bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Binding Moral Foundations on Prejudiced Attitudes toward Migrants: The Mediation Role of Perceived Realistic and Symbolic Threats
Authors: Bianco Fleur , Kosic Ankica
Published: September 2023

(1) Background: This study explores how threat perception mediates the relationship between binding moral foundations and prejudice toward migrants. We hypothesized that the relationship between binding moral foundations and prejudice against migrants, which is already established in the literature, is mediated through realistic and symbolic threat perception. (2) Methods: Two separate samples were gathered, in Malta (N = 191) and Italy (N = 189). The participants responded to an anonymous questionnaire containing several scales: the Moral Foundation Questionnaire, perceived threat from migrants, prejudice toward migrants, and social distance from several macro-categories of migrants. (3) Results: We confirmed a significant relationship between binding moral foundations and explicit prejudice toward migrants, and also found that this relationship was mediated by perceived realistic and symbolic threats in both countries. However, when the indices of social distance were considered as criterion variables, the direct relationship between binding moral foundations and social distance was not confirmed for all the migrant macro-groups. In addition, in some migrant groups, we found that this relationship was mediated by perceived realistic and symbolic threats. (4) Conclusions: This study indicates that the perception of realistic threats may have a significant role in determining the effect of binding moral foundations; this may have theoretical and practical implications.
Influence of Schistosity Orientation on Failure Mode and Indirect Tensile Strength of Mica Schist
Authors: Hudyma Nick , Avar B. Burçin , Chittoori Bhaskar
Published: September 2023

The indirect tension test is an important laboratory test for rock characterization. The presence of rock fabric, such as schistosity, complicates the assessment of test results. One hundred and forty-five indirect tension tests were conducted on mica schist specimens to investigate the effect of schistosity orientation on failure mode and tensile strength. Tensile strength results did not provide a clear relationship between schistosity orientation and tensile strength, so the failure patterns were investigated. A new naming scheme for failure modes was developed, incorporating fracture patterns observed in the specimen faces and edges. The Single Mode failure group specimens had only one failure pattern that appeared on both specimen faces, either axial failure (seventy-three specimens), schistosity failure (six specimens), or out-of-plane failure (seven specimens). The Mixed Mode failure group had thirty-two specimens that exhibited one failure pattern on one face and another on the other. The Hybrid Mode failure group had twenty-seven specimens with multiple failure patterns on both specimen faces. It was noted that Mixed Mode and Hybrid Mode specimens with components of axial failure had higher indirect tensile strengths than specimens without elements of axial failures. Statistical analyses of the tensile strength data using Levene’s Test for equal variances and two-sample t-tests showed no statistical difference between the Mixed Mode and Hybrid Mode failure groups. However, there was a statistical difference between the tensile strengths of the Single Mode axial failure specimens and the combined Mixed Mode and Hybrid Mode failure groups. These results clearly emphasize that indirect tensile strength should be assessed using schistosity orientation and failure mode.
Service Design of a Loss Prevention Device for Older Adults with Dementia
Authors: Hsu Cheng-Kun , Liu Cheng-Chang , Chang Tung , Liao Jing-Jing , Shu Chi-Min
Published: September 2023

This aim of this research was to explore the appraisal of the use of smart alert bracelets by older adults diagnosed with dementia. Convenience sampling was adopted to recruit older adults with dementia in Yunlin County, Taiwan. A manual questionnaire survey was conducted, and SPSS 26.0 statistical software was used for analysis. The results of this study showed noticeable positive correlation results in the post-test for the modes “wearing device”, “degree of dementia”, and “field configuration”. Based on the experimental results, the following suggestions are provided: (1) in terms of statistical calculation, the statistical results were affected by changes in some participants; (2) as for the design of equipment, to be more suitable for adult use, the size and color of bracelets need to be optimized; (3) as for the problem of battery charging of the device, because the charging location of the device is not easy to find, it is better to extend device standby time; (4) regarding the selection of equipment, older adults with early-stage dementia could be concerned about the function of the wearable device, so it is recommended to provide a device designed with clear functions, such as a watch, so that older adults are more willing to wear it. Patients diagnosed with moderate and severe dementia should be advised to use concealed non-sensory devices, such as charms and cards, to better facilitate assistance from caregivers in wearing them; and (5) as for the device, in case of a loss event, in addition to mobile phone notifications, other light and sound device notifications can be added, allowing caregivers to pay more attention to information in real time. In summary, the feedback from caregivers and older adults suggests that if the device is to be used without charging, the overall design should be light and small, which is more suitable for service designs.
Differences in Improvement of Physical Function in Older Adults with Long-Term Care Insurance with and without Falls: A Retrospective Cohort Study
Authors: Kitamura Masahiro , Umeo Junichi , Kurihara Kyohei , Yamato Takuji , Nagasaki Takayuki , Mizota Katsuhiko , Kogo Haruki , Tanaka Shinichi , Yoshizawa Takashi
Published: September 2023

(1) Background: This study examined the differences in changes in physical function with and without falls after daycare use among frail older adults with long-term care insurance (LTCI). (2) Methods: In this retrospective cohort study, 82 of 96 consecutive daycare center users met the inclusion criteria. The participants were divided into two groups based on the presence or absence of falls 6–12 months after use. Participant characteristics in the fall and non-fall groups and physical function at baseline and six months in each group were compared. Using analysis of covariance, we analyzed physical function and its changes between the two groups, and cut-off values were calculated using receiver operating characteristic curves. (3) Results: Gait speed, timed up-and-go test, and 30 s chair stand test (CS30) improved significantly over six months in the no-fall group (n = 70) and all participants (n = 82) (p < 0.01). Gait speed in the fall group (n = 12) improved significantly over six months (p = 0.04). The fall group had significantly lower adjusted ΔCS30 scores than the no-fall group (p = 0.03), with a cutoff value of 2 (p = 0.024). (4) Conclusions: In older adults with LTCI, physical function with and without falls after daycare use differed by ΔCS30, with a cutoff value of 2.
Telerehabilitation Intervention in Transitional Care for People with COVID-19: Pre-Post Study with a Non-Equivalent Control Group
Authors: Reis Neuza , Costa Dias Maria José , Sousa Luís , Canedo Filipa , Rico Miguel Toscano , Henriques Maria Adriana , Baixinho Cristina Lavareda
Published: September 2023

SARS-CoV-2 infection and its resulting sequelae have increased the prevalence of people with respiratory symptoms, with impacts on functional capacity, quality of life, anxiety, depression, and mental health. To mitigate this problem, one challenge has been the design and implementation of interventions that simultaneously allow for education, rehabilitation, and monitoring of people with long COVID, at a time when health services were on the verge of rupture due to the volume of people with active COVID and in need of intensive care. Telerehabilitation emerged as a mode for providing rehabilitative care that brought professionals closer to patients and enabled continuity of care. The present study aimed to evaluate the results of a telerehabilitation intervention for people with injuries associated with SARS-CoV-2 infection in hospital-community transitions, considering their degree of dependence in performing activities of daily living, respiratory symptoms, fatigue, gait capacity, muscle strength, and experience with anxiety and depression. A pre-post study with a non-equivalent control group was carried out with a total of 49 participants (intervention group n = 24; control group n = 25). The post-intervention results showed an increase in saturation, a decrease in heart rate, an improvement in the impact of post-COVID functionality, a decrease in fatigue, a decrease in perceived effort, and a decrease in depressive and anxiety symptoms. The telerehabilitation intervention, which combined educational strategies with respiratory and motor rehabilitation, helped improve global functionality and self-care, with clinical and functional impacts.
Cystitis and Utipro® Plus: Real-World Evidence
Authors: Kostev Karel , Cai Tommaso
Published: September 2023

Background: The emergence of drug resistance in the etiological agents of uncomplicated urinary tract infections (UTIs) emphasizes the need to shift the paradigm towards alternative therapeutic strategies. The objective of the present study was to evaluate the use of a medical device containing xyloglucan, hibiscus, and propolis for reducing UTI symptomatic episodes, antibiotic prescription, and days of sick leave. Materials and Methods: It used retrospective, cross-sectional study data provided by office-based physicians from Germany (Disease Analyzer, IQVIA database), including those on 3586 patients with a diagnosis of UTI treated with Utipro® Plus (Noventure, Barcelona, Spain) from January 2015 to December 2020. Results: The majority of patients were women (94.2%) and had a mean age (standard deviation, SD) of 57.7 years (19.0). Within 12 months after the prescription and compared to the 12 months before, it was observed that there was a reduction in the proportion of patients with at least one UTI diagnosis (from 79.4% to 36.4%, p < 0.001), in antibiotic prescriptions (from 33.5% to 22.1%, p < 0.001), and in the proportion of patients with at least one day of sick leave (from 4.1% to 2.7%). Conclusions: The use of Utipro® Plus is able to decrease UTI recurrence and can lead to the reduction of antibiotic prescriptions and disease burden in individuals affected by uncomplicated cystitis.
Pandemic Preparedness: A Scoping Review of Best and Worst Practices from COVID-19
Authors: Maccaro Alessia , Audia Camilla , Stokes Katy , Masud Haleema , Sekalala Sharifah , Pecchia Leandro , Piaggio Davide
Published: September 2023

The COVID-19 pandemic highlighted the scale of global unpreparedness to deal with the fast-arising needs of global health threats. This problem was coupled with a crisis of governance and presented in the context of globally hitting climate crisis and disasters. Although such a pandemic was predictable due to the known effects of human intervention on the surrounding environment and its devastating secondary effects, such as climate change and increased zoonoses, most countries were unprepared to deal with the scale and scope of the pandemic. In this context, such as that of the climate crisis, the Global North and Global South faced several common challenges, including, first and foremost, the scarcity of resources required for health, policy, wellbeing and socioeconomic wellness. In this paper, we review the most recent evidence available in the literature related to pandemic preparedness and governance, focusing on principles and practices used during the COVID-19 pandemic, and we place it in the context of a European Parliament Interest Group meeting (this event took place on 21 March 2023 during the “European Health Tech Summit”) to ground it within ongoing discussions and narratives of policy and praxis. The review identified key practices and principles required to better face future health threats and emergencies. Beyond health practices relying on technology and innovation, it is useful to mention the importance of contextualising responses and linking them to clear goals, improving the agreement between science and policymaking, thus building trust and enabling transparent communication with the general public based on clear ethical frameworks.
Workload, Job Satisfaction and Quality of Nursing Care in Italy: A Systematic Review of Native Language Articles
Authors: Serra Nicola , Botti Stefano , Guillari Assunta , Simeone Silvio , Latina Roberto , Iacorossi Laura , Torreggiani Martina , Guberti Monica , Cicolini Giancarlo , Lupo Roberto , Capuano Angela , Pucciarelli Gianluca , Gargiulo Gianpaolo , Tomietto Marco , Rea Teresa
Published: September 2023

Nursing research is rapidly increasing, yet contributions from numerous countries that may interest the international nursing community are impeded because many research articles are published in authors’ native language and not in English. The objectives of this work were to systematically review papers published in Italian related to job satisfaction and the quality of nursing care, and to discuss their findings in light of the international literature. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was used. The Directory of Open Access Journals (DOAJ) and Indice della Letteretura Italiana di Scienze Infermieristiche (ILISI) databases were consulted for eligible studies published from January 2015 to November 2022. Two hundred sixteen papers were identified, 11 of which were selected for review: 8 on job satisfaction, two on workload issues, and 1 on quality of nursing care. The quality of included studies was assessed through the Effective Public Health Practice Project quality assessment tool (EPHPP). The results of our review were in line with those of international literature, and they can help to fill the knowledge gap on the quality of nursing performance in Italian care settings. In addition, the proposed method can provide further elements of discussion among literature providers and reviewers.
New Chemical Systems for the Removal of Calcareous Encrustations on Monumental Fountains: A Case Study of the Nymphaeum of Cerriglio
Authors: Squarciafico Claudia , Salatino Giorgia , La Russa Mauro Francesco , Peluso Teresa , Basile Lorenzo , Barbagallo Fina Serena , Coppola Monica , Macchia Andrea
Published: September 2023

This study aims to compare the effects of some chemical agents on the removal of calcareous encrustations, which are characterized by the presence of both calcium and silicon. The experimentation was conducted during the conservation treatments of Cerriglio’s nymphaeum (Massa Lubrense, Naples, Italy). Tests were carried out in the laboratory on specimens and in situ to define the most efficient choice between several chelant agents, in the recovery of calcium and silicon, using ICP/OES and spectrocolorimetric and microscopic analyses.
Social Media as Lieux for the Convergence of Collective Trajectories of Holocaust Memory—A Study of Online Users in Germany and Italy
Authors: Manca Stefania , Passarelli Marcello
Published: September 2023

By articulating a shared victimhood or guilt or responsibility, memorial museums are designed as ethical projects that encourage visitors to learn from the past to build a “better future”. In contemporary Europe, Holocaust memorials and museums constitute a trajectory of remembrance about public Holocaust memory that consolidates political legitimacy and articulates national narratives of the legacy of WWII. In parallel, increasing adoption and spread of digital technologies have resulted in a convergence and a globalisation of themes and user interests associated with Holocaust memory. The purpose of this study is to investigate the perspectives and interests of users of the social media profiles of a group of Holocaust museums and memorials in Germany and Italy. Using a primarily quantitative approach, the study sought to understand the motivations, interests, and online activities of users of nine Holocaust museums and memorials. While national narratives regarding public policy continue to diverge in the two countries, users express a convergence of interests and motivations when using these social media profiles. This dual venture of Holocaust memory is a complex yet powerful example of how the globalisation of digital media is playing an increasingly significant role in European contemporary society.
Ethnologist as Foreign Body: A Systemic Explanation
Authors: Arsenault Maude
Published: September 2023

During an ethnographic experience, which took place in a rehabilitation clinic, I had to deal with situations that required me to make a series of adjustments to my role in the clinic, so as to reduce my involvement with both patients and therapists. Although I expected to feel more at ease as the field progressed, instead, I felt as if my presence were more and more disruptive, and gradually becoming problematic. The systemic approach thus seemed the most relevant for clarifying the complexity of the interactions that were at play, and that shaped my experience, as I had to venture beyond reflexivity. The aim of this methodological article is to shed light on the need for constant adaptation in the ethnologist, in order to maintain their presence in the field, and obtain information to carry out research. In order to do so, a systemic triangulation has been performed based on the Donnadieu and Karsky method, leading to an analysis of some of the difficulties encountered, as highlighted via systemic thinking.
Inhibitory Effect of Aqueous Extracts from Egeria densa Planch. on Cyanobacteria Microcystis aeruginosa (Kützing) Lemmermann Growth
Authors: Wijesinghe Ashika , Senavirathna Mudalige Don Hiranya Jayasanka , Fujino Takeshi
Published: September 2023

This study aimed to investigate the allelopathic effect of live Egeria densa Planch. and its aqueous extracts in inhibiting the cyanobacterium Microcystis aeruginosa (Kützing) Lemmermann through a possible growth inhibition pathway. Under coexistence, the presence of live E. densa reduced the growth of M. aeruginosa by 48% compared to when M. aeruginosa was alone. Consequently, we prepared two separate aqueous extracts with distilled water: one from E. densa plants collected from monocultures, and the other from E. densa plants collected from co-cultivation with M. aeruginosa. At a concentration of 0.5 g/L, both extracts successfully suppressed the growth of M. aeruginosa throughout the 5-day exposure period. The extracts obtained from E. densa plants grown in a combined culture with M. aeruginosa showed significant growth-inhibiting capabilities compared to the extracts obtained from E. densa monoculture (p < 0.05). They showed 22% more growth inhibition compared to cultures exposed to monoculture extracts at day 5, indicating that the production of allelochemicals in E. densa was induced during co-existence with cyanobacteria. However, the higher concentrations (2 and 4 g/L) of both extracts did not effectively exhibit a successful inhibitive ability, possibly due to the presence of high nutrient concentrations, specifically PO43−, which may be potentially suppressing the activity of allelochemicals. Further studies are recommended in identifying the specific allelochemicals and exploring their practical implementation in the field.
Multisensory Stimuli, Restorative Effect, and Satisfaction of Visits to Forest Recreation Destinations: A Case Study of the Jhihben National Forest Recreation Area in Taiwan
Authors: Chiang Yu-Jen
Published: September 2023

The perceived quality of the restorative environment of forest resources should be a key consideration for forest recreational areas in managing ecosystem services to provide health benefits to visitors. However, previous studies on utilizing forests as a resource for restorative services have rarely explored the simultaneous integration of on-site sensory experiences from a multisensory perspective or evaluated visitor satisfaction from a service-oriented standpoint. Therefore, this study aimed to understand the association among multisensory stimuli, perceived restorativeness, and satisfaction with visits to forest recreation areas and clarify the mediating role of perceived restorativeness in the relationship between multisensory stimuli and satisfaction. This study deployed a questionnaire and collected 458 valid responses from visitors to the Jhihben National Forest Recreation Area in Taiwan. Structural equation modeling was conducted to test the study hypotheses. The results indicated that visual sensations, auditory sensations, olfactory sensations, and tactile sensations had significant positive effects on perceived restorativeness and satisfaction and that perceived restorativeness also had a significant positive effect on satisfaction. Perceived restorativeness played a partial mediating role in this causal model. This study verified the psychological model of the relationships among a natural setting’s multisensory stimuli, perceived restorativeness, and satisfaction. In practice, the findings of this study offer guidance for forest recreation areas to develop strategies for ecological services, encompassing the establishment of restorative environmental management and visitor service management approaches.
Assessment of the Negative Impact of Urban Air Pollution on Population Health Using Machine Learning Method
Authors: Temirbekov Nurlan , Temirbekova Marzhan , Tamabay Dinara , Kasenov Syrym , Askarov Seilkhan , Tukenova Zulfiya
Published: September 2023

This study focuses on assessing the level of morbidity among the population of Almaty, Kazakhstan, and investigating its connection with atmospheric air pollution using machine learning algorithms. The use of these algorithms is aimed at analyzing the relationship between air pollution levels and the state of public health, as well as the correlations between COVID-19 infection and the development of respiratory diseases. This study analyzes the respiratory diseases of the population of Almaty and the level of air pollution as a result of suspended particles for the period of 2017–2022. The study includes recommendations to reduce harmful emissions into the atmosphere using machine learning methods. The results of the study show that air pollution is a critical factor affecting the increase in the number of diseases of the respiratory system. The study recommends taking measures to reduce air pollution and improve air quality in order to prevent the development of chronic respiratory diseases. The study offers recommendations to industrial enterprises, traffic management organizations, thermal power plants, the Department of Environmental Protection, and local executive bodies in order to reduce respiratory diseases among the population.
Parents’ Perspectives of an Arts Engagement Program Supporting Children with Anxiety
Authors: Macdonald Diane , Han Jin , Elder Emma , Boydell Katherine M.
Published: September 2023

Arts engagement programs (AEPs) are non-clinical, structured programs led by artists and educators to support mental health and wellbeing. While evidence demonstrates positive mental health outcomes in adult AEPs, studies of childhood AEPs remain sparse. We created a gallery-based AEP (Culture Dose for Kids) for children with anxiety based on a successful arts engagement pilot for adults with depression. We questioned whether our tailored-for-children adult program would effectively and feasibly support children’s mental health. Through parents’ perspectives and feedback, this study tested the program’s acceptability, feasibility, and effectiveness with children with anxiety. Quantitative and qualitative measures were used to determine whether the program was an effective and acceptable mental health support for children with anxiety. Our findings revealed that the program positively and significantly impacted parental perceptions of their child’s anxiety. Our findings illustrate depictions of improved mood, confidence, and sense of empowerment in the child, qualities associated with resilience and mental wellbeing. Open-ended activities provided opportunities for connection, creativity, and experimentation—sources of strength for improving mental health. This study adds to the small but growing evidence base supporting the role of arts-based community care in youth mental health and wellbeing.
Environment Degradation, Health Threats, and Legality at the Artisanal Small-Scale Gold Mining Sites in Indonesia
Authors: Meutia Ami A. , Bachriadi Dianto , Gafur Nurfitri Abdul
Published: September 2023

Artisanal Small-scale Gold Mining (ASGM) activities, despite offering numerous economic incentives, inflict negative impacts on the environment and public health due to the use of mercury or cyanide. This study aims to compare three ASGM locations in Indonesia in terms of environmental impacts and potential health problems in the community. As part of this research, field surveys at three ASGM illegal locations with different conditions, observations, literature studies, and interviews with the community and stakeholders were conducted. At each of the survey sites, the potential threat to public health due to the use of mercury was determined to be high. Additionally, many of the environmental impacts detected were deemed to have reached a high-alert stage, in some cases even posing a level of extreme danger. Based on these results, it has become clear that a form of mining management which reduces the negative impacts on the surrounding environment and community health is needed. The suggestions put forward in this paper, including the call for greater control of ASGM, may also be applied in other developing countries which suffer from similar problems and conditions.
A Latent-Factor-Model-Based Approach for Traffic Data Imputation with Road Network Information
Authors: Su Xing , Sun Wenjie , Song Chenting , Cai Zhi , Guo Limin
Published: September 2023

With the rapid development of the economy, car ownership has grown rapidly, which causes many traffic problems. In recent years, intelligent transportation systems have been used to solve various traffic problems. To achieve effective and efficient traffic management, intelligent transportation systems need a large amount of complete traffic data. However, the current traffic data collection methods result in different forms of missing data. In the last twenty years, although many approaches have been proposed to impute missing data based on different mechanisms, these all have their limitations, which leads to low imputation accuracy, especially when the collected traffic data have a large amount of missing values. To this end, this paper proposes a latent-factor-model-based approach to impute the missing traffic data. In the proposed approach, the spatial information of the road network is first combined with the spatiotemporal matrix of the original traffic data. Then, the latent-factor-model-based algorithm is employed to impute the missing data in the combined matrix of the traffic data. Based on the real traffic data from METR-LA, we found that the imputation accuracy of the proposed approach was better than that of most of the current traffic-data-imputation approaches, especially when the original traffic data are limited.
Protonated Organic Diamines as Templates for Layered and Microporous Structures: Synthesis, Crystal Chemistry, and Structural Trends among the Compounds Formed in Aqueous Systems Transition Metal Halide or Nitrate–Diamine–Selenious Acid
Authors: Charkin Dmitri O. , Nazarchuk Evgeny V. , Dmitriev Dmitri N. , Grishaev Vasili Yu. , Omelchenko Timofey A. , Spiridonova Darya V. , Siidra Oleg I.
Published: September 2023

Systematic studies of crystalline compounds formed in aqueous systems containing aliphatic diamines, divalent transition metal halides, and selenious acid resulted in the discovery of a large family of new complex species corresponding to several new structure types. With ethylenediamine (en), layered (enH2)[M(HSeO3)2X2] compounds are the most commonly formed species which constitute a significant contribution to the family of layered hydrogen selenites containing neutral [M(HSeO3)2] (M = Mg, Mn, Co, Ni, Cu, Zn, Cd) 2D building blocks. In contrast to some previous suggestions, piperazine (pip), as well as its homologue N-methylpiperazine, mostly give rise to quite different, sometimes more complex, structures of varied dimensionality while the (pipH2)[M(HSeO3)2X2] compounds are formed only with M = Cu and Cd. In addition, metal-, halide-, or selenium-free by-product species are observed. The SeIV can be present in a multitude of forms, including H2SeO3, HSeO3−, SeO32−, and Se2O52−, reflecting amazing adaptability to the shape of the templating cations.
Cost-Efficient Detection of NTRK1/2/3 Gene Fusions: Single-Center Analysis of 8075 Tumor Samples
Authors: Romanko Aleksandr A. , Mulkidjan Rimma S. , Tiurin Vladislav I. , Saitova Evgeniya S. , Preobrazhenskaya Elena V. , Krivosheyeva Elena A. , Mitiushkina Natalia V. , Shestakova Anna D. , Belogubova Evgeniya V. , Ivantsov Alexandr O. , Iyevleva Aglaya G. , Imyanitov Evgeny N.
Published: September 2023

The majority of NTRK1, NTRK2, and NTRK3 rearrangements result in increased expression of the kinase portion of the involved gene due to its fusion to an actively transcribed gene partner. Consequently, the analysis of 5′/3′-end expression imbalances is potentially capable of detecting the entire spectrum of NTRK gene fusions. Archival tumor specimens obtained from 8075 patients were subjected to manual dissection of tumor cells, DNA/RNA isolation, and cDNA synthesis. The 5′/3′-end expression imbalances in NTRK genes were analyzed by real-time PCR. Further identification of gene rearrangements was performed by variant-specific PCR for 44 common NTRK fusions, and, whenever necessary, by RNA-based next-generation sequencing (NGS). cDNA of sufficient quality was obtained in 7424/8075 (91.9%) tumors. NTRK rearrangements were detected in 7/6436 (0.1%) lung carcinomas, 11/137 (8.0%) pediatric tumors, and 13/851 (1.5%) adult non-lung malignancies. The highest incidence of NTRK translocations was observed in pediatric sarcomas (7/39, 17.9%). Increased frequency of NTRK fusions was seen in microsatellite-unstable colorectal tumors (6/48, 12.5%), salivary gland carcinomas (5/93, 5.4%), and sarcomas (7/143, 4.9%). None of the 1293 lung carcinomas with driver alterations in EGFR/ALK/ROS1/RET/MET oncogenes had NTRK 5′/3′-end expression imbalances. Variant-specific PCR was performed for 744 tumors with a normal 5′/3′-end expression ratio: there were no rearrangements in 172 EGFR/ALK/ROS1/RET/MET-negative lung cancers and 125 pediatric tumors, while NTRK3 fusions were detected in 2/447 (0.5%) non-lung adult malignancies. In conclusion, this study describes a diagnostic pipeline that can be used as a cost-efficient alternative to conventional methods of NTRK1–3 analysis.
Alkylresorcinols as New Modulators of the Metabolic Activity of the Gut Microbiota
Authors: Zabolotneva Anastasia A. , Gaponov Andrei M. , Roumiantsev Sergey A. , Vasiliev Ilya Yu. , Grigoryeva Tatiana V. , Kit Oleg I. , Zlatnik Elena Yu. , Maksimov Aleksey Yu. , Goncharova Anna S. , Novikova Inna A. , Appolonova Svetlana A. , Markin Pavel A. , Shestopalov Aleksandr V.
Published: September 2023

Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (−/−) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol’s regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (−/−) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (−/−) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.
Evaluating the Antibacterial and Antivirulence Activities of Floxuridine against Streptococcus suis
Authors: Li Jie , Han Ning , Li Yangyang , Zhao Feifei , Xiong Wenguang , Zeng Zhenling
Published: September 2023

Streptococcus suis is an emerging zoonotic pathogen that can cause fatal diseases such as meningitis and sepsis in pigs and human beings. The overuse of antibiotics is leading to an increased level of resistance in S. suis, and novel antimicrobial agents or anti-virulence agents for the treatment of infections caused by S. suis are urgently needed. In the present study, we investigated the antibacterial activity, mode of action and anti-virulence effects of floxuridine against S. suis. Floxuridine showed excessive antibacterial activity against S. suis both in vivo and in vitro; 4 × MIC of floxuridine could kill S. suis within 8 h in a time–kill assay. Meanwhile, floxuridine disrupted the membrane structure and permeability of the cytoplasmic membrane. Molecular docking revealed that floxuridine and SLY can be directly bind to each other. Moreover, floxuridine effectively inhibited the hemolytic capacity and expression levels of the virulence-related genes of S. suis. Collectively, these results indicate that the FDA-approved anticancer drug floxuridine is a promising agent and a potential virulence inhibitor against S. suis.
SYNE1 Mutation Is Associated with Increased Tumor Mutation Burden and Immune Cell Infiltration in Ovarian Cancer
Authors: Harbin Laura M. , Lin Nan , Ueland Frederick R. , Kolesar Jill M.
Published: September 2023

SYNE1, a nuclear envelope protein critical for cellular structure and signaling, is downregulated in numerous malignancies. SYNE1 alterations are found in 10% of gynecologic malignancies and 5% of epithelial ovarian cancers. Previous studies demonstrated an association between SYNE1 mutation, increased tumor mutation burden (TMB), and immunotherapy response. This study evaluates the SYNE1 mutation frequency, association with TMB, and downstream effects of SYNE1 mutation in ovarian cancer. Genetic information, including whole-exome sequencing, RNA analysis, and somatic tumor testing, was obtained for consenting ovarian cancer patients at an academic medical center. Mutation frequencies were compared between the institutional cohort and The Cancer Genome Atlas (TCGA). Bioinformatics analyses were performed. In our cohort of 50 patients, 16 had a SYNE1 mutation, and 15 had recurrent disease. Median TMB for SYNE1 mutated patients was 25 compared to 7 for SYNE1 wild-type patients (p < 0.0001). Compared to the TCGA cohort, our cohort had higher SYNE1 mutation rates (32% vs. 6%, p < 0.001). Gene expression related to immune cell trafficking, inflammatory response, and immune response (z > 2.0) was significantly increased in SYNE1 mutated patients. SYNE1 mutation is associated with increased TMB and immune cell infiltration in ovarian cancer and may serve as an additional biomarker for immunotherapy response.
The Anion Channel TMEM16a/Ano1 Modulates CFTR Activity, but Does Not Function as an Apical Anion Channel in Colonic Epithelium from Cystic Fibrosis Patients and Healthy Individuals
Authors: Salari Azam , Xiu Renjie , Amiri Mahdi , Pallenberg Sophia Theres , Schreiber Rainer , Dittrich Anna-Maria , Tümmler Burkhard , Kunzelmann Karl , Seidler Ursula
Published: September 2023

Studies in human colonic cell lines and murine intestine suggest the presence of a Ca2+-activated anion channel, presumably TMEM16a. Is there a potential for fluid secretion in patients with severe cystic fibrosis transmembrane conductance regulator (CFTR) mutations by activating this alternative pathway? Two-dimensional nondifferentiated colonoid–myofibroblast cocultures resembling transit amplifying/progenitor (TA/PE) cells, as well as differentiated monolayer (DM) cultures resembling near-surface cells, were established from both healthy controls (HLs) and patients with severe functional defects in the CFTR gene (PwCF). F508del mutant and CFTR knockout (null) mice ileal and colonic mucosa was also studied. HL TA/PE monolayers displayed a robust short-circuit current response (ΔIeq) to UTP (100 µM), forskolin (Fsk, 10 µM) and carbachol (CCH, 100 µM), while ΔIeq was much smaller in differentiated monolayers. The selective TMEM16a inhibitor Ani9 (up to 30 µM) did not alter the response to luminal UTP, significantly decreased Fsk-induced ΔIeq, and significantly increased CCH-induced ΔIeq in HL TA/PE colonoid monolayers. The PwCF TA/PE and the PwCF differentiated monolayers displayed negligible agonist-induced ΔIeq, without a significant effect of Ani9. When TMEM16a was localized in intracellular structures, a staining in the apical membrane was not detected. TMEM16a is highly expressed in human colonoid monolayers resembling transit amplifying cells of the colonic cryptal neck zone, from both HL and PwCF. While it may play a role in modulating agonist-induced CFTR-mediated anion currents, it is not localized in the apical membrane, and it has no function as an apical anion channel in cystic fibrosis (CF) and healthy human colonic epithelium.
FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway
Authors: Wang Lihui , Cheng Feiyan , Pan Rumeng , Cui Zhiwei , She Jing , Zhang Yidan , Yang Xinyuan
Published: September 2023

Premature ovarian failure (POF) is a complicated disorder related to the apoptosis of granulosa cells. The incidence of chemotherapy-associated POF is rising dramatically owing to the increasing proportion of cancer in adolescents. According to previous studies, oxidative stress caused by chemotherapeutic agents plays an important role in the development of POF. However, the exact effects of nuclear factor-erythroid 2-related factor2 (NRF2), a pivotal anti-oxidative factor, are still unknown in chemotherapy-associated POF. Firstly, we manipulated NRF2 expressions on a genetic or pharmaceutical level in cisplatin-injured granulosa cell models. The results indicate that the increasing NRF2 in cisplatin-injured cells was just compensatory and not enough to resist the accumulated stress. Upregulation of NRF2 could protect granulosa cells against cisplatin via elevating autophagic level by using an autophagic activator (rapamycin) and inhibitor (chloroquine). Additionally, exogenous FGF2 exerted a protective role by increasing NRF2 expression and promoting its nuclear translocation. Meanwhile, the results in cisplatin-POF mice models were consistent with what was found in injured cells. In conclusion, our research proved that FGF2 rescued cisplatin-injured granulosa cells through the NRF2-autophagy pathway and might provide a possible alternative treatment choice by targeting NRF2 for POF patients who are intolerant or unsuitable to FGF2.
Beetroot (Beta vulgaris) Extract against Salmonella Typhimurium via Apoptosis-Like Death and Its Potential for Application in Cooked Pork
Authors: Gong Shaoying , Jiao Chaoqin , Guo Ling , Jiang Yujun
Published: September 2023

Salmonella Typhimurium is a common foodborne pathogen in meat and meat products, causing significant harm and losses to producers and consumers. The aim of this study was to investigate the antibacterial activity and possible mechanisms of beetroot (Beta vulgaris) extract against S. Typhimurium, as well as the application potential in cooked pork. The results suggested beetroot extract could inhibit S. Typhimurium with a minimum inhibitory concentration (MIC) of 20 mg/mL. After treatment with beetroot extract (1 or 2 MIC), S. Typhimurium exhibited the characteristics of apoptotic-like death (ALD), such as membrane depolarization, phosphatidylserine (PS) externalization, caspase-like protein activation, and DNA fragmentation. Further research has shown that the ALD induced by beetroot extract in S. Typhimurium was caused by reactive oxygen species (ROS) consumption, which was different from most natural products. The treatment of cooked pork with beetroot extract could reduce the number of S. Typhimurium, lower pH, defer lipid oxidation, and improve the colour. These results indicate that beetroot extract can inhibit S. Typhimurium through the ALD mechanism and has potential as an antibacterial agent against S. Typhimurium in ready-to-eat meat products.
Unraveling the Antioxidant Activity of 2R,3R-dihydroquercetin
Authors: Xu Yaping , Li Zhengwen , Wang Yue , Li Chujie , Zhang Ming , Chen Haiming , Chen Wenxue , Zhong Qiuping , Pei Jianfei , Chen Weijun , Haenen Guido R. M. M. , Moalin Mohamed
Published: September 2023

It has been reported that in an oxidative environment, the flavonoid 2R,3R-dihydroquercetin (2R,3R-DHQ) oxidizes into a product that rearranges to form quercetin. As quercetin is a very potent antioxidant, much better than 2R,3R-DHQ, this would be an intriguing form of targeting the antioxidant quercetin. The aim of the present study is to further elaborate on this targeting. We can confirm the previous observation that 2R,3R-DHQ is oxidized by horseradish peroxidase (HRP), with H2O2 as the oxidant. However, HPLC analysis revealed that no quercetin was formed, but instead an unstable oxidation product. The inclusion of glutathione (GSH) during the oxidation process resulted in the formation of a 2R,3R-DHQ-GSH adduct, as was identified using HPLC with IT-TOF/MS detection. GSH adducts appeared on the B-ring of the 2R,3R-DHQ quinone, indicating that during oxidation, the B-ring is oxidized from a catechol to form a quinone group. Ascorbate could reduce the quinone back to 2R,3R-DHQ. No 2S,3R-DHQ was detected after the reduction by ascorbate, indicating that a possible epimerization of 2R,3R-DHQ quinone to 2S,3R-DHQ quinone does not occur. The fact that no epimerization of the oxidized product of 2R,3R-DHQ is observed, and that GSH adducts the oxidized product of 2R,3R-DHQ on the B-ring, led us to conclude that the redox-modulating activity of 2R,3R-DHQ quinone resides in its B-ring. This could be confirmed by chemical calculation. Apparently, the administration of 2R,3R-DHQ in an oxidative environment does not result in ‘biotargeting’ quercetin.
Organ-Chips Enhance the Maturation of Human iPSC-Derived Dopamine Neurons
Authors: Otero Maria G. , Bell Shaughn , Laperle Alexander H. , Lawless George , Myers Zachary , Castro Marian A. , Villalba Jaquelyn M. , Svendsen Clive N.
Published: September 2023

While cells in the human body function in an environment where the blood supply constantly delivers nutrients and removes waste, cells in conventional tissue culture well platforms are grown with a static pool of media above them and often lack maturity, limiting their utility to study cell biology in health and disease. In contrast, organ-chip microfluidic systems allow the growth of cells under constant flow, more akin to the in vivo situation. Here, we differentiated human induced pluripotent stem cells into dopamine neurons and assessed cellular properties in conventional multi-well cultures and organ-chips. We show that organ-chip cultures, compared to multi-well cultures, provide an overall greater proportion and homogeneity of dopaminergic neurons as well as increased levels of maturation markers. These organ-chips are an ideal platform to study mature dopamine neurons to better understand their biology in health and ultimately in neurological disorders.
Transcriptomic and Metabolomic Analyses Reveal the Key Genes Related to Shade Tolerance in Soybean
Authors: Jiang Aohua , Liu Jiaqi , Gao Weiran , Ma Ronghan , Zhang Jijun , Zhang Xiaochun , Du Chengzhang , Yi Zelin , Fang Xiaomei , Zhang Jian
Published: September 2023

Soybean (Glycine max) is an important crop, rich in proteins, vegetable oils and several other phytochemicals, which is often affected by light during growth. However, the specific regulatory mechanisms of leaf development under shade conditions have yet to be understood. In this study, the transcriptome and metabolome sequencing of leaves from the shade-tolerant soybean ‘Nanxiadou 25′ under natural light (ND1) and 50% shade rate (SHND1) were carried out, respectively. A total of 265 differentially expressed genes (DEGs) were identified, including 144 down-regulated and 121 up-regulated genes. Meanwhile, KEGG enrichment analysis of DEGs was performed and 22 DEGs were significantly enriched in the top five pathways, including histidine metabolism, riboflavin metabolism, vitamin B6 metabolism, glycerolipid metabolism and cutin, suberine and wax biosynthesis. Among all the enrichment pathways, the most DEGs were enriched in plant hormone signaling pathways with 19 DEGs being enriched. Transcription factors were screened out and 34 differentially expressed TFs (DETFs) were identified. Weighted gene co-expression network analysis (WGCNA) was performed and identified 10 core hub genes. Combined analysis of transcriptome and metabolome screened out 36 DEGs, and 12 potential candidate genes were screened out and validated by quantitative real-time polymerase chain reaction (qRT-PCR) assay, which may be related to the mechanism of shade tolerance in soybean, such as ATP phosphoribosyl transferase (ATP-PRT2), phosphocholine phosphatase (PEPC), AUXIN-RESPONSIVE PROTEIN (IAA17), PURPLE ACID PHOSPHATASE (PAP), etc. Our results provide new knowledge for the identification and function of candidate genes regulating soybean shade tolerance and provide valuable resources for the genetic dissection of soybean shade tolerance molecular breeding.
Is Cell-Free DNA Testing in Hepatocellular Carcinoma Ready for Prime Time?
Authors: Jeepalyam Sravan , Sheel Ankur , Ejaz Aslam , Miller Eric , Manne Ashish
Published: September 2023

Revamping the current biomarker landscape of hepatocellular carcinoma (HCC) with cell-free DNA (cfDNA) could improve overall outcomes. The use of commercially available cfDNA testing (also known as liquid biopsy) is limited by the low prevalence of targetable mutations and does not have any prognostic or predictive value. Thus, current cfDNA testing cannot be relied upon for perioperative risk stratification (POR), including early detection of recurrence, long-term surveillance, predicting outcomes, and treatment response. Prior evidence on cfDNA mutation profiling (non-specific detection or gene panel testing) suggests that it can be a reliable tool for POR and prognostication, but it still requires significant improvements. cfDNA methylation changes or epigenetic markers have not been explored extensively, but early studies have shown potential for it to be a prognostic biomarker tool. The predictive value of cfDNA (mutations and EM) to assist treatment selection (systemic therapy, immune-checkpoint inhibitor vs. tyrosine kinase inhibitor) and to monitor response to systemic and locoregional therapies should be a future area of focus. We highlighted the unmet needs in the HCC management and the current role of cfDNA testing in HCC in addressing them.