bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factors-related molecular subtypes and risk prognostic model: exploring the immunogenicity landscape and potential drug targets in hepatocellular carcinoma
Authors: Wang Meixia , Guo Hanyao , Zhang Bo , Shang Yanan , Zhang Sidi , Liu Xiaoyu , Cao Pengxiu , Fan Yumei , Tan Ke 
Published: January 2024

Abstract
Background
Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, with a high mortality rate and poor prognosis. Mutated or dysregulated transcription factors (TFs) are significantly associated with carcinogenesis. The aim of this study was to develop a TF-related prognostic risk model to predict the prognosis and guide the treatment of HCC patients.

Methods
RNA sequencing data were obtained from the TCGA database. The ICGC and GEO databases were used as validation datasets. The consensus clustering algorithm was used to classify the molecular subtypes of TFs. Kaplan‒Meier survival analysis and receiver operating characteristic (ROC) analysis were applied to evaluate the prognostic value of the model. The immunogenic landscape differences of molecular subtypes were evaluated by the TIMER and xCell algorithms. Autodock analysis was used to predict possible binding sites of trametinib to TFs. RT‒PCR was used to verify the effect of trametinib on the expression of core TFs.

Results
According to the differential expression of TFs, HCC samples were divided into two clusters (C1 and C2). The survival time, signaling pathways, abundance of immune cell infiltration and responses to chemotherapy and immunotherapy were significantly different between C1 and C2. Nine TFs with potential prognostic value, including HMGB2, ESR1, HMGA1, MYBL2, TCF19, E2F1, FOXM1, CENPA and ZIC2, were identified by Cox regression analysis. HCC patients in the high-risk group had a poor prognosis compared with those in the low-risk group (p < 0.001). Moreover, the area under the ROC curve (AUC) values of the 1-year, 2-year and 3-year survival rates were 0.792, 0.71 and 0.695, respectively. The risk model was validated in the ICGC database. Notably, trametinib sensitivity was highly correlated with the expression of core TFs, and molecular docking predicted the possible binding sites of trametinib with these TFs. More importantly, the expression of core TFs was downregulated under trametinib treatment.

Conclusions
A prognostic signature with 9 TFs performed well in predicting the survival rate and chemotherapy/immunotherapy effect of HCC patients. Trimetinib has potential application value in HCC by targeting TFs.
Intragastric free cancer cells may be attached to automatic staplers during anastomosis in patients with gastric cancer
Authors: Ohki Atsuko , Takagi Taisuke , Kojima Yohei , Tsurumi Masanao , Hashimoto Yoshikazu , Takeuchi Hirohisa , Kamma Hiroshi , Sakamoto Yoshihiro , Sunami Eiji , Abe Nobutsugu 
Published: January 2024

Abstract
Background
Automatic staplers are often used to reconstruct the digestive tract during surgeries for gastric cancer. Intragastric free cancer cells adhering to automatic staplers may come in contact with the laparoscopic port area and progress to port site recurrence. This study aimed to investigate the presence/absence of cancer cells adhering to automatic staplers during gastric cancer surgery using cytological examinations. We further determined the positive predictive clinicopathological factors and clinical implications of free cancer cells attached to automatic staplers.

Methods
This study included 101 patients who underwent distal gastrectomy for gastric cancer. Automatic staplers used for anastomosis in gastric cancer surgeries were shaken in 150 ml of saline solution to collect the attached cells. Papanicolaou stains were performed. We tested the correlation between cancer-cell positivity and clinicopathological factors to identify risk factors arising from the presence of attached cancer cells to the staplers.

Results
Based on the cytology, cancer cells were detected in 7 of 101 (6.9%) stapler washing fluid samples. Univariate analysis revealed that circular staplers, type 1 tumors, and positive lymph nodes were significantly associated with higher detection of free cancer cells adhering to staplers. No significant differences in other factors were detected. Of the seven cases with positive cytology, one developed anastomotic recurrence.

Conclusions
Exfoliated cancer cells adhered to the automatic staplers used for anastomoses in 6.9% of the staplers used for distal gastrectomies in patients with gastric cancer. Staplers used for gastric cancer surgeries should be handled carefully.
Risk factors for peripherally inserted central catheter-related venous thrombosis in adult patients with cancer
Authors: Wang Pinghu , He Lianxiang , Yuan Qiong , Lu Juan , Ji Qingqiong , Peng An , Liu Wanli 
Published: January 2024

Abstract
Purpose
The purpose of this study was to understand and analyze the risk factors of peripherally inserted central catheter (PICC)-related venous thrombosis in adult patients with cancer.

Methods
This observational cohort study included adult patients with cancer who underwent color Doppler ultrasound at the Xiangya Hospital of Central South University, Hunan Provincial Maternal and Child Healthcare Hospital, and Xiangya Changde Hospital, Hunan Province, from January 1, 2017 to December 31, 2021. Univariate and multivariate logistic regression analyses were performed to determine the risk factors of PICC-related venous thrombosis.

Results
After risk adjustment, multivariate logistic regression analysis revealed statistically significant associations between PICC-related venous thrombosis and age > 65 years old (OR: 1.791, CI: 1.343–2.389), male sex (OR: 1.398, CI: 1.057–1.849), white blood cell count > 9.5 × 109 /L (OR: 1.422, CI: 1.041–1.942), APTT < 25 s (OR: 2.006, CI: 1.431–2.811), gastrointestinal tumor (OR: 2.191, CI: 1.406–3.414), infection (OR:7.619, CI: 5.783–10.037), the use of cisplatin (OR: 2.374, CI: 1.714–3.214), vincristine (OR: 2.329, CI: 1.447–3.749), the use of polyurethane (OR: 2.449, CI: 1.863–3.219) and open-ended catheters (OR:1.660, CI: 1.131–2.439), keeping time of the catheter (days) (OR: 1.003, CI: 1.001–1.005) were associated with PICC-related venous thrombosis.

Conclusion
We identified that the presence of age > 65 years old, male sex, white blood cell count > 9.5 × 109 /L, APTT < 25 s, gastrointestinal tumor, infection, the use of cisplatin and vincristine, the use of polyurethane, open-ended catheters and keeping time of the catheter (days), were associated with PICC-related venous thrombosis.
A primary pulmonary artery sarcoma masquerading pulmonary embolism: a case report and literature review
Authors: Liu Zhiyue , Fan Lili , Liang Shichu , Wu Zhong , Huang He 
Published: January 2024

Abstract
Background
Primary pulmonary artery sarcoma (PAS) is an extremely rare malignant tumor with a poor prognosis. The clinical manifestations of PAS are diverse, including dyspnea, chest pain, cough, and hemoptysis. The poor prognosis is often due to delayed diagnosis caused by similarity in imaging findings with pulmonary thromboembolism (PTE). These cues of diagnosis include the “wall eclipsing sign”, lobulated bulging margins, gadolinium enhancement during MRI imaging, and FDG uptake during PET/CT imaging. However, there are still many misdiagnoses.

Case presentation
This article reports a woman of reproductive age presenting with a pulmonary artery mass. The computed tomographic pulmonary angiography and positron emission tomography/computed tomography did not show obvious signs of pulmonary artery sarcoma, however, contrast-enhanced echocardiography showed moderate perfusion, which helped differentiate between pulmonary artery sarcoma and pulmonary artery thrombosis, leading to timely surgical treatment.

Conclusions
PAS is a rare form of cancer that can occasionally be visually similar to PTE on radiographic images. Early diagnosis of PAS is of vital importance to the prognosis of the patients. There are several visual cues that can help differentiate between the two conditions. Additionally, contrast-enhanced echocardiography provides additional information on tumor perfusion, offering another effective approach for a prompt and accurate diagnosis.
Risk factors for carotid plaque formation in type 2 diabetes mellitus
Authors: Chen Jin , Li Wenwen , Cao Jingzhu , Lu Yuhan , Wang Chaoqun , Lu Jin 
Published: January 2024

Abstract
Object
Patients with type 2 diabetes mellitus (T2DM) are at higher risk of developing atherosclerosis. Previous studies have analyzed the factors associated with diabetic macrovascular disease, although whether these factors are applicable to T2DM patients with carotid atherosclerosis remains unclear. Therefore, the aim of this study was to investigate the risk factors for the formation of carotid atherosclerotic plaque in hospitalized T2DM patients and to provide a theoretical basis for early prevention and treatment of carotid atherosclerosis in these patients.

Methods
A total of 949 patients with T2DM were included in the study. Carotid ultrasound identified 531 patients with carotid atherosclerotic plaque. The waist-to-hip ratio (WHR), blood glucose, liver and kidney function, blood lipid profile, islet function, and other indicators were measured at the same time to identify the risk factors and predictive significance of T2DM carotid plaque.

Results
The proportions of men, diabetes nephropathy (DN) and hypertension in T2DM patients with carotid plaque are higher than those without carotid plaque(P < 0.05). Age, duration of diabetes, WHR, Postprandial glucose (PPG), lipoprotein (a) [Lip (a)], carcinoembryonic antigen(CEA) and estimated glomerular filtration rate (eGFR) in T2DM patients with carotid plaque were higher than those without plaque (P < 0.05). Age, WHR, duration of diabetes, hypertension, males, and Lip (a) were independent risk factors for T2DM patients with carotid plaque. Age, WHR, duration of diabetes, and Lip (a) had a higher AUC to predict T2DM with carotid artery plaque (AUC: 0.750, 0.640, 0.678, 0.552 respectively; P all < 0.001). After constructing the logit (P) value of the above risk factors, the area under the ROC curve was 0.816 (0.789–0.842, P < 0.001).

Conclusion
Age, WHR, duration of diabetes, hypertension, males, and Lip (a) levels are the main risk factors for the formation of carotid plaque in T2DM patients. Combining the above risk factors provides a better prediction of carotid plaque formation in T2DM.
Identification of female-enriched and disease-associated microglia (FDAMic) contributes to sexual dimorphism in late-onset Alzheimer’s disease
Authors: Wu Deng , Bi Xiaoman , Chow Kim Hei-Man 
Published: January 2024

AbstractBackgroundLate-onset Alzheimer’s disease (LOAD) is the most common form of dementia; it disproportionally affects women in terms of both incidence rates and severity of progression. The cellular and molecular mechanisms underlying this clinical phenomenon remain elusive and ill-defined.MethodsIn-depth analyses were performed with multiple human LOAD single-nucleus transcriptome datasets to thoroughly characterize cell populations in the cerebral cortex. ROSMAP bulk human brain tissue transcriptome and DNA methylome datasets were also included for validation. Detailed assessments of microglial cell subpopulations and their relevance to sex-biased changes at the tissue level were performed. Clinical trait associations, cell evolutionary trajectories, and transcription regulon analyses were conducted.ResultsThe relative numbers of functionally defective microglia were aberrantly increased uniquely among affected females. Substratification of the microglia into different subtypes according to their transcriptomic signatures identified a group of female-enriched and disease-associated microglia (FDAMic), the numbers of which were positively associated with disease severity. Phenotypically, these cells exhibit transcriptomic signatures that support active proliferation, MHC class II autoantigen presentation and amyloid-β binding, but they are also likely defective in phagocytosis. FDAMic are likely evolved from female activated response microglia (ARMic) with anAPOE4background and compromised estrogen receptor (ER) signaling that is deemed to be active among most subtypes of microglia.ConclusionThis study offered important insights at both the cellular and molecular levels into how ER signaling affects microglial heterogeneity and function. FDAMic are associated with more advanced pathologies and severe trends of cognitive decline. Their emergence could, at least in part, explain the phenomenon of greater penetrance of theAPOE4genotype found in females. The biases of FDAMic emergence toward female sex andAPOE4 status may also explain why hormone replacement therapy is more effective inAPOE4carriers. The pathologic nature of FDAMic suggests that selective modulations of these cells may help to regain brain neuroimmune homeostasis, serving as a new target for future drug development.
Gut microbiota, circulating cytokines and dementia: a Mendelian randomization study
Authors: Ji Dong , Chen Wen-Zhu , Zhang Lei , Zhang Zhi-Hua , Chen Li-Jian 
Published: January 2024

AbstractBackgroundSome studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear.MethodsGut microbiota, cytokines, and five dementia types, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson’s disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia.ResultsThere were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors.ConclusionsGut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.
Peripheral blood amyloid-β involved in the pathogenesis of Alzheimer’s disease via impacting on peripheral innate immune cells
Authors: Shi Mingchao , Chu Fengna , Zhu Feiqi , Zhu Jie 
Published: January 2024

AbstractA key pathological factor of Alzheimer’s disease (AD), the most prevalent form of age-related dementia in the world, is excessive β-amyloid protein (Aβ) in extracellular aggregation in the brain. And in the peripheral blood, a large amount of Aβ is derived from platelets. So far, the causality between the levels of peripheral blood Aβ and its aggregation in the brain, particularly the role of the peripheral blood Aβ in the pathology of AD, is still unclear. And the relation between the peripheral blood Aβ and tau tangles of brain, another crucial pathologic factor contributing to the pathogenesis of AD, is also ambiguous. More recently, the anti-Aβ monoclonal antibodies are approved for treatment of AD patients through declining the peripheral blood Aβ mechanism of action to enhance plasma and central nervous system (CNS) Aβ clearance, leading to a decrease Aβ burden in brain and improving cognitive function, which clearly indicates that the levels of the peripheral blood Aβ impacted on the Aβ burden in brain and involved in the pathogenesis of AD. In addition, the role of peripheral innate immune cells in AD remains mostly unknown and the results obtained were controversial. In the present review, we summarize recent studies on the roles of peripheral blood Aβ and the peripheral innate immune cells in the pathogenesis of AD. Finally, based on the published data and our own work, we believe that peripheral blood Aβ plays an important role in the development and progression of AD by impacting on the peripheral innate immune cells.
Characterization of an imported HIV-1 A1/A7/G recombinant in China
Authors: Li Qing-Hai , Zhang Yun-Qi , Li En-Long , Guo Qi , Chen Xiao-Hong , Wang Fu-Xiang , Wang Jia-Ye 
Published: January 2024

AbstractBackgroundInternational migration has accelerated the HIV-1 spread across national borders, gradually reducing the restrictions on the geographical distribution of HIV-1 subtypes. Subtypes A and G are globally recognized as the third and sixth most dominant HIV-1 genotypes, mainly prevalent in Africa, but rarely detected in China. Here we reported an imported HIV-1 recombinant which was composed of sub-subtypes A1 and A7 of subtype A and subtype G genes in a Chinese female. This virus was the first HIV-1 recombinant including A7 genes reported in the world.Case presentationThe near full-length genome (NFLG) was obtained from the plasma sample of the female in an HIV-1 molecular epidemiological survey with 853 participants in China. Phylogenetic analyses showed that this NFLG sequence contains three A7 segments, four G segments and one A1 segment with seven breakpoints, and all these segments were closely related to HIV-1 references circulating in Africa. The evidence from epidemiological investigation indicated that this female participant had a more-than-two-years heterosexual contact history with a fixed partner from Nigeria, a country in west Africa, which further supported the results of phylogenetic analyses. By the Bayesian phylogenetic analyses, the times of most recent common ancestors (tMRCA) of the partialpolgene (nt2308-3284, A7 region) and full-lengthvpr-vpuplus partialenvgene (nt5534-6858, G region) were estimated around 1989 and 1984, respectively.ConclusionsIn this study, by using the NFLG sequencing, we identified an imported HIV-1 A1/A7/G recombinant which was estimated to originate around 1980s in Africa and introduced into China with international migration. This study highlighted the complexity of the global HIV-1 epidemic, the necessity of using genome sequences to determine HIV-1 genotypes and the importance of real-time monitoring of HIV-1 infection among international migrants and travelers.
From beer to breadboards: yeast as a force for biological innovation
Authors: Gaikani Hamid Kian , Stolar Monika , Kriti Divya , Nislow Corey , Giaever Guri 
Published: January 2024

AbstractThe history of yeast Saccharomyces cerevisiae, aka brewer’s or baker’s yeast, is intertwined with our own. Initially domesticated 8,000 years ago to provide sustenance to our ancestors, for the past 150 years, yeast has served as a model research subject and a platform for technology. In this review, we highlight many ways in which yeast has served to catalyze the fields of functional genomics, genome editing, gene–environment interaction investigation, proteomics, and bioinformatics—emphasizing how yeast has served as a catalyst for innovation. Several possible futures for this model organism in synthetic biology, drug personalization, and multi-omics research are also presented.
Comparison of T-cell receptor diversity of people with myalgic encephalomyelitis versus controls
Authors: Dibble Joshua J , Ferneyhough Ben , Roddis Matthew , Millington Sam , Fischer Michael D , Parkinson Nick J , Ponting Chris P 
Published: January 2024

Abstract
Objective
Myalgic Encephalomyelitis (ME; sometimes referred to as Chronic Fatigue Syndrome) is a chronic disease without laboratory test, detailed aetiological understanding or effective therapy. Its symptoms are diverse, but it is distinguished from other fatiguing illnesses by the experience of post-exertional malaise, the worsening of symptoms even after minor physical or mental exertion. Its frequent onset after infection suggests autoimmune involvement or that it arises from abnormal T-cell activation.

Results
To test this hypothesis, we sequenced the genomic loci of α/δ, β and γ T-cell receptors (TCR) from 40 human blood samples from each of four groups: severely affected people with ME; mildly or moderately affected people with ME; people diagnosed with Multiple Sclerosis, as disease controls; and, healthy controls. Seeking to automatically classify these individuals’ samples by their TCR repertoires, we applied P-SVM, a machine learning method. However, despite working well on a simulated data set, this approach did not allow statistically significant partitioning of samples into the four subgroups. Our findings do not support the hypothesis that blood samples from people with ME frequently contain altered T-cell receptor diversity.
The impact of SLC10A3 on prognosis and immune microenvironment in colorectal adenocarcinoma
Authors: Wang Bangting , Fan Wentao , Tao Yuwen , Zhang Shijie , Wang Jiankun , Fan Zhining , Liu Li , Wang Yan 
Published: January 2024

Abstract
Background
SLC10A3, a gene upregulated in pan-cancer, lacks full understanding regarding its prognostic implications and association with immune infiltration in colorectal cancer (CRC). This study comprehensively analyzed SLC10A3 in CRC, evaluating its prognostic significance and influence on the tumor's immune microenvironment.

Methods
Transcriptomic data from TCGA were obtained to compare SLC10A3 expression in both colorectal cancer (CRC) and normal tissues. Prognostic value was assessed for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). DNA methylation patterns of SLC10A3 and correlation with DNA mismatch repair (MMR) were explored. Genetic alterations in SLC10A3 were scrutinized. The study also delved into the influence of SLC10A3 on the immune microenvironment of CRC, including immune cell infiltration and chemokines. Involvement of cancer-associated fibroblasts (CAFs) was explored. Methylation status of specific CpG islands in the SLC10A3 gene correlated with CRC patient prognosis. CRC tissue microarray was performed to verify the expression of SLC10A3 and its relationship with prognosis.

Results
The research revealed that SLC10A3 is significantly upregulated in CRC and holds promise as a potential diagnostic marker. Elevated SLC10A3 expression was linked to poorer OS, DSS, and PFI. Methylation patterns of SLC10A3 displayed prognostic relevance, and genetic alterations in the gene were identified. SLC10A3 was shown to impact the immune microenvironment, with significant correlations observed between its expression and various immune cell types, chemokines, and markers associated with CAFs. Furthermore, an inverse relationship between SLC10A3 and MMR molecules was established. Methylation status of specific CpG islands within the SLC10A3 gene was associated with CRC patient prognosis. Tissue microarray showed that SLC10A3 was highly expressed in CRC and significantly correlated with poor prognosis.

Conclusion
The study underscores the importance of elevated SLC10A3 in CRC, associating it with decreased survival and immune infiltration, proposing it as a diagnostic biomarker and appealing immunotherapy target, given its significant overexpression and influence on the immune microenvironment and prognosis through methylation patterns.

Graphical Abstract