bluuebunny/crossref_metadata_2025 huggingface dataset:
Age as a Dynamic Moderator of Relations between Exposure to Political Conflict and Mental Health in Belfast, Northern Ireland
Authors: Merrilees Christine E. , Taylor Laura K. , Goeke-Morey Marcie C. , Shirlow Peter , Cummings E. Mark
Published: July 2022

Identifying how, when, and under what conditions exposure to political conflict is associated with youth mental health problems is critical to developing programming to help youth exposed to various forms of political violence. The current study uses Time Varying Effects Modeling (TVEM) to examine how relations between exposure to ethno-politically motivated antisocial behavior and mental health problems change as a function of age in a sample of youth from Belfast, Northern Ireland. Young people (N = 583, Mage 16.51 wave 1, 17.23 wave 2) self-reported their exposure to sectarian antisocial behavior, nonsectarian antisocial behavior, and mental health problems as part of a longitudinal study of youth across multiple neighborhoods in Belfast. The results suggest mental health problems and associations with exposure to sectarian antisocial behavior change in nonlinear patterns throughout adolescence, with the strongest links between exposure to political conflict and mental health between ages 16 and 19. Significant relations between nonsectarian antisocial behavior and mental health problems were not indicated for the full sample but the results suggested a relation emerged in later adolescence for Protestant youth, the historical majority group. The value of this exploratory approach to examining relations between key context and psychological variables for youth in contexts of political tension and violence is discussed.
Prevalence of Adverse Childhood Experiences in the First Decade of Life: A Study in the Portuguese Cohort, Generation XXI
Authors: Soares Sara , Abrahamyan Armine , Amorim Mariana , Santos Ana Cristina , Fraga Sílvia
Published: July 2022

Adverse childhood experiences (ACEs) are a modifiable risk factor for diseases throughout life. This study estimates the prevalence of ACEs in children, addressing associated sociodemographic characteristics and examining the relationship of ACEs with the child’s health and behaviors. We used information on 5295 participants at 10 years old, of the birth cohort Generation XXI, established in Porto, Portugal. Children answered a self-administered questionnaire on ACEs, based on the original ACEs study. Principal component analysis was used to group correlated ACEs, and a score was computed to assess their cumulative effect. Overall, 96.2% of children reported having been exposed to at least one ACE. The most prevalent ACE was a household member shouting, yelling, or screaming at the child (57.7%). Boys were more likely than girls to report “abuse”, “school problems”, and “death/severe disease”. Low parental education, income, and unemployment were associated with an increased risk of “school problems”, “death/severe disease”, and “household dysfunction”. We observed that the dimensions of ACEs could be identified at 10 years of age. A disadvantaged socioeconomic environment was associated with dimensions of ACEs. These data illustrate the natural history of dimensions of ACEs and their potential social patterning.
The Effect of the Long-Term Calcipotriol/Betamethasone Dipropionate Local Therapy on Tissue Resident Memory Cells Markers in Psoriatic Eruptions
Authors: Kasprowicz-Furmańczyk Marta , Czerwińska Joanna , Placek Waldemar , Owczarczyk-Saczonek Agnieszka
Published: July 2022

Background: The natural course of psoriasis is characterized by the long-term persistence of lesions and a predilection for relapse in the same area. It is caused by the inherence of TRM (tissue resident memory T cells) in apparently healthy skin. These cells are able to initiate an inflammatory cascade and induce relapse of the disease. These cells are characterized by high resistance to damaging factors and apoptosis, which determines their longevity. Aim: The aim of our study was to evaluate the presence of TRM in psoriatic plaques before, during and after 12 weeks of therapy in patients treated with topical calcipotriol and betamethasone dipropionate (Cal/BD) foam. Methods: TRM markers (CD4, CD8, CD103, CD69, CD49, CXCR6) and tissue expression of cytokines (IL-17A, IL-22) in the lesional psoriatic skin from 10 patients compared to 10 healthy skin samples were estimated by immunohistochemistry. Biopsy samples from the area of the same psoriatic plaque were collected three times: before the initiation of therapy, 4 and 12 weeks after its initiation. Results: The presence of TRM markers in the epidermis and dermis of psoriatic lesions was significantly higher when compared to the skin of control group patients. A reduction in the expression of the characteristic TRM markers (CD8, CD4, CD103, CD69, CXCR6, IL-17A and IL-22) was observed in the epidermis on week 12 of therapy, while a depletion in the expression of TRM in the dermis was demonstrated only in CD4 and IL-22. Conclusions: Topical treatment with Cal/BD foam significantly decreased the expression of TRM markers mainly in the epidermis, and to a lesser extent in the dermis, during the 12-week observation period. It probably results from a worse penetration of the drug into the dermis and the effect of the preparation mainly on the epidermis. The persistence of a high expression of TRM markers in the dermis may result in the rapid recurrence of lesions after discontinuation of topical treatment.
Moral Distress Events and Emotional Trajectories in Nursing Narratives during the COVID-19 Pandemic
Authors: Lemmo Daniela , Vitale Roberta , Girardi Carmela , Salsano Roberta , Auriemma Ersilia
Published: July 2022

The COVID-19 pandemic produced several ethical challenges for nurses, impacting their mental health and moral distress. In the moral distress model the categories of events related to moral distress are: constraint, dilemma, uncertainty, conflict, and tension, each one related to different emotions. This study explored moral events’ memories and emotions in narratives of a sample of 43 Italian nurses who worked during the COVID-19 pandemic. We constructed an ad-hoc narrative interview asking nurses to narrate the memory, and the associated emotion, of an event in which they felt they could not do the right thing for the patient. We conducted a theory-driven analysis, using the categories proposed by the literature, identifying the main emotion for each category. Results show that 36 memories of events are representative of moral distress; among these, 7 are representative of none of the categories considered, and we categorized them as moral compromise. The main emotional trajectories are powerlessness, worthlessness, anger, sadness, guilt, and helplessness. From a clinical psychological point of view, our findings highlight the narration of the memories of moral events as a tool to use in the ethical sense-making of critical experiences, in order to promote well-being and moral resilience among nurses in emergency situations.
Analysis of Spatial and Temporal Changes of AQI in Wuhan City under the Urban Blockade of COVID-19 Pandemic
Authors: Yang Nai , Sun Xin , Chao Yi
Published: July 2022

Wuhan was the primary city in the world to adopt lockdown measures during the Coronavirus Disease 2019 pandemic. The influence of the abrupt halt of human activities on the air quality of Wuhan is a subject of considerable attention. This study is based on air quality data from 21 monitoring stations in Wuhan from 2016 to 2020. The lag effect and seasonal factors of AQI were taken into account to analyze the changes in air quality in Wuhan under the influence of the pandemic blockade. The results showed the following during the city closure: (1) A lagging effect is observed in air quality changes, with the change point occurring on the 14th day after the city closure; (2) the air quality index is substantially decreased, demonstrating a reduction in spatial differences; (3) NO2, PM10, and PM2.5 significantly decreased whilst O3 increased, and SO2 and CO did not change significantly; (4) except for the insignificant changes in spatial differences of PM10, all pollutants demonstrated a changing pattern of decreasing geographical differences. This paper provides a reference for studying the influence of human activities on the natural environment.
Essential Factors for a Healthy Microbiome: A Scoping Review
Authors: Grace-Farfaglia Patricia , Frazier Heather , Iversen Maura Daly
Published: July 2022

Recent discoveries of the purpose and potential of microbial interactions with humans have broad implications for our understanding of metabolism, immunity, the host–microbe genetic interactions. Bioavailability and bioaccessibility of phytonutrients in foods not only enrich microbial diversity in the lower human gastrointestinal tract (GIT) but also direct the functioning of the metagenome of the microbiota. Thus, healthy choices must include foods that contain nutrients that satisfy both the needs of humans and their microbes. Physical activity interventions at a moderate level of intensity have shown positive effects on metabolism and the microbiome, while intense training (>70% VO2max) reduces diversity in the short term. The microbiome of elite endurance athletes is a robust producer of short-chain fatty acids. A lifestyle lacking activity is associated with the development of chronic disease, and experimental conditions simulating weightlessness in humans demonstrate loss of muscle mass occurring in conjunction with a decline in gut short-chain fatty acid (SCFA) production and the microbes that produce them. This review summarizes evidence addressing the relationship between the intestinal microbiome, diet, and physical activity. Data from the studies reviewed suggest that food choices and physical fitness in developed countries promote a resource “curse” dilemma for the microbiome and our health.
eHealth Literacy in German Skin Cancer Patients
Authors: Stege Henner , Schneider Sara , Forschner Andrea , Eigentler Thomas , Nashan Dorothée , Huening Svea , Meiss Frank , Lehr Saskia , Kaatz Martin , Kuchen Robert , Kaehler Katharina C. , Haist Maximilian , Huebner Jutta , Loquai Carmen
Published: July 2022

The global incidence of skin cancer has steadily increased in recent years, and malignant melanoma still has one of the fastest-growing incidence rates among all malignant tumors in the western world. Thus, newly diagnosed patients have an increased need for health information concerning their disease. Using a standardized questionnaire, our study aims to investigate our patients’ primary sources of health-related information as well as their self-proclaimed eHealth literacy. We received 714 questionnaires. Regardless of age, the primary source of information was the treating dermato-oncologist, followed by the treating general practitioner and the Internet. However, with increasing age, the usage of the Internet decreased. Hence, younger participants were better equipped to find health-related information while using the Internet. Additionally, comprehending health-related information and gaining medical knowledge was significantly increased in better-educated participants. Overall, our study shows that with increased use of eHealth services, accessing web-based information increased, correlating with a better eHealth literacy of our patients. eHealth technologies are increasingly becoming more prevalent as a primary source of information in our modern health care system. Thus, it is crucial to educate cancer patients in eHealth literacy to make autonomous, informed decisions and gain more confidence in dealing with their disease.
Improved Electron Efficiency of Zero-Valent Iron towards Cr(VI) Reduction after Sequestering in Al2O3 Microspheres
Authors: Wang Chuan , Wang Sha , Song Cheng , Liu Hong , Yang Jingxin
Published: July 2022

Zero-valent iron (ZVI) is widely used for groundwater remediation, but suffers from high electron consumption because of its free contact with non-target substrates such as O2. Here, ZVI-ALOX particles were prepared via in situ NaBH4 aqueous-phase reduction of ferrous ions (Fe2+) preabsorbed into Al2O3 microspheres. The electron efficiency (EE) and long-term performance of the material were improved by sequestering ZVI in the interspace of the Al2O3 microspheres (ZVI-ALOX). During long-term (350 days) continuous flow, Cr(VI) was removed to below the detection limit for over 23 days. Based on the high reactivity of ZVI towards Cr(VI), the EE of ZVI-ALOX was evaluated by measuring its Cr(VI) removal efficiency at neutral pH and comparing it with that of ZVI. The results showed that the EE of ZVI-ALOX during long-term continuous flow could reach 39.1%, which was much higher than that of ZVI (8.68%). The long-term continuous flow results also demonstrated that treatment of the influent solution achieved higher EE values than in the batch mode, where the presence of dissolved oxygen reduced EE values. At lower pollutant concentrations, the sequestering of ZVI was beneficial to its performance and long-term utility. In addition, measurement of the acute toxicity of treated column effluent using the indicator organism Photobacterium phosphoreum T3 showed that ZVI-ALOX could reduce the toxicity of 5 mg/L Cr(VI) solution by ~70% in 350 d. The results from this study provide a basis for the development of permeable reactive barriers for groundwater remediation based on sequestered ZVI.
Exploring Contributing Factors of Solitary Drinking among Hong Kong Chinese Adolescents and Young Adults: A Descriptive Phenomenology
Authors: Ho Ka-Yan , Lam Katherine-Ka-Wai , Wu Cynthia-Sau-Ting , Tong Man-Nok , Tang Lai-Ngo , Mak Yim-Wah
Published: July 2022

Adolescents and young adults mostly drink alcohol because of social activities. However, some drink outside of normative social contexts, exhibiting a behaviour pattern known as solitary drinking. Increasing evidence indicates that solitary drinking is strongly associated with problematic drinking in adolescents and young adults. However, it remains unclear why individuals initiate and maintain this drinking habit. To address this gap in the existing literature, the current study explored the factors contributing to solitary drinking in this population. Descriptive phenomenology was used. A convenience sample of 44 solitary drinkers aged between 10 and 24 were invited to undergo individual semi-structured interviews. All interviews were audio-recorded and transcribed verbatim. The data were analysed by two researchers separately using Colaizzi’s method. Using qualitative descriptions, the following factors were identified as explaining the initiation and continuation of solitary drinking among adolescents and young adults: (1) enhancement and coping drinking motives, (2) social discomfort, (3) reduced self-control, (4) automatic mental process, and (5) a desperate response to stressors. Since reduced self-control plays an important role in long-term addiction, future studies should be conducted to determine potential applications of mindfulness-based interventions to improve self-control, which may prevent the progression from solitary drinking to alcohol use disorder.
Validity and Reliability of the Leomo Motion-Tracking Device Based on Inertial Measurement Unit with an Optoelectronic Camera System for Cycling Pedaling Evaluation
Authors: Plaza-Bravo José Manuel , Mateo-March Manuel , Sanchis-Sanchis Roberto , Pérez-Soriano Pedro , Zabala Mikel , Encarnación-Martínez Alberto
Published: July 2022

Background: The use of inertial measurement sensors (IMUs), in the search for a more ecological measure, is spreading among sports professionals with the aim of improving the sports performance of cyclists. The kinematic evaluation using the Leomo system (TYPE-R, Leomo, Boulder, CO, USA) has become popular. Purpose: The present study aimed to evaluate the reliability and validity of the Leomo system by measuring the angular kinematics of the lower extremities in the sagittal plane during pedaling at different intensities compared to a gold-standard motion capture camera system (OptiTrack, Natural Point, Inc., Corvallis, OR, USA). Methods: Twenty-four elite cyclists recruited from national and international cycling teams performed two 6-min cycles of cycling on a cycle ergometer at two different intensities (first ventilatory threshold (VT1) and second ventilatory threshold (VT2)) in random order, with a 5 min rest between intensity conditions. The reliability and validity of the Leomo system versus the motion capture system were evaluated. Results: Both systems showed high validity and were consistently excellent in foot angular range Q1 (FAR (Q1)) and foot angular range (FAR) (ICC-VT1 between 0.91 and 0.95 and ICC-VT2 between 0.88 and 0.97), while the variables leg angular range (LAR) and pelvic angle showed a modest validity (ICC-VT1 from 0.52 to 0.71 and ICC-VT2 between 0.61 and 0.67). Compared with Optitrack, Leomo overestimated all the variables, especially the LAR and pelvic angle values, in a range between 12 and 15°. Conclusions: Leomo is a reliable and valid tool for analyzing the ranges of motion of the cyclist’s lower limbs in the sagittal plane, especially for the variables FAR (Q1) and FAR. However, its systematic error for FAR and Pelvic Angle values must be considered in sports performance analysis.
Ragging, a Form of University Violence in Sri Lanka—Prevalence, Self-Perceived Health Consequences, Help-Seeking Behavior and Associated Factors
Authors: Wickramasinghe Ayanthi , Essén Birgitta , Ziaei Shirin , Surenthirakumaran Rajendra , Axemo Pia
Published: July 2022

Ragging is an initiation ritual practiced in Sri Lankan universities for generations, although research is scarce. This practice has several adverse consequences such as physical, psychological, and behavioral effects and increased university dropouts. The aim of this study was to investigate the prevalence of different types of ragging: emotional/verbal, physical and sexual ragging, self-perceived health consequences, help-seeking behavior, and factors associated with the experience of ragging. A cross-sectional study was conducted among 623, second- and third-year students from the medical, and technology faculties in Jaffna University. Bivariate associations were assessed using chi-squared tests. Logistic regression was used to evaluate factors associated with any type of ragging. Ragging was experienced by 59% of the students, emotional/verbal ragging being the most common. A total of 54% of students suffered one or more health consequences and mainly sought help from friends and family, with few seeking formal help. Factors associated with any type of ragging were faculty and year of study. This study emphasizes the urgent need to address this public health problem. It is important that there are adequate student support services, planning and implementation of effective interventions, as well as ensuring that existing policies are strengthened, to reduce or eliminate ragging in Sri Lanka.
Machine Learning Quantitative Structure–Property Relationships as a Function of Ionic Liquid Cations for the Gas-Ionic Liquid Partition Coefficient of Hydrocarbons
Authors: Toots Karl Marti , Sild Sulev , Leis Jaan , Acree William E. , Maran Uko
Published: July 2022

Ionic liquids (ILs) are known for their unique characteristics as solvents and electrolytes. Therefore, new ILs are being developed and adapted as innovative chemical environments for different applications in which their properties need to be understood on a molecular level. Computational data-driven methods provide means for understanding of properties at molecular level, and quantitative structure–property relationships (QSPRs) provide the framework for this. This framework is commonly used to study the properties of molecules in ILs as an environment. The opposite situation where the property is considered as a function of the ionic liquid does not exist. The aim of the present study was to supplement this perspective with new knowledge and to develop QSPRs that would allow the understanding of molecular interactions in ionic liquids based on the structure of the cationic moiety. A wide range of applications in electrochemistry, separation and extraction chemistry depends on the partitioning of solutes between the ionic liquid and the surrounding environment that is characterized by the gas-ionic liquid partition coefficient. To model this property as a function of the structure of a cationic counterpart, a series of ionic liquids was selected with a common bis-(trifluoromethylsulfonyl)-imide anion, [Tf2N]−, for benzene, hexane and cyclohexane. MLR, SVR and GPR machine learning approaches were used to derive data-driven models and their performance was compared. The cross-validation coefficients of determination in the range 0.71–0.93 along with other performance statistics indicated a strong accuracy of models for all data series and machine learning methods. The analysis and interpretation of descriptors revealed that generally higher lipophilicity and dispersion interaction capability, and lower polarity in the cations induces a higher partition coefficient for benzene, hexane, cyclohexane and hydrocarbons in general. The applicability domain analysis of models concluded that there were no highly influential outliers and the models are applicable to a wide selection of cation families with variable size, polarity and aliphatic or aromatic nature.
Nicotinamide Mononucleotide and Coenzyme Q10 Protects Fibroblast Senescence Induced by Particulate Matter Preconditioned Mast Cells
Authors: Chang Tsong-Min , Yang Ting-Ya , Huang Huey-Chun
Published: July 2022

Particulate matter (PM) pollutants impose a certain degree of destruction and toxicity to the skin. Mast cells in the skin dermis could be activated by PMs that diffuse across the blood vessel after being inhaled. Mast cell degranulation in the dermis provides a kind of inflammatory insult to local fibroblasts. In this study, we evaluated human dermal fibroblast responses to conditioned medium from KU812 cells primed with PM. We found that PM promoted the production of proinflammatory cytokines in mast cells and that the cell secretome induced reactive oxygen species and mitochondrial reactive oxygen species production in dermal fibroblasts. Nicotinamide mononucleotide or coenzyme Q10 alleviated the generation of excessive ROS and mitochondrial ROS induced by the conditioned medium from PM-activated KU812 cells. PM-conditioned medium treatment increased the NF-κB expression in dermal fibroblasts, whereas NMN or Q10 inhibited p65 upregulation by PM. The reduced sirtuin 1 (SIRT 1) and nuclear factor erythroid 2-related Factor 2 (Nrf2) expression induced by PM-conditioned medium was reversed by NMN or Q10 in HDFs. Moreover, NMN or Q10 attenuated the expression of senescent β-galactosidase induced by PM-conditioned KU812 cell medium. These findings suggest that NMN or Q10 ameliorates PM-induced inflammation by improving the cellular oxidative status, suppressing proinflammatory NF-κB, and promoting the levels of the antioxidant and anti-inflammatory regulators Nrf2 and SIRT1 in HDFs. The present observations help to understand the factors that affect HDFs in the dermal microenvironment and the therapeutic role of NMN and Q10 as suppressors of skin aging.
Cannabinerol and NSC-34 Transcriptomic Analysis: Is the Dose Who Makes Neuronal Differentiation?
Authors: Valeri Andrea , Chiricosta Luigi , Gugliandolo Agnese , Pollastro Federica , Salamone Stefano , Zingale Valeria Domenica , Silvestro Serena , Mazzon Emanuela
Published: July 2022

Cannabis sativa L. proved to be a source of several phytocompounds able to help patients facing different diseases. Moreover, these phytocompounds can help ameliorate general conditions and control certain unpleasant effects of diseases. Some cannabinoids, however, provided more benefits applicable to settings other than palliative care. Using the NSC-34 cell line, we evaluated the barely known phytocompound named cannabinerol (CBNR) at different doses, in order to understand its unique characteristics and the ones shared with other cannabinoids. The transcriptomic analysis suggests a possible ongoing neuronal differentiation, principally due to the activation of cannabinoid receptor 1 (CB1), to which the phosphorylation of serine–threonine protein kinase (Akt) followed, especially between 20 and 7.5 µM. The increase of Neurod1 and Map2 genes at 7.5 µM, accompanied by a decrease of Vim, as well as the increase of Syp at all the other doses, point toward the initiation of differentiation signals. Our preliminary results indicate CBNR as a promising candidate to be added to the list of cannabinoids with neuronal differentiation-enhancer properties. However, further studies are needed to confirm this initial insight.
Tumor-Localized Administration of α-GalCer to Recruit Invariant Natural Killer T Cells and Enhance Their Antitumor Activity against Solid Tumors
Authors: Li Yan-Ruide , Zhou Yang , Wilson Matthew , Kramer Adam , Hon Ryan , Zhu Yichen , Fang Ying , Yang Lili
Published: July 2022

Invariant natural killer T (iNKT) cells have the capacity to mount potent anti-tumor reactivity and have therefore become a focus in the development of cell-based immunotherapy. iNKT cells attack tumor cells using multiple mechanisms with a high efficacy; however, their clinical application has been limited because of their low numbers in cancer patients and difficulties in infiltrating solid tumors. In this study, we aimed to overcome these critical limitations by using α-GalCer, a synthetic glycolipid ligand specifically activating iNKT cells, to recruit iNKT to solid tumors. By adoptively transferring human iNKT cells into tumor-bearing humanized NSG mice and administering a single dose of tumor-localized α-GalCer, we demonstrated the rapid recruitment of human iNKT cells into solid tumors in as little as one day and a significantly enhanced tumor killing ability. Using firefly luciferase-labeled iNKT cells, we monitored the tissue biodistribution and pharmacokinetics/pharmacodynamics (PK/PD) of human iNKT cells in tumor-bearing NSG mice. Collectively, these preclinical studies demonstrate the promise of an αGC-driven iNKT cell-based immunotherapy to target solid tumors with higher efficacy and precision.
Extensive Sampling of Molecular Dynamics Simulations to Identify Reliable Protein Structures for Optimized Virtual Screening Studies: The Case of the hTRPM8 Channel
Authors: Gervasoni Silvia , Talarico Carmine , Manelfi Candida , Pedretti Alessandro , Vistoli Giulio , Beccari Andrea R.
Published: July 2022

(1) Background: Virtual screening campaigns require target structures in which the pockets are properly arranged for binding. Without these, MD simulations can be used to relax the available target structures, optimizing the fine architecture of their binding sites. Among the generated frames, the best structures can be selected based on available experimental data. Without experimental templates, the MD trajectories can be filtered by energy-based criteria or sampled by systematic analyses. (2) Methods: A blind and methodical analysis was performed on the already reported MD run of the hTRPM8 tetrameric structures; a total of 50 frames underwent docking simulations by using a set of 1000 ligands including 20 known hTRPM8 modulators. Docking runs were performed by LiGen program and involved the frames as they are and after optimization by SCRWL4.0. For each frame, all four monomers were considered. Predictive models were developed by the EFO algorithm based on the sole primary LiGen scores. (3) Results: On average, the MD simulation progressively enhances the performance of the extracted frames, and the optimized structures perform better than the non-optimized frames (EF1% mean: 21.38 vs. 23.29). There is an overall correlation between performances and volumes of the explored pockets and the combination of the best performing frames allows to develop highly performing consensus models (EF1% = 49.83). (4) Conclusions: The systematic sampling of the entire MD run provides performances roughly comparable with those previously reached by using rationally selected frames. The proposed strategy appears to be helpful when the lack of experimental data does not allow an easy selection of the optimal structures for docking simulations. Overall, the reported docking results confirm the relevance of simulating all the monomers of an oligomer structure and emphasize the efficacy of the SCRWL4.0 method to optimize the protein structures for docking calculations.
Tracking Prostate Carcinogenesis over Time through Urine Proteome Profiling in an Animal Model: An Exploratory Approach
Authors: Moreira-Pais Alexandra , Nogueira-Ferreira Rita , Reis Stephanie , Aveiro Susana , Barros António , Melo Tânia , Matos Bárbara , Duarte José , Seixas Fernanda , Domingues Pedro , Amado Francisco , Fardilha Margarida , Oliveira Paula , Ferreira Rita , Vitorino Rui
Published: July 2022

Prostate cancer (PCa) is one of the most lethal diseases in men, which justifies the search for new diagnostic tools. The aim of the present study was to gain new insights into the progression of prostate carcinogenesis by analyzing the urine proteome. To this end, urine from healthy animals and animals with prostate adenocarcinoma was analyzed at two time points: 27 and 54 weeks. After 54 weeks, the incidence of pre-neoplastic and neoplastic lesions in the PCa animals was 100%. GeLC-MS/MS and subsequent bioinformatics analyses revealed several proteins involved in prostate carcinogenesis. Increased levels of retinol-binding protein 4 and decreased levels of cadherin-2 appear to be characteristic of early stages of the disease, whereas increased levels of enolase-1 and T-kininogen 2 and decreased levels of isocitrate dehydrogenase 2 describe more advanced stages. With increasing age, urinary levels of clusterin and corticosteroid-binding globulin increased and neprilysin levels decreased, all of which appear to play a role in prostate hyperplasia or carcinogenesis. The present exploratory analysis can be considered as a starting point for studies targeting specific human urine proteins for early detection of age-related maladaptive changes in the prostate that may lead to cancer.
A Broad-Based Characterization of a Cell-Penetrating, Single Domain Camelid Bi-Specific Antibody Monomer That Targets STAT3 and KRAS Dependent Cancers
Authors: Singh Sunanda , Murillo Genoveva , Richner Justin , Singh Samara P. , Berleth Erica , Kumar Vijay , Mehta Rajendra , Ramiya Vijay , Parihar Ashutosh S.
Published: July 2022

STAT3 and KRAS regulate cell proliferation, survival, apoptosis, cell migration, and angiogenesis. Aberrant expression of STAT3 and mutant active forms of KRAS have been well-established in the induction and maintenance of multiple cancers. STAT3 and KRAS mutant proteins have been considered anti-cancer targets; however, they are also considered to be clinically “undruggable” intracellular molecules, except for KRAS(G12C). Here we report a first-in-class molecule, a novel, single domain camelid VHH antibody (15 kDa), SBT-100, that binds to both STAT3 and KRAS and can penetrate the tumor cell membrane, and significantly inhibit cancer cell growth. Additionally, SBT-100 inhibits KRAS GTPase activity and downstream phosphorylation of ERK in vitro. In addition, SBT-100 inhibits the growth of multiple human cancers in vitro and in vivo. These results demonstrate the feasibility of targeting hard-to-reach aberrant intracellular transcription factors and signaling proteins simultaneously with one VHH to improve cancer therapies.
Comparing Worldwide, National, and Independent Notifications about Adverse Drug Reactions Due to COVID-19 Vaccines
Authors: Branda Francesco , Tosi Davide
Published: July 2022

The rapid development of effective vaccines against COVID-19 is an extraordinary achievement. However, no medical product can ever be considered risk-free. Several countries have a pharmacovigilance system that detects, assesses, understands, and prevents possible adverse effects of a drug. To benefit from such huge data sources, specialists and researchers need advanced big data analysis tools able to extract value and find valuable insights. This paper defines a general framework for a pharmaceutical data analysis application that provides a predefined (but extensible) set of functions for each data processing step (i.e., data collection, filtering, enriching, analysis, and visualization). As a case study, we present here an analysis of the potential side effects observed following the administration of the COVID-19 vaccines. The experimental evaluation shows that: (i) most adverse events can be classified as non-serious and concern muscle/joint pain, chills and nausea, headache, and fatigue; (ii) the notification rate is higher in the age group 20–39 years and decreases in older age groups and in very young people.
Particularities of the Hermetia illucens (L.) (Diptera: Stratiomyidae) Ovipositing Behavior: Practical Applications
Authors: Bogdan Georgescu , Ioan Struți Dănuț , Mihai Șuteu , Elena Moldovan Lavinia , Vasile Moldovan Dorin , Mihaela Boaru Anca
Published: July 2022

The industrial rearing of Hermetia illucens offers sustainable solutions to the acute challenges of modern society associated with the accumulation of increasing amounts of organic waste, the substantial reduction of natural ocean fish stocks, and the imminent food crisis. Detailed knowledge of the reproductive particularities and reproductive behavior of the species is essential for increasing the efficiency of the breeding technology. This study aimed to identify the affinity shown by females regarding the size of the oviposition slots (1, 2, 3, 4 and 5 mm), the vertical distribution of the ovipositing rate, and the influence of the substrate’s moisture on ovipositing behavior (dry matter/water: 1:0.5; 1:1; 1:1.5; 1:2). Over 90% of females oviposited in the 1-, 2- and 3-mm slots, with most of the eggs (58.57%) being oviposited in the 1-mm slots. There was a positive correlation between the size of the oviposition slots and the average weight of the clutches (r = 0.985). The vertical distribution of ovipositing followed a fluctuating trend, with a tendency to oviposit closer to the attractive substrate. The females avoided ovipositing close to substrates with low humidity (1:0.5); indeed, only 6.8% oviposited under these conditions, the differences being significant compared to substrates with higher humidity (p < 0.001). The vast majority of females (43.2%) oviposited on substrates with an average humidity of 1:1 (p < 0.001). These results provide new insights into the ovipositing behavior of H. illucens, which allow for a differentiated harvest of large-sized clutches, providing practical applications with significant impact on the economic efficiency of the species’ industrial growth technology.
Aerodynamic Load Prediction on a Patrol Vessel Using Computational Fluid Dynamics
Authors: Islam Hafizul , Sutulo Serge , Guedes Soares C.
Published: July 2022

Aerodynamic loads and moments on a naval patrol vessel are investigated using computational fluid dynamic simulations based on the OpenFOAM solver. After the initial turbulence, time, and grid dependency study, model scale simulations were performed for a wide range of inflow angles to predict aerodynamic forces and moments acting on the vessel at different heading conditions. For validation, model scale results were compared with wind tunnel data for similar hull forms. Finally, full-scale simulations were performed for a few cases to investigate possible scale effects on simulation results. The revealed scale effect turned out significant only for the yaw moment response. In this study, we aimed to produce reliable aerodynamic load data for the high-speed vessel, which is essential to developing reliable manoeuvring models. We conclude that Computational Fluid Dynamics is capable of providing reliable aerodynamic load predictions for high-speed vessels with sophisticated superstructures, in an economical manner.
Sea Level Change in the Canary Current System during the Satellite Era
Authors: Marrero-Betancort Nerea , Marcello Javier , Rodríguez-Esparragón Dionisio , Hernández-León Santiago
Published: July 2022

Understanding the causes of global sea level rise is considered as an important goal of climate research on a regional scale, especially around islands, owing to their vulnerability to this phenomenon. In the case of the Canary Islands, these alterations entail an increase in territorial risks. The Canary Islands span the transitional zone linking the Northwest African upwelling system and the open ocean waters of the subtropical gyre. Here, we used satellite altimeter data to perform a detailed statistical analysis of sea level anomaly from 1993 to 2019. A seasonal study was carried out at two different regions and sea level anomaly was compared with temperature variability in the area. A total rise in the sea level of around 7.94 cm was obtained for the last 27 years in both areas. Sea level anomaly was strongly influenced by sea surface temperature, as expected. In addition, we found differences between the annual cycle in the open ocean and the upwelling zone, showing different patterns in both sites. The expected increase in sea level for the year 2050 in the coastal zone of the archipelago was estimated to be 18.10 cm, affecting the coastal economy of the islands, which is strongly based on the use of beaches for tourism.
Quantifying Spatial Heterogeneity of Tumor-Infiltrating Lymphocytes to Predict Survival of Individual Cancer Patients
Authors: Suwalska Aleksandra , Zientek Lukasz , Polanska Joanna , Marczyk Michal
Published: July 2022

Tumor-infiltrating lymphocytes (TILs), identified on HE-stained histopathological images in the cancer area, are indicators of the adaptive immune response against cancers and play a major role in personalized cancer immunotherapy. Recent works indicate that the spatial organization of TILs may be prognostic of disease-specific survival and recurrence. However, there are a limited number of methods that were proposed and tested in analyses of the spatial structure of TILs. In this work, we evaluated 14 different spatial measures, including the one developed for other omics data, on 10,532 TIL maps from 23 cancer types in terms of reproducibility, uniqueness, and impact on patient survival. For each spatial measure, 16 different scenarios for the definition of prognostic factor were tested. We found no difference in survival prediction when TIL maps were stored as binary images or continuous TIL probability scores. When spatial measures were discretized into a low and high category, a higher correlation with survival was observed. Three measures with the highest cancer prognosis capability were spatial autocorrelation, GLCM M1, and closeness centrality. Most of the tested measures could be further tuned to increase prediction performance.
Revisiting the Risk Factors for Endometriosis: A Machine Learning Approach
Authors: Blass Ido , Sahar Tali , Shraibman Adi , Ofer Dan , Rappoport Nadav , Linial Michal
Published: July 2022

Endometriosis is a condition characterized by implants of endometrial tissues into extrauterine sites, mostly within the pelvic peritoneum. The prevalence of endometriosis is under-diagnosed and is estimated to account for 5–10% of all women of reproductive age. The goal of this study was to develop a model for endometriosis based on the UK-biobank (UKB) and re-assess the contribution of known risk factors to endometriosis. We partitioned the data into those diagnosed with endometriosis (5924; ICD-10: N80) and a control group (142,723). We included over 1000 variables from the UKB covering personal information about female health, lifestyle, self-reported data, genetic variants, and medical history prior to endometriosis diagnosis. We applied machine learning algorithms to train an endometriosis prediction model. The optimal prediction was achieved with the gradient boosting algorithms of CatBoost for the data-combined model with an area under the ROC curve (ROC-AUC) of 0.81. The same results were obtained for women from a mixed ethnicity population of the UKB (7112; ICD-10: N80). We discovered that, prior to being diagnosed with endometriosis, affected women had significantly more ICD-10 diagnoses than the average unaffected woman. We used SHAP, an explainable AI tool, to estimate the marginal impact of a feature, given all other features. The informative features ranked by SHAP values included irritable bowel syndrome (IBS) and the length of the menstrual cycle. We conclude that the rich population-based retrospective data from the UKB are valuable for developing unified machine learning endometriosis models despite the limitations of missing data, noisy medical input, and participant age. The informative features of the model may improve clinical utility for endometriosis diagnosis.
Zombie Firms during and after Crisis
Authors: Blažková Ivana , Chmelíková Gabriela
Published: July 2022

The phenomenon of zombie firms is gaining the attention of economists across different countries of the world; the increased interest is particularly evident after periods of economic crises. In our study, we focus on the development of zombie firms in the period before and after the 2008 crisis within two different economies, i.e., Germany and the Czech Republic, to provide insight into how different conditions and the overall economic context affect the fact that companies are more prone to becoming zombie firms. We implemented a difference-in-differences regression model to estimate the treatment effect by comparing the change (difference) in the differences in observed outcomes between these two countries. The data were obtained from two databases—the database Albertina by Bisnode a.s. providing financial statements of enterprises in the Czech Republic, and the database provided by Creditreform AG, which includes annual report data for a large sample of German companies. The dataset of German enterprises included 1,444,698 observations, i.e., 338,923 firms, and the dataset of Czech enterprises included 2,139,462 observations, i.e., 523,542 firms, both across the years 2000–2016, i.e., the data sample covered the period before and after the 2008 crisis. The different development of the share of zombie firms after the great financial crisis between Germany and the Czech Republic was proven as statistically significant. The findings confirm Germany is a country with a more stable economy and with a significantly lower risk of zombie firms’ persistence, while the Czech Republic is at the level of the European average in terms of zombie share. The results also suggest an influence of post-crisis monetary policy on companies and the possible link between low interest rates and a growing share of zombies.
Using Marginal Land Resources to Solve the Shortage of Rural Entrepreneurial Land in China
Authors: Zhu Lei , Yang Chenyujing , Zhang Yuanyuan , Xue Yongji
Published: July 2022

Rural entrepreneurship is an important way to promote rural revitalization, narrow the gap between urban and rural areas and increase farmers’ income. With the acceleration of urbanization, land resources have become scarcer than capital, technology, and human resources in China. At the same time, food-security pressure makes the stock of rural construction land in China extremely tight. Therefore, how to meet the demand for rural entrepreneurial land without touching the red line of cultivated land or occupying the existing rural construction land available is an urgent problem that needs to be solved. Reviewing the relevant literature, it was found that some regions in China innovated the way of “capital compensation and land equity” to obtain the use rights of marginal land resources such as idle farmhouses, workshops and school buildings and transformed them into entrepreneurial development spaces, which alleviated the scarcity of entrepreneurial construction land. At the same time, it also promoted the local residents’ employment and economic development. We believe that according to the social and economic conditions of different regions, the in-depth tapping of rural marginalized land is an effective way to solve the lack of development space for rural entrepreneurship and should be implemented worldwide.
Estimation of Heavy Metal Content in Soil Based on Machine Learning Models
Authors: Shi Shuaiwei , Hou Meiyi , Gu Zifan , Jiang Ce , Zhang Weiqiang , Hou Mengyang , Li Chenxi , Xi Zenglei
Published: July 2022

Heavy metal pollution in soil is threatening the ecological environment and human health. However, field measurement of heavy metal content in soil entails significant costs. Therefore, this study explores the estimation method of soil heavy metals based on remote sensing images and machine learning. To accurately estimate the heavy metal content, we propose a hybrid artificial intelligence model integrating least absolute shrinkage and selection operator (LASSO), genetic algorithm (GA) and error back propagation neural network (BPNN), namely the LASSO-GA-BPNN model. Meanwhile, this study compares the accuracy of the LASSO-GA-BPNN model, SVR (Support Vector Regression), RF (Random Forest) and spatial interpolation methods with Huanghua city as an example. Furthermore, the study uses the LASSO-GA-BPNN model to estimate the content of eight heavy metals (including Ni, Pb, Cr, Hg, Cd, As, Cu, and Zn) in Huanghua and visualize the results in high resolution. In addition, we calculate the Nemerow index based on the estimation results. The results denote that, the simultaneous optimization of BPNN by LASSO and GA can greatly improve the estimation accuracy and generalization ability. The LASSO-GA-BPNN model is a more accurate model for the estimate heavy metal content in soil compared to SVR, RF and spatial interpolation. Moreover, the comprehensive pollution level in Huanghua is mainly low pollution. The overall spatial distribution law of each heavy metal content is very similar, and the local spatial distribution of each heavy metal is different. The results are of great significance for soil pollution estimation.
Extraction from Present Participle Adjuncts: The Relevance of the Corresponding Declaratives
Authors: Kehl Andreas
Published: July 2022

In this article, I will argue that many of the theoretical approaches to extraction from participle adjunct islands suffer from the fact that the focus of investigation lies on perceived grammaticality differences in interrogative structures. Following approaches which make an explicit connection between extraction asymmetries and properties of the underlying proposition, I will argue that there is good evidence for the existence of similar differences in declarative adjunct constructions which can explain most of the grammaticality patterns observed for interrogatives. A crucial distinction to the majority of previous theories is the focus on acceptability rather than grammaticality, and the assumption that acceptability in declaratives is determined by a variety of semantic and syntactic complexity factors which do not influence how strongly extraction degrades the structure. This line of argumentation is more compatible with approaches to island phenomena that explain the low acceptability of some extractions by independent effects such as processing complexity and discourse function instead of syntactic principles blocking the extraction. I will also discuss a partially weighted, multifactorial model for the acceptability of declarative and interrogative participle adjunct constructions, which explains the judgment patterns in the literature without the need for additional, complex licensing conditions for extraction.