bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil in the suppressed immune microenvironment: Critical prognostic factor for lung adenocarcinoma patients with KEAP1 mutation
Authors: Wang Zhongzhao , Wang Haojue , Liu Mingjia , Ning Xinhang , Chen Yang , Tang Hao 
Published: June 2024

PurposeIt is still unclear whether KEAP1 mutation is detrimental to immunotherapy of lung adenocarcinoma (LUAD) patients, we try to analyse the exact changes in the TME in LUAD patients with KEAP1 mutations and to identify key factors influencing prognosis.Experimental designA total of 1,029 patients with lung squamous carcinoma (LUSC) or LUAD with data obtained from The Cancer Genome Atlas were included in this study. The TME and OS of patients with LUAD stratified by mutant versus wild-type KEAP1 status were comprehensively measured. Moreover, we classified LUAD patients with KEAP1 mutations into three subtypes, by unsupervised consensus clustering. We further analysed the TME, OS, commutated genes and metabolic pathways of different subgroups. A total of 40 LUAD patients underwent immunotherapy were collected and classified into mutant KEAP1 group and wild-type KEAP1 group. We also conducted immunohistochemical staining in KEAP1-MT groups.ResultSuppressed TME was observed not only in LUAD patients but also in LUSC patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than wild-type KEAP1. Unsupervised consensus clustering analysis suggested that the three subtypes of patients exhibited different densities of neutrophil infiltration and had different OS results: cluster 2 patients had significantly higher levels of neutrophils had significantly worse prognoses than those of patients in clusters 1 and 3 and patients with wild-type KEAP1. Univariate and multivariate Cox analyses proved that a high density of neutrophils was significantly associated with worse OS and immunohistochemical staining proved that shorter PFS showed high density of neutrophils.ConclusionKEAP1 mutation significantly suppresses the tumour immune microenvironment in LUAD patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than with wild-type KEAP1. Neutrophils may play an important role in the prognosis of LUAD patients with KEAP1 mutations and may provide a promising therapeutic target.
Tobacco crop rotation enhances the stability and complexity of microbial networks
Authors: Yan Huilin , Wu Shaolong , Li Ping , Jin Xin , Shi Dejun , Tu Danjia , Zeng Wei-ai , Tan Lin 
Published: June 2024

IntroductionThe effects of continuous cropping and rotation cropping, two important tobacco cultivation practices, on soil microbial communities at different stages remain unclear. Different planting patterns have been shown to influence soil physical and chemical properties, which in turn can affect the composition and diversity of soil microbial communities.MethodsIn order to investigate the impact of different planting methods on soil microbial community structure, we selected two representative planting methods: continuous cropping (tobacco) and rotational cropping (tobacco-maize). These methods were chosen as the focal points of our research to explore the potential effects on soil microbial communities. High-throughput sequencing technology was employed to investigate the structure of soil microbial communities, as well as their relationships with soil environmental factors, by utilizing the 16S rRNA, ITS, and 18S genes. Furthermore, the interaction among microorganisms was explored through the application of the Random Matrix Theory (RMT) molecular ecological network approach.ResultsThere was no significant difference in α diversity, but significant difference in β diversity based on Jaccard distance test. Compared to continuous cropping, crop rotation significantly increased the abundance of beneficial prokaryotes Verrucomicrobia and Rhodanobacter. These findings indicate that crop rotation promotes the enrichment of Verrucomicrobia and Rhodanobacter in the soil microbial community. AP and NH4-N had a greater effect on the community structure of prokaryotes and fungi in tobacco soil, while only AP had a greater effect on the community structure of protist. Molecular ecological network analysis showed that the network robustness and Cohesion of rotation were significantly higher than that of continuous cropping, indicating that the complexity and stability of molecular ecological networks were higher in the rotational, and the microbial communities cooperated more effectively, and the community structure was more stable.DiscussionFrom this point of view, rotational cropping is more conducive to changing the composition of soil microbial community, enhancing the stability of microbial network structure, and enhancing the potential ecological functions in soil.
Assessment of metabolomic variations among individuals returning to plain areas after exposure to high altitudes: a metabolomic analysis of human plasma samples with high-altitude de-acclimatization syndrome
Authors: Tan Zhen , Shen Pan , Wen Yi , Sun Hong-yu , Liang Hong-yin , Qie Hua-ji , Dai Rui-wu , Gao Yue , Huang Zhu , Zhou Wei , Tang Li-jun 
Published: June 2024

BackgroundHigh altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA.MethodsWe established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites.ResultAlthough significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5).ConclusionWe observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.
The effectiveness and predictors influencing the outcome of onabotulinumtoxinA treatment in chronic migraine: understanding from diverse patient profiles in a single session
Authors: Ilgaz Aydinlar Elif , Erdogan Soyukibar Tuba , Yalinay Dikmen Pinar 
Published: June 2024

ObjectiveThis real-world study aimed to investigate how onabotulinumtoxinA affects the outcome of migraine, along with accompanying anxiety, depression, and bruxism among a group of patients with chronic migraine (CM) and define predictors of good response.MethodsPatients diagnosed with CM who received onabotulinumtoxinA were included in this single-center, real-world retrospective cohort study. Monthly headache days (MHDs), monthly migraine days (MMDs), headache intensity (numeric rating scale-NRS) and headache characteristics were evaluated at baseline and 12 weeks post-treatment. Patient-reported outcome measures (PROMs) included Migraine Disability Assessment Scale (MIDAS), Headache Impact Test-6 (HIT-6) scores, 12-item Allodynia Symptom Checklist (ASC-12), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). Response to onabotulinumtoxinA (% reduction in MHDs) and treatment-related adverse events (TRAEs) were also evaluated. OnabotulinumA was applied to the masseter muscles in patients complaining of bruxism.ResultsA total of 72 patients (mean ± SD age: 36.3 ± 8.5 years; 91.7% were female) diagnosed with CM were included. OnabotulinumtoxinA revealed significant decrease in median (IQR) MHDs [from 20(15–25) at baseline to 6(4–10), p &lt; 0.001], MMDs [from 9(6–12) to 3(1–6), p &lt; 0.001] and NRS [from 9(8–10) to 7(6–8), p &lt; 0.001], and the MIDAS [from 54(30–81) to 16(7–24), p &lt; 0.001], HIT-6 [from 67(65–69) to 58(54–64), p &lt; 0.001], ASC-12 [from 6(1.5–9) to 2(0–9), p = 0.002], BAI [from 12(6.5–19) to 9(3–17), p &lt; 0.001] and BDI [from 11(6.5–17) to 3(2–7) p &lt; 0.001] scores at 12 weeks post-treatment. Patients complaining of bruxism received onabotulinumtoxinA injections in the first n = 27 (37.5%) and 12. week post-treatment n = 19 (70.4%) periods. Overall, 70.8% of patients responded (≥50% reduction in MHDs), while 29.2% did not (&lt;50% reduction). Both groups showed similar characteristics in demographics, migraine history, baseline PROMs scores, comorbidities, and prior treatments.ConclusionOnabotulinumtoxinA is an effective treatment option that rapidly improves migraine outcomes, disability, and impact while also alleviating comorbid depression and/or anxiety. This study’s noteworthy finding is that onabotulinumtoxinA is effective in a majority of CM patients, irrespective of their prior treatment history, migraine characteristics, or concurrent comorbidities. Furthermore, we identified no specific predictors for a favorable response to onabotulinumtoxinA. Applying onabotulinumtoxinA to the masseter muscles can relieve discomfort associated with concurrent bruxism; however, it does not impact migraine outcomes.
The comparison of DBS and RNS for adult drug-resistant epilepsy: a systematic review and meta-analysis
Authors: Li Qinghua , Shan Yongzhi , Wei Penghu , Zhao Guoguang 
Published: June 2024

ObjectiveNeuromodulation has been proven to be a promising alternative treatment for adult patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) and responsive neurostimulation (RNS) were approved by many countries for the treatment of DRE. However, there is a lack of systematic studies illustrating the differences between them. This meta-analysis is performed to assess the efficacy and clinical characteristics of DBS and RNS in adult patients with DRE.MethodsPubMed, Web of Science, and Embase were retrieved to obtain related studies including adult DRE patients who accepted DBS or RNS. The clinical characteristics of these patients were compiled for the following statistical analysis.ResultsA total of 55 studies (32 of DBS and 23 of RNS) involving 1,568 adult patients with DRE were included in this meta-analysis. There was no significant difference in seizure reduction and responder rate between DBS and RNS for DRE. The seizure reduction of DBS and RNS were 56% (95% CI 50–62%, p &gt; 0.05) and 61% (95% CI 54–68%, p &gt; 0.05). The responder rate of DBS and RNS were 67% (95% CI 58–76%, p &gt; 0.05) and 71% (95% CI 64–78%, p &gt; 0.05). Different targets of DBS did not show significant effect on seizure reduction (p &gt; 0.05). Patients with DRE who accepted DBS were younger than those of RNS (32.9 years old vs. 37.8 years old, p &lt; 0.01). The mean follow-up time was 47.3 months for DBS and 39.5 months for RNS (p &gt; 0.05).ConclusionBoth DBS and RNS are beneficial and alternative therapies for adult DRE patients who are not eligible to accept resection surgery. Further and larger studies are needed to clarify the characteristics of different targets and provide tailored treatment for patients with DRE.
Association of oxidative balance score with hearing loss and tinnitus: NHANES 1999–2018
Authors: Lai Haohong , Yin Jiyuan , Yang Haidi 
Published: June 2024

BackgroundOxidative stress is associated with the occurrence of hearing loss and tinnitus. The oxidative balance score (OBS), a composite indicator evaluating the balance between antioxidant and pro-oxidative components across various dietary and lifestyle factors, indicates the overall oxidative balance status. However, the association of OBS with hearing loss and tinnitus has not been reported previously.MethodsCross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were analyzed. Weighted multivariable logistic regression, weighted multivariable linear regression, and restricted cubic spline curve (RCS) regression were employed to explore the relationship between OBS and hearing loss at speech, low, and high frequencies, along with tinnitus. Subgroup analysis and sensitivity analysis were used to ascertain the consistency across subgroups and stability of the results.ResultsWe included 13,715 and 21,644 individuals to investigate the association between OBS and hearing loss, as well as between OBS and tinnitus, respectively. The second, third, and fourth quartiles of OBS were significantly associated with a lower risk of hearing loss at speech, low, and high frequencies, as well as tinnitus, compared to the lowest quartile. The RCS regression analysis indicated a negative linear association of OBS with hearing loss and tinnitus. Most associations were maintained in subgroup analysis and sensitivity analysis. Additionally, the dietary and lifestyle OBS independently contribute to the protection against hearing loss and tinnitus.ConclusionOBS is negatively correlated with the risk of hearing loss and tinnitus. The findings suggest that combined antioxidant diet and lifestyle hold promise as potential strategies for reducing the prevalence of hearing loss and tinnitus.
Improving skin cancer detection by Raman spectroscopy using convolutional neural networks and data augmentation
Authors: Zhao Jianhua , Lui Harvey , Kalia Sunil , Lee Tim K. , Zeng Haishan 
Published: June 2024

BackgroundOur previous studies have demonstrated that Raman spectroscopy could be used for skin cancer detection with good sensitivity and specificity. The objective of this study is to determine if skin cancer detection can be further improved by combining deep neural networks and Raman spectroscopy.Patients and methodsRaman spectra of 731 skin lesions were included in this study, containing 340 cancerous and precancerous lesions (melanoma, basal cell carcinoma, squamous cell carcinoma and actinic keratosis) and 391 benign lesions (melanocytic nevus and seborrheic keratosis). One-dimensional convolutional neural networks (1D-CNN) were developed for Raman spectral classification. The stratified samples were divided randomly into training (70%), validation (10%) and test set (20%), and were repeated 56 times using parallel computing. Different data augmentation strategies were implemented for the training dataset, including added random noise, spectral shift, spectral combination and artificially synthesized Raman spectra using one-dimensional generative adversarial networks (1D-GAN). The area under the receiver operating characteristic curve (ROC AUC) was used as a measure of the diagnostic performance. Conventional machine learning approaches, including partial least squares for discriminant analysis (PLS-DA), principal component and linear discriminant analysis (PC-LDA), support vector machine (SVM), and logistic regression (LR) were evaluated for comparison with the same data splitting scheme as the 1D-CNN.ResultsThe ROC AUC of the test dataset based on the original training spectra were 0.886±0.022 (1D-CNN), 0.870±0.028 (PLS-DA), 0.875±0.033 (PC-LDA), 0.864±0.027 (SVM), and 0.525±0.045 (LR), which were improved to 0.909±0.021 (1D-CNN), 0.899±0.022 (PLS-DA), 0.895±0.022 (PC-LDA), 0.901±0.020 (SVM), and 0.897±0.021 (LR) respectively after augmentation of the training dataset (p&lt;0.0001, Wilcoxon test). Paired analyses of 1D-CNN with conventional machine learning approaches showed that 1D-CNN had a 1–3% improvement (p&lt;0.001, Wilcoxon test).ConclusionsData augmentation not only improved the performance of both deep neural networks and conventional machine learning techniques by 2–4%, but also improved the performance of the models on spectra with higher noise or spectral shifting. Convolutional neural networks slightly outperformed conventional machine learning approaches for skin cancer detection by Raman spectroscopy.
Activation of non-classical Wnt signaling pathway effectively enhances HLA-A presentation in acute myeloid leukemia
Authors: Ma YuHan , Yue JunShuai , Gao Ling , Zhou JingXin , Chen Wei , Su Jing , Yao JinRong , Shi QiaoMei , Zhao XiaoDong , Hu Na 
Published: June 2024

ObjectiveThe escape from T cell-mediated immune surveillance is an important cause of death for patients with acute myeloid leukemia (AML). This study aims to identify clonal heterogeneity in leukemia progenitor cells and explore molecular or signaling pathways associated with AML immune escape.MethodsSingle-cell RNA sequencing (scRNA-seq) was performed to identified AML-related cellular subsets, and intercellular communication was analyzed to investigate molecular mechanisms associated with AML immune escape. Bulk RNA sequencing (RNA-seq) was performed to screen differentially expressed genes (DEGs) related to hematopoietic stem cell progenitors (HSC-Prog) in AML, and critical ore signaling pathways and hub genes were found by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The mRNA level of the hub gene was verified using quantitative real-time PCR (qRT-PCR) and the protein level of human leukocyte antigen A (HLA-A) using enzyme-linked immuno sorbent assay (ELISA).ResultsscRNA-seq analysis revealed a large heterogeneity of HSC-Prog across samples, and the intercellular communication analysis indicated a strong association between HSC-Prog and CD8+-T cells, and HSC-Prog also had an association with HLA-A. Transcriptome analysis identified 1748 DEGs, enrichment analysis results showed that non-classical wnt signaling pathway was associated with AML, and 4 pathway-related genes (RHOA, RYK, CSNK1D, NLK) were obtained. After qRT-PCR and ELISA validation, hub genes and HLA-A were found to be down-regulated in AML and up-regulated after activation of the non-classical Wnt signaling pathway.ConclusionIn this study, clonal heterogeneity of HSC-Prog cells in AML was identified, non-classical wnt signaling pathways associated with AML were identified, and it was verified that HLA-A could be upregulated by activation of non-classical wnt signaling, thereby increasing antigen presentation.
Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy
Authors: Piñana José Luis , Vazquez Lourdes , Heras Inmaculada , Aiello Tommaso Francesco , López-Corral Lucia , Arroyo Ignacio , Soler-Espejo Eva , García-Cadenas Irene , Garcia-Gutierrez Valentín , Aroca Cristina , Chorao Pedro , Olave María T. , Lopez-Jimenez Javier , Gómez Marina Acera , Arellano Elena , Cuesta-Casas Marian , Avendaño-Pita Alejandro , González-Santillana Clara , Hernández-Rivas José Ángel , Roldán-Pérez Alicia , Mico-Cerdá Mireia , Guerreiro Manuel , Morell Julia , Rodriguez-Galvez Paula , Labrador Jorge , Campos Diana , Cedillo Ángel , Vidal Carolina Garcia , Martino Rodrigo , Solano Carlos 
Published: June 2024

IntroductionScarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era.PurposeTo assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting.MethodsA retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed.ResultsNearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality.ConclusionsThe results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.