Chemotherapy in synergy with innate immune agonists enhances T cell priming for checkpoint inhibitor treatment in pancreatic cancer.

Background: The combination of conventional chemotherapy and immune checkpoint inhibitors (ICIs) has been unsuccessful for pancreatic ductal adenocarcinoma (PDAC). Administration of maximum tolerated dose of chemotherapy drugs may have immunosuppressive effects.

Methods: We thus tested, by using the preclinical model of PDACs including the genetically engineered mouse KPC spontaneous pancreatic tumor model and the pancreatic KPC tumor orthotopic implant model, the combinations of synthetic innate immune agonists including STING and NLRP3 agonist, respectively, and ICIs with or without chemotherapy.

Epidemiology of Coronavirus Disease 2019-Associated Fungal Infections in the Intensive Care Unit: A Single-Center Retrospective Study.

Introduction: Invasive fungal disease (IFD) is a morbid superinfection that can arise in critically ill patients with COVID-19 infection. Studies evaluating the full spectrum of COVID-19-associated fungal infections remain limited.

Methods: Single-center retrospective study assessing IFD in patients with COVID-19, hospitalized for ≥ 72 h in the intensive care unit (ICU) between 02/25/20 and 02/28/22 (n = 1410).

Cancer associated fibroblasts drive epithelial to mesenchymal transition and classical to basal change in pancreatic ductal adenocarcinoma cells with loss of IL-8 expression.

Pancreatic ductal adenocarcinoma (PDAC) carries an extremely poor prognosis, in part resulting from cellular heterogeneity that supports overall tumorigenicity. Cancer associated fibroblasts (CAF) are key determinants of PDAC biology and response to systemic therapy. While CAF subtypes have been defined, the effects of patient-specific CAF heterogeneity and plasticity on tumor cell behavior remain unclear.

Investigation and successful control of a outbreak at a tertiary health care facility in Kenya.

Objectives: This study aimed to conduct an epidemiological and genomic investigation of a hospital outbreak of , and implement measures for its control.

Methods: We collected demographic and clinical data from medical records of patients with from January 2017 to June 2019 after identifying increased cases in April 2019. Point-prevalence surveys for colonisation were conducted in the critical care units (CCU).

Emergency department discharges directly to hospice: Longitudinal assessment of a streamlined referral program.

Introduction: 80 % of Americans wish to die somewhere other than a hospital, and hospice is an essential resource for providing such care. The emergency department (ED) is an important location for identifying patients with end-of-life care needs and providing access to hospice. The objective of this study was to analyze a quality improvement (QI) program designed to increase the number of patients referred directly to hospice from the ED, without the need for an observation stay and without access to in-hospital hospice.

Recognition of Antifungal-Resistant Dermatophytosis by Infectious Diseases Specialists, United States.

Antifungal-resistant dermatophyte infections have recently emerged as a global public health concern. A survey of US infectious diseases specialists found that only 65% had heard of this issue and just 39% knew how to obtain testing to determine resistance. Increased clinician awareness and access to testing for antifungal-resistant dermatophytosis are needed.

PanIN and CAF transitions in pancreatic carcinogenesis revealed with spatial data integration.

This study introduces a new imaging, spatial transcriptomics (ST), and single-cell RNA-sequencing integration pipeline to characterize neoplastic cell state transitions during tumorigenesis. We applied a semi-supervised analysis pipeline to examine premalignant pancreatic intraepithelial neoplasias (PanINs) that can develop into pancreatic ductal adenocarcinoma (PDAC). Their strict diagnosis on formalin-fixed and paraffin-embedded (FFPE) samples limited the single-cell characterization of human PanINs within their microenvironment.

Overcome the challenge for intratumoral injection of STING agonist for pancreatic cancer by systemic administration.

Due to the challenge for intratumoral administration, innate agonists have not made it beyond preclinical studies for efficacy testing in most tumor types. Pancreatic ductal adenocarcinoma (PDAC) has a hostile tumor microenvironment that renders T cells dysfunctional. Innate agonist treatments may serve as a T cell priming mechanism to sensitize PDACs to anti-PD-1 antibody (a-PD-1) treatment.

Molecular and Epidemiological Investigation of Fluconazole-resistant -Georgia, United States, 2021.

Background: Reports of fluconazole-resistant bloodstream infections are increasing. We describe a cluster of fluconazole-resistant bloodstream infections identified in 2021 on routine surveillance by the Georgia Emerging Infections Program in conjunction with the Centers for Disease Control and Prevention.

Methods: Whole-genome sequencing was used to analyze bloodstream infections isolates.

Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells.

Candida auris in US Correctional Facilities.

Candida auris is an emerging fungal pathogen that typically affects patients in healthcare settings. Data on C. auris cases in correctional facilities are limited but are needed to guide public health recommendations.

screening practices at healthcare facilities in the United States: An Emerging Infections Network survey.

We surveyed members of the Emerging Infections Network about screening practices at US healthcare facilities. Only 37% of respondents reported conducting screening; among these, 75% reported detection of at least 1 case in the last year. Increased screening could improve detection and prevent spread.

Genomic epidemiology and antifungal-resistant characterization of , Colombia, 2016-2021.

Unlabelled: Since 2016, in Colombia, ongoing transmission of has been reported in multiple cities. Here, we provide an updated description of genomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates from cases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences from cases were described in a phylogenetic analysis.

Genomic description of acquired fluconazole- and echinocandin-resistance in patients with serial isolates.

is one of the most common causes of systemic candidiasis, often resistant to antifungal medications. To describe the genomic context of emerging resistance, we conducted a retrospective analysis of 82 serially collected isolates from 33 patients from population-based candidemia surveillance in the United States. We used whole-genome sequencing to determine the genetic relationships between isolates obtained from the same patient.

Persistent colonization of among inpatients rescreened as part of a weekly surveillance program.

We established a surveillance program to evaluate persistence of colonization among hospitalized patients. Overall, 17 patients (34%) had ≥1 negative result followed by a positive test, and 7 (41%) of these patients had ≥2 consecutive negative tests.

CD4 T cell-activating neoantigens enhance personalized cancer vaccine efficacy.

Personalized cancer vaccines aim to activate and expand cytotoxic antitumor CD8+ T cells to recognize and kill tumor cells. However, the role of CD4+ T cell activation in the clinical benefit of these vaccines is not well defined. We previously established a personalized neoantigen vaccine (PancVAX) for the pancreatic cancer cell line Panc02, which activates tumor-specific CD8+ T cells but required combinatorial checkpoint modulators to achieve therapeutic efficacy.

Rapid Environmental Contamination With Candida auris and Multidrug-Resistant Bacterial Pathogens Near Colonized Patients.

Background: Environmental contamination is suspected to play an important role in Candida auris transmission. Understanding speed and risks of contamination after room disinfection could inform environmental cleaning recommendations.

Methods: We conducted a prospective multicenter study of environmental contamination associated with C.

Treatment of Sulfur Mustard Corneal Injury by Augmenting the DNA Damage Response (DDR): A Novel Approach.

Sulfur mustard (SM) is a highly reactive organic chemical has been used as a chemical warfare agent and terrorist threat since World War I. The cornea is highly sensitive to SM toxicity and exposure to low vapor doses can cause incapacitating acute injuries. Exposure to higher doses can elicit persistent secondary keratopathies that cause reduced quality of life and impaired or lost vision.

Public Health Research Priorities for Fungal Diseases: A Multidisciplinary Approach to Save Lives.

Fungal infections can cause severe disease and death and impose a substantial economic burden on healthcare systems. Public health research requires a multidisciplinary approach and is essential to help save lives and prevent disability from fungal diseases. In this manuscript, we outline the main public health research priorities for fungal diseases, including the measurement of the fungal disease burden and distribution and the need for improved diagnostics, therapeutics, and vaccines.