Post-Chimeric Antigen Receptor T-Cell Therapy Hepatitis B Virus Reactivation After 23 Months of Entecavir Prophylaxis.

Hepatitis B virus (HBV) reactivation can occur in immunosuppressed patients. Specifically, HBV reactivation after chimeric antigen receptor T-cell (CAR T-cell) therapy is a known complication with few case reports and specific treatment guidelines. Our patient experienced HBV reactivation 27 months after CAR T-cell therapy even with 23 months of entecavir prophylaxis.

Evaluation and Assessment of the ABATE Framework to Enhance Implicit Bias Training for Virtual Interviews in Medical Schools.

Introduction: The influence of implicit biases in virtual interviews must be addressed to ensure equity within the admissions process. ABATE is a mnemonic framework of five specific categories of implicit bias (affinity-based, backdrop-based, appearance-based, technology and media-based, and enunciation-based biases) that should be anticipated and mitigated for faculty, staff, health professionals, and medical students who conduct virtual interviews at medical schools.

Methods: A 60-minute workshop was developed to educate medical school admissions interviewers about the ABATE model and strategies to mitigate implicit bias during virtual interviews.

Economic returns and the perceived obstacles to adopting active management in the forest-grassland transition ecoregion in south-central USA.

Forest-grassland ecotones are a mosaic of grassland, savanna, and upland forest. As such, landowners may have opportunities to choose to manage their lands for multiple objectives. We estimated the economic returns from managing forest and rangeland in southeastern Oklahoma, USA to produce different combinations of timber, cattle forage, and white-tailed deer (Odocoileus virginianus Zimmermann) browse for a 40-year period.

Confidence, Connection & Collaboration: Creating a Scalable Bias Reduction Improvement Coaching Train-the-Trainer Program to Mitigate Implicit Bias across a Medical Center.

Academic medical centers need to mitigate the negative effects of implicit bias with approaches that are empirically-based, scalable, sustainable, and specific to departmental needs. Guided by Kotter's Model of Change to create and sustain cultural change, we developed the Bias Reduction Improvement Coaching Program (BRIC), a two-year, train-the-trainer implicit bias coaching program designed to meet the increasing demand for bias training across a university medical center. BRIC trained a cohort of faculty and staff as coaches during four quarterly training sessions in Year 1 that covered 1) the science of bias, 2) bias in selection and hiring, 3) bias in mentoring, and 4) bias in promotion, retention, and workplace culture.

Review and synthesis of the global literature on domestic cat impacts on wildlife.

A vast global literature documents that free-roaming domestic cats (Felis catus) have substantial negative effects on wildlife, including through predation, fear, disease and competition-related impacts that have contributed to numerous wildlife extinctions and population declines worldwide. However, no study has synthesized this literature on cat impacts on wildlife to evaluate its overarching biases and major gaps. To direct future research and conservation related to cat impacts on wildlife, we conducted a global literature review that entailed evaluation and synthesis of patterns and gaps in the literature related to the geographic context, methods and types of impacts studied.

An institutional analysis of graduate outcomes reveals a contemporary workforce footprint for biomedical master's degrees.

There is continued growth in the number of master's degrees awarded in the life sciences to address the evolving needs of the biomedical workforce. Academic medical centers leverage the expertise of their faculty and industry partners to develop one to two year intensive and multidisciplinary master's programs that equip students with advanced scientific skills and practical training experiences. However, there is little data published on the outcomes of these graduates to evaluate the effectiveness of these programs and to inform the return on investment of students.

Gastric Emptying Scans: Poor Adherence to National Guidelines.

Background: Accurately diagnosing gastroparesis relies upon gastric emptying scintigraphy (GES) being performed correctly. Jointly published protocol guidelines have long been available; however, the extent to which practitioners adhere to these guidelines is unknown.

Aims: This study aimed to assess national compliance with established GES protocol guidelines.

Framework for advancing rigorous research.

There is a pressing need to increase the rigor of research in the life and biomedical sciences. To address this issue, we propose that communities of 'rigor champions' be established to campaign for reforms of the research culture that has led to shortcomings in rigor. These communities of rigor champions would also assist in the development and adoption of a comprehensive educational platform that would teach the principles of rigorous science to researchers at all career stages.

Novel recombinant papillomavirus genomes expressing selectable genes.

Papillomaviruses infect and replicate in keratinocytes, but viral proteins are initially expressed at low levels and there is no effective and quantitative method to determine the efficiency of infection on a cell-to-cell basis. Here we describe human papillomavirus (HPV) genomes that express marker proteins (antibiotic resistance genes and Green Fluorescent Protein), and can be used to elucidate early stages in HPV infection of primary keratinocytes. To generate these recombinant genomes, the late region of the oncogenic HPV18 genome was replaced by CpG free marker genes.

Brd4 Activates Early Viral Transcription upon Human Papillomavirus 18 Infection of Primary Keratinocytes.

Unlabelled: Human papillomaviruses (HPVs) replicate in the cutaneous and mucosal epithelia, and the infectious cycle is synchronous with the differentiation program of the host keratinocytes. The virus initially infects dividing cells in the lower layers of the epithelium, where it establishes a persistent infection. The viral genome is maintained as a low-copy-number, extrachromosomal element in these proliferating cells but switches to the late stage of the life cycle in differentiated cells.

The Role of the DNA Damage Response throughout the Papillomavirus Life Cycle.

The DNA damage response (DDR) maintains genomic integrity through an elaborate network of signaling pathways that sense DNA damage and recruit effector factors to repair damaged DNA. DDR signaling pathways are usurped and manipulated by the replication programs of many viruses. Here, we review the papillomavirus (PV) life cycle, highlighting current knowledge of how PVs recruit and engage the DDR to facilitate productive infection.

Co-opting the Fanconi anemia genomic stability pathway enables herpesvirus DNA synthesis and productive growth.

DNA damage associated with viral DNA synthesis can result in double-strand breaks that threaten genome integrity and must be repaired. Here, we establish that the cellular Fanconi anemia (FA) genomic stability pathway is exploited by herpes simplex virus 1 (HSV-1) to promote viral DNA synthesis and enable its productive growth. Potent FA pathway activation in HSV-1-infected cells resulted in monoubiquitination of FA effector proteins FANCI and FANCD2 (FANCI-D2) and required the viral DNA polymerase.

Global reprogramming of the cellular translational landscape facilitates cytomegalovirus replication.

Unlike many viruses that suppress cellular protein synthesis, host mRNA translation and polyribosome formation are stimulated by human cytomegalovirus (HCMV). How HCMV impacts the translationally regulated cellular mRNA repertoire and its contribution to virus biology remains unknown. Using polysome profiling, we show that HCMV presides over the cellular translational landscape, selectively accessing the host genome to extend its own coding capacity and regulate virus replication.

A new role for the cellular PABP repressor Paip2 as an innate restriction factor capable of limiting productive cytomegalovirus replication.

The capacity of polyadenylate-binding protein PABPC1 (PABP1) to stimulate translation is regulated by its repressor, Paip2. Paradoxically, while PABP accumulation promotes human cytomegalovirus (HCMV) protein synthesis, we show that this is accompanied by an analogous increase in the abundance of Paip2 and EDD1, an E3 ubiquitin ligase that destabilizes Paip2. Coordinate control of PABP1, Paip2, and EDD1 required the virus-encoded UL38 mTORC1 activator and resulted in augmented Paip2 synthesis, stability, and association with PABP1.

Poly(A) binding protein abundance regulates eukaryotic translation initiation factor 4F assembly in human cytomegalovirus-infected cells.

By commandeering cellular translation initiation factors, or destroying those dispensable for viral mRNA translation, viruses often suppress host protein synthesis. In contrast, cellular protein synthesis proceeds in human cytomegalovirus (HCMV)-infected cells, forcing viral and cellular mRNAs to compete for limiting translation initiation factors. Curiously, inactivating the host translational repressor 4E-BP1 in HCMV-infected cells stimulates synthesis of the cellular poly(A) binding protein (PABP), significantly increasing PABP abundance.

Translational control of the abundance of cytoplasmic poly(A) binding protein in human cytomegalovirus-infected cells.

Irrespective of their effects on ongoing host protein synthesis, productive replication of the representative alphaherpesvirus herpes simplex virus type 1, the representative gammaherpesvirus Kaposi's sarcoma herpesvirus, and the representative betaherpesvirus human cytomegalovirus [HCMV] stimulates the assembly of the multisubunit, cap-binding translation factor eIF4F. However, only HCMV replication is associated with an increased abundance of eIF4F core components (eIF4E, eIF4G, eIF4A) and the eIF4F-associated factor poly(A) binding protein (PABP). Here, we demonstrate that the increase in translation factor concentration was readily detected in an asynchronous population of HCMV-infected primary human fibroblasts, abolished by prior UV inactivation of virus, and genetically dependent upon viral immediate-early genes.

Cysteine scanning mutagenesis of TM5 reveals conformational changes in OxlT, the oxalate transporter of Oxalobacter formigenes.

We constructed a single-cysteine panel encompassing TM5 of the oxalate transporter, OxlT. The 25 positions encompassed by TM5 were largely tolerant of mutagenesis, and functional product was recovered for 21 of the derived variants. For these derivatives, thiol-directed MTS-linked agents (MTSEA, MTSCE, and MTSES) were used as probes of transporter function, yielding 11 mutants that responded to probe treatment, as indicated by effects on oxalate transport.

Enzymatically inactive U(S)3 protein kinase of Marek's disease virus (MDV) is capable of depolymerizing F-actin but results in accumulation of virions in perinuclear invaginations and reduced virus growth.

Marek's disease (MD) is a highly contagious, lymphoproliferative disease of chickens caused by the cell-associated MD virus (MDV), a member of the alphaherpesvirus subfamily. In a previous study we showed that the absence of the serine/threonine protein kinase (pU(S)3) encoded in the MDV unique-short region resulted in accumulation of primarily enveloped virions in the perinuclear space and significant impairment of virus growth in vitro. It was also shown that pU(S)3 is involved in actin stress fiber breakdown [Schumacher, D.