Prognostic significance of CRLF2 in patients with acute lymphoblastic leukemia: a meta-analysis and systematic review.

The association between cytokine receptor-like factor 2 (CRLF2) and clinical outcomes in acute lymphoblastic leukemia (ALL) has been a topic of ongoing debate, with divergent findings. This article intended to investigate the influence of CRLF2 alterations on ALL prognosis. Following the PRISMA 2020 guidelines, this meta-analysis was conducted. Hazard ratio (HR) values and confidence intervals (CIs) were the primary statistical measures used. Data heterogeneity was judged using the chi-square test and I2 statistic. Publication bias was appraised with funnel plots, Begg's test, and Egger's test. 16 studies with 6771 patients were finally screened out. CRLF2 over-expression (CRLF2 OE) was associated with poorer event-free survival (EFS) (HR = 1.70, 95% CI = 1.18-2.44, P = 0.004) and relapse-free survival (RFS) (HR = 1.70, 95% CI = 1.28-2.24, P = 0.000) in pediatric ALL. Patients with CRLF2-deregulation (CRLF2-d), also known as CRLF2 rearrangement, exhibited shorter overall survival (OS) (HR = 2.22, 95% CI = 1.49-3.32, P = 0.000), EFS (HR = 1.93, 95% CI = 1.43-2.60, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53-3.18, P = 0.000) compared to those without CRLF2-d. Subgroup analysis of multivariate HRs and corresponding CIs indicated that childhood with CRLF2 OE had a shorter RFS (HR = 1.70, 95% CI = 1.28-2.24, P = 0.006), and CRLF2-d was identified as an independent prognostic biomarker for OS (HR = 2.22, 95% CI = 1.49-3.32, P = 0.000), EFS (HR = 1.95, 95% CI = 1.44-2.64, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53-3.18, P = 0.000) in pediatric ALL patients. Both CRLF2 OE and CRLF2-d are associated with poor prognosis in ALL patients.

Association Between the XRCC1, GSTM1, and GSTT1 Polymorphisms in Model of Thyroid Cancer: A Meta-Analysis.

Thyroid cancer is the most common malignant tumor of the endocrine system, and its incidence is increasing worldwide each year. This study aimed to explore the association between XRCC1, GSTM1, and GSTT1 polymorphisms in the model of thyroid cancer. The experiment was conducted by searching PubMed, Embase, and Web of Science, with the last search performed in March 2022. A total of 12 studies were included in this meta-analysis, with sample sizes ranging from 211 to 1124. The proportion of XRCC1 polymorphisms (rs25489, GG) in thyroid cancer was slightly lower than that of the normal control group, but the difference was not statistically significant (Mean difference=1.13, 95% CI: 0.99-1.28, p=0.08). The proportion of XRCC1 polymorphisms (rs25489, GA) in thyroid cancer was significantly lower than that of the normal control group (Mean difference=1.32, 95% CI: 1.16-1.52, p<0.00001). The proportion of XRCC1 polymorphisms (rs25489, AA) in thyroid cancer was slightly lower than that of the normal control group, but again, the difference was not statistically significant (Mean difference=0.78, 95% CI: 0.61-1.01, p=0.06). Similarly, the proportion of XRCC1 polymorphisms (rs25487, GG) and (rs25487, GA) in thyroid cancer was lower than that of the normal control group, but the differences were not statistically significant (p=0.22 and p=0.49, respectively). In conclusion, this study found that the proportion of XRCC1 polymorphisms (rs25489, AA) in thyroid cancer was lower than that of the normal control group.

Construction of a prognosis model of head and neck squamous cell carcinoma pyroptosis and an analysis of immuno-phenotyping based on bioinformatics.

Background: Head and neck squamous cell carcinoma (HNSCC) is currently the sixth most common cancer worldwide, and its prevalence and recurrence rates are gradually increasing. To study the relationship between HNSCC and cell pyroptosis and provide new treatment options for HNSCC, a prognostic model of pyroptosis-related genes (PRGs) was established to predict the prognosis of patients with HNSCC, and an immune correlation analysis was performed. Methods: A total of 53 PRGs were selected. We comprehensively analyzed the role of these PRGs in HNSCC through multiple omics data-set integration. We then identified two different molecular subtypes and found that changes in multi-layer PRGs were associated with clinicopathological characteristics, prognosis, and tumor microenvironment cell-infiltration characteristics in patients. Next, prognostic models were generated for nine PRGs; that is, cytotoxic T lymphocyte antigen 4 (CTLA4), V-set and immunoglobulin domain containing 4 (VSIG4), heparin-binding-epidermal growth factor (HBEGF), aquaporin-1 (AQP1), sodium channel epithelial 1 subunit delta (SCNN1D), argininosuccinate synthase 1 (ASS1), family with sequence similarity 83 member (FAM83), cyclin dependent kinase inhibitor 2A (CDKN2A), and serine protease inhibitor Kazal 6 (SPINK6). Finally, a risk-score model was constructed, and the Kaplan-Meier method was used to evaluate overall survival. In addition, the immune environment and drug sensitivity were analyzed. Results: This study showed that pyroptosis is closely related to HNSCC. The scores generated by the risk markers based on the new nine PRGs were identified as independent risk factors for predicting HNSCC. The differentially expressed genes between the low- and high-risk groups were further found to be related to the tumor immune cells and pathways. In addition, the risk score was found to be significantly correlated with chemosensitivity. Conclusions: Our comprehensive analysis of PRGs revealed their potential role in the tumor immune microenvironment, clinicopathological characteristics, and prognosis. These findings may improve our understanding of pyroptosis in HNSCC and may provide new ideas for evaluating prognosis and developing more effective immunotherapy strategies.

Transient Fever: the Sole Treatment-Related Adverse Event associated with Mesenchymal Stromal Cells and Solid Clues from the Real World.

BACKGROUND: The number of trials investigating mesenchymal stromal cells (MSCs) soars within 3 years which urges a study analysing emerging MSC treatment-related adverse events. AIM: To assess the safety of MSC therapy and provide solid evidence for clinical translation of MSC. METHODS: A meta-analysis of randomized clinical trials (RCTs) published up to April 20th, 2023 was performed. Odds ratio (OR) and 95% confidential intervals (CIs) were used to display pooled results. RESULTS: 152 randomized clinical trials (RCTs) that incorporated 9228 individuals treated with MSCs from autologous or allogenic adipose tissue, bone marrow, Wharton's Jelly, and placenta tissue were included in the analysis. We discovered appropriate 21 MSC treatment-related adverse events (TRAEs), of which fever [OR, 1.61, 95% CI: 1.22-2.11, p<0.01] was the sole event that was closely associated with MSC therapy. MSCs also trended to lower the incidence rate of tachycardia [OR, 0.83, 95% CI: 0.64-1.09, p=0.14] and fatigue [OR, 0.18, 95% CI: 0.61-1.07, p=0.18]. A separate analysis of studies with long-term follow-up (more than 1 year) demonstrated the close relationship between MSCs and fever [OR, 1.75, 95% CI: 1.26-2.24, p<0.01]. The rest TRAEs did not associate themselves with MSC therapy. Dose-response was also conducted for fever, linearity was discovered between MSCs from allogeneic tissue and Wharton's Jelly and fever. CONCLUSION: To date, our results suggest that fever is the only AE closely associated with MSCs.

T cell-mediated tumor killing patterns in head and neck squamous cell carcinoma identify novel molecular subtypes, with prognosis and therapeutic implications.

As an important process in cancer immunotherapy, T cell-mediated tumor killing (TTK) enhances the immune response of patients. However, the role of TTK in Head and Neck Squamous Cell Carcinoma (HNSCC) patients still needs further exploration. Therefore, we comprehensively analyzed the gene expression information and clinical characteristics of 1063 HNSCC in five cohorts. Univariate regression, differential expression analysis, and gene mutation profiling were combined to identify the important genes regulating the sensitivity of tumor cells to T cell-mediated killing (GSTTK) in HNSCC. A total of 20 GSTTK were identified as important genes of HNSCC. Patients were divided into C1 and C2 subgroups (TTK patterns) and displayed significant prognostic differences. Patients with C2 subtype had dismal prognosis characteristic compared to C1 subtype in all validation cohorts. Patients with C1 subgroup exhibited robust immune profile and C1 subgroup patients were significantly enriched in metabolically relevant functions. Notably, the multi-omics analysis found that C1 subgroup have higher mutation burden and C2 subgroup patients had significantly higher copy number variation. Drug sensitivity analysis found that multiple first-line chemotherapeutic drugs were more sensitive in patients with subgroup C1. In conclusion, the establishment of GSTTK provides guidance and assistance to clinicians in the personalized management and treatment of HNSCC patients.

A pseudoproxy emulation of the PAGES 2k database using a hierarchy of proxy system models.

Paleoclimate reconstructions are now integral to climate assessments, yet the consequences of using different methodologies and proxy data require rigorous benchmarking. Pseudoproxy experiments (PPEs) provide a tractable and transparent test bed for evaluating climate reconstruction methods and their sensitivity to aspects of real-world proxy networks. Here we develop a dataset that leverages proxy system models (PSMs) for this purpose, which emulates the essential physical, chemical, biological, and geological processes that translate climate signals into proxy records, making these synthetic proxies more relevant to the real world. We apply a suite of PSMs to emulate the widely-used PAGES 2k dataset, including realistic spatiotemporal sampling and error structure. A hierarchical approach allows us to produce many variants of this base dataset, isolating the impact of sampling bias in time and space, representation error, sampling error, and other assumptions. Combining these various experiments produces a rich dataset ("pseudoPAGES2k") for many applications. As an illustration, we show how to conduct a PPE with this dataset based on emerging climate field reconstruction techniques.

A novel necroptosis-related LncRNA signature for prediction of prognosis and therapeutic responses of head and neck squamous cell carcinoma.

Background: Long non-coding RNAs (lncRNAs) play an essential role in the occurrence and prognosis of tumors, and it has great potential as biomarkers of tumors. However, the roles of Necroptosis-related lncRNA (NRLs) in Head and neck squamous cell carcinoma (HNSCC) remain elusive. Methods: We comprehensively analyzed the gene expression and clinical information of 964 HNSCC in four cohorts. LASSO regression was utilized to construct a necroptosis-related lncRNA prognosis signature (NLPS). We used univariate and multivariate regression to assess the independent prognostic value of NLPS. Based on the optimal cut-off, patients were divided into high- and low-risk groups. In addition, the immune profile, multi-omics alteration, and pharmacological landscape of NLPS were further revealed. Results: A total of 21 NRLs associated with survival were identified by univariate regression in four cohorts. We constructed and validated a best prognostic model (NLPS). Compared to the low-risk group, patients in the high group demonstrated a more dismal prognosis. After adjusting for clinical features by multivariate analysis, NLPS still displayed independent prognostic value. Additionally, further analysis found that patients in the low-risk group showed more abundant immune cell infiltration and immunotherapy response. In contrast, patients in the high-risk group were more sensitive to multiple chemotherapeutic agents. Conclusion: As a promising tool, the establishment of NLPS provides guidance and assistance in the clinical management and personalized treatment of HNSCC.

Predictors of early postoperative hypocalcemia in patients with secondary hyperparathyroidism undergoing total parathyroidectomy.

OBJECTIVE: To summarize the clinical features of secondary hyperparathyroidism (SHPT) in patients with chronic renal failure and to explore the predictive factors of postoperative hypocalcemia after total parathyroidectomy in these patients. METHODS: The clinical data of 87 patients admitted to Guangdong Electric Power Hospital from May 2013 to February 2020 were reviewed. All patients underwent total parathyroid resection and sternocleidomastoid microtransplantation. Age, sex, and the serum calcium, phosphorus, alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) concentrations were analyzed as predictive factors of postoperative hypocalcemia. RESULTS: Bone pain was the most common clinical manifestation in this study population, and all 87 patients experienced relief from their clinical symptoms after the surgical procedure. Age and the preoperative serum calcium, ALP, and iPTH concentrations were determined to be early predictive factors of postoperative hypocalcemia. CONCLUSIONS: Age and the preoperative calcium, ALP, and iPTH concentrations are independent risk factors for postoperative hypocalcemia in patients with SHPT and renal disease who undergo total parathyroidectomy with sternocleidomastoid microtransplantation. These factors can help identify high-risk patients who can be managed by a multidisciplinary team to improve graft survival and quality of life.