The Next Chapter in Immunotherapy and Radiation Combination Therapy: Cancer-Specific Perspectives.

Immunotherapeutic agents have revolutionized cancer treatment over the past decade. However, most patients fail to respond to immunotherapy alone. A growing body of preclinical studies highlights the potential for synergy between radiation therapy and immunotherapy, but the outcomes of clinical studies have been mixed.

A Fiji process for quantifying fluorescent puncta in linear cellular structures.

Understanding the cell biology of protein trafficking and homeostasis requires reproducible methods for identifying and quantifying proteins within cells or cellular structures. Imaging protocols for measuring punctate protein accumulation in linear structures, for example the neurites of have relied on proprietary software for a full range of analysis capabilities. Here we describe a set of macros written for the NIH-supported imaging software ImageJ or Fiji (Fiji is Just ImageJ) that reliably identify protein puncta so that they can be analyzed with respect to intensity, density, and width at half-maximum intensity (Full-Width, Half-Maximum, FWHM).

Healthcare Professionals' Perspectives on Improving Dietary Supplement Documentation in the Electronic Medical Record: Current Challenges and Opportunities to Enhance Quality of Care and Patient Safety.

Background: Around half the US population uses dietary supplements (DS), and concomitant use with medications is common. Many DS include bioactive substances that can interact with medications; therefore, accurate tracking is critical for patient safety. Unfortunately, documentation of patients' DS use is often missing or incomplete in the electronic medical record (EMR), leaving patients susceptible to potential adverse events.

Using viral sequence diversity to estimate time of HIV infection in infants.

Age at HIV acquisition may influence viral pathogenesis in infants, and yet infection timing (i.e. date of infection) is not always known.

Self-Reported Food Security in Adolescents with Type 1 Diabetes: Association with Hemoglobin A and Mental Health Symptoms Independent of Household Food Security.

Background: Typically, child exposure to food insecurity is assessed by caregiver reports of household food security. Child report has the potential for greater accuracy because it pertains only to the child whose experiences may differ from caregiver reports.

Objective: We assessed if adolescent-reported food insecurity was associated with levels of hemoglobin A (HbA), acute diabetes-related complications, depressive symptoms, and disordered eating behaviors in adolescents with type 1 diabetes, independently from household food security.

Unveiling the link between genetic alterations in gamma secretase and BCMA surface density in multiple myeloma.

Cattaneo et al. report a unique case of a multiple myeloma patient with elevated B-cell maturation antigen (BCMA) surface density, potentially due to genetic alterations in the gamma-secretase protease complex-responsible for BCMA cleavage from plasma cells. No mutations in the BCMA gene were detected, but there was partial deletion of PSEN1 and amplification of PSEN2 (components of the gamma-secretase complex), which may explain the lack of response to the gamma-secretase inhibitor DAPT.

Identification of 1600 replication origins in .

There are approximately 500 known origins of replication in the yeast genome, and the process by which DNA replication initiates at these locations is well understood. In particular, these sites are made competent to initiate replication by loading of the Mcm replicative helicase prior to the start of S phase; thus, "a site to which MCM is bound in G1" might be considered to provide an operational definition of a replication origin. By fusing a subunit of Mcm to micrococcal nuclease, a technique referred to as "Chromatin Endogenous Cleavage", we previously showed that known origins are typically bound by a single Mcm double hexamer, loaded adjacent to the ARS consensus sequence (ACS).

Assessing vaccine-mediated protection in an ultra-low dose Mycobacterium tuberculosis murine model.

Despite widespread immunization with Bacille-Calmette-Guérin (BCG), the only currently licensed tuberculosis (TB) vaccine, TB remains a leading cause of mortality globally. There are many TB vaccine candidates in the developmental pipeline, but the lack of a robust animal model to assess vaccine efficacy has hindered our ability to prioritize candidates for human clinical trials. Here we use a murine ultra-low dose (ULD) Mycobacterium tuberculosis (Mtb) challenge model to assess protection conferred by BCG vaccination.

Dynamics and durability of HIV-1 neutralization are determined by viral replication.

Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART).

The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies.

The wide endemic range of mosquito-vectored flaviviruses-such as Zika virus and dengue virus serotypes 1-4-places hundreds of millions of people at risk of infection every year. Despite this, there are no widely available vaccines, and treatment of severe cases is limited to supportive care. An avenue toward development of more widely applicable vaccines and targeted therapies is the characterization of monoclonal antibodies that broadly neutralize all these viruses.

Data analytics improves the diagnostic accuracy of serum free light chain results for detecting monoclonal gammopathy.

Objectives: To evaluate the real-world performance and reference intervals of the Binding Site Freelite serum free light chain (SFLC) assay (Thermo Fisher Scientific), a global standard for diagnosis, prognostication, and response assessment for monoclonal gammopathies.

Methods: An informatics-based approach was used to retrospectively evaluate concordance between SFLC and the orthogonal Sebia HYDRASYS immunofixation assay results in a large clinical data set consecutively reported between 2010 and 2020.

Results: Among patients with monoclonal-negative results by both SFLC and Sebia HYDRASYS immunofixation assays, 25% (1226/5057) had κ/λ ratios (KLRs) outside the manufacturer-defined and International Myeloma Working Group-cited normal reference interval of 0.

Context-specific synthetic T cell promoters from assembled transcriptional elements.

Genetic engineering of human lymphocytes for therapeutic applications is constrained by a lack of transgene transcriptional control, resulting in a compromised therapeutic index. Incomplete understanding of transcriptional logic limits the rational design of contextually responsive genetic modules1. Here, we juxtaposed rationally curated transcriptional response element (TRE) oligonucleotides by random concatemerization to generate a library from which we selected context-specific inducible synthetic promoters (iSynPros).

Significance of SF3B1 Mutations in Myeloid Neoplasms.

Myelodysplastic neoplasm with low blasts and SF3B1 mutation (MDS-LB-SF3B1) has undergone significant classification changes in the past year with the publication of the 5th edition of the World Health Organization Classification of Tumors of Haematopoietic and Lymphoid Tissues and the International Consensus Classification. This article reviews the basic biology of SF3B1, iron metabolism, and dysfunction that leads to the formation of ring sideroblasts. It highlights neoplastic and non-neoplastic considerations to the differential diagnoses.

Flow Cytometric Assessment of Myelodysplastic Syndromes/Neoplasms.

Myelodysplastic syndromes/neoplasms (MDS) are a heterogeneous class of hematopoietic stem cell neoplasms characterized by ineffective hematopoiesis leading to peripheral cytopenias. This group of diseases is typically diagnosed using a combination of clinical, morphologic, and genetic criteria. Many studies have described the value of multiparametric flow cytometry (MFC) in the diagnosis, classification, and prognostication of MDS.

The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies.

Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches.

Failure to launch? Or a 30-year career detour? A users' manual for supporting second-career scientists in your immunology lab.

Laboratory science sometimes looks like it's built exclusively for young people, but if you look closely, you'll find another group of scientists waiting to join your lab: those of us who didn't quite launch our careers on a normal trajectory. Welcoming a second-career scientist into your lab takes time and resources, but may just be well worth it. Here's what one second-career scientist wants you to know about supporting second careers in immunology.

Protocol for evaluating mechanistic pathways associated with HIV acquisition via nested Least Absolute Shrinkage and Selective Operator analysis.

Statistical analysis to evaluate mechanistic pathways can be limited by non-causal associations as well as co-linearity of high-dimensional data. Here, we present a protocol evaluating statistical associations between multiple exposure variables (sociodemographic and behavioral), immune biomarkers, and HIV acquisition. We describe steps for study setup, combining Least Absolute Shrinkage and Selective Operator with the standard regression approach, and building nested models.

Inequities in Definitive Treatment for Localized Prostate Cancer Among Those With Clinically Significant Mental Health Disorders.

Introduction: Patients with mental health disorders are at risk for receiving inequitable cancer treatment, likely resulting from various structural, social, and health-related factors. This study aims to assess the relationship between mental health disorders and the use of definitive treatment in a population-based cohort of those with localized, clinically significant prostate cancer.

Methods: We conducted a cohort study analysis in SEER (Surveillance, Epidemiology, and End Results)-Medicare (2004-2015).

Having a Say Matters: The Association Between Home Health Aides' Voice and Job Satisfaction.

Purpose: Despite a rapidly growing need for home health aides (HHAs), turnover rates are high. While this is driven in large part by the demanding nature of their work and low wages, another factor may be that HHAs are often not considered part of the medical team which can leave them feeling unheard by other healthcare professionals. We sought to determine whether this concept, or HHAs' perceived voice, was associated with job satisfaction.

Versatile Tissue-Injectable Hydrogels with Extended Hydrolytic Release of Bioactive Protein Therapeutics.

Hydrogels generally have broad utilization in healthcare due to their tunable structures, high water content, and inherent biocompatibility. FDA-approved applications of hydrogels include spinal cord regeneration, skin fillers, and local therapeutic delivery. Drawbacks exist in the clinical hydrogel space, largely pertaining to inconsistent therapeutic exposure, short-lived release windows, and difficulties inserting the polymer into tissue.

Partner testing with HIV self-test distribution by Ugandan pregnant women living with HIV: a randomized trial.

Introduction: Secondary distribution of HIV self-tests (HIVST) by HIV-negative pregnant women to male partners increases men's testing rates. We examined whether this strategy promotes male partner testing for pregnant women living with HIV (PWLHIV).

Methods: We conducted an open-label individually randomized trial in Kampala, Uganda, in which PWLHIV ≥18 years who reported a partner of unknown HIV status were randomized 2:1 to secondary distribution of HIVST for male partner(s) or standard-of-care (SOC; invitation letter to male partner for fast-track testing).