bluuebunny/crossref_metadata_2025_split huggingface dataset:
Future projections of extreme temperature events in Southwest China using nine models in CMIP6
Authors: Li Xiehui , Chen Zifan , Wang Lei , Liu Huan 
Published: August 2022

Southwest China, which is close to the Qinghai-Tibet Plateau, presents complex topography. As a result of the combined influence of the South Asian monsoon, East Asian monsoon, and plateau monsoon, climate in this region is unique. Since Southwest China is one of the areas where extreme weather events occur more frequently, this region is sensitive and vulnerable to climate change. In the present research, daily temperature from 1969 to 2020 recorded at 93 weather stations in Southwest China, and data from nine models for the period 1995 to 2040 were used in CMIP6 (Coupled Model Intercomparison Project Phase 6) to calculate 17 ETIs (Extreme Temperature Indices). Furthermore, we analyzed and compared the annual change rate, temporal and spatial change trend, and mean change of extreme temperature events in Southwest China and four subzones during historical period and under SSP2-4.5 scenario for the next 20 years. The results showed: 1) The 8 ECTIs (Extreme Cold Temperature Indices) and the 8 EWTIs (Extreme Warm Temperature Indices) in 1969–2020 were corroborated. These results indicated a warming trend. Also, DTR (Diurnal temperature range) showed a decreasing trend, and different degrees of warming were observed in the four subzones. 2) From 2021 to 2040 and under the SSP2-4.5 scenario, the annual rates of change for 17 ETIs in Southwest China showed that extreme cold events will continue to decrease. On the other hand, extreme warm events will continue to increase. 3) Under the SSP2-4.5 scenario in the next 20 years, CSDI (cold spell duration indicator) will decrease, while WSDI (warm spell duration indicator), TMINmean (average daily minimum temperature), and TMAXmean (average daily maximum temperature) will increase. Moreover, the decrease in amplitude of CSDI was smaller than the increase in amplitude of WSDI. Also, the increase in amplitude of TMINmean was slightly smaller than that of TMAXmean. The projected WSDI, TMINmean, and TMAXmean obtained with the preferred three models and MEM-9 (nine-Model Ensemble Mean) showed an overall growing trend with respect to space; however, the increased range fluctuated in different regions. 4) In 2021–2040, mean values of 4 ETIs in different subzones indicated that the lowest TMINmean and TMAXmean were observed in the ZP (Zoigê Plateau), the highest in the YGP (Yunnan-Guizhou Plateau), and intermediate higher in the SB (Sichuan Basin). Compared with the 4 ETI mean values corresponding to 1969–2020, the persistence and average state of extreme cold and warm events in different subzones showed that future change trends depend on altitude.
Weather Extremes Led to Large Variability in O3 Pollution and Associated Premature Deaths in East of China
Authors: Wan Yu , Yin Zhicong , Huo Qianyi , Zhou Botao , Wang Huijun 
Published: August 2022

As global warming intensifies, hot extremes and heavy precipitation frequently happen in East of China. Meanwhile, severe surface ozone (O3) pollution resulting from the interactions of anthropogenic emissions and meteorological conditions also occur more frequently. In this study, we quantified the impact of weather extremes on ground-level O3 concentration during the summers of 2015–2021 and associated premature deaths in East of China. The O3 pollution influenced by hot extremes [maximum 8-h average O3 concentration (MDA8 O3) = 152.7 μg m−3] was 64.2% more severe than that associated with heavy rain (MDA8 O3 = 93 μg m−3) on the daily time scale. The compound hot and dry air extremes had a larger impact, and the associated MDA8 O3 could be up to 165.5 μg m−3. Thus, weather extremes could drastically perturb the O3 level in the air to exhibit large variability. Based on GEOS-Chem simulations with fixed anthropogenic emissions, forcing of weather extremes could successfully reproduce the large daily variability of O3 concentration because the weather extremes significantly influenced the physicochemical processes in the atmosphere. Furthermore, hot extremes magnified the single-day O3-related premature death to 153% of that under other-condition events, while heavy rain events decreased it to 70% in East of China. The findings of the present study have the potential to promote daily to weekly O3 forecasts and further improve our comprehensive understanding of the health effects of weather extremes and air pollution.
Comparison of clinicopathological features and prognosis of papillary thyroid carcinoma and microcarcinoma: A population-based propensity score matching analysis
Authors: Qian Bei , Hu Longqing , Zhang Shoupeng , Zhu Junlin , Mei Li , Huang Tao , Qu Xincai 
Published: August 2022

BackgroundOvertreatment of papillary thyroid microcarcinoma (PTMC) has become a common concern. This study aimed to compare clinicopathological features between PTMC and papillary thyroid carcinoma (PTC) and to explore whether surgery can confer significant survival benefits in all patients with PTC or PTMC.MethodsData of 145,951 patients with PTC registered in Surveillance, Epidemiology, and End Results (SEER) database and 8,751 patients with PTC in our institution were retrospectively collected. Patients with tumors less than 10 mm in diameter were classified as PTMC cohort and the rest as PTC cohort. Clinicopathological features between PTMC and PTC were compared on the basis of SEER cohort and validated with institutional data. Survival analysis was conducted to explore the effect of surgery on the prognosis of patients. To minimize potential confounders and selection bias, we performed propensity score matching (PSM) analysis to match more comparable cohorts.ResultsCompared with PTC, PTMC exhibited the following characteristics: more common in women and whites, older age at diagnosis, lower proportion of follicular variants, intraglandular dissemination, extraglandular and capsular invasion, higher proportion of multifocality, fewer lymph node and distant metastases, and higher cancer-specific survival (CSS) and overall survival (OS) (all p-value &lt; 0.05). Regarding treatment, patients with PTMC received a lower proportion of radiotherapy, chemotherapy, and total thyroidectomy but a higher proportion of lobectomy and/or isthmectomy. There was no significant difference in CSS for patients with PTMC at stage T1N0M0 with or without surgery (P = 0.36).ConclusionGenerally, PTMC showed higher biological indolence than PTC, which meant a higher survival rate for patients in both OS and CSS. For patients with PTMC at staged T1N0M0, active surveillance (AS) may be a potentially feasible management strategy. However, the maintenance of good medical compliance and the management of psychological burden cannot be ignored for patients included in AS.
A bibliometric and visualization analysis of glucocorticoid-induced osteoporosis research from 2012 to 2021
Authors: Jiang Buchan , Feng Chengyao , Li Chenbei , Tu Chao , Li Zhihong 
Published: August 2022

IntroductionGlucocorticoid-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis. Although many studies related to GIOP have been published, there was no bibliometric analysis in this field. This study aimed to investigate the research trends on GIOP by using bibliometric analysis.Materials and MethodsAll data were collected from the Web of Science Core Collection (WoSCC). All original research articles regarding GIOP from 2012 to 2021 were retrieved. CiteSpace was used to analyze the distribution of countries, institutions, journals, authors, and keywords. We revealed hotspots and trends in the field by drawing co-occurrence keyword maps and identifying burst keywords.ResultsFrom 2012 to 2021, 685 relevant articles were published, with a peak in 2018 in the annual number of publications. China and McMaster University were the leading country and institution in this field with 208 and 12 publications, respectively. Osteoporosis International was the journal with the most studies, while Journal of Bone and Mineral Research was the most cited journal. “Bone mineral density”, “fracture”, “postmenopausal women”, “prevention” and “therapy” were the most high-frequency keywords, while “bone mineral density”, “bisphosphonate” and “metabolism” were the top high-centrality keywords.ConclusionThe results from this bibliometric study provided insight into the status and research trends in GIOP of the past decade, which could help researchers quickly determine the current hotspots and frontier trends in this field.
Identification of the alpha linolenic acid metabolism-related signature associated with prognosis and the immune microenvironment in nasopharyngeal carcinoma
Authors: Fang Zhijie , Huang Hua , Wang Liyu , Lin Zhiqiang 
Published: August 2022

BackgroundTumor metabolism is important for cancer progression. Nevertheless, the role of the metabolism pathway and related molecules in nasopharyngeal carcinoma (NPC) is limited.MethodsOpen-accessed data was downloaded from The Cancer Genome Atlas database. All the analysis was performed using the R software and the package in R environments.ResultsIn our study, we firstly explored the role of 21 metabolism-related pathways in NPC patients. We found that the steroid biosynthesis and biosynthesis of unsaturated fatty acids were risk factors, while the alpha linolenic acid metabolism was a protective factor. Then, the alpha linolenic acid metabolism aroused our interest. A total of 128 differentially expressed genes (DEGs) were identified, including 71 downregulated and 57 upregulated genes identified between high and low alpha linolenic acid metabolism level. Based on these DEGs, we constructed a prognosis model including DEFB4B, FOXL2NB, MDGA2, RTL1, SLURP2, TMEM151B and TSPAN19, which showed great prediction efficiency in both training and validation cohorts. Clinical correlation analysis showed that high-risk patients might have worse clinical pathology parameters. Pathway enrichment analysis showed that riskscore was positively correlated with angiogenesis, DNA repair, G2/M checkpoints, IL6/JAK/STAT3 signaling, KRAS signaling up, WNT beta-catenin signaling, PI3K/AKT/mTOR signaling, yet positively correlated with inflammatory response, xenobiotic metabolism, TNF-α signaling via NFKB and interferon-gamma response. Immune infiltration analysis showed that the riskscore was positively correlated with the M2 and M0 macrophages, but negatively correlated with neutrophils, plasma cells, follicular helper T cells and resting dendritic cells Moreover, we found that the low-risk patients might be more sensitive to immunotherapy and lapatinib.ConclusionsIn all, our study identified the genes associated with alpha linolenic acid metabolism and constructed an effective prognosis model which could robustly predict NPC patients prognosis.
A systematic analysis of C5ORF46 in gastrointestinal tumors as a potential prognostic and immunological biomarker
Authors: Jiang Yuhong , Wang Xiaobo , Li Lun , He Jun , Jin Qianqian , Long Dongju , Liu Chao , Zhou Weihan , Liu Kuijie 
Published: August 2022

Background: Chromosome 5 open reading frame 46 (C5ORF46), also known as antimicrobial peptide with 64 amino acid residues (AP-64) and skin and saliva-secreted protein 1 (SSSP1), belongs to the family of open reading frame genes and encodes a small exosomal protein. C5ORF46 has been implicated in antibacterial activity and associated with patient prognosis in pancreatic cancer, colorectal cancer, and stomach cancer. These findings highlight the importance of C5ORF46 in gastrointestinal (GI) tumor inception and development. However, the prognostic and immunological value of C5ORF46 in human GI tumors remains largely unknown. In this study, we sought to explore the potential value of C5ORF46 in GI tumor prognosis and immunology.Method: RNA sequencing (RNA-seq) was performed on the tumor and tumor-adjacent normal samples we collected to identify potential target genes for GI tumors. Apart from our RNA-seq data, all original data were downloaded from The Cancer Genome Atlas (TCGA) database and integrated via Strawberry Perl (v 5.32.0) and R (v 4.1.1). The differential expression of C5ORF46 was examined with Oncomine, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas (HPA) and TCGA databases. The c-BioPortal database was used to investigate the genomic alterations of C5ORF46. The effect of C5ORF46 on prognosis and clinical phenotypes was explored via bioinformatics analyses on the TCGA and GEPIA databases. We used the bioinformatics analyses based on the TCGA database to analyze tumor mutational burden (TMB), microsatellite instability (MSI), tumor immune cell infiltration, and the correlations between C5ORF46 expression and several immune-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out via the DAVID website and presented as bubble charts using ShengXinRen online tools. Gene set enrichment analysis (GSEA) was performed using R scripts based on data downloaded from the GSEA website. Immunohistochemistry (IHC) was used to validate the expression of C5ORF46 in GI tumors.Results: The results of our RNA-seq data indicated a critical role for C5ORF46 in colon carcinogenesis. Consistently, we demonstrated that C5ORF46 was highly expressed in tumor tissues compared to normal tissues in human GI tumors. Moreover, a strong correlation was observed between C5ORF46 expression levels and patient prognosis, staging, TMB, MSI, and immune cell infiltration. Further, C5ORF46 presented as an important regulator in the tumor microenvironment (TME) and was active in the regulation of cancer immune functions. C5ORF46 is significantly correlated with genes regulating inflammation and immune responses.Conclusion:C5ORF46 may serve as a biomarker for GI tumor prognosis and immunology. C5ORF46 could be a novel target for GI tumor immunotherapy.
Efficacy and safety of atezolizumab plus bevacizumab combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma
Authors: Xin Yujing , Cao Fei , Yang Hongcai , Zhang Xinyuan , Chen Yi , Cao Xiaojing , Zhou Xiang , Li Xiao , Zhou Jinxue 
Published: August 2022

BackgroundAtezolizumab plus bevacizumab has been proved to have promising antitumor activity and tolerable safety in patients with unresectable hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) also demonstrated high response rates and favorable survival for patients with advanced HCC. This study aimed to explore the preliminary clinical efficacy and safety of atezolizumab plus bevacizumab combined with HAIC for patients with treatment-naive advanced HCC.MethodsBetween October 2020 and September 2021, patients with advanced HCC who initially received atezolizumab plus bevacizumab combined with HAIC of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) from three hospitals in China were reviewed for eligibility. The efficacy was evaluated by tumor response rate and survival, and the safety was evaluated by the frequency of key adverse events (AEs).ResultsIn total, 52 eligible patients with advanced HCC who received triple therapy were included in this study. The objective response rates (ORRs) based on mRECIST and RECIST1.1 criteria were 67.3% and 44.2%, respectively. The median progression-free survival (PFS) of patients was 10.6 months (95% CI, 8.37–13.8), and the overall survival (OS) was not reached. Extrahepatic metastasis was an independent risk factor associated with PFS. All AEs were controlled and no treatment-related deaths occurred.ConclusionAtezolizumab plus bevacizumab combined with HAIC-FOLFOX had a significant therapeutic effect and manageable AEs in patients with advanced HCC, which may be a potential treatment option for advanced HCC.
Features of patients with advanced EGFR-mutated non-small cell lung cancer benefiting from immune checkpoint inhibitors
Authors: Chen Qian , Shang Xiaoling , Liu Ni , Ma Xinchun , Han Wenfei , Wang Xiuwen , Liu Yanguo 
Published: August 2022

BackgroundAlthough immune checkpoint inhibitors (ICIs) generally show poor therapeutic efficacy in patients with epidermal growth factor receptor (EGFR) mutations, certain research indicate that a small proportion of these patients do respond to ICIs. The present study sought to identify the features of patients with EGFR mutations who might benefit from ICIs from multiple studies and discussed the optimal treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations.MethodsThe profiles of 114 advanced NSCLC patients with EGFR mutations who received ICIs treatment were retrospectively reviewed. EGFR subtypes, programmed cell death ligand 1 (PD-L1) expression, and clinical characteristics regarding their impact on the efficacy of ICIs were investigated.ResultsPatients with major EGFR mutations (L858R or 19Del) had a shorter progression-free survival (PFS) and a lower objective response rate (ORR) as compared to patients with rare (20ins or G719X) and other EGFR mutations. Although not statistically significant, median overall survival (OS) tended to be longer in patients with negative (&lt;1%) PD-L1 expression than with positive (≥1%) PD-L1 expression (15.61 vs. 7.40 months, p = 0.138). Median PFS and OS were significantly shorter in heavily treated patients (prior lines of therapy ≥3 lines vs. &lt;3 lines: mPFS, 1.80 vs. 2.50 months, p = 0.003; mOS, 6.70 vs. 14.00 months, p = 0.031). ORR was also lower in patients who had received ≥3 prior lines of therapy compared to in those &lt;3 prior lines of therapy (0.00% vs. 21.67%, p = 0.002).ConclusionPatients with major EGFR mutations showed poorer responses to ICIs than those with rare EGFR mutations. EGFR-mutated patients with lower PD-L1 expression showed a trend towards a longer OS after receiving ICIs. ICIs should be administered as early as possible to previously treated EGFR-mutated NSCLC patients. ICI-based combined therapies may be a direction for treatment of these patient subtypes in the future.
Case report: Revealing a special and rare autoimmune GFAP astrocytopathy in the spinal cord succeeding Neurobrucellosis infection
Authors: He Qiang , Liu Junxian , Zhu Zehua , Tang Yongxiang , Long Lili , Hu Kai 
Published: August 2022

Brucellosis, a zoonosis, can cause an inflammatory response in most organs and continues to be a public health problem in some endemic areas, whereas neurobrucellosis is a morbid form of brucellosis that affects the central nervous system (CNS) with poor prognosis. Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an autoimmune disease, and there have been no reports of a Brucella infection, leading to GFAP astrocytopathy. We report the case of a patient with a positive and high level of GFAP antibodies in the cerebrospinal fluid (CSF), following a Brucella infection. Although this patient did not show any responsible lesions in the diffusion sequence of the magnetic resonant imaging (MRI) scan, we found an evidence of thoracolumbar (T12) involvement on fluorodeoxyglucose (FDG) positron emission tomography (PET). The symptoms of spinal cord involvement were only partly relieved after initial treatment [doxycycline (0.1 g Bid) and rifampicin (0.6 g Qd) for 6 weeks]; however, they markedly improved after the subsequent immunosuppressive therapy [intravenous methylprednisolone (1,000 mg for 3 days)], followed by a 50% reduction from the preceding dose after 3 days, and subsequently, oral prednisone tablets (60 mg/day) was started, which was then gradually tapered [reduced to 10 mg/day every 1–2 weeks)]. The positive response to immunosuppressive therapy and treatment outcome strongly indicated the presence of an autoimmune neurological disease probably triggered by some infectious factors. Therefore, our findings reveal that a Brucella infection is one of the causes of autoimmune GFAP astrocytopathy, and when this infection is difficult to be identified by regular MRI, FDG PET can be used as a supplementary method for diagnosis and treatment.
Integration of transcriptomics, proteomics, and metabolomics data to reveal HER2-associated metabolic heterogeneity in gastric cancer with response to immunotherapy and neoadjuvant chemotherapy
Authors: Yuan Qihang , Deng Dawei , Pan Chen , Ren Jie , Wei Tianfu , Wu Zeming , Zhang Biao , Li Shuang , Yin Peiyuan , Shang Dong 
Published: August 2022

BackgroundCurrently available prognostic tools and focused therapeutic methods result in unsatisfactory treatment of gastric cancer (GC). A deeper understanding of human epidermal growth factor receptor 2 (HER2)-coexpressed metabolic pathways may offer novel insights into tumour-intrinsic precision medicine.MethodsThe integrated multi-omics strategies (including transcriptomics, proteomics and metabolomics) were applied to develop a novel metabolic classifier for gastric cancer. We integrated TCGA-STAD cohort (375 GC samples and 56753 genes) and TCPA-STAD cohort (392 GC samples and 218 proteins), and rated them as transcriptomics and proteomics data, resepectively. 224 matched blood samples of GC patients and healthy individuals were collected to carry out untargeted metabolomics analysis.ResultsIn this study, pan-cancer analysis highlighted the crucial role of ERBB2 in the immune microenvironment and metabolic remodelling. In addition, the metabolic landscape of GC indicated that alanine, aspartate and glutamate (AAG) metabolism was significantly associated with the prevalence and progression of GC. Weighted metabolite correlation network analysis revealed that glycolysis/gluconeogenesis (GG) and AAG metabolism served as HER2-coexpressed metabolic pathways. Consensus clustering was used to stratify patients with GC into four subtypes with different metabolic characteristics (i.e. quiescent, GG, AAG and mixed subtypes). The GG subtype was characterised by a lower level of ERBB2 expression, a higher proportion of the inflammatory phenotype and the worst prognosis. However, contradictory features were found in the mixed subtype with the best prognosis. The GG and mixed subtypes were found to be highly sensitive to chemotherapy, whereas the quiescent and AAG subtypes were more likely to benefit from immunotherapy.ConclusionsTranscriptomic and proteomic analyses highlighted the close association of HER-2 level with the immune status and metabolic features of patients with GC. Metabolomics analysis highlighted the co-expressed relationship between alanine, aspartate and glutamate and glycolysis/gluconeogenesis metabolisms and HER2 level in GC. The novel integrated multi-omics strategy used in this study may facilitate the development of a more tailored approach to GC therapy.