Giant Cell Tumor of the Frontal Bone: A Rare Case Report and Review of Literature.

Giant cell tumors (GCTs), typically benign, predominantly manifest in individuals aged 20-40, with the most common locations being the metaphysis or epiphysis of the femur or tibia. Infrequently, they may occur in the skull. Despite their benign nature, these tumors can exhibit aggressive behavior and have the potential to metastasize. In the case at hand, a 20-year-old female presented to the hospital with a progressively enlarging right frontal swelling over the preceding months. The patient reported intermittent headaches, alleviated by analgesics, and exhibited a normal neurological examination along with a Glasgow Coma Scale (GCS) score of 15 out of 15. Imaging revealed an expansive soft tissue mass in the right frontal bone involving both inner and outer tables. Surgical intervention was pursued through a right frontal incision followed by tumor excision. Histopathological examination of the specimen confirmed the presence of a GCT. The limited existing literature on this topic highlights the need for further research and insights into effective strategies. This case contributes to addressing this gap in knowledge, offering valuable information to enhance our understanding of the challenges associated with similar rare cases and improve patient outcomes.

Enhanced cluster detection and noise reduction for geospatial time series data of COVID-19.

Spatial-temporal analysis of the COVID-19 cases is critical to find its transmitting behaviour and to detect the possible emerging clusters. Poisson's prospective space-time analysis has been successfully implemented for cluster detection of geospatial time series data. However, its accuracy, number of clusters, and processing time are still a major problem for detecting small-sized clusters. The aim of this research is to improve the accuracy of cluster detection of COVID-19 at the county level in the U.S.A. by detecting small-sized clusters and reducing the noisy data. The proposed system consists of the Poisson prospective space-time analysis along with Enhanced cluster detection and noise reduction algorithm (ECDeNR) to improve the number of clusters and decrease the processing time. The results of accuracy, processing time, number of clusters, and relative risk are obtained by using different COVID-19 datasets in SaTScan. The proposed system increases the average number of clusters by 7 and the average relative risk by 9.19. Also, it provides a cluster detection accuracy of 91.35% against the current accuracy of 83.32%. It also gives a processing time of 5.69 minutes against the current processing time of 7.36 minutes on average. The proposed system focuses on improving the accuracy, number of clusters, and relative risk and reducing the processing time of the cluster detection by using ECDeNR algorithm. This study solves the issues of detecting the small-sized clusters at the early stage and enhances the overall cluster detection accuracy while decreasing the processing time.

Age-related loss of chromosome Y is associated with levels of sex hormone binding globulin and clonal hematopoiesis defined by TET2, TP53, and CBL mutations.

Mosaic loss of the Y-chromosome (LOY) in peripheral blood leukocytes is the most common somatic alteration in men and linked to wide range of malignant and nonmalignant conditions. LOY is associated with age, smoking, and constitutional genetics. Here, we aimed to assess the relationships between LOY, serum biomarkers, and clonal hematopoiesis (CH). LOY in U.K. Biobank was strongly associated with levels of sex hormone binding globulin (SHBG), a key regulator of testosterone bioavailability. Mendelian randomization suggested a causal effect of SHBG on LOY but there was no evidence for an effect of LOY on SHBG. In contrast, age-related CH defined by somatic driver mutations was not associated with SHBG but was associated with LOY at clonal fractions above 30%. TET2, TP53, and CBL mutations were enriched in LOY cases, but JAK2 V617F was depleted. Our findings thus identify independent relationships between LOY, sex hormone levels, and CH.

Clonal myelopoiesis promotes adverse outcomes in chronic kidney disease.

We sought to determine the relationship between age-related clonal hematopoiesis (CH) and chronic kidney disease (CKD). CH, defined as mosaic chromosome abnormalities (mCA) and/or driver mutations was identified in 5449 (2.9%) eligible UK Biobank participants (n = 190,487 median age = 58 years). CH was negatively associated with glomerular filtration rate estimated from cystatin-C (eGFR.cys; ß = -0.75, P = 2.37 × 10-4), but not with eGFR estimated from creatinine, and was specifically associated with CKD defined by eGFR.cys < 60 (OR = 1.02, P = 8.44 × 10-8). In participants without prevalent myeloid neoplasms, eGFR.cys was associated with myeloid mCA (n = 148, ß = -3.36, P = 0.01) and somatic driver mutations (n = 3241, ß = -1.08, P = 6.25 × 10-5) associated with myeloid neoplasia (myeloid CH), specifically mutations in CBL, TET2, JAK2, PPM1D and GNB1 but not DNMT3A or ASXL1. In participants with no history of cardiovascular disease or myeloid neoplasms, myeloid CH increased the risk of adverse outcomes in CKD (HR = 1.6, P = 0.002) compared to those without myeloid CH. Mendelian randomisation analysis provided suggestive evidence for a causal relationship between CH and CKD (P = 0.03). We conclude that CH, and specifically myeloid CH, is associated with CKD defined by eGFR.cys. Myeloid CH promotes adverse outcomes in CKD, highlighting the importance of the interaction between intrinsic and extrinsic factors to define the health risk associated with CH.

Genome-wide association study identifies novel susceptibility loci for KIT D816V positive mastocytosis.

Mastocytosis is a rare myeloid neoplasm characterized by uncontrolled expansion of mast cells, driven in >80% of affected individuals by acquisition of the KIT D816V mutation. To explore the hypothesis that inherited variation predisposes to mastocytosis, we performed a two-stage genome-wide association study, analyzing 1,035 individuals with KIT D816V positive disease and 17,960 healthy control individuals from five European populations. After quality control, we tested 592,007 SNPs at stage 1 and 75 SNPs at stage 2 for association by using logistic regression and performed a fixed effects meta-analysis to combine evidence across the two stages. From the meta-analysis, we identified three intergenic SNPs associated with mastocytosis that achieved genome-wide significance without heterogeneity between cohorts: rs4616402 (pmeta = 1.37 × 10-15, OR = 1.52), rs4662380 (pmeta = 2.11 × 10-12, OR = 1.46), and rs13077541 (pmeta = 2.10 × 10-9, OR = 1.33). Expression quantitative trait analyses demonstrated that rs4616402 is associated with the expression of CEBPA (peQTL = 2.3 × 10-14), a gene encoding a transcription factor known to play a critical role in myelopoiesis. The role of the other two SNPs is less clear: rs4662380 is associated with expression of the long non-coding RNA gene TEX41 (peQTL = 2.55 × 10-11), whereas rs13077541 is associated with the expression of TBL1XR1, which encodes transducin (ß)-like 1 X-linked receptor 1 (peQTL = 5.70 × 10-8). In individuals with available data and non-advanced disease, rs4616402 was associated with age at presentation (p = 0.009; beta = 4.41; n = 422). Additional focused analysis identified suggestive associations between mastocytosis and genetic variation at TERT, TPSAB1/TPSB2, and IL13. These findings demonstrate that multiple germline variants predispose to KIT D816V positive mastocytosis and provide novel avenues for functional investigation.

Clonal myelopoiesis in the UK Biobank cohort: ASXL1 mutations are strongly associated with smoking.

We sought to determine the significance of myeloid clonal hematopoiesis (CH) in the UK Biobank cohort (n = 502,524, median age = 58 years). Utilizing SNP array (n = 486,941) and whole exome sequencing data (n = 49,956), we identified 1166 participants with myeloid CH, defined by myeloid-associated mosaic chromosome abnormalities (mCA) and/or likely somatic driver mutations in DNMT3A, TET2, ASXL1, JAK2, SRSF2, or PPM1D. Myeloid CH increased by 1.1-fold per annum (myeloid mCA, P = 1.57 × 10-38; driver mutations, P = 5.89 × 10-47). Genome-wide association analysis identified two distinct signals within TERT that predisposed to myeloid CH, plus a weaker signal corresponding to the JAK2 46/1 haplotype. Specific subtypes of myeloid CH were associated with several blood features and clinical phenotypes, including TET2 mutations and chronic obstructive pulmonary disease. Smoking history was significantly associated with myeloid CH: 53% of myeloid CH cases were smokers compared to 44% of controls (P = 3.38 × 10-6), a difference principally due to current (OR = 1.10; P = 6.14 × 10-6) rather than past smoking (P = 0.08). Breakdown of CH by specific mutation type revealed that ASXL1 loss of function mutations were most strongly associated with current smoking status (OR = 1.07; P = 1.92 × 10-5), and the only abnormality associated with past smoking (OR = 1.04; P = 0.0026). We suggest that the inflammatory environment induced by smoking may promote the outgrowth of ASXL1-mutant clones.

Scleral thinning after transcleral diode laser cycloablation.

BACKGROUND AND OBJECTIVE: To highlight the occurrence of scleral thinning after transcleral diode laser cycloablation therapy. PATIENTS AND METHODS: A retrospective chart review was done of consecutive patients from the glaucoma and pediatric ophthalmology clinics of a tertiary eye care center in whom the presence of scleral thinning was noted after transcleral diode laser cycloablation therapy. RESULTS: Eleven eyes of 9 patients with various types of glaucoma (traumatic, congenital, juvenile, steroid induced, uveitic, and secondary angle closure) were found to have scleral thinning after undergoing transcleral diode laser cycloablation therapy for refractory glaucoma. Seven patients had undergone only 1 session before new scleral thinning was noted. Two patients had bilateral transcleral diode laser cycloablation therapy and subsequent bilateral thinning. CONCLUSIONS: Scleral thinning may occur after diode laser cycloablation therapy even with only 1 treatment session and intact sclera, and young patients may be more susceptible to thinning.