bluuebunny/crossref_metadata_2025_split huggingface dataset:
Past and future behavior of the valley glaciers in the Italian Alps
Authors: Serandrei-Barbero Rossana , Donnici Sandra , Zecchetto Stefano 
Published: October 2022

The behavior of the valley glaciers of the Italian Alps as a result of the climate changes expected for the 21st century has been investigated. From 1980 to 2017 the average length reduction of these glaciers has been 13% and their average areal reduction was around 22%. The mean climate sensitivity of the considered glaciers is 410 mK−1 and their mean observed shortening was about 500 m for a temperature increase of 1.4°C. To quantify the valley glacier life expectancy, a model estimating their length variations from the air temperature variations of the EuroCordex climatological projections of six different models under the RCP4.5 and RCP8.5 scenarios has been used. The ensemble mean temperatures in the Italian Alps region under these scenarios indicate increases in the temperature of ∼2°C and ∼4°C from 2018 to 2100 respectively. The glacier projections are mean values, taking into account the errors due to the model (6–16%) and the different climatological forcings (up to 20–30%). Under the RCP4.5 scenario, the glacier model projections show a constant retreat until the 2080s, with a weakening around 2090s and the 87% of glaciers surviving. Under the RCP8.5 scenario, only three glaciers could reach the end of the century, while 80% of them will probably disappear between the 2060s and the 2080s.
Dynamic changes and early predictive value of branched-chain amino acids in gestational diabetes mellitus during pregnancy
Authors: Wang Xiaoxin , Zhang Ya , Zheng Wei , Wang Jia , Wang Yuanyuan , Song Wei , Liang Shengnan , Guo Cuimei , Ma Xu , Li Guanghui 
Published: October 2022

ObjectiveBranched-chain amino acids (BCAAs) are closely associated with type 2 diabetes mellitus, but their roles in gestational diabetes mellitus (GDM) are still controversial. This study aims to explore the dynamic changes of BCAAs during pregnancy and identify potential early biomarkers for GDM.MethodsThis study is a nested case-control study involved 49 women with GDM and 50 age- and body mass index (BMI)-matched healthy pregnant women. The dynamic changes of valine (Val), isoleucine (Ile), and leucine (Leu) were detected in the first (8-12 weeks) and second trimesters (24-28 weeks) by liquid chromatography-mass spectrometry.ResultsSerum Val, Ile, and Leu were higher in GDM patients than in controls in the first trimester. Compared with the first trimester, the serum Val, Ile, and Leu in GDM patients were decreased in the second trimester. In addition, Val, Ile, and Leu in the first trimester were the risk factors for GDM, and Ile presented a high predictive value for GDM. Ile + age (≥ 35) + BMI (≥ 24) exhibited the highest predictive value for GDM (AUC = 0.902, sensitivity = 93.9%, specificity = 80%).ConclusionMaternal serum Ile in the first trimester was a valuable biomarker for GDM. Ile combined with advanced maternal age and overweight may be used for the early prediction of GDM.
Genetic evidence suggests that depression increases the risk of erectile dysfunction: A Mendelian randomization study
Authors: Ma Kai , Song Pan , Liu Zhenghuan , Yang Luchen , Wang Linchun , Zhou Jing , Chen Junhao , Dong Qiang 
Published: October 2022

Background: The causal relationship between depression and erectile dysfunction (ED) is still uncertain.Objectives: To identify the genetically predicted causality of depression on ED through Mendelian randomization (MR).Materials and methods: A comprehensive GWAS meta-analysis comprising 807,553 Europeans provided single-nucleotide polymorphism (SNP) information for depression, and another genome-wide association analysis involving 223,805 European ancestries measured SNPs for ED. The inverse variance weighted (IVW) method was used as the primary MR analysis method to evaluate causal effects. In addition, the maximum likelihood method, MR-Egger, weighted median, robust adjusted contour score (MR.RAPS), and MR pleiotropic residual and outlier (MR-PRESSO) methods were used as supplements for sensitivity analysis.Results: According to the IVW analysis, depression significantly increases the incidence of ED (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.38–2.05, p &lt; 0.001). In sensitivity analyses, the ORs for the maximum likelihood method, MR-Egger, weighted median, MR.RAPS, and MR-PRESSO are 1.70 (95% CI = 1.39–2.08, p &lt; 0 .001), 1.94 (95% CI = 0.63–6.01, p &gt; 0 .05), 1.59 (95% CI = 1.21–2.10, p &lt; 0 .001), 1 .70 (95% CI = 1.39–2.08, p &lt; 0 .001), and 1.68 (95% CI = 1.40–2.04, p &lt; 0 .001). There is no clear indication of potential heterogeneity or pleiotropy (p for the MR-Egger intercept = 0.804; p for the global test = 0.594; and p for Cochran’s Q statistics &gt;0.05).Conclusion: Genetically predicted depression plays a potentially causal role in the occurrence of ED.
Establishment of m7G-related gene pair signature to predict overall survival in colorectal cancer
Authors: Li Kai , Wang Weixing 
Published: October 2022

Background: N7-methylguanosine (m7G) is an emerging research hotspot in the field of RNA methylation, and its role in tumor regulation is becoming increasingly recognized. However, its role in colorectal cancer (CRC) remains unclear. Hence, our study explored the role of m7G in CRC.Methods: The mRNA expression data and the corresponding clinical information of the patients with CRC were obtained from The Cancer Genome Atlas (TCGA). A m7G-related gene pair signature was established using the Cox and LASSO regression analyses. A series of in silico analyses based on the signature included analysis of prognosis, correlation analysis, immune-related analysis, and estimation of tumor mutational burden (TMB), microsatellite instability (MSI), and response to immunotherapy. A nomogram prediction model was then constructed.Results: In total, 2156 m7G-related gene pairs were screened based on 152 m7G-related genes. Then, a prognostic signature of seven gene pairs was constructed, and the patients were stratified into high- or low-risk groups. Better overall survival (OS), left-sided tumor, early stage, immune activity, and low proportion of MSI-low and MSI-high were all associated with a low risk score. High-risk patients had a higher TMB, and patients with a high TMB had a poor OS. Furthermore, the risk score was linked to immune checkpoint expression (including PD-L1), the tumor immune dysfunction and exclusion (TIDE) score, and chemotherapy sensitivity. We also created an accurate nomogram to increase the clinical applicability of the risk score.Conclusion: We identified an m7G pair-based prognostic signature associated with prognosis, immune landscape, immunotherapy, and chemotherapy in CRC. These findings could help us to better understand the role of m7G in CRC, as well as pave the path for novel methods to assess prognosis and design more effective individualized therapeutic strategies.
Strain level and comprehensive microbiome analysis in inflammatory bowel disease via multi-technology meta-analysis identifies key bacterial influencers of disease
Authors: Ravichandar Jayamary Divya , Rutherford Erica , Chow Cheryl-Emiliane T. , Han Andrew , Yamamoto Mitsuko Lynn , Narayan Nicole , Kaplan Gilaad G. , Beck Paul L. , Claesson Marcus J. , Dabbagh Karim , Iwai Shoko , DeSantis Todd Z. 
Published: October 2022

ObjectiveInflammatory bowel disease (IBD) is a heterogenous disease in which the microbiome has been shown to play an important role. However, the precise homeostatic or pathological functions played by bacteria remain unclear. Most published studies report taxa-disease associations based on single-technology analysis of a single cohort, potentially biasing results to one clinical protocol, cohort, and molecular analysis technology. To begin to address this key question, precise identification of the bacteria implicated in IBD across cohorts is necessary.MethodsWe sought to take advantage of the numerous and diverse studies characterizing the microbiome in IBD to develop a multi-technology meta-analysis (MTMA) as a platform for aggregation of independently generated datasets, irrespective of DNA-profiling technique, in order to uncover the consistent microbial modulators of disease. We report the largest strain-level survey of IBD, integrating microbiome profiles from 3,407 samples from 21 datasets spanning 15 cohorts, three of which are presented for the first time in the current study, characterized using three DNA-profiling technologies, mapping all nucleotide data against known, culturable strain reference data.ResultsWe identify several novel IBD associations with culturable strains that have so far remained elusive, including two genome-sequenced but uncharacterized Lachnospiraceae strains consistently decreased in both the gut luminal and mucosal contents of patients with IBD, and demonstrate that these strains are correlated with inflammation-related pathways that are known mechanisms targeted for treatment. Furthermore, comparative MTMA at the species versus strain level reveals that not all significant strain associations resulted in a corresponding species-level significance and conversely significant species associations are not always re-captured at the strain level.ConclusionWe propose MTMA for uncovering experimentally testable strain-disease associations that, as demonstrated here, are beneficial in discovering mechanisms underpinning microbiome impact on disease or novel targets for therapeutic interventions.
Untargeted muscle tissue metabolites profiling in young, adult, and old rats supplemented with tocotrienol-rich fraction
Authors: Saud Gany Siti Liyana , Tan Jen Kit , Chin Kok Yong , Hakimi Nur Haleeda , Ab Rani Nazirah , Ihsan Nurhazirah , Makpol Suzana 
Published: October 2022

The greatest significant influence on human life span and health is inevitable ageing. One of the distinguishing characteristics of ageing is the gradual decrease of muscle mass and physical function. There has been growing evidence that tocotrienol can guard against age-associated chronic diseases and metabolic disorders. This study aimed to elucidate the effects of tocotrienol-rich fraction (TRF) on muscle metabolomes and metabolic pathways in ageing Sprague Dawley (SD) rats. Three months, 9 months, and 21 months old male SD rats were divided into control and treated groups with 10 rats per group. Rats in control and treated groups were given 60 mg/kg body weight/day of palm olein and 60 mg/kg body weight/day of TRF, respectively, via oral gavage for 3 months. Muscle performance was assessed at 0 and 3 months of treatment by measuring muscle strength and function. Our results showed that TRF treatment caused a significant increase in the swimming time of the young rats. Comparison in the control groups showed that metabolites involved in lipid metabolisms such as L-palmitoyl carnitine and decanoyl carnitine were increased in ageing. In contrast, several metabolites, such as 3-phosphoglyceric acid, aspartic acid and aspartyl phenylalanine were decreased. These findings indicated that muscle metabolomes involved in lipid metabolism were upregulated in aged rats. In contrast, the metabolites involved in energy and amino acid metabolism were significantly downregulated. Comparison in the TRF-supplemented groups showed an upregulation of metabolites involved in energy and amino acid metabolism. Metabolites such as N6-methyl adenosine, spermine, phenylalanine, tryptophan, aspartic acid, histidine, and N-acetyl neuraminic acid were up-regulated, indicating promotion of amino acid synthesis and muscle regeneration. Energy metabolism was also improved in adult and old rats with TRF supplementation as indicated by the upregulation of nicotinamide adenine dinucleotide and glycerol 3-phosphate compared to the control group. In conclusion, the mechanism underlying the changes in skeletal muscle mass and functions in ageing was related to carbohydrate, lipid and amino acid metabolism. Tocotrienol supplementation showed beneficial effects in alleviating energy and amino acid synthesis that may promote the regeneration and renewal of skeletal muscle in ageing rats.
Psychopathic tendency in violent offenders is associated with reduced aversive Pavlovian inhibition of behavior and associated striatal BOLD signal
Authors: Geurts Dirk E. M. , von Borries Katinka , Huys Quentin J. M. , Bulten Berend H. , Verkes Robbert-Jan , Cools Roshan 
Published: October 2022

BackgroundViolent offenders with psychopathic tendencies are characterized by instrumental, i.e., planned, callous, and unemotional (aggressive) behavior and have been shown to exhibit abnormal aversive processing. However, the consequences of abnormal aversive processing for instrumental action and associated neural mechanisms are unclear.Materials and methodsHere we address this issue by using event-related functional magnetic resonance imaging (fMRI) in 15 violent offenders with high psychopathic tendencies and 18 matched controls during the performance of an aversive Pavlovian-to-instrumental transfer paradigm. This paradigm allowed us to assess the degree to which aversive Pavlovian cues affect instrumental action and associated neural signaling.ResultsPsychopathic tendency scores were associated with an attenuation of aversive Pavlovian inhibition of instrumental action. Moreover, exploratory analyses revealed an anomalous positive association between aversive inhibition of action and aversive inhibition of BOLD signal in the caudate nucleus of violent offenders with psychopathic tendencies. In addition, psychopathic tendency also correlated positively with amygdala reactivity during aversive versus neutral cues in Pavlovian training.ConclusionThese findings strengthen the hypothesis that psychopathic tendencies in violent offenders are related to abnormal impact of aversive processing on instrumental behavior. The neural effects raise the possibility that this reflects deficient transfer of aversive Pavlovian inhibitory biases onto neural systems that implement instrumental action, including the caudate nucleus.
Atypical metanephric adenoma: Shares similar histopathological features and molecular changes of metanephric adenoma and epithelial-predominant Wilms’ tumor
Authors: Yin Xiaoxue , Zhang Xingming , Pan Xiuyi , Tan Junya , Zheng Linmao , Zhou Qiao , Chen Ni 
Published: October 2022

BackgroundMetanephric adenomas (MAs) are rare, benign renal tumors. Wilms’ tumors (WTs) are malignant embryonic tumors that originated from nephrogenic blastemal cells. However, some tumors have similar morphology to both MA and epithelial-predominant WT, which makes differential diagnosis difficult. We aimed to analyze the morphological, immunophenotypic and molecular changes in overlapping cases to explore their attribution.Methods and resultsTwenty MAs, ten WTs, and nine cases with MA/WT overlapping histological features were studied. Twenty tumors demonstrated the typical morphological spectrum of MA with high cellularity and were composed of tightly packed small, uniform, round acini with a lower Ki67 index. Almost all MAs (94.7%, 18/19) were detected with BRAF V600E mutation. The ten WTs were epithelial-predominant WTs with glands, rosettes and glomerular structures, which also showed a higher Ki-67 index (up to 60%), invasive growth patterns, and a lack of BRAF mutation. However, the other nine overlapping cases showed two components: typical MA-like areas and epithelial WT-like areas. The cells of the WT-like areas were tubular, columnar and showed marked cytological atypia, with a Ki-67 proliferative index of up to 30%. The immunophenotype of these overlapping lesions was not significantly different from that of typical MA and they positively expressed WT1 and CD57. The BRAF V600E mutation was detected in both WT-like and MA-like areas in nine overlapping tumors. The follow-up data of 31 patients were analyzed, with a median follow-up time of 66 months (range, 8-45 months). Even though most patients with WT underwent radiotherapy or chemotherapy after surgery, two died, and one had liver metastasis. No MA or overlapping cases showed any evidence of recurrence or metastasis after surgery.ConclusionsThe molecular changes in tumors with overlapping morphological features were the same as those of typical MA; thus, we think that these tumors should be classified as MA and further called atypical MA. It is important to note that atypical MA is not a neglected subtype of MA. It possesses different histological morphology and a higher Ki-67 index but has the common imaging characteristics, immunophenotype and gene expression as typical MA, and patients usually have a good prognosis.
Nomogram development and validation to predict Ki-67 expression of hepatocellular carcinoma derived from Gd-EOB-DTPA-enhanced MRI combined with T1 mapping
Authors: Liu Ziwei , Yang Shaomin , Chen Xinjie , Luo Chun , Feng Jieying , Chen Haixiong , Ouyang Fusheng , Zhang Rong , Li Xiaohong , Liu Wei , Guo Baoliang , Hu Qiugen 
Published: October 2022

ObjectiveAs an important biomarker to reflect tumor cell proliferation and tumor aggressiveness, Ki-67 is closely related to the high early recurrence rate and poor prognosis, and pretreatment evaluation of Ki-67 expression possibly provides a more accurate prognosis assessment and more better treatment plan. We aimed to develop a nomogram based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) combined with T1 mapping to predict Ki-67 expression in hepatocellular carcinoma (HCC).MethodsThis two-center study retrospectively enrolled 148 consecutive patients who underwent preoperative Gd-EOB-DTPA-enhanced MRI T1 mapping and surgically confirmed HCC from July 2019 to December 2020. The correlation between quantitative parameters from T1 mapping, ADC, and Ki-67 was explored. Three cohorts were constructed: a training cohort (n = 73) and an internal validation cohort (n = 31) from Shunde Hospital of Southern Medical University, and an external validation cohort (n = 44) from the Sixth Affiliated Hospital, South China University of Technology. The clinical variables and MRI qualitative and quantitative parameters associational with Ki-67 expression were analyzed by univariate and multivariate logistic regression analyses. A nomogram was developed based on these associated with Ki-67 expression in the training cohort and validated in the internal and external validation cohorts.ResultsT1rt-Pre and T1rt-20min were strongly positively correlated with Ki-67 (r = 0.627, r = 0.607, P &lt; 0.001); the apparent diffusion coefficient value was moderately negatively correlated with Ki-67 (r = -0.401, P &lt; 0.001). Predictors of Ki-67 expression included in the nomogram were peritumoral enhancement, peritumoral hypointensity, T1rt-20min, and tumor margin, while arterial phase hyperenhancement (APHE) was not a significant predictor even included in the regression model. The nomograms achieved good concordance indices in predicting Ki-67 expression in the training and two validation cohorts (0.919, 0.925, 0.850), respectively.ConclusionsT1rt-Pre and T1rt-20min had a strong positive correlation with the Ki-67 expression in HCC, and Gd-EOB-DTPA enhanced MRI combined with T1 mapping-based nomogram effectively predicts high Ki-67 expression in HCC.
Pathologic response and safety to neoadjuvant PD-1 inhibitors and chemotherapy in resectable squamous non-small-cell Lung cancer
Authors: Shi Liang , Meng Qiyi , Tong Li , Li Hongxia , Dong Yujie , Su Chongyu , Liu Zhe 
Published: October 2022

BackgroundSeveral randomized studies have shown that the combination of programmed cell death 1 (PD-1) inhibitor and chemotherapy is efficacious as a treatment for advanced non-small-cell lung cancer (NSCLC). However, in the neoadjuvant setting, there is scarce evidence of the effectiveness and safety of the combinations in squamous NSCLC. We conducted a retrospective study to evaluate neoadjuvant PD-1 inhibitor plus chemotherapy in resectable squamous NSCLC.MethodsPatients from Beijing Chest Hospital, Capital Medical University, between October 2019 and October 2021, treated with PD-1 inhibitors and chemotherapy for resectable squamous NSCLC were retrospectively studied. The primary objectives were to assess the pathological tumor response and safety of neoadjuvant PD-1 inhibitors and chemotherapy.Results63 patients with resectable squamous NSCLC stage IIA-IIIB were included. Two to four cycles of PD-1 inhibitors (37 cases with camrelizumab, 11 cases with toripalimab, 8 cases with tislelizumab, and 7 cases with sintilimab) and chemotherapy were administered prior to surgery. 42 patients (66.7%) achieved a major pathologic response (MPR), including 25 (39.7%) with a pathologic complete response (pCR). Twenty-one patients (33.3%) experienced grade 3 neoadjuvant treatment-related adverse events (TRAEs), and no patient had grade 4 or 5 TRAE.ConclusionNeoadjuvant PD-1 inhibitors and chemotherapy are feasible therapies for resectable squamous NSCLC. It was associated with a 66.7% MPR rate, 39.7% pCR rate, and tolerable toxicity.
The expression of cuproptosis-related genes in hepatocellular carcinoma and their relationships with prognosis
Authors: Zhao Xueying , Chen Jin , Yin Shangqi , Shi Jingren , Zheng Mei , He Chaonan , Meng Huan , Han Ying , Han Jinyu , Guo Jingjing , Yuan Zhengrong , Wang Yajie 
Published: October 2022

BackgroundThe mechanism of cuproptosis has recently been reported in lipoylated proteins of the tricarboxylic acid (TCA) cycle. Besides, the role of copper was previously recognized in cancer progression. We evaluated the prognostic value of cuproptosis-related gene expression in hepatocellular carcinoma (HCC).MethodsRemarkable genes were selected both in differential expression analysis and Kaplan-Meier survival analysis from ninety-six cuproptosis-related genes using The Cancer Genome Atlas (TCGA) database. The relationships between clinical characteristics and gene expression were performed with Wilcoxon signed-rank test, Kruskal-Wallis test, and logistic regression. Clinicopathologic factors correlated with overall survival in HCCs conducting univariate and multivariate Cox regression analysis. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Human Protein Atlas (HPA) databases were utilized to verify the results. Furthermore, Gene Set Enrichment Analysis (GSEA) identified the potential key pathways that dominate cuproptosis in HCC.ResultsElevated ATP7A, SLC25A3, SCO2, COA6, TMEM199, ATP6AP1, LIPT1, DLAT, PDHA1, MTF1, ACP1, FDX2, NUBP2, CIAPIN1, ISCA2 and NDOR1 expression, as well as declined AOC1, FDX1, MT-CO1, and ACO1 expression were significantly emerged in HCC tumor tissues and were significantly associated with HCCs poor survival. The expressions of screened cuproptosis-related genes were prominently related to clinical features. GSEA analysis reported many key signaling pathways (such as natural killer cell mediated cytotoxicity, TCA cycle, glutathione metabolism, ATP-binding cassette (ABC) transporters, Notch signaling pathway, ErbB signaling pathway, and metabolism of xenobiotics by cytochrome p450) were differentially enriched in HCCs with varying degrees of cuproptosis-related genes expression.ConclusionsThe twenty cuproptosis-related genes might be utilized as new candidate prognostic biomarkers for HCC.