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

Rationale and concerns for using JAK inhibitors in axial spondyloarthritis

Lay Summary: What does this mean for patients? Axial spondyloarthritis (axSpA) is a lifelong disease that has a significant impact on quality of life. It is initially manifested by inflammatory back pain and can be associated with inflammation in other body parts, such as the eyes, bowel and skin. Treatment options have advanced over recent years and have become more targeted, including biologic treatments and, more recently, small molecule oral drugs called Janus kinase inhibitors. These newer agents have a rapid onset of action, can be taken orally and have efficacy in reducing inflammation across the whole spectrum of disease. Treatments for individual patients need to be tailored to whichever organ is inflamed at that point in time but should also consider the presence of other inflamed organs, comorbidities, long-term safety and cost. axSpA is a treatable condition where low disease activity or remission should be the target in most patients. Our review summarizes the clinical trial and real-world data that underpin current treatment guidelines

Commercial Teas Highlight Plant DNA Barcode Identification Successes and Obstacles

Appearance does not easily identify the dried plant fragments used to prepare teas to species. Here we test recovery of standard DNA barcodes for land plants from a large array of commercial tea products and analyze their performance in identifying tea constituents using existing databases. Most (90%) of 146 tea products yielded rbcL or matK barcodes using a standard protocol. Matching DNA identifications to listed ingredients was limited by incomplete databases for the two markers, shared or nearly identical barcodes among some species, and lack of standard common names for plant species. About 1/3 of herbal teas generated DNA identifications not found on labels. Broad scale adoption of plant DNA barcoding may require algorithms that place search results in context of standard plant names and character-based keys for distinguishing closely-related species. Demonstrating the importance of accessible plant barcoding, our findings indicate unlisted ingredients are common in herbal teas

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

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

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