bluuebunny/crossref_metadata_2025 huggingface dataset:
A Moderated Mediation Analysis of the Effects of the COVID-19 Pandemic on Well-Being and Sport Readiness of Italian Team Sports Players: The Role of Perceived Safety of the Training Environment
Authors: Vitali Francesca , Bisagno Elisa , Coco Marinella , Cadamuro Alessia , Maldonato Nelson Mauro , Di Corrado Donatella
Published: February 2022

Background: The protective restrictions (e.g., lockdowns, quarantines, social and physical distancing) consequent to the global pandemic caused by COVID-19 posited new challenges to athletes practicing competitive team sports. This study aimed to gain an understanding of the impact of the ongoing COVID-19 pandemic on the well-being and sports readiness to train and to compete of competitive female and male athletes practicing outdoor (i.e., rugby, soccer) and indoor (i.e., volleyball, basketball) team sports who were active during the Italian first and second waves of COVID-19. Methods: An online survey assessing demographic characteristics, perceived safety of the training environment, COVID-19 risk, fear of COVID-19, well-being, and sport (training and competition) readiness was administered to 619 team sports players. We examined differences by gender, previous COVID-19 experience, and team sport setting (i.e., outdoor vs. indoor). A moderated mediation analysis was conducted to assess the impact of perceived COVID-19 risk and fear of COVID-19 on athletes’ well-being and sports readiness, using perceived safety of the training environment as a mediator and gender and sport setting as moderators. Results: Indoor team sports and female athletes showed higher perceived COVID-19 risk, while athletes with no-COVID-19 experience reported higher fear of COVID-19. Perceived COVID-19 risk (directly and via perceived safety of the training environment) and fear of COVID-19 were negatively associated with athletes’ well-being and sports readiness. Conclusions: This study highlighted an understanding of the psychological implications of the COVID-19 pandemic, emphasizing the role of the perceived safety of the training environment on athletes’ well-being and sports readiness. Future studies may advance safety-based interventions to promote well-being and a safer return to sport.
Study on the Influence of Opposing Glare from Vehicle High-Beam Headlights Based on Drivers’ Visual Requirements
Authors: Hu Jiangbi , Guo Yunpeng , Wang Ronghua , Ma Sen , Yu Aolin
Published: February 2022

The anti-glare facilities in median strips are designed to block opposing headlights in order to avoid disability glare, but a large amount of headlight leakage results in uncomfortable glare, to the point that drivers can barely detect dangerous obstacles or road conditions. This paper aims to explore the glare range under high-beam headlights on drivers’ visual requirements. Based on an analysis of the mechanism of headlight glare, this paper proposes a subjective headlight glare scale, and classifies glare discomfort into two categories: interference glare, and acceptability glare. Combining the scales, 24 drivers and a standard light-emitting diode automotive headlamp were used to conduct glare effect tests. The size of the laboratory that closes to scotopic vision is 12 m × 6 m. The illuminance thresholds of disability glare–interference glare (DGIG) and interference glare–acceptability glare (IGAG), along with the spatial distribution of each glare level, were collected at the longitudinal distances of 3 m, 5 m, 7 m, 10 m, and 12 m. Meanwhile, the illuminance threshold and the spatial distribution of each glare level up to a longitudinal distance of 120 m were calculated. The results indicate that disability glare is distributed in the central area, while interference glare and acceptability glare are distributed from the center to the margins. At the same longitudinal distance, the vertical illuminance of the driver’s eye under the same glare level is almost equal. In the range of a longitudinal distance of 120 m, the spatial distribution of each glare level enlarges with each increase in longitudinal distance. The results can provide scientific evidence for calculating the reasonable heights of anti-glare facilities for expressways with different alignments.
Credibility and Involvement of Social Media in Education—Recommendations for Mitigating the Negative Effects of the Pandemic among High School Students
Authors: Tkacová Hedviga , Králik Roman , Tvrdoň Miroslav , Jenisová Zita , Martin José García
Published: February 2022

In the context of considerations on the potential attenuation of the negative consequences of the COVID-19 pandemic with the use of credible social media in online education during a pandemic, the subject of our own research was the fulfillment of two goals. The main research goals were to identify, categorize, and evaluate the possibilities of using social media in online education during the pandemic from the perspective of selected teachers and students from secondary schools in Slovakia. The research methods of the first phase (qualitative) of the research involved brainstorming among nine secondary school teachers. The second research phase (quantitative) used a questionnaire, which was completed by 102 high school students from all over Slovakia. The collection of both quantitative and qualitative data was used in this research. The research results revealed the most representative opinions of teachers on the current and real possibilities of engaging credible social media in online education and the views of high school students on their desired use and involvement of social media in online education. The intersection of the two findings presents a picture of the possibilities of using credible social media in online education, which can help maintain students’ interest in online education during a pandemic. Based on these findings, it can be stated that the opinions identified in the research group of teachers correspond to a large extent with the desired use of social media in education from the perspective of students. In addition, however, students would welcome more opportunities to use and engage social media in today’s online education. The result of this research is an analysis of social media patterns applied to online education, which are of greater interest to students and could act as elements for reducing the negative consequences of the COVID-19 pandemic, i.e., six forms of online education and 24 educational activities that could contribute, inter alia, to mitigating the different negative effects of the pandemic among youth generation. The findings also benefit from the presentation of many specific options and recommendations for the use of social media in online education during a pandemic.
The Construct of Medical and Non-Medical Marijuana—Critical Review
Authors: Silczuk Andrzej , Smułek Daria , Kołodziej Marcin , Gujska Julia
Published: February 2022

The rising popularity of medical marijuana and its potential therapeutic uses has resulted in passionate discussions that have mainly focused on its possible benefits and applications. Although the concept itself seems promising, the multitude of presented information has noticeable ramifications—terminological chaos being one. This work aimed to synthesize and critically analyze scientific evidence on the therapeutic uses of cannabinoids in the field of psychiatry. Emphasis was placed on the anxiolytic effects of cannabis constituents and their effects on post-traumatic stress disorder, anxiety disorders, schizophrenia spectrum, and other psychotic disorders. The review was carried out from an addictological perspective. A database search of interchangeably combined keywords resulted in the identification of subject-related records. The data were then analyzed in terms of relevance, contents, methodologies, and cited papers. The results were clear in supporting one common conclusion: while most findings provide support for beneficial applications of medical marijuana in psychiatry, no certain conclusions can be drawn until larger-scaled, more methodologically rigorous, and (preferably) controlled randomized trials verify these discoveries.
Concurrent Heat Waves and Extreme Ozone (O3) Episodes: Combined Atmospheric Patterns and Impact on Human Health
Authors: Khomsi Kenza , Chelhaoui Youssef , Alilou Soukaina , Souri Rania , Najmi Houda , Souhaili Zineb
Published: February 2022

More recurrent heat waves and extreme ozone (O3) episodes are likely to occur during the next decades and a key question is about the concurrence of those hazards, the atmospheric patterns behind their appearance, and their joint effect on human health. In this work, we use surface maximum temperature and O3 observations during extended summers in two cities from Morocco: Casablanca and Marrakech, between 2010 and 2019. We assess the connection between these data and climate indices (North Atlantic Oscillation (NAO), Mediterranean Oscillation (MO), and Saharan Oscillation (SaO)). We then identify concurrent heat waves and O3 episodes, the weather type behind this concurrence, and the combined health risks. Our findings show that the concurrence of heat waves and O3 episodes depends both on the specific city and the large-scale atmospheric circulation. The likely identified synoptic pattern is when the country is under the combined influence of an anticyclonic area in the north and the Saharan trough extending the depression centered in the south. This pattern generates a warm flow and may foster photochemical pollution. Our study is the first step toward the establishment of an alert system. It will help to provide recommendations for coping with concurrent heat waves and air pollution episodes.
Analysis of Drought and Flood Variations on a 200-Year Scale Based on Historical Environmental Information in Western China
Authors: Liu Yinge , Wen Yanjun , Zhao Yaqian , Hu Haonan
Published: February 2022

Historical environmental evidence has been characterized by time accuracy, high spatial resolution and rich information, which may be widely used in the reconstruction of historical data series. Taking the upper reaches of the Weihe River as an example in Western China, the grades and index sequences of the drought and flood disasters from 1800 to 2016 were reconstructed based on various historical environmental information and standardized precipitation indicator (SPI). Moreover, the characteristics of droughts and floods were analyzed using statistical diagnostic methods, and the mechanisms affecting centennial-scale droughts and floods were discussed. The validity of reconstruction sequence of droughts/floods was verified, which showed that the reconstruction sequence may reasonably indicate the status of drought and flood. The reconstruction indicated the following periods of drought/flood: a period of extreme and big droughts in 1835s–1893s, 1924s–1943s and 1984s–2008s, a period of extreme and big floods in 1903s–1923s, and a period of extreme and big droughts/floods in 1944s–1983s. Moreover, the droughts were more serious in the western part of this region and the floods were relatively severe in the east of this region, while the droughts and floods have long-term period of about 100 years and mutation. The influence mechanism of external environmental forcing factors driving floods/droughts were revealed. The results showed that the cycle of El Niño Southern Oscillation (ENSO) and sunspot activities were closely related to the variations of drought/flood, meanwhile, ENSO has a significant lag time scale cumulative influence on droughts and floods, especially the 15-year sliding effect was the most obvious. In the peak year of sunspots, the probability of heavy drought/extreme floods was large, and the 102-year sunspot cycle has a more significant effect on drought and flood disasters. The mutation of droughts and floods occurred in the context of the drastic changes in the ground environment, and transformation of precipitation and land use structure. These results will enhance the understandings of historical environmental climate characteristics and mechanisms over the hundred years, and be useful for the future regional water resources and assessment, and ecological environment management.
Caregiving of Older Persons during the COVID-19 Pandemic in the Russian Arctic Province: Challenges and Practice
Authors: Golubeva Elena , Emelyanova Anastasia , Kharkova Olga , Rautio Arja , Soloviev Andrey
Published: February 2022

Older people and their families were particularly affected during the COVID-19 pandemic in 2020, but not much is known about the context of the Arctic regions of Russia. In this study, we identified the changes in family care before and during the pandemic using a questionnaire for the informal caregivers of older people. We investigated how and to what extent the pandemic has affected the relationships between caregiver and older person, and how the mental and physical health of older people and caregivers were affected by self-isolation in the Arkhangelsk region of Russia. The pandemic has changed the contribution of care from various actors: the share of care by charities, churches, and other aid agencies increased, while that of municipal services decreased. Sixteen percent of female and forty percent of male caregivers informed the study that COVID-19-related restrictions led to deterioration in the health of older people cared for at home. Family caregivers’ own health worsened, especially mental health: 28% of caregivers reported aggravated stress during the COVID-19 pandemic and expressed various fears. Our data show that the main resources in overcoming the period of self-isolation have been telephone communication, personal contact, reading/music, friends, as well as the help of social services and maintaining a positive attitude.
Exploring the Peer Effect of Physicians’ and Patients’ Participation Behavior: Evidence from Online Health Communities
Authors: Yin Qiuju , Fan Haoyue , Wang Yijie , Guo Chenxi , Cui Xingzhi
Published: February 2022

Background: Little research has studied the peer effect of physicians and patients in online health communities (OHCs) simultaneously. The study investigates the impact of the focal physician’s peers (F-peers) on the focal physician (F-physician), and the impact of patients of the focal physician’s peers (F-P-patients) on the focal physician’s patients (F-patients). Moreover, based on brand extension and accessible–diagnosable theories, this study explores the moderating effects of the intensity of F-peers’ knowledge sharing behavior and department reputation. Methods: This study collects data of 3297 physicians and related patients from Haodf.com platform between January 2019 and December 2019. Both two-way fixed effect and panel negative binomial regression are adopted to quantify the effects. Results: Results show that the behavior of F-peers positively affects the behavior of the F-physician, while the behavior of F-P-patients positively affects the behavior of F-patients. Moreover, both the intensity of F-peers’ knowledge sharing behavior and department reputation have a compound moderating effect. Conclusions: This study contributes to the literature of peer effects by constructing the conceptual framework of different types of individual participation behaviors in OHCs. The findings offer practical guides for establishing an incentive mechanism and formulating peer incentives or competition strategies in OHCs.
Healthcare Utilisation and Clinical Outcomes in Older Cardiovascular Patients Receiving Comprehensive Medication Management Services: A Nonrandomised Clinical Study
Authors: Brajković Andrea , Bosnar Lorena , Nascimento Mariana Martins Gonzaga do , Prkačin Ingrid , Balenović Antonija , Ramalho de Oliveira Djenane , Mucalo Iva
Published: February 2022

The objective of this study was to evaluate the impact of comprehensive medication management (CMM) services on healthcare utilisation and cardiovascular risk factors among older patients with established cardiovascular diseases (CVDs). This quasi-experimental study that was performed at the Croatian primary care ambulatory clinic included patients aged 65 to 80 years. Patients were divided into intervention (65 patients) and control groups (68 patients) and were followed-up for one year. Pharmacists provided face-to-face consultations to patients from the intervention group. Groups were compared with regards to the clinical parameters (blood pressure, HbA1c, LDL, TC) and healthcare utilisation (hospital admission, emergency visits, unplanned GP visits). The CMM intervention significantly improved systolic blood pressure (p = 0.038), diastolic blood pressure (p = 0.001), total cholesterol (p = 0.014), low-density lipoprotein cholesterol (p = 0.005), and glycosylated haemoglobin (p = 0.045) in comparison with the control group. Patients included in CMM services had statistically and clinically lower systolic (−9.02 mmHg, p < 0.001) and diastolic blood pressure (−4.99 mmHg, p < 0.001) at the end of the study. The number of hospital admissions and unplanned GPs visits were 3.35 (95% CI 1.16–10.00) and 2.34 (95% CI 1.52–3.57) times higher in the control group compared to the intervention group, respectively. This study demonstrated that pharmacists providing CMM services can significantly contribute to better clinical outcomes and lower healthcare utilisation, thus potentially contributing to total healthcare savings.
Could a Behavioral Model Explain Adherence to Second-Level Colonoscopy for Colon Cancer Screening? Results of a Cross-Sectional Study of the Palermo Province Population
Authors: Minutolo Giuseppa , Immordino Palmira , Dolce Alessia , Valenza Mario , Amodio Emanuele , Mazzucco Walter , Casuccio Alessandra , Restivo Vincenzo
Published: February 2022

According to Italian Essential Levels of Assistance (ELA), a colonoscopy is strongly recommended after a positive fecal occult blood test (FOBT) due to its effectiveness in early colorectal cancer detection. Despite the evidence, the Palermo province population (Italy), after a positive FOBT, have a lower colonoscopy adherence compared to Italian standards. This cross-sectional study analyzed patients’ perceptions of colonoscopy procedures to understand the reasons for non-adherence. Patients with a positive FOBT who did not undergo a colonoscopy within the national organized screening program were administered a telephone interview based on the Health Belief Model (HBM) questionnaire. The number of non-compliant patients with a colonoscopy after a positive FOBT were 182, of which 45 (25.7%) patients had undergone a colonoscopy in another healthcare setting. Among the HBM items, in a multivariate analysis only perceived benefits were significantly associated with colonoscopy adherence (aOR = 6.7, p = 0.03). Health promotion interventions should focus on the importance of the benefits of colorectal screening adherence to prevent colorectal cancer, implementing health communication by healthcare workers that have closer contacts with people, as general practitioners.
Total Factor Productivity and High-Quality Economic Development: A Theoretical and Empirical Analysis of the Yangtze River Economic Belt, China
Authors: Zeng Shaolong , Shu Xianfan , Ye Wenxian
Published: February 2022

This paper focuses on the total factor productivity (TFP) and high-quality economic development in China by examining 11 Chinese provinces and cities in the Yangtze River Economic Belt from 2007 to 2018. We use the Solow residual method to calculate the TFP growth rate of the 11 provinces and cities. Based on the panel data, we have analyzed the influencing factors of TFP theoretically and empirically from the overall region and upstream region, and midstream region and downstream region, respectively. The regression results show that: (1) The whole characteristics generally show the TFP growth trend of the upstream region, midstream region and downstream region are consistent with that of the overall region, and the growth rate of TFP slows down gradually. Meanwhile the differences in TFP growth between the upstream region, midstream region and downstream region show an increase at first and then a decrease. (2) Regarding the influencing factors, there are differences in the direction and extent of the impact of each factor such as the level of openness, R&D investment, industrial structure, government expenditure and human capital on the TFP of the overall region, upstream region, midstream region and downstream region. (3) Based on the results of the theoretical and empirical analysis, we have proposed a series of measures for the sustainable high-quality development of the Yangtze River Economic Belt.
Occurrence of No-Harm Incidents and Adverse Events in Hospitalized Patients with Ischemic Stroke or TIA: A Cohort Study Using Trigger Tool Methodology
Authors: Nowak Bartosch , Schwendimann René , Lyrer Philippe , Bonati Leo H. , De Marchis Gian Marco , Peters Nils , Zúñiga Franziska , Saar Lili , Unbeck Maria , Simon Michael
Published: February 2022

Adverse events (AEs)—healthcare caused events leading to patient harm or even death—are common in healthcare. Although it is a frequently investigated topic, systematic knowledge on this phenomenon in stroke patients is limited. To determine cumulative incidence of no-harm incidents and AEs, including their severity and preventability, a cohort study using trigger tool methodology for retrospective record review was designed. The study was carried out in a stroke center at a university hospital in the German speaking part of Switzerland. Electronic records from 150 randomly selected patient admissions for transient ischemic attack (TIA) or ischemic stroke, with or without acute recanalization therapy, were used. In total, 170 events (108 AEs and 62 no-harm incidents) were identified, affecting 83 patients (55.3%; 95% CI 47 to 63.4), corresponding to an event rate of 113 events/100 admissions or 142 events/1000 patient days. The three most frequent AEs were ischemic strokes (n = 12, 7.1%), urinary tract infections (n = 11, 6.5%) and phlebitis (n = 10, 5.9%). The most frequent no-harm incidents were medication events (n = 37, 21.8%). Preventability ranged from 12.5% for allergic reactions to 100% for medication events and pressure ulcers. Most of the events found (142; 83.5%; 95% CI 76.9 to 88.6) occurred throughout the whole stroke care. The remaining 28 events (16.5%; 95% CI 11.4 to 23.1) were detected during stroke care but were related to care outside the stroke pathway. Trigger tool methodology allows detection of AEs and no-harm incidents, showing a frequent occurrence of both event types in stroke and TIA patients. Further investigations into events’ relationships with organizational systems and processes will be needed, first to achieve a better understanding of these events’ underlying mechanisms and risk factors, then to determine efforts needed to improve patient safety.
Integrating Human Barriers in Human Reliability Analysis: A New Model for the Energy Sector
Authors: Guglielmi Dina , Paolucci Alessio , Cozzani Valerio , Mariani Marco Giovanni , Pietrantoni Luca , Fraboni Federico
Published: February 2022

Human reliability analysis (HRA) is a major concern for organizations. While various tools, methods, and instruments have been developed by the scientific community to assess human error probability, few of them actually consider human factors impact in their analysis. The active role that workers have in shaping their own performance should be taken into account in order to understand the causal factors that may lead to errors while performing a task and identifying which human factors may prevent errors from occurring. In line with this purpose, the aim of this study is to present a new methodology for the assessment of human reliability. The proposed model relies on well-known HRA methodologies (such as SPAR-H and HEART) and integrates them in a unified framework in which human factors assume the role of safety barriers against human error. A test case of the new method was carried out in a logistics hub of an energy company. Our results indicate that human factors play a significant role in preventing workers from making errors while performing tasks by reducing human error probability. The limits and implications of the study are discussed.
Modeling Buildings in CityGML LOD1: Building Parts, Terrain Intersection Curve, and Address Features
Authors: Shirinyan Evgeny , Petrova-Antonova Dessislava
Published: February 2022

3D city models integrate heterogeneous urban data from multiple sources in a unified geospatial representation, combining both semantics and geometry. Although in past decades they have predominantly been used for visualization, today they are used in a large range of tasks related to exploration, analysis, and management across multiple domains. The complexity of urban processes and the diversity of urban environments bring challenges to the implementation of 3D city models. To address such challenges, this paper presents the development process of a 3D city model of a single neighborhood in the city of Sofia based on the CityGML 2.0 standard. The model represents the buildings in LOD1, focusing on CityGML features, including building parts, the terrain intersection curve, and the address. Similar building models of 18 cities provided as open datasets are explored and compared to extract good modeling practices. As a result, workflows for the generation of 3D building models in LOD1 are elaborated on and improvements in the feature modeling are proposed. Two building model options are examined: (1) the modeling of a building as a single solid with differentiated rooftops and (2) the modeling of a building with separate building parts. The developed 3D building model contains 471 buildings and 198 addresses in both cases of building parts modeling. In addition, the terrain intersection curve (TIC) is modeled and a method for removing the duplicating TIC features is applied. Consequently, the overall count of vertices of the TIC is lowered from 12,112 to 8042. Finally, the possibilities for visualization of the model in popular platforms such as ArcGIS Pro and Cesium Ion are explored.
Immunotherapy in Advanced Prostate Cancer—Light at the End of the Tunnel?
Authors: von Amsberg Gunhild , Alsdorf Winfried , Karagiannis Panagiotis , Coym Anja , Kaune Moritz , Werner Stefan , Graefen Markus , Bokemeyer Carsten , Merkens Lina , Dyshlovoy Sergey A.
Published: February 2022

Immunotherapeutic treatment approaches are now an integral part of the treatment of many solid tumors. However, attempts to integrate immunotherapy into the treatment of prostate cancer have been disappointing so far. This is due to a highly immunosuppressive, “cold” tumor microenvironment, which is characterized, for example, by the absence of cytotoxic T cells, an increased number of myeloid-derived suppressor cells or regulatory T cells, a decreased number of tumor antigens, or a defect in antigen presentation. The consequence is a reduced efficacy of many established immunotherapeutic treatments such as checkpoint inhibitors. However, a growing understanding of the underlying mechanisms of tumor–immune system interactions raises hopes that immunotherapeutic strategies can be optimized in the future. The aim of this review is to provide an overview of the current status and future directions of immunotherapy development in prostate cancer. Background information on immune response and tumor microenvironment will help to better understand current therapeutic strategies under preclinical and clinical development.
Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis
Authors: Morrison Gareth , Buckley Jonathan , Ostrow Dejerianne , Varghese Bino , Cen Steven Y. , Werbin Jeffrey , Ericson Nolan , Cunha Alexander , Lu Yi-Tsung , George Thaddeus , Smith Jeffrey , Quinn David , Duddalwar Vinay , Triche Timothy , Goldkorn Amir
Published: February 2022

Integrating liquid biopsies of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) with other minimally invasive measures may yield more comprehensive disease profiles. We evaluated the feasibility of concurrent cellular and molecular analysis of CTCs and cfDNA combined with radiomic analysis of CT scans from patients with metastatic castration-resistant PC (mCRPC). CTCs from 22 patients were enumerated, stained for PC-relevant markers, and clustered based on morphometric and immunofluorescent features using machine learning. DNA from single CTCs, matched cfDNA, and buffy coats was sequenced using a targeted amplicon cancer hotspot panel. Radiomic analysis was performed on bone metastases identified on CT scans from the same patients. CTCs were detected in 77% of patients and clustered reproducibly. cfDNA sequencing had high sensitivity (98.8%) for germline variants compared to WBC. Shared and unique somatic variants in PC-related genes were detected in cfDNA in 45% of patients (MAF > 0.1%) and in CTCs in 92% of patients (MAF > 10%). Radiomic analysis identified a signature that strongly correlated with CTC count and plasma cfDNA level. Integration of cellular, molecular, and radiomic data in a multi-parametric approach is feasible, yielding complementary profiles that may enable more comprehensive non-invasive disease modeling and prediction.
Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury
Authors: Sánchez-Navarro Andrea , Martínez-Rojas Miguel Ángel , Albarrán-Godinez Adrián , Pérez-Villalva Rosalba , Auwerx Johan , de la Cruz Abigail , Noriega Lilia G. , Rosetti Florencia , Bobadilla Norma A.
Published: February 2022

Acute kidney injury (AKI) is a public health problem worldwide. Sirtuins are a family of seven NAD+-dependent deacylases, Overexpression of Sirtuin 1, 3, and 5 protect against AKI. However, the role of Sirtuin 7 (Sirt7) in AKI is not known. Here, we analyzed how Sirt7 deficient mice (KO-Sirt7) were affected by AKI. As expected, wild-type and Sirt7 heterozygotes mice that underwent renal ischemia/reperfusion (IR) exhibited the characteristic hallmarks of AKI: renal dysfunction, tubular damage, albuminuria, increased oxidative stress, and renal inflammation. In contrast, the KO-Sirt7+IR mice were protected from AKI, exhibiting lesser albuminuria and reduction in urinary biomarkers of tubular damage, despite similar renal dysfunction. The renoprotection in the Sirt7-KO+IR group was associated with reduced kidney weight, minor expression of inflammatory cytokines and less renal infiltration of inflammatory cells. This anti-inflammatory effect was related to diminished p65 expression and in its active phosphorylation, as well as by a reduction in p65 nuclear translocation. Sirt7 deficient mice are protected from AKI, suggesting that this histone deacetylase promotes tubular damage and renal inflammation. Therefore, our findings indicate that Sirt7 inhibitors may be an attractive therapeutic target to reduce NFκB signaling.
Characterization of Recruited Mononuclear Phagocytes following Corneal Chemical Injury
Authors: Lamy Ricardo , Wolf Marie , Bispo Claudia , Clay Selene M. , Zheng Siyu , Wolfreys Finn , Pan Peipei , Chan Matilda F.
Published: February 2022

Mononuclear phagocytes (MP) have central importance in innate immunity, inflammation, and fibrosis. Recruited MPs, such as macrophages, are plastic cells and can switch from an inflammatory to a restorative phenotype during the healing process. However, the role of the MPs in corneal wound healing is not completely understood. The purpose of this study is to characterize the kinetics of recruited MPs and evaluate the role of macrophage metalloelastase (MMP12) in the healing process, using an in vivo corneal chemical injury model. Unwounded and wounded corneas of wild-type (WT) and Mmp12−/− mice were collected at 1, 3, and 6 days after chemical injury and processed for flow cytometry analysis. Corneal MP phenotype significantly changed over time with recruited Ly6Chigh (proinflammatory) cells being most abundant at 1 day post-injury. Ly6Cint cells were highly expressed at 3 days post-injury and Ly6Cneg (patrolling) cells became the predominant cell type at 6 days post-injury. CD11c+ dendritic cells were abundant in corneas from Mmp12−/− mice at 6 days post-injury. These findings show the temporal phenotypic plasticity of recruited MPs and provide valuable insight into the role of the MPs in the corneal repair response, which may help guide the future development of MP-targeted therapies.
Design, Synthesis, and Anticancer Activity of a Selenium-Containing Galectin-3 and Galectin-9N Inhibitor
Authors: Di Gaetano Sonia , Pirone Luciano , Galdadas Ioannis , Traboni Serena , Iadonisi Alfonso , Pedone Emilia , Saviano Michele , Gervasio Francesco Luigi , Capasso Domenica
Published: February 2022

Galectins are soluble β-D-galactoside-binding proteins whose implication in cancer progression and disease outcome makes them prominent targets for therapeutic intervention. In this frame, the development of small inhibitors that block selectively the activity of galectins represents an important strategy for cancer therapy which is, however, still relatively underdeveloped. To this end, we designed here a rationally and efficiently novel diglycosylated compound, characterized by a selenoglycoside bond and the presence of a lipophilic benzyl group at both saccharide residues. The relatively high binding affinity of the new compound to the carbohydrate recognition domain of two galectins, galectin 3 and galectin 9, its good antiproliferative and anti-migration activity towards melanoma cells, as well as its anti-angiogenesis properties, pave the way for its further development as an anticancer agent.
Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages
Authors: Behera Ananyaashree , Jain Preeti , Ganguli Geetanjali , Biswas Mainak , Padhi Avinash , Pattanaik Kali Prasad , Nayak Barsa , Ergün Süleyman , Hagens Kristine , Redinger Natalja , Saqib Mohd , Mishra Bibhuti B. , Schaible Ulrich E. , Karnati Srikanth , Sonawane Avinash
Published: February 2022

Mycobacterium tuberculosis (Mtb) inhibits host oxidative stress responses facilitating its survival in macrophages; however, the underlying molecular mechanisms are poorly understood. Here, we identified a Mtb acetyltransferase (Rv3034c) as a novel counter actor of macrophage oxidative stress responses by inducing peroxisome formation. An inducible Rv3034c deletion mutant of Mtb failed to induce peroxisome biogenesis, expression of the peroxisomal β-oxidation pathway intermediates (ACOX1, ACAA1, MFP2) in macrophages, resulting in reduced intracellular survival compared to the parental strain. This reduced virulence phenotype was rescued by repletion of Rv3034c. Peroxisome induction depended on the interaction between Rv3034c and the macrophage mannose receptor (MR). Interaction between Rv3034c and MR induced expression of the peroxisomal biogenesis proteins PEX5p, PEX13p, PEX14p, PEX11β, PEX19p, the peroxisomal membrane lipid transporter ABCD3, and catalase. Expression of PEX14p and ABCD3 was also enhanced in lungs from Mtb aerosol-infected mice. This is the first report that peroxisome-mediated control of ROS balance is essential for innate immune responses to Mtb but can be counteracted by the mycobacterial acetyltransferase Rv3034c. Thus, peroxisomes represent interesting targets for host-directed therapeutics to tuberculosis.
Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders
Authors: Mahaling Binapani , Low Shermaine W. Y. , Beck Molly , Kumar Devesh , Ahmed Simrah , Connor Thomas B. , Ahmad Baseer , Chaurasia Shyam S.
Published: February 2022

Damage-associated molecular patterns (DAMPs) are endogenous danger molecules released from the extracellular and intracellular space of damaged tissue or dead cells. Recent evidence indicates that DAMPs are associated with the sterile inflammation caused by aging, increased ocular pressure, high glucose, oxidative stress, ischemia, mechanical trauma, stress, or environmental conditions, in retinal diseases. DAMPs activate the innate immune system, suggesting their role to be protective, but may promote pathological inflammation and angiogenesis in response to the chronic insult or injury. DAMPs are recognized by specialized innate immune receptors, such as receptors for advanced glycation end products (RAGE), toll-like receptors (TLRs) and the NOD-like receptor family (NLRs), and purine receptor 7 (P2X7), in systemic diseases. However, studies describing the role of DAMPs in retinal disorders are meager. Here, we extensively reviewed the role of DAMPs in retinal disorders, including endophthalmitis, uveitis, glaucoma, ocular cancer, ischemic retinopathies, diabetic retinopathy, age-related macular degeneration, rhegmatogenous retinal detachment, proliferative vitreoretinopathy, and inherited retinal disorders. Finally, we discussed DAMPs as biomarkers, therapeutic targets, and therapeutic agents for retinal disorders.
Biological Functions and Applications of Virus-Related Bacterial Nanoparticles: A Review
Authors: Nagakubo Toshiki
Published: February 2022

Accumulating evidence suggests that microorganisms produce various nanoparticles that exhibit a variety of biological functions. The structure of these bacterial nanoparticles ranges from membrane vesicles composed of membrane lipids to multicomponent proteinaceous machines. Of bacterial nanoparticles, bacterial phage tail-like nanoparticles, associated with virus-related genes, are found in bacteria from various environments and have diverse functions. Extracellular contractile injection systems (eCISs), a type of bacterial phage tail-like nanostructure, have diverse biological functions that mediate the interactions between the producer bacteria and target eukaryote. Known gram-negative bacterial eCISs can act as protein translocation systems and inject effector proteins that modulate eukaryotic cellular processes by attaching to the target cells. Further investigation of the functions of eCISs will facilitate the application of these nanomachines as nano-sized syringes in the field of nanomedicine and vaccine development. This review summarises the recent progress in elucidating the structures and biological functions of nanoparticles that resemble the tail components of phages that infect bacteria and discusses directions for future research to improve the clinical applicability of virus-related bacterial nanoparticles.
Characterization and Identification of a Ripening-Related Gene AaPG18 in Actinidia arguta
Authors: Li Yukuo , Huang Hailei , Abid Muhammad , Gu Hong , Fang Jinbao , Cheng Zhongping , Qi Xiujuan
Published: February 2022

Actinidia arguta (A. arguta) is a kind of climacteric fruit that quickly softens and limits fruit shelf-life and commercial value. Therefore, it is of great significance to develop kiwifruit genotypes with an extended shelf-life of fruit. However, the ripening and softening mechanisms remain unclear in A. arguta. Here, we demonstrated that a key polygalacturonase (PG)-encoding gene AaPG18 was involved in A. arguta ripening through the degradation of the cell wall. Fruits were harvested at three developmental stages (S1, S2, and S3) for high-throughput transcriptome sequencing, based on which two candidate transcripts c109562_g1 and c111961_g1 were screened. The genome-wide identification of the PG gene family assigned c109562_g1 and c111961_g1 to correspond to AaPG4 and AaPG18, respectively. The expression profiles of candidate genes at six preharvest stages of fruit showed significantly higher expression levels of AaPG18 than AaPG4, indicating AaPG18 might be a key gene during fruit ripening processes. The subcellular localization displayed AaPG18 was located at the cytoplasmic membrane. The transient overexpression of AaPG18 in strawberry and the following morphological observation suggested AaPG18 played a key role in maintaining the stability of cell morphology. The homologous transient transformation in A. arguta “RB-4” proved the crucial function of AaPG18 in fruit ripening processes by causing the rapid redness of the fruit, which was an indicator of fruit maturity. All in all, our results identified AaPG18 as a key candidate gene involved in cell wall degeneration, which provides a basis for the subsequent exploration of the molecular mechanisms underlying the ripening and softening of A. arguta fruit.
Conformational Dynamics of the Soluble and Membrane-Bound Forms of Interleukin-1 Receptor Type-1: Insights into Linker Flexibility and Domain Orientation
Authors: Luís João P. , Mata Ana I. , Simões Carlos J. V. , Brito Rui M. M.
Published: February 2022

Interleukin-1 receptor type 1 (IL-1R1) is a key player in inflammation and immune responses. This receptor regulates IL-1 activity in two forms: as a membrane-bound form and as a soluble ectodomain. The details and differences between the conformational dynamics of the membrane-bound and the soluble IL-1R1 ectodomains (ECDs) remain largely elusive. Here, we study and compare the structural dynamics of the soluble and membrane-bound IL-1R1-ECDs using molecular dynamics (MD) simulations, focusing on the flexible interdomain linker of the ECD, as well as the spatial rearrangements between the Ig-like domains of the ECD. To explore the membrane-bound conformations, a full-length IL-1R1 structural model was developed and subjected to classical equilibrium MD. Comparative analysis of multiple MD trajectories of the soluble and the membrane-bound IL-1R1-ECDs reveals that (i) as somewhat expected, the extent of the visited “open-to-closed” transitional states differs significantly between the soluble and membrane-bound forms; (ii) the soluble form presents open-closed transitions, sampling a wider rotational motion between the Ig-like domains of the ECD, visiting closed and “twisted” conformations in higher extent, whereas the membrane-bound form is characterized by more conformationally restricted states; (iii) interestingly, the backbone dihedral angles of residues Glu202, Glu203 and Asn204, located in the flexible linker, display the highest variations during the transition between discrete conformational states detected in IL-1R1, thus appearing to work as the “central wheel of a clock’s movement”. The simulations and analyses presented in this contribution offer a deeper insight into the structure and dynamics of IL-1R1, which may be explored in a drug discovery setting.
Estrogen Receptors Mediated Negative Effects of Estrogens and Xenoestrogens in Teleost Fishes—Review
Authors: Wojnarowski Konrad , Cholewińska Paulina , Palić Dušan , Bednarska Małgorzata , Jarosz Magdalena , Wiśniewska Iga
Published: February 2022

Estrogen receptors (ERs) play a key role in many biochemical and physiological processes, that are involved in maintaining organism homeostasis. At the most basic level, they can be divided into nuclear estrogen receptors and membrane estrogen receptors that imply their effect in two ways: slower genomic, and faster non-genomic. In these ways, estrogens and xenoestrogens can negatively affect animal health and welfare. Most of the available literature focuses on human and mammalian physiology, and clearly, we can observe a need for further research focusing on complex mutual interactions between different estrogens and xenoestrogens in aquatic animals, primarily fishes. Understanding the mechanisms of action of estrogenic compounds on the ERs in fishes and their negative consequences, may improve efforts in environmental protection of these animals and their environment and benefit society in return. In this review, we have summarized the ER-mediated effects of xenoestrogens and estrogens on teleost fishes metabolism, their carcinogenic potential, immune, circulatory, and reproductive systems.
More than Addiction—The Nucleus Accumbens Contribution to Development of Mental Disorders and Neurodegenerative Diseases
Authors: Bayassi-Jakowicka Martyna , Lietzau Grazyna , Czuba Ewelina , Patrone Cesare , Kowiański Przemysław
Published: February 2022

Stress and negative emotions evoked by social relationships and working conditions, frequently accompanied by the consumption of addictive substances, and metabolic and/or genetic predispositions, negatively affect brain function. One of the affected structures is nucleus accumbens (NAc). Although its function is commonly known to be associated with brain reward responses and addiction, a growing body of evidence also suggests its role in some mental disorders, such as depression and schizophrenia, as well as neurodegenerative diseases, such as Alzheimer’s, Huntington’s, and Parkinson’s. This may result from disintegration of the extensive connections based on numerous neurotransmitter systems, as well as impairment of some neuroplasticity mechanisms in the NAc. The consequences of NAc lesions are both morphological and functional. They include changes in the NAc’s volume, cell number, modifications of the neuronal dendritic tree and dendritic spines, and changes in the number of synapses. Alterations in the synaptic plasticity affect the efficiency of synaptic transmission. Modification of the number and structure of the receptors affects signaling pathways, the content of neuromodulators (e.g., BDNF) and transcription factors (e.g., pCREB, DeltaFosB, NFκB), and gene expression. Interestingly, changes in the NAc often have a different character and intensity compared to the changes observed in the other parts of the basal ganglia, in particular the dorsal striatum. In this review, we highlight the role of the NAc in various pathological processes in the context of its structural and functional damage, impaired connections with the other brain areas cooperating within functional systems, and progression of the pathological processes.
Ebola Entry Inhibitors Discovered from Maesa perlarius
Authors: Tsang Nga Yi , Li Wan-Fei , Varhegyi Elizabeth , Rong Lijun , Zhang Hong-Jie
Published: February 2022

Ebola virus disease (EVD), a disease caused by infection with Ebola virus (EBOV), is characterized by hemorrhagic fever and a high case fatality rate. With limited options for the treatment of EVD, anti-Ebola viral therapeutics need to be urgently developed. In this study, over 500 extracts of medicinal plants collected in the Lingnan region were tested against infection with Ebola-virus-pseudotyped particles (EBOVpp), leading to the discovery of Maesa perlarius as an anti-EBOV plant lead. The methanol extract (MPBE) of the stems of this plant showed an inhibitory effect against EBOVpp, with an IC50 value of 0.52 µg/mL, which was confirmed by testing the extract against infectious EBOV in a biosafety level 4 laboratory. The bioassay-guided fractionation of MPBE resulted in three proanthocyanidins (procyanidin B2 (1), procyanidin C1 (2), and epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin (3)), along with two flavan-3-ols ((+)-catechin (4) and (−)-epicatechin (5)). The IC50 values of the compounds against pseudovirion-bearing EBOV-GP ranged from 0.83 to 36.0 µM, with 1 as the most potent inhibitor. The anti-EBOV activities of five synthetic derivatives together with six commercially available analogues, including EGCG ((−)-epigallocatechin-3-O-gallate (8)), were further investigated. Molecular docking analysis and binding affinity measurement suggested the EBOV glycoprotein could be a potential molecular target for 1 and its related compounds.