bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review of Evidence-Based Family Interventions for Trauma-Affected Refugees
Authors: Mak Chansophal , Wieling Elizabeth
Published: August 2022

Family connections are crucial for trauma-affected refugees from collectivistic cultures. Evidence-based family interventions are consistently promoted to support a host of mental and relational health needs of families exposed to traumatic stressors; however, there is still limited research focused on cultural adaptation and the testing of the effectiveness of these interventions on some of the most disenfranchised populations in the aftermath of forced displacement. This systematic review was conducted to examine the reach of existing evidence-based family interventions implemented with newly resettled refugees globally. Studies included in this review include those testing the effectiveness of a systemic treatment with pre and post intervention evaluation, studies with or without control groups, and studies that include at least one family member in addition to the target participants. Twelve studies met the inclusion criteria. Barriers to conducting randomized control trials with displaced refugee populations are discussed. Recommendations are made for future studies to include a focus on scientifically rigorous multi-method designs, specific cultural adaptation frameworks, and the integration of relational aspects rather than focusing only on individual adjustment. Global displacement continues to rise; therefore, it is imperative that the mental health and wellbeing of displaced populations be treated with a comprehensive, multi-level framework.
Migration of Trivalent Praseodymium from Tombarthite Sewage by Microtubule Ultrafiltration Reactor with Organophosphorus in Fuel Oil
Authors: Pei Liang , Wang Liming
Published: August 2022

A microtubule ultrafiltration reactor (MUFR), with an organophosphorus system containing a sewage section with buffer liquid acetic acid and an enrichment section with aqua fortis liquid and organophosphorus dissolved in fuel oil, has been studied for praseodymium(III) migration. Many factors of praseodymium(III) migration using MUFR need to be explored, including hydrogen ion molarity (or pH), cinit of praseodymium(III), the different ionic strengths of rare-earth mine sewage, the volume ratio of organophosphorus fuel oil and aqua fortis liquid (O/A), aqua fortis’ molarity, organophosphorus’ molarity, and the effects of different acid liquids in the enrichment section on praseodymium(III) migration with MUFR. The virtues of MUFR compared to conventional migration were explored. The effects of the hydrodynamic properties (stability and flow velocity) and UF system parameters (internal diameter of the microtubule, tubule shell thickness, void ratio), etc., on the mass migration performance of the MUFR process for praseodymium(III) migration were also studied. The experimental results show that the best migration prerequisites of praseodymium(III) were obtained as follows: an aqua fortis molarity of 4.00 mol/L, an organophosphorus molarity of 0.200 mol/L, an O/A of 0.6 in the enrichment section, and a pH value of 4.80 in the sewage section. The ionic strength of rare-earth mine sewage had no obvious effect on praseodymium(III) migration. When the cinit of praseodymium(III) molarity was 1.58 × 10−4 mol/L, the migration percentage of praseodymium(III) reached 95.2% in 160 min.
Does the Physiological Response of a Triathlete Change in the Use or Absence of Drafting?
Authors: Mancha-Triguero David , Pérez-Murillo Pablo , Ibáñez Sergio J. , Antúnez Antonio
Published: August 2022

Background: Currently, tactics play an important and decisive role in sprint distance triathlons. One of the most decisive tactical elements is drafting in the cycling sector, depending on whether or not it is allowed by the test regulations. The objective was to analyze the physiological responses in running, in relation to drafting in the cycling sector, according to level and sex. Methods: To do this, a total of n = 44 subjects were divided into two levels (elite: they got a podium in the national championship, 15.68 ± 0.82 years; amateurs: they compete at the regional level, 15.68 ± 1.62 and 37.9 ± 1.74 years), undergoing two training sessions of four cycling-running multitransitions with variability in the permissibility of drafting were analyzed. A descriptive analysis of the variables was carried out, together with an inferential analysis to know the relationships and associations between the dependent and independent variables. Results: The results showed significant differences in the parameters, as related to running technique, heart rate, speed, and displacement (both between levels and sex). Conclusions: This study concludes that drafting in the cycling sector generates decisive physiological responses for the running sector.
Planning and Implementation of COVID-19 Isolation and Quarantine Facilities in Hawaii: A Public Health Case Report
Authors: Fan Victoria Y. , Yamaguchi Craig T. , Pal Ketan , Geib Stephen M. , Conlon Leocadia , Holmes Joshua R. , Sutton Yara , Aiona Amihan , Curtis Amy B. , Mersereau Edward
Published: August 2022

In response to the second surge of COVID-19 cases in Hawaii in the fall of 2020, the Hawaii State Department of Health Behavioral Health Administration led and contracted a coalition of agencies to plan and implement an isolation and quarantine facility placement service that included food, testing, and transportation assistance for a state capitol and major urban center. The goal of the program was to provide safe isolation and quarantine options for individual residents at risk of not being able to comply with isolation and quarantine mandates. Drawing upon historical lived experiences in planning and implementing the system for isolation and quarantine facilities, this qualitative public health case study report applies the plan-do-study-act (PDSA) improvement model and framework to review and summarize the implementation of this system. This case study also offers lessons for a unique opportunity for collaboration led by a public behavioral health leadership that expands upon traditionally narrow infectious disease control, by developing a continuum of care that not only addresses immediate COVID-19 concerns but also longer-term supports and services including housing, access to mental health services, and other social services. This case study highlights the role of a state agency in building a coalition of agencies, including a public university, to respond to the pandemic. The case study also discusses how continuous learning was executed to improve delivery of care.
Assessing Recent Efforts to Improve Organization of Cancer Care in Poland: What Does the Evidence Tell Us?
Authors: Sagan Anna , Kowalska-Bobko Iwona , Gałązka-Sobotka Małgorzata , Holecki Tomasz , Maciejczyk Adam , McKee Martin
Published: August 2022

Poland has implemented two major organizational changes in recent years to improve cancer care. In 2015, a dedicated ‘fast pathway’ to diagnostics and treatment was implemented for patients suspected of having cancer. In 2019, the National Oncology Network began pilots in four regions of care pathways for cancer at five sites. Neither has been evaluated—no baseline information was collected, and what assessments were undertaken were limited to process measures. While the 2019 initiative was at least piloted, a national rollout has been announced even while the pilot is still ongoing and when concerns about certain aspects of the model have been raised. Given that cancer is the second largest cause of death in Poland and that cancer outcomes are worse compared to Western European averages, there is a particular need to ensure that models of care are informed by the evidence and adapted to the realities of the Polish healthcare system.
The Perceptions of Children and Adolescents with Cancer Regarding Nurses’ Communication Behaviors during Needle Procedures
Authors: Gómez-Gamboa Encarna , Rodrigo-Pedrosa Olga , San-Millán Marta , Saz-Roy Maria Angeles , Negre-Loscertales Anna , Puig-Llobet Montserrat
Published: August 2022

Background: Communicating with children and adolescents with cancer during a needle procedure can prove challenging for healthcare professionals. Objective: Our aim was to explore the perceptions of children and adolescents with cancer regarding communication with nurses during needle procedures. Method: Thus was a qualitative phenomenological study. Data were gathered through seven in-depth interviews with a convenience sample of children and adolescents with cancer. Data were analyzed using a grounded theory approach to identify themes in the participants’ narratives. Results: The analysis revealed three themes describing participants’ experience: (1) nurses need to explain clearly what they are going to do while also allowing children to express their emotions without feeling coerced; (2) nurses need to be honest and approachable and relate to children as active participants in the treatment process; and (3) it is distressing to hear other children who are undergoing a needle procedure cry out in pain. Further application of the constant comparison method yielded a core theme: (4) the pressures faced by oncology nurses lead them to focus on the technical side of procedures at the expense of their young patients’ communication needs. Conclusions: We suggest that hospital managers need to ensure that oncology nurses have sufficient training in communication skills and are confident in their ability to respect and respond to the communication preferences and needs of patients.
Prediction of Dichloroethene Concentration in the Groundwater of a Contaminated Site Using XGBoost and LSTM
Authors: Xia Feiyang , Jiang Dengdeng , Kong Lingya , Zhou Yan , Wei Jing , Ding Da , Chen Yun , Wang Guoqing , Deng Shaopo
Published: August 2022

Chlorinated aliphatic hydrocarbons (CAHs) are widely used in agriculture and industries and have become one of the most common groundwater contaminations. With the excellent performance of the deep learning method in predicting, LSTM and XGBoost were used to forecast dichloroethene (DCE) concentrations in a pesticide-contaminated site undergoing natural attenuation. The input variables included BTEX, vinyl chloride (VC), and five water quality indicators. In this study, the predictive performances of long short-term memory (LSTM) and extreme gradient boosting (XGBoost) were compared, and the influences of variables on models’ performances were evaluated. The results indicated XGBoost was more likely to capture DCE variation and was robust in high values, while the LSTM model presented better accuracy for all wells. The well with higher DCE concentrations would lower the model’s accuracy, and its influence was more evident in XGBoost than LSTM. The explanation of the SHapley Additive exPlanations (SHAP) value of each variable indicated high consistency with the rules of biodegradation in the real environment. LSTM and XGBoost could predict DCE concentrations through only using water quality variables, and LSTM performed better than XGBoost.
Effects of Various Numbers of Runs on the Success of Hamstring Injury Prevention Program in Sprinters
Authors: Sugiura Yusaku , Sakuma Kazuhiko , Fujita Shimpei , Aoki Kazuhiro , Takazawa Yuji
Published: August 2022

Studies have not adequately addressed the influence of fatigue, which is considered a major risk factor for hamstring injuries. Therefore, this study aimed to clarify how a muscle fatigue condition affects the success of hamstring injury prevention programs in sprinters. The study subjects were 613 collegiate male sprinters. They employed submaximal/maximal running for a large number of runs and supramaximal running for a small number of runs in daily training. The hamstring injury prevention program had become the most effective strategy in the past 24 seasons of track and field for preventing hamstring injuries. The number of sprinters who experienced hamstring injuries in three periods over the 24 seasons was recorded. The incidents of hamstring injuries during supramaximal running per athlete-seasons were 137.9, 60.6, and 6.7 for Periods I, II, and III, respectively, showing a significant decline (p < 0.01). Furthermore, the incidents of hamstring injuries during submaximal and maximal running per season showed no significant change. The results of this study indicate that by inducing muscle fatigue, a small number of runs makes hamstring injury prevention programs effective.
Who Is Able to Resist What Is Forbidden?—The Relationship between Health Literacy and Risk Behaviours in Secondary School Students in the Broader Social and Educational Context
Authors: Kleszczewska Dorota , Mazur Joanna , Porwit Katarzyna , Kowalewska Anna
Published: August 2022

In the last Health Behaviour in School-Aged Children (HBSC) survey conducted in Poland in 2018, a group of 17-year-old adolescents (n = 1663; mean age 17.63 ± 0.36 years) was included outside the international protocol. This allowed an assessment to be made of their level of health literacy (HL) using the 10-point HBSC research tool. The aim of the study was to investigate the relationship between HL and risk behaviours (RB). A standardised index of RB in the last 30 days was considered as an outcome measure. This index was significantly higher in the group with low HL (0.318 ± 1.269) in comparison with the group with high HL (−0.083 ± 0.962). In a multivariate linear regression model, the strongest predictors of RB were gender, academic performance and level of regional deprivation, but the association with HL remained significant. This significant association persisted in general schools and in girls but disappeared in vocational schools and in boys. It was also shown that in rural areas, good academic performance has a less significant impact on RB if the HL level is low. The analyses led to the conclusion that when examining the relationship between HL and RB in older adolescents, it is advisable to take into account gender, the educational track and neighbourhood characteristics.
Monitoring Psychometric States of Recovery to Improve Performance in Soccer Players: A Brief Review
Authors: Selmi Okba , Ouergui Ibrahim , Muscella Antonella , My Giulia , Marsigliante Santo , Nobari Hadi , Suzuki Katsuhiko , Bouassida Anissa
Published: August 2022

In order to maximize adaptations and to avoid nonfunctional overreaching syndrome or noncontact injury, coaches in high-performance sports must regularly monitor recovery before and after competitions/important training sessions and maintain well-being status. Therefore, quantifying and evaluating psychometric states of recovery during the season in sports teams such as soccer is important. Over the last years, there has been substantial growth in research related to psychometric states of recovery in soccer. The increase in research on this topic is coincident with the increase in popularity obtained by subjective monitoring of the pre-fatigue state of the players before each training sessions or match with a strong emphasis on the effects of well-being or recovery state. Among the subjective methods for players’ control, the Hooper index (HI) assesses the quality of sleep during the previous night, overall stress, fatigue, and delayed-onset muscle soreness. Additionally, the total quality of recovery (TQR) scale measures recovery status. The HI and TQR recorded before each training session or match were affected by the variability of training load (TL) and influenced the physical and technical performances, and the affective aspects of soccer players. Researchers have recommended wellness monitoring soccer players’ psychometric state of recovery before each training session or match in order to detect early signs of fatigue and optimize high-level training performance. This method allows for better detecting signs of individual fatigue and allows coaches to adapt and readjust the TL, and avoid physical and technical gaps in order to improve the performance of soccer players.
Effect of Parameters of Pool Geometry on Flow Structure in Nature-like Fishway
Authors: Hu Qiaoyi , Wang Xiaogang , Zhu Long , Du Shuai , He Feifei
Published: August 2022

Many uncertainties such as variable irregular structure and complex flow conditions bring difficulties to the design of a nature-like fishway. This study defines the main factors and parameters affecting flow conditions such as permeability ratio, offset ratio, bottom slope and pool length to simplify and generalize the irregular geometry of the nature-like fishway. According to the engineering requirements of the Mopiling nature-like fishway, the effect of the above parameters of pool geometry on the flow structure is investigated through a 3D turbulent numerical simulation, and the parameter thresholds are summarized according to the optimization of the flow conditions. The results show that under the same conditions, the maximum velocity of the control section increases with the increase in permeability ratio, bottom slope and pool length, and the offset ratio has limited effect on the maximum velocity of the control section. It is recommended that when the bottom slope is 1/250 and the pool length is 10 m, the permeability ratio should not be greater than 0.30 and the offset ratio should be located between 0.15 and 0.60. When the bottom slope is adjusted to 1/200, it is recommended to control the permeability ratio below 0.20, the offset ratio between 0.30 and 0.60, and the pool length can be adjusted to 8 m. Within the above threshold range of the design parameters, the maximum velocity in the fishway can be basically controlled at about 1.0 m/s. The mainstream in the pool is clear and the flow pattern is good, which can basically satisfy the requirements of fish passing. The relevant design parameters and optimization strategies can provide reference for similar projects.
A Spatial Adaptation Strategy for Safe Campus Open Spaces during the COVID-19 Pandemic: The Case of Korea University
Authors: Manifesty Odilia Renaningtyas , Lee Junga
Published: August 2022

Open spaces on campus offer various opportunities for students. However, the coronavirus disease (COVID-19) pandemic has affected students’ comfort when occupying open spaces on campus. The purpose of this study is to investigate possible spatial adaptation strategies for safe campus open spaces during the COVID-19 pandemic. For this research, a case study was conducted using a mixed methodology with behavioral mapping that investigated students’ perceptions at Korea University, Seoul, Korea. A qualitative approach was first conducted with behavioral mapping; the results show that despite some behavioral and spatial changes, people still occupy open spaces on campus for various meaningful activities. A quantitative approach with structural equation modeling (SEM) was also conducted to understand the required spatial modifications to improve the safety of open spaces on campus. The positive correlation between (i) social distancing measures, (ii) health protocols, and (iii) accessibility and occupational comfort with (iv) individuals’ fear of COVID-19 as a positive moderation are the four hypotheses proposed in this study. The results suggest that social distancing measures have no correlation with occupational comfort, while accessibility has the largest positive correlation. Suggestions are presented for providing accessible and equally distributed open spaces on campus to avoid overcrowding. Spatial health protocols are also found to positively correlate with occupational comfort, and the perception of the severity of COVID-19 strengthens this correlation. Tangible physical measures to prevent the spread of the virus are necessary to improve students’ sense of comfort and safety in open spaces on campus.
Characteristics Analysis and Identification of Key Sectors of Air Pollutant Emissions in China from the Perspective of Complex Metabolic Network
Authors: Song Jiekun , Jiang Lina , He Zeguo , Liu Zhicheng , Leng Xueli
Published: August 2022

Presently, China is in a critical period of economic transformation and upgrading. At the same time, it is also facing the pressure of serious atmospheric environmental pollution, which seriously threatens human health and hinders the sustainable economic development. Air pollutants are closely related to economic sectors, which together constitute a complex network. Air pollutants form an input–output ecological metabolic relationship among different sectors. Therefore, from the perspective of complex metabolic network, this study first constructs an environmental input–output model and then comprehensively uses the relevant methods of ecological network analysis and complex network analysis to analyze the characteristics of China’s air pollutant emission system. Secondly, the key joint sectors of NOx and PM emissions are determined from the supply side and the demand side, respectively. Finally, the corresponding emission reduction measures are proposed for the identified key sectors.
The Effects of High-Intensity Power Training versus Traditional Resistance Training on Exercise Performance
Authors: Chang Yu-Hua , Chou Yi-Chen , Chang Yun-Chi , Tan Kok-Hwa , Wu Mei-Hsuan
Published: August 2022

Background: High-intensity interval training (HIIT) features short, repeated bursts of relatively vigorous exercise with intermittent periods of rest or low-intensity exercise. High-intensity power training (HIPT), in combination with HIIT and traditional resistance training (TRT), is characterized as multijoint high-intensity resistance exercises with low interset rest periods. HIPT requires people to finish the exercise as fast as possible, which increases acute physiological demands. The aim of the study was to investigate the differences between eight-week HIPT or TRT on exercise performance. Methods: Twenty-four college students were recruited and randomly assigned to either the HIPT or TRT group in a counterbalanced order. The power of upper and lower limbs (50% 1RM bench press and vertical jump) and anaerobic power were tested before and after the training (weeks 0 and 9). The results were analyzed by two-way analysis of variance (ANOVA) or Friedman’s test with a significance level of α = 0.05 to compare the effects of the intervention on exercise performance. Results: There were significant differences in the explosive force of the upper and lower limbs between the pretest and post-test in both the HIPT and TRT groups (p < 0.05). However, only the HIPT group showed a significant difference in the mean power on the Wingate anaerobic test between the pretest and post-test (p < 0.05). Conclusions: Both HIPT and TRT can improve upper and lower limb explosive force. HIPT is an efficient training protocol, which took less time and produced a better improvement in mean anaerobic power.
Clinical and Epidemiological Approach to Delirium in an Acute Care Unit: A Cross-Sectional Study
Authors: Jorge-Samitier Pablo , Juárez-Vela Raúl , Santolalla-Arnedo Iván , Cobos-Rincón Ana , Santos-Sánchez José Ángel , Gea-Caballero Vicente , Satústegui-Dorda Pedro José , Anguas-Gracia Ana , Tejada-Garrido Clara Isabel , Urcola-Pardo Fernando , Fernández-Rodrigo María Teresa
Published: August 2022

During hospital admissions, the union of various factors, those related to acute pathology, dependency conditions, cognitive impairment, change of habitual environment, and others, can cause delirium. Acute delirium in the elderly (ADE) occurs in around a third of patients over 70 years of age. The syndrome generates serious complications that increase hospital morbidity and mortality and a high cost for the health administration. This study aimed to determine the clinical and epidemiological profile of ADE in an internal medicine unit. A descriptive cross-sectional study was carried out using a convenience test. A total of 356 patients participated between September and November 2021. Sociodemographic variables, predisposing and precipitating factors of ADE, methods of action against ADE, and the impact on functional and cognitive deterioration were analyzed. A total of 35.1% of the patients developed ADE, mostly of the hyperactive type and of nocturnal appearance. ADE was mainly treated with psychoactive drugs and 22% required mechanical restraint, with non-pharmacological preventive strategies, support, and caregiver training being the main tools for controlling ADE during hospital admission.
Norovirus Intestinal Infection and Lewy Body Disease in an Older Patient with Acute Cognitive Impairment
Authors: Moreno-Valladares Manuel , Moncho-Amor Veronica , Bernal-Simon Iraide , Agirre-Iturrioz Eñaut , Álvarez-Satta María , Matheu Ander
Published: August 2022

We present a case report on an older woman with unspecific symptoms and predominant long-term gastrointestinal disturbances, acute overall health deterioration with loss of autonomy for daily activities, and cognitive impairment. Autopsy revealed the presence of alpha-synuclein deposits spread into intestinal mucosa lesions, enteric plexuses, pelvic and retroperitoneal nerves and ganglia, and other organs as well as Lewy pathology in the central nervous system (CNS). Moreover, we isolated norovirus from the patient, indicating active infection in the colon and detected colocalization of norovirus and alpha-synuclein in different regions of the patient’s brain. In view of this, we report a concomitant norovirus infection with synthesis of alpha-synuclein in the gastrointestinal mucosa and Lewy pathology in the CNS, which might support Braak’s hypothesis about the pathogenic mechanisms underlying synucleinopathies.
Inflammation in Health and Disease: New Insights and Therapeutic Avenues
Authors: Scotece Morena , Conde-Aranda Javier
Published: August 2022

The inflammatory response is an adaptive mechanism that evolved to fight against infections and tissue damage [...]
Molecular Mechanisms Underlying Intensive Care Unit-Acquired Weakness and Sarcopenia
Authors: Kanova Marcela , Kohout Pavel
Published: August 2022

Skeletal muscle is a highly adaptable organ, and its amount declines under catabolic conditions such as critical illness. Aging is accompanied by a gradual loss of muscle, especially when physical activity decreases. Intensive care unit-acquired weakness is a common and highly serious neuromuscular complication in critically ill patients. It is a consequence of critical illness and is characterized by a systemic inflammatory response, leading to metabolic stress, that causes the development of multiple organ dysfunction. Muscle dysfunction is an important component of this syndrome, and the degree of catabolism corresponds to the severity of the condition. The population of critically ill is aging; thus, we face another negative effect—sarcopenia—the age-related decline of skeletal muscle mass and function. Low-grade inflammation gradually accumulates over time, inhibits proteosynthesis, worsens anabolic resistance, and increases insulin resistance. The cumulative consequence is a gradual decline in muscle recovery and muscle mass. The clinical manifestation for both of the above conditions is skeletal muscle weakness, with macromolecular damage, and a common mechanism—mitochondrial dysfunction. In this review, we compare the molecular mechanisms underlying the two types of muscle atrophy, and address questions regarding possible shared molecular mechanisms, and whether critical illness accelerates the aging process.
Large-Scale Identification of Multiple Classes of Host Defense Peptide-Inducing Compounds for Antimicrobial Therapy
Authors: Lyu Wentao , Mi Dehui , Vinson Paige N. , Xiao Yingping , Zhang Guolong
Published: August 2022

The rapid emergence of antibiotic resistance demands new antimicrobial strategies that are less likely to develop resistance. Augmenting the synthesis of endogenous host defense peptides (HDPs) has been proven to be an effective host-directed therapeutic approach. This study aimed to identify small-molecule compounds with a strong ability to induce endogenous HDP synthesis for further development as novel antimicrobial agents. By employing a stable HDP promoter-driven luciferase reporter cell line known as HTC/AvBD9-luc, we performed high-throughput screening of 5002 natural and synthetic compounds and identified 110 hits with a minimum Z-score of 2.0. Although they were structurally and functionally diverse, half of these hits were inhibitors of class I histone deacetylases, the phosphoinositide 3-kinase pathway, ion channels, and dopamine and serotonin receptors. Further validations revealed mocetinostat, a benzamide histone deacetylase inhibitor, to be highly potent in enhancing the expression of multiple HDP genes in chicken macrophage cell lines and jejunal explants. Importantly, mocetinostat was more efficient than entinostat and tucidinostat, two structural analogs, in promoting HDP gene expression and the antibacterial activity of chicken macrophages. Taken together, mocetinostat, with its ability to enhance HDP synthesis and the antibacterial activity of host cells, could be potentially developed as a novel antimicrobial for disease control and prevention.
Copper Foam as Active Catalysts for the Borylation of α, β-Unsaturated Compounds
Authors: Zheng Kewang , Liu Miao , Meng Zhifei , Xiao Zufeng , Zhong Fei , Wang Wei , Qin Caiqin
Published: August 2022

The use of simple, inexpensive, and efficient methods to construct carbon–boron and carbon–oxygen bonds has been a hot research topic in organic synthesis. We demonstrated that the desired β-boronic acid products can be obtained under mild conditions using copper foam as an efficient heterogeneous catalyst. The structure of copper foam before and after the reaction was investigated by polarized light microscopy (PM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), and the results have shown that the structure of the catalyst copper foam remained unchanged before and after the reaction. The XPS test results showed that the Cu(0) content increased after the reaction, indicating that copper may be involved in the boron addition reaction. The specific optimization conditions were as follows: CH3COCH3 and H2O were used as mixed solvents, 4-methoxychalcone was used as the raw material, 8 mg of catalyst was used and the reaction was carried out at room temperature and under air for 10 h. The yield of the product obtained was up to 92%, and the catalytic efficiency of the catalytic material remained largely unchanged after five cycles of use.
New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer’s Disease Research
Authors: Koźmiński Przemysław , Niedziałek Dorota , Wieczorek Grzegorz , Halik Paweł K. , Czarnecka Kamila , Rogut Aleksandra , Cheda Łukasz , Rogulski Zbigniew , Szymański Paweł , Gniazdowska Ewa
Published: August 2022

Viral pneumonia caused by highly infectious SARS-CoV-2 poses a higher risk to older people and those who have underlying health conditions, including Alzheimer’s disease. In this work we present newly designed tacrine-based radioconjugates with physicochemical and biological properties that are crucial for the potential application as diagnostic radiopharmaceuticals. A set of ten tacrine derivatives was synthesized, labelled with gallium-68 and fully characterized in the context of their physicochemical properties. Based on these results, the final two most promising radioconjugates, [68Ga]Ga-NODAGA-Bn-NH(CH2)9Tac and [68Ga]Ga-THP-NH(CH2)9Tac, were selected for biodistribution studies. The latter compound was proven to be a good inhibitor of cholinesterases with significant affinity toward the lungs, according to the biodistribution studies. On the basis of molecular modelling combined with in vitro studies, we unraveled which structural properties of the developed tacrine derivatives are crucial for high affinity toward acetylcholinesterase, whose increased levels in lung tissues in the course of coronavirus disease indicate the onset of pneumonia. The radiopharmaceutical [68Ga]Ga-THP-NH(CH2)9Tac was ultimately selected due to its increased accuracy and improved sensitivity in PET imaging of lung tissue with high levels of acetylcholinesterase, and it may become a novel potential diagnostic modality for the determination of lung perfusion, including in inflammation after COVID-19.
Dual Costimulatory and Coinhibitory Targeting with a Hybrid Fusion Protein as an Immunomodulatory Therapy in Lupus Nephritis Mice Models
Authors: Guiteras Jordi , Crespo Elena , Fontova Pere , Bolaños Nuria , Gomà Montse , Castaño Esther , Bestard Oriol , Grinyó Josep M. , Torras Joan
Published: August 2022

Systemic lupus erythematosus is a complex autoimmune disorder mostly mediated by B-cells in which costimulatory signals are involved. This immune dysregulation can cause tissue damage and inflammation of the kidney, resulting in lupus nephritis and chronic renal failure. Given the previous experience reported with CTLA4-Ig as well as recent understanding of the PD-1 pathway in this setting, our group was encouraged to evaluate, in the NZBWF1 model, a human fusion recombinant protein (Hybri) with two domains: CTLA4, blocking the CD28—CD80 costimulatory pathway, and PD-L2, exacerbating the PD-1–PD-L2 coinhibitory pathway. After achieving good results in this model, we decided to validate the therapeutic effect of Hybri in the more severe MRL/lpr model of lupus nephritis. The intraperitoneal administration of Hybri prevented the progression of proteinuria and anti-dsDNA antibodies to levels like those of cyclophosphamide and reduced the histological score, infiltration of B-cells, T-cells, and macrophages and immune deposition in both lupus-prone models. Additionally, Hybri treatment produced changes in both inflammatory-related circulating cytokines and kidney gene expression. To summarize, both in vivo studies revealed that the Hybri effect on costimulatory-coinhibitory pathways may effectively mitigate lupus nephritis, with potential for use as a maintenance therapy.
Relaxin Affects Airway Remodeling Genes Expression through Various Signal Pathways Connected with Transcription Factors
Authors: Wieczfinska Joanna , Pawliczak Rafal
Published: August 2022

Fibrosis is one of the parameters of lung tissue remodeling in asthma. Relaxin has emerged as a natural suppressor of fibrosis, showing efficacy in the prevention of a multiple models of fibrosis. Therefore, the aim of this study was to analyze the aptitudes of relaxin, in the context of its immunomodulatory properties, in the development of airway remodeling. WI-38 and HFL1 fibroblasts, as well as epithelial cells (NHBE), were incubated with relaxin. Additionally, remodeling conditions were induced with two serotypes of rhinovirus (HRV). The expression of the genes contributing to airway remodeling were determined. Moreover, NF-κB, c-Myc, and STAT3 were knocked down to analyze the pathways involved in airway remodeling. Relaxin decreased the mRNA expression of collagen I and TGF-β and increased the expression of MMP-9 (p < 0.05). Relaxin also decreased HRV-induced expression of collagen I and α-SMA (p < 0.05). Moreover, all the analyzed transcription factors—NF-κB, c-Myc, and STAT3—have shown its influence on the pathways connected with relaxin action. Though relaxin requires further study, our results suggest that this natural compound offers great potential for inhibition of the development, or even reversing, of factors related to airway remodeling. The presented contribution of the investigated transcription factors in this process additionally increases its potential possibilities through a variety of its activity pathways.
Tracking Immature Testicular Tissue after Vitrification In Vitro and In Vivo for Pre-Pubertal Fertility Preservation: A Translational Transgenic Mouse Model
Authors: Lu Buo-Jia , Huang Ya-Li , Liu Yung-Liang , Chen Brian Shiian , Lin Bou-Zenn , Chen Chi-Huang
Published: August 2022

Pediatric cancer survivors experiencing gonadotoxic chemoradiation therapy may encounter subfertility or permanent infertility. However, previous studies of cryopreservation of immature testicular tissue (ITT) have mainly been limited to in vitro studies. In this study, we aim to evaluate in vitro and in vivo bioluminescence imaging (BLI) for solid surface-vitrified (SSV) ITT grafts until adulthood. The donors and recipients were transgenic and wild-type mice, respectively, with fresh ITT grafts used as the control group. In our study, the frozen ITT grafts remained intact as shown in the BLI, scanning electron microscopy (SEM) and immunohistochemistry (IHC) analyses. Graft survival was analyzed by BLI on days 1, 2, 5, 7, and 31 after transplantation. The signals decreased by quantum yield between days 2 and 5 in both groups, but gradually increased afterwards until day 31, which were significantly stronger than day 1 after transplantation (p = 0.008). The differences between the two groups were constantly insignificant, suggesting that both fresh and SSV ITT can survive, accompanied by spermatogenesis, until adulthood. The ITT in both groups presented similar BLI intensity and intact cells and ultrastructures for spermatogenesis. This translational model demonstrates the great potential of SSV for ITT in pre-pubertal male fertility preservation.
Substrates of the Human Brain Proton-Organic Cation Antiporter and Comparison with Organic Cation Transporter 1 Activities
Authors: Doetsch David A. , Ansari Salim , Jensen Ole , Gebauer Lukas , Dücker Christof , Brockmöller Jürgen , Sachkova Alexandra
Published: August 2022

Many organic cations (OCs) may be transported through membranes by a genetically still uncharacterized proton-organic cation (H + OC) antiporter. Here, we characterized an extended substrate spectrum of this antiporter. We studied the uptake of 72 drugs in hCMEC/D3 cells as a model of the human blood–brain barrier. All 72 drugs were tested with exchange transport assays and the transport of 26 of the drugs was studied in more detail concerning concentration-dependent uptake and susceptibility to specific inhibitors. According to exchange transport assays, 37 (51%) drugs were good substrates of the H + OC antiporter. From 26 drugs characterized in more detail, 23 were consistently identified as substrates of the H + OC antiporter in six different assays and transport kinetic constants could be identified with intrinsic clearances between 0.2 (ephedrine) and 201 (imipramine) mL × minute−1 × g protein−1. Excellent substrates of the H + OC antiporter were no substrates of organic cation transporter OCT1 and vice versa. Good substrates of the H + OC antiporter were more hydrophobic and had a lower topological polar surface area than non-substrates or OCT1 substrates. These data and further research on the H + OC antiporter may result in a better understanding of pharmacokinetics, drug–drug interactions and variations in pharmacokinetics.
Aggregated Genomic Data as Cohort-Specific Allelic Frequencies can Boost Variants and Genes Prioritization in Non-Solved Cases of Inherited Retinal Dystrophies
Authors: Iancu Ionut-Florin , Perea-Romero Irene , Núñez-Moreno Gonzalo , de la Fuente Lorena , Romero Raquel , Ávila-Fernandez Almudena , Trujillo-Tiebas María José , Riveiro-Álvarez Rosa , Almoguera Berta , Martín-Mérida Inmaculada , Del Pozo-Valero Marta , Damián-Verde Alejandra , Cortón Marta , Ayuso Carmen , Minguez Pablo
Published: August 2022

The introduction of NGS in genetic diagnosis has increased the repertoire of variants and genes involved and the amount of genomic information produced. We built an allelic-frequency (AF) database for a heterogeneous cohort of genetic diseases to explore the aggregated genomic information and boost diagnosis in inherited retinal dystrophies (IRD). We retrospectively selected 5683 index-cases with clinical exome sequencing tests available, 1766 with IRD and the rest with diverse genetic diseases. We calculated a subcohort’s IRD-specific AF and compared it with suitable pseudocontrols. For non-solved IRD cases, we prioritized variants with a significant increment of frequencies, with eight variants that may help to explain the phenotype, and 10/11 of uncertain significance that were reclassified as probably pathogenic according to ACMG. Moreover, we developed a method to highlight genes with more frequent pathogenic variants in IRD cases than in pseudocontrols weighted by the increment of benign variants in the same comparison. We identified 18 genes for further studies that provided new insights in five cases. This resource can also help one to calculate the carrier frequency in IRD genes. A cohort-specific AF database assists with variants and genes prioritization and operates as an engine that provides a new hypothesis in non-solved cases, augmenting the diagnosis rate.
Genome-Wide Identification and Analysis of the BBX Gene Family and Its Role in Carotenoid Biosynthesis in Wolfberry (Lycium barbarum L.)
Authors: Yin Yue , Shi Hongyan , Mi Jia , Qin Xiaoya , Zhao Jianhua , Zhang Dekai , Guo Cong , He Xinru , An Wei , Cao Youlong , Zhu Jianhua , Zhan Xiangqiang
Published: August 2022

The B-box proteins (BBXs) are a family of zinc-finger transcription factors with one/two B-Box domain(s) and play important roles in plant growth and development as well as stress responses. Wolfberry (Lycium barbarum L.) is an important traditional medicinal and food supplement in China, and its genome has recently been released. However, comprehensive studies of BBX genes in Lycium species are lacking. In this study, 28 LbaBBX genes were identified and classified into five clades by a phylogeny analysis with BBX proteins from Arabidopsis thaliana and the LbaBBXs have similar protein motifs and gene structures. Promoter cis-regulatory element prediction revealed that LbaBBXs might be highly responsive to light, phytohormone, and stress conditions. A synteny analysis indicated that 23, 20, 8, and 5 LbaBBX genes were orthologous to Solanum lycopersicum, Solanum melongena, Capsicum annuum, and Arabidopsis thaliana, respectively. The gene pairs encoding LbaBBX proteins evolved under strong purifying selection. In addition, the carotenoid content and expression patterns of selected LbaBBX genes were analyzed. LbaBBX2 and LbaBBX4 might play key roles in the regulation of zeaxanthin and antheraxanthin biosynthesis. Overall, this study improves our understanding of LbaBBX gene family characteristics and identifies genes involved in the regulation of carotenoid biosynthesis in wolfberry.
Influence of Polydatin on the Tumor Microenvironment In Vitro: Studies with a Colon Cancer Cell Model
Authors: De Gregorio Alex , Krasnowska Ewa Krystyna , Zonfrillo Manuela , Ravagnan Giampietro , Bordignon Valentina , Bonmassar Enzo , Fuggetta Maria Pia
Published: August 2022

The tumor microenvironment of colon carcinoma, the site at which tumor cells and the host immune system interact, is influenced by signals from tumor cells, immunocompetent cells, and bacterial components, including LPS. A large amount of LPS is available in the colon, and this could promote inflammation and metastasis by enhancing tumor cell adhesion to the endothelium. Polydatin (PD), the 3-β-D-glucoside of trans-resveratrol, is a polyphenol with anti-cancer, anti-inflammatory, and immunoregulatory effects. This study was designed to explore whether PD is able to produce antiproliferative effects on three colon cancer lines, to reduce the expression of adhesion molecules that are upregulated by LPS on endothelial cells, and to decrease the proinflammatory cytokines released in culture supernatants. Actually, we investigated the effects of PD on tumor growth in a coculture model with human mononuclear cells (MNCs) that mimics, at least in part, an in vitro tumor microenvironment. The results showed that PD alone or in combination with MNC exerts antiproliferative and proapoptotic effects on cancer cells, inhibits the production of the immunosuppressive cytokine IL-10 and of the proinflammatory cytokines upregulated by LPS, and reduces E-selectin and VCAM-1 on endothelial cells. These data provide preclinical support to the hypothesis that PD could be of potential benefit as a therapeutic adjuvant in colon cancer treatment and prevention.
Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma
Authors: Kanno Hidenori , Naito Sei , Obara Yutaro , Ito Hiromi , Ichiyanagi Osamu , Narisawa Takafumi , Kato Tomoyuki , Nagaoka Akira , Tsuchiya Norihiko
Published: August 2022

(1) Background: Extracellular signal-regulating kinase 5 (ERK5) has been implicated in many cellular functions, including survival, proliferation, and vascularization. Our objectives were to examine the expression and effect of ERK5 in clear cell renal cell carcinoma (ccRCC). (2) Methods: The expressions of ERK5 and its regulating micro-RNA miR-143 were investigated using immunohistochemistry and quantitative reverse transcriptase PCR in surgical specimens of ccRCC patients. With invitro and in vivo studies, we used pharmacologic ERK5 inhibitor XMD8-92, RNA interference, pre-miR-143 transduction, Western blotting, MTS assay, apoptosis assay, and subcutaneous xenograft model. (3) Results: A strong ERK5 expression in surgical specimen was associated with high-grade (p = 0.01), high-recurrence free rate (p = 0.02), and high cancer-specific survival (p = 0.03). Expression levels of ERK5 and miR-143 expression level were correlated (p = 0.049). Pre-miR-143 transduction into ccRCC cell A498 suppressed ERK5 expression. ERK5 inhibition enhanced cyclin-dependent kinase inhibitor p21 expression and decreased anti-apoptotic molecules BCL2, resulting in decreased cell proliferation and survival both in ccRCC and endothelial cells. In the xenograft model, ERK5 inhibitor XMD8-92 suppressed tumor growth. (4) Conclusions: ERK5 is regulated by miR-143, and ERK5 inhibition is a promising target for ccRCC treatment.
Thiosulfate-Cyanide Sulfurtransferase a Mitochondrial Essential Enzyme: From Cell Metabolism to the Biotechnological Applications
Authors: Buonvino Silvia , Arciero Ilaria , Melino Sonia
Published: August 2022

Thiosulfate: cyanide sulfurtransferase (TST), also named rhodanese, is an enzyme widely distributed in both prokaryotes and eukaryotes, where it plays a relevant role in mitochondrial function. TST enzyme is involved in several biochemical processes such as: cyanide detoxification, the transport of sulfur and selenium in biologically available forms, the restoration of iron–sulfur clusters, redox system maintenance and the mitochondrial import of 5S rRNA. Recently, the relevance of TST in metabolic diseases, such as diabetes, has been highlighted, opening the way for research on important aspects of sulfur metabolism in diabetes. This review underlines the structural and functional characteristics of TST, describing the physiological role and biomedical and biotechnological applications of this essential enzyme.
CSatDTA: Prediction of Drug–Target Binding Affinity Using Convolution Model with Self-Attention
Authors: Ghimire Ashutosh , Tayara Hilal , Xuan Zhenyu , Chong Kil To
Published: August 2022

Drug discovery, which aids to identify potential novel treatments, entails a broad range of fields of science, including chemistry, pharmacology, and biology. In the early stages of drug development, predicting drug–target affinity is crucial. The proposed model, the prediction of drug–target affinity using a convolution model with self-attention (CSatDTA), applies convolution-based self-attention mechanisms to the molecular drug and target sequences to predict drug–target affinity (DTA) effectively, unlike previous convolution methods, which exhibit significant limitations related to this aspect. The convolutional neural network (CNN) only works on a particular region of information, excluding comprehensive details. Self-attention, on the other hand, is a relatively recent technique for capturing long-range interactions that has been used primarily in sequence modeling tasks. The results of comparative experiments show that CSatDTA surpasses previous sequence-based or other approaches and has outstanding retention abilities.