bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel signature combing cuproptosis- and ferroptosis-related genes in sepsis-induced cardiomyopathy
Authors: Song Juanjuan , Ren Kairui , Zhang Dexin , Lv Xinpeng , Sun Lin , Deng Ying , Zhu Huadong 
Published: March 2023

Objective: Cardiac dysfunction caused by sepsis, usually termed sepsis-induced cardiomyopathy (SIC), is one of the most serious complications of sepsis, and ferroptosis can play a key role in this disease. In this study, we identified key cuproptosis- and ferroptosis-related genes involved in SIC and further explored drug candidates for the treatment of SIC.Methods: The GSE79962 gene expression profile of SIC patients was downloaded from the Gene Expression Omnibus database (GEO). The data was used to identify differentially expressed genes (DEGs) and to perform weighted correlation network analysis (WGCNA). Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. Then, gene set enrichment analysis (GSEA) was applied to further analyze pathway regulation, with an adjusted p-value &lt;0.05 and a false discovery rate (FDR) &lt;0.25. Ferroptosis-related genes were obtained from the FerrDb V2 database, and cuproptosis-related genes were obtained from the literature. We constructed a novel signature (CRF) by combing cuproptosis-related genes with ferroptosis-related genes using the STRING website. The SIC hub genes were obtained by overlapping DEGs, WGCNA-based hub genes and CRF genes, and receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of hub genes. A transcription factor-microRNA-hub gene network was also constructed based on the miRnet database. Finally, potential therapeutic compounds for SIC were predicted based on the Drug Gene Interaction Database.Results: We identified 173 DEGs in SIC patients. Four hub modules and 411 hub genes were identified by WGCNA. A total of 144 genes were found in the CRF. Then, POR, SLC7A5 and STAT3 were identified as intersecting hub genes and their diagnostic values were confirmed with ROC curves. Drug screening identified 15 candidates for SIC treatment.Conclusion: We revealed that the cuproptosis- and ferroptosis-related genes, POR, SLC7A5 and STAT3, were significantly correlated with SIC and we also predicted therapeutic drugs for these targets. The findings from this study will make contributions to the development of treatments for SIC.
Dissected subgroups predict the risk of recurrence of stage II colorectal cancer and select rational treatment
Authors: Wang Fulong , Lu Shixun , Zhou Xin , Di Xiaotang , Wu Rujia , Chen Gong , Tian Sun 
Published: March 2023

BackgroundStage II colorectal cancer(CRC) patients after surgery alone have a five-year survival rate of ~60-80%; the incremental benefit of adjuvant chemotherapy is &lt;5%. Predicting risk of recurrence and selecting effective personalized adjuvant drugs for stage II CRC using formalin-fixed, paraffin-embedded(FFPE) samples is a major challenge.Methods1319 stage II CRC patients who enrolled in 2011-2019 at Sun Yat-sen University Cancer Center were screened. RNAseq data of FFPE tumor samples of 222 stage II microsatellite stable(MSS) CRC patients(recurrence (n=47), norecurrence (n=175), median follow-up=41 months) were used to develop a method TFunctionalProg for dissecting heterogeneous subgroups of recurrence and predicting risk of recurrence.ResultsTFunctionalProg showed significant predictive values in 222 stage II MSS CRCs. The TFunctionalProg low-risk group had significantly better recurrence free survival (validation set: HR=4.78, p-value=1e-4, low-risk group three-year recurrence free survival=92.6%, high-risk group three-year recurrence free survival=59.7%). TFunctionalProg dissected two subgroups of transition states of stage II MSS CRCs at a high risk of recurrence; each state displays distinct levels of hybrid epithelial-mesenchymal traits, CD8+ T cell suppression mechanisms and FOLFOX resistance. Based on mechanisms in two subgroups, TFunctionalProg proposed personalized rational adjuvant drug combinations of immunotherapy, chemotherapy and repurposed CNS drugs. TFunctionalProg provides different utilities from ctDNA-based prognostic biomarkers.ConclusionTFunctionalProg was validated using FFPE samples to predict the risk of recurrence and propose rational adjuvant drug combinations for stage II CRC.
Monoacylglycerol lipase regulates macrophage polarization and cancer progression in uveal melanoma and pan-cancer
Authors: Tan Yao , Pan Juan , Deng Zhenjun , Chen Tao , Xia Jinquan , Liu Ziling , Zou Chang , Qin Bo 
Published: March 2023

BackgroundAlthough lipid metabolism has been proven to play a key role in the development of cancer, its significance in uveal melanoma (UM) has not yet been elucidated in the available literature.MethodsTo identify the expression patterns of lipid metabolism in 80 UM patients from the TCGA database, 47 genes involved in lipid metabolism were analyzed. Consensus clustering revealed two distinct molecular groups. ESTIMATE, TIMER, and ssGSEA analyses were done to identify the differences between the two subgroups in tumor microenvironment (TME) and immune state. Using Cox regression and Lasso regression analysis, a risk model based on differentially expressed genes (DEGs) was developed. To validate the expression of monoacylglycerol lipase (MGLL) and immune infiltration in diverse malignancies, a pan-cancer cohort from the UCSC database was utilized. Next, a single-cell sequencing analysis on UM patients from the GEO data was used to characterize the lipid metabolism in TME and the role of MGLL in UM. Finally, in vitro investigations were utilized to study the involvement of MGLL in UM.ResultsTwo molecular subgroups of UM patients have considerably varied survival rates. The majority of DEGs between the two subgroups were associated with immune-related pathways. Low immune scores, high tumor purity, a low number of immune infiltrating cells, and a comparatively low immunological state were associated with a more favorable prognosis. An examination of GO and KEGG data demonstrated that the risk model based on genes involved with lipid metabolism can accurately predict survival in patients with UM. It has been demonstrated that MGLL, a crucial gene in this paradigm, promotes the proliferation, invasion, and migration of UM cells. In addition, we discovered that MGLL is strongly expressed in macrophages, specifically M2 macrophages, which may play a function in the M2 polarization of macrophages and M2 macrophage activation in cancer cells.ConclusionThis study demonstrates that the risk model based on lipid metabolism may be useful for predicting the prognosis of patients with UM. By promoting macrophage M2 polarization, MGLL contributes to the evolution of malignancy in UM, suggesting that it may be a therapeutic target for UM.
Spatial distribution and seasonal variation of fish larvae in the upper 200 m of the Philippine Sea
Authors: Fang Chen , Wang Xiaogu , Sun Dong , Zhai Hongchang , Zhang Dongsheng , Liao Guanghong , Wang Chunsheng 
Published: March 2023

The Philippine Sea, owing to its complicated circulation pattern and the presence of numerous seamounts, is considered to be a hotspot for biodiversity and an important fishing ground. However, to date, few studies on ichthyoplankton in the Philippine Sea have been conducted. During the summer, autumn, and winter of 2020–2021, a series of investigations were conducted to study the spatial and temporal structure of fish larvae in the Philippine Sea. A total of 65 samples were collected by vertical hauling from a depth of 200 m to the surface. A total of 882 fish larvae representing 81 distinct taxa, 49 genera, and 23 families were identified. A seasonal pattern was also observed based on the differences in abundance and dominant taxa. The abundance of fish larvae was 11.35 ± 12.46 ind./100 m3 (mean ± sd.) in summer, 5.83 ± 7.03 ind./100 m3 in autumn, and 2.57 ± 2.73 ind./100 m3 in winter. The dominant species were Vinciguerria nimbaria, Encrasicholina punctifer, and Cyclothone sp. in summer, V. nimbaria, and Ceratoscopelus warmingii in autumn, and Diaphus spp., D. garmani, and Sigmops sp. in winter. A significant latitudinal variation in fish larvae assemblages was found via cluster analysis, and two geographic groups were separated by the northern boundary of the North Equatorial Current. In addition, the fish larvae species diversity also showed a significant latitudinal gradient in autumn, which disappeared in summer. Canonical correspondence analysis indicated that the structure of fish larvae assemblages was affected by average temperature, salinity, and net primary productivity in the upper ocean and sea level anomaly. All dominant species were associated with specific niche environments. This study suggests that latitudinal zonation of fish larvae also occurs in the oligotrophic low latitude Pacific Ocean and is enhanced in autumn. These results provide multi-seasonal baseline data of fish larvae assemblage in the upper Philippine Sea, being an important reference for the planning of marine protected areas in the high seas.
Spatial distribution of CD3- and CD8-positive lymphocytes as pretest for POLE wild-type in molecular subgroups of endometrial carcinoma
Authors: Jungen Samuel H. , Noti Luca , Christe Lucine , Galvan Jose A. , Zlobec Inti , Müller Michael D. , Imboden Sara , Siegenthaler Franziska , Carlson Joseph W. , Pellinen Teijo , Heredia-Soto Victoria , Ruz-Caracuel Ignacio , Hardisson David , Redondo Andres , Mendiola Marta , Rau Tilman T. 
Published: March 2023

IntroductionOver the years, the molecular classification of endometrial carcinoma has evolved significantly. Both POLEmut and MMRdef cases share tumor biological similarities like high tumor mutational burden and induce strong lymphatic reactions. While therefore use case scenarios for pretesting with tumor-infiltrating lymphocytes to replace molecular analysis did not show promising results, such testing may be warranted in cases where an inverse prediction, such as that of POLEwt, is being considered. For that reason we used a spatial digital pathology method to quantitatively examine CD3+ and CD8+ immune infiltrates in comparison to conventional histopathological parameters, prognostics and as potential pretest before molecular analysis.MethodsWe applied a four-color multiplex immunofluorescence assay for pan-cytokeratin, CD3, CD8, and DAPI on 252 endometrial carcinomas as testing and compared it to further 213 cases as validation cohort from a similar multiplexing assay. We quantitatively assessed immune infiltrates in microscopic distances within the carcinoma, in a close distance of 50 microns, and in more distant areas.ResultsRegarding prognostics, high CD3+ and CD8+ densities in intra-tumoral and close subregions pointed toward a favorable outcome. However, TCGA subtyping outperforms prognostication of CD3 and CD8 based parameters. Different CD3+ and CD8+ densities were significantly associated with the TCGA subgroups, but not consistently for histopathological parameter. In the testing cohort, intra-tumoral densities of less than 50 intra-tumoral CD8+ cells/mm2 were the most suitable parameter to assume a POLEwt, irrespective of an MMRdef, NSMP or p53abn background. An application to the validation cohort corroborates these findings with an overall sensitivity of 95.5%.DiscussionMolecular confirmation of POLEmut cases remains the gold standard. Even if CD3+ and CD8+ cell densities appeared less prognostic than TCGA, low intra-tumoral CD8+ values predict a POLE wild-type at substantial percentage rates, but not vice versa. This inverse correlation might be useful to increase pretest probabilities in consecutive POLE testing. Molecular subtyping is currently not conducted in one-third of cases deemed low-risk based on conventional clinical and histopathological parameters. However, this percentage could potentially be increased to two-thirds by excluding sequencing of predicted POLE wild-type cases, which could be determined through precise quantification of intra-tumoral CD8+ cells.
A novel loop-mediated isothermal amplification-lateral flow dipstick method for Helicobacter pylori detection
Authors: Liu Wenwen , Lu Gang , Wang Yu , Chen Zhenghong , Gao Yunyun , Yin Zhipeng , Wu Yi , Lv Xiaoqian , Guo Pengbo , Zhao Yinghui 
Published: March 2023

IntroductionTo eradicate Helicobacter pylori (H. pylori) and reduce the risk of gastric cancer, a sensitive, specific, convenient, and simple detection method is needed. This study aimed to establish a novel loop-mediated isothermal amplification-lateral flow dipstick (LAMP-LFD) method for H. pylori detection.MethodsLAMP primer design software was used to design primers for the conserved sites of the H. pylori ureB gene. UreB-FIP-labeled biotin was used for LAMP amplification, and FAM-labeled probes were specifically hybridized with LAMP amplification products, which were then detected by LFD. In addition, a clinical study was conducted to assess LAMP-LFD in 20 fecal samples.ResultsThe results of the optimization indicated that H. pylori could be specifically detected by LFD without cross-reaction with other non-H. pylori bacteria when the LAMP was performed at 65°C for 60 min. The lower limit of the detection method was 102 copies/μL, which was 100 times the sensitivity of polymerase chain reaction (PCR). H. pylori-positive fecal samples were detected by LAMP-LFD in 13/20 patients.DiscussionIn conclusion, a new LAMP-LFD assay has been fully established and confirmed for H. pylori detection. The entire process can be completed in approximately 1.5 h, with the advantages of strong specificity, high sensitivity, and simple operation. This study provides a novel potential method for the detection of H. pylori in the clinical settings of primary hospitals and low-resource countries.
Predictive microbial feature analysis in patients with depression after acute ischemic stroke
Authors: Yao Shanshan , Xie Huijia , Wang Ya , Shen Nan , Chen Qionglei , Zhao Yiting , Gu Qilu , Zhang Junmei , Liu Jiaming , Sun Jing , Tong Qiuling 
Published: March 2023

IntroductionPost-stroke depression (PSD) is the most common emotional problem following a stroke, which requires early diagnosis to improve the prognosis. Gut microbiota plays important role in the pathological mechanisms of acute ischemic stroke and influences the outcome of patients. However, the relationship between PSD and gut microbiota remains unknown. Here, we explored whether the microbial signatures of gut microbiota in the patients with stroke could be an appropriate predictor of PSD.MethodsFecal samples were collected from 232 acute ischemic stroke patients and determined by 16s rRNA sequencing. All patients then received 17-Hamilton Depression Rating Scale (HAMD-17) assessment 3 months after discharge, and were further divided into PSD group and non-PSD group. We analyzed the differences of gut microbiota between these groups. To identify gut microbial biomarkers, we then established microbial biomarker model.ResultsOur results showed that the composition of gut microbiota in the PSD patients differed significantly from that in non-PSD patients. The genus Streptococcus, Akkermansia, and Barnesiella were significantly increased in PSD patients compared to non-PSD, while the genus Escherichia-Shigella, Butyricicoccus, and Holdemanella were significantly decreased. Correlation analyses displayed that Akkermansia, Barnesiella, and Pyramidobacter were positively correlated with HAMD score, while Holdemanella was negatively correlated with HAMD score. The optimal microbial markers were determined, and the combination achieved an area under the curve (AUC) value of 0.705 to distinguish PSD from non-PSD.ConclusionsOur findings suggest that PSD patients had distinct gut microbiota compared to non-PSD patients, and explore the potential of microbial markers, which might provide clinical decision-making in PSD.
Prefrontal EEG slowing, synchronization, and ERP peak latency in association with predementia stages of Alzheimer’s disease
Authors: Choi Jungmi , Ku Boncho , Doan Dieu Ni Thi , Park Junwoo , Cha Wonseok , Kim Jaeuk U. , Lee Kun Ho 
Published: March 2023

BackgroundEarly screening of elderly individuals who are at risk of dementia allows timely medical interventions to prevent disease progression. The portable and low-cost electroencephalography (EEG) technique has the potential to serve it.ObjectiveWe examined prefrontal EEG and event-related potential (ERP) variables in association with the predementia stages of Alzheimer’s disease (AD).MethodsOne hundred elderly individuals were recruited from the GARD cohort. The participants were classified into four groups according to their amyloid beta deposition (A+ or A−) and neurodegeneration status (N+ or N−): cognitively normal (CN; A−N−, n = 27), asymptomatic AD (aAD; A + N−, n = 15), mild cognitive impairment (MCI) with AD pathology (pAD; A+N+, n = 16), and MCI with non-AD pathology (MCI(−); A−N+, n = 42). Prefrontal resting-state eyes-closed EEG measurements were recorded for five minutes and auditory ERP measurements were recorded for 8 min. Three variables of median frequency (MDF), spectrum triangular index (STI), and positive-peak latency (PPL) were employed to reflect EEG slowing, temporal synchrony, and ERP latency, respectively.ResultsDecreasing prefrontal MDF and increasing PPL were observed in the MCI with AD pathology. Interestingly, after controlling for age, sex, and education, we found a significant negative association between MDF and the aAD and pAD stages with an odds ratio (OR) of 0.58. Similarly, PPL exhibited a significant positive association with these AD stages with an OR of 2.36. Additionally, compared with the MCI(-) group, significant negative associations were demonstrated by the aAD group with STI and those in the pAD group with MDF with ORs of 0.30 and 0.42, respectively.ConclusionSlow intrinsic EEG oscillation is associated with MCI due to AD, and a delayed ERP peak latency is likely associated with general cognitive impairment. MCI individuals without AD pathology exhibited better cortical temporal synchronization and faster EEG oscillations than those with aAD or pAD.SignificanceThe EEG/ERP variables obtained from prefrontal EEG techniques are associated with early cognitive impairment due to AD and non-AD pathology. This result suggests that prefrontal EEG/ERP metrics may serve as useful indicators to screen elderly individuals’ early stages on the AD continuum as well as overall cognitive impairment.
Deep brain stimulation in posterior subthalamic area for Holmes tremor: Case reports with review of the literature
Authors: Kamo Hikaru , Oyama Genko , Ito Masanobu , Iwamuro Hirokazu , Umemura Atsushi , Hattori Nobutaka 
Published: March 2023

BackgroundHolmes tremor (HT) is a refractory tremor associated with cortico-basal ganglia loops and cerebellothalamic tract abnormalities. Various drug treatments have been attempted; however, no treatment method has yet been established. Historically, thalamic deep brain stimulation (DBS) has been performed in medically refractory cases. Recently, the posterior subthalamic area (PSA) has been used for HT. Here, we report cases of HT and review the effectiveness and safety of PSA-DBS for HT.CasesWe conducted a retrospective chart review of two patients with HT who underwent PSA-DBS. Improvement in tremors was observed 1 year after surgery without apparent complications.Literature reviewWe identified 12 patients who underwent PSA-DBS for HT, including our cases. In six patients, PSA was targeted alone; for the rest, the ventralis intermediate nucleus (Vim) of the thalamus and PSA were simultaneously targeted. The Fahn–Tolosa–Marin Tremor Rating Scale improvement rates were 56.8% (range, 33.9–82.1%; n = 6) and 77.8% (range, 42.6–100%; n = 5) for the PSA-DBS and PSA+Vim-DBS, respectively.ConclusionReasonable improvements in HT were observed after PSA-DBS. PSA might be an appropriate target for improving the symptoms of HT. Long-term observations, accumulation of cases, and randomized studies are required in future.
Dried fruit intake causally protects against low back pain: A Mendelian randomization study
Authors: Huang Jian , Xie Zheng-Fu 
Published: March 2023

BackgroundLow back pain is the leading cause of years lived with disability worldwide. The aim of this study was to evaluate whether dried fruit intake causally protects against low back pain using two-sample Mendelian randomization (MR).MethodsWe obtained summary-level data for dried fruit intake (N = 421,764) from the IEU Open GWAS Project. Forty-one independent genetic variants proxied dried fruit intake. The corresponding data for low back pain were derived from the FinnGen project (13,178 cases and 164,682 controls; discovery data) and the Neale lab (5,423 cases and 355,771 controls; replication data). We conducted univariable and multivariable MR analyses.ResultsIn the univariable MR analysis, the inverse variance weighted estimate showed that greater dried fruit intake was associated with decreased risk of low back pain [odds ratio (OR) = 0.435, 95% confidence interval (CI): 0.287–0.659, P = 8.657 × 10−5]. Sensitivity analyses using the MR-Egger (OR = 0.078, 95% CI: 0.013–0.479, P = 0.009), maximum likelihood (OR = 0.433, 95% CI: 0.295–0.635, P = 1.801 × 10−5), weighted median (OR = 0.561, 95% CI: 0.325–0.967, P = 0.038) and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) (OR = 0.454, 95% CI: 0.302–0.683, P = 4.535 × 10−4) methods showed consistent results. No evidence of directional pleiotropy was identified according to the Egger intercept (intercept P-value = 0.065) or applying the MR-PRESSO method (global test P-value = 0.164). The replication analysis yielded similar results. The multivariable MR revealed that the inverse association between dried fruit intake and low back pain was consistent after adjustment for fresh fruit intake, body mass index, current tobacco smoking, alcohol intake frequency, total body bone mineral density, serum 25-hydroxyvitamin D levels, and vigorous physical activity.ConclusionThis MR study provides evidence to support that dried fruit intake causally protects against low back pain.