Heavy chain-only antibodies with a stabilized human VH in transgenic chickens for therapeutic antibody discovery.

Heavy chain-only antibodies have found many applications where conventional heavy-light heterodimeric antibodies are not favorable. Heavy chain-only antibodies with their single antigen-binding domain offer the advantage of a smaller size and higher stability relative to conventional antibodies, and thus, the potential for novel targeting modalities. Domain antibodies have commonly been sourced from camelids with humanization or transgenic rodents expressing heavy chains without light chains, but these host species are all mammalian, limiting their capacity to elicit robust immune responses to conserved mammalian targets.

Tambjamines as Fast-Acting Multistage Antimalarials.

Well-tolerated and novel antimalarials that can combat multiple stages of the parasite life cycle are desirable but challenging to discover and develop. Herein, we report results for natural product-inspired novel tambjamine antimalarials. We show that they are potent against liver, asexual erythrocytic, and sexual erythrocytic parasite life cycle stages.

Optimization of B-Ring-Functionalized Antimalarial Tambjamines and Prodiginines.

Malaria has been a deadly enemy of mankind throughout history, affecting over 200 million people annually, along with approximately half a million deaths. Resistance to current therapies is of great concern, and there is a dire need for novel and well-tolerated antimalarials that operate by clinically unexploited mechanisms. We have previously reported that both tambjamines and prodiginines are highly potent novel antiplasmodial agents, but they required rigor optimizations to enhance the oral efficacy, safety, and physicochemical properties.

Avoidable admissions after minimally invasive hysterectomy.

Objective: To determine the rate of avoidable admissions following anticipated same-day discharge for patients undergoing minimally invasive hysterectomy and to identify risk factors associated with such admissions.

Methods: A retrospective review was performed of patients who underwent a minimally invasive hysterectomy between March 2019 and July 2021 for a suspected gynecologic malignancy at a single tertiary care center. Pre-operatively, patients were assessed for same-day discharge versus planned admission.

Discovery and Optimization of Tambjamines as a Novel Class of Antileishmanial Agents.

Leishmaniasis is a neglected tropical disease that is estimated to afflict over 12 million people. Current drugs for leishmaniasis suffer from serious deficiencies, including toxicity, high cost, modest efficacy, primarily parenteral delivery, and emergence of widespread resistance. We have discovered and developed a natural product-inspired tambjamine chemotype, known to be effective against spp, as a novel class of antileishmanial agents.

Small bite fascial closure technique reduces incisional hernia rates in gynecologic oncology patients.

Background: The potential for the technique of small bite fascial closure in mitigating incisional hernias in gynecologic oncology patients still needs to be investigated.

Objective: To evaluate the impact of closure of small fascial bites compared with prior standard closure on incisional hernia rates in gynecologic oncology patients.

Methods: This is a retrospective cohort study comparing patient outcomes before and after the intervention at a single institution at a comprehensive cancer center.

Chickens with a Truncated Light Chain Transgene Express Single-Domain H Chain-Only Antibodies.

H chain-only Igs are naturally produced in camelids and sharks. Because these Abs lack the L chain, the Ag-binding domain is half the size of a traditional Ab, allowing this type of Ig to bind to targets in novel ways. Consequently, the H chain-only single-domain Ab (sdAb) structure has the potential to increase the repertoire and functional range of an active humoral immune system.

UV-C LED-induced cyclobutane pyrimidine dimer formation, lesion repair and mutagenesis in the biofilm-forming diatom, .

The use of ultraviolet-C (UV-C) irradiation in marine biofouling control is a relatively new and potentially disruptive technology. This study examined effects of UV-C exposure on the biofilm-forming diatom, . UV-C-induced mutations were identified Illumina HiSeq.

Implementation of routine venous thromboembolism prophylaxis during neoadjuvant chemotherapy for patients with ovarian cancer.

Objective: To compare the venous thromboembolism (VTE) rate in patients with ovarian cancer undergoing neoadjuvant chemotherapy before and after implementing routine thromboprophylaxis.

Methods: This is a quasi-experimental pre-post study evaluating the VTE rate in patients with ovarian cancer who received neoadjuvant chemotherapy following a quality improvement initiative of routine thromboprophylaxis within a single healthcare system that started in January 2017. Patients were excluded if VTE was diagnosed before initiating chemotherapy.

Provider compliance with a tailored opioid prescribing calculator in gynecologic surgery.

Objective: To evaluate the impact a tailored opioid prescription calculator has on meeting individual patient opioid needs while avoiding opioid over prescriptions.

Methods: Our group previously developed and published an opioid prescribing calculator incorporating patient risk factors (history of depression, anxiety, chronic opioid use, substance abuse disorder, and/or chronic pain) and type of surgery (laparotomy or laparoscopy). This calculator was implemented on 1/1/2021 and its impact on opioid prescriptions was evaluated until 12/31/21.

A computational model for microbial colonization of an antifouling surface.

Biofouling of marine surfaces such as ship hulls is a major industrial problem. Antifouling (AF) paints delay the onset of biofouling by releasing biocidal chemicals. We present a computational model for microbial colonization of a biocide-releasing AF surface.

NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

Optimization of postoperative opioid prescriptions in gynecologic oncology: Striking a balance between opioid reduction and pain control.

Objective: To implement a quality-improvement initiative to assess the impact various patient and procedural factors have on postoperative opioid use. To develop a tailored opioid prescribing algorithm for gynecologic oncology patients.

Methods: A retrospective cohort study was performed of patients who underwent a laparoscopy or laparotomy procedure for a suspected or known gynecologic malignancy between 3/2019-9/2020.

Total Synthesis and Antimalarial Activity of 2-(-Hydroxybenzyl)-prodigiosins, Isoheptylprodigiosin, and Geometric Isomers of Tambjamine MYP1 Isolated from Marine Bacteria.

Highly efficient and straightforward synthetic routes toward the first total synthesis of 2-(-hydroxybenzyl)-prodigiosins (-), isoheptylprodigiosin (), and geometric isomers of tambjamine MYP1 ((/)-) have been developed. The crucial steps involved in these synthetic routes are the construction of methoxy-bipyrrole-carboxaldehydes (MBCs) and a 20-membered macrocyclic core and a regioselective demethylation of MBC analogues. These new synthetic routes enabled us to generate several natural prodiginines - in larger quantity.

Multidisciplinary Clinical Considerations in the Treatment of Pediatric Epithelial Ovarian Cancer.

Background: Epithelial ovarian cancers are a rare subset of the less than 1% of ovarian cancers diagnosed in children. This case highlights considerations when caring for these patients.

Case: Evaluation of a 12-year-old postmenarchal girl who presented with suprapubic pain revealed a solid/cystic pelvic mass involving bilateral adnexa and elevated Cancer Antigen 125 (CA-125) level.

Common light chain chickens produce human antibodies of high affinity and broad epitope coverage for the engineering of bispecifics.

Bispecific antibodies are an important and growing segment in antibody therapeutics, particularly in the immuno-oncology space. Manufacturing of a bispecific antibody with two different heavy chains is greatly simplified if the light chains can be the same for both arms of the antibody. Here, we introduce a strain of common light chain chickens, called OmniClic®, that produces antibody repertoires largely devoid of light chain diversity.

NCCN Guidelines Insights: Cervical Cancer, Version 1.2020.

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

Lead Optimization of Second-Generation Acridones as Broad-Spectrum Antimalarials.

The global impact of malaria remains staggering despite extensive efforts to eradicate the disease. With increasing drug resistance and the absence of a clinically available vaccine, there is an urgent need for novel, affordable, and safe drugs for prevention and treatment of malaria. Previously, we described a novel antimalarial acridone chemotype that is potent against both blood-stage and liver-stage malaria parasites.

Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer.

BACKGROUNDEpidemiologic studies suggest that metformin has antitumor effects. Laboratory studies indicate metformin impacts cancer stem-like cells (CSCs). As part of a phase II trial, we evaluated the impact of metformin on CSC number and on carcinoma-associated mesenchymal stem cells (CA-MSCs) and clinical outcomes in nondiabetic patients with advanced-stage epithelial ovarian cancer (EOC).

Using Quality Improvement Methodology to Reduce Costs while Improving Efficiency and Provider Satisfaction in a Busy, Academic Musculoskeletal Radiology Division.

Within an everchanging healthcare system, continuous evaluation of standard operating procedures must be performed to ensure optimization of system level organization, communication, and efficiency. Using the Lean management approach, our institution introduced modifications to our musculoskeletal (MSK) radiology workflow in order to facilitate beneficial change that improved clinical workflow efficiency, reduced moonlighting costs, and improved radiologist satisfaction without sacrificing quality of care. The scope of our study included the MSK division of adult inpatient and outpatient populations at three hospitals in a single academic medical center.

Thermoplastic, rubber-like marine antifouling coatings with micro-structures mechanical embossing.

New processing routes and materials for non-biocidal, antifouling (AF) coatings with an improved performance are currently much sought after for a range of marine applications. Here, the processing, physical properties and marine AF performance of a fluorinated coating based on a thermoplastic (non-crosslinked) fluorinated polymer are reported. It was found that the addition of lubricating oil and hydrodynamic drag reducing microstructures improved the AF properties substantially, i.

Implementation of a standardized voiding management protocol to reduce unnecessary re-catheterization - A quality improvement project.

Objective: To design and implement a standardized postoperative voiding management protocol that accurately identifies patients with urinary retention and reduces unnecessary re-catheterization.

Methods: A postoperative voiding management protocol was designed and implemented in patients undergoing major, inpatient, non-radical abdominal surgery with a gynecologic oncologist. No patients had epidural catheters.

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

Nonfreezable Water and Polymer Swelling Control the Marine Antifouling Performance of Polymers with Limited Hydrophilic Content.

Zwitterionic chemical groups have well-documented resistance to marine fouling species when presented as homogeneous polymer brushes. These model formulations are not, however, suitable for practical fouling-control applications. It is presently unknown if a uniform film of zwitterions is required to elicit nonfouling character via the binding of interfacial water or if the incorporation of zwitterionic functionality into a more practical bulk polymer system will suffice.

Trends in surgical complexity and treatment modalities utilized in the management of ovarian cancer in an era of neoadjuvant chemotherapy.

Objectives: To investigate the impact of the increased use of neoadjuvant chemotherapy on the complexity of cytoreductive surgeries for ovarian cancer.

Methods: Using the National Cancer Database, we performed a retrospective cohort study of women diagnosed between 2004 and 2015 with stage III or IV epithelial ovarian cancer who underwent either primary cytoreductive surgery (PDS) followed by adjuvant chemotherapy, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery. Cases were assigned a surgical complexity category as 1) Inadequate, 2) Low, 3) Moderate and, 4) High complexity.