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Introduction: Adverse drug responses are unpleasant side effects of commonly used or recently begun medications, and they are most often in the skin. Cutaneous drug responses (CDR) are widespread and often manifest as moderate, self-limiting lesions, however, certain severe versions can be fatal [1-2]. Multiple medications with similar chemical structures can create some types of lesions. Lips, legs, hands, cheeks, genitalia, and oral mucosa are common sites for lesions that generate a burning sensation. Bullae can form as a result of a fixed medication eruption (EDE). Intranasal injection of phenylephrine resulted in fast systemic absorption, which is linked with a clinically modest elevation in blood pressure [3]. Case Presentation: Here we discuss a case of a 19-year-old female patient who reported to our hospital with blebs on the skin throughout her legs and torso. The drug eruption or adverse drug response was linked with itching, had a slow beginning, and progressed. Her medical history indicated that she had been taking phenylephrine 10 mg orally twice a day. On the sixth day, she experienced an adverse medication response caused by the medicine phenylephrine. Phenylephrine was stopped immediately and the other medications, such as levocetirizine, montelukast, and nasal spray, were continued. The patient was told not to use phenylephrine, either alone or in combination with FDCs. There are no other complaints. As a result, the patient was diagnosed with phenylephrine-induced eruption. Conclusion: We present this case to highlight the importance of inspiring a pharmacovigilance mindset among all clinicians providing care as an alert routine drug, phenylephrine-induced drug eruption.

Background: Intra-Cytoplasmic Sperm Injection (ICSI) has revolutionized the reproductive outcomes for couples with male factor infertility. Especially in azoospermic men, use of ICSI with surgically retrieved testicular sperm has helped them have their own biological child. However, considering the immature nature of testicular sperm safety of testicular sperm has been debated. Aims: To compare reproductive outcomes, neonatal outcomes and the incidence of congenital malformations in children born after intracytoplasmic sperm injection (ICSI), using different sperm origins. Settings and Design: This is a retrospective study in which a total of 989 participants were enrolled. Study group (Testicular Sperm Aspiration (TESA) ICSI group) had 552 couples with female partners aged ≤37 and had self gamete cycles. ICSI cycles with ejaculated sperm (EJS) acted as the control group. Materials and Methods: All male patients underwent surgical sperm retrieval and all the women underwent controlled ovarian stimulation and transvaginal oocyte retrieval and Ovum Pick Up (OPU) as per the standard operating procedures of the clinic. Frozen embryo transfer with two good-grade blastocysts, which had shown 100% survival, were transferred in subsequent cycles. Statistical Analysis Used: The Student's t-test was performed for age distribution; odds ratio was performed to find the confounding factors. Results: Embryonic and reproductive outcomes were comparable and not statistically significant in the study and control groups. Incidence of congenital anomalies was observed in singleton live births and twin live births in both the TESA-ICSI group and the EJS-ICSI group, but the difference was not statistically significant. Conclusions: Our study revealed that congenital malformations in children born out of ICSI using testicular sperm and EJS were similar; no difference was observed in miscarriages between the testicular sperm-ICSI and EJS-ICSI group. Our data suggests that surgical sperm retrieval in couples with male factor infertility does not alter their reproductive outcome.

Breast cancer is a leading cause of death nowadays in women throughout the world. In developed countries, it is the most common type of cancer in women, and it is the second or third most common malignancy in developing countries. The cancer incidence is gradually increasing and remains a significant public health concern. The limitations of mammography as a screening and diagnostic modality, especially in young women with dense breasts, necessitated the development of novel and more effective strategies with high sensitivity and specificity. Thermal imaging (thermography) is a noninvasive imaging procedure used to record the thermal patterns using Infrared (IR) camera. The aim of this study is to evaluate the feasibility of using thermal imaging as a potential tool for detecting breast cancer. In this work, we have used 50 IR breast images (25 normal and 25 cancerous) collected from Singapore General Hospital, Singapore. Texture features were extracted from co-occurrence matrix and run length matrix. Subsequently, these features were fed to the Support Vector Machine (SVM) classifier for automatic classification of normal and malignant breast conditions. Our proposed system gave an accuracy of 88.10%, sensitivity and specificity of 85.71% and 90.48% respectively.

Diabetes is a condition of increase in the blood sugar level higher than the normal range. Prolonged diabetes damages the small blood vessels in the retina resulting in diabetic retinopathy (DR). DR progresses with time without any noticeable symptoms until the damage has occurred. Hence, it is very beneficial to have the regular cost effective eye screening for the diabetes subjects. This paper documents a system that can be used for automatic mass screenings of diabetic retinopathy. Four classes are identified: normal retina , non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and macular edema (ME) . We used 238 retinal fundus images in our analysis. Five different texture features such as homogeneity, correlation, short run emphasis, long run emphasis, and run percentage were extracted from the digital fundus images. These features were fed into a support vector machine classifier (SVM) for automatic classification. SVM classifier of different kernel functions (linear, radial basis function, polynomial of order 1, 2, and 3) was studied. Receiver operation characteristics (ROC) curves were plotted to select the best classifier. Our proposed system is able to identify the unknown class with an accuracy of 85.2%, and sensitivity, specificity, and area under curve (AUC) of 98.9%, 89.5%, and 0.972 respectively using SVM classifier with polynomial kernel of order 3. We have also proposed a new integrated DR index (IDRI) using different features, which is able to identify the different classes with 100% accuracy.

The cyber-physical power system (CPPS) is a modern infrastructure utilising information and communication technology that has become more vulnerable to cyberattacks in recent years. The attack magnitude injected by the adversary is stealthier and it cannot be detected using conventional bad data detection techniques. Protecting sensitive data from data integrity attacks (DIA) is essential for ensuring system security and reliability. A tragic event will occur if the attack goes unreported. Therefore, DIA detection is highly vital for the operator in the control centre to make important decisions. This paper addresses the attack impact on WAC applications and attack detection using the model-based method and data-driven-based methods. On the basis of the validation of performance indicators, various detection approaches are simulated and compared to determine the best detection strategy. Simulation results show that in the model-based anomaly detection method, the recursive polynomial model estimator (RPME) has better detection performance than the recursive least square estimator (RLSE). The convolutional neural network- (CNN-) based data-driven anomaly detection technique outperforms other machine learning (ML) techniques such as support vector machine (SVM), K-nearest neighbour (KNN), and random forest (RF). On the WSCC 3 machine 9-bus system, the efficacy of the suggested methods is evaluated.

The newly emerged ribonucleic acid (RNA) enveloped human beta-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection caused the COVID-19 pandemic, severely affects the respiratory system, and may lead to death. Lacking effective diagnostics and therapies made this pandemic challenging to manage since the SARS-CoV-2 transmits via human-to-human, enters via ACE2 and TMPSSR2 receptors, and damages organs rich in host cells, spreads via symptomatic carriers and is prominent in an immune-compromised population. New SARS-CoV-2 informatics (structure, strains, like-cycles, functional sites) motivated bio-pharma experts to investigate novel therapeutic agents that act to recognize, inhibit, and knockdown combinations of drugs, vaccines, and antibodies, have been optimized to manage COVID-19. However, successful targeted delivery of these agents to avoid off-targeting and unnecessary drug ingestion is very challenging. To overcome these obstacles, this mini-review projects nanomedicine technology, a pharmacologically relevant cargo of size within 10 to 200 nm, for site-specific delivery of a therapeutic agent to recognize and eradicate the SARS-CoV-2, and improving the human immune system. Such combinational therapy based on compartmentalization controls the delivery and releases of a drug optimized based on patient genomic profile and medical history. Nanotechnology could help combat COVID-19 via various methods such as avoiding viral contamination and spraying by developing personal protective equipment (PPE) to increase the protection of healthcare workers and produce effective antiviral disinfectants surface coatings capable of inactivating and preventing the virus from spreading. To quickly recognize the infection or immunological response, design highly accurate and sensitive nano-based sensors. Development of new drugs with improved activity, reduced toxicity, and sustained release to the lungs, as well as tissue targets; and development of nano-based immunizations to improve humoral and cellular immune responses. The desired and controlled features of suggested personalized therapeutics, nanomedicine, is a potential therapy to manage COVID-19 successfully. The state-of-the-art nanomedicine, challenges, and prospects of nanomedicine are carefully and critically discussed in this report, which may serve as a key platform for scholars to investigate the role of nanomedicine for higher efficacy to manage the COVID-19 pandemic.

Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor (VEGF) receptors 1–3, fibroblast growth factor (FGF) receptors 1–4, platelet‐derived growth factor receptor‐α (PDGFRα), KIT, and RET that have been implicated in pathogenic angiogenesis, tumor growth, and cancer. The primary objective of this work was to evaluate, by establishing quantitative relationships, whether lenvatinib exposure and longitudinal serum biomarker data (VEGF, Ang‐2, Tie‐2, and FGF‐23) are predictors for change in longitudinal tumor size which was assessed based on data from 558 patients with radioiodine‐refractory differentiated thyroid cancer (RR‐DTC) receiving either lenvatinib or placebo treatment. Lenvatinib PK was best described by a 3‐compartment model with simultaneous first‐ and zero‐order absorption and linear elimination from the central compartment with significant covariates (body weight, albumin <30 g/dL, ALP>ULN, RR‐DTC, RCC, HCC subjects, and concomitant CYP3A inhibitors). Except for body weight, none of the covariates have any clinically meaningful effect on exposure to lenvatinib. Longitudinal biomarker measurements over time were reasonably well defined by a PK/PD model with common EC50, Emax, and a slope for disease progression for all biomarkers. Longitudinal tumor measurements over time were reasonably well defined by a tumor growth inhibition Emax model, which in addition to lenvatinib exposure, included model‐predicted relative changes from baseline over time for Tie‐2 and Ang‐2 as having significant association with tumor response. The developed PK/PD models pave the way for dose optimization and potential prediction of clinical response.

Sarcomatoid carcinoma of the esophagus, a mixed tumor comprising both carcinomatous and sarcomatoid components and known as carcinosarcoma, is a rare malignancy. Clinically and radiologically, it presents like other esophageal cancers. Here we discuss the case of a 69-year-old male patient with sarcomatoid carcinoma of the esophagus who developed Stevens-Johnson syndrome (SJS) after chemotherapy with carboplatin and paclitaxel. The patient was evaluated for dysphagia and odynophagia. He was initially misdiagnosed to have an esophageal polyp and underwent excision for the same. He presented with recurrent growth at the local site, with histopathological examination showing sarcomatoid carcinoma of the esophagus. After the development of paclitaxel-carboplatin-induced SJS, the patient was subsequently treated with palliative radiotherapy at the primary site for symptomatic relief. He underwent feeding gastrostomy as a supportive nutritional measure and was on best supportive care after a multidisciplinary tumor board discussion. Paclitaxel-carboplatin-induced SJS poses numerous diagnostic conundrums, on account of there being only one reported incident prior to this in literature, to the best of our knowledge. In this report, we explore the diagnostic and therapeutic predicaments associated with a rare disease that is under-reported and understudied in literature and delve into the various treatment modalities that can benefit the patients. The case also demonstrates the delicate balance between cancer chemotherapeutics and their Pandora’s box of adverse effects.

This paper presents a novel design and analysis of a low-k source-side asymmetrical spacer halo-doped nanowire MOSFET. The utilization of high-k spacer materials in MOSFETs enhances electrostatic control and minimizes short-channel effects in nanoscale devices. However, the performance of dynamic circuits suffers, with higher fringe capacitance brought on by high-k spacers. Our method focuses on reducing gate capacitance by promising utilization of high-k spacer material. The proposed device is constructed in Silvaco TCAD software, and results show that the low-k source-side asymmetrical spacer halo-doped nanowire MOSFET design exhibits noticeably lower gate capacitance and intrinsic delay, with values of 1.23 × 10 - 17 F and 1.11 × 10 - 12 s, respectively. The CMOS inverter delay and three-stage ring oscillator operating frequency for the proposed device are 1.82 × 10 - 12 s and 91.61 GHz, respectively. The proposed device demonstrates better performance than other spacer engineering devices, making it a strong candidate for digital applications.

A broad chemical genetic screen in Mycobacterium tuberculosis ( Mtb ) identified compounds (BRD-8000.3 and BRD-9327) that inhibit the essential efflux pump EfpA. To understand the mechanisms of inhibition, we determined the structures of EfpA with these inhibitors bound at 2.7-3.4 Å resolution. Our structures reveal different mechanisms of inhibition by the two inhibitors. BRD-8000.3 binds in a tunnel contacting the lipid bilayer and extending toward the central cavity to displace the fatty acid chain of a lipid molecule bound in the apo structure, suggesting its blocking of an access route for a natural lipidic substrate. Meanwhile, BRD-9327 binds in the outer vestibule without complete blockade of the substrate path to the outside, suggesting its possible inhibition of the movement necessary for alternate access of the transporter. Our results show EfpA as a potential lipid transporter, explain the basis of the synergy of these inhibitors and their potential for combination anti-tuberculosis therapy. A chemical genetic screen identified inhibitors of an essential transporter from Mycobacterium tuberculosis. Here authors determine atomic structures of EfpA that indicate that it is a lipid transporter, and multiple modes of inhibition that can act synergistically against tuberculosis.