Topological Structures in the Space of Treatment-Naïve Patients with Chronic Lymphocytic Leukemia.

Patients are complex and heterogeneous; clinical data sets are complicated by noise, missing data, and the presence of mixed-type data. Using such data sets requires understanding the high-dimensional "space of patients", composed of all measurements that define all relevant phenotypes. The current state-of-the-art merely defines spatial groupings of patients using cluster analyses.

SillyPutty: Improved clustering by optimizing the silhouette width.

Clustering is an important task in biomedical science, and it is widely believed that different data sets are best clustered using different algorithms. When choosing between clustering algorithms on the same data set, reseachers typically rely on global measures of quality, such as the mean silhouette width, and overlook the fine details of clustering. However, the silhouette width actually computes scores that describe how well each individual element is clustered.

Extracellular Vesicle - MDM2-DNA as a Potential Liquid Biopsy Biomarker for Disease Identification in Retroperitoneal Liposarcoma.

Objective: We aimed to assess the levels of MDM2-DNA within extracellular vesicles (EVs) isolated from the serum of retroperitoneal liposarcoma (RLS) patients versus healthy donors, as well as within the same patients at the time of surgery versus post-operative surveillance visits. To determine whether EV-MDM2 may serve as a possible first-ever biomarker of liposarcoma recurrence.

Background: A hallmark of well-differentiated and de-differentiated (WD/DD) retroperitoneal liposarcoma is elevated MDM2 due to genome amplification, with recurrence rates of >50% even after complete resection.

SillyPutty: Improved clustering by optimizing the silhouette width.

Unsupervised clustering is an important task in biomedical science. We developed a new clustering method, called SillyPutty, for unsupervised clustering. As test data, we generated a series of datasets using the Umpire R package.

Feasibility study of the Nox-T3 device to detect swallowing and respiration pattern in neurologically impaired patients in the acute phase.

Dysphagia is a frequent complication in neurologically impaired patients, which can lead to aspiration pneumonia and thus prolonged hospitalization or even death. It is essential therefore, to detect and assess dysphagia early for best patient care. Fiberoptic endoscopic and Videofluoroscopy evaluation of swallowing are the gold standard exams in swallowing studies but neither are perfectly suitable for patients with disorders of consciousness (DOC).

Mysterious Bilateral Foot Pain in a Child With Crouzon Syndrome.

Crouzon syndrome (CS) is a rare autosomal dominant disorder that requires care from a multidisciplinary team and early surgical management to minimize complications. Despite the shared similarities across craniosynostoses, CS can be differentiated by the presence of normal bone development of the hands and feet and hypertelorism (large distance between the eyes). Other common features include midface hypoplasia, shallow orbits, ocular proptosis, and dental abnormalities including possible bifid uvula or V-shaped maxillary arch.

Transcriptome Complexity Disentangled: A Regulatory Molecules Approach.

Transcription factors (TFs) and microRNAs (miRNAs) are fundamental regulators of gene expression, cell state, and biological processes. This study investigated whether a small subset of TFs and miRNAs could accurately predict genome-wide gene expression. We analyzed 8895 samples across 31 cancer types from The Cancer Genome Atlas and identified 28 miRNA and 28 TF clusters using unsupervised learning.

Oncogenic role and target properties of the lysine-specific demethylase KDM1A in chronic lymphocytic leukemia.

In chronic lymphocytic leukemia (CLL), epigenetic alterations are considered to centrally shape the transcriptional signatures that drive disease evolution and underlie its biological and clinical subsets. Characterizations of epigenetic regulators, particularly histone-modifying enzymes, are very rudimentary in CLL. In efforts to establish effectors of the CLL-associated oncogene T-cell leukemia 1A (TCL1A), we identified here the lysine-specific histone demethylase KDM1A to interact with the TCL1A protein in B cells in conjunction with an increased catalytic activity of KDM1A.

Remdesivir-Associated Acute Liver Failure in a COVID-19 Patient: A Case Report and Literature Review.

There is a broad classification of the causes of acute liver failure (ALF) that include drug-induced liver injury (DILI). In this report, we aim to discuss the association between remdesivir, a novel therapeutic drug for hypoxic coronavirus disease 2019 (COVID-19) pneumonia, and DILI with subsequent ALF in a patient who was recently treated with the drug in question. Remdesivir, which is a direct-acting nucleoside RNA polymerase inhibitor, is one of the only FDA-approved drugs on the market for COVID-19 pneumonia associated with hypoxia.

Onlay Versus Inlay Biceps Tenodesis for Long Head of Biceps Tendinopathy: A Systematic Review and Meta-analysis.

Introduction: Proximal biceps tenodesis is a common surgical treatment of tendinosis of the long head of the biceps tendon. Two of the most common techniques incorporate onlay and inlay fixation methods, which can be done arthroscopically or open and in a variety of anatomic locations. The purpose of this meta-analysis was to compare the clinical outcomes between onlay versus inlay humeral fixation for biceps tenodesis for long head of the biceps tendon pathology.

Hemophagocytic Lymphohistiocytosis Following COVID-19 Infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with multiple inflammatory symptoms involving several organ systems, including hematologic manifestations. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome caused by excessive inflammation in the absence of immune regulation. We present the case of a patient with HLH secondary to dysregulated inflammatory response following COVID-19; we also describe the diagnostic and management challenges associated with the condition.

Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration.

Unlabelled: The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines identified a previously undescribed form of structural variation, "heterocateny," characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer. Unique breakpoints shared across structural variants facilitated stepwise reconstruction of their evolution from a common molecular ancestor.

A Rare Initial Presentation of Aortic Intramural Hematoma: A Case Report and Literature Review.

Aortic intramural hematoma (AIH) is a life-threatening emergency that involves aortic wall integrity and is characterized by either a direct rupture of the vasa vasorum or spontaneous bleeding of an arterial plaque located in the tunica media of the aortic wall. A notable difference between AIH and acute aortic dissection is the absence of an intimal flap, a finding discernable on computed tomography angiography (CTA). Follow-up imaging allows for the monitoring of disease progression or early findings of impending complications.

An Uncommon Case of Acute Coronary Stent Thrombosis.

Coronary stent thrombosis is an uncommon complication of percutaneous coronary intervention, which can result in myocardial infarction and often death. We present a case of acute stent thrombosis in a patient with newly diagnosed triple vessel coronary artery disease occurring within less than an hour of stent placement along with a review of the literature.

Gut-brain axis: Review on the association between Parkinson's disease and plant lectins.

Gastrointestinal (GI) involvement in the pathogenesis of Parkinson's Disease (PD) has been widely recognized and supported in recent literature. Prospective and retrospective studies found non-motor symptoms within the GI, specifically constipation, precede cardinal signs and cognitive decline by almost 20 years. In 2002, Braak et al.

Review of applied health informatics courses in a multidisciplinary biomedical informatics department.

Introduction: Applied health informatics infrastructure is a requirement for learning health systems and it is imperative that we train a workforce that can support this infrastructure. Our department offers courses in several interdisciplinary programs with topics ranging from bioinformatics to population health informatics. Due to changes in the field and our faculty members, we sought to assess our courses relevant to applied health informatics.

CEDA: integrating gene expression data with CRISPR-pooled screen data identifies essential genes with higher expression.

Motivation: Clustered regularly interspaced short palindromic repeats (CRISPR)-based genetic perturbation screen is a powerful tool to probe gene function. However, experimental noises, especially for the lowly expressed genes, need to be accounted for to maintain proper control of false positive rate.

Methods: We develop a statistical method, named CRISPR screen with Expression Data Analysis (CEDA), to integrate gene expression profiles and CRISPR screen data for identifying essential genes.

Sequences of Events from the Electronic Medical Record and the Onset of Infection.

We present a novel model of time-series analysis to learn from electronic health record (EHR) data when infection occurred in the intensive care unit (ICU) by translating methods from proteomics and Bayesian statistics. Using 48,536 patients hospitalized in an ICU, we describe each hospital course as an 'alphabet' of 23 physician actions ('events') in temporal order. We analyze these as k-mers of length 3-12 events and apply a Bayesian model of (cumulative) relative risk (RR).

An R package for visualizing and analyzing a spatial model of intratumor heterogeneity.

Cancer progression, including the development of intratumor heterogeneity, is inherently a spatial process. Mathematical models of tumor evolution may be a useful starting point for understanding the patterns of heterogeneity that can emerge in the presence of spatial growth. A commonly studied spatial growth model assumes that tumor cells occupy sites on a lattice and replicate into neighboring sites.

Diverse tumorigenic consequences of human papillomavirus integration in primary oropharyngeal cancers.

Human papillomavirus (HPV) causes 5% of all cancers and frequently integrates into host chromosomes. The HPV oncoproteins E6 and E7 are necessary but insufficient for cancer formation, indicating that additional secondary genetic events are required. Here, we investigate potential oncogenic impacts of virus integration.

RCytoGPS: an R package for reading and visualizing cytogenetics data.

Summary: Cytogenetics data, or karyotypes, are among the most common clinically used forms of genetic data. Karyotypes are stored as standardized text strings using the International System for Human Cytogenomic Nomenclature (ISCN). Historically, these data have not been used in large-scale computational analyses due to limitations in the ISCN text format and structure.

Simulation-derived best practices for clustering clinical data.

Introduction: Clustering analyses in clinical contexts hold promise to improve the understanding of patient phenotype and disease course in chronic and acute clinical medicine. However, work remains to ensure that solutions are rigorous, valid, and reproducible. In this paper, we evaluate best practices for dissimilarity matrix calculation and clustering on mixed-type, clinical data.