The Importance of Social Determinants of Health for Cancer Patients in the Era of COVID-19.

The COVID-19 pandemic has proven to be a challenge for public health professionals, researchers, clinicians, and patients. One group that has experienced significant difficulties during this time is cancer patients. Data regarding this vulnerable population is scarce, despite novel information about vaccine efficacy, therapeutics, mutations, and comorbidities. In this article, we discuss the need for a greater study of social determinants of health (SDOH) for cancer patients in the context of the COVID-19 pandemic. The effects of SDOH on population health are generally well-understood, but their effects on cancer patients are poorly understood. We further pose questions that may be starting points for the investigation of SDOH in cancer patients during this time. Using SDOH as a tool for more effective clinical care will promote the development of targeted interventions to study and improve outcomes in this population.

Concurrent Nephrotoxicity and Neurotoxicity Induced by Oral Valacyclovir in a Patient With Previously Normal Kidney Function.

Drug-induced nephrotoxicity and neurotoxicity are commonly encountered problems in clinical practice. We describe a case of concurrent valacyclovir-induced nephrotoxicity and neurotoxicity in a 64-year-old man with no history of renal disease who developed acute renal injury and neurological symptoms after he received two weeks of the standard dose of oral valacyclovir for herpes zoster meningitis. His clinical condition improved significantly after the initiation of hemodialysis. Although nephrotoxicity due to intravenous infusion of valacyclovir and/or acyclovir is not uncommon, oral valacyclovir therapy is rarely associated with nephrotoxicity in patients with no history of renal insufficiency. Additionally, concurrent nephrotoxicity and neurotoxicity due to valacyclovir and/or acyclovir are rarely reported. Clinicians should be aware of these adverse events as immediate recognition and intervention are necessary to prevent morbidity.

Social Determinants of Health in Oncology: Towards a More Personalized and Equitable Delivery of Cancer Care.

Social determinants of health (SDOH) are defined as the set of modifiable social and physical risk factors that affect health. It is known that SDOH directly influence the population's overall health, but their effects on patients with cancer are considerably less elucidated. Here, we review the literature describing the effects of SDOH outlined by the Healthy People 2020 framework on patients diagnosed with cancer. We have found that while some SDOH are well-defined in cancer patients, evidence surrounding several variables is scarce. In addition, we have found that many SDOH are associated with disparities at the screening stage, indicating that upstream interventions are necessary before addressing the clinical outcomes themselves. Further investigation is warranted to understand how SDOH affect screenings and outcomes in multiple disciplines of oncology and types of cancers as well as explore how SDOH affect the treatments sought by these vulnerable patients.

State-of-the-Art Data Management: Improving the Reproducibility, Consistency, and Traceability of Structural Biology and in Vitro Biochemical Experiments.

Efficient and comprehensive data management is an indispensable component of modern scientific research and requires effective tools for all but the most trivial experiments. The LabDB system developed and used in our laboratory was originally designed to track the progress of a structure determination pipeline in several large National Institutes of Health (NIH) projects. While initially designed for structural biology experiments, its modular nature makes it easily applied in laboratories of various sizes in many experimental fields. Over many years, LabDB has transformed into a sophisticated system integrating a range of biochemical, biophysical, and crystallographic experimental data, which harvests data both directly from laboratory instruments and through human input via a web interface. The core module of the system handles many types of universal laboratory management data, such as laboratory personnel, chemical inventories, storage locations, and custom stock solutions. LabDB also tracks various biochemical experiments, including spectrophotometric and fluorescent assays, thermal shift assays, isothermal titration calorimetry experiments, and more. LabDB has been used to manage data for experiments that resulted in over 1200 deposits to the Protein Data Bank (PDB); the system is currently used by the Center for Structural Genomics of Infectious Diseases (CSGID) and several large laboratories. This chapter also provides examples of data mining analyses and warnings about incomplete and inconsistent experimental data. These features, together with its capabilities for detailed tracking, analysis, and auditing of experimental data, make the described system uniquely suited to inspect potential sources of irreproducibility in life sciences research.

Albumin-Based Transport of Nonsteroidal Anti-Inflammatory Drugs in Mammalian Blood Plasma.

Every day, hundreds of millions of people worldwide take nonsteroidal anti-inflammatory drugs (NSAIDs), often in conjunction with multiple other medications. In the bloodstream, NSAIDs are mostly bound to serum albumin (SA). We report the crystal structures of equine serum albumin complexed with four NSAIDs (ibuprofen, ketoprofen, etodolac, and nabumetone) and the active metabolite of nabumetone (6-methoxy-2-naphthylacetic acid, 6-MNA). These compounds bind to seven drug-binding sites on SA. These sites are generally well-conserved between equine and human SAs, but ibuprofen binds to both SAs in two drug-binding sites, only one of which is common. We also compare the binding of ketoprofen by equine SA to binding of it by bovine and leporine SAs. Our comparative analysis of known SA complexes with FDA-approved drugs clearly shows that multiple medications compete for the same binding sites, indicating possibilities for undesirable physiological effects caused by drug-drug displacement or competition with common metabolites. We discuss the consequences of NSAID binding to SA in a broader scientific and medical context, particularly regarding achieving desired therapeutic effects based on an individual's drug regimen.

Molstack: A platform for interactive presentations of electron density and cryo-EM maps and their interpretations.

In the Special Issue on Tools for Protein Science in 2018, we presented Molstack: a concept of a cloud-based platform for sharing electron density maps and their interpretations. Molstack is a web platform that allows the interactive visualization of density maps through the simultaneous presentation of multiple datasets and models in a way that allows for easy pairwise comparison. We anticipated that the users of this conceptually simple platform would find many different uses for their projects, and we were not mistaken. We have observed researchers use Molstack to present experimental evidence for their models in the form of electron density maps, omit maps, and anomalous difference density maps. Users also employed Molstack to present alternative interpretations of densities, including rerefinements and speculative interpretations. While we anticipated these types of projects to be the main use cases, we were pleased to see Molstack used to display superpositions of different models, as a tool for story-driven presentations, and for collaboration as well. Here, we present developments in the platform that were driven by user feedback, highlight several cases that used Molstack to enhance the publication, and discuss possible directions for the platform.

Testosterone meets albumin - the molecular mechanism of sex hormone transport by serum albumins.

Serum albumin is the most abundant protein in mammalian blood plasma and is responsible for the transport of metals, drugs, and various metabolites, including hormones. We report the first albumin structure in complex with testosterone, the primary male sex hormone. Testosterone is bound in two sites, neither of which overlaps with the previously suggested Sudlow site I. We determined the binding constant of testosterone to equine and human albumins by two different methods: tryptophan fluorescence quenching and ultrafast affinity extraction. The binding studies and similarities between residues comprising the binding sites on serum albumins suggest that testosterone binds to the same sites on both proteins. Our comparative analysis of albumin complexes with hormones, drugs, and other biologically relevant compounds strongly suggests interference between a number of compounds present in blood and testosterone transport by serum albumin. We discuss a possible link between our findings and some phenomena observed in human patients, such as low testosterone levels in diabetic patients.