Other than an association with HPV infection, little is known about the genetic alterations determining the development of penile cancer. Although penile cancer is rare in the developed world, it presents a significant burden in developing countries. Here, we report the findings of whole-exome sequencing (WES) to determine the somatic mutational landscape of penile cancer. WES was performed on penile cancer and matched germline DNA from 27 patients undergoing surgical resection. Targeted resequencing of candidate genes was performed in an independent 70 patient cohort. Mutation data were also integrated with DNA methylation and copy-number information from the same patients. We identified an HPV-associated APOBEC mutation signature and an NpCpG signature in HPV-negative disease. We also identified recurrent mutations in the novel penile cancer tumor suppressor genes CSN1(GPS1) and FAT1. Expression of CSN1 mutants in cells resulted in colocalization with AGO2 in cytoplasmic P-bodies, ultimately leading to the loss of miRNAmediated gene silencing, which may contribute to disease etiology. Our findings represent the first comprehensive analysis of somatic alterations in penile cancer, highlighting the complex landscape of alterations in this malignancy.

Polyethylene terephthalate (PET) is the most widely used polymer in the world. For the first time, the laser‐driven integration of aluminum nanoparticles (Al NPs) into PET to realize a laser‐induced graphene/Al NPs/polymer composite, which demonstrates excellent toughness and high electrical conductivity with the formation of aluminum carbide into the polymer is shown. The conductive structures show an impressive mechanical resistance against >10000 bending cycles, projectile impact, hammering, abrasion, and structural and chemical stability when in contact with different solvents (ethanol, water, and aqueous electrolytes). Devices including thermal heaters, carbon electrodes for energy storage, electrochemical and bending sensors show this technology's practical application for ultra‐robust polymer electronics. This laser‐based technology can be extended to integrating other nanomaterials and create hybrid graphene‐based structures with excellent properties in a wide range of flexible electronics’ applications.

Purpose: Penile cancer is a rare malignancy in the developed world with just more than 1,600 new cases diagnosed in the United States per year; however, the incidence is much higher in developing countries. Although HPV is known to contribute to tumorigenesis, little is known about the genetic or epigenetic alterations defining penile cancer.Experimental Design: Using high-density genome-wide methylation arrays, we have identified epigenetic alterations associated with penile cancer. Q-MSP was used to validate lymph node metastasis markers in 50 cases. A total of 446 head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESCC) samples were used to validate HPV-associated epigenetic alterations.Results: We defined 6,933 methylation variable positions (MVP) between normal and tumor tissue, which includes 997 hypermethylated differentially methylated regions associated with tumor supressor genes, including CDO1, AR1, and WT1. Analysis of penile cancer tumors identified a 4 gene episignature which accurately predicted lymph node metastasis in an independent cohort (AUC of 89%). Finally, we explored the epigenetic alterations associated with penile cancer HPV infection and defined a 30 loci lineage-independent HPV specific epi-signature which predicts HPV status and survival in independent HNSCC, CESC cohorts. Epi-signature-negative patients have a significantly worse overall survival [HNSCC P ¼ 0.00073; 95% confidence interval (CI), 0.021-0.78; CESC P ¼ 0.0094; HR ¼ 3.91, 95% CI ¼ 0.13-0.78], HPV epi-signature is a better predictor of survival than HPV status alone.Conclusions: These data demonstrate for the first time genome-wide epigenetic events involved in an aggressive penile cancer phenotype and define the epigenetic alterations common across multiple HPV-driven malignancies.

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Background & Objective: The high-throughput analysis of circulating microRNAs (miRNAs) is an active area of biomarker research. The oral cancer remains a common cancer among Pakistani males that continues to present at an advance stage, thus exhibiting poor survival. MiRNA 21 (miR-21) is the most consistently over-expressed miRNA in different types of tumor tissues. However, information regarding expression of miR-21 in plasma remains to be resolved. Therefore, present study was designed to investigate if miR-21 was expressed in plasma of patients with oral cancer, and further explore its diagnostic and prognostic potential. Methods: Present study was conducted at Ziauddin University and Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). Histologically confirmed cases of oral squamous cell carcinoma were recruited from Oncology Department of Ziauddin Hospital between 2013 and 2017. Controls were carefully selected after considering age, gender and socioeconomic condition. MiRNA was extracted and immediately reverse transcribed to cDNA. MiR-21 expression was evaluated using probes specifically designed for Real time quantitative polymerase chain reaction. Results: A significant over expression of miRNA 21 was observed in histologically confirmed cases as compared to controls. The increased expression of miRNA 21 was also reported to be associated with tumor size, metastasis and local invasion (p<0.05). Conclusion: The expression of circulating miR-21 in plasma samples of oral cancer patients makes it a promising diagnostic and prognostic marker. doi: https://doi.org/10.12669/pjms.35.5.331 How to cite this:Mahmood N, Hanif M, Ahmed A, Jamal Q, Mushtaq S, Khan A, et al. Circulating miR-21 as a prognostic and predictive biomarker in oral squamous cell carcinoma. Pak J Med Sci. 2019;35(5):---------. doi: https://doi.org/10.12669/pjms.35.5.331 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A memristor is a fundamental electronic device that operates like a biological synapse and is considered as the solution of classical von Neumann computers. Here, a fully printed and flexible memristor is fabricated by depositing a thin film of metal–non-metal (chromium-nitrogen)-doped titanium dioxide (TiO2). The resulting device exhibited enhanced performance with self-rectifying and forming free bipolar switching behavior. Doping was performed to bring stability in the performance of the memristor by controlling the defects and impurity levels. The forming free memristor exhibited characteristic behavior of bipolar resistive switching with a high on/off ratio (2.5 × 103), high endurance (500 cycles), long retention time (5 × 103 s) and low operating voltage (±1 V). Doping the thin film of TiO2 with metal–non-metal had a significant effect on the switching properties and conduction mechanism as it directly affected the energy bandgap by lowering it from 3.2 eV to 2.76 eV. Doping enhanced the mobility of charge carriers and eased the process of filament formation by suppressing its randomness between electrodes under the applied electric field. Furthermore, metal–non-metal-doped TiO2 thin film exhibited less switching current and improved non-linearity by controlling the surface defects.

Performance of an electronic device relies heavily on the availability of a suitable functional material. One of the simple, easy, and cost-effective ways to obtain novel functional materials with improved properties for desired applications is to make composites of selected materials. In this work, a novel composite of transparent n-type zinc oxide (ZnO) with a wide bandgap and a unique structure of graphene in the form of a graphene flower (GrF) is synthesized and used as the functional layer of a humidity sensor. The (GrF/ZnO) composite was synthesized by a simple sol–gel method. Morphological, elemental, and structural characterizations of GrF/ZnO composite were performed by a field emission scanning electron microscope (FESEM), energy-dispersive spectroscopy (EDS), and an x-ray diffractometer (XRD), respectively, to fully understand the properties of this newly synthesized functional material. The proposed humidity sensor was tested in the relative humidity (RH) range of 15% RH% to 86% RH%. The demonstrated sensor illustrated a highly sensitive response to humidity with an average current change of 7.77 μA/RH%. Other prominent characteristics shown by this device include but were not limited to high stability, repeatable results, fast response, and quick recovery time. The proposed humidity sensor was highly sensitive to human breathing, thus making it a promising candidate for various applications related to health monitoring.