Ovarian cancer mutational processes drive site-specific immune evasion.

High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability patterned by distinct mutational processes, tumour heterogeneity and intraperitoneal spread. Immunotherapies have had limited efficacy in HGSOC, highlighting an unmet need to assess how mutational processes and the anatomical sites of tumour foci determine the immunological states of the tumour microenvironment. Here we carried out an integrative analysis of whole-genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumour sites from 42 treatment-naive patients with HGSOC.

Multimodal data integration using machine learning improves risk stratification of high-grade serous ovarian cancer.

Patients with high-grade serous ovarian cancer suffer poor prognosis and variable response to treatment. Known prognostic factors for this disease include homologous recombination deficiency status, age, pathological stage and residual disease status after debulking surgery. Recent work has highlighted important prognostic information captured in computed tomography and histopathological specimens, which can be exploited through machine learning.

Harnessing multimodal data integration to advance precision oncology.

Advances in quantitative biomarker development have accelerated new forms of data-driven insights for patients with cancer. However, most approaches are limited to a single mode of data, leaving integrated approaches across modalities relatively underdeveloped. Multimodal integration of advanced molecular diagnostics, radiological and histological imaging, and codified clinical data presents opportunities to advance precision oncology beyond genomics and standard molecular techniques.

Incidence of Traumatic Delayed Intracranial Hemorrhage Among Patients Using Direct Oral Anticoagulants.

Background: Emergency department visits due to head injury in the United States have increased significantly over the past decade, and parallel the increasing use of direct oral anticoagulants (DOACs).

Objective: We investigated the incidence of delayed intracranial hemorrhage (DICH) in patients with head injury who were taking DOACs.

Methods: We conducted a single-center retrospective study at a level II trauma center.

Update on Neurological Manifestations of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2, the source of COVID-19, causes numerous clinical findings including respiratory and gastrointestinal findings. Evidence is now growing for increasing neurological symptoms. This is thought to be from direct in-situ effects in the olfactory bulb caused by the virus.

Utility of INR For Prediction of Delayed Intracranial Hemorrhage Among Warfarin Users with Head Injury.

Background: Incidence of delayed intracranial hemorrhage (DICH) in patients on warfarin has been controversial. No previous literature has reported the utility of international normalized ratio (INR) in predicting traumatic DICH.

Objectives: Utilizing INR to risk stratify head trauma patients who may be managed without repeat imaging.

Characterization of Recurrences Following Second Breast-Conserving Surgery with Intraoperative Radiotherapy.

Background: Breast-conserving surgery with breast re-irradiation is an emerging technique in the treatment of selected cases of locally recurrent breast cancer. Further information is needed to characterize factors that may select for an appropriate patient population for this treatment approach.

Methods: We report herein a single-institution retrospective analysis of patients with ipsilateral breast cancer recurrence treated with a second breast-conserving therapy with intraoperative radiotherapy.

Systematic Review of the Effects of Phosphodiesterase-5 Inhibitors and Dexamethasone on High Altitude Pulmonary Edema (HAPE).

Objective: To review and synthesize the current available evidence of the effects of phosphodiesterase-5 inhibitors and dexamethasone on the outcomes of individuals affected by acute mountain sickness symptoms and High Altitude Pulmonary Edema (HAPE).

Methods: In 2015, two authors independently performed separate searches using three different databases (PubMed, Ovid and Web of Science) later reviewed by the third author. The searches used the following terms "High Altitude Pulmonary Edema" and "Phosphodiesterase-5 Inhibitors" while the second search used "High Altitude Pulmonary Edema" and "Dexamethasone".

Predicting peptide presentation by major histocompatibility complex class I: an improved machine learning approach to the immunopeptidome.

Background: To further our understanding of immunopeptidomics, improved tools are needed to identify peptides presented by major histocompatibility complex class I (MHC-I). Many existing tools are limited by their reliance upon chemical affinity data, which is less biologically relevant than sampling by mass spectrometry, and other tools are limited by incomplete exploration of machine learning approaches. Herein, we assemble publicly available data describing human peptides discovered by sampling the MHC-I immunopeptidome with mass spectrometry and use this database to train random forest classifiers (ForestMHC) to predict presentation by MHC-I.

An Atypical Case of Transverse Diverticulitis and the Changing Management of Diverticular Disease.

Diverticulitis is an inflammation of an out pouching of the lower gastrointestinal tract, particularly in the large intestine. Although the condition is taught to medical students as typically occurring in the left lower quadrant of the abdomen, right-sided and transverse forms diverticulitis can occur. Uncomplicated, e.

Accuracy of Patient Height, Weight and Ideal Body Weight Estimates in the Emergency Department.

Context: The purpose of this study was to establish the accuracy of emergency medicine professionals' estimates of a sample of patients' heights, weights and ideal body weights (IBW).

Methods: This was a cross-sectional survey study with 69 emergency medicine professionals concerning estimates of five standardized patients. Board-certified emergency physicians, emergency medicine residents and emergency department nurses were asked to estimate patient height, weight and (IBW) by looking at a series of photographs of five standardized patients with varied body types.

Transient Hyperammonemia Seen in Post Seizure Activity: A Series of Six Case Reports.

Elevations in serum ammonia levels (i.e., hyperammonemia) have often been interpreted as signs of liver failure or errors in metabolism.

First Report of Survival in Refractory Ventricular Fibrillation After Dual-Axis Defibrillation and Esmolol Administration.

There is a subset of patients who suffer a witnessed ventricular fibrillation (VF) arrest and despite receiving reasonable care with medications (epinephrine and amiodarone) and multiple defibrillations (3+ attempts at 200 joules of biphasic current) remain in refractory VF (RVF), also known as electrical storm. The mortality for these patients is as high as 97%. We present the case of a patient who, with a novel approach, survived RVF to outpatient follow up.

Improved Prediction of CYP-Mediated Metabolism with Chemical Fingerprints.

Molecule and atom fingerprints, similar to path-based Daylight fingerprints, can substantially improve the accuracy of P450 site-of-metabolism prediction models. Only two chemical fingerprints have been used in metabolism prediction, so little is known about the importance of fingerprint parameters on site of metabolism predictions. It is possible that different fingerprints might yield more accurate models.

Retrievable stent thrombectomy in the treatment of acute ischemic stroke: analysis of a revolutionizing treatment technique.

Acute ischemic stroke resulting from intracranial vessel occlusion is associated with high morbidity and mortality. The mainstays of therapy are fibrinolytics and mechanical thrombectomy in properly selected patients. A new Food and Drug Administration-approved technology to perform thrombectomy, retrievable stenting, may provide superior revascularization rates and improved patient outcomes.

An Acute Ibuprofen Overdose Masking a Severe Staphylococcus aureus Meningitis: A Case Report.

Acute bacterial meningitis has a low incidence (3/100,000 in the United States) and yet high fatality rate (approximately 14-16%) and classically presents as a triad of fever, neck stiffness, and altered mental status. However, less than half of patients with meningitis present with this classic triad. We present the clinical course of a patient who initially presented to the emergency department after overdosing on ibuprofen for what he described as back pain secondary to mechanical injury.

Pacemaker related infective endocarditis from Staphylococcus lugdunensis: a case report.

Staphylococcus lugdunensis is a common skin flora not typically associated with infection. There are, however, several cases reported in the literature of Staphylococcus lugdunensis as a causative bacterium of various infections. This paper reports an additional case of pacemaker associated endocarditis with Staphylococcus lugdunensis as the causative bacterium.

Improved data normalization methods for reverse phase protein microarray analysis of complex biological samples.

Reverse phase protein microarrays (RPMA) are designed for quantitative, multiplexed analysis of proteins, and their posttranslational modified forms, from a limited amount of sample. To correct for sample to sample variability due to the number of cells in each lysate and the presence of extracellular proteins or red blood cells, a normalization method is required that is independent of these potentially confounding parameters. We adopted a gene microarray algorithm for use with RPMA to optimize the proteomic data normalization process and developed a systematic approach to RPMA processing and analysis, tailored to the study set.