bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-Effectiveness Analysis of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Venous Thromboembolism in China
Authors: Sun Ke-Xin , Cui Bin , Cao Shan-Shan , Huang Qi-Xiang , Xia Ru-Yi , Wang Wen-Jun , Wang Jing-Wen , Yu Feng , Ding Yi
Published: October 2021

Background: The drug therapy of venous thromboembolism (VTE) presents a significant economic burden to the health-care system in low- and middle-income countries. To understand which anticoagulation therapy is most cost-effective for clinical decision-making , the cost-effectiveness of apixaban (API) versus rivaroxaban (RIV), dabigatran (DAB), and low molecular weight heparin (LMWH), followed by vitamin K antagonist (VKA), in the treatment of VTE in China was assessed.

Methods: To access the quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs), a long-term cost-effectiveness analysis was constructed using a Markov model with 5 health states. The Markov model was developed using patient data collected from the Xijing Hospital from January 1, 2016 to January 1, 2021. The time horizon was set at 30 years, and a 6-month cycle length was used in the model. Costs and ICERs were reported in 2020 U.S. dollars. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were used to test the uncertainties. A Chinese health-care system perspective was used.

Results: In the base case, the data of 231 VTE patients were calculated in the base case analysis retrospectively. The RIV group resulted in a mean VTE attributable to 95% effective treatment. API, DAB, and VKA have a negative ICER (−187017.543, −284,674.922, and −9,283.339, respectively) and were absolutely dominated. The Markov model results confirmed this observation. The ICER of the API and RIV was negative (−216176.977), which belongs to the absolute inferiority scheme, and the ICER value of the DAB and VKA versus RIV was positive (110,577.872 and 836,846.343). Since the ICER of DAB and VKA exceeds the threshold, RIV therapy was likely to be the best choice for the treatment of VTE within the acceptable threshold range. The results of the sensitivity analysis revealed that the model output varied mostly with the cost in the DAB on-treatment therapy. In a probabilistic sensitivity analysis of 1,000 patients for 30 years, RIV has 100% probability of being cost-effective compared with other regimens when the WTP is $10973 per QALY. When WTP exceeded $148,000, DAB was more cost-effective than RIV.

Conclusions: Compared with LMWH + VKA and API, the results proved that RIV may be the most cost-effective treatment for VTE patients in China. Our findings could be helpful for physicians in clinical decision-making to select the appropriate treatment option for VTE.
Exosome CTLA-4 Regulates PTEN/CD44 Signal Pathway in Spleen Deficiency Internal Environment to Promote Invasion and Metastasis of Hepatocellular Carcinoma
Authors: Wang Yongdan , Li Pan , Mao Shuai , Mo Zhuomao , Cao Zhirui , Luo Jin , Zhou Meiling , Liu Xifeng , Zhang Shijun , Yu Ling
Published: October 2021

Hepatocellular carcinoma (HCC) is one of the most common primary cancers, and its pathogenesis is complicated and difficult to screen. Currently, there is no effective treatment. In traditional Chinese medicine, a large proportion of patients with HCC have been diagnosed with spleen deficiency (SD) syndrome and treated with tonifying traditional Chinese medicine, which has significant clinical efficacy. However, the role and molecular mechanism of SD in HCC remain unclear. In this study, 40 mice were randomly divided into four groups: control, SD, HCC, and SD-HCC groups. The liver cancer model of SD was established by reserpine induction and orthotopic transplantation. The effects of SD on the proliferation, apoptosis, invasion, and metastasis of HCC cells were studied by cell proliferation, cell apoptosis, cell scratch, and transwell assay. We found that compared with the HCC group, the protein expressions of cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), phosphatase and tensin homolog (PTEN), and AKT (also known as protein kinase B or PKB) in the exosomes of the SD-HCC group were upregulated. In addition, the metastases and self-renewal of exosomes in the SD-HCC group were more aggressive than those in the HCC group, which could be partially reversed with the addition of CTLA-4 inhibitors. Further studies showed that in the internal environment of SD, CTLA-4 promoted tumor invasion and metastasis by regulating the PTEN/CD44 pathway. In conclusion, our findings suggest that during SD in the internal environment, exosome CTLA-4 regulates the PTEN/CD44 signal pathway to promote the proliferation, self-renewal, and metastasis of liver cancer.
Dimerized Translationally Controlled Tumor Protein-Binding Peptide 2 Attenuates Systemic Anaphylactic Reactions Through Direct Suppression of Mast Cell Degranulation
Authors: Cho Hyunsoo , Park Jiyoung , Kim Hyo Kyeong , Hwang Eun Sook , Lee Kyunglim
Published: October 2021

Dimerized translationally controlled tumor protein (dTCTP) amplifies allergic responses through activation of several types of immune cells and release of inflammatory mediators. In particular, dTCTP plays an important role in histamine release by triggering mast cells and has been proposed as a target in the treatment of allergic diseases. dTCTP-binding peptide 2 (dTBP2) is known to attenuate severe allergic rhinitis and asthma through inhibition of dTCTP activity on airway epithelial cells and T cells; however, it is unclear whether dTBP2 affects mast cell function and mast cell disease. In this study, we explored the effects of dTBP2 on mast cell degranulation and allergen-induced anaphylactic reactions. We found that bacterial product lipopolysaccharide increased the expression of dTCTP in mast cells and rapidly released dTCTP by the mast cell stimulator compound 48/80. Interestingly, the released dTCTP further promoted mast cell degranulation in an autocrine activation manner and increased calcium mobilization in mast cells, which is essential for degranulation. Furthermore, dTBP2 directly and dose-dependently inhibitedin vitromast cell degranulation enhanced by compound 48/80, suggesting a direct and potent anti-anaphylactic activity of dTBP2. dTBP2 also significantly suppressed the dTCTP-induced degranulation and histamine release through inhibition of the p38 MAPK signaling pathway and suppression of lysosomal expansion and calcium mobilization in mast cells. More importantly,in vivoadministration of dTBP2 decreased mortality and significantly attenuated histamine release and inflammatory cytokine production in compound 48/80-induced systemic anaphylactic reactions. These results suggest that dTBP2 is beneficial for the control of anaphylaxis with increased dTCTP.
Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation
Authors: de Maar Josanne S. , Rousou Charis , van Elburg Benjamin , Vos Hendrik J. , Lajoinie Guillaume P.R. , Bos Clemens , Moonen Chrit T.W. , Deckers Roel
Published: October 2021

Chemotherapy efficacy is often reduced by insufficient drug uptake in tumor cells. The combination of ultrasound and microbubbles (USMB) has been shown to improve drug delivery and to enhance the efficacy of several drugs in vitro and in vivo, through effects collectively known as sonopermeation. However, clinical translation of USMB therapy is hampered by the large variety of (non-clinical) US set-ups and US parameters that are used in these studies, which are not easily translated to clinical practice. In order to facilitate clinical translation, the aim of this study was to prove that USMB therapy using a clinical ultrasound system (Philips iU22) in combination with clinically approved microbubbles (SonoVue) leads to efficient in vitro sonopermeation. To this end, we measured the efficacy of USMB therapy for different US probes (S5-1, C5-1 and C9-4) and US parameters in FaDu cells. The US probe with the lowest central frequency (i.e. 1.6 MHz for S5-1) showed the highest USMB-induced intracellular uptake of the fluorescent dye SYTOX™ Green (SG). These SG uptake levels were comparable to or even higher than those obtained with a custom-built US system with optimized US parameters. Moreover, USMB therapy with both the clinical and the custom-built US system increased the cytotoxicity of the hydrophilic drug bleomycin. Our results demonstrate that a clinical US system can be used to perform USMB therapy as efficiently as a single-element transducer set-up with optimized US parameters. Therefore, future trials could be based on these clinical US systems, including validated US parameters, in order to accelerate successful translation of USMB therapy.
CRISPA: A Non-viral, Transient Cas9 Delivery System Based on Reengineered Anthrax Toxin
Authors: Hirschenberger Maximilian , Stadler Nicole , Fellermann Maximilian , Sparrer Konstantin M. J. , Kirchhoff Frank , Barth Holger , Papatheodorou Panagiotis
Published: October 2021

Translating the CRISPR/Cas9 genome editing technology into clinics is still hampered by rather unspecific, unsafe and/or inconvenient approaches for the delivery of its main components - the Cas9 endonuclease and a guide RNA - into cells. Here, we describe the development of a novel transient and non-viral Cas9 delivery strategy based on the translocation machinery of the Bacillus anthracis anthrax toxin, PA (protective antigen). We show that Cas9 variants fused to the N-terminus of the lethal factor or to a hexahistidine tag are shuttled through channels formed by PA into the cytosol of human cells. As proof-of-principle, we applied our new approach, denoted as CRISPA, to knock out lipolysis-stimulated lipoprotein receptor (LSR) in the human colon cancer cell line HCT116 and green-fluorescent protein (GFP) in human embryonic kidney 293T cells stably expressing GFP. Notably, we confirmed that the transporter PA can be adapted to recognize specific host cell-surface receptor proteins and may be optimized for cell type-selective delivery of Cas9. Altogether, CRISPA provides a novel, transient and non-viral way to deliver Cas9 into specific cells. Thus, this system is an additional step towards safe translation of the CRISPR/Cas9 technology into clinics.
Association Between Changes in Serum and Skeletal Muscle Metabolomics Profile With Maximum Power Output Gains in Response to Different Aerobic Training Programs: The Times Study
Authors: Castro Alex , Duft Renata G. , de Oliveira-Nunes Silas Gabriel , de Andrade André L. L. , Cavaglieri Claudia R. , Chacon-Mikahil Mara Patricia Traina
Published: October 2021

Purpose: High heterogeneity of the response of cardiorespiratory fitness (CRF) to standardized exercise doses has been reported in different training programs, but the associated mechanisms are not widely known. This study investigated whether changes in the metabolic profile and pathways in blood serum and the skeletal muscle are associated with the inter-individual variability of CRF responses to 8-wk of continuous endurance training (ET) or high-intensity interval training (HIIT).

Methods: Eighty men, young and sedentary, were randomized into three groups, of which 70 completed 8 wk of intervention (> 90% of sessions): ET, HIIT, or control. Blood and vastus lateralis muscle tissue samples, as well as the measurement of CRF [maximal power output (MPO)] were obtained before and after the intervention. Blood serum and skeletal muscle samples were analyzed by 600 MHz 1H-NMR spectroscopy (metabolomics). Associations between the pretraining to post-training changes in the metabolic profile and MPO gains were explored via three analytical approaches: (1) correlation between pretraining to post-training changes in metabolites' concentration levels and MPO gains; (2) significant differences between low and high MPO responders; and (3) metabolite contribution to significantly altered pathways related to MPO gains. After, metabolites within these three levels of evidence were analyzed by multiple stepwise linear regression. The significance level was set at 1%.

Results: The metabolomics profile panel yielded 43 serum and 70 muscle metabolites. From the metabolites within the three levels of evidence (15 serum and 4 muscle metabolites for ET; 5 serum and 1 muscle metabolites for HIIT), the variance in MPO gains was explained: 77.4% by the intervention effects, 6.9, 2.3, 3.2, and 2.2% by changes in skeletal muscle pyruvate and valine, serum glutamine and creatine phosphate, respectively, in ET; and 80.9% by the intervention effects; 7.2, 2.2, and 1.2% by changes in skeletal muscle glycolate, serum creatine and creatine phosphate, respectively, in HIIT. The most changed and impacted pathways by these metabolites were: arginine and proline metabolism, glycine, serine and threonine metabolism, and glyoxylate and dicarboxylate metabolism for both ET and HIIT programs; and additional alanine, aspartate and glutamate metabolism, arginine biosynthesis, glycolysis/gluconeogenesis, and pyruvate metabolism for ET.

Conclusion: These results suggest that regulating the metabolism of amino acids and carbohydrates may be a potential mechanism for understanding the inter-individual variability of CRF in responses to ET and HIIT programs.
Protective Effect of γ-Aminobutyric Acid Against Chilling Stress During Reproductive Stage in Tomato Plants Through Modulation of Sugar Metabolism, Chloroplast Integrity, and Antioxidative Defense Systems
Authors: Abd Elbar Ola H. , Elkelish Amr , Niedbała Gniewko , Farag Reham , Wojciechowski Tomasz , Mukherjee Soumya , Abou-Hadid Ayman F. , El-Hennawy Hussien M. , Abou El-Yazied Ahmed , Abd El-Gawad Hany G. , Azab Ehab , Gobouri Adil A. , El Nahhas Nihal , El-Sawy Ahmed M. , Bondok Ahmed , Ibrahim Mohamed F. M.
Published: October 2021

Despite the role of γ-aminobutyric acid (GABA) in plant tolerance to chilling stress having been widely discussed in the seedling stage, very little information is clear regarding its implication in chilling tolerance during the reproductive stage of the plant. Here, we investigated the influence of GABA (1 and 2mM) as a foliar application on tomato plants (Solanum lycopersicum L. cv. Super Marmande) subjected to chilling stress (5°C for 6h/day) for 5 successive days during the flowering stage. The results indicated that applied GABA differentially influenced leaf pigment composition by decreasing the chlorophyll a/b ratio and increasing the anthocyanin relative to total chlorophyll. However, carotenoids were not affected in both GABA-treated and non-treated stressed plants. Root tissues significantly exhibited an increase in thermo-tolerance in GABA-treated plants. Furthermore, applied GABA substantially alleviated the chilling-induced oxidative damage by protecting cell membrane integrity and reducing malondialdehyde (MDA) and H2O2. This positive effect of GABA was associated with enhancing the activity of phenylalanine ammonia-lyase (PAL), catalase (CAT), superoxide dismutase (SOD), and ascorbate peroxidase (APX). Conversely, a downregulation of peroxidase (POX) and polyphenol oxidase (PPO) was observed under chilling stress which indicates its relevance in phenol metabolism. Interesting correlations were obtained between GABA-induced upregulation of sugar metabolism coinciding with altering secondary metabolism, activities of antioxidant enzymes, and maintaining the integrity of plastids’ ultrastructure Eventually, applied GABA especially at 2mM improved the fruit yield and could be recommended to mitigate the damage of chilling stress in tomato plants.
Drought Responsive Putative Marker-Trait Association in Tall Fescue as Influenced by the Presence of a Novel Endophyte
Authors: Talukder Shyamal K. , Islam Md. Shofiqul , Krom Nick , Chang Junil , Saha Malay C.
Published: October 2021

Tall fescue (Festuca arundinaceaSchreb.) is one of the most important cool-season perennial obligatory outcrossing forage grasses in the United States. The production and persistence of tall fescue is significantly affected by drought in the south-central United States. Shoot-specific endophyte (Epichloë coenophiala)-infected tall fescue showed superior performance under both biotic and abiotic stress conditions. We performed a genome-wide association analysis using clonal pairs of novel endophyte AR584-positive (EP) and endophyte-free (EF) tall fescue populations consisting of 205 genotypes to identify marker-trait associations (MTAs) that contribute to drought tolerance. The experiment was performed through November 2014 to June 2018 in the field, and phenotypic data were taken on plant height, plant spread, plant vigor, and dry biomass weight under natural summer conditions of sporadic drought. Genotyping-by-sequencing of the population generated 3,597 high quality single nucleotide polymorphisms (SNPs) for further analysis. We identified 26 putative drought responsive MTAs (17 specific to EP, eight specific to EF, and one in both EP and EF populations) and nine of them (i.e., V.ep_10, S.ef_12, V.ep_27, HSV.ef_31, S.ep_30, SV.ef_32, V.ep_68, V.ef_56, and H.ef_57) were identified within 0.5 Mb region in the tall fescue genome (44.5–44.7, 75.3–75.8, 77.5–77.9 and 143.7–144.2 Mb). Using 26 MTAs, 11 tall fescue genotypes were selected for subsequent study to develop EP and EF drought tolerant tall fescue populations. Ten orthologous genes (six for EP and four for EF population) were identified inBrachypodiumgenome as potential candidates for drought tolerance in tall fescue, which were also earlier reported for their involvement in abiotic stress tolerance. The MTAs and candidate genes identified in this study will be useful for marker-assisted selection in improving drought tolerance of tall fescue as well opening avenue for further drought study in tall fescue.
CdgC, a Cyclic-di-GMP Diguanylate Cyclase of Azospirillum baldaniorum Is Involved in Internalization to Wheat Roots
Authors: Sierra Cacho Daniel , Zamorano Sánchez David S. , Xiqui-Vázquez Maria Luisa , Viruega Góngora Víctor Iván , Ramírez-Mata Alberto , Baca Beatriz E.
Published: October 2021

Azospirillum baldaniorum is a plant growth-promoting rhizobacterium (PGPR) capable of fixing nitrogen, the synthesis of several phytohormones including indole-acetic acid, and induction of plant defenses against phytopathogens. To establish a successful and prolonged bacteria-plant interaction, A. baldaniorum can form biofilms, bacterial communities embedded in a self-made matrix formed by extracellular polymeric substances which provide favorable conditions for survival. A key modulator of biofilm formation is the second messenger bis-(3′–5′)-cyclic-dimeric-GMP (c-di-GMP), which is synthesized by diguanylate cyclases (DGC) and degraded by specific phosphodiesterases. In this study, we analyzed the contribution of a previously uncharacterized diguanylate cyclase designated CdgC, to biofilm formation and bacterial-plant interaction dynamics. We showed that CdgC is capable of altering c-di-GMP levels in a heterologous host, strongly supporting its function as a DGC. The deletion of cdgC resulted in alterations in the three-dimensional structure of biofilms in a nitrogen-source dependent manner. CdgC was required for optimal colonization of wheat roots. Since we also observed that CdgC played an important role in exopolysaccharide production, we propose that this signaling protein activates a physiological response that results in the strong attachment of bacteria to the roots, ultimately contributing to an optimal bacterium-plant interaction. Our results demonstrate that the ubiquitous second messenger c-di-GMP is a key factor in promoting plant colonization by the PGPR A. baldaniorum by allowing proficient internalization in wheat roots. Understanding the molecular basis of PGPR-plant interactions will enable the design of better biotechnological strategies of agro-industrial interest.
The Relationships Between Hardiness and Life Satisfaction or Expectation of Korean Multicultural Children: Focused on Mediating Effect of Acculturative Stress Moderated by Resilience
Authors: Kim Bok-Hee , Suh Kyung-Hyun
Published: October 2021

This study identified the relationship between hardiness and life satisfaction or expectation of multicultural Korean children, and examined the mediating models of acculturative stress moderated by resilience on hardiness and life satisfaction or life expectation. The participants in the study were 201 male and female children from Korean multicultural families. PROCESS Macro 3.5 Model 14 was used for the analysis of the moderated mediating effects. The results revealed that hardiness and resilience were positively correlated with life satisfaction and life expectation, whereas acculturative stress was negatively correlated with life satisfaction and life expectation of multicultural children. In a moderated mediating model for life satisfaction, there was no interaction effect of acculturative stress and resilience, but a conditionally indirect effect of acculturative stress was only significant in groups with low resilience. In a moderated mediating model for life expectation, there was a significant interaction effect of acculturative stress and resilience, and a conditionally indirect effect of acculturative stress was only significant in groups with low resilience and with very high resilience. These findings suggest that only when multicultural children have low resilience, the mediating effect of acculturative stress is significant in relations of hardiness and life satisfaction, as well as hardiness and life expectation. In particular, resilience moderates the influence of acculturative stress on life expectations.
Research on Acoustic Environment in the Building of Nursing Homes Based on Sound Preference of the Elderly People: A Case Study in Harbin, China
Authors: Cui Peng , Zhang Jun , Li Ting Ting
Published: October 2021

Nursing homes are the facilities where the elderly conduct their daily activities. This may lead to a complicated acoustic environment which would potentially affect the ability of the elderly to function. In this study, the main indoor public space of a nursing home in Harbin was taken as the research object, and the methods of field observation, sound measurement, and questionnaire survey were used to explore the sound perception and preference of the elderly. The results revealed that in terms of the temporal and spatial distribution of sound pressure level (SPL), the unit living space had the highest SPL, which was above 60 dB (A). The reverberation time (RT) of the unit living space, medical and health care center corridor, was 2.15 and 2.13 s, respectively, at a frequency of 1,000 Hz, which was within the discomfort range. The results also revealed that an acoustic environment had a strong correlation with humidity and a weak correlation with temperature. However, no significant correlation could be assessed with a luminous environment. The elderly people were generally willing to accept the natural sound sources. The factors of gender and offspring numbers had no significant impact on the evaluation of acoustic environment comfort, whereas marriage and income status affected the comfort. This study may help improve the quality of life of the elderly in the nursing home and provide a reference for the construction and design of pension facilities.
Differences Between Readmitted and Non-readmitted Women in an Italian Forensic Unit: A Retrospective Study
Authors: Rossetto Ilaria , Clerici Massimo , Franconi Filippo , Felthous Alan R. , Carabellese Fulvio , Di Vella Giancarlo , Gandellini Maria Gloria , Parente Lia , Carabellese Felice
Published: October 2021

The main objective of this study was to compare readmitted (RW) and non-readmitted (NRW) female psychiatric patients after being conditionally or unconditionally released from Italian inpatient forensic psychiatry services, in order to identify variables that were significantly linked with readmission. This study included all patients who were discharged from the female Residences for the Execution of the Security Measure (REMS) of Castiglione delle Stiviere from January 2008 to June 2015 who were not readmitted until December 31, 2018 (48). In addition, data were collected on female patients who were discharged from the same REMS before 2008 and readmitted from January 2008 to December 2018 (42). A key finding of our study was that the readmission into a female REMS was positively associated with the presence of substance use disorders (SUD) and a primary diagnosis on Axis II. To a lesser extent, younger age, being unconditionally discharged when first released, having had a shorter length of inpatient stay and having committed a crime against property for the first REMS admission was also variables that were apparently linked with readmission. The present research continues the previous research on gender-specific mentally ill offenders. Hence, the decision to proceed separately with a sample of men only and one of women only. For all these reasons, young female patients with personality disorder and SUD perhaps should remain longer in REMS and be released with conditions. In most European countries, the length of stay depends on the clinical condition and risk assessment, with some exceptions where the courts set a maximum length of stay at the outset, as in Italy. All the factors listed above influence the risk assessment. Finally, from integrating these findings into the increasing international literature on conditional release and considering the recent changes in the Italian forensic treatment model, we recommend continuing research on individual risk and protective factors as well as risk assessment instruments on conditionally and unconditionally released inpatients with genders studied separately.
Factors Affecting Consumers’ Online Choice Intention: A Study Based on Bayesian Network
Authors: Deng Weibin , Su Ting , Zhang Yiming , Tan Chunli
Published: October 2021

In China, the mature development of online retail channels provides consumers with multiple consumption choices, and the factors that affect whether consumers choose to search or purchase online are numerous and complex. In this context, this paper reports on experimental research regarding consumers’ willingness to choose channels based on the two-stage decision-making theory. Using structural equation modeling, the factors influencing consumers’ online search intention and purchase willingness and the relationship between them are studied. In particular, the perceived benefits, channel trust, and channel transfer costs are explored. Furthermore, a Bayesian network is used in order to analyze the degree of influence of each factor quantitatively. It is found that online trust is an important factor affecting consumers’ online search intention, and the most important factor for consumers’ online purchase intention is their perceived benefits of online shopping. At the same time, there is a positive relationship between online search intention and purchase intention. This study can provide management decision support for online retail enterprises and help to promote the healthy development of online shopping.
Micropoetry Meets Neurocognitive Poetics: Influence of Associations on the Reception of Poetry
Authors: Hugentobler Katharina Gloria , Lüdtke Jana
Published: October 2021

Reading and understanding poetic texts is often described as an interactive process influenced by the words and phrases building the poems and all associations and images induced by them in the readers mind. Iser, for example, described the understanding process as the closing of a good Gestalt promoted by mental images. Here, we investigate the effect that semantic cohesion, that is the internal connection of a list words, has on understanding and appreciation of poetic texts. To do this, word lists are presented as modern micropoems to the participants and the (ease of) extraction of underlying concepts as well as the affective and aesthetic responses are implicitly and explicitly measured. We found that a unifying concept is found more easily and unifying concepts vary significantly less between participants when the words composing a micropoem are semantically related. Moreover these items are liked better and are understood more easily. Our study shows evidence for the assumed relationship between building spontaneous associations, forming mental imagery, and understanding and appreciation of poetic texts. In addition, we introduced a new method well-suited to manipulate backgrounding features independently of foregrounding features which allows to disentangle the effects of both on poetry reception.
The Effect of Music Therapy on Perceived Pain, Mental Health, Vital Signs, and Medication Usage of Burn Patients Hospitalized in the Intensive Care Unit: A Randomized Controlled Feasibility Study Protocol
Authors: Ettenberger Mark , Maya Rafael , Salgado-Vasco Andrés , Monsalve-Duarte Sofia , Betancourt-Zapata William , Suarez-Cañon Nicolas , Prieto-Garces Sergio , Marín-Sánchez Juliana , Gómez-Ortega Viviana , Valderrama Mario
Published: October 2021

Background:Burn patients experience major physiological and psychological stressors during treatment and rehabilitation, including elevated levels of pain, anxiety, stress, or depression. Music interventions inclusive of music therapy (MT) have been shown to improve such symptoms, but rigorous clinical trials investigating specific music therapy methods in adult burn patients are scarce.

Methods:This is a single center Randomized Controlled Trial (RCT) protocol with two parallel arms. Participants are 81 adult burn patients admitted to the Intensive Care Unit (ICU) of the University Hospital Fundación Santa Fe de Bogotá in Colombia. The intervention consists of a Music Assisted Relaxation (MAR) protocol, a music therapy technique composed of entrained live music combined with a guided relaxation and/or the use of imagery. The effects of the MAR will be compared to a control group (treatment as usual) over a period of maximum 2 weeks or six interventions. The primary outcome measure is perceived background pain, as measured with a Visual Analog Scale (VAS) before and after each intervention. Secondary outcomes are anxiety and depression levels; vital signs; and the use of pain medication. Additionally, some patients in the intervention group will be invited to participate in electroencephalography, electromyography, and electrocardiography recordings during the MAR.

Discussion:This study protocol follows the SPIRIT guidelines for defining items of clinical trials and is the first study in Colombia to evaluate the effects of music therapy for adult burn patients. With this RCT it is hoped to gather new knowledge about the potential of music therapy to help critical care patients cope and recover from their injuries during the hospitalization in the ICU.

Trial registration:www.clinicaltrials.gov, Identifier: NCT04571255.

Protocol version:V1.0, May 24th 2021
Mental Distress, Help Seeking, and Use of Health Services Among University Students. The SHoT-Study 2018, Norway
Authors: Sæther Marie Husøy , Sivertsen Børge , Bjerkeset Ottar
Published: October 2021

Background:Existing studies have documented high levels of mental distress in University and college students, complemented with poor help-seeking behavior. Colleges and universities offer a unique setting to address mental health problems that might overcome some of the most prominent barriers to help-seeking.

Objective:We aim to describe the use of campus-based health care services and health services available in the near-by community among students in Norwegian student welfare organizations. We compare health care service use between non-local (in-movers) and local students, students at large and small welfare organizations, and students with severe and medium-low levels of mental distress.

Methods:Data stem from the SHoT study (Students' Health and Well-being Study), a national survey from 2018 of all students aged 18–35 undertaking higher education in Norway. Mental distress was assessed using the Hopkins Symptom Checklist-25 (HSCL-25), and we also obtained self-report data on use of health care services. Data on health care services offered at Norwegian student welfare organizations was obtained from semi-structural telephone interviews.

Results:Non-local students used health care services that are low threshold, easily accessible and close to campus (health clinics and services organized by the student welfare organization) to a larger extent than local students. Students with symptoms of severe mental distress used almost all types of health services more than other students. We found big differences in reported use of health services in large and small organizations, yet these differences mirrored services available, and not necessarily student demand and preferences.

Conclusion:Services offered by the student welfare organizations seem to play a particularly important role for non-local students and students reporting symptoms of severe mental distress.
Impact of Early Life Stress on Reward Circuit Function and Regulation
Authors: Hanson Jamie L. , Williams Alexia V. , Bangasser Debra A. , Peña Catherine J.
Published: October 2021

Early life stress – including experience of child maltreatment, neglect, separation from or loss of a parent, and other forms of adversity – increases lifetime risk of mood, anxiety, and substance use disorders. A major component of this risk may be early life stress-induced alterations in motivation and reward processing, mediated by changes in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Here, we review evidence of the impact of early life stress on reward circuit structure and function from human and animal models, with a focus on the NAc. We then connect these results to emerging theoretical models about the indirect and direct impacts of early life stress on reward circuit development. Through this review and synthesis, we aim to highlight open research questions and suggest avenues of future study in service of basic science, as well as applied insights. Understanding how early life stress alters reward circuit development, function, and motivated behaviors is a critical first step toward developing the ability to predict, prevent, and treat stress-related psychopathology spanning mood, anxiety, and substance use disorders.
Genetic Predisposition Between COVID-19 and Four Mental Illnesses: A Bidirectional, Two-Sample Mendelian Randomization Study
Authors: Liu Ningning , Tan Jiang-Shan , Liu Lu , Wang Yufeng , Hua Lu , Qian Qiujin
Published: October 2021

Background: The outbreak of 2019 coronavirus disease (COVID-19) has become a global pandemic. Although it has long been suspected that COVID-19 could contribute to the development of mental illness, and individuals with a pre-existing mental illness may have a higher risk of and poorer outcomes from COVID-19 infection, no evidence has established a causal association between them thus far.

Methods: To investigate associations in support of a causal association between the severity of COVID-19 and mental illnesses, we leveraged large-scale genetic summary data from genome-wide association study (GWAS) summary datasets, including attention-deficit/hyperactivity disorder (ADHD) (n = 55,374), schizophrenia (n = 77,096), bipolar disorder (n = 51,710), and depression (n = 173,005), based on a previous observational study. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and MR-Egger approaches and multiple sensitivity analyses assessing horizontal pleiotropy and removing outliers in two different COVID-19 databases.

Results: The Mendelian randomization (MR) analysis indicated that ADHD [odds ratio (OR) = 1.297; 95% confidence interval (CI), 1.029–1.634; p = 0.028] increased the risk of hospitalization due to COVID-19. A similar association was obtained in MR sensitivity analyses of the weighted median. In addition, genetically predicted COVID-19 was significantly associated with schizophrenia (OR = 1.043; 95% CI, 1.005–1.082; p = 0.027).

Conclusions: Although many studies have reported a causal relationship between COVID-19 and mental illness, our study shows that this increased risk is modest. However, considering the characteristics of ADHD that might further increase the individuals' vulnerability to being infected by COVID-19, the ongoing massive worldwide exposure to COVID-19, and the high burden of schizophrenia, we believe that it is necessary to offer preventative measures to these populations and to provide more evidence in understanding the neurological impact of COVID-19.
Applying C. elegans to the Industrial Drug Discovery Process to Slow Aging
Authors: Weinkove David , Zavagno Giulia
Published: October 2021

The increase in our molecular understanding of the biology of aging, coupled with a recent surge in investment, has led to the formation of several companies developing pharmaceuticals to slow aging. Research using the tiny nematode worm Caenorhabditis elegans was the first to show that mutations in single genes can extend lifespan, and subsequent research has shown that this model organism is uniquely suited to testing interventions to slow aging. Yet, with a few notable exceptions, C. elegans is not in the standard toolkit of longevity companies. Here we discuss the paths to overcome the barriers to using C. elegans in industrial drug discovery. We address the predictive power of C. elegans for human aging, how C. elegans research can be applied to specific challenges in the typical drug discovery pipeline, and how standardised and quantitative assays will help C. elegans fulfil its potential in the biotech and pharmaceutical industry. We argue that correct application of this model and its knowledge base will significantly accelerate progress to slow human aging.
Matrix Profile-Based Interpretable Time Series Classifier
Authors: Guidotti Riccardo , D’Onofrio Matteo
Published: October 2021

Time series classification (TSC) is a pervasive and transversal problem in various fields ranging from disease diagnosis to anomaly detection in finance. Unfortunately, the most effective models used by Artificial Intelligence (AI) systems for TSC are not interpretable and hide the logic of the decision process, making them unusable in sensitive domains. Recent research is focusing on explanation methods to pair with the obscure classifier to recover this weakness. However, a TSC approach that is transparent by design and is simultaneously efficient and effective is even more preferable. To this aim, we propose an interpretable TSC method based on the patterns, which is possible to extract from the Matrix Profile (MP) of the time series in the training set. A smart design of the classification procedure allows obtaining an efficient and effective transparent classifier modeled as a decision tree that expresses the reasons for the classification as the presence of discriminative subsequences. Quantitative and qualitative experimentation shows that the proposed method overcomes the state-of-the-art interpretable approaches.
A Mini-Review of Accreting Pulsating White Dwarfs
Authors: Szkody Paula
Published: October 2021

The discovery in 1998 of a pulsating white dwarf in the cataclysmic variable GW Lib opened up a new avenue of exploration in the asteroseismology of white dwarfs. Since dwarf novae undergo outbursts which heat the white dwarf and then subsequently cool, the temperature changes allow a study of the mode changes that occur as the white dwarf moves out of the instability zone and back. These changes occur on timescales of months-years, instead of the millennia for evolutionary cooling of single white dwarfs. At the current time, there are 18 known accreting white dwarf pulsators. This mini-review will summarize the results that have been achieved so far from coordinated space and ground observations, from sky surveys, and what is needed in the future to make further progress.
Olympic Sports Science—Bibliometric Analysis of All Summer and Winter Olympic Sports Research
Authors: Millet Grégoire P. , Brocherie Franck , Burtscher Johannes
Published: October 2021

Introduction:The body of scientific literature on sports and exercise continues to expand. The summer and winter Olympic games will be held over a 7-month period in 2021–2022.

Objectives:We took this rare opportunity to quantify and analyze the main bibliometric parameters (i.e., the number of articles and citations) across all Olympic sports to weigh and compare their importance and to assess the structure of the “sport sciences” field. The present review aims to perform a bibliometric analysis of Olympic sports research. We quantified the following topics: (1) the most investigated sports; (2) the main journals in which the studies are published; (3) the main factors explaining sport-specific scientific attractiveness; (4) the influence of being in the Olympic programme, economic weight, and local influences on research output; and (5) which research topic is the most investigated across sports.

Methods:We searched 116 sport/exercise journals on PubMed for the 40 summer and 10 winter Olympic sports. A total of 34,038 articles were filtered for a final selection of 25,003 articles (23,334 articles on summer sports and 1,669 on winter sports) and a total of 599,820 citations.

Results and Discussion:Nine sports [football (soccer), cycling, athletics, swimming, distance & marathon running, basketball, baseball, tennis, and rowing] were involved in 69% of the articles and 75% of the citations. Football was the most cited sport, with 19.7 and 26.3% of the total number of articles and citations, respectively. All sports yielded some scientific output, but 11 sports (biathlon, mountain biking, archery, diving, trampoline, skateboarding, skeleton, modern pentathlon, luge, bobsleigh, and curling) accumulated a total of fewer than 50 publications. While ice hockey is the most prominently represented winter sport in the scientific literature, winter sports overall have produced minor scientific output. Further analyses show a large scientific literature on team sports, particularly American professional sports (i.e., baseball, basketball, and ice hockey) and the importance of inclusion in the Olympic programme to increasing scientific interest in “recent” sports (i.e., triathlon and rugby sevens). We also found local/cultural influence on the occurrence of a sport in a particular “sport sciences” journal. Finally, the relative distribution of six main research topics (i.e., physiology, performance, training and testing, injuries and medicine, biomechanics, and psychology) was large across sports and reflected the specific performance factors of each sport.
Assessment of Three-Dimensional Reconstruction in Percutaneous Nephrolithotomy for Complex Renal Calculi Treatment
Authors: Tan Haotian , Xie Yaqi , Zhang Xuebao , Wang Wenting , Yuan Hejia , Lin Chunhua
Published: October 2021

Introduction: Three-dimensional (3D) reconstruction is a novel imaging technique widely used to improve surgical operations. Some studies have identified its role in Urology for percutaneous nephrolithotomy (PCNL).

Objective: To explore the potential benefits of 3D reconstruction technology in PCNL for complex renal calculi treatment.

Methods: A retrospective study involving 139 patients with complex kidney stones who underwent PCNL was conducted between September 30, 2018, to September 30, 2019. Group A patients (72) underwent the 3D reconstruction technique before PCNL, while group B (67) did not. The operation time, the duration of the hospital stay, the puncture accuracy, the decrease in hemoglobin concentration, the stone clearance rate, and the postoperative complications were noted and compared between the two groups.

Results: The initial stone clearance rates 2 weeks after PCNL were 81.9 and 64.2% in groups A and B, respectively (P < 0.05). The first-time puncture success rates were 87.5 and 47.8 % in groups A and B, respectively (P < 0.05). Group A had a shorter operation time than group B (62 vs. 79 min, P < 0.05). Besides, the 3D reconstructive technique-assisted patients (91.7%) had no or mild complications, compared with (74.6%) group B patients. There was no significant difference in hemoglobin decline and hospital stay between the two groups.

Conclusions: The 3D reconstruction technology is an effective adjunct to PCNL in the complex renal calculi treatment.
Evolution, Interspecies Transmission, and Zoonotic Significance of Animal Coronaviruses
Authors: Parkhe Prapti , Verma Subhash
Published: October 2021

Coronaviruses are single-stranded RNA viruses that affect humans and a wide variety of animal species, including livestock, wild animals, birds, and pets. These viruses have an affinity for different tissues, such as those of the respiratory and gastrointestinal tract of most mammals and birds and the hepatic and nervous tissues of rodents and porcine. As coronaviruses target different host cell receptors and show divergence in the sequences and motifs of their structural and accessory proteins, they are classified into groups, which may explain the evolutionary relationship between them. The interspecies transmission, zoonotic potential, and ability to mutate at a higher rate and emerge into variants of concern highlight their importance in the medical and veterinary fields. The contribution of various factors that result in their evolution will provide better insight and may help to understand the complexity of coronaviruses in the face of pandemics. In this review, important aspects of coronaviruses infecting livestock, birds, and pets, in particular, their structure and genome organization having a bearing on evolutionary and zoonotic outcomes, have been discussed.
Gastrointestinal Development and Microbiota Responses of Geese to Honeycomb Flavonoids Supplementation
Authors: He Chenxin , Wu Huadong , Lv Yaning , You Hongnan , Zha Liqing , Li Qin , Huang Yani , Tian Jinghong , Chen Qiuchun , Shen Yiwen , Xiong Shiyuan , Xue Fuguang
Published: October 2021

Background: Geese are conventionally considered to be herbivorous, which could also be raised with concentrate feeding diets without green grass because of the similar gastrointestinal tract with other poultry. However, the geese gut microbiota profiles and their interactions with epithelial cells are still of limited study. Flavonoids were well-documented to shape gut microbiota and promote epithelial barrier functions individually or cooperatively with other metabolites. Therefore, in the present study, honeycomb flavonoids (HF) were supplemented to investigate the effects on growth performances, intestinal development, and gut microbiome of geese.

Material and Methods: A total of 400 1-day-old male lion-head geese with similar birth weight (82.6 ± 1.4 g) were randomly divided into five treatments: the control treatment (CON) and the HF supplementation treatments, HF was supplemented arithmetically to increase from 0.25 to 1%. Growth performance, carcass performances, and intestines' development parameters were measured to determine the optimum supplement. Junction proteins including ZO-1 and ZO-2 and cecal microbiota were investigated to demonstrate the regulatory effects of HF on both microbiota and intestinal epithelium.

Results: Results showed that 0.5% of HF supplement had superior growth performance, carcass performance, and the total parameters of gastrointestinal development to other treatments. Further research showed that tight junction proteins including ZO-1 and ZO-2 significantly up-regulated, while Firmicutes and some probiotics including Clostridiales, Streptococcus, Lachnoclostridium, and Bifidobacterium, remarkably proliferated after HF supplement. In conclusion, HF supplement in concentrate-diet feeding geese effectively increased the growth performances by regulating the gut microbiota to increase the probiotic abundance to promote the nutrient digestibility and fortify the epithelial development and barrier functions to facilitate the nutrient absorption and utilization.