bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis and identification of subtypes and hub genes of high immune response in lung adenocarcinoma
Authors: Li Han , Lei Yuting , Lai Xianwen , Huang Ruina , Xiang Yuanyuan , Zhao Zhao , Fang Zhenfu , Lai Tianwen 
Published: July 2024

Abstract
Background
The advent of immunotherapy targeting immune checkpoints has conferred significant clinical advantages to patients with lung adenocarcinoma (LUAD); However, only a limited subset of patients exhibit responsiveness to this treatment. Consequently, there is an imperative need to stratify LUAD patients based on their response to immunotherapy and enhance the therapeutic efficacy of these treatments.

Methods
The differentially co-expressed genes associated with CD8 + T cells were identified through weighted gene co-expression network analysis (WGCNA) and the Search Tool for the Retrieval of Interacting Genes (STRING) database. These gene signatures facilitated consensus clustering for TCGA-LUAD and GEO cohorts, categorizing them into distinct immune subtypes (C1, C2, C3, and C4). The Tumor Immune Dysfunction and Exclusion (TIDE) model and Immunophenoscore (IPS) analysis were employed to assess the immunotherapy response of these subtypes. Additionally, the impact of inhibitors targeting five hub genes on the interaction between CD8 + T cells and LUAD cells was evaluated using CCK8 and EDU assays. To ascertain the effects of these inhibitors on immune checkpoint genes and the cytotoxicity mediated by CD8 + T cells, flow cytometry, qPCR, and ELISA methods were utilized.

Results
Among the identified immune subtypes, subtypes C1 and C3 were characterized by an abundance of immune components and enhanced immunogenicity. Notably, both C1 and C3 exhibited higher T cell dysfunction scores and elevated expression of immune checkpoint genes. Multi-cohort analysis of Lung Adenocarcinoma (LUAD) suggested that these subtypes might elicit superior responses to immunotherapy and chemotherapy. In vitro experiments involved co-culturing LUAD cells with CD8 + T cells and implementing the inhibition of five pivotal genes to assess their function. The inhibition of these genes mitigated the immunosuppression on CD8 + T cells, reduced the levels of PD1 and PD-L1, and promoted the secretion of IFN-γ and IL-2.

Conclusions
Collectively, this study delineated LUAD into four distinct subtypes and identified five hub genes correlated with CD8 + T cell activity. It lays the groundwork for refining personalized therapy and immunotherapy strategies for patients with LUAD.
Evaluating malocclusion patterns in children with autism spectrum disorder using the index of complexity, outcome and need: a cross-sectional study
Authors: Farzanegan Fahimeh , Shadmehri Sahar Ahmadi , Shooshtari Zahra , Hamidi Amir Reza , Shahri Arsalan 
Published: July 2024

Abstract
Background
The purpose of this study was to evaluate the complexity of malocclusion and existing patterns in children with autism spectrum disorders (ASD) using the index of complexity, outcome and need (ICON).

Methods
This cross-sectional study included children diagnosed with ASD, aged 9–15 years. A group of healthy children with the same demographic characteristics was randomly selected as the control group. Malocclusion was assessed according to ICON scoring protocol. The following parameters were recorded: dental aesthetics, upper arch crowding/spacing, presence of crossbite, anterior-vertical relationship (open and deep bite) and buccal segment anterior-posterior relationship. Finally, an overall ICON score was derived and reported for each patient. Descriptive analysis was performed for all investigated variables. Significance level was set at p < 0.05.

Results
A total of 324 children, divided into ASD (162) and control (162) groups, comprised the study population. Our results demonstrated that the average overall ICON score was significantly higher in the ASD group compared to the control group (38.77 vs. 27.43, p < 0.001). ASD children also obtained significantly higher scores regarding the dental aesthetics component (3.84 vs 2.78, p < 0.001). Study groups were significantly different in terms of the prevalence of incisor overbite and open bite (p = 0.002 and p < 0.001, respectively). Patients in the ASD group showed a higher prevalence of Class II and Class III malocclusions (p < 0.001).

Conclusion
ASD children obtained significantly higher overall ICON scores, indicating more complex and severe malocclusions. These children also exhibited a greater tendency towards Class II and III malocclusions.
Knowledge, attitudes, and practices among patients with combined dentition defect and non-functional impacted teeth toward tooth autotransplantation
Authors: Zhao Liang , Hou Yuzhuan , Wang Juan 
Published: July 2024

Abstract
Background
Tooth autotransplantation (TAT) is a surgical procedure involving the extraction of a tooth from one location and its subsequent transplantation into another alveolar socket within the same individual. This innovative treatment approach holds significant promise. Nonetheless, the potential recipients exhibit a limited level of awareness and understanding of this procedure. This study investigated the knowledge, attitudes, and practices (KAP) among patients with combined dentition defects and non-functional impacted teeth toward TAT.

Methods
This web-based cross-sectional study was conducted between December 2022 and February 2023 at one hospital. A self-designed questionnaire was developed to collect demographic information of the patients and assess their knowledge, attitudes, and practices toward TAT.

Results
A total of 533 valid questionnaires were collected. The mean knowledge, attitude, and practice scores were 5.55 ± 2.38 (possible range: 0–10), 26.82 ± 2.46 (possible range, 8–40), and 27.45 ± 7.40 (possible range, 9–45), respectively.

Conclusion
The participants had insufficient knowledge, negative attitudes, and passive practices toward TAT. Targeted interventions should be implemented to improve the understanding and practice of TAT among patients with dentition defects.
How intervention studies measure the effectiveness of medication safety-related clinical decision support systems in primary and long-term care: a systematic review
Authors: Lampe David , Grosser John , Grothe Dennis , Aufenberg Birthe , Gensorowsky Daniel , Witte Julian , Greiner Wolfgang 
Published: July 2024

Abstract
Background
Medication errors and associated adverse drug events (ADE) are a major cause of morbidity and mortality worldwide. In recent years, the prevention of medication errors has become a high priority in healthcare systems. In order to improve medication safety, computerized Clinical Decision Support Systems (CDSS) are increasingly being integrated into the medication process. Accordingly, a growing number of studies have investigated the medication safety-related effectiveness of CDSS. However, the outcome measures used are heterogeneous, leading to unclear evidence. The primary aim of this study is to summarize and categorize the outcomes used in interventional studies evaluating the effects of CDSS on medication safety in primary and long-term care.

Methods
We systematically searched PubMed, Embase, CINAHL, and Cochrane Library for interventional studies evaluating the effects of CDSS targeting medication safety and patient-related outcomes. We extracted methodological characteristics, outcomes and empirical findings from the included studies. Outcomes were assigned to three main categories: process-related, harm-related, and cost-related. Risk of bias was assessed using the Evidence Project risk of bias tool.

Results
Thirty-two studies met the inclusion criteria. Almost all studies (n = 31) used process-related outcomes, followed by harm-related outcomes (n = 11). Only three studies used cost-related outcomes. Most studies used outcomes from only one category and no study used outcomes from all three categories. The definition and operationalization of outcomes varied widely between the included studies, even within outcome categories. Overall, evidence on CDSS effectiveness was mixed. A significant intervention effect was demonstrated by nine of fifteen studies with process-related primary outcomes (60%) but only one out of five studies with harm-related primary outcomes (20%). The included studies faced a number of methodological problems that limit the comparability and generalizability of their results.

Conclusions
Evidence on the effectiveness of CDSS is currently inconclusive due in part to inconsistent outcome definitions and methodological problems in the literature. Additional high-quality studies are therefore needed to provide a comprehensive account of CDSS effectiveness. These studies should follow established methodological guidelines and recommendations and use a comprehensive set of harm-, process- and cost-related outcomes with agreed-upon and consistent definitions.

Prospero registration
CRD42023464746
Adaptation and validation of moral distress thermometer in Chinese nurses
Authors: Tian Xu , Gan Xiuni , Ren Yi , Li Feili , Herrera Maria F. Jimenez , Liu Fangrong 
Published: July 2024

AbstractBackgroundMoral distress seriously affects professional nurses, and a number of instruments have been developed to measure the level of moral distress. The moral distress thermometer (MDT) is one of the commonly used instruments that can rapidly measure real-time moral distress; however, it remains unclear whether it is still useful in the Chinese cultural context.AimThis study aimed to adapt and validate the MDT among Chinese registered nurses.Research designAn online, cross-sectional, survey study of adapting and validating Chinese version of MDT.Participants and research contextA total of 182 registered nurses effectively finished this survey. The correlation between MDT score and the score of the moral distress scale-revised version (MDS-R) was used for evaluating convergent validity, and MDT scores of registered nurses who working in different departments and who made different actions to the final question of the MDS-R were compared by using one-way ANOVA to evaluate construct validity.Ethical considerationsThe Ethics Committee of Chongqing Traditional Chinese Medicine Hospital approved this study.ResultsThe Chinese version of MDT was described as relevant to measure moral distress, with a reported item-level content validity index (I-CVI) and scale-level CVI (S-CVI) of 1. The mean MDT score and mean MDS-R score were 2.54 and 38.66, respectively, and the correlation between these two scores was significantly moderate (r = 0.41). Nurses working different departments reported different levels of moral distress, and those working in intensive care unit reported the highest level of moral distress than those working in other departments (p = 0.04). The MDT scores between nurses who presented different actions to their position were also significantly different, and those who had ever left and those who had considered leaving but did not leave reported significantly higher moral distress.ConclusionThe MDT is a reliable, valid, and easy-to-use instrument to rapidly measure the real-time moral distress of registered nurses in China.
Microbial diversity and ecological complexity emerging from environmental variation and horizontal gene transfer in a simple mathematical model
Authors: Babajanyan Sanasar G. , Garushyants Sofya K. , Wolf Yuri I. , Koonin Eugene V. 
Published: July 2024

Abstract
Background
Microbiomes are generally characterized by high diversity of coexisting microbial species and strains, and microbiome composition typically remains stable across a broad range of conditions. However, under fixed conditions, microbial ecology conforms with the exclusion principle under which two populations competing for the same resource within the same niche cannot coexist because the less fit population inevitably goes extinct. Therefore, the long-term persistence of microbiome diversity calls for an explanation.

Results
To explore the conditions for stabilization of microbial diversity, we developed a simple mathematical model consisting of two competing populations that could exchange a single gene allele via horizontal gene transfer (HGT). We found that, although in a fixed environment, with unbiased HGT, the system obeyed the exclusion principle, in an oscillating environment, within large regions of the phase space bounded by the rates of reproduction and HGT, the two populations coexist. Moreover, depending on the parameter combination, all three major types of symbiosis were obtained, namely, pure competition, host-parasite relationship, and mutualism. In each of these regimes, certain parameter combinations provided for synergy, that is, a greater total abundance of both populations compared to the abundance of the winning population in the fixed environment.

Conclusions
The results of this modeling study show that basic phenomena that are universal in microbial communities, namely, environmental variation and HGT, provide for stabilization and persistence of microbial diversity, and emergence of ecological complexity.
Natural variation in yeast reveals multiple paths for acquiring higher stress resistance
Authors: Scholes Amanda N. , Stuecker Tara N. , Hood Stephanie E. , Locke Cader J. , Stacy Carson L. , Zhang Qingyang , Lewis Jeffrey A. 
Published: July 2024

Abstract
Background
Organisms frequently experience environmental stresses that occur in predictable patterns and combinations. For wild Saccharomyces cerevisiae yeast growing in natural environments, cells may experience high osmotic stress when they first enter broken fruit, followed by high ethanol levels during fermentation, and then finally high levels of oxidative stress resulting from respiration of ethanol. Yeast have adapted to these patterns by evolving sophisticated “cross protection” mechanisms, where mild ‘primary’ doses of one stress can enhance tolerance to severe doses of a different ‘secondary’ stress. For example, in many yeast strains, mild osmotic or mild ethanol stresses cross protect against severe oxidative stress, which likely reflects an anticipatory response important for high fitness in nature.

Results
During the course of genetic mapping studies aimed at understanding the mechanisms underlying natural variation in ethanol-induced cross protection against H2O2, we found that a key H2O2 scavenging enzyme, cytosolic catalase T (Ctt1p), was absolutely essential for cross protection in a wild oak strain. This suggested the absence of other compensatory mechanisms for acquiring H2O2 resistance in that strain background under those conditions. In this study, we found surprising heterogeneity across diverse yeast strains in whether CTT1 function was fully necessary for acquired H2O2 resistance. Some strains exhibited partial dispensability of CTT1 when ethanol and/or salt were used as mild stressors, suggesting that compensatory peroxidases may play a role in acquired stress resistance in certain genetic backgrounds. We leveraged global transcriptional responses to ethanol and salt stresses in strains with different levels of CTT1 dispensability, allowing us to identify possible regulators of these alternative peroxidases and acquired stress resistance in general.

Conclusions
Ultimately, this study highlights how superficially similar traits can have different underlying molecular foundations and provides a framework for understanding the diversity and regulation of stress defense mechanisms.
A meta-ethnography of the factors that shape link workers’ experiences of social prescribing
Authors: Turk Amadea , Tierney Stephanie , Hogan Bernie , Mahtani Kamal R. , Pope Catherine 
Published: July 2024

AbstractBackgroundSocial prescribing is gaining traction internationally. It is an approach which seeks to address non-medical and health-related social needs through taking a holistic person-centred and community-based approach. This involves connecting people with and supporting them to access groups and organisations within their local communities. It is hoped that social prescribing might improve health inequities and reduce reliance on healthcare services. In the UK, social prescribing link workers have become core parts of primary care teams. Despite growing literature on the implementation of social prescribing, to date there has been no synthesis that develops a theoretical understanding of the factors that shape link workers’ experiences of their role.MethodsWe undertook a meta-ethnographic evidence synthesis of qualitative literature to develop a novel conceptual framework that explains how link workers experience their roles. We identified studies using a systematic search of key databases, Google alerts, and through scanning reference lists of included studies. We followed the eMERGe guidance when conducting and reporting this meta-ethnography.ResultsOur synthesis included 21 studies and developed a “line of argument” or overarching conceptual framework which highlighted inherent and interacting tensions present at each of the levels that social prescribing operates. These tensions may arise from a mismatch between the policy logic of social prescribing and the material and structural reality, shaped by social, political, and economic forces, into which it is being implemented.ConclusionsThe tensions highlighted in our review shape link workers’ experiences of their role. They may call into question the sustainability of social prescribing and the link worker role as currently implemented, as well as their ability to deliver desired outcomes such as reducing health inequities or healthcare service utilisation. Greater consideration should be given to how the link worker role is defined, deployed, and trained. Furthermore, thought should be given to ensuring that the infrastructure into which social prescribing is being implemented is sufficient to meet needs. Should social prescribing seek to improve outcomes for those experiencing social and economic disadvantage, it may be necessary for social prescribing models to allow for more intensive and longer-term modes of support.
A novel start-loss mutation of the SLC29A3 gene in a consanguineous family with H syndrome: clinical characteristics, in silico analysis and literature review
Authors: Rezaie Nahid , Mansour Samaei Nader , Ghorbani Ayda , Gholipour Naghmeh , Vosough Shohreh , Rafigh Mahboobeh , Amini Abolfazl 
Published: July 2024

AbstractBackgroundTheSLC29A3gene, which encodes a nucleoside transporter protein, is primarily located in intracellular membranes. The mutations in this gene can give rise to various clinical manifestations, including H syndrome, dysosteosclerosis, Faisalabad histiocytosis, and pigmented hypertrichosis with insulin-dependent diabetes. The aim of this study is to present two Iranian patients with H syndrome and to describe a novel start-loss mutation inSLC29A3gene.MethodsIn this study, we employed whole-exome sequencing (WES) as a method to identify genetic variations that contribute to the development of H syndrome in a 16-year-old girl and her 8-year-old brother. These siblings were part of an Iranian family with consanguineous parents. To confirmed the pathogenicity of the identified variant, we utilized in-silico tools and cross-referenced various databases to confirm its novelty. Additionally, we conducted a co-segregation study and verified the presence of the variant in the parents of the affected patients through Sanger sequencing.ResultsIn our study, we identified a novel start-loss mutation (c.2T > A, p.Met1Lys) in the SLC29A3 gene, which was found in both of two patients. Co-segregation analysis using Sanger sequencing confirmed that this variant was inherited from the parents. To evaluate the potential pathogenicity and novelty of this mutation, we consulted various databases. Additionally, we employed bioinformatics tools to predict the three-dimensional structure of the mutant SLC29A3 protein. These analyses were conducted with the aim of providing valuable insights into the functional implications of the identified mutation on the structure and function of the SLC29A3 protein.ConclusionOur study contributes to the expanding body of evidence supporting the association between mutations in theSLC29A3gene and H syndrome. The molecular analysis of diseases related toSLC29A3is crucial in understanding the range of variability and raising awareness of H syndrome, with the ultimate goal of facilitating early diagnosis and appropriate treatment. The discovery of this novel biallelic variant in the probands further underscores the significance of utilizing genetic testing approaches, such as WES, as dependable diagnostic tools for individuals with this particular condition.
Associations of metabolic changes and polygenic risk scores with cardiovascular outcomes and all-cause mortality across BMI categories: a prospective cohort study
Authors: Li Cancan , Meng Xiaoni , Zhang Jie , Wang Haotian , Lu Huimin , Cao Meiling , Sun Shengzhi , Wang Youxin 
Published: July 2024

Abstract
Background
Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories.

Methods
In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories.

Results
During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed.

Conclusions
MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.

Graphical abstract