Integrative deep learning analysis improves colon adenocarcinoma patient stratification at risk for mortality.

Background: Colorectal cancers are the fourth most diagnosed cancer and the second leading cancer in number of deaths. Many clinical variables, pathological features, and genomic signatures are associated with patient risk, but reliable patient stratification in the clinic remains a challenging task. Here we assess how image, clinical, and genomic features can be combined to predict risk.

Coronavirus pandemic in the South Asia region: Health policy and economy trade-off.

Background: The South Asian Association for Regional Cooperation (SAARC) covers Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. We conducted a comparative analysis of the trade-off between the health policies for the prevention of COVID-19 spread and the impact of these policies on the economies and livelihoods of the South Asia populations.

Methods: We analyzed COVID-19 data on epidemiology, public health and health policy, health system capacity, and macroeconomic indicators from January 2020 to March 2021 to determine temporal trends by conducting joinpoint regression analysis using average weekly percent change (AWPC).

Quantitative, Spatially Defined Expression of Leukocyte-associated Immunoglobulin-like Receptor in Non-small Cell Lung Cancer.

Unlabelled: Targeting the interaction of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) and its ligands has been shown to reinstate antitumor immunity. In addition, the introduction of the LAIR-1 decoy protein, LAIR-2, sensitizes previously resistant lung tumors to programmed death-1 (PD-1) blockade, indicating the potential of LAIR-1 as an alternative marker for anti-PD-1 resistance in lung cancer. Here, we assessed LAIR-1 as compared with programmed death-ligand 1 (PD-L1) expression in various tumors, with a focus on non-small cell lung cancer (NSCLC) and its histologic subtypes using multiplexed quantitative immunofluorescence (mQIF) in 287 (discovery cohort) and 144 (validation cohort) patients with NSCLC.

Spatial characterization and quantification of CD40 expression across cancer types.

Background: CD40, a TNF receptor family member, is expressed by a variety of immune cells and is involved in the activation of both adaptive and innate immune responses. Here, we used quantitative immunofluorescence (QIF) to evaluate CD40 expression on the tumor epithelium of solid tumors in large patient cohorts of lung, ovarian, and pancreatic cancers.

Methods: Tissue samples from nine different solid tumors (bladder, breast, colon, gastric, head and neck, non-small cell lung cancer (NSCLC), ovarian, pancreatic and renal cell carcinoma), constructed in tissue microarray format, were initially assessed for CD40 expression by QIF.

Coronavirus pandemic in the Nordic countries: Health policy and economy trade-off.

Background: Countries making up the Nordic region - Denmark, Finland, Iceland, Norway, and Sweden - have minimal socioeconomic, cultural, and geographical differences between them, allowing for a fair comparative analysis of the health policy and economy trade-off in their national approaches towards mitigating the impact of the COVID-19 pandemic.

Methods: This study utilized publicly available COVID-19 data of the Nordic countries from January 2020 to January 3, 2021. COVID-19 epidemiology, public health and health policy, health system capacity, and macroeconomic data were analysed for each Nordic country.

Deep learning trained on hematoxylin and eosin tumor region of Interest predicts HER2 status and trastuzumab treatment response in HER2+ breast cancer.

The current standard of care for many patients with HER2-positive breast cancer is neoadjuvant chemotherapy in combination with anti-HER2 agents, based on HER2 amplification as detected by in situ hybridization (ISH) or protein immunohistochemistry (IHC). However, hematoxylin & eosin (H&E) tumor stains are more commonly available, and accurate prediction of HER2 status and anti-HER2 treatment response from H&E would reduce costs and increase the speed of treatment selection. Computational algorithms for H&E have been effective in predicting a variety of cancer features and clinical outcomes, including moderate success in predicting HER2 status.

Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a novel deep neural network.

Background: The nextwave of COVID-19 pandemic is anticipated to be worse than the initial one and will strain the healthcare systems even more during the winter months. Our aim was to develop a novel machine learning-based model to predict mortality using the deep learning Neo-V framework. We hypothesized this novel machine learning approach could be applied to COVID-19 patients to predict mortality successfully with high accuracy.

An Open-Source, Automated Tumor-Infiltrating Lymphocyte Algorithm for Prognosis in Triple-Negative Breast Cancer.

Purpose: Although tumor-infiltrating lymphocytes (TIL) assessment has been acknowledged to have both prognostic and predictive importance in triple-negative breast cancer (TNBC), it is subject to inter and intraobserver variability that has prevented widespread adoption. Here we constructed a machine-learning based breast cancer TIL scoring approach and validated its prognostic potential in multiple TNBC cohorts.

Experimental Design: Using the QuPath open-source software, we built a neural-network classifier for tumor cells, lymphocytes, fibroblasts, and "other" cells on hematoxylin-eosin (H&E)-stained sections.

Sheep as a Potential Model of Intradiscal Infection by the Bacterium .

The anaerobic bacterium has been increasingly linked to the development of degenerative disc disease (DDD), although causality is yet to be conclusively proven. To better study how this organism could contribute to the aetiology of DDD, improved animal models that are more reflective of human disc anatomy, biology and mechanical properties are required. Against this background, our proof-of concept study aimed to be the first demonstration that could be safely administered percutaneously into sheep intervertebral discs (IVDs) for in vivo study.

Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen .

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1β, may be further evidence of the role of the anaerobic bacterium (previously ) in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1β, and other known IL-1β-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with for up to 48 h. Upon infection, significant upregulation of IL-1β, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls.

Is the "Common Cold" Our Greatest Ally in the Battle Against SARS-CoV-2?

The discovery of T-cell responses to SARS-CoV-2 in non-infected individuals indicates cross-reactive immune memory from prior exposure to human coronaviruses (HCoV) that cause the common cold. This raises the possibility that "immunity" could exist within populations at rates that may be higher than serology studies estimate. Besides specialized research labs, however, there is limited ability to measure HCoV CD4+ and CD8+ T-cell responses to SARS-CoV-2 infection, which currently impedes interpretation of any potential correlation between COVID-19 disease pathogenesis and the calibration of pandemic control measures.

A statistically rigorous deep neural network approach to predict mortality in trauma patients admitted to the intensive care unit.

Background: Trauma patients admitted to critical care are at high risk of mortality because of their injuries. Our aim was to develop a machine learning-based model to predict mortality using Fahad-Liaqat-Ahmad Intensive Machine (FLAIM) framework. We hypothesized machine learning could be applied to critically ill patients and would outperform currently used mortality scores.

PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer.

Purpose: In both the IMpassion 130 trial in the metastatic setting and in Keynote 522 in the neoadjuvant setting, patients with triple-negative breast cancer (TNBC) showed benefit from PD-1 axis immunotherapy. Here, we assess PD-L1 expression on both tumor and immune cells using quantitative immunofluorescence to assess association with benefit from neoadjuvant durvalumab concurrent with chemotherapy in TNBC.

Experimental Design: Pretreatment core needle biopsies ( = 69) were obtained from patients who participated in a phase I/II clinical trial (NCT02489448).

Benign lymph node microenvironment is associated with response to immunotherapy.

Introduction: Benign lymph nodes have been considered the hubs of immune surveillance in cancer patients. The microenvironment of these lymphoid tissues can be immune suppressed, hence allowing for tumor progression. Understanding the spectrum of benign findings in bystander lymph nodes in immune checkpoint blockade therapy could prove to be key to understanding the mechanism and assessing treatment response.

An open source automated tumor infiltrating lymphocyte algorithm for prognosis in melanoma.

Assessment of tumor infiltrating lymphocytes (TILs) as a prognostic variable in melanoma has not seen broad adoption due to lack of standardization. Automation could represent a solution. Here, using open source software, we build an algorithm for image-based automated assessment of TILs on hematoxylin-eosin stained sections in melanoma.

Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy.

Purpose: Programmed death ligand 1 (PD-L1) is expressed in tumor cells and immune cells, and both have been associated with response to anti-PD-1 axis immunotherapy. Here, we examine the expression of PD-L1 to determine which cell type carries the predictive value of the test.

Experimental Design: We measured the expression of PD-L1 in multiple immune cells with two platforms and confocal microscopy on three retrospective Yale NSCLC cohorts (425 nonimmunotherapy-treated cases and 62 pembrolizumab/nivolumab/atezolizumab-treated cases).

Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non-Small Cell Lung Cancer.

Introduction: CKLF like MARVEL transmembrane domain containing 6 (CMTM6) has been described as a programmed death ligand 1 (PD-L1) regulator at the protein level by modulating stability through ubiquitination. In this study, we describe the patterns of CMTM6 expression and assess its association with response to programmed cell death 1 pathway blockade in NSCLC.

Methods: We used multiplexed quantitative immunofluorescence to determine the expression of CMTM6 and PD-L1 in 438 NSCLCs represented in tissue microarrays, including in two independent retrospective cohorts of immunotherapy-treated (n = 69) and non-immunotherapy-treated (n = 258) patients and a third collection of EGFR- and KRAS-genotyped tumors (n = 111).

A review of microscopy-based evidence for the association of Propionibacterium acnes biofilms in degenerative disc disease and other diseased human tissue.

Purpose: Recent research shows an increasing recognition that organisms not traditionally considered infectious in nature contribute to disease processes. Propionibacterium acnes (P. acnes) is a gram-positive, aerotolerant anaerobe prevalent in the sebaceous gland-rich areas of the human skin.

Importance of Propionibacterium acnes hemolytic activity in human intervertebral discs: A microbiological study.

Most patients with chronic lower back pain (CLBP) exhibit degenerative disc disease. Disc specimens obtained during initial therapeutic discectomies are often infected/colonized with Propionibacterium acnes, a Gram-positive commensal of the human skin. Although pain associated with infection is typically ascribed to the body's inflammatory response, the Gram-positive bacterium Staphylococcus aureus was recently observed to directly activate nociceptors by secreting pore-forming α-hemolysins that disrupt neuronal cell membranes.

Impact of Methamphetamine Abuse: A Rare Case of Rapid Cerebral Aneurysm Growth with Review of Literature.

Methamphetamine or "meth" is a sympathomimetic amine of the amphetamine-type substances (ATS) class with an extremely high potential for abuse. Illicitly abused neurostimulants like cocaine and meth predispose patients to the aneurysmal formation with reported rupture at a younger age and in much smaller sized aneurysms. However, very rapid growth of aneurysm within less than 2 weeks with methamphetamine abuse is very rarely observed or reported.

Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy.

Background: In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination.

Prevalence of Propionibacterium acnes in Intervertebral Discs of Patients Undergoing Lumbar Microdiscectomy: A Prospective Cross-Sectional Study.

Background: The relationship between intervertebral disc degeneration and chronic infection by Propionibacterium acnes is controversial with contradictory evidence available in the literature. Previous studies investigating these relationships were under-powered and fraught with methodical differences; moreover, they have not taken into consideration P. acnes' ability to form biofilms or attempted to quantitate the bioburden with regard to determining bacterial counts/genome equivalents as criteria to differentiate true infection from contamination.

Prothrombin Time and Activated Partial Thromboplastin Time Testing: A Comparative Effectiveness Study in a Million-Patient Sample.

Background: A substantial fraction of all American healthcare expenditures are potentially wasted, and practices that are not evidence-based could contribute to such waste. We sought to characterize whether Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) tests of preoperative patients are used in a way unsupported by evidence and potentially wasteful.

Methods And Findings: We evaluated prospectively-collected patient data from 19 major teaching hospitals and 8 hospital-affiliated surgical centers in 7 states (Delaware, Florida, Maryland, Massachusetts, New Jersey, New York, Pennsylvania) and the District of Columbia.