Cotargeting EBV lytic as well as latent cycle antigens increases T-cell potency against lymphoma.

The remarkable efficacy of Epstein-Barr virus (EBV)-specific T cells for the treatment of posttransplant lymphomas has not been reproduced for EBV-positive (EBV+) malignancies outside the transplant setting. This is because of, in part, the heterogeneous expression and poor immunogenicity of the viral antigens expressed, namely latent membrane proteins 1 and 2, EBV nuclear antigen 1, and BamHI A rightward reading frame 1 (type-2 [T2] latency). However, EBV lytic cycle proteins are also expressed in certain EBV+ malignancies and, because several EBV lytic cycle proteins are abundantly expressed, have oncogenic activity, and likely contribute to malignancy, we sought and identified viral lytic-cycle transcripts in EBV+ Hodgkin lymphoma biopsies.

Genital Tucking Practices in Transgender and Gender Diverse Patients.

Genital tucking (tucking) is the practice of hiding or minimizing the appearance of one's genitals and gonads. We aimed to better understand the prevalence of tucking and its potential effect on behavior and health. An online questionnaire was distributed to adults with a diagnosis of gender dysphoria or gender incongruence (n = 98).

Assessing efficacy of a web-based smoking cessation tool - QuitAdvisorMD: Protocol for a practice-based, clustered, randomized control trial.

Background: Smoking remains the leading cause of preventable death, yet physicians inconsistently provide best-practices cessation advice to smokers. Point-of-care digital health tools can prompt and assist physicians to provide improved smoking cessation counseling. QuitAdvisorMD is a comprehensive web-based counseling and management digital health tool designed to guide smoking cessation counseling at the point-of-care.

Constitutive Interleukin-7 Cytokine Signaling Enhances the Persistence of Epstein-Barr Virus-Specific T-Cells.

The efficacy of therapeutic T-cells is limited by a lack of positive signals and excess inhibitory signaling in tumor microenvironments. We previously showed that a constitutively active IL7 receptor (C7R) enhanced the persistence, expansion, and anti-tumor activity of T-cells expressing chimeric antigen receptors (CARs), and C7R-modified GD2.CAR T-cells are currently undergoing clinical trials.

Engaging Family Medicine Residents in a Structured Patient Panel Reassignment Process.

Background And Objectives: The patient panels of graduating residents must be reassigned by the end of residency. This process affects over 1 million patients annually within the specialty of family medicine. The purpose of this project was to implement a structured, year-end reassignment system in a family medicine residency program.

Enhancing your scholarship as a family medicine junior faculty member.

Family medicine faculty are often expected to produce some form of scholarship as members of academic departments. However, this can be challenging given a range of contextual factors, including limited research capacity in many departments, increased competition for funding and individual challenges around balancing multiple roles, unclear expectations and lack of mentorship, to name a few. The purpose of this reflection is to discuss seven content areas that might be addressed by faculty in order to promote scholarship, particularly among junior faculty.

Utilizing the F3App to Capture Learner Feedback About Faculty Teaching.

Background And Objectives: The Accreditation Council for Graduate Medical Education requires soliciting learner feedback on faculty teaching, although gathering meaningful feedback is challenging in the medical education environment. We developed the Faculty Feedback Facilitator (F3App), a mobile application that allows for real-time capture of narrative feedback by residents. The purpose of our study was to assess efficacy, usability, and acceptability of the F3App in family medicine residency programs.

Fat-Phobic and Non-Fat-Phobic Anorexia Nervosa: A Conjoint Analysis on the Importance of Shape and Weight.

With the introduction of new diagnostic criteria in DSM-5, fear of weight gain no longer represents a sine qua non-criterion for the diagnosis of anorexia nervosa (AN). This is of relevance as a subgroup of individuals with AN denies fear of weight gain as the reason for restrictive eating but still remain at a very low weight. As self-reports are susceptible to bias, other methods are needed to confirm the existence of the subtype in order to provide adapted treatment.

Common Medical Concerns of the Female Athlete.

Women are increasingly participating in more and more sporting activities. For years, women athletes have been treated as the "female" equivalent of male athletes, with similar medical approaches but this is changing. The concept that women are unique in their "athletic arena" is further underscored with emerging scientific evidence--from the physiologic details not visible to the eye, to the more overt biomechanical and anatomic differences.

T-Cell Receptor Stimulation Enhances the Expansion and Function of CD19 Chimeric Antigen Receptor-Expressing T Cells.

Purpose: Current protocols for CD19 chimeric antigen receptor-expressing T cells (CD19.CAR-T cells) require recipients to tolerate preinfusion cytoreductive chemotherapy, and the presence of sufficient target antigen on normal or malignant B cells.

Patients And Methods: We investigated whether additional stimulation of CD19.

Residency Faculty Teaching Evaluation: What Do Faculty, Residents, and Program Directors Want?

Background And Objectives: The Accreditation Council for Graduate Medical Education Common Residency Program Requirements stipulate that each faculty member's performance be evaluated annually. Feedback is essential to this process, yet the culture of medicine poses challenges to developing effective feedback systems. The current study explores existing and ideal characteristics of faculty teaching evaluation systems from the perspectives of key stakeholders: faculty, residents, and residency program directors (PDs).

School Absenteeism in Children and Adolescents.

Frequent school absenteeism has immediate and long-term negative effects on academic performance, social functioning, high school and college graduation rates, adult income, health, and life expectancy. Previous research focused on distinguishing between truancy and anxiety-driven school refusal, but current policy has shifted to reducing absenteeism for any reason. Chronic absenteeism appears to be driven by overlapping medical, individual, family, and social factors, including chronic illness, mental health conditions, bullying, perceived lack of safety, health problems or needs of other family members, inconsistent parenting, poor school climate, economic disadvantage, and unreliable transportation.

Efficacy of intracellular immune checkpoint-silenced DC vaccine.

Background: DC-based tumor vaccines have had limited clinical success thus far. SOCS1, a key inhibitor of inflammatory cytokine signaling, is an immune checkpoint regulator that limits DC immunopotency.

Methods: We generated a genetically modified DC (gmDC) vaccine to perform immunotherapy.

Celiac Disease and Gluten Sensitivity.

Celiac disease is an immune-mediated enteropathy triggered by gluten that affects genetically predisposed individuals, typically causing intestinal symptoms and malabsorption. Diagnosis requires stepwise evaluation with anti-tissue transglutaminase IgA and histologic analysis of the small bowel. Strict adherence to a gluten-free diet is the primary treatment.

Comprehensive Approach for Identifying the T Cell Subset Origin of CD3 and CD28 Antibody-Activated Chimeric Antigen Receptor-Modified T Cells.

The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45ROCCR7 effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population.

Large-Scale Culture and Genetic Modification of Human Natural Killer Cells for Cellular Therapy.

Recent advances in methods for the ex vivo expansion of human natural killer (NK) cells have facilitated the use of these powerful immune cells in clinical protocols. Further, the ability to genetically modify primary human NK cells following rapid expansion allows targeting and enhancement of their immune function. We have successfully adapted an expansion method for primary NK cells from peripheral blood mononuclear cells or from apheresis products in gas permeable rapid expansion devices (G-Rexes).

Early transduction produces highly functional chimeric antigen receptor-modified virus-specific T-cells with central memory markers: a Production Assistant for Cell Therapy (PACT) translational application.

Background: Virus-specific T-cells (VSTs) proliferate exponentially after adoptive transfer into hematopoietic stem cell transplant (HSCT) recipients, eliminate virus infections, then persist and provide long-term protection from viral disease. If VSTs behaved similarly when modified with tumor-specific chimeric antigen receptors (CARs), they should have potent anti-tumor activity. This theory was evaluated by Cruz et al.

Responding to a changing nation: are faculty prepared for cross-cultural conversations and care?

Background And Objectives: The United States is becoming increasingly diverse. Health disparities continue with little improvement despite national policies and standards. Medical institutions are modifying their curricula; however, little is known about faculty attitudes and comfort in addressing cultural issues.

Improving smoking cessation counseling using a point-of-care health intervention tool (IT): from the Virginia Practice Support and Research Network (VaPSRN).

Purpose: Primary care practices are an ideal setting for reducing national smoking rates because >70% of smokers visit their physician annually, yet smoking cessation counseling is inconsistently delivered to patients. We designed and created a novel software program for handheld computers and hypothesized that it would improve clinicians' ability to provide patient-tailored smoking cessation counseling at the point of care.

Methods: A handheld computer software program was created based on smoking cessation guidelines and an adaptation of widely accepted behavioral change theories.

Evaluation of long-term transgene expression in piggyBac-modified human T lymphocytes.

The piggyBac transposon system is a promising nonviral method to genetically modify T cells for immunotherapeutic applications. To evaluate the regulation and stability of transgene expression in human T cells modified with piggyBac-transposons, peripheral blood mononuclear cells were nucleofected with transposase and an enhanced green fluorescence protein (eGFP)-expressing transposon. Single-cell clones that were subsequently stimulated and expanded exhibited homogenous eGFP expression for >26 weeks in culture.

Evaluation of a screening and counseling tool for alcohol misuse: a Virginia Practice Support and Research Network (VaPSRN) trial.

Background: Surveys reveal limited screening and counseling for alcohol misuse by primary care physicians despite evidence-based recommendations. We developed and evaluated an alcohol screening and misuse counseling tool designed to assist clinicians at the point of care (POC).

Methods: This was a mixed methods, prospective cohort study conducted with licensed clinicians in a practice-based research network.

Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications.

Background Aims: Interest in natural killer (NK) cell-based immunotherapy has resurged since new protocols for the purification and expansion of large numbers of clinical-grade cells have become available.

Methods: We have successfully adapted a previously described NK expansion method that uses K562 cells expressing interleukin (IL)-15 and 4-1 BB Ligand (BBL) (K562-mb15-41BBL) to grow NK cells in novel gas-permeable static cell culture flasks (G-Rex).

Results: Using this system we produced up to 19 × 10(9) functional NK cells from unseparated apheresis products, starting with 15 × 10(7) CD3(-) CD56 (+) NK cells, within 8-10 days of culture.