bluuebunny/crossref_metadata_2025 huggingface dataset:
A ‘Hybrid’ Radiotherapy Regimen Designed for Immunomodulation: Combining High-Dose Radiotherapy with Low-Dose Radiotherapy
Authors: Ji Hongshan , Zhou Zhiguo
Published: July 2022

Radiotherapy (RT) affects anti-tumor immunity. However, the exact impact of RT on anti-tumor immune response differs among cancer types, RT dose and fractions, patients’ innate immunity, and many other factors. There are conflicting findings on the optimal radiation dose and fractions to stimulate effective anti-tumor immunity. High-dose radiotherapy (HDRT) acts in the same way as a double-edged sword in stimulating anti-tumor immunity, while low-dose radiotherapy (LDRT) seems to play a vital role in modulating the tumor immune microenvironment. Recent preclinical data suggest that a ‘hybrid’ radiotherapy regimen, which refers to combining HDRT with LDRT, can reap the advantages of both. Clinical data have also indicated a promising potential. However, there are still questions to be addressed in order to put this novel combination therapy into clinical practice. For example, the selection of treatment site, treatment volume, the sequencing of high-dose radiotherapy and low-dose radiotherapy, combined immunotherapy, and so on. This review summarizes the current evidence supporting the use of HDRT + LDRT, explains possible immune biology mechanisms of this ‘hybrid’ radiotherapy, raises questions to be considered when working out individualized treatment plans, and lists possible avenues to increase efficiency in stimulating anti-tumor immunity using high-dose plus low-dose radiotherapy.
A Deep-Learning Based System for Rapid Genus Identification of Pathogens under Hyperspectral Microscopic Images
Authors: Tao Chenglong , Du Jian , Tang Yingxin , Wang Junjie , Dong Ke , Yang Ming , Hu Bingliang , Zhang Zhoufeng
Published: July 2022

Infectious diseases have always been a major threat to the survival of humanity. Additionally, they bring an enormous economic burden to society. The conventional methods for bacteria identification are expensive, time-consuming and laborious. Therefore, it is of great importance to automatically rapidly identify pathogenic bacteria in a short time. Here, we constructed an AI-assisted system for automating rapid bacteria genus identification, combining the hyperspectral microscopic technology and a deep-learning-based algorithm Buffer Net. After being trained and validated in the self-built dataset, which consists of 11 genera with over 130,000 hyperspectral images, the accuracy of the algorithm could achieve 94.9%, which outperformed 1D-CNN, 2D-CNN and 3D-ResNet. The AI-assisted system we developed has great potential in assisting clinicians in identifying pathogenic bacteria at the single-cell level with high accuracy in a cheap, rapid and automatic way. Since the AI-assisted system can identify the pathogenic genus rapidly (about 30 s per hyperspectral microscopic image) at the single-cell level, it can shorten the time or even eliminate the demand for cultivating. Additionally, the system is user-friendly for novices.
Developmental Cues and Molecular Drivers in Myelinogenesis: Revisiting Early Life to Re-Evaluate the Integrity of CNS Myelin
Authors: Dermitzakis Iasonas , Manthou Maria Eleni , Meditskou Soultana , Miliaras Dimosthenis , Kesidou Evangelia , Boziki Marina , Petratos Steven , Grigoriadis Nikolaos , Theotokis Paschalis
Published: July 2022

The mammalian central nervous system (CNS) coordinates its communication through saltatory conduction, facilitated by myelin-forming oligodendrocytes (OLs). Despite the fact that neurogenesis from stem cell niches has caught the majority of attention in recent years, oligodendrogenesis and, more specifically, the molecular underpinnings behind OL-dependent myelinogenesis, remain largely unknown. In this comprehensive review, we determine the developmental cues and molecular drivers which regulate normal myelination both at the prenatal and postnatal periods. We have indexed the individual stages of myelinogenesis sequentially; from the initiation of oligodendrocyte precursor cells, including migration and proliferation, to first contact with the axon that enlists positive and negative regulators for myelination, until the ultimate maintenance of the axon ensheathment and myelin growth. Here, we highlight multiple developmental pathways that are key to successful myelin formation and define the molecular pathways that can potentially be targets for pharmacological interventions in a variety of neurological disorders that exhibit demyelination.
Intensive Follow-Up Program and Oncological Outcomes of Biliary Tract Cancer Patients after Curative-Intent Surgery: A Twenty-Year Experience in a Single Tertiary Medical Center
Authors: Rizzo Alessandro , Carloni Riccardo , Frega Giorgio , Palloni Andrea , Di Federico Alessandro , Ricci Angela Dalia , De Luca Raffaele , Tavolari Simona , Brandi Giovanni
Published: July 2022

Aim. The aim of this research was to assess the impact of an intensive follow-up program on BTC patients who had received surgery with curative intent at a tertiary referral hospital. Methods. BTC patients were followed-up every three months during the first two years after their first surgery and every six months from the third to the fifth post-operative year. Results. A total of 278 BTC patients who received R0/R1 surgery were included. A total of 17.7% of patients underwent a second surgery following disease relapse, and none of these patients experienced additional disease relapse. Conclusions. An intensive follow-up after surgical resection may help in the early identification of disease relapse, leading to early treatment and prolonged survival in selected cases.
Drugs and Drug Candidates: A Challenging Project
Authors: Vanden Eynde Jean
Published: July 2022

Taking the lead of a Journal emerges, each time, as a highly challenging project [...]
A Statistical Journey through the Topological Determinants of the β2 Adrenergic Receptor Dynamics
Authors: Di Paola Luisa , Poudel Humanath , Parise Mauro , Giuliani Alessandro , Leitner David M.
Published: July 2022

Activation of G-protein-coupled receptors (GPCRs) is mediated by molecular switches throughout the transmembrane region of the receptor. In this work, we continued along the path of a previous computational study wherein energy transport in the β2 Adrenergic Receptor (β2-AR) was examined and allosteric switches were identified in the molecular structure through the reorganization of energy transport networks during activation. In this work, we further investigated the allosteric properties of β2-AR, using Protein Contact Networks (PCNs). In this paper, we report an extensive statistical analysis of the topological and structural properties of β2-AR along its molecular dynamics trajectory to identify the activation pattern of this molecular system. The results show a distinct character to the activation that both helps to understand the allosteric switching previously identified and confirms the relevance of the network formalism to uncover relevant functional features of protein molecules.
Interference Signal Feature Extraction and Pattern Classification Algorithm Based on Deep Learning
Authors: Qin Jiangyi , Zhang Fei , Wang Kai , Zuo Yuan , Deng Chenxi
Published: July 2022

Aiming at the scarcity of Low Earth Orbit (LEO) satellite spectrum resources, this paper proposes an algorithm of interference signal feature extraction and pattern classification based on deep learning to further improve the stability of satellite–ground communication links. The algorithm can successfully predict the interference signal pattern, start–stop time, frequency change range and other parameters, and has the advantages of excellent interference detection performance, high detection accuracy and small parameter prediction error, etc. It can be applied in the field of channel monitoring of communication satellite-to-ground communication links, and realize the repeated and efficient utilization of spectrum resources. Experiments show that the precision and recall of the algorithm for detecting five kinds of interference signals are all close to 100%, the prediction error of starting and ending time is less than 4 ms, and the prediction error of starting and ending frequency is less than 6 KHz.
A Cloud-Edge-Smart IoT Architecture for Speeding Up the Deployment of Neural Network Models with Transfer Learning Techniques
Authors: Hsu Tz-Heng , Wang Zhi-Hao , See Aaron Raymond
Published: July 2022

Existing edge computing architectures do not support the updating of neural network models, nor are they optimized for storing, updating, and transmitting different neural network models to a large number of IoT devices. In this paper, a cloud-edge smart IoT architecture for speeding up the deployment of neural network models with transfer learning techniques is proposed. A new model deployment and update mechanism based on the share weight characteristic of transfer learning is proposed to address the model deployment issues associated with the significant number of IoT devices. The proposed mechanism compares the feature weight and parameter difference between the old and new models whenever a new model is trained. With the proposed mechanism, the neural network model can be updated on IoT devices with just a small quantity of data sent. Utilizing the proposed collaborative edge computing platform, we demonstrate a significant reduction in network bandwidth transmission and an improved deployment speed of neural network models. Subsequently, the service quality of smart IoT applications can be enhanced.
Numerical Comparative Study on the In-Cylinder Mixing Performance of Port Fuel Injection and Direct Injection Gas-Fueled Engine
Authors: Wang Tianbo , Zhang Lanchun , Li Li , Wu Jiahui , Wang Hongchen
Published: July 2022

In recent decades, research on alternative fuel engines is becoming more and more popular. Compressed natural gas (CNG) has the advantages of abundant reserves and a lower cost. It can reduce vehicle emissions relatively quickly and has little impact on the entire transportation infrastructure. As the fourth generation of a gas fuel supply method, gas fuel direct injection (DI) technology can effectively avoid volumetric efficiency reduction and power reduction problems of the port fuel injection (PFI) method. However, the former’s mixing path and duration are shortened greatly, which often leads to poor mixing uniformity. In order to improve the in-cylinder mixing uniformity, the in-cylinder mixing process of the CNG-fueled engine is taken as the research object in this study. The computational fluid dynamics (CFDs) models of the mixing process for the PFI and DI modes are established, and their mixing uniformities are compared. Besides, based on the authors’ previous research, the influence mechanism of the piston crown shape and fuel injection angle on the mixing process of the CNG DI engine is explored. The results show that the probability distribution frequency (PDF) of the best mixture concentration region (BMCR) is as high as 72% for the PFI mode, which is much higher than for the DI mode. The shorter jet impingement distance of the flat top piston leads to higher turbulent kinetic energy (TKE) intensity, and the in-cylinder mixing uniformity will be improved. When gas fuel is injected into an area with a higher in-cylinder TKE, the average in-cylinder TKE will be higher, and the in-cylinder mixture will be more homogeneous.
Wind Turbine Performance Decline with Age
Authors: Astolfi Davide , Pandit Ravi
Published: July 2022

Wind turbines, as any technical system, are expected to have an efficiency that declines in time [...]
Atypical, Composite, or Blended Phenotypes: How Different Molecular Mechanisms Could Associate in Double-Diagnosed Patients
Authors: Rosina Erica , Pezzani Lidia , Pezzoli Laura , Marchetti Daniela , Bellini Matteo , Pilotta Alba , Calabrese Olga , Nicastro Emanuele , Cirillo Francesco , Cereda Anna , Scatigno Agnese , Milani Donatella , Iascone Maria
Published: July 2022

In the last few years, trio-Whole Exome Sequencing (WES) analysis has revolutionized the diagnostic process for patients with rare genetic syndromes, demonstrating its potential even in non-specific clinical pictures and in atypical presentations of known diseases. Multiple disorders in a single patient have been estimated to occur in approximately 2–7.5% of diagnosed cases, with higher frequency in consanguineous families. Here, we report the clinical and molecular characterisation of eight illustrative patients for whom trio-WES allowed for identifing more than one genetic condition. Double homozygosity represented the causal mechanism in only half of them, whereas the other half showed peculiar multilocus combinations. The paper takes into consideration difficulties and learned lessons from our experience and therefore supports the powerful role of wide analyses for ascertaining multiple genetic diseases in complex patients, especially when a clinical suspicion could account for the majority of clinical signs. It finally makes clear how a patient’s “deep phenotyping” might not be sufficient to suggest the presence of multiple genetic diagnoses but remains essential to validate an unexpected multilocus result from genetic tests.
Health Literacy and Its Associations with Understanding and Perception of Front-of-Package Nutrition Labels among Higher Education Students
Authors: Hoge Axelle , Labeye Mathilde , Donneau Anne-Françoise , Nekoee Halehsadat Zahraei , Husson Eddy , Guillaume Michèle
Published: July 2022

(1) Background: Nutrition labels on the front of food packages have increasingly become the focus of research. However, too few studies have placed special emphasis on nutritionally at-risk subpopulations, such as young adults or those with low literacy/numeracy skills. The present study aimed to assess both the perception and objective understanding of three front-of-package labeling (FOPL) formats currently in use on the Belgian market, i.e., the Nutri-Score, Reference Intakes, and Multiple Traffic Lights, among students of varying health literacy (HL) levels. (2) Methods: A web-based survey was carried out among 2295 students of tertiary education in the province of Liège, Belgium. The questionnaire included questions related to general characteristics, objective understanding, and perception in response to the assigned FOPL format and level of HL. (3) Results: With respect to objective understanding, the Nutri-Score outperformed all other labels across all HL levels, and it was similarly understood in students of varying HL levels. Several students’ characteristics appeared to be associated with each cluster of perception, with the Nutri-Score cluster having the highest percentages of disadvantaged students, i.e., those with inadequate HL, from non-university institutions, with low self-estimated nutrition knowledge, and with low self-estimated diet quality. (4) Conclusion: Overall, the findings supported the Nutri-Score as particularly effective in guiding students in their food choices. Of particular importance is the fact that the summarized and graded color-coded nutritional label would be a useful strategy for those disadvantaged by limited HL.
Indoor Air Pollution and the Health of Vulnerable Groups: A Systematic Review Focused on Particulate Matter (PM), Volatile Organic Compounds (VOCs) and Their Effects on Children and People with Pre-Existing Lung Disease
Authors: Maung Tun Z. , Bishop Jack E. , Holt Eleanor , Turner Alice M. , Pfrang Christian
Published: July 2022

Air pollution affects health, but much of the focus to this point has been on outdoor air. Higher indoor pollution is anticipated due to increasingly energy-efficient and less leaky buildings together with more indoor activities. Studies of indoor air pollution focusing on children and people with respiratory disease from the database Web of Science (1991–2021) were systemically reviewed according to the PRISMA guidelines, with 69 studies included in the final selection. Emissions from building materials affected indoor air quality, and ventilation also had an influence. The main indoor air pollutants are Volatile Organic Compounds (VOCs) and Particulate Matter (PM). PM sources included smoking, cooking, heating, candles, and insecticides, whereas sources of coarse particles were pets, housework and human movements. VOC sources included household products, cleaning agents, glue, personal care products, building materials and vehicle emissions. Formaldehyde levels were particularly high in new houses. Personal exposure related to both indoor and outdoor pollutant levels, highlighting home characteristics and air exchange rates as important factors. Temperature, humidity, educational level, air purifiers and time near sources were also related to personal exposure. There was an association between PM and Fractional exhaled Nitric Oxide (FeNO), lung function, oxygen saturation, childhood asthma and symptoms of chronic obstructive pulmonary disease (COPD) patients. High VOCs were associated with upper airways and asthma symptoms and cancer. Effective interventional studies for PM in the future might focus on human behavior together with air purifiers and increased ventilation, whereas VOC interventions might center more on building materials and household products, alongside purification and ventilation.
Emission Characteristics and Health Risks of Volatile Organic Compounds (VOCs) Measured in a Typical Recycled Rubber Plant in China
Authors: Wang Shuang , Yan Yucheng , Gao Xueying , Zhang Hefeng , Cui Yang , He Qiusheng , Wang Yuhang , Wang Xinming
Published: July 2022

The continued development of the automotive industry has led to a rapid increase in the amount of waste rubber tires, the problem of “black pollution” has become more serious but is often ignored. In this study, the emission characteristics, health risks, and environmental effects of volatile organic compounds (VOCs) from a typical, recycled rubber plant were studied. A total of 15 samples were collected by summa canisters, and 100 VOC species were detected by the GC/MS-FID system. In this study, the total VOCs (TVOCs) concentration ranged from 1000 ± 99 to 19,700 ± 19,000 µg/m3, aromatics and alkanes were the predominant components, and m/p-xylene (14.63 ± 4.07%–48.87 ± 3.20%) could be possibly regarded as a VOCs emission marker. We also found that specific similarities and differences in VOCs emission characteristics in each process were affected by raw materials, production conditions, and process equipment. The assessment of health risks showed that devulcanizing and cooling had both non-carcinogenic and carcinogenic risks, yarding had carcinogenic risks, and open training and refining had potential carcinogenic risks. Moreover, m/p-xylene and benzene were the main non-carcinogenic species, while benzene, ethylbenzene, and carbon tetrachloride were the dominant risk compounds. In the evaluation results of LOH, m/p-xylene (25.26–67.87%) was identified as the most key individual species and should be prioritized for control. In conclusion, the research results will provide the necessary reference to standardize the measurement method of the VOCs source component spectrum and build a localized source component spectrum.
Location-Allocation Model to Improve the Distribution of COVID-19 Vaccine Centers in Jeddah City, Saudi Arabia
Authors: Alhothali Areej , Alwated Budoor , Faisal Kamil , Alshammari Sultanah , Alotaibi Reem , Alghanmi Nusaybah , Bamasag Omaimah , Bin Yamin Manal
Published: July 2022

The correct distribution of service facilities can help keep fixed and overhead costs low while increasing accessibility. When an appropriate location is chosen, public-sector facilities, such as COVID-19 centers, can save lives faster and provide high-quality service to the community at a low cost. The purpose of the research is to highlight the issues related to the location of COVID-19 vaccine centers in the city of Jeddah, Saudi Arabia. In particular, this paper aims to analyze the accessibility of COVID-19 vaccine centers in Jeddah city using maximal coverage location problems with and without constraint on the number and capacity of facilities. A maximal coverage model is first used to analyze the COVID-19 vaccination coverage of Jeddah districts with no restriction on the facility capacity. Then, a maximize capacitated coverage method is utilized to assess the centers’ distribution and demand coverage with capacity constraints. Finally, the minimize facilities model is used to identify the most optimal location required to satisfy all demand points with the least number of facilities. The optimization approaches consider the objective function of minimizing the overall transportation time and travel distance to reduce wastage on the service rate provided to the patients. The optimization model is applied to a real-world case study in the context of the COVID-19 vaccination center in Jeddah. The results of this study provide valuable information that can help decision-makers locate and relocate COVID-19 centers more effectively under different constraints conditions.
Sociodemographic and Health-Related Factors Influencing Drug Intake among the Elderly Population
Authors: Pietraszek Alicja , Agrawal Siddarth , Dróżdż Mateusz , Makuch Sebastian , Domański Igor , Dudzik Tomasz , Dudek Krzysztof , Sobieszczańska Małgorzata
Published: July 2022

Excessive drugs intake among the elderly population, including self-medication, constitutes an important public health problem. Polypharmacy may lead to numerous adverse health effects, which become more prevalent when combined with biological changes in seniors. In this cross-sectional study, 500 Polish adults aged ≥60 years (M = 67.9 ± 4.2) were asked to complete a questionnaire via telephone calls, allowing us to identify sociodemographic and health-related factors influencing the daily medications consumption. Our findings revealed that all of the participants were receiving medications; 60.2% of them receive at least 1 to 3 drugs per day (301/500). The most commonly used medications included antihypertensive drugs and analgesics (51.0% and 46.0%, respectively). Taking into account clinical conditions, independent predictors of receiving over 3 medications per day turned out to be (1) coronary artery disease (OR = 6.77; CI 95%, 2.86–16.1), (2) diabetes (OR = 3.23, CI 95%, 1.75–5.95), (3) asthma (OR = 4.87, CI 95%, 2.13–11.1), (4) heart failure (OR = 3.38, CI 95%, 1.59–7.19) and (5) gastroesophageal reflux disease (OR = 1.93, CI 95%, 1.03–3.62). Participants suffering from depression were more likely to take drugs for hypertension (OR = 1.70, CI 95%, 1.04–2.78), while those with anxiety and social loneliness took more painkillers (OR = 2.59, CI 95%, 1.58–4.26 and OR = 2.08, CI 95%, 1.38–3.13, respectively). The most significant sociodemographic factors increasing the drugs intake among the population included in our study were high body mass and subsequent increased BMI values (OR = 2.68, CI 95%, 1.50–4.77). Furthermore, living in a city with over 400,000 inhabitants increased the likelihood of taking antidepressants (OR = 2.18, CI 95%, 1.20–3.94). Our study revealed factors increasing the risk of excessive medications intake and hence, increased susceptibility to some iatrogenic diseases among the elderly population. These factors should be considered by primary care physicians while prescribing appropriate drugs to elderly patients.
The Advantages of the Zero-COVID-19 Strategy
Authors: Su Zhaohui , Cheshmehzangi Ali , McDonnell Dean , Ahmad Junaid , Šegalo Sabina , Xiang Yu-Tao , da Veiga Claudimar Pereira
Published: July 2022

Introduction: To curb the COVID-19 pandemic, countries across the globe have adopted either a mitigation or anelimination policy, such as the zero-COVID-19 strategy. However, further research is needed to systematically investigate the advantages of the zero-COVID-19 strategy in the literature. To bridge the research gap, this study examines the zero-COVID-19 strategy in terms of its advantages as a global anti-pandemic framework. Methods: A literature review was conducted in PubMed, PsycINFO, and Scopus to locate academic articles that discussed the advantages of the zero-COVID-19 strategy. Braun and Clarke’s thematic analysis approach was adopted to guide the data analysis process. Results: The findings of our study show that the advantages of the zero-COVID-19 strategy range from short-term (e.g., limited virus infections, hospitalizations, and deaths), to medium-term (e.g., reduced presence of other infectious diseases), and long-term (e.g., low incidence of long COVID-19). While local residents mainly leverage these advantages, they also impact the global community (e.g., stable global supply of essentials, such as COVID-19 vaccines). Conclusions: COVID-19 is catastrophic, yet controllable. Our study examined the advantages of the zero-COVID-19 strategy from a nuanced perspective and discussed how these advantages benefit both the local and the global community in pandemic control and management. Future studies could investigate the shortcomings of the zero-COVID-19 strategy, especially its unintended consequences, such as adverse impacts on vulnerable populations’ mental health, so that society could more efficiently, economically, and empathetically capitalize on the potential of the zero-COVID-19 strategy for the betterment of personal and public health.
Effects of Particulate Matter on Inflammation and Thrombosis: Past Evidence for Future Prevention
Authors: Hantrakool Sasinee , Kumfu Sirinart , Chattipakorn Siriporn C. , Chattipakorn Nipon
Published: July 2022

Ambient air pollution has become a common problem worldwide. Exposure to pollutant particles causes many health conditions, having a particular impact on pulmonary and cardiovascular disease. Increased understanding of the pathological processes related to these conditions may facilitate the prevention of the adverse impact of air pollution on our physical health. Evidence from in vitro, in vivo, and clinical studies has consistently shown that exposure to particulate matter could induce the inflammatory responses such as IL-6, TNF-α, IL-1β, as well as enhancing the oxidative stress. These result in vascular injury, adhesion molecule release, platelet activation, and thrombin generation, ultimately leading to a prothrombotic state. In this review, evidence on the effects of particulate matter on inflammation, oxidative stress, adhesion molecules, and coagulation pathways in enhancing the risk of thrombosis is comprehensively summarized and discussed. The currently available outcomes of interventional studies at a cellular level and clinical reports are also presented and discussed.
Different Areas of Chronic Stress and Their Associations with Depression
Authors: Hussenoeder Felix S. , Conrad Ines , Pabst Alexander , Luppa Melanie , Stein Janine , Engel Christoph , Zachariae Silke , Zeynalova Samira , Yahiaoui-Doktor Maryam , Glaesmer Heide , Hinz Andreas , Witte Veronica , Wichmann Gunnar , Kirsten Toralf , Löffler Markus , Villringer Arno , Riedel-Heller Steffi G.
Published: July 2022

Background: Research shows a connection between stress and depression, but there is little differentiation between areas of stress, making it difficult to identify and address specific areas in the context of public health measures. We utilized a multi-dimensional approach to chronic stress to better understand the relationship between different areas of stress and depression. Methods: We conducted linear regression analyses and used data from a sub-sample of the LIFE-Adult-Study (N = 1008) to analyze the connection between nine different areas of chronic stress (TICS) and depression (CES-D). In the second analysis, we controlled for sociodemographic variables, personality, physical activity, and social support. Results: There was a significant positive association between the stress domains Excessive Demands from Work, Lack of Social Recognition, Social Isolation, and Chronic Worrying and depression and a significant negative association between Pressure to Perform and depression. After adding control variables, only Pressure to Perform, Social Isolation, and Chronic Worrying remained significant predictors. Conclusions: By focusing on the connections between chronic stress and depression, researchers can help identify the areas that matter most and contribute to the creation of meaningful and efficient interventions. On the basis of our results, measures for the prevention of depression that focus on the reduction of worrying and social isolation are recommended.
Risk Factors for Lung Cancer in the Province of Lecce: Results from the PROTOS Case–Control Study in Salento (Southern Italy)
Authors: Minichilli Fabrizio , Gorini Francesca , De Filippis Giovanni , Bustaffa Elisa , Raho Anna Maria , Melcarne Anna , Quarta Fabrizio , Maggiore Giuseppe , Idolo Adele , Serio Francesca , Grassi Tiziana , Bagordo Francesco , Castorini Idelberto Francesco , Imbriani Giovanni , Bianchi Fabrizio , Piscitelli Prisco
Published: July 2022

In the province of Lecce (southern Italy), a higher incidence of lung cancer (LC) among men compared to regional and national data was reported. In a sub-area in the center of the province (cluster area), the incidence and mortality for LC was even higher. PROTOS is a case–control study aimed at investigating possible risk factors for LC in the province area. A total of 442 patients with LC and 1326 controls matched by sex and age living in the province of Lecce for at least 10 years were enrolled and georeferenced; they filled in a questionnaire with their personal information and exposures. For each risk factor, an Odds Ratio adjusted for all the other variables was calculated. The risk of LC increased with excessive use of alcohol in women, for those subjects with a family cancer history, for each increase in pack/year of cigarettes, for men more exposed considering the industrial district in the cluster area, and for those using pesticides in agriculture without wearing personal protective equipment. The higher incidence of adenocarcinoma in both sexes suggests that, in addition to cigarette smoking, concurrent exposures to other environmental, occupational, and life-style factors may play a role in increased cancer risk and should be more deeply explored.
Leveraging Citizen Science and Low-Cost Sensors to Characterize Air Pollution Exposure of Disadvantaged Communities in Southern California
Authors: Lu Tianjun , Liu Yisi , Garcia Armando , Wang Meng , Li Yang , Bravo-villasenor German , Campos Kimberly , Xu Jia , Han Bin
Published: July 2022

Assessing exposure to fine particulate matter (PM2.5) across disadvantaged communities is understudied, and the air monitoring network is inadequate. We leveraged emerging low-cost sensors (PurpleAir) and engaged community residents to develop a community-based monitoring program across disadvantaged communities (high proportions of low-income and minority populations) in Southern California. We recruited 22 households from 8 communities to measure residential outdoor PM2.5 concentrations from June 2021 to December 2021. We identified the spatial and temporal patterns of PM2.5 measurements as well as the relationship between the total PM2.5 measurements and diesel PM emissions. We found that communities with a higher percentage of Hispanic and African American population and higher rates of unemployment, poverty, and housing burden were exposed to higher PM2.5 concentrations. The average PM2.5 concentrations in winter (25.8 µg/m3) were much higher compared with the summer concentrations (12.4 µg/m3). We also identified valuable hour-of-day and day-of-week patterns among disadvantaged communities. Our results suggest that the built environment can be targeted to reduce the exposure disparity. Integrating low-cost sensors into a citizen-science-based air monitoring program has promising applications to resolve monitoring disparity and capture “hotspots” to inform emission control and urban planning policies, thus improving exposure assessment and promoting environmental justice.
Impact of High-Molecular-Weight Hyaluronic Acid on Gene Expression in Rabbit Achilles Tenocytes In Vitro
Authors: Miescher Iris , Wolint Petra , Opelz Christine , Snedeker Jess G. , Giovanoli Pietro , Calcagni Maurizio , Buschmann Johanna
Published: July 2022

(1) Background: Surgical tendon repair often leads to adhesion formation, leading to joint stiffness and a reduced range of motion. Tubular implants set around sutured tendons might help to reduce peritendinous adhesions. The lubricant hyaluronic acid (HA) is a viable option for optimizing such tubes with the goal of further enhancing the anti-adhesive effect. As the implant degrades over time and diffusion is presumed, the impact of HA on tendon cells is important to know. (2) Methods: A culture medium of rabbit Achilles tenocytes was supplemented with high-molecular-weight (HMW) HA and the growth curves of the cells were assessed. Additionally, after 3, 7 and 14 days, the gene expression of several markers was analyzed for matrix assembly, tendon differentiation, fibrosis, proliferation, matrix remodeling, pro-inflammation and resolution. (3) Results: The addition of HA decreased matrix marker genes, downregulated the fibrosis marker α-SMA for a short time and slightly increased the matrix-remodeling gene MMP-2. Of the pro-inflammatory marker genes, only IL-6 was significantly upregulated. IL-6 has to be kept in check, although IL-6 is also needed for a proper initial inflammation and efficient resolution. (4) Conclusions: The observed effects in vitro support the intended anti-adhesion effect and therefore, the use of HMW HA is promising as a biodegradable implant for tendon repair.
An Epilepsy-Associated Mutation of Salt-Inducible Kinase 1 Increases the Susceptibility to Epileptic Seizures and Interferes with Adrenocorticotropic Hormone Therapy for Infantile Spasms in Mice
Authors: Pang Bo , Mori Takuma , Badawi Moataz , Zhou Mengyun , Guo Qi , Suzuki-Kouyama Emi , Yanagawa Toru , Shirai Yoshinori , Tabuchi Katsuhiko
Published: July 2022

Six mutations in the salt-inducible kinase 1 (SIK1) have been identified in developmental and epileptic encephalopathy (DEE-30) patients, and two of the mutations are nonsense mutations that truncate the C-terminal region of SIK1. In a previous study, we generated SIK1 mutant (SIK1-MT) mice recapitulating the C-terminal truncated mutations using CRISPR/Cas9-mediated genome editing and found an increase in excitatory synaptic transmission and enhancement of neural excitability in neocortical neurons in SIK1-MT mice. NMDA was injected into SIK1-MT males to induce epileptic seizures in the mice. The severity of the NMDA-induced seizures was estimated by the latency and the number of tail flickering and hyperflexion. Activated brain regions were evaluated by immunohistochemistry against c-fos, Iba1, and GFAP. As another epilepsy model, pentylenetetrazol was injected into the adult SIK1 mutant mice. Seizure susceptibility induced by both NMDA and PTZ was enhanced in SIK1-MT mice. Brain regions including the thalamus and hypothalamus were strongly activated in NMDA-induced seizures. The epilepsy-associated mutation of SIK1 canceled the pharmacological effects of the ACTH treatment on NMDA-induced seizures. These results suggest that SIK1 may be involved in the neuropathological mechanisms of NMDA-induced spasms and the pharmacological mechanism of ACTH treatment.
Microbial Biofilms and Antibiofilm Agents 2.0
Authors: Batoni Giovanna , Maisetta Giuseppantonio , Esin Semih
Published: July 2022

It is estimated that <0 [...]
A Comparative Molecular Dynamics Study of Selected Point Mutations in the Shwachman–Bodian–Diamond Syndrome Protein SBDS
Authors: Spinetti Elena , Delre Pietro , Saviano Michele , Siliqi Dritan , Lattanzi Gianluca , Mangiatordi Giuseppe Felice
Published: July 2022

The Shwachman–Diamond Syndrome (SDS) is an autosomal recessive disease whose majority of patients display mutations in a ribosome assembly protein named Shwachman–Bodian–Diamond Syndrome protein (SBDS). A specific therapy for treating this rare disease is missing, due to the lack of knowledge of the molecular mechanisms responsible for its pathogenesis. Starting from the observation that SBDS single-point mutations, localized in different domains of the proteins, are responsible for an SDS phenotype, we carried out the first comparative Molecular Dynamics simulations on three SBDS mutants, namely R19Q, R126T and I212T. The obtained 450-ns long trajectories were compared with those returned by both the open and closed forms of wild type SBDS and strongly indicated that two distinct conformations (open and closed) are both necessary for the proper SBDS function, in full agreement with recent experimental observations. Our study supports the hypothesis that the SBDS function is governed by an allosteric mechanism involving domains I and III and provides new insights into SDS pathogenesis, thus offering a possible starting point for a specific therapeutic option.
Evaluation of a Novel Thiol–Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells
Authors: Burchak Vadym , Koch Fritz , Siebler Leonard , Haase Sonja , Horner Verena K. , Kempter Xenia , Stark G. Björn , Schepers Ute , Grimm Alisa , Zimmermann Stefan , Koltay Peter , Strassburg Sandra , Finkenzeller Günter , Simunovic Filip , Lampert Florian
Published: July 2022

Introduction: Three-dimensional bioprinting can be considered as an advancement of the classical tissue engineering concept. For bioprinting, cells have to be dispersed in hydrogels. Recently, a novel semi-synthetic thiolene hydrogel system based on norbornene-functionalized gelatin (GelNB) and thiolated gelatin (GelS) was described that resulted in the photoclick hydrogel GelNB/GelS. In this study, we evaluated the printability and biocompatibility of this hydrogel system towards adipose-tissue-derived mesenchymal stem cells (ASCs). Methods: GelNB/GelS was synthesized with three different crosslinking densities (low, medium and high), resulting in different mechanical properties with moduli of elasticity between 206 Pa and 1383 Pa. These hydrogels were tested for their biocompatibility towards ASCs in terms of their viability, proliferation and differentiation. The extrusion-based bioprinting of ASCs in GelNB/GelS-high was performed to manufacture three-dimensional cubic constructs. Results: All three hydrogels supported the viability, proliferation and chondrogenic differentiation of ASCs to a similar extent. The adipogenic differentiation of ASCs was better supported by the softer hydrogel (GelNB/GelS-low), whereas the osteogenic differentiation was more pronounced in the harder hydrogel (GelNB/GelS-high), indicating that the differentiation fate of ASCs can be influenced via the adaption of the mechanical properties of the GelNB/GelS system. After the ex vivo chondrogenic differentiation and subcutaneous implantation of the bioprinted construct into immunocompromised mice, the production of negatively charged sulfated proteoglycans could be observed with only minimal inflammatory signs in the implanted material. Conclusions: Our results indicate that the GelNB/GelS hydrogels are very well suited for the bioprinting of ASCs and may represent attractive hydrogels for subsequent in vivo tissue engineering applications.
Genomewide Identification and Characterization of the Genes Involved in the Flowering of Cotton
Authors: Li Xiao , Wu Yuanlong , Chi Huabin , Wei Hengling , Wang Hantao , Yu Shuxun
Published: July 2022

Flowering is a prerequisite for flowering plants to complete reproduction, and flowering time has an important effect on the high and stable yields of crops. However, there are limited reports on flowering-related genes at the genomic level in cotton. In this study, genomewide analysis of the evolutionary relationship of flowering-related genes in different cotton species shows that the numbers of flowering-related genes in the genomes of tetraploid cotton species Gossypium hirsutum and Gossypium barbadense were similar, and that these numbers were approximately twice as much as the number in diploid cotton species Gossypium arboretum. The classification of flowering-related genes shows that most of them belong to the photoperiod and circadian clock flowering pathway. The distribution of flowering-related genes on the chromosomes of the At and Dt subgenomes was similar, with no subgenomic preference detected. In addition, most of the flowering-related core genes in Arabidopsis thaliana had homologs in the cotton genome, but the copy numbers and expression patterns were disparate; moreover, flowering-related genes underwent purifying selection throughout the evolutionary and selection processes. Although the differentiation and reorganization of many key genes of the cotton flowering regulatory network occurred throughout the evolutionary and selection processes, most of them, especially those involved in the important flowering regulatory networks, have been relatively conserved and preferentially selected.
Protein Abundance of Drug Transporters in Human Hepatitis C Livers
Authors: Droździk Marek , Lapczuk-Romanska Joanna , Wenzel Christoph , Skalski Łukasz , Szeląg-Pieniek Sylwia , Post Mariola , Syczewska Marta , Kurzawski Mateusz , Oswald Stefan
Published: July 2022

Transmembrane drug transport in hepatocytes is one of the major determinants of drug pharmacokinetics. In the present study, ABC transporters (P-gp, MRP1, MRP2, MRP3, MRP4, BCRP, and BSEP) and SLC transporters (MCT1, NTCP, OAT2, OATP1B1, OATP1B3, OATP2B1, OCT1, and OCT3) were quantified for protein abundance (LC-MS/MS) and mRNA levels (qRT-PCR) in hepatitis C virus (HCV)-infected liver samples from the Child–Pugh class A (n = 30), B (n = 21), and C (n = 7) patients. Protein levels of BSEP, MRP3, MCT1, OAT2, OATP1B3, and OCT3 were not significantly affected by HCV infection. P-gp, MRP1, BCRP, and OATP1B3 protein abundances were upregulated, whereas those of MRP2, MRP4, NTCP, OATP2B1, and OCT1 were downregulated in all HCV samples. The observed changes started to be seen in the Child–Pugh class A livers, i.e., upregulation of P-gp and MRP1 and downregulation of MRP2, MRP4, BCRP, and OATP1B3. In the case of NTCP, OATP2B1, and OCT1, a decrease in the protein levels was observed in the class B livers. In the class C livers, no other changes were noted than those in the class A and B patients. The results of the study demonstrate that drug transporter protein abundances are affected by the functional state of the liver in hepatitis C patients.
Spatial and Functional Crosstalk between the Mitochondrial Na+-Ca2+ Exchanger NCLX and the Sarcoplasmic Reticulum Ca2+ Pump SERCA in Cardiomyocytes
Authors: Takeuchi Ayako , Matsuoka Satoshi
Published: July 2022

The mitochondrial Na+-Ca2+ exchanger, NCLX, was reported to supply Ca2+ to sarcoplasmic reticulum (SR)/endoplasmic reticulum, thereby modulating various cellular functions such as the rhythmicity of cardiomyocytes, and cellular Ca2+ signaling upon antigen receptor stimulation and chemotaxis in B lymphocytes; however, there is little information on the spatial relationships of NCLX with SR Ca2+ handling proteins, and their physiological impact. Here we examined the issue, focusing on the interaction of NCLX with an SR Ca2+ pump SERCA in cardiomyocytes. A bimolecular fluorescence complementation assay using HEK293 cells revealed that the exogenously expressed NCLX was localized in close proximity to four exogenously expressed SERCA isoforms. Immunofluorescence analyses of isolated ventricular myocytes showed that the NCLX was localized to the edges of the mitochondria, forming a striped pattern. The co-localization coefficients in the super-resolution images were higher for NCLX–SERCA2, than for NCLX–ryanodine receptor and NCLX–Na+/K+ ATPase α-1 subunit, confirming the close localization of endogenous NCLX and SERCA2 in cardiomyocytes. The mathematical model implemented with the spatial and functional coupling of NCLX and SERCA well reproduced the NCLX inhibition-mediated modulations of SR Ca2+ reuptake in HL-1 cardiomyocytes. Taken together, these results indicated that NCLX and SERCA are spatially and functionally coupled in cardiomyocytes.
Disruption of a Conservative Motif in the C-Terminal Loop of the KCNQ1 Channel Causes LQT Syndrome
Authors: Karlova Maria , Abramochkin Denis V. , Pustovit Ksenia B. , Nesterova Tatiana , Novoseletsky Valery , Loussouarn Gildas , Zaklyazminskaya Elena , Sokolova Olga S.
Published: July 2022

We identified a single nucleotide variation (SNV) (c.1264A > G) in the KCNQ1 gene in a 5-year-old boy who presented with a prolonged QT interval. His elder brother and mother, but not sister and father, also had this mutation. This missense mutation leads to a p.Lys422Glu (K422E) substitution in the Kv7.1 protein that has never been mentioned before. We inserted this substitution in an expression plasmid containing Kv7.1 cDNA and studied the electrophysiological characteristics of the mutated channel expressed in CHO-K1, using the whole-cell configuration of the patch-clamp technique. Expression of the mutant Kv7.1 channel in both homo- and heterozygous conditions in the presence of auxiliary subunit KCNE1 results in a significant decrease in tail current densities compared to the expression of wild-type (WT) Kv7.1 and KCNE1. This study also indicates that K422E point mutation causes a dominant negative effect. The mutation was not associated with a trafficking defect; the mutant channel protein was confirmed to localize at the cell membrane. This mutation disrupts the poly-Lys strip in the proximal part of the highly conserved cytoplasmic A–B linker of Kv7.1 that was not shown before to be crucial for channel functioning.
Comparative Tolerance Levels of Maize Landraces and a Hybrid to Natural Infestation of Fall Armyworm
Authors: Lima Andreísa Fabri , Bernal Julio , Venâncio Maria Gabriela Silva , de Souza Bruno Henrique Sardinha , Carvalho Geraldo Andrade
Published: July 2022

Insect pests such as Spodoptera frugiperda cause significant losses to maize (Zea mays mays). Control of S. frugiperda is difficult, but the use of insect resistant cultivars, including tolerant cultivars, is a promising alternative, and landraces are a potential source of insect resistance. This study investigated tolerance to S. frugiperda in five Brazilian landraces, Amarelão, Aztequinha, Branco Antigo, Palha Roxa, and São Pedro, in relation to one conventional (non-Bt) hybrid, BM207, under field conditions. We assessed tolerance as the ratio of insecticide-free to insecticide-protected plants for plant height, stem diameter, and leaf chlorophyll content at two plant stages. Tolerance ratios varied across the maize genotypes, but inconsistently across plant variables, and cluster analysis revealed three groups based on tolerance ratios. A first group contained genotypes similarly tolerant to S. frugiperda, BM207, Palha Roxa, São Pedro, and Aztequinha, while the second and third groups each contained single genotypes, Amarelão, and Branco Antigo, which were considered not tolerant. Overall, the landraces Palha Roxa, São Pedro, and Aztequinha compared favorably to BM207 in terms of tolerance, and therefore may be valuable for management of this pest, and as germplasm sources to improve tolerance in other cultivars.