bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of polysaccharides on turbot Scophthalmus maximus: evaluation with a head kidney macrophage cellular model
Authors: Dong XF , Wang XX , Qin ZH
Published: July 2024

Polysaccharides exhibit a multitude of biological activities, including antioxidant, antitumor, immunoregulatory, hepatoprotective, and anti-inflammatory effects, but it is not known whether such effects occur in fish. Head kidney macrophages from turbot Scophthalmus maximus L. were isolated and cultured to examine the responsiveness to natural polysaccharides as potential immune stimulators. Polysaccharides used in the research included Echinacea purpurea polysaccharide (EPP), Astragalus polysaccharide (APS), lentinan (LNT), seaweed polysaccharide (SPS), and laminarin (LAM). The test compounds were added to the cultures and assessed for their effects on the growth and immunomodulatory functions of the cells. Based on the results of cell activity, reactive oxygen species, and nitic oxide assays, APS was selected as an immune stimulator. After addition of APS to the culture medium, a comprehensive proteomic analysis was conducted to identify signaling pathways responsible for the immune effects on macrophages. Specific immune pathway proteins were upregulated in cells in response to the addition of APS, including macrophage migration inhibitory factor, myosin-α, metalloproteinase inhibitor, and collagenase type III. In particular, compared with non-stimulated cells, the expression level of the TLR22 receptor was significantly increased in stimulated macrophages (p < 0.01). A KEGG pathway analysis indicated that relevant pathways were activated, including TNF, PI3K-Akt, and NF-κB signaling pathways. ELISA and qRT-PCR analysis also indicated that APS reduced IL-1β and TNF-α levels in the cells following lipopolysaccharide (LPS) stimulation. These data suggest that APS produced an immunoprotective effect on the head kidney macrophages of turbot at 800 µg ml-1, and enhanced cell proliferation. Our results provide evidence for anti-inflammatory properties of APS. As such, APS could be a candidate immunopotentiating agent for fish.
On ‘Thick’ Confucian Relationality from the Perspective of Contextual Individuality
Authors: Yang 楊宇舟 Yuzhou
Published: July 2024

Relationality is a multifaceted idea that displays one of the distinctive characteristics of Chinese philosophy. In Confucianism, it is primarily associated with the issue of human relations. Drawing on John Dewey’s proposition of ‘relationally constituted individuality’, Roger T. Ames identifies a ‘thick’ nature in Confucian relationality whose cosmic foundation may be novel to the West. This thick relationality corresponds with a narrative approach to human nature ( xing 性), inspires a Confucian neologism of ‘human becomings’ and challenges the conventional idea of ‘human being’ that implies a Western foundational individualism. Through a proposed theme of ‘contextual individuality’, this study aims to evaluate whether Confucian relationality could be too ‘thick’ for individuality (in a non-atomistic/non-foundational sense) and uncover the implication of thick relationality on the study of comparative philosophy in general.
Rewriting Chinese Stories: Gender in Chinese Translation of Amy Tan
Authors: Tang Beibei
Published: July 2024

This article explores the intricate process of translating Chinese stories within the work of Chinese American women writers, focusing on Amy Tan. Tan navigates feminist themes by using and rewriting traditional Chinese stories within her novels The Joy Luck Club and The Kitchen God’s Wife. This can create challenges for her translators. Analysis looks at how translators ‘rewrite’ Tan, and uncovers some divergences between the work of male and female translators respectively, highlighting the influence of gender consciousness on translation practices. By examining the interplay between gender, culture, and translation, it underscores the role of gender in either perpetuating or challenging cultural and gender norms within translated texts.
Morphology and novel classification of proximal humeral fractures
Authors: Liu Jichao , Zhang Ziyan , Ding Jie , Zhang Jian , Sheng Qian , Piao Chengdong
Published: July 2024

Background: The morphology of proximal humeral fractures (PHFs) is complex, and the fixation and selection of implants need to be guided by the fracture type and classification, which requires an accurate understanding of the fracture line. This study had three purposes. 1) Define and analyze the fracture lines and morphological features of all types PHFs by three-dimensional (3D) mapping technology. 2) Determine the osteotomy position of the biomechanical model of the PHFs according to the fracture heat map. 3) Based on the analysis of the pathological morphology and distribution of a large number of consecutive cases of PHFs, propose a novel classification of PHFs.

Methods: We retrospectively collected 220 cases of PHFs and generated a 3D fracture map and heat map based on computed tomography (CT) imaging. Through analysis of the fracture morphology of the 220 PHFs, a novel classification was proposed. The primary criterion for staging was the continuity between the humeral head and the greater tuberosity and lesser tuberosity, and the secondary criterion was the relationship between the humeral head segment and the humeral shaft.

Results: The fracture line was primarily found around the metaphyseal zone of region of the surgical neck, with the most extensive distribution being below the larger tuberosity and on the posterior medial side of the epiphysis. We suggest that the osteotomy gap should be immediately (approximately 5–10 mm) below the lower edge of the articular surface. The most common type of fracture was type I3 (33 cases, 15.0%), followed by type IV3 fracture (23 cases, 10.4%), and type III2 fracture (22 cases, 10.0%). Interobserver and intraobserver reliability analysis for the fracture classification revealed a k value (95% confidence interval) of 0.639 (0.57–0.71) and 0.841, P < 0.01, respectively.

Conclusion: In this study, the fracture line and morphological characteristics of PHFs were clarified in detail by 3D mapping technique. In addition, a new classification method was proposed by analysis of the morphological characteristics of 220 PHFs, A two-part fracture model for PHFs is also proposed.
Functional determination of site-mutations in rdxA involved in metronidazole resistance of Helicobacter pylori
Authors: Huang Jia , Li Zhiyu , Ge Fulin , Sun Chao , Deng Zixin , Yao Weiyan , He Xinyi
Published: July 2024

Background

Metronidazole (MTZ) is among the first-line drugs against the human gastric pathogen Helicobacter pylori (H. pylori). MTZ is used as a prodrug that is activated by an oxygen-insensitive enzyme NADPH nitroreductase (RdxA). Loss-of-function mutations in rdxA make H. pylori MTZ resistant; however, experimental proof is lacking.

Methods

We collected 139 gastric biopsy samples from patients suspected of H. pylori infection in Shanghai, and amplified Hp-specific rdxA gene from 134 samples. All these rdxA genes were sequenced and phylogenetically compared. The effect of mutations on RdxA function was measured by expressing them in Escherichia coli DH5α by using the MTZ sensitivity test.

Results

In total, 134 gastric biopsy samples were identified as H. pylori positive. Of the 134 samples, 74 and 6 had point mutations at the various sites or promoter region of rdxA, generating truncated and extended fused proteins, respectively. The remaining 54 were full-length with single nucleotide variation (SNV) compared with the wild-type RdxA from H. pylori, with 49 clustering with hpEastAsia, 3 with hpEurope, and 2 with hpNEAfrica. All 134 rdxA were expressed in E. coli DH5α; 22 and 112 resultant strains showed MTZ-sensitive and MTZ-resistant phenotypes, respectively. Comparative analysis of single nucleotide polymorphisms (SNPs) in the functional and inactivated RdxA revealed 14 novel mutations in RdxA, 5 of which conferred MTZ resistance: S18F, D59S, L62I, S79N, and A187V.

Conclusion

The occurrence of MTZ resistance induced by site-mutation of RdxA in patients with H. pylori infection was 83.6% (112/134) in the Shanghai region. The major form of loss-of-function mutation was truncation of RdxA translation at a rate of 58/112 (51.8%). Molecular detection reliably determined the resistance of H. pylori to MTZ. Thus, the functional mutants involved in MTZ resistance facilitate clinical diagnosis and medication based on sequence analysis.
Relevance of objective and subjective profile: creative behavior assessment in higher education students
Authors: Alvarez-Icaza Inés , Suárez-Brito Paloma , Alvarez Jaime , Molina-Espinosa José Martín
Published: July 2024

Creativity is a 21st Century skill. Promoting problem-solving and attending to global complex issues in formative learning experiences and professional endeavors is considered necessary. The assessment of creativity in higher education is a challenge itself due to few objective instruments for Spanish speakers and Latin populations considering this skill as key for current and future challenges. In addition to formal creativity training, which is based on curricula formed by a set of tools and processes, there is also the role of self-perception over this skill. The objective profile is the expected performance, while the subjective is seen as a self-declared ability. In this sense, having a proper assessment of creative behavior allows to align the intentions of institutions and educators toward an integrated professional profile in a multidisciplinary manner. In this study, the Creative Behavior Assessment Instrument was applied to pre-graduates from Creative Studies (CS; Design, Architecture, Digital Animation, and Communication) areas and other disciplines to answer three main research questions (1) Are CS students more creative than other discipline students?; (2) How does fluency vary between students from different disciplines?; (3) Is there coherence between the objective and subjective responses to the instrument? The methodological approach for this study is mixed methods, focusing on total score, visuospatial ability, fluidity, and self-perception. Results are discussed in terms of the difference shown by the students’ objective/subjective profiles in relation to their discipline, the relevance of promoting creativity in higher education, and the implications of individual differences regarding the subjective profile.
Do gender and science success moderate the effects of science learning self-efficacy on science identity?
Authors: Belova Tatyana , Islamov Artem E. , Rozhnov Artemiy A. , Zhdanov Sergei P. , Sokolova Ekaterina I. , Tsomartova Dibakhan A.
Published: July 2024

Introduction

This study investigates the relationship between science learning self-efficacy and science identity, examining how gender and science success moderate this relationship.

Methods

Using a quantitative approach with Partial Least Squares Structural Equation Modeling, data from high school students in Moscow, Almetyevsk, Khabarovsk cities from Russia were analyzed.

Results

The research highlights the significant positive impact of integrative science competence, practical science application, and science communication efficacy on science identity. Interestingly, gender did not significantly influence the efficacy-identity relationship, suggesting its minimal role in this context. Conversely, science success, particularly in conjunction with science communication efficacy, played a notable role, indicating a complex interplay that could affect students’ science identity.

Discussion

These findings emphasize the need for educational strategies that bolster students’ self-efficacy in science, catering to the development of a strong science identity. Future research should explore the nuanced effects of success and communication efficacy on science identity, aiming to inform interventions that support diverse and equitable participation in science education and careers.
Exploring the role of cellular senescence in cancer prognosis across multiple tumor types
Authors: Xu Qi , Feng Xiaoying
Published: July 2024

Background

Cellular senescence is a common biological process with a well-established link to cancer. However, the impact of cellular senescence on tumor progression remains unclear. To investigate this relationship, we utilized transcriptomic data from a senescence gene set to explore the connection between senescence and cancer prognosis.

Methods

We developed the senescence score by the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. We obtained transcriptomic information of the senescence gene set from The Cancer Genome Atlas (TCGA) program. Additionally, we created a nomogram that integrates these senescence scores with clinical characteristics, providing a more comprehensive tool for prognosis evaluation.

Results

We calculated the senescence score based on the expression level of 42 senescence-related genes. We established the nomogram based on the senescence score and clinical characteristics. The senescence score showed a positive correlation with epithelial-to-mesenchymal transition, cell cycle, and glycolysis, and a negative correlation with autophagy. Furthermore, we carried out Gene Ontology (GO) analysis to explore the signaling pathways and biological process in different senescence score groups.

Conclusions

The senescence score, a novel tool constructed in this study, shows promise in predicting survival outcomes across various cancer types. These findings not only highlight the complex interplay between senescence and cancer but also indicate that cellular senescence might serve as a biomarker for tumor prognosis.
Mendelian randomization study and mediation analysis about the relation of inflammatory bowel disease and diabetic retinopathy: the further exploration of gut-retina axis
Authors: Lin Jiayi , Cheng Yaqi , Gu Simin , Song Siqi , Zhang Huini , Li Jianbing , Ling Shiqi
Published: July 2024

Background

The concept of the gut-retinal axis proposed by previous scholars primarily focused on the relationship between intestinal microbiota and retinal diseases, and few further expanded the relationship between intestinal diseases and retinal diseases. To further substantiate the concept of the gut-retinal axis, we analyzed inflammatory bowel disease (IBD) and diabetic retinopathy (DR) using Mendelian randomization (MR), and use mediation analysis to further explore the potential substances that influence this causal relationship.

Methods

The genome-wide association study’s (GWAS) summary statistics for genetic variations were utilized in a Mendelian randomization (MR) investigation. GWAS data on IBD (including ulcerative colitis (UC), Crohn’s disease (CD), and IBD) for non-Finnish Europeans (NFE) were sourced from published articles. In contrast, data on DR (including DR and diabetic maculopathy (DMP)) were obtained from FinnGen R9. The causal relationship has been investigated using inverse variance weighted (IVW), MR-Egger, and weighted median and sensitivity analysis was applied to verify the stability of the results. In addition, we applied mediation analysis to investigate whether circulating inflammatory proteins and plasma lipids played a mediating role, and calculated its effect ratio.

Results

The causal relationship between IBD and DR was discovered by employing the inverse variance weighted (IVW) method and weighted median method. In forward MR, UC was significantly associated with lower risk of DR (IVW: OR=0.874; 95%CI= 0.835–0.916; P value= 1.28E-08) (Weighted median: OR=0.893; 95%CI= 0.837–0.954; P value= 7.40E-04). In reverse MR, it was shown that DR (IVW: OR=0.870; 95%CI= 0.828–0.914; P value= 2.79E-08)(Weighted median: OR=0.857; 95%CI= 0.801–0.916; P value= 6.40E-06) and DMP (IVW: OR=0.900; 95%CI= 0.865–0.937; P value= 3.34E-07)(Weighted median: OR=0.882; 95%CI= 0.841–0.924; P value= 1.82E-07) could reduce the risk of CD. What’s more, DR is associated with a lower risk of IBD according to genetic prediction (IVW: OR=0.922; 95%CI= 0.873–0.972; P value= 0.002) (Weighted median: OR=0.924; 95%CI= 0.861–0.992; P value= 0.029). Fibroblast growth factor 21 (FGF21), phosphatidylcholine (PC), and triacylglycerol (TG) serve as mediators in these relationships.

Conclusions

Our research offers novel insights and sources for investigating the gut-retina axis in the genetic relationship between IBD and DR. We discover four mediators and more about the association between the intestine and retinal disorders and provide more evidence for the gut-retinal axis theory.
Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial
Authors: Cao YongSheng , Cao Shujie , Zhao Jiangang , Zhao Jianqin , Zhao Yanan , Liu Ying
Published: July 2024

Objective

This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management.

Methods

This study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks.

Results

Overall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of −29.3% (95% confidence interval [CI]: −34.8, −23.7), compared to that of −31.8% in the dapagliflozin group (95% CI: −34.8, −23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by −1.30% (95% CI: −1.43, −1.18) in the PEG-Loxe group and by −1.29% (95% CI: −1.42, −1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by −0.56 mmol/L (95% CI: −0.71, −0.42) in the PEG-Loxe group and −0.33 mmol/L (95% CI: −0.48, −0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group.

Conclusions

PEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options.

Clinical Trial Registration

www.chictr.org.cn, identifier ChiCTR2300070919.
Runtime support for CPU-GPU high-performance computing on distributed memory platforms
Authors: Thomadakis Polykarpos , Chrisochoides Nikos
Published: July 2024

Introduction

Hardware heterogeneity is here to stay for high-performance computing. Large-scale systems are currently equipped with multiple GPU accelerators per compute node and are expected to incorporate more specialized hardware. This shift in the computing ecosystem offers many opportunities for performance improvement; however, it also increases the complexity of programming for such architectures.

Methods

This work introduces a runtime framework that enables effortless programming for heterogeneous systems while efficiently utilizing hardware resources. The framework is integrated within a distributed and scalable runtime system to facilitate performance portability across heterogeneous nodes. Along with the design, this paper describes the implementation and optimizations performed, achieving up to 300% improvement on a single device and linear scalability on a node equipped with four GPUs.

Results

The framework in a distributed memory environment offers portable abstractions that enable efficient inter-node communication among devices with varying capabilities. It delivers superior performance compared to MPI+CUDA by up to 20% for large messages while keeping the overheads for small messages within 10%. Furthermore, the results of our performance evaluation in a distributed Jacobi proxy application demonstrate that our software imposes minimal overhead and achieves a performance improvement of up to 40%.

Discussion

This is accomplished by the optimizations at the library level and by creating opportunities to leverage application-specific optimizations like over-decomposition.
Detection of minimal residual disease in acute myeloid leukemia: evaluating utility and challenges
Authors: Álvarez Noemí , Martín Alejandro , Dorado Sara , Colmenares Rafael , Rufián Laura , Rodríguez Margarita , Giménez Alicia , Carneros Laura , Sanchez Ricardo , Carreño Gonzalo , Rapado Inmaculada , Heredia Yanira , Martínez-López Joaquín , Barrio Santiago , Ayala Rosa
Published: July 2024

This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation sequencing (NGS). AML prognosis is based on various factors, including genetic alterations. NGS has revealed the molecular complexity of AML and helped refine risk stratification and personalized therapies. The long-term survival rates for AML patients are low, and MRD assessment is crucial in predicting prognosis. Currently, the most common methods for MRD detection are flow cytometry and quantitative PCR, but NGS is being incorporated into clinical practice due to its ability to detect genomic aberrations in the majority of AML patients. Typically, bone marrow samples are used for MRD assessment, but using peripheral blood samples or liquid biopsies would be less invasive. Leukemia originates in the bone marrow, along with the cfDNA obtained from peripheral blood. This study aimed to assess the utility of cell-free DNA (cfDNA) from peripheral blood samples for MRD detection in AML patients. A cohort of 20 AML patients was analyzed using NGS, and a correlation between MRD assessment by cfDNA and circulating tumor cells (CTCs) in paired samples was observed. Furthermore, a higher tumor signal was detected in cfDNA compared to CTCs, indicating greater sensitivity. Challenges for the application of liquid biopsy in MRD assessment were discussed, including the selection of appropriate markers and the sensitivity of certain markers. This study emphasizes the potential of liquid biopsy using cfDNA for MRD detection in AML patients and highlights the need for further research in this area.
Defining correlates of protection for mammalian livestock vaccines against high-priority viral diseases
Authors: Davis Samantha K. , Jia Fan , Wright Quentin G. , Islam Md. Tanjir , Bean Andrew , Layton Daniel , Williams David T. , Lynch Stacey E.
Published: July 2024

Enhancing livestock biosecurity is critical to safeguard the livelihoods of farmers, global and local economies, and food security. Vaccination is fundamental to the control and prevention of exotic and endemic high-priority infectious livestock diseases. Successful implementation of vaccination in a biosecurity plan is underpinned by a strong understanding of correlates of protection—those elements of the immune response that can reliably predict the level of protection from viral challenge. While correlates of protection have been successfully characterized for many human viral vaccines, for many high-priority livestock viral diseases, including African swine fever and foot and mouth disease, they remain largely uncharacterized. Current literature provides insights into potential correlates of protection that should be assessed during vaccine development for these high-priority mammalian livestock viral diseases. Establishment of correlates of protection for biosecurity purposes enables immune surveillance, rationale for vaccine development, and successful implementation of livestock vaccines as part of a biosecurity strategy.
Efficacy and safety of PD-1/L1 inhibitors as first-line therapy for metastatic colorectal cancer: a meta-analysis
Authors: Huang Zhilong , Li Chunyan , Huang Yanping , Liang Weiming , Tao Haiyun
Published: July 2024

Objective

To evaluate the efficacy and safety of PD-1/L1 inhibitors as first-line therapy in metastatic colorectal cancer(mCRC).

Method

Articles evaluating first-line PD-1/L1 inhibitors for mCRC were sought in four databases (Pubmed, Embase, Web of Science, and the Cochrane Library) from the inception of the databases until 11 November 2023. Meta-analyses were conducted to assess the rates of progression-free survival (PFS), overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), disease control rate (DCR), and grade ≥ 3 treatment-related adverse events (trAEs).

Results

Totally nine studies were included for meta-analysis. A subgroup analysis was performed based on mismatch repair(MMR) status and regimens. In patients diagnosed with mismatch repair-deficient(dMMR) mCRC who received PD-1/L1 inhibitors as their first-line treatment, the ORR was 0.54 (95% CI, 0.39 to 0.68), the median PFS was 53.2 months, the Grade≥ 3 TRAEs rate was 0.33(95% CI, 0.12 to 0.60) and the median OS was not determined. For patients with proficient mismatch repair (pMMR) mCRC who underwent a combined treatment of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody and chemotherapy as their first-line therapy, the ORR was 0.62 (95% CI, 0.56 to 0.68), the median PFS was 10.1 months, the median OS was 26.7 months, and the Grade≥ 3 TRAEs rate was 0.59(95% CI, 0.39 to 0.77).

Conclusion

Our results revealed that the utilization of PD-1/L1 inhibitors as first-line therapy for dMMR mCRC yielded highly favorable outcomes, while maintaining an acceptable level of safety. Administering a combination of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody, and chemotherapy as first-line treatment in patients with pMMR mCRC led to an improved ORR. However, there was no significant improvement in the long-term prognosis of the tumor.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506196, identifier CRD42024506196.
Is OSPAR 98/3 science-based politics or politics-based science?
Authors: Paces Nicole , Davies Abigail J. , Hastings Astley
Published: July 2024

Man-made structures in the marine environment such as offshore Oil & Gas infrastructure are known to provide a hard substrate that enables ecosystems to develop on and around them. Current decommissioning practices on the UK Continental Shelf are mandated by the OSPAR Decision 98/3 with the premise of a clean seabed at its core, meaning that it is the expectation that all infrastructure is completely removed at the end of its operation life, leaving a clear seabed behind. This study critically reviewed 49 peer-reviewed articles relating to the ecosystem and the impact to these ecosystems by current removal practices. The results clearly demonstrate that current science-based evidence shows that existing O&G platform substructures act as multipurpose artificial reefs upon which rich ecosystems have developed and that their removal degrades the overall North Sea marine environment. Furthermore, this study shows that clear-sea bed policies, such as OSPAR 98/3, do not reflect, nor understand the complex relationship and interdependencies between biology and man-made structures and do not reflect current scientific knowledge. It is concluded that based on current knowledge, it is no longer scientifically justifiable to mandate the removal of all O&G infrastructure during decommissioning and that applying the principle of a clean seabed according to the OSPAR Commission should be re-considered.
Integrative computational framework to decipher the functions of shell proteins in biomineralization
Authors: Dong Wentao , Xie Liping , Zhang Rongqing
Published: July 2024

Mollusk shells contain biominerals with remarkable mechanical properties enabled by a small fraction of embedded organic matrix proteins. However, the specific molecular functions of most shell proteins have remained elusive. Traditional genomics and functional studies are extremely laborious to identify key components. To address this, we developed an in-silico pipeline integrating protein structure modeling, molecular dynamics simulations, and machine learning to elucidate the critical ion protein interactions governing shell formation. Using the pearl oyster Pinctada fucata as a test case, our framework successfully recapitulated known protein functions and predicted roles of uncharacterized proteins to guide future experiments. Moreover, the pipeline’s modular design enables versatile applications for rapidly elucidating structure-function relationships in diverse biomineralization systems, complementing conventional wet-lab methods. Overall, this computational approach leverages automatic simulations and analytics to unlock molecular insights into shell protein ion dynamics, accelerating the discovery of key crystallization regulators for bioinspired materials design.
Impact of a passive upper-body exoskeleton on muscular activity and precision in overhead single and dual tasks: an explorative randomized crossover study
Authors: Gräf Julia , Grospretre Sidney , Argubi-Wollesen Andreas , Wollesen Bettina
Published: July 2024

Introduction

Tasks performed at or above head height in industrial workplaces pose a significant challenge due to their association with musculoskeletal disorders. Upper-body exoskeletons have been identified as a potential solution for mitigating musculoskeletal loads and fighting against excessive muscular fatigue. However, the influence of such support on fine motor control, as well as on cognitive-motor interference, has received limited attention thus far. Therefore, this crossover randomized study aimed to investigate the impact of the use of a passive upper-body exoskeleton in the presence of muscular fatigue or not. Additionally, focusing on differences between single (ST) and dual (DT) industrial tasks consisting of overhead speed and accuracy exercises.

Methods

In both scenarios, N = 10 participants (5 male/5 female) engaged in an overhead precision task using a nail gun to precisely target specific areas on three differently sized regions, based on Fitts’ law paradigm (speed-accuracy trade-off task). This was done with and without the passive upper-body exoskeleton, before and immediately after a fatiguing exercise of shoulder and leg muscles. In addition, a second task (dual-task, DT) was carried out in which the occurrence of an auditory signal had to be counted. The main outcomes were muscular activation of the shoulder girdle as well as the time to perform speed-accuracy tasks of different difficulty indexes (calculated by means of Fitts’ law).

Results and discussion

In the absence of fatigue, the exoskeleton did not affect the speed-accuracy trade-off management of participants in the single task, but it did in the dual-task conditions. However, after muscle fatigue, the speed-accuracy trade-off was differently affected when comparing its execution with or without the exoskeleton. In general, the dual task resulted in longer times to perform the different tasks, whether it was with or without the exoskeleton. Furthermore, the use of the exoskeleton decreased muscle activity, which is associated with less physical effort, but only significantly for the M. deltoideus and M. trapezius when compared by tasks. Overall, these study findings highlight the potential supportive effects of using an upper-body exoskeleton for industrial overhead tasks.
Association of high fibrinogen to albumin ratio with long-term mortality in patients with spontaneous intracerebral hemorrhage
Authors: Chen Shiping , Zhang Yu , Xiao Yangchun , Cheng Xin , Peng Liyuan , Tian Yixin , Li Tiangui , He Jialing , Hao Pengfei , Chong Weelic , Hai Yang , You Chao , Fang Fang
Published: July 2024

Background

The association between fibrinogen-to-albumin ratio (FAR) and in-hospital mortality in patients with spontaneous intracerebral hemorrhage (ICH) has been established. However, the association with long-term mortality in spontaneous ICH remains unclear. This study aims to investigate the association between FAR and long-term mortality in these patients.

Methods

Our retrospective study involved 3,538 patients who were diagnosed with ICH at West China Hospital, Sichuan University. All serum fibrinogen and serum albumin samples were collected within 24 h of admission and participants were divided into two groups according to the FAR. We conducted a Cox proportional hazard analysis to evaluate the association between FAR and long-term mortality.

Results

Out of a total of 3,538 patients, 364 individuals (10.3%) experienced in-hospital mortality, and 750 patients (21.2%) succumbed within one year. The adjusted hazard ratios (HR) showed significant associations with in-hospital mortality (HR 1.61, 95% CI 1.31–1.99), 1-year mortality (HR 1.45, 95% CI 1.25–1.67), and long-term mortality (HR 1.45, 95% CI 1.28–1.64). Notably, the HR for long-term mortality remained statistically significant at 1.47 (95% CI, 1.15–1.88) even after excluding patients with 1-year mortality.

Conclusion

A high admission FAR was significantly correlated with an elevated HR for long-term mortality in patients with ICH. The combined assessment of the ICH score and FAR at admission showed higher predictive accuracy for long-term mortality than using the ICH score in isolation.
Effects of perioperative hydrogen inhalation on brain edema and prognosis in patients with glioma: a single-center, randomized controlled study
Authors: Wu Fan , Liang Tao , Liu Yang , Wang Chenhui , Sun Yongxing , Wang Baoguo
Published: July 2024

Introduction

Brain edema is a life-threatening complication that occurs after glioma surgery. There are no noninvasive and specific treatment methods for brain edema. Hydrogen is an anti-inflammatory and antioxidant gas that has demonstrated therapeutic and preventative effects on several diseases, particularly in the nervous system. This study aimed to determine the therapeutic effects of hydrogen administration on brain edema following glioma surgery and elucidate its mechanism.

Methods

A single-center, randomized controlled clinical trial of hydrogen inhalation was conducted (China Clinical Trial Registry [ChiCTR-2300074362]). Participants in hydrogen (H) group that inhaled hydrogen experienced quicker alleviation of postoperative brain edema compared with participants in control (C) group that inhaled oxygen.

Results

The volume of brain edema before discharge was significantly lower in the H group (p < 0.05). Additionally, the regression rate of brain edema was higher in the H group than in the C group, which was statistically significant (p < 0.05). Furthermore, 3 days after surgery, the H group had longer total sleep duration, improved sleep efficiency, shorter sleep latency, and lower numerical rating scale (NRS) scores (p < 0.05).

Discussion

In conclusion, hydrogen/oxygen inhalation effectively reduced postoperative brain edema in glioma patients. Further research is necessary to understand the underlying mechanisms of hydrogen’s therapeutic effects. Hydrogen is expected to become a new target for future adjuvant therapy for brain edema.
Methodological challenges of measuring brain volumes and cortical thickness in idiopathic normal pressure hydrocephalus with a surface-based approach
Authors: Del Giovane Martina , David Michael C. B. , Kolanko Magdalena A. , Gontsarova Anastasia , Parker Thomas , Hampshire Adam , Sharp David J. , Malhotra Paresh A. , Carswell Christopher
Published: July 2024

Identifying disease-specific imaging features of idiopathic Normal Pressure Hydrocephalus (iNPH) is crucial to develop accurate diagnoses, although the abnormal brain anatomy of patients with iNPH creates challenges in neuroimaging analysis. We quantified cortical thickness and volume using FreeSurfer 7.3.2 in 19 patients with iNPH, 28 patients with Alzheimer's disease (AD), and 30 healthy controls (HC). We noted the frequent need for manual correction of the automated segmentation in iNPH and examined the effect of correction on the results. We identified statistically significant higher proportion of volume changes associated with manual edits in individuals with iNPH compared to both HC and patients with AD. Changes in cortical thickness and volume related to manual correction were also partly correlated with the severity of radiological features of iNPH. We highlight the challenges posed by the abnormal anatomy in iNPH when conducting neuroimaging analysis and emphasise the importance of quality checking and correction in this clinical population.
Targeting heme degradation pathway augments prostate cancer cell sensitivity to docetaxel-induced apoptosis and attenuates migration
Authors: Salloom Ramia J. , Ahmad Iman M. , Abdalla Maher Y.
Published: July 2024

Introduction

Chemotherapy, notably docetaxel (Doc), stands as the primary treatment for castration-resistant prostate cancer (CRPC). However, its efficacy is hindered by side effects and chemoresistance. Hypoxia in prostate cancer (PC) correlates with chemoresistance to Doc-induced apoptosis via Heme Oxygenase-1 (HO-1) modulation, a key enzyme in heme metabolism. This study investigated targeting heme degradation pathway via HO-1 inhibition to potentiate the therapeutic efficacy of Doc in PC.

Methods

Utilizing diverse PC cell lines, we evaluated HO-1 inhibition alone and with Doc on viability, apoptosis, migration, and epithelial- to- mesenchymal transition (EMT) markers and elucidated the underlying mechanisms.

Results

HO-1 inhibition significantly reduced PC cell viability under hypoxic and normoxic conditions, enhancing Doc-induced apoptosis through interconnected mechanisms, including elevated reactive oxygen species (ROS) levels, glutathione cycle disruption, and modulation of Signal Transducer and Activator of Transcription 1 (STAT1) pathway. The interplay between STAT1 and HO-1 suggests its reliance on HO-1 activation. Additionally, a decrease in cell migration and downregulation of EMT markers (vimentin and snail) were observed, indicating attenuation of mesenchymal phenotype.

Discussion

In conclusion, the combination of HO-1 inhibition with Doc holds promise for improving therapeutic outcomes and advancing clinical management in PC.
RAB42 overexpression correlates with poor prognosis, immune cell infiltration and chemoresistance
Authors: Wang Yang , Xie Youbang , Qian Luomeng , Ding Ran , Pang Rongqing , Chen Ping , Zhang Qing , Zhang Sihe
Published: July 2024

Background

RAB42 (Ras-related protein 42) is a new small GTPase that controls the vesicular trafficking from endosomes to trans-Golgi network in mammalian cells. However, the role of RAB42 in multiple cancers, especially in liver hepatocellular carcinoma (LIHC), has not been well investigated.

Methods

A variety of cancer-related databases and online tools, including TCGA, GTEx, TARGET, QUANTISEQ, EPIC, RNAactDrug, CTR-DB, TIMER algorithms and Sangerbox, were applied to explore the correlation of RAB42 expression with prognosis, immune microenvironment, immune regulatory network, RNA modification, pathway activation and drug sensitivity in pan-cancer. The prognostic, immunomodulatory and tumor-promoting effects of RAB42 were verified in various malignancies and determined by a series of in vitro cellular experiments.

Results

RAB42 is significantly overexpressed in most cancers with advanced pathological stages. Its overexpression is correlated with poor survival in pan-cancer. RAB42 overexpression has a high diagnostic accuracy of various cancers (AUC > 0.80). RAB42 overexpression not only correlates with distinct stromal immune infiltration and level of immune checkpoint molecules, but also associates with weak immune cell infiltration, immunomodulatory genes expression, and immunotherapeutic response to immune checkpoint inhibitors (ICIs). Additionally, RAB42 overexpression correlates with enhanced expression of m6A RNA methylation-related genes (MRGs) and its interactors. Moreover, overexpression of RAB42 serves as a drug-resistant marker to certain chemotherapies and acts as a potential biomarker for LIHC. Notably, RAB42 overexpression or activation promotes the cellular proliferation, migration and invasion of LIHC.

Conclusion

Overexpressed RAB42 serves as a potential prognostic biomarker and therapeutic target in pan-cancer, especially in LIHC.
Cost-effectiveness analysis of pharmaceutical care in adult critically ill patients: based on a prospective cohort study
Authors: Wei Chunyan , Hu Ming , Chen Guanghui , Yan Zhijing , Yin Wanhong , Wu Zhiang
Published: July 2024

Background

The medication regimen for critically ill patients is complex and dynamic, leading to a high incidence of drug-related problems. This study aimed to assess the effectiveness and economic efficiency of pharmaceutical care for these patients.

Methods

In this prospective cohort study conducted in a tertiary hospital, adult patients were assigned either to a clinical pharmaceutical care group or a control group based on existing clinical grouping rules. Health outcomes and economic indicators were collected, followed by a cost-effectiveness analysis.

Results

The acceptance rate for clinical pharmacist interventions was 89.31%. The pharmaceutical care group exhibited significant reductions in the rate of medication errors (40.65% vs. 61.69%, P < 0.001) and adverse drug events (44.52% vs. 56.45%, P = 0.020). The usage rates for special-grade antibiotics (85.16% vs. 91.13%, P = 0.009) and proton pump inhibitors (77.42% vs. 88.71%, P = 0.002) were also lower in the pharmaceutical care group. Secondary outcomes did not show significant differences in total hospital stay (21 days vs. 22 days, P = 0.092). However, ICU stay was significantly shorter (9 days vs. 11 days, P = 0.003) in the pharmaceutical care group. Cost-effectiveness analysis demonstrated that each 1% reduction in adverse drug events associated with ICU pharmaceutical care saved $226.75 in ICU hospitalization costs and $203.42 in total ICU drug costs. A 1% reduction in the medication error rate saved $128.57 in ICU hospitalization costs and $115.34 in total ICU drug costs.

Conclusions

Pharmaceutical care significantly reduces adverse drug events and medication errors, promotes rational use of medications, decreases the length of ICU stay, and lowers treatment costs in critically ill patients, establishing a definitive advantage in terms of cost-effectiveness.
Genetic mapping of stripe rust resistance in a geographically diverse barley collection and selected biparental populations
Authors: Singh Davinder , Ziems Laura , Chettri Mumta , Dracatos Peter , Forrest Kerrie , Bhavani Sridhar , Singh Ravi , Barnes Charles W. , Zapata Patricio Javier Noroña , Gangwar Om , Kumar Subodh , Bhardwaj Subhash , Park Robert F.
Published: July 2024

Barley stripe or yellow rust (BYR) caused by Puccinia striiformis f. sp. hordei (Psh) is a significant constraint to barley production. The disease is best controlled by genetic resistance, which is considered the most economical and sustainable component of integrated disease management. In this study, we assessed the diversity of resistance to Psh in a panel of international barley genotypes (n = 266) under multiple disease environments (Ecuador, India, and Mexico) using genome-wide association studies (GWASs). Four quantitative trait loci (QTLs) (three on chromosome 1H and one on 7H) associated with resistance to Psh were identified. The QTLs were validated by mapping resistance to Psh in five biparental populations, which detected key genomic regions on chromosomes 1H (populations Pompadour/Zhoungdamei, Pompadour/Zug161, and CI9214/Baudin), 3H (Ricardo/Gus), and 7H (Fumai8/Baronesse). The QTL RpshQ.GWA.1H.1 detected by GWAS and RpshQ.Bau.1H detected using biparental mapping populations co-located were the most consistent and stable across environments and are likely the same resistance region. RpshQ.Bau.1H was saturated using population CI9214/Baudin by enriching the target region, which placed the resistance locus between 7.9 and 8.1 Mbp (flanked by markers sun_B1H_03, 0.7 cM proximal to Rpsh_1H and sun_B1H_KASP_02, 3.2 cM distal on 1HS) in the Morex reference genome v.2. A Kompetitive Allele Specific PCR (KASP) marker sun_B1H_KASP_01 that co-segregated for RpshQ.Bau.1H was developed. The marker was validated on 50 Australian barley cultivars, showing well-defined allelic discrimination and presence in six genotypes (Baudin, Fathom, Flagship, Grout, Sakurastar, and Shepherd). This marker can be used for reliable marker-assisted selection and pyramiding of resistance to Psh and in diversifying the genetic base of resistance to stripe rust.
Adaptation of Ustilago maydis to phenolic and alkaloid responsive metabolites in maize B73
Authors: Guo Xuanyue , Yang Zhen , Zhang Jinjin , Hua Juan , Luo Shihong
Published: July 2024

The adaptation of pathogenic fungi to plant-specialized metabolites is necessary for their survival and reproduction. The biotrophic fungus Ustilago maydis can cause maize smut and produce tumors in maize (Zea mays), resulting in reduced maize yield and significant economic losses. Qualitative analysis using UPLC-MS/MS revealed that the infection of maize variety B73 with U. maydis resulted in increased levels of phytohormones, phenolics, and alkaloids in maize seedling tissues. However, correlation analysis showed that nearly all compounds in the mechanical damage group were significantly negatively correlated with the shoot growth indexes of maize B73. The correlation coefficients of 2-hydroxy-7-methoxy-1,4-benzoxazin-3-one (HMBOA) and maize B73 shoot length and shoot weight were r = -0.56 (p < 0.01) and r = -0.75 (p < 0.001), respectively. In the inoculation group, these correlations weakened, with the correlation coefficients between HMBOA and maize B73 shoot length and shoot weight being r = 0.02 and r = -0.1, respectively. The correlation coefficients between 6-methoxy-2-benzoxazolinone (MBOA) and the shoot weight were r = -0.73 (p < 0.001) and r = -0.15 in the mechanical damage group and inoculation group, respectively. These findings suggest that increased concentrations of these compounds are more positively associated with mechanical damage than with U. maydis infection. At high concentrations, most of these compounds had an inhibitory effect on U. maydis. This study investigated the ability of U. maydis to regulate various compounds, including phytohormones, phenolic acids, and alkaloids in maize B73, providing evidence that U. maydis has adapted to the specialized metabolites produced by maize B73.