Targeted protein degradation using chimeric human E2 ubiquitin-conjugating enzymes.

Proteins can be targeted for degradation by engineering biomolecules that direct them to the eukaryotic ubiquitination machinery. For instance, the fusion of an E3 ubiquitin ligase to a suitable target binding domain creates a 'biological Proteolysis-Targeting Chimera' (bioPROTAC). Here we employ an analogous approach where the target protein is recruited directly to a human E2 ubiquitin-conjugating enzyme via an attached target binding domain.

How well do faculty do in providing general surgery EPA feedback?

Introduction: Entrustable Professional Activities (EPAs) provide a framework for competency-based assessment in surgery. EPA descriptions include observable behaviors by trainees at progressive levels of autonomy. The American Board of Surgery (ABS) required all General Surgery (GS) residency programs to implement assessment of 18 EPAs at the beginning of academic year 2023-2024.

Multi-institutional study examining intraoperative entrustment and resident sex.

Introduction: Single-site studies have found variable associations between gender and entrustment-based interactions during surgical residency. We sought to assess the relationship between resident sex and intraoperative entrustment at multiple institutions.

Methods: Surgical cases were observed at four university-based training programs.

Providing a Safe Pregnancy Experience for Surgeons: A Review.

Importance: Childbearing has been a particular barrier to successful recruitment and retention of women in surgery. Pregnant surgeons are more likely to have major pregnancy complications, such as preterm delivery, intrauterine growth restriction, infertility, and miscarriage, compared with nonsurgeons. The average obstetric complication rate for surgeons ranges between 25% and 82% in the literature and is considerably higher than that in the general US population at 5% to 15%.

Understanding futility in pancreaticoduodenectomy: Insights from a national cohort.

Background And Objectives: Pancreaticoduodenectomy (PD), the only surgical option for right-sided pancreatic ductal adenocarcinoma (PDAC), carries significant morbidity. Not all patients may be deriving a survival benefit from this operation. We sought to identify the rate of futile PD and its associated factors in a large national cohort.

Characterization of mAbs against type 3 fimbriae isolated in a target-independent phage display campaign.

We used phage display, antibody engineering, and high-throughput assays to identify antibody-accessible targets of . We report the discovery of monoclonal antibodies (mAbs) binding to type 3 fimbrial proteins, including MrkA. We found that anti-MrkA mAbs were cross-reactive to a diverse panel of clinical isolates, representing different O-serotypes.

Goals, Structure, and Financing of Surgical Residency Training: A Subcommittee Report of the Blue Ribbon Committee II.

Objective: As part of the Blue Ribbon Committee II, review current goals, structure and financing of surgical training in Graduate Medical Education (GME) and recommend needed changes.

Background: Surgical training has continually undergone major transitions with the 80-hour work week, earlier specialization (vascular, plastics, and cardiovascular), and now entrustable professional activities as part of competency-based medical education (CBME). Changes are needed to ensure the efficiencies of CBME are utilized, that stable graduate medical education funding is secured, and that support for surgeons who teach is made available.

Decision-Making Confidence of Clinical Competency Committees for Entrustable Professional Activities.

Importance: A competency-based assessment framework using entrustable professional activities (EPAs) was endorsed by the American Board of Surgery following a 2-year feasibility pilot study. Pilot study programs' clinical competency committees (CCCs) rated residents on EPA entrustment semiannually using this newly developed assessment tool, but factors associated with their decision-making are not yet known.

Objective: To identify factors associated with variation in decision-making confidence of CCCs in EPA summative entrustment decisions.

Predictability of B cell clonal persistence and immunosurveillance in breast cancer.

B cells and T cells are important components of the adaptive immune system and mediate anticancer immunity. The T cell landscape in cancer is well characterized, but the contribution of B cells to anticancer immunosurveillance is less well explored. Here we show an integrative analysis of the B cell and T cell receptor repertoire from individuals with metastatic breast cancer and individuals with early breast cancer during neoadjuvant therapy.

Validity of Entrustable Professional Activities in a National Sample of General Surgery Residency Programs.

Background: The American Board of Surgery has endorsed competency-based education as vital to the assessment of surgical training. From 2018 to 2020, a national pilot study was conducted at 28 general surgery programs to evaluate feasibility of implementing entrustable professional activities (EPAs) for 5 common general surgical conditions. ACGME core competency Milestones were also rated for each resident by program clinical competency committees.

Faculty Entrustment and Resident Entrustability.

Importance: As the surgical education paradigm transitions to entrustable professional activities, a better understanding of the factors associated with resident entrustability are needed. Previous work has demonstrated intraoperative faculty entrustment to be associated with resident entrustability. However, larger studies are needed to understand if this association is present across various surgical training programs.

Rapid discovery of high-affinity antibodies via massively parallel sequencing, ribosome display and affinity screening.

Developing therapeutic antibodies is laborious and costly. Here we report a method for antibody discovery that leverages the Illumina HiSeq platform to, within 3 days, screen in the order of 10 antibody-antigen interactions. The method, which we named 'deep screening', involves the clustering and sequencing of antibody libraries, the conversion of the DNA clusters into complementary RNA clusters covalently linked to the instrument's flow-cell surface on the same location, the in situ translation of the clusters into antibodies tethered via ribosome display, and their screening via fluorescently labelled antigens.

Enhancing the Value of Surgical Entrustable Professional Activities through Integrative Learning Analytics.

Objective: To demonstrate the value of integrating surgical resident Entrustable Professional Activity (EPA) data into a learning analytics platform that provides meaningful feedback for formative and summative decision-making.

Design: Description of the Surgical Entrustable Professional Activities (SEPA) analytics dashboard, and examples of summary analytics and intuitive display features.

Setting: Department of Surgery, University of Wisconsin Hospital and Clinics.

Repeated parallel differentiation of social learning differences in benthic and limnetic threespine stickleback fish.

Individuals can reduce sampling costs and increase foraging efficiency by using information provided by others. One simple form of social information use is delayed local enhancement or increased interest in a location because of the past presence of others. We tested for delayed local enhancement in two ecomorphs of stickleback fish, benthic and limnetic, from three different lakes with putative independent evolutionary origins.

Implementation of Entrustable Professional Activities in General Surgery: Results of a National Pilot Study.

Objective: The ongoing complexity of general surgery training has led to an increased focus on ensuring the competence of graduating residents. Entrustable professional activities (EPAs) are units of professional practice that provide an assessment framework to drive competency-based education. The American Board of Surgery convened a group from the American College of Surgeons, Accreditation Council for Graduate Medical Education (ACGME) Surgery Review Committee, and Association of Program Directors in Surgery to develop and implement EPAs in a pilot group of residency programs across the country.

Triplication of the interferon receptor locus contributes to hallmarks of Down syndrome in a mouse model.

Down syndrome (DS), the genetic condition caused by trisomy 21, is characterized by variable cognitive impairment, immune dysregulation, dysmorphogenesis and increased prevalence of diverse co-occurring conditions. The mechanisms by which trisomy 21 causes these effects remain largely unknown. We demonstrate that triplication of the interferon receptor (IFNR) gene cluster on chromosome 21 is necessary for multiple phenotypes in a mouse model of DS.

Implementation of entrustable professional activities into fellowship council accredited programs: a pilot project.

Objective: The Fellowship Council (FC) is transitioning to a competency-based medical education (CBME) model, including the introduction of Entrustable Professional Activities (EPAs) for training and assessment of Fellows. This study describes the implementation process employed by the FC during a ten-month pilot project and presents data regarding feasibility and perceived value.

Methods: The FC coordinated the development of EPAs in collaboration with the sponsoring societies for Advanced GI/MIS, Bariatrics, Foregut, Endoscopy and Hepatopancreaticobiliary (HPB) fellowships encompassing the preoperative, intraoperative, and postoperative phases of care for key competencies.

TrustEd: A Tool for Developing Intraoperative Entrustment Skills.

Objective: Toolkits to assess progressive resident autonomy are integral to the movement toward competency-based surgical education. OpTrust is one such tool validated for intraoperative assessment of both faculty and resident entrustment behaviors. We developed a supplementary tool to OpTrust that would aid faculty and residents in making meaningful improvements in entrustment behavior by providing talking points and reflection items tailored to different motivational styles as defined by Regulatory Focus Theory (RFT).

Multi-disciplinary assessment of the entrustable professional activities of surgery residents.

Purpose: Medicine is practiced in a collaborative and interdisciplinary manner. However, medical training and assessment remain largely isolated in traditional departmental silos. Two Entrustable Professional Activities (EPAs) developed by the American Board of Surgery are multidisciplinary in nature and offer a unique opportunity to study interdisciplinary assessment.

Phenotypic whole-cell screening identifies a protective carbohydrate epitope on .

The increasing global occurrence of recalcitrant multi-drug resistant infections warrants the investigation of alternative therapy options, such as the use of monoclonal antibodies (mAbs). We used a target-agnostic phage display approach to bacteria lacking bulky, highly variable surface polysaccharides in order to isolate antibodies targeting conserved epitopes among clinically relevant strains. One antibody population contained a high proportion of unique carbohydrate binders, and biolayer interferometry revealed these antibodies bound to lipopolysaccharide (LPS).

Imaging Assessment of Pancreatic Cancer Resectability After Neoadjuvant Therapy: Expert Panel Narrative Review.

Despite important innovations in the treatment of pancreatic ductal adenocarcinoma (PDAC), PDAC remains a disease with poor prognosis and high mortality. A key area for potential improvement in the management of PDAC, aside from earlier detection in patients with treatable disease, is the improved ability of imaging techniques to differentiate treatment response after neoadjuvant therapy (NAT) from worsening disease. It is well established that current imaging techniques cannot reliably make this distinction.

Trisomy of Human Chromosome 21 Orthologs Mapping to Mouse Chromosome 10 Cause Age and Sex-Specific Learning Differences: Relevance to Down Syndrome.

Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), is the most common genetic cause of intellectual disability. The Dp10(1)Yey (Dp10) is a mouse model of DS that is trisomic for orthologs of 25% of the Hsa21 protein-coding genes, the entirety of the Hsa21 syntenic region on mouse chromosome 10. Trisomic genes include several involved in brain development and function, two that modify and regulate the activities of sex hormones, and two that produce sex-specific phenotypes as null mutants.