Multiplex PCR for Detection of Herpes Simplex Viruses Type-1 and Type-2, Cytomegalovirus, Varicella-zoster Virus, and Adenovirus in Ocular Viral Infections

Purpose: Most common viruses causing ocular infections are Herpes Simplex Viruses (HSV) type 1 and type 2, Cytomegalovirus (CMV), Varicella-zoster Virus (VZV), and few strains of Adenovirus. Diagnosis of these infections through clinical manifestations and using conventional methods has a number of limitations. The purpose of this study was to develop a multiplex Polymerase Chain Reaction (PCR) for simultaneous detection of all pathogenic viruses from ocular infections. Methods: Ten uniplex PCRs were standardized, two each for HSV type 1 (HSV-1) and type 2 (HSV-2), CMV, VZV, and Adenovirus. Various multiplexing combinations of above PCRs were put to finalize targets and reaction conditions enabling diagnosis of all in a single reaction. The uniplex and multiplex PCRs were run for known positive and negative controls, and samples from clinically suspected patients and healthy controls. Results: Out of the 170 samples from suspected ocular infections, 24.7% were positive by uniplex PCR and 22.9% were correctly identified by multiplex PCR. None of the samples negative by uniplex PCRs was positive by the multiplex PCR. The sensitivity and specificity of multiplex PCR compared to the commonly used uniplex PCRs as gold standard was 92.86% and 100%, respectively. The prevalence of different viral pathogens was 13.5% for HSV-1, followed by 5.9% for Adenovirus, 2.4% for VZV, 1.8% for HSV-2, and 1.2% for CMV. Conclusion: The establishment of multiplex PCR has found immediate application in diagnosing ocular viral pathogens in a single reaction, thus saving time, manpower, and resources by fivefold

Maximum Reward Formulation In Reinforcement Learning

Reinforcement learning (RL) algorithms typically deal with maximizing the expected cumulative return (discounted or undiscounted, finite or infinite horizon). However, several crucial applications in the real world, such as drug discovery, do not fit within this framework because an RL agent only needs to identify states (molecules) that achieve the highest reward within a trajectory and does not need to optimize for the expected cumulative return. In this work, we formulate an objective function to maximize the expected maximum reward along a trajectory, derive a novel functional form of the Bellman equation, introduce the corresponding Bellman operators, and provide a proof of convergence. Using this formulation, we achieve state-of-the-art results on the task of molecule generation that mimics a real-world drug discovery pipeline.Comment: 13 pages, 5 figure

Advancing early leukemia diagnostics: a comprehensive study incorporating image processing and transfer learning.

Disease recognition has been revolutionized by autonomous systems in the rapidly developing field of medical technology. A crucial aspect of diagnosis involves the visual assessment and enumeration of white blood cells in microscopic peripheral blood smears. This practice yields invaluable insights into a patient's health, enabling the identification of conditions of blood malignancies such as leukemia. Early identification of leukemia subtypes is paramount for tailoring appropriate therapeutic interventions and enhancing patient survival rates. However, traditional diagnostic techniques, which depend on visual assessment, are arbitrary, laborious, and prone to errors. The advent of ML technologies offers a promising avenue for more accurate and efficient leukemia classification. In this study, we introduced a novel approach to leukemia classification by integrating advanced image processing, diverse dataset utilization, and sophisticated feature extraction techniques, coupled with the development of TL models. Focused on improving accuracy of previous studies, our approach utilized Kaggle datasets for binary and multiclass classifications. Extensive image processing involved a novel LoGMH method, complemented by diverse augmentation techniques. Feature extraction employed DCNN, with subsequent utilization of extracted features to train various ML and TL models. Rigorous evaluation using traditional metrics revealed Inception-ResNet's superior performance, surpassing other models with F1 scores of 96.07% and 95.89% for binary and multiclass classification, respectively. Our results notably surpass previous research, particularly in cases involving a higher number of classes. These findings promise to influence clinical decision support systems, guide future research, and potentially revolutionize cancer diagnostics beyond leukemia, impacting broader medical imaging and oncology domains

Morphometric and morphological evaluation of mastoid emissary canal using cone-beam computed tomography

Objectives: This study aimed to determine mastoid emissary canal’s (MEC) and mastoid foramen (MF) prevalence and morphometric characteristics on cone-beam computed tomography (CBCT) images to underline its clinical significance and discuss its surgical consequences. Methods: In the retrospective analysis, two oral and maxillofacial radiologists analyzed the CBCT images of 135 patients (270 sides). The biggest MF and MEC were measured in the images evaluated in MultiPlanar Reconstruction (MPR) views. The MF and MEC mean diameters were calculated. The mastoid foramina number was recorded. The prevalence of MF was studied according to gender and side of the patient. Results: The overall prevalence of MEC and MF was 119 (88.1%). The prevalence of MEC and MF is 55.5% in females and 44.5% in males. MEC and MF were identified as bilateral in 80 patients (67.20%) and unilateral in 39 patients (32.80%). The mean diameter of MF was 2.4 ± 0.9 mm. The mean height of MF was 2.3 ± 0.9. The mean diameter of the MEC was 2.1 ± 0.8, and the mean height of the MEC was 2.1 ± 0.8. There is a statistical difference between the genders (p = 0.043) in foramen diameter. Males had a significantly larger mean diameter of MF in comparison to females. Conclusion: MEC and MF must be evaluated thoroughly if the surgery is contemplated. Radiologists and surgeons should be aware of mastoid emissary canal morphology, variations, clinical relevance, and surgical consequences while operating in the suboccipital and mastoid areas to avoid unexpected and catastrophic complications. CBCT may be a reliable imaging diagnostic technique

Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival

The use of digital pathology for the histomorphologic profiling of pathological specimens is expanding the precision and specificity of quantitative tissue analysis at an unprecedented scale; thus, enabling the discovery of new and functionally relevant histological features of both predictive and prognostic significance. In this study, we apply quantitative automated image processing and computational methods to profile the subcellular distribution of the multi-functional transcriptional regulator, Kaiso (ZBTB33), in the tumors of a large racially diverse breast cancer cohort from a designated health disparities region in the United States. Multiplex multivariate analysis of the association of Kaiso’s subcellular distribution with other breast cancer biomarkers reveals novel functional and predictive linkages between Kaiso and the autophagy-related proteins, LC3A/B, that are associated with features of the tumor immune microenvironment, survival, and race. These findings identify effective modalities of Kaiso biomarker assessment and uncover unanticipated insights into Kaiso’s role in breast cancer progression.Fil: Singhal, Sandeep K.. North Dakota State University; Estados UnidosFil: Byun, Jung S.. National Institutes of Health; Estados UnidosFil: Park, Samson. National Institutes of Health; Estados UnidosFil: Yan, Tingfen. National Institutes of Health; Estados UnidosFil: Yancey, Ryan. Columbia University; Estados UnidosFil: Caban, Ambar. Columbia University; Estados UnidosFil: Hernandez, Sara Gil. National Institutes of Health; Estados UnidosFil: Hewitt, Stephen M.. U.S. Department of Health & Human Services. National Institute of Health. National Cancer Institute; Estados UnidosFil: Boisvert, Heike. Ultivue, Inc; Reino UnidoFil: Hennek, Stephanie. Ultivue Inc.; Reino UnidoFil: Bobrow, Mark. Ultivue Inc.; Reino UnidoFil: Ahmed, Md Shakir Uddin. Tuskegee University; Estados UnidosFil: White, Jason. Tuskegee University; Estados UnidosFil: Yates, Clayton. Tuskegee University; Estados UnidosFil: Aukerman, Andrew. Columbia University; Estados UnidosFil: Vanguri, Rami. Columbia University; Estados UnidosFil: Bareja, Rohan. Columbia University; Estados UnidosFil: Lenci, Romina. Columbia University; Estados UnidosFil: Farré, Paula Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Nápoles, Anna María. National Institutes of Health; Estados UnidosFil: Vohra, Nasreen. East Carolina University; Estados UnidosFil: Gardner, Kevin. Columbia University; Estados Unido

Rapid assessment of price instability and paucity of medicines and protection for COVID-19 across Asia : findings and public health implications for the future

Background: Countries have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE), with some countries adopting preventative strategies earlier than others. However, there has been considerable controversy surrounding some treatments. This includes hydroxychloroquine where the initial hype and misinformation lead to shortages, price rises and suicides. Price rises and shortages have also been seen for PPE. Such activities can have catastrophic effects on patients where there are high co-payment levels and issues of affordability. Consequently, there is a need to investigate this further. Objective: Assess changes in the availability, utilization and prices of relevant medicines and PPE during the pandemic among a range of Asian countries. Our approach: Narrative literature review combined with interviews among community pharmacists to assess changes in consumption, prices and shortages of medicines and PPE from the beginning of March 2020 until end of May 2020. In addition, suggestions on ways to reduce misinformation. Results: 308 pharmacists took part from five Asian countries. There was an appreciable increase in the utilization of antimicrobials in Pakistan (in over 88% of pharmacies), with lower increases or no change in Bangladesh, India, Malaysia and Vietnam. Encouragingly, there was increased use of vitamins/immune boosters and PPE across the countries, as well as limited price rises for antimicrobials in India, Malaysia and Vietnam, although greater price rises seen for analgesics and vitamin C/immune boosters. Appreciable price increases were also seen for PPE across some countries. Conclusion: Encouraging to see increases in utilization of vitamins/immune boosters and PPE. However, increases in the utilization and prices of antimicrobials is a concern that needs addressing alongside misinformation and any unintended consequences from the pandemic. Community pharmacists can play a key role in providing evidence-based advice, helping to moderate prices, as well as helping address some of the unintended consequences of the pandemic

Inhibition of FGF receptor blocks adaptive resistance to RET inhibition in CCDC6-RET-rearranged thyroid cancer.

Genetic alterations in RET lead to activation of ERK and AKT signaling and are associated with hereditary and sporadic thyroid cancer and lung cancer. Highly selective RET inhibitors have recently entered clinical use after demonstrating efficacy in treating patients with diverse tumor types harboring RET gene rearrangements or activating mutations. In order to understand resistance mechanisms arising after treatment with RET inhibitors, we performed a comprehensive molecular and genomic analysis of a patient with RET-rearranged thyroid cancer. Using a combination of drug screening and proteomic and biochemical profiling, we identified an adaptive resistance to RET inhibitors that reactivates ERK signaling within hours of drug exposure. We found that activation of FGFR signaling is a mechanism of adaptive resistance to RET inhibitors that activates ERK signaling. Combined inhibition of FGFR and RET prevented the development of adaptive resistance to RET inhibitors, reduced cell viability, and decreased tumor growth in cellular and animal models of CCDC6-RET-rearranged thyroid cancer