A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade.

Immune checkpoint inhibitors demonstrate clinical activity in many tumor types, however, only a fraction of patients benefit. Combining CD137 agonists with these inhibitors increases anti-tumor activity preclinically, but attempts to translate these observations to the clinic have been hampered by systemic toxicity. Here we describe a human CD137xPD-L1 bispecific antibody, MCLA-145, identified through functional screening of agonist- and immune checkpoint inhibitor arm combinations.

Parsaclisib Is a Next-Generation Phosphoinositide 3-Kinase Inhibitor with Reduced Hepatotoxicity and Potent Antitumor and Immunomodulatory Activities in Models of B-Cell Malignancy.

The clinical use of first-generation phosphoinositide 3-kinase (PI3K) inhibitors in B-cell malignancies is hampered by hepatotoxicity, requiring dose reduction, treatment interruption, and/or discontinuation of therapy. In addition, potential molecular mechanisms by which resistance to this class of drugs occurs have not been investigated. Parsaclisib (INCB050465) is a potent and selective next-generation PI3K inhibitor that differs in structure from first-generation PI3K inhibitors and has shown encouraging anti-B-cell tumor activity and reduced hepatotoxicity in phase 1/2 clinical studies.

INCB050465 (Parsaclisib), a Novel Next-Generation Inhibitor of Phosphoinositide 3-Kinase Delta (PI3Kδ).

A medicinal chemistry effort focused on identifying a structurally diverse candidate for phosphoinositide 3-kinase delta (PI3Kδ) led to the discovery of clinical candidate INCB050465 (, parsaclisib). The unique structure of contains a pyrazolopyrimidine hinge-binder in place of a purine motif that is present in other PI3Kδ inhibitors, such as idelalisib (), duvelisib (), and INCB040093 (, dezapelisib). Parsaclisib () is a potent and highly selective inhibitor of PI3Kδ with drug-like ADME properties that exhibited an excellent in vivo profile as demonstrated through pharmacokinetic studies in rats, dogs, and monkeys and through pharmacodynamic and efficacy studies in a mouse Pfeiffer xenograft model.

Mobile Health Divide Between Clinicians and Patients in Cancer Care: Results From a Cross-Sectional International Survey.

Background: Mobile technologies are increasingly being used to manage chronic diseases, including cancer, with the promise of improving the efficiency and effectiveness of care. Among the myriad of mobile technologies in health care, we have seen an explosion of mobile apps. The rapid increase in digital health apps is not paralleled by a similar trend in usage statistics by clinicians and patients.

Interprofessional education and practice guide: interprofessional team writing to promote dissemination of interprofessional education scholarship and products.

Collaborations to develop, implement, evaluate, replicate, and write about interprofessional education (IPE) activities within and across institutions are wonderful opportunities to experience teamwork, team communication, ethics and values, and the roles and responsibilities of interprofessional team writing. Just as effective communication in interprofessional team-based care is essential for providing safe, high-quality health care, similar communication strategies are necessary to produce high-quality scholarship of IPE curricula and activities. Relationship and communication issues that affect health care teams' abilities to work together effectively (e.

Preclinical characterization of INCB053914, a novel pan-PIM kinase inhibitor, alone and in combination with anticancer agents, in models of hematologic malignancies.

The Proviral Integration site of Moloney murine leukemia virus (PIM) serine/threonine protein kinases are overexpressed in many hematologic and solid tumor malignancies and play central roles in intracellular signaling networks important in tumorigenesis, including the Janus kinase-signal transducer and activator of transcription (JAK/STAT) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. The three PIM kinase isozymes (PIM1, PIM2, and PIM3) share similar downstream substrates with other key oncogenic kinases and have differing but mutually compensatory functions across tumors. This supports the therapeutic potential of pan-PIM kinase inhibitors, especially in combination with other anticancer agents chosen based on their role in overlapping signaling networks.

Effectiveness of the South African expanded program of immunization against hepatitis B in children infected with human immunodeficiency virus-1 living in a resource-limited setting of Kwazulu-Natal.

Prevalence of Human-Immunodeficiency-Virus/Hepatitis-B-virus (HIV/HBV) coinfection and HBV vaccination response in children are unknown in Kwazulu-Natal. This study included 183 HIV-infected and 108 HIV-uninfected children aged between 5 and 15 years screened for HBV infection and vaccination. HBV infection occurred in 2.

Findings from a mixed-methods study of an interprofessional faculty development program.

Forty faculty members from eight schools participated in a year-long National Faculty Development Program (NFDP) conducted in 2012-2013, aimed at developing faculty knowledge and skills for interprofessional education (IPE). The NFDP included two live conferences. Between conferences, faculty teams implemented self-selected IPE projects at their home institutions and participated in coaching and peer-support conference calls.

The cancer experience map: an approach to including the patient voice in supportive care solutions.

The perspective of the patient, also called the "patient voice", is an essential element in materials created for cancer supportive care. Identifying that voice, however, can be a challenge for researchers and developers. A multidisciplinary team at a health information company tasked with addressing this issue created a representational model they call the "cancer experience map".

A model to support shared decision making in electronic health records systems.

Shared decision making (SDM) is an approach to medical care based on collaboration between provider and patient, with both sharing in medical decisions. When patients' values and preferences are incorporated in decision making, care is more appropriate, ethically sound, and often lower in cost. However, SDM is difficult to implement in routine practice because of the time required for SDM methods, the lack of integration of SDM approaches into electronic health record (EHR) systems, and absence of explanatory mechanisms for providers on the results of patients' use of decision aids.

Interprofessional Education and Practice Guide No. 1: developing faculty to effectively facilitate interprofessional education.

With the growth of interprofessional education (IPE) and practice in health professional schools, faculty members are being asked to assume new roles in leading or delivering interprofessional curriculum. Many existing faculty members feel ill-prepared to face the challenges of this curricular innovation. From 2012-2013, University of Missouri - Columbia and University of Washington partnered with six additional academic health centers to pilot a faculty development course to prepare faculty leaders for IPE.

Broad-range direct detection and identification of fungi by use of the PLEX-ID PCR-electrospray ionization mass spectrometry (ESI-MS) system.

The PLEX-ID system is a novel technology that couples PCR amplification and electrospray ionization-mass spectrometry to identify pathogens directly in clinical specimens. The analytical performance of the PLEX-ID Broad Fungal assay was compared with that of traditional culture identification by using 91 characterized fungal culture isolates (64 manufacturer-claimed and 27 nonclaimed organisms) and directly by using 395 respiratory specimens. Discordant results were resolved by D2 large-subunit ribosomal DNA fungal sequencing.

The second victim of adverse health care events.

Nurses and other professionals drawn to health care by their desire to help others may be traumatized because they are involved in situations that bring harm rather than healing to patients. Health systems should develop early warning systems to alert unit or team leaders when health workers are at risk of harm from adverse events. This article focuses on health professionals who become second victims of adverse events that occur to patients.

Evaluation of the Sensititre MycoTB plate for susceptibility testing of the Mycobacterium tuberculosis complex against first- and second-line agents.

The Sensititre MycoTB plate (TREK Diagnostic Systems, Cleveland, OH) uses a microtiter plate MIC format for susceptibility testing of Mycobacterium tuberculosis complex isolates against first- and second-line antituberculosis agents. Categorical agreement versus the agar proportion method for 122 M. tuberculosis complex isolates was 94% to 100%.

Formic acid-based direct, on-plate testing of yeast and Corynebacterium species by Bruker Biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry.

An on-plate testing method using formic acid was evaluated on the Bruker Biotyper matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry system using 90 yeast and 78 Corynebacterium species isolates, and 95.6 and 81.1% of yeast and 96.

Evaluation of the Yeast Traffic Light PNA FISH probes for identification of Candida species from positive blood cultures.

The Yeast Traffic Light PNA FISH kit (YTL) correctly identified Candida spp. in 207/216 (96%) positive blood cultures. Discordant results were seen with known cross-reacting species and cultures containing Candida lambica and Rhodotorula mucilaginosa.

Dermatophyte identification using matrix-assisted laser desorption ionization-time of flight mass spectrometry.

The performance of the Bruker Biotyper matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometer (MS) for the identification of dermatophytes from clinical cultures was compared to that of dermatophyte identification using 28S rRNA gene sequencing. The MALDI Biotyper library (MBL; version 3.0) was used alone and in combination with a supplemented library containing an additional 20 dermatophyte spectra (S-MBL).

A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3.

Purpose: The c-MET receptor tyrosine kinase plays important roles in the formation, progression, and dissemination of human cancer and presents an attractive therapeutic target. This study describes the preclinical characterization of INCB28060, a novel inhibitor of c-MET kinase.

Experimental Design: Studies were conducted using a series of in vitro and in vivo biochemical and biological experiments.

Molecular methods and platforms for infectious diseases testing a review of FDA-approved and cleared assays.

The superior sensitivity and specificity associated with the use of molecular assays has greatly improved the field of infectious disease diagnostics by providing clinicians with results that are both accurate and rapidly obtained. Herein, we review molecularly based infectious disease diagnostic tests that are Food and Drug Administration approved or cleared and commercially available in the United States as of December 31, 2010. We describe specific assays and their performance, as stated in the Food and Drug Administration's Summary of Safety and Effectiveness Data or the Office of In Vitro Diagnostic Device Evaluation and Safety's decision summaries, product inserts, or peer-reviewed literature.

Detection of Blastomyces dermatitidis and Histoplasma capsulatum from culture isolates and clinical specimens by use of real-time PCR.

Blastomyces dermatitidis and Histoplasma capsulatum are dimorphic fungi that often cause self-limited respiratory infections. However, they may also cause severe disseminated disease, depending on the level of the exposure to the organism and the host immune status. In addition, patients with infections caused by these fungi may have very similar clinical presentations.

Antimicrobial susceptibility testing of Mycobacterium tuberculosis complex for first and second line drugs by broth dilution in a microtiter plate format.

The rapid detection of antimicrobial resistance is important in the effort to control the increase in resistant Mycobacterium tuberculosis (Mtb). Antimicrobial susceptibility testing (AST) of Mtb has traditionally been performed by the agar method of proportion or by macrobroth testing on an instrument such as the BACTEC (Becton Dickinson, Sparks, MD), VersaTREK (TREK Diagnostics, Cleveland, OH) or BacT/ALERT (bioMérieux, Hazelwood, MO). The agar proportion method, while considered the "gold" standard of AST, is labor intensive and requires calculation of resistance by performing colony counts on drug-containing agar as compared to drug-free agar.

Performance and cost analysis of matrix-assisted laser desorption ionization-time of flight mass spectrometry for routine identification of yeast.

Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry was compared to phenotypic testing for yeast identification. MALDI-TOF mass spectrometry yielded 96.3% and 84.

Caring for our own: deploying a systemwide second victim rapid response team.

A unique rapid response system was designed to provide social, psychological, emotional, and professional support for health care providers who are "second victims"--traumatized as a result of their involvement in an unanticipated adverse event, medical error, or patient-related injury.