Rising mortality due to cancer has led to the development and identification of newer targets and molecules to cure the disease. Telomerase is one of the attractive targets for design of many chemotherapeutic drugs. This research highlights the designing of novel telomerase inhibitors using ligand-based (3D-QSAR) and structure-based (molecular docking and molecular dynamics simulation) approaches. For the development of the 3D-QSAR model, 37 synthetic molecules reported earlier as telomerase inhibitors were selected from diversified literature. Three different alignment methods were explored; among them, distill alignment was found to be the best method with good statistical results and was used for the generation of QSAR model. Statistically significant CoMSIA model with a correlation coefficient (r2ncv) value of 0.974, leave one out (q2) value of 0.662 and predicted correlation coefficient (r2pred) value of 0.560 was used for the analysis of QSAR. For the MDS study, A-chain of telomerase was stabilised for 50 ns with respect to 1-atm pressure, with an average temperature of 299.98 k and with potential energy of 1,145,336 kJ/m converged in 997 steps. Furthermore, the behaviour study of variants towards the target revealed that active variable gave better affinity without affecting amino acid sequences and dimensions of protein which was accomplished through RMSD, RMSF and Rg analysis. Results of molecular docking study supported the outcomes of QSAR contour maps as ligand showed similar interactions with surrounded amino acids which were identified in contour map analysis. The results of the comprehensive study might be proved valuable for the development of potent telomerase inhibitors.The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensu and (3) “suspicious for,” or “squamous cell carcinoma.” Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.Otosclerosis is a pagetoid proliferation of bone remodeling, vascular proliferation, bone resorption and new bone formation in the tympanic region of the temporal bone. The resulting anklyosis of the stapes footplate as it articulates with the oval window is the most common cause of conductive hearing loss in young to middle aged, predominantly Caucasian individuals. The characteristic histologic features have been well documented by autopsy studies of the temporal bone. Although stapedectomy is the surgical treatment for otosclerosis, the stapes specimen may be submitted for gross examination only or not examined at all. A retrospective study of 73 stapedectomy specimens (2008-2019) not including the stapes footplate. Clinical features from the electronic medical record as well as standard histologic sections from surgical specimens were reviewed. FHT1015 Neither the stapedal head nor crura showed histologic features of otosclerosis. There was mild osteoarthritis affecting the head, possibly as a consequence of persistent ossicular vibration superimposed on the ankylosed rigidity. The most common changes were surface fissuring (65%), cartilaginous erosion (49%) and irregularity of the osteochondral interface (51%). An occasional osteophyte (8%) was observed. The ear ossicles, embryologically analogous to long bones of the extremities, develop via endochondral ossification and exhibit articular surfaces of hyaline cartilage. The present observations suggest that a consequence of otosclerotic ankylosis is osteoarthritis of the stapedal head. In this study, the histological features could not be correlated with the severity of hearing loss or duration of clinical disease.Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) play vital roles in the tumorigenesis of esophageal squamous cell carcinoma (ESCC). Nevertheless, the mechanism and regulatory network associated with this process remain largely unknown. In this study, we performed a comprehensive analysis of the expression of mRNAs, lncRNAs, and circRNAs by RNA-seq. A total of 3265 mRNAs, 1084 lncRNAs, and 38 circRNAs were found to be differentially expressed. Among these, 269 mRNAs were found to encode transcription factors (TFs). Functional enrichment analysis indicated that the dysregulated TFs are associated with the Hedgehog, Jak-STAT, TGF-beta, and MAPK signaling pathways. Furthermore, we constructed co-expression networks to screen the core lncRNAs and circRNAs involved in the regulation of transcription factors in these four pathways. Finally, we constructed a competing endogenous RNA (ceRNA) network of ESCC based on the abovementioned pathways. Our findings provide important insight into the role of lncRNAs and circRNAs in ESCC; the differentially expressed lncRNAs and circRNAs may represent potential targets for ESCC diagnosis and therapy.According to the Construction-Integration model (Kintsch 1988; Kintsch 1998), two forms of representation are activated during the reading and the comprehension of a text 1) the text base, which includes semantic propositions and 2) the situation model, corresponding to the integration of the information contained in the text to the memories and knowledge of the reader. Functional neuroimaging studies in healthy subjects have shown that the text base is underpinned by frontal regions and lateral temporal regions whereas the situation model would rather depend on the posterior cingulate cortex, the precuneus and other regions depending on the dimension studied. However, the brain regions highlighted so far were only involved in comprehension and not necessary for this cognitive ability. For the first time, we explored the brain structures necessary to understand texts using a combined VBM/DTI approach in neuropsychological patients with whom we obtained comprehension scores (text base and situation model) after the reading of narrative texts.