Nonclinical immunogenicity risk assessment for knobs-into-holes bispecific IgG antibodies.

Bispecific antibodies, including bispecific IgG, are emerging as an important new class of antibody therapeutics. As a result, we, as well as others, have developed engineering strategies designed to facilitate the efficient production of bispecific IgG for clinical development. For example, we have extensively used knobs-into-holes (KIH) mutations to facilitate the heterodimerization of antibody heavy chains and more recently Fab mutations to promote cognate heavy/light chain pairing for efficient assembly of bispecific IgG in single host cells.

Accessory lacrimal gland secretion mimicking seidel positivity following complex cataract surgery: Case report.

Purpose: To describe the presentation of lacrimal gland secretions mimicking a positive Seidel test following combined complex cataract surgery and endocyclophotocoagulation (ECP).

Observation: The patient presented with a posterior subcapsular cataract (PSC) most likely secondary to chronic steroid use for a history of chemical burns from a firework injury in 2019. This injury resulted in symblepharon formation and limbal stem cell deficiency.

Variable domain mutational analysis to probe the molecular mechanisms of high viscosity of an IgG antibody.

Subcutaneous injection is the preferred route of administration for many antibody therapeutics for reasons that include its speed and convenience. However, the small volume limit (typically 2 mL) for subcutaneous delivery often necessitates antibody formulations at high concentrations (commonly ≥100 mg/mL), which may lead to physicochemical problems. For example, antibodies with large hydrophobic or charged patches can be prone to self-interaction giving rise to high viscosity.

Hepatitis C: A Rare Cause of Subacute Paralysis.

The effects of the hepatitis C virus (HCV) on the nervous system have been primarily reported with a pathology of the peripheral nervous system through the involvement of a vasculitic process via cryoglobulinemia. A review of the recent literature reinforced the likely association between chronic HCV infection and transverse myelitis (TM), but the causal relationship remains elusive. Here, we present a rare case of acute TM developing over the course of days from symptom onset and a concomitant new diagnosis of HCV infection.

A Rare Case of Primary Anorectal Hodgkin Lymphoma in an HIV-Positive Patient: A Case Report and Literature Review.

Lymphoma is a well-known complication related to HIV infection; of these, non-Hodgkin lymphoma (NHL) is the most common subtype with Hodgkin lymphoma (HL) occurring less frequently. We present a rare case of a 35-year-old male with a history of HIV/AIDS well-controlled on antiretroviral therapy (ART) with an atypical HL presentation. He arrived at the emergency department with rectal bleeding, 30-pound unintentional weight loss, and subjective fever.

Evaluating and mitigating bias in machine learning models for cardiovascular disease prediction.

Objective: The study aims to investigate whether machine learning-based predictive models for cardiovascular disease (CVD) risk assessment show equivalent performance across demographic groups (such as race and gender) and if bias mitigation methods can reduce any bias present in the models. This is important as systematic bias may be introduced when collecting and preprocessing health data, which could affect the performance of the models on certain demographic sub-cohorts. The study is to investigate this using electronic health records data and various machine learning models.

Evaluating Predictive Value of Surgical Resected Proximal Bone Margins in Diabetic Foot Osteomyelitis With Clinical Outcomes at 1 Year.

Background: Osteomyelitis of the diabetic foot remains a significant complication that may result in the need for amputation. Proximal surgical margin histopathology after limb-sparing amputation could be used to guide antimicrobial duration and prognostic management but remains debatable. Here we evaluate if negative proximal bone margins predict outcomes of diabetic foot osteomyelitis at 1 year.

Management of Renal Angiomyolipomas in Tuberous Sclerosis Complex: A Case Report and Literature Review.

We report a case of misdiagnosed tuberous sclerosis complex (TSC) in a patient without TSC gene variant presenting with bilateral renal angiomyolipomas and seizures in the context of strong family history of polycystic kidney disease. Clinical diagnosis of tuberous sclerosis complex was made and treatment with everolimus reduced size of renal angiomyolipomas. In this case, report we discuss the association between tuberous sclerosis complex and polycystic kidney disease and novel treatment for TSC.

Glacial isostatic adjustment: physical models and observational constraints.

By far the most prescient insights into the interior structure of the planet have been provided on the basis of elastic wave seismology. Analysis of the travel times of shear or compression wave phases excited by individual earthquakes, or through analysis of the elastic gravitational free oscillations that individual earthquakes of sufficiently large magnitude may excite, has been the central focus of Earth physics research for more than a century. Unfortunately, data provide no information that is directly relevant to understanding the solid state 'flow' of the polycrystalline outer 'mantle' shell of the planet that is involved in the thermally driven convective circulation that is responsible for powering the 'drift' of the continents and which controls the rate of planetary cooling on long timescales.

Infective Endocarditis Presenting with Embolic Splenic and Renal Infarcts and Spinal Discitis.

(. ) is a Gram-positive, coagulase-negative bacteria that occurs as a normal commensal organism on the skin and may rarely cause native valve endocarditis (NVE). We present a 62-year-old male with type 2 diabetes mellitus, coronary artery disease, and hypertension presenting with fever and abdominal pain.

Integrating gene expression and clinical data to identify drug repurposing candidates for hyperlipidemia and hypertension.

Discovering novel uses for existing drugs, through drug repurposing, can reduce the time, costs, and risk of failure associated with new drug development. However, prioritizing drug repurposing candidates for downstream studies remains challenging. Here, we present a high-throughput approach to identify and validate drug repurposing candidates.

Epidemiology of Sepsis-Associated Acute Kidney Injury in Beijing, China: A Descriptive Analysis.

Background: Sepsis is the most common contributing factor towards development of acute kidney injury (AKI), which is strongly associated to poor prognostic outcomes. There are numerous epidemiological studies about sepsis-associated acute kidney injury (S-AKI), however current literature is limited with the majority of studies being conducted only in the intensive care unit (ICU) setting. The aim of this study was to assess the epidemiology of S-AKI in all hospitalized in-patients.

Gender-Related Differences in Chronic Kidney Disease-Associated Vascular Calcification Risk and Potential Risk Mediators: A Scoping Review.

Vascular calcification (VC) involves the deposition of calcium apatite in vascular intima or media. Individuals of advanced age, having diabetes mellitus or chronic kidney disease (CKD) are particularly at risk. The pathogenesis of CKD-associated VC evolves considerably.

Sequence2Script: A Web-Based Tool for Translation of Pharmacogenetic Data Into Evidence-Based Prescribing Recommendations.

Pharmacogenomic (PGx) testing has emerged as an effective strategy for informing drug selection and dosing. This has led to an increase in the use of PGx testing in the clinic and has catalyzed the emergence of a burgeoning commercial PGx testing industry. However, not all PGx tests are equivalent in their approach to translating testing results into prescribing recommendations, due to an absence of regulatory standards.

DDIWAS: High-throughput electronic health record-based screening of drug-drug interactions.

Objective: We developed and evaluated Drug-Drug Interaction Wide Association Study (DDIWAS). This novel method detects potential drug-drug interactions (DDIs) by leveraging data from the electronic health record (EHR) allergy list.

Materials And Methods: To identify potential DDIs, DDIWAS scans for drug pairs that are frequently documented together on the allergy list.

Survival Factors and Metabolic Pathogenesis in Elderly Patients (≥65) With COVID-19: A Multi-Center Study.

Elderly patients infected with COVID-19 are reported to be facing a substantially increased risk of mortality. Clinical characteristics, treatment options, and potential survival factors remain under investigation. This study aimed to fill this gap and provide clinically relevant factors associated with survival of elderly patients with COVID-19.