: December 2021

This study presents the results of a survey of 1591 hesitant U.S. essential workers, conducted over Pollfish in December 2020 when they were the only group eligible for the vaccine, aiming to describe their concerns regarding COVID-19 vaccine safety, effectiveness and distribution policies. We computed frequencies using the SAS software for each answer, using chi-squared statistics and Cochran–Armitage trend tests to determine how informational needs differ by age, gender, level of education, race, source of COVID-19 information and levels of vaccine acceptance. The results of this study show that freedom of choice, equal access to the vaccine and being able to live a life with no restrictions once vaccinated were important concerns since the early days of the distribution campaign, with 53% (836/1591), 42% (669/1591) and 35% (559/1591) of hesitant respondents, respectively, indicating they would be more likely to receive the COVID-19 vaccine if they felt these issues were satisfactorily addressed. Early risk communication and immunization campaign strategies should address not only the reported efficacy and safety of new vaccines, but, as equally important, the population’s perceptions and beliefs regarding personal choice, effectiveness and adverse consequences.
Early Diagnosis of Oral Mucosal Alterations in Smokers and E-Cigarette Users Based on Micronuclei Count: A Cross-Sectional Study among Dental Students
Authors: Pop Anca Maria , Coroș Raluca , Stoica Alexandra Mihaela , Monea Monica
Published: December 2021

The presence of micronuclei in oral epithelial cells is considered a marker of genotoxicity, which can be identified using exfoliative cytology. The aim of this study was to investigate cytotoxic damage through the evaluation of micronuclei in the oral mucosa of smokers and e-cigarette users compared to nonsmokers. We obtained smears from the buccal mucosa of 68 participants divided in 3 groups (smokers, e-cigarette users and nonsmokers), which were further processed with Papanicolaou stain. The frequencies of micronuclei and micronucleated cells were recorded and statistically analyzed at a level of significance of p < 0.05. The mean micronuclei values per 1000 cells were 3.6 ± 1.08 for smokers, 3.21 ± 1.12 for e-cigarette users and 1.95 ± 1.05 for nonsmokers. The mean values of micronucleated cells per 1000 cells were 2.48 ± 0.91 for smokers, 2.39 ± 1.07 for e-cigarette users and 1.4 ± 0.68 for nonsmokers. Smokers and e-cigarette users had significantly higher values of micronuclei and micronucleated cells compared to nonsmokers, but there were no significant differences between smokers and e-cigarette users. We concluded that the micronuclei count can be used as an early indicator for alterations of oral mucosa and exfoliative cytology represents an accessible tool which could be applied for mass screening.
Undergraduate Students’ Online Health Information-Seeking Behavior during the COVID-19 Pandemic
Authors: Hsu Wan-Chen
Published: December 2021

As the COVID-19 pandemic has swept across the world, the amount of health-related information available has skyrocketed. Individuals can easily access health information through the internet, which may influence their thoughts or behavior, causing potential technological risks that may affect their lives. This study examined the online health information-seeking behavior of undergraduate students. Taking health issues as a guiding framework, content analysis was adopted to assess participants’ online health information-seeking behavior using a computer screen recording software, and coding analysis was conducted. The study was conducted during the COVID-19 pandemic with a formal sample of 101 participants. In terms of online health information-seeking behavior, 59% of the study participants used nouns as keywords, only 27% used Boolean logic retrieval techniques, 81% paid attention to the date of the data, and 85% did not consider the author’s professionalism. The results indicate that health information-seeking behavior and outcome judgments may be a missing piece of the puzzle in higher education. Consequently, the development of online health information-seeking skills through programs for undergraduate students is suggested to ensure that online readers have access to appropriate health information.
Fitting Assistive Technology for People with Hearing Loss: The Importance of Remote Microphone Systems′ Electroacoustic Verification
Authors: Jacob Regina Tangerino de Souza , Paccola Elaine Cristina Moreto , Bucuvic Érika Cristina , Salgado Manoel Henrique
Published: December 2021

The remote microphone system (RMS) must be appropriately working when fitting it in a person with hearing loss. For this verification process, the concept of transparency is adopted. If it is not transparent, the hearing aid (HA) may not capture the user’s voice and his peers appropriately, or the RMS may not have the advantage in gain needed to emphasize the speaker’s voice. This study investigates the influence of the receiver’s gain setting on the transparency of different brands and models of RMS and HAs. It is a retrospective chart review with 277 RMS from three distinct brands (RMA, RMB, and RMC) and HAs. There was an association of the receiver’s gain setting with the variables: brand of the transmitter/receiver (p = 0.005), neck loop’s receiver vs. universal and dedicated receivers (p = 0.022), and between brands of HA and transmitter/receiver (p < 0.001). RMS transmitter (odds ratio [OR = 7.9]) and the type of receiver (neckloop [OR = 3.4]; universal [OR = 0.78]) presented a higher risk of not achieving transparency in default gain, confirming and extolling the need to include electroacoustic verification in the protocol of fitting, verification, and validation of RMS and HA.