bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the efficacy and safety of medications in adults with hypertrophic cardiomyopathy: a systematic review and network meta-analysis
Authors: Mi Keying , Wu Sijia , Lv Chanyuan , Meng Yongkang , Yin Wenchao , Li Hongkai , Li Jiangbing , Yuan Haitao
Published: August 2023

Background

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. The purpose of this study was to evaluate the efficacy and safety of several medications and recommend better drug treatments for adults with HCM.

Methods

A review of PubMed, Embase, the Cochrane Controlled Register of Trials (CENTRAL), ClinicalTrials.gov and CNKI databases was conducted for studies on the efficacy and safety of drugs for adults with HCM. A frequentist random effects model was used in this network analysis.

Results

This network meta-analysis included 7 studies assessing seven medications, 6 studies evaluating monotherapy and 1 study evaluating combination therapy. Based on the network meta-analysis results, xiaoxinbi formula plus metoprolol (MD −56.50% [−72.43%, −40.57%]), metoprolol (MD −47.00% [−59.07%, −34.93%]) and mavacamten (MD −34.50% [−44.75%, −24.25%]) significantly reduced the resting left ventricular outflow tract gradient (LVOTG) in comparison with placebo. Resting LVOTG could also be reduced with N-acetylcysteine (NAC). The incidence of adverse drug reactions was not significantly different between the placebo group and the treatment group.

Conclusion

For adults with HCM, the top 4 treatments included xiaoxinbi formula plus metoprolol, metoprolol, mavacamten and NAC.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=374222], identifier [CRD42022374222].
Adipokines in atherosclerosis: unraveling complex roles
Authors: Luo Jiaying , He Zhiwei , Li Qingwen , Lv Mengna , Cai Yuli , Ke Wei , Niu Xuan , Zhang Zhaohui
Published: August 2023

Adipokines are biologically active factors secreted by adipose tissue that act on local and distant tissues through autocrine, paracrine, and endocrine mechanisms. However, adipokines are believed to be involved in an increased risk of atherosclerosis. Classical adipokines include leptin, adiponectin, and ceramide, while newly identified adipokines include visceral adipose tissue-derived serpin, omentin, and asprosin. New evidence suggests that adipokines can play an essential role in atherosclerosis progression and regression. Here, we summarize the complex roles of various adipokines in atherosclerosis lesions. Representative protective adipokines include adiponectin and neuregulin 4; deteriorating adipokines include leptin, resistin, thrombospondin-1, and C1q/tumor necrosis factor-related protein 5; and adipokines with dual protective and deteriorating effects include C1q/tumor necrosis factor-related protein 1 and C1q/tumor necrosis factor-related protein 3; and adipose tissue-derived bioactive materials include sphingosine-1-phosphate, ceramide, and adipose tissue-derived exosomes. However, the role of a newly discovered adipokine, asprosin, in atherosclerosis remains unclear. This article reviews progress in the research on the effects of adipokines in atherosclerosis and how they may be regulated to halt its progression.
Educating for the sustainable development goals through service-learning: University students’ perspectives about the competences developed
Authors: Ribeiro Luísa Mota , Miranda Francisca , Themudo Carmo , Gonçalves Helena , Bringle Robert G. , Rosário Pedro , Aramburuzabala Pilar
Published: August 2023

The purpose of this study was to examine the perceived impact of a Service-Learning (SL) experience titled “Educating for Sustainable Development Goals (SDGs),” at the Porto campus of Universidade Católica Portuguesa (UCP), in which 15 university students from different programs were challenged to train other students about the SDGs. The main aim of the SL project was to raise awareness about the SDGs among the recipients (200 high school students, 20 students from a University in Angola and 40 from a University in Brazil). Besides the development of soft skills in UCP students, the learning objectives also focused on training socially responsible citizens who can take the SDGs into their future professions and help create a better and more sustainable world. UCP students were asked to reflect on their SL experience in the middle and at the end of the semester, based on structured reflection prompts. Based on these reflections, the present study aimed to understand the perceived impact of the SL experience on UCP students, particularly on their understanding of sustainable development (e.g., knowledge of SDGs), and the recipients (e.g., knowledge of strategies to achieve SDGs). Qualitative analysis was performed through NVIVO software. The results showed an impact not only on the academic learning and the UCP students’ personal and professional domains, but also on their literacy about the SDGs. According to the UCP students’ perceptions, the SL experience was particularly helpful in promoting SDGs awareness in the recipients and predisposing them to change attitudes and behaviors. Therefore, we conclude that the SL project accomplished its purpose of promoting awareness of the SDGs among the recipients. The implications of these findings are discussed in the context of the role of higher education institutions and SL experiences in sustainable development.
Diabetic foot complications among Indigenous peoples in Canada: a scoping review through the PROGRESS-PLUS equity lens
Authors: Blanchette Virginie , Patry Jérôme , Brousseau-Foley Magali , Todkar Shweta , Libier Solène , Leclerc Anne-Marie , Armstrong David G. , Tremblay Marie-Claude
Published: August 2023

Introduction

Indigenous peoples in Canada face a disproportionate burden of diabetes-related foot complications (DRFC), such as foot ulcers, lower extremity amputations (LEA), and peripheral arterial disease. This scoping review aimed to provide a comprehensive understanding of DRFC among First Nations, Métis, and Inuit peoples in Canada, incorporating an equity lens.

Methods

A scoping review was conducted based on Arksey and O’Malley refined by the Joanna Briggs Institute. The PROGRESS-Plus framework was utilized to extract data and incorporate an equity lens. A critical appraisal was performed, and Indigenous stakeholders were consulted for feedback. We identified the incorporation of patient-oriented/centered research (POR).

Results

Of 5,323 records identified, 40 studies were included in the review. The majority of studies focused on First Nations (92%), while representation of the Inuit population was very limited populations (< 3% of studies). LEA was the most studied outcome (76%). Age, gender, ethnicity, and place of residence were the most commonly included variables. Patient-oriented/centered research was mainly included in recent studies (16%). The overall quality of the studies was average. Data synthesis showed a high burden of DRFC among Indigenous populations compared to non-Indigenous populations. Indigenous identity and rural/remote communities were associated with the worse outcomes, particularly major LEA.

Discussion

This study provides a comprehensive understanding of DRFC in Indigenous peoples in Canada of published studies in database. It not only incorporates an equity lens and patient-oriented/centered research but also demonstrates that we need to change our approach. More data is needed to fully understand the burden of DRFC among Indigenous peoples, particularly in the Northern region in Canada where no data are previously available. Western research methods are insufficient to understand the unique situation of Indigenous peoples and it is essential to promote culturally safe and quality healthcare.

Conclusion

Efforts have been made to manage DRFC, but continued attention and support are necessary to address this population’s needs and ensure equitable prevention, access and care that embraces their ways of knowing, being and acting.

Systematic review registration

Open Science Framework https://osf.io/j9pu7, identifier j9pu7.
Mainstreaming civic tech and citizen sensing: a research agenda on co-creation methods, data interfaces, and impact pathways
Authors: Raetzsch Christoph , Hamm Andrea , Shibuya Yuya
Published: August 2023

In this perspective article, we propose an interdisciplinary research agenda that addresses citizen science approaches embedded in civic tech initiatives and citizen sensing scenarios. The proposed agenda builds on the multi-level perspective framework (Geels, 2004; Geels, 2019) to inform research on how such ‘niche innovations’ like citizen sensing become mainstreamed in broader socio-technical systems and modes of governance. To support research across use case scenarios and make analyses more comparable internationally, we identify three core areas of interdisciplinary future research and practice development: 1) uses of co-creation methods to develop project objectives and align stakeholders; 2) designs of interfaces for gathering, communicating, and archiving civic data for different types of users; and 3) modeling impact pathways of individual projects that include civic tech activists and citizen scientists, academic researchers, journalists, and policymakers. For impact pathways, we highlight the importance of collaborations with data-driven approaches in journalism.
The impact of innate immunity on malaria parasite infection dynamics in rodent models
Authors: Herbert Mainero Alejandra , Spence Philip J. , Reece Sarah E. , Kamiya Tsukushi
Published: August 2023

Decades of research have probed the molecular and cellular mechanisms that control the immune response to malaria. Yet many studies offer conflicting results on the functional impact of innate immunity for controlling parasite replication early in infection. We conduct a meta-analysis to seek consensus on the effect of innate immunity on parasite replication, examining three different species of rodent malaria parasite. Screening published studies that span four decades of research we collate, curate, and statistically analyze infection dynamics in immune-deficient or -augmented mice to identify and quantify general trends and reveal sources of disagreement among studies. Additionally, we estimate whether host factors or experimental methodology shape the impact of immune perturbations on parasite burden. First, we detected meta-analytic mean effect sizes (absolute Cohen’s h) for the difference in parasite burden between treatment and control groups ranging from 0.1475 to 0.2321 across parasite species. This range is considered a small effect size and translates to a modest change in parasitaemia of roughly 7-12% on average at the peak of infection. Second, we reveal that variation across studies using P. chabaudi or P. yoelii is best explained by stochasticity (due to small sample sizes) rather than by host factors or experimental design. Third, we find that for P. berghei the impact of immune perturbation is increased when young or female mice are used and is greatest when effector molecules (as opposed to upstream signalling molecules) are disrupted (up to an 18% difference in peak parasitaemia). Finally, we find little evidence of publication bias suggesting that our results are robust. The small effect sizes we observe, across three parasite species, following experimental perturbations of the innate immune system may be explained by redundancy in a complex biological system or by incomplete (or inappropriate) data reporting for meta-analysis. Alternatively, our findings might indicate a need to re-evaluate the efficiency with which innate immunity controls parasite replication early in infection. Testing these hypotheses is necessary to translate understanding from model systems to human malaria.
Clinical application of serum NLRP3 on the diagnosis and prognosis of sepsis patients complicated with acute respiratory distress syndrome
Authors: Yang Qing , Zhang Xiaojun , Luo Le , Shen Jinglian
Published: August 2023

Introduction

Acute respiratory distress syndrome (ARDS) is a common complication of sepsis, which significantly increases the mortality rate. This work explored the diagnostic value of serum NOD-like receptor family pyrin domain containing 3 (NLRP3) concentration in patients with sepsis for ARDS, and the predictive value of serum NLRP3 concentration at the time of diagnosis for death 28 days after treatment.

Methods

A total of 150 sepsis patients were included in this study, including age-matched two groups of patients, 75 patients with ARDS and 75 patients without ARDS. In addition, 60 age-matched healthy patients with physical examination were recruited in this study. Serum NLRP3 concentration was determined by enzyme-linked immunosorbent assay (ELISA). The diagnostic values of serum NLRP3 concentration for ARDS in sepsis patients were evaluated by receiver operating characteristics (ROC) analysis. Correlation of serum NLRP3 with APACHE II score and SOFA were performed by Spearman correlation analysis.

Results

Pulmonary infection, APACHE II score and serum NLRP3 concentration were risk factors for patients with sepsis complicated with ARDS. ROC curve results showed that the specificity of serum NLRP3 concentration was 74.67%, the sensitivity was 76.00%, and the area under the curve (AUC) was 0.82 (p<0.001). APACHE II score and SOFA were significantly positively correlated with serum NLRP3 concentration. Baseline serum NLRP3 levels had significant predictive value for 28-day mortality in sepsis patients complicated with ARDS.

Conclusion

Serum NLRP3 concentration has clinical value in the diagnosis of sepsis complicated with ARDS.
Co-occurrence of non-alcoholic steatohepatitis exacerbates psoriasis associated with decreased adiponectin expression in a murine model
Authors: Takezaki Daiki , Morizane Shin , Ikeda Kenta , Iseki Masanori , Sakamoto Yuma , Kawakami Yoshio , Hashiguchi Taishi , Shirakata Yuka , Nishina Sohji , Mukai Tomoyuki
Published: August 2023

Introduction

Clinical studies have suggested a bidirectional association between non-alcoholic steatohepatitis (NASH) and psoriasis, affecting each other’s development and severity. Here, we explored bidirectional causal linkages between NASH and psoriasis using a murine model.

Methods

NASH was induced in mice by streptozotocin injection at 2 days of age and by high-fat diet feeding (STAM™ model). Psoriasis was induced by topical application of imiquimod (IMQ) on the ear. The severities of liver damage and psoriatic skin changes were determined using histological analysis. Gene expression in the skin tissues was evaluated using quantitative PCR analysis. Serum cytokine levels were determined using enzyme-linked immunosorbent assay. To examine the innate immune responses of normal human epidermal keratinocytes (NHEKs), the cells were treated with interleukin (IL)-17A, tumor necrosis factor (TNF)-α, and AdipoRon, an adiponectin receptor agonist.

Results and Discussion

There were no differences in the degree of liver tissue damage (fat deposition, inflammation, and fibrosis) between NASH mice with and those without psoriasis. Conversely, the co-occurrence of NASH significantly augmented psoriatic skin changes, represented by epidermal hyperplasia, in psoriatic mice. Pro-inflammatory cytokines were expressed in the inflamed skin of psoriatic mice, and the expression of genes, especially Il23a, Il1b, Il36g, and Mip2, was significantly upregulated by the co-occurrence of NASH. The expression of keratinocyte activation marker genes Defb4b and Krt16 was also upregulated by the co-occurrence of NASH. The serum TNF-α and IL-17 levels were increased by the co-occurrence of NASH and psoriasis. The serum adiponectin levels decreased in NASH mice compared with that in non-NASH mice. In NHEK culture, TNF-α and IL-17A synergistically upregulated CXCL1, CXCL8, and IL1B expression. The upregulated pro-inflammatory gene expression was suppressed by AdipoRon treatment, reflecting the anti-inflammatory capacity of adiponectin.

Conclusion

The co-occurrence of NASH exacerbated psoriatic skin changes associated with increased serum inflammatory cytokine levels and decreased serum adiponectin levels. Combined with in vitro findings, increased inflammatory cytokine levels and decreased adiponectin levels likely promote innate immune responses in epidermal keratinocytes in psoriatic skin lesions. Overall, therapeutic intervention for co-occurring NASH is essential to achieve a favorable prognosis of psoriasis in clinical practice.
Novel anti-CD30/CD3 bispecific antibodies activate human T cells and mediate potent anti-tumor activity
Authors: Faber Mary L. , Oldham Robyn A. A. , Thakur Archana , Rademacher Mary Jo , Kubicka Ewa , Dlugi Theresa A. , Gifford Steven A. , McKillop William M. , Schloemer Nathan J. , Lum Lawrence G. , Medin Jeffrey A.
Published: August 2023

CD30 is expressed on Hodgkin lymphomas (HL), many non-Hodgkin lymphomas (NHLs), and non-lymphoid malignancies in children and adults. Tumor expression, combined with restricted expression in healthy tissues, identifies CD30 as a promising immunotherapy target. An anti-CD30 antibody-drug conjugate (ADC) has been approved by the FDA for HL. While anti-CD30 ADCs and chimeric antigen receptors (CARs) have shown promise, their shortcomings and toxicities suggest that alternative treatments are needed. We developed novel anti-CD30 x anti-CD3 bispecific antibodies (biAbs) to coat activated patient T cells (ATCs) ex vivo prior to autologous re-infusions. Our goal is to harness the dual specificity of the biAb, the power of cellular therapy, and the safety of non-genetically modified autologous T cell infusions. We present a comprehensive characterization of the CD30 binding and tumor cell killing properties of these biAbs. Five unique murine monoclonal antibodies (mAbs) were generated against the extracellular domain of human CD30. Resultant anti-CD30 mAbs were purified and screened for binding specificity, affinity, and epitope recognition. Two lead mAb candidates with unique sequences and CD30 binding clusters that differ from the ADC in clinical use were identified. These mAbs were chemically conjugated with OKT3 (an anti-CD3 mAb). ATCs were armed and evaluated in vitro for binding, cytokine production, and cytotoxicity against tumor lines and then in vivo for tumor cell killing. Our lead mAb was subcloned to make a Master Cell Bank (MCB) and screened for binding against a library of human cell surface proteins. Only huCD30 was bound. These studies support a clinical trial in development employing ex vivo-loading of autologous T cells with this novel biAb.
Fibroblasts – the cellular choreographers of wound healing
Authors: Knoedler Samuel , Broichhausen Sonja , Guo Ruiji , Dai Ruoxuan , Knoedler Leonard , Kauke-Navarro Martin , Diatta Fortunay , Pomahac Bohdan , Machens Hans-Guenther , Jiang Dongsheng , Rinkevich Yuval
Published: August 2023

Injuries to our skin trigger a cascade of spatially- and temporally-synchronized healing processes. During such endogenous wound repair, the role of fibroblasts is multifaceted, ranging from the activation and recruitment of innate immune cells through the synthesis and deposition of scar tissue to the conveyor belt-like transport of fascial connective tissue into wounds. A comprehensive understanding of fibroblast diversity and versatility in the healing machinery may help to decipher wound pathologies whilst laying the foundation for novel treatment modalities. In this review, we portray the diversity of fibroblasts and delineate their unique wound healing functions. In addition, we discuss future directions through a clinical-translational lens.
Malaria in pregnancy: adverse pregnancy outcomes and the future of prevention
Authors: Berhe Anne D. , Doritchamou Justin Y. A. , Duffy Patrick E.
Published: August 2023

Malaria in pregnancy (MiP) poses a dangerous health risk to both mothers and their fetuses, causing severe outcomes such as preterm delivery, intrauterine growth restriction, miscarriage, stillbirth, and neonatal and maternal death. Plasmodium falciparum infected erythrocytes sequester in placental intervillous spaces causing placental malaria (PM), eliciting inflammatory responses associated with severe sequelae. Current MiP prevention strategies have improved pregnancy outcomes, but serious morbidity and mortality persist. Vaccines to prevent MiP and PM are under development and are expected to improve pregnancy outcomes. To prepare for safety and efficacy trials of these vaccines, the incidence of adverse pregnancy outcomes including those caused by MiP should be documented at clinical sites. This review summarizes reported key adverse pregnancy outcomes attributable to MiP, providing important baseline context to define measurable safety and efficacy endpoints for malaria vaccine trials in pregnancy.
Socio-oceanography: an opportunity to integrate marine social and natural sciences
Authors: Popova Ekaterina , Aksenov Yevgeny , Amoudry Laurent O. , Becker Amani , Bricheno Lucy , Brown Jennifer M. , Clare Michael A. , Evans Alan , Evans Claire , Fowell Sara E. , Jevrejeva Svetlana , Jacobs Zoe , Jones Daniel O. B. , Hibbert Angela , O’Hara Fran , McKinley Emma , Payo-Payo Marta , Pearce Christopher R. , Taylor Sarah F. W. , Sams Christine , Yool Andrew
Published: August 2023

Marine natural sciences have been instrumental in helping society understand how ocean systems operate and the threats they face. However, there is a growing realisation that the societal challenges related to the marine environment can only be addressed through more effective integration with all aspects of social sciences. Nevertheless, to date, social sciences remain insufficiently integrated into marine research. Recognising historical weaknesses and drawing on the authors’ own experience of interdisciplinary research, albeit writing primarily from a natural marine science perspective, we propose a series of steps to promote integrated marine research inclusive of strong social science. We suggest that changing the perspectives and attitudes of natural scientists is key. The inherent interconnectivity between the ocean and society ensures that nearly everything we do in the marine natural sciences has the potential to influence and, perhaps address, ongoing and future societal challenges. Consequently, a key challenge for natural scientists is to recognise and communicate this in an accessible manner outside their own disciplines. To attempt to address these issues, we introduce the concept of “Socio-oceanography” which we define as an area of research that takes a “whole system” approach to the marine environment. It focuses on the challenges which require advancement of both natural and social science components, especially on those where the feedbacks between social and natural components are beginning to emerge. Here, we discuss its scope, challenges to its effective application and key steps to catalyse interdisciplinary approaches using this concept.
Symbiotic communities associated with nursery-reared and natural corals: are they similar?
Authors: Britayev T. A. , Zvonareva S. S. , Lishchenko F. V. , Deart Y. V.
Published: August 2023

Coral aquaculture techniques have been developed for many species based on a well-documented understanding of the factors that affect coral growth and fitness. However, there is limited knowledge about the composition and structure of ectosymbiotic communities associated with cultured coral colonies. To address this gap, we conducted a study ofPocillopora verrucosacolonies reared from fragments in fixed nurseries and exposed for 6 and 12 months, as well as natural colonies in the same location. Our analysis focused on the species composition, species richness, and density of obligate and facultative ectosymbionts associated with the colonies. Obtained results indicate that the community associated with nursery-reared colonies was highly diverse, comprising 25 ectosymbionts, including 9 obligate and 16 facultative species. The prevalence, species richness, and density of the communities associated with natural colonies were significantly higher than those associated with reared ones. We also observed differences in the communities associated with reared colonies of different exposures, but we were able to group them as stages of the same community based on the size and exposure of the colonies. The differences between communities associated with reared and natural colonies may be related to the microhabitat properties of the symbiotic communities, as the former were elevated above the substrate, while the latter were attached to it. The age of natural colonies was also estimated to be more than three times higher than that of reared colonies of the same size, contributing to the differences. Our study clearly demonstrates that coral nurseries not only serve as a means of propagating corals but also offer artificial habitats for the maintenance and conservation of associated fauna. These findings have important implications for the management and conservation of coral reefs.
Microplastics in the Arctic: a transect through the Barents Sea
Authors: Emberson-Marl H. , Coppock R. L. , Cole M. , Godley B. J. , Mimpriss N. , Nelms S. E. , Lindeque P. K.
Published: August 2023

Globally, the abundance of microplastics in our oceans is increasing, including within the remote locations of the polar regions. The Barents Sea, which adjoins the Arctic Ocean, is an area of high primary productivity that, owing to the convergence of regional currents, has been mooted as a potential sixth ocean gyre that may coalesce high concentrations of plastic debris. This study aimed to explore data collected from large volume samples of sub-surface water collected from transects through the Barents Sea to quantify and characterise microplastics in this region, with a focus on potential impacts to zooplankton. Overall, the mean microplastic abundance in the Barents Sea was 0.011 microplastics m-3(range: 0.007 – 0.015 m-3). Microplastics were found in higher abundances nearer land mass at the southern end of the transect and northwards towards the ice edge, recording 0.015 microplastics m-3during both transect legs. Microplastics were predominantly fibrous (92.1%) and typically blue (79%) or red (17%) in colour. A range of polymers were identified including polyester (3.8%), copolymer blends (2.7%), elastomers (7.1%) and acrylics (10.6%), however semi-synthetic polymers dominated, comprising 74.4% of particles found. Higher microplastic concentrations in the northernmost transect may stem from melting sea-ice, while the higher concentrations in the southernmost transect likely derive from the long-range transport of microplasticsviacurrents from Europe.
Impact of exercise and leucine-enriched protein supplementation on physical function, body composition, and inflammation in pre-frail older adults: a quasi-experimental study
Authors: Merchant Reshma Aziz , Chan Yiong Huak , Anbarasan Denishkrshna , Seetharaman Santhosh , Au Lydia , Nachammai Vidhya , Lai Alexa , Ho Vanda , Wong Beatrix Ling Ling , Pang Eunice , Bhaskaran Kalpana
Published: August 2023

Background

Exercise and a protein-enriched diet are essential for muscle protein synthesis, cellular growth, mitochondrial function, and immune function. The U.S. Food and Nutrition Board's current guideline on recommended dietary allowance for protein in older adults is 0.8 g/kg per day, which may not be sufficient in vulnerable pre-frail older adults.

Aims

This study aimed to evaluate the impact of leucine-enriched protein supplementation with or without exercise over 3 months in pre-frail older adults who consumed ≤1 g/kg/day of protein on improving (i) physical function, (ii) body composition measures, and (iii) inflammatory biomarkers such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α).

Methods

A non-randomized cluster quasi-experimental study guided by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist of 178 pre-frail older adults [112 control, 44 nutrition (Nu), and 22 in the nutrition with exercise (Nu+Ex) group] comparing the effect of Nu+Ex and Nu on physical function, body composition, and inflammation. At 0, 3, and 6 months, questionnaires on demographics, depression, perceived health, and cognition were administered. Physical function assessment (short physical performance battery [SPPB] test, gait speed, handgrip strength, 5× sit-to-stand [STS]) was conducted, and body composition analysis was performed using a bioelectrical impedance analysis machine. IL-6 and TNF-α were measured at 0 and 3 months.

Results

At 3 months, there were significant improvements in gait speed, 5× STS, SPPB scores, depression, perceived health, fat-free mass, and appendicular skeletal muscle mass indices in the Nu+Ex group. Both Nu+Ex and Nu groups had improvements in body cell mass and reductions in IL-6 and TNF-α. The improvements were not sustained after 6 months.

Conclusion

Our study results need to be validated in future longitudinal randomized studies with a larger sample size focusing on populations at risk.
Associations between gut microbiota and sleep: a two-sample, bidirectional Mendelian randomization study
Authors: Wu Jun , Zhang Baofu , Zhou Shengjie , Huang Ziyi , Xu Yindong , Lu Xinwu , Zheng Xiangtao , Ouyang Dong
Published: August 2023

Introduction

Previous research has reported that the gut microbiota performs an essential role in sleep through the microbiome–gut–brain axis. However, the causal association between gut microbiota and sleep remains undetermined.

Methods

We performed a two-sample, bidirectional Mendelian randomization (MR) analysis using genome-wide association study summary data of gut microbiota and self-reported sleep traits from the MiBioGen consortium and UK Biobank to investigate causal relationships between 119 bacterial genera and seven sleep-associated traits. We calculated effect estimates by using the inverse-variance weighted (as the main method), maximum likelihood, simple model, weighted model, weighted median, and MR-Egger methods, whereas heterogeneity and pleiotropy were detected and measured by the MR pleiotropy residual sum and outlier method, Cochran’s Q statistics, and MR-Egger regression.

Results

In forward MR analysis, inverse-variance weighted estimates concluded that the genetic forecasts of relative abundance of 42 bacterial genera had causal effects on sleep-associated traits. In the reverse MR analysis, sleep-associated traits had a causal effect on 39 bacterial genera, 13 of which overlapped with the bacterial genera in the forward MR analysis.

Discussion

In conclusion, our research indicates that gut microbiota may be involved in the regulation of sleep, and conversely, changes in sleep-associated traits may also alter the abundance of gut microbiota. These findings suggest an underlying reciprocal causal association between gut microbiota and sleep.
Cerebellar and basal ganglia inputs define three main nuclei in the mouse ventral motor thalamus
Authors: Alonso-Martínez Carmen , Rubio-Teves Mario , Casas-Torremocha Diana , Porrero César , Clascá Francisco
Published: August 2023

The thalamus is a central link between cortical and subcortical brain motor systems. Axons from the deep nuclei of the cerebellum (DCN), or the output nuclei of the basal ganglia system (substantia nigra reticulata, SNr; and internal pallidum GPi/ENT) monosynaptically innervate the thalamus, prominently some nuclei of the ventral nuclear group. In turn, axons from these ventral nuclei innervate the motor and premotor areas of the cortex, where their input is critical for planning, execution and learning of rapid and precise movements. Mice have in recent years become a widely used model in motor system research. However, information on the distribution of cerebellar and basal ganglia inputs in the rodent thalamus remains poorly defined. Here, we mapped the distribution of inputs from DCN, SNr, and GPi/ENT to the ventral nuclei of the mouse thalamus. Immunolabeling for glutamatergic and GABAergic neurotransmission markers delineated two distinct main territories, characterized each by the presence of large vesicular glutamate transporter type 2 (vGLUT2) puncta or vesicular GABA transporter (vGAT) puncta. Anterograde labeling of axons from DCN revealed that they reach virtually all parts of the ventral nuclei, albeit its axonal varicosities (putative boutons) in the vGAT-rich sector are consistently smaller than those in the vGLUT2-rich sector. In contrast, the SNr axons innervate the whole vGAT-rich sector, but not the vGLUT2-rich sector. The GPi/ENT axons were found to innervate only a small zone of the vGAT-rich sector which is also targeted by the other two input systems. Because inputs fundamentally define thalamic cell functioning, we propose a new delineation of the mouse ventral motor nuclei that is consistent with the distribution of DCN, SNr and GPi/ENT inputs and resembles the general layout of the ventral motor nuclei in primates.
Clinical-radiomics-based treatment decision support for KIT Exon 11 deletion in gastrointestinal stromal tumors: a multi-institutional retrospective study
Authors: Zhang Yu , Yue Xiaofei , Zhang Peng , Zhang Yuying , Wu Linxia , Diao Nan , Ma Guina , Lu Yuting , Ma Ling , Tao Kaixiong , Li Qian , Han Ping
Published: August 2023

Objective

gastrointestinal stromal tumors (GISTs) with KIT exon 11 deletions have more malignant clinical outcomes. A radiomics model was constructed for the preoperative prediction of KIT exon 11 deletion in GISTs.

Methods

Overall, 126 patients with GISTs who underwent preoperative enhanced CT were included. GISTs were manually segmented using ITK-SNAP in the arterial phase (AP) and portal venous phase (PVP) images of enhanced CT. Features were extracted using Anaconda (version 4.2.0) with PyRadiomics. Radiomics models were constructed by LASSO. The clinical-radiomics model (combined model) was constructed by combining the clinical model with the best diagnostic effective radiomics model. ROC curves were used to compare the diagnostic effectiveness of radiomics model, clinical model, and combined model. Diagnostic effectiveness among radiomics model, clinical model and combine model were analyzed in external cohort (n=57). Statistics were carried out using R 3.6.1.

Results

The Radscore showed favorable diagnostic efficacy. Among all radiomics models, the AP-PVP radiomics model exhibited excellent performance in the training cohort, with an AUC of 0.787 (95% CI: 0.687-0.866), which was verified in the test cohort (AUC=0.775, 95% CI: 0.608-0.895). Clinical features were also analyzed. Among the radiomics, clinical and combined models, the combined model showed favorable diagnostic efficacy in the training (AUC=0.863) and test cohorts (AUC=0.851). The combined model yielded the largest AUC of 0.829 (95% CI, 0.621–0.950) for the external validation of the combined model. GIST patients could be divided into high or low risk subgroups of recurrence and mortality by the Radscore.

Conclusion

The radiomics models based on enhanced CT for predicting KIT exon 11 deletion mutations have good diagnostic performance.
An integrated network analysis, RNA-seq and in vivo validation approaches to explore the protective mechanism of Mongolian medicine formulae Ruda-6 against indomethacin-induced gastric ulcer in rats
Authors: Feng Lan , A. Lisha , Bao Terigele , Mu Xiyele , Ta Na , Duan Qiang , Ta La , Chen Yongsheng , Bai Laxinamujila , Fu Minghai
Published: August 2023

Graphical Abstract
Impact of clinical pharmacist-led intervention for drug-related problems in neonatal intensive care unit a randomized controlled trial
Authors: Yalçın Nadir , Kaşıkcı Merve , Çelik Hasan Tolga , Allegaert Karel , Demirkan Kutay , Yiğit Şule
Published: August 2023

Introduction: Drug-related problems (DRPs) incidence is higher in neonatal intensive care units (NICUs), compared to other pediatric wards due to aspects like off-label medications, pharmacokinetic/dynamic variability, or organ dysfunction/immaturity. This study aimed to determine whether and to what extent a clinical pharmacist intervention improves medication safety and prevents DRPs [medication errors (MEs), adverse drug reactions (ADRs), drug-drug interactions (DDIs)].

Methods: A prospective, randomized, double blind, controlled study in NICU-admitted neonates was conducted. NICU patients were randomly assigned to the intervention (clinical pharmacist-led) (IG) or control group (standard care such as clinical diagnosis, pharmacotherapy) (CG). The clinical pharmacist was involved in the IG to identify-prevent-intervene MEs, or identify and monitor ADRs and DDIs. The primary outcome was the number of neonates who developed at least one DRP compared with those seen across IG and CG. Secondary outcomes included length of hospital stay, total number of drugs or DRP type.

Results: Neonates were randomly assigned to CG (n = 52) or IG (n = 48). In total, 45%, 42%, and 16% of patients had at least 1 MEs, ADRs, and clinically significant DDIs, respectively. The number of patients with at least 1 ME was 28 (53%) and 17 (35%) in the CG and IG (p>0.05). The median (range) number of ME was higher in CG [1 (0–7)] than in IG [0 (0–4)] (p = 0.003). Applying regression analysis, the CG had 2.849 times more MEs than the IG (p<0.001). Furthermore, the number of patients (CG to IG) with at least one detected ADR or clinical DDI was 19 (36%) to 23 (47%) (p>0.05) and 4 (7%) to 12 (25%), respectively (p = 0.028).

Conclusion: Clinical pharmacist availability to systematically and standardized identify, prevent and resolve DRPs among NICU patients is effective. Daily detailed clinical pharmacist observations and interventions enables prevention and monitoring of DRPs.

Clinical Trial RegistrationClinicalTrials.gov, identifier NCT04899960.
The rootstock shape microbial diversity and functionality in the rhizosphere of Vitis vinifera L. cultivar Falanghina
Authors: Zuzolo Daniela , Ranauda Maria Antonietta , Maisto Maria , Tartaglia Maria , Prigioniero Antonello , Falzarano Alessandra , Marotta Giuseppe , Sciarrillo Rosaria , Guarino Carmine
Published: August 2023

The rhizosphere effect occurring at the root-soil interface has increasingly been shown to play a key role in plant fitness and soil functionality, influencing plants resilience. Here, for the first time, we investigated whether the rootstock genotype on which Vitis vinifera L. cultivar Falanghina is grafted can influence the rhizosphere microbiome. Specifically, we evaluated to which extent the 5BB and 1103P rootstocks are able to shape microbial diversity of rhizosphere environment. Moreover, we explored the potential function of microbial community and its shift under plant genotype influence. We investigated seven vineyards subjected to the same pedo-climatic conditions, similar age, training system and management and collected twelve rhizosphere soil samples for metagenomic analyses and composite soil samples for physical-chemical properties. In this study, we used 16S rRNA gene-based metagenomic analysis to investigate the rhizosphere bacterial diversity and composition. Liner discriminant analysis effect size (LEFSe) was conducted for metagenomic biomarker discovery. The functional composition of sampled communities was determined using PICRUSt, which is based on marker gene sequencing profiles. Soil analyses involved the determination of texture, pH, Cation Exchange Capacity (CSC), Organic Carbon (OC), electrical conductivity (EC), calcium (Ca), magnesium (Mg), potassium (K) content, Phosphorous (P), nitrogen (N). The latter revealed that soil features were quite homogenous. The metagenomic data showed that the bacterial alpha-diversity (Observed OTUs) significantly increased in 1103P rhizosphere microbiota. Irrespective of cultivar, Pseudomonadota was the dominant phylum, followed by Actinomycetota > Bacteroidota > Thermoproteota. However, Actinomycetota was the major marker phyla differentiating the rhizosphere microbial communities associated with the different rootstock types. At the genus level, several taxa belonging to Actinomycetota and Alphaproteobacteria classes were enriched in 1103P genotype rhizosphere. Investigating the potential functional profile, we found that most key enzyme-encoding genes involved in N cycling were significantly more abundant in 5BB rootstock rhizosphere soil. However, we found that 1103P rhizosphere was enriched in genes involved in C cycle and Plant Growth Promotion (PGP) functionality. Our results suggest that the different rootstocks not only recruit specific bacterial communities, but also specific functional traits within the same environment.
The chemical profiling of Salvia plebeia during different growth periods and the biosynthesis of its main flavonoids ingredients
Authors: Dai Yiqun , Ye Ziyu , Liu Hui , Zhu Ruirui , Sun Lanlan , Li Shuai , Xie Guoyong , Zhu Yan , Zhao Yucheng , Qin Minjian
Published: August 2023

Salvia plebeia (Lamiaceae) is a valuable medicinal plant widely distributed across Asia and Oceania. However, the composition and accumulation patterns of its active ingredients in different organs during the growth and their biosynthetic mechanism remain unknown. Therefore, we conducted metabolite profiling, transcriptomic analysis, and biological functional verification to explore the distribution, accumulation, and biosynthesis mechanisms of flavonoids in S. plebeia. We identified 70 metabolites including 46 flavonoids, 16 phenolic acids, seven terpenoids, and one organic acid, of which 21 were previously unreported in S. plebeia. Combining metabolomic-transcriptomic analysis and biological functional verification, we identified the key genes involved in biosynthesis of its main active ingredients, hispidulin and homoplantaginin, including SpPAL, SpC4H, Sp4CL2, Sp4CL5, SpCHS1, SpCHI, SpFNS, SpF6H1, SpF6OMT1, SpF6OMT2, SpUGT1, SpUGT2, and SpUGT3. Using the identified genes, we reconstructed the hispidulin and homoplantaginin biosynthesis pathways in Escherichia coli, and obtained a yield of 5.33 and 3.86 mg/L for hispidulin and homoplantaginin, respectively. Our findings provide valuable insights into the changes in chemical components in different organs of S. plebeia during different growth and harvest stages and establishes a foundation for identifying and synthesizing its active components.
Promoting appetitive learning of consensual, empowered vulnerability: a contextual behavioral conceptualization of intimacy
Authors:   Louisiana Contextual Science Research Group
Published: August 2023

Vulnerability is emphasized in a number of theoretical models of intimacy (e.g., Intimacy Process Model), including from behavioral and contextual behavioral perspectives. Vulnerability is generally defined as susceptibility to harm and involves behaviors that have been historically met with aversive social consequences. From these perspectives, intimacy is fostered when vulnerable behavior is met with reinforcement. For example, interventions have trained intimacy by building skills in emotional expression and responsiveness with promising results. Vulnerability has divergent functions, however, depending on the interpersonal context in which it occurs. Functional intimacy is explored through the lens of functional relations, which play a key role in interpersonal processes of power, privilege, and consent. This conceptualization suggests that vulnerability must be under appetitive functional relations, consensual, and empowered for safe intimacy to emerge. The responsibility to promote appetitive learning of consensual, empowered vulnerability to foster intimacy falls to the person with more power in a particular interaction and relationship. Recommendations are offered for guiding this process.
Acute effects of exergaming on young adults’ energy expenditure, enjoyment, and self-efficacy
Authors: Gu Dandong , Gu Chenling , Oginni John , Ryu Suryeon , Liu Wenxi , Li Xianxiong , Gao Zan
Published: August 2023

This study investigated the effects of a dance-based exergaming on Chinese college students’ energy expenditure, self-efficacy, and enjoyment in comparison with the traditional aerobic dance exercise. Forty young adults (33 females; Mage = 21.55 years, SD = 2.06) completed two separate 20 min exercise sessions with 10 min intervals on the same day: (1) Xbox 360 Kinect Just Dance exergaming session; and (2) a traditional instructor-led aerobic dance exercise session. Participants’ energy expenditure (Kcal/session) was measured by the ActiGraph GT9X Link accelerometers, and their perceived self-efficacy and enjoyment were assessed via validated surveys following each session. Dependent t-test indicated significant differences in participants’ enjoyment (t = −1.83,p = 0.04). Specifically, participants in the dance-based exergaming session reported a higher level of enjoyment (M = 3.96, SD = 0.65) as compared to the aerobic dance session (M = 3.61, SD = 0.54). However, there was no significant difference in energy expenditure and self-efficacy between the two sessions. Findings suggest that college students had comparable energy expenditure as the traditional aerobic dance session while experiencing more fun and enjoyment. This suggests that exergaming can be a fun exercise alternative for promoting physical activity among young adults.
Cross-cultural differences in early caregiving: levels of mind-mindedness and instruction in UK and India
Authors: Bozicevic Laura , Hill Jonathan , Chandra Prabha S. , Omirou Agni , Holla Chaithra , Wright Nicola , Sharp Helen
Published: August 2023

Introduction

Most studies on parenting and its role in child development are conducted in Western countries, but it cannot be assumed that characteristics of parental practices are similar in non-Western settings. Research characterizing cultural differences in parenting is required to inform the focus of studies designed to test differential outcomes from such practices in children over time and across cultures. The present cross-cultural study examined differences in maternal speech during mother–child interactions, and, specifically, in the use of mind-mindedness, instruction and control, and the expression of warmth (i.e., positive comments).

Methods

We observed 100 dyads (50 from the UK and 50 from India) during mother-infant play interactions at 7 months. Maternal speech was transcribed and translated prior to independent coding, and this was coded using established measures together with a newly developed measure of “Instructions”.

Results

Substantially large differences between UK and Indian mothers were observed. Compared with UK mothers, Indian mothers made fewer mind-minded comments about their infants, and they issued more instructions and made more controlling and positive comments. Findings from this study might reflect cultural differences in how parental style might be expressed according to cultural priorities and values.

Conclusions

The implications of these very large differences in parenting across cultures for child development remain to be investigated and are discussed in the present paper.