bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ensemble learning with active sampling to predict the prognosis of postoperative non-small cell lung cancer patients
Authors: Hu Danqing , Zhang Huanyao , Li Shaolei , Duan Huilong , Wu Nan , Lu Xudong 
Published: September 2022

Abstract
Background
Lung cancer is the leading cause of cancer death worldwide. Prognostic prediction plays a vital role in the decision-making process for postoperative non-small cell lung cancer (NSCLC) patients. However, the high imbalance ratio of prognostic data limits the development of effective prognostic prediction models.

Methods
In this study, we present a novel approach, namely ensemble learning with active sampling (ELAS), to tackle the imbalanced data problem in NSCLC prognostic prediction. ELAS first applies an active sampling mechanism to query the most informative samples to update the base classifier to give it a new perspective. This training process is repeated until no enough samples are queried. Next, an internal validation set is employed to evaluate the base classifiers, and the ones with the best performances are integrated as the ensemble model. Besides, we set up multiple initial training data seeds and internal validation sets to ensure the stability and generalization of the model.

Results
We verified the effectiveness of the ELAS on a real clinical dataset containing 1848 postoperative NSCLC patients. Experimental results showed that the ELAS achieved the best averaged 0.736 AUROC value and 0.453 AUPRC value for 6 prognostic tasks and obtained significant improvements in comparison with the SVM, AdaBoost, Bagging, SMOTE and TomekLinks.

Conclusions
We conclude that the ELAS can effectively alleviate the imbalanced data problem in NSCLC prognostic prediction and demonstrates good potential for future postoperative NSCLC prognostic prediction.
Health systems resilience in practice: a scoping review to identify strategies for building resilience
Authors: Forsgren Lena , Tediosi Fabrizio , Blanchet Karl , Saulnier Dell D 
Published: September 2022

Abstract
Background
Research on health systems resilience has focused primarily on the theoretical development of the concept and its dimensions. There is an identified knowledge gap in the research on how to build resilience in health systems in practice and ‘what works’ in different contexts. The aim of this study is to identify practical strategies for building resilient health systems from the empirical research on health systems resilience.

Methods
A scoping review included empirical research on health systems resilience from peer-reviewed literature. The search in the electronic databases PubMed, Web of Science, Global Health was conducted during January to March 2021 for articles published in English between 2013 to February 2021. A total of 1771 articles were screened, and data was extracted from 22 articles. The articles included empirical, applied research on strategies for resilience, that observed or measured resilience during shocks or chronic stress through collection of primary data or analysis of secondary data, or if they were a review study of empirical research. A narrative summary was done by identifying action-oriented strategies, comparing them, and presenting them by main thematic areas.

Results
The results demonstrate examples of strategies used or recommended within nine identified thematic areas; use of community resources, governance and financing, leadership, surveillance, human resources, communication and collaboration, preparedness, organizational capacity and learning and finally health system strengthening.

Conclusions
The findings emphasize the importance of improved governance and financing, empowered middle-level leadership, improved surveillance systems and strengthened human resources. A re-emphasized focus on health systems strengthening with better mainstreaming of health security and international health regulations are demonstrated in the results as a crucial strategy for building resilience. A lack of strategies for recovery and lessons learnt from crises are identified as gaps for resilience in future.
A social network analysis to explore collaborative practice in home care: research protocol
Authors: Schorderet Chloé , Bastiaenen Caroline H. G. , Verloo Henk , de Bie Robert A. , Allet Lara 
Published: September 2022

AbstractBackgroundThe conceptualization of the home as a care environment and maintaining a high standard of care requires different professionals to collaborate. This study will explore collaborative practice in home care, needs and expectations of the stakeholders involved, and identify their roles and tasks. Secondly, it will investigate possible strategies to improve home care management and, more particularly, optimize collaborative practice in home care.MethodsThe study will be conducted during three distinct consecutive phases, within a multiphase mixed-methods design.Phase 1will use a quantitative approach in which a social network analysis will be conducted to have an overview of collaborative practice in home care in French-speaking Switzerland.Phases 2and3will be qualitative and focus on three different situations involving different locations (rural and urban) and different home care functioning (home care provided by agencies and home care providing by independent caregivers). In each situation, semi-structured interviews will be conducted with home care recipients and their home caregivers. Inphase 2, results ofphase 1’s network analysis will be discussed, such as roles, needs, and expectations of all stakeholders involved in home care. Inphase 3,phase 2’s findings will be discussed and strategies to improve home care and to optimize collaborative practice will be explored.DiscussionOver the past years, home care has grown considerably. Therefore, more and more different caregivers are involved in the recipients' homes. Since optimal coordination between these different caregivers is a prerequisite for quality and safe care, it is essential to investigate the existing collaborative practice and how it is functioning. This study will provide knowledge on roles, needs and expectations of different caregivers involved in home care. It will also allow for strategies to optimize collaborative practice and thus ensure comprehensive care for recipients. Finally, it will serve as a basis for future studies that can be conducted to address identified needs.
Exploring the biological function of immune cell-related genes in human immunodeficiency virus (HIV)-1 infection based on weighted gene co-expression network analysis (WGCNA)
Authors: Bai Ruojing , Li Zhen , Lv Shiyun , Hua Wei , Dai Lili , Wu Hao 
Published: September 2022

Abstract
Background
Acquired immunodeficiency syndrome (AIDS) is a chronic infectious disease characterized by consistent immune dysfunction. The objective of this study is to determine whether immune cell-related genes can be used as biomarkers for the occurrence of AIDS and potential molecular mechanisms.

Methods
A weighted gene co-expression network analysis was performed using the GSE6740 dataset from the Gene Expression Synthesis Database to identify the Hub gene, which contained microarray data from HIV-1 positive (HIV-1+) and HIV-1 negative (HIV-1−) individuals. The HIV-1+-related differentially expressed genes were then identified using the limma package. Subsequently, the characteristic immune cell-related genes were identified as diagnostic biomarkers for HIV-1+ using the random forest model (RF), support vector machine model, and generalized linear model.

Results
MEdarkgreen exhibited the strongest correlation with HIV clinical features of any of these modules. As the best model for diagnosing HIV-1±, RF was used to select four critical immune cell-related genes, namely, ARRB1, DPEP2, LTBP3, and RGCC, and a nomogram model was created to predict the occurrence of HIV-1 infection based on four key immune cell-related genes. Diagnostic genes were shown to be engaged in immune-related pathways, suggesting that immunological molecules, immune cells, and immune pathways all have a role in HIV-1 infection. The CTD database was explored for prospective medications or molecular compounds that might be utilized to treat HIV-1+ patients. = Moreover, in HIV-1+ individuals, the ceRNA network revealed that ARRB1, DPEP2, LTBP3, and RGCC could be regulated by lncRNAs through the corresponding miRNAs. Ultimately, RT-PCR results from clinical blood samples demonstrated that the four diagnostic genes were significantly downregulated in HIV-1+ patients.

Conclusion
We screened four immune cell-related genes, ARRB1, DPEP2, LTBP3, and RGCC, which may be considered as the diagnostic markers for HIV-1/AIDS. Our findings reveal that immune related genes and pathways involved in HIV-1 pathogenesis were regulated on both genetic and epigenetic levels by constructing a ceRNA network associated with lncRNA.
Immune-inflammatory biomarkers and the risk of cardiac injury in COVID-19 patients with diabetes: a retrospective cohort study
Authors: Bo Yi , Yuli Cai , Ye Wang , Junfeng Li , Xiaolin Chen , Yan Bao , Zhongyuan Wen 
Published: September 2022

Abstract
Background
To determine the risk-assessment role of the immune-inflammatory biomarkers on myocardial damage in COVID-19 patients with diabetes mellitus (DM).

Methods
This retrospective study was conducted on 822 COVID-19 inpatients from 1 January to 10 March 2020 at Renmin Hospital of Wuhan University. The demographic data, clinical data, and immune-inflammatory parameters of participants were collected. The predictors of cardiac injury were assessed by Logistics regression analysis.

Results
A total of 246 COVID-19 inpatients were diagnosed with DM (29.9%). The incidence of cardiac injury was higher in patients with DM than in non-DM cases (28.9% vs 9.0%, p < 0.001), even grouped by age, gender, and the level of fasting plasma glucose (FPG). The mortality in diabetic COVID-19 patients with cardiac injury and without cardiac injury was 42.9% and 3.4%, respectively (p < 0.001). COVID-19 patients with DM and cardiac injury presented a decreased number of immunocyte subsets, lower C3 concentration, and a higher level of interleukin-6 (IL-6) and immunoglobulin A (IgA). The independent risk factors for cardiac injury in COVID-19 patients with DM were CD3+CD4+ T cells counts ≤ 288 cells/μl (adjusted Odds ratio (OR), 2.501; 95% confidence interval (CI) 1.282–4.877; p = 0.007) and IL-6 > 25.68mpg/ml (adjusted OR, 4.345; 95% CI 2.192–10.374; p < 0.001) (all Pinteraction < 0.05).

Conclusions
For diabetic patients with COVID-19, cardiac injury not only induce severer immune-inflammatory responses, but also increase in-hospital mortality. The decreased number of CD3+CD4+ T cells and increased IL-6 are recommended to distinguish the people who refer to high risk of cardiac injury and mortality from those persons. However, it remains a testable theory whether decision-making strategies based on the risk status of cardiac injury in COVID-19 patients, especially with DM, would be expected to get better outcomes.
An accurate strategy for pointing the key biocatalytic sites of bre2691A protein for modification of the brevilaterin from Brevibacillus laterosporus
Authors: Han Panpan , Chen Zhou , Liu Yangliu , Ma Aijin , Li Siting , Jia Yingmin 
Published: September 2022

Abstract
Background
Brevilaterin A-E, a novel class of multi-component cationic antimicrobial lipopeptides, were biosynthesized by a non-ribosomal peptides synthetase (NRPS) in Brevibacillus laterosporus. However, the antimicrobial abilities of different brevilaterin components varied greatly, and this multi-component form was impeding the scale production of the excellent component, and a little information about the brevilaterin biosynthesis mechanism was available to apply in brevilaterin design modification. In this study, we used an accurate strategy that revealed the reason for producing multi-component was the substrate selectivity of bre2691A protein being not enough specific and pinpointed the key design sites to make the specificity of bre2691A enhanced.

Results
Bioinformatic analysis revealed that the biocatalytic site of bre2691A, which was an adenylation domain catalyzed and recognized methionine, leucine, valine and isoleucine and thus introduced them into brevilaterins and caused different components (brevilaterin A-E), was consisted of A1 ~ A10 residues named specificity-conferring code. Coupling molecular docking simulations with mutation studies identified A2 and A7 as critical residues, where determined substrate-specificity and impacted activity. The in virto activity assay showed that the A2 mutant (G193A) would lose activity against methionine and have no effect on the other three amino acids, the A7 mutant (G285C) would enhance the catalytic activity against four substrates, especially against leucine at almost a double activity. When the A2 and A7 residues were synchronously mutated, this mutant would be more focused on recognizing leucine.

Conclusions
An accurate strategy that combined with bioinformatics and site-directed mutation techniques revealed the pivotal site A2 and A7 positions of bre2691A protein that could be used to design and modify brevilaterins, thus further providing a reasonable direction of genetic engineering for Brevibacillus laterosporus. A deeper understanding of the function of crucial residues in the adenylation domain would make it get more accurate and highly efficient design and more fully utilized. Furthermore, it would contribute to biotechnological applications, namely for the large centralized synthesis of antimicrobial peptides, or for the optimization of their production.

Graphic Abstract
Implementation of a high cell density fed-batch for heterologous production of active [NiFe]-hydrogenase in Escherichia coli bioreactor cultivations
Authors: Fan Qin , Waldburger Saskia , Neubauer Peter , Riedel Sebastian L. , Gimpel Matthias 
Published: September 2022

Abstract
Background
O2-tolerant [NiFe]-hydrogenases offer tremendous potential for applications in H2-based technology. As these metalloenzymes undergo a complicated maturation process that requires a dedicated set of multiple accessory proteins, their heterologous production is challenging, thus hindering their fundamental understanding and the development of related applications. Taking these challenges into account, we selected the comparably simple regulatory [NiFe]-hydrogenase (RH) from Cupriavidus necator as a model for the development of bioprocesses for heterologous [NiFe]-hydrogenase production. We already reported recently on the high-yield production of catalytically active RH in Escherichia coli by optimizing the culture conditions in shake flasks.

Results
In this study, we further increase the RH yield and ensure consistent product quality by a rationally designed high cell density fed-batch cultivation process. Overall, the bioreactor cultivations resulted in ˃130 mg L−1 of catalytically active RH which is a more than 100-fold increase compared to other RH laboratory bioreactor scale processes with C. necator. Furthermore, the process shows high reproducibility of the previously selected optimized conditions and high productivity.

Conclusions
This work provides a good opportunity to readily supply such difficult-to-express complex metalloproteins economically and at high concentrations to meet the demand in basic and applied studies.
Intratumoral delivery of TransCon™ TLR7/8 Agonist promotes sustained anti-tumor activity and local immune cell activation while minimizing systemic cytokine induction
Authors: Zúñiga Luis Alejandro , Leßmann Torben , Uppal Karan , Bisek Nicola , Hong Enping , Rasmussen Caroline E. , Karlsson Jens-Jakob , Zettler Joachim , Holten-Andersen Lars , Bang Kathy , Thakar Dhruv , Lee Yu-Chi , Martinez Salomon , Sabharwal Simran Singh , Stark Sebastian , Faltinger Frank , Kracker Oliver , Weisbrod Samuel , Müller Robin , Voigt Tobias , Bigott Kornelia , Tabrizifard Mohammad , Breinholt Vibeke Miller , Mirza Amer M. , Rosen David B. , Sprogøe Kennett , Punnonen Juha 
Published: September 2022

Abstract
Background
Intratumoral (IT) delivery of toll-like receptor (TLR) agonists has shown encouraging anti-tumor benefit in preclinical and early clinical studies. However, IT delivery of TLR agonists may lead to rapid effusion from the tumor microenvironment (TME), potentially limiting the duration of local inflammation and increasing the risk of systemic adverse events.

Methods
To address these limitations, TransCon™ TLR7/8 Agonist—an investigational sustained-release prodrug of resiquimod that uses a TransCon linker and hydrogel technology to achieve sustained and predictable IT release of resiquimod—was developed. TransCon TLR7/8 Agonist was characterized for resiquimod release in vitro and in vivo, in mice and rats, and was assessed for anti-tumor efficacy and pharmacodynamic activity in mice.

Results
Following a single IT dose, TransCon TLR7/8 Agonist mediated potent tumor growth inhibition which was associated with sustained resiquimod release over several weeks with minimal induction of systemic cytokines. TransCon TLR7/8 Agonist monotherapy promoted activation of antigen-presenting cells in the TME and tumor-draining lymph nodes, with evidence of activation and expansion of CD8+ T cells in the tumor-draining lymph node and TME. Combination of TransCon TLR7/8 Agonist with systemic immunotherapy further promoted anti-tumor activity in TransCon TLR7/8 Agonist-treated tumors. In a bilateral tumor setting, combination of TransCon TLR7/8 Agonist with systemic IL-2 potentiated tumor growth inhibition in both injected and non-injected tumors and conferred protection against tumor rechallenge following complete regressions.

Conclusions
Our findings show that a single dose of TransCon TLR7/8 Agonist can mediate sustained local release of resiquimod in the TME and promote potent anti-tumor effects as monotherapy and in combination with systemic immunotherapy, supporting TransCon TLR7/8 Agonist as a novel intratumoral TLR agonist for cancer therapy. A clinical trial to evaluate the safety and efficacy of TransCon TLR7/8 Agonist, as monotherapy and in combination with pembrolizumab, in cancer patients is currently ongoing (transcendIT-101; NCT04799054).
In utero particulate matter exposure in association with newborn mitochondrial ND4L10550A>G heteroplasmy and its role in overweight during early childhood
Authors: Cosemans Charlotte , Wang Congrong , Alfano Rossella , Martens Dries S. , Sleurs Hanne , Dockx Yinthe , Vanbrabant Kenneth , Janssen Bram G. , Vanpoucke Charlotte , Lefebvre Wouter , Smeets Karen , Nawrot Tim S. , Plusquin Michelle 
Published: September 2022

AbstractBackgroundMitochondria play an important role in the energy metabolism and are susceptible to environmental pollution. Prenatal air pollution exposure has been linked with childhood obesity. Placental mtDNA mutations have been associated with prenatal particulate matter exposure and MT-ND4L10550A>Gheteroplasmy has been associated with BMI in adults. Therefore, we hypothesized that in utero PM2.5exposure is associated with cord blood MT-ND4L10550A>Gheteroplasmy and early life growth. In addition, the role of cord blood MT-ND4L10550A>Gheteroplasmy in overweight during early childhood is investigated.MethodsThis study included 386 mother-newborn pairs. Outdoor PM2.5concentrations were determined at the maternal residential address. Cord blood MT-ND4L10550A>Gheteroplasmy was determined using Droplet Digital PCR. Associations were explored using logistic regression models and distributed lag linear models. Mediation analysis was performed to quantify the effects of prenatal PM2.5exposure on childhood overweight mediated by cord blood MT-ND4L10550A>Gheteroplasmy.ResultsPrenatal PM2.5exposure was positively associated with childhood overweight during the whole pregnancy (OR = 2.33; 95% CI: 1.20 to 4.51;p = 0.01), which was mainly driven by the second trimester. In addition, prenatal PM2.5exposure was associated with cord blood MT-ND4L10550A>Gheteroplasmy from gestational week 9 – 13. The largest effect was observed in week 10, where a 5 µg/m3increment in PM2.5was linked with cord blood MT-ND4L10550A>Gheteroplasmy (OR = 0.93; 95% CI: 0.87 to 0.99). Cord blood MT-ND4L10550A>Gheteroplasmy was also linked with childhood overweight (OR = 3.04; 95% CI: 1.15 to 7.50;p = 0.02). The effect of prenatal PM2.5exposure on childhood overweight was mainly direct (total effect OR = 1.18; 95% CI: 0.99 to 1.36; natural direct effect OR = 1.20; 95% CI: 1.01 to 1.36)) and was not mediated by cord blood MT-ND4L10550A>Gheteroplasmy.ConclusionsCord blood MT-ND4L10550A>Gheteroplasmy was linked with childhood overweight. In addition, in utero exposure to PM2.5during the first trimester of pregnancy was associated with cord blood MT-ND4L10550A>Gheteroplasmy in newborns. Our analysis did not reveal any mediation of cord blood MT-ND4L10550A>Gheteroplasmy in the association between PM2.5exposure and childhood overweight.
Fat-to-muscle ratio as a predictor for dyslipidaemia in transitional-age youth
Authors: Zhang Jia-Xing , Li Wen , Tao Xiu-Juan , Chen Chen , Wang Qing-An , Liu Wan-Lu , Yang Chan , Wang Kai-Rong , Qiu Jiang-Wei , Zhao Yi , Zhang Yu-Hong 
Published: September 2022

Abstract
Background
Although dyslipidaemia may have a crucial impact on cardiovascular health in adults, there is a lack of specific data in transitional-age youth. Therefore, this study attempted to evaluate the association of dyslipidaemia with fat-to-muscle ratio (FMR), and establish FMR thresholds for diagnosing dyslipidaemia in transitional-age youth.

Methods
One thousand six hundred sixty individuals aged 16 to 24 years from the baseline of a subcohort in the Northwest China Natural Population Cohort: Ningxia Project were analysed. Anthropometric characteristics were gauged by a bioelectrical impedance analyser, and dyslipidaemia components were measured using a Beckman AU480 chemistry analyser. Additionally, this study used logistic regression to estimate the risk of dyslipidaemia based on FMR quintiles, and calculate the gender-specific ideal cut-off values of dyslipidaemia and its components by the receiver operating characteristic (ROC) curve.

Results
Of the 1660 participants, aged 19.06 ± 1.14 years, 558 males and 1102 females. The prevalence of dyslipidaemia was 13.4% and was significantly associated with FMR quintiles among all participants (P < 0.05). The ideal values of FMR in diagnosing dyslipidaemia were 0.2224 for males and 0.4809 for females, while males had a higher AUC than females (0.7118 vs. 0.6656). Meanwhile, high FMR values were significantly associated with adverse outcomes of dyslipidaemia, hypercholesterolemia and hypertriglyceridaemia (P < 0.05).

Conclusions
The FMR was positively correlated with the prevalence of dyslipidaemia. The FMR can be used as an effective body composition index for diagnosing dyslipidaemia, especially in males, and preventive strategies should be initiated in transitional-age youth to decrease obesity-related dyslipidaemia.