Background: The quality of cancer care affects patient outcomes. It is therefore important to understand what factors and/or barriers shape a cancer patient's decision about where to seek care. We sought to understand factors influencing decision-making for historically marginalized communities in a large metropolitan area with multiple options for cancer care, including a National Cancer Institute (NCI)-designated comprehensive cancer center.
View Article and Find Full Text PDFThe first results of the study of high-energy electron neutrino (ν_{e}) and muon neutrino (ν_{μ}) charged-current interactions in the FASERν emulsion-tungsten detector of the FASER experiment at the LHC are presented. A 128.8 kg subset of the FASERν volume was analyzed after exposure to 9.
View Article and Find Full Text PDFThe engineering of novel protein-ligand binding interactions, particularly for complex drug-like molecules, is an unsolved problem, which could enable many practical applications of protein biosensors. In this work, we analyzed two engineered biosensors, derived from the plant hormone sensor PYR1, to recognize either the agrochemical mandipropamid or the synthetic cannabinoid WIN55,212-2. Using a combination of quantitative deep mutational scanning experiments and molecular dynamics simulations, we demonstrated that mutations at common positions can promote protein-ligand shape complementarity and revealed prominent differences in the electrostatic networks needed to complement diverse ligands.
View Article and Find Full Text PDFAntibodies are engineerable quantities in medicine. Learning antibody molecular recognition would enable the in silico design of high affinity binders against nearly any proteinaceous surface. Yet, publicly available experiment antibody sequence-binding datasets may not contain the mutagenic, antigenic, or antibody sequence diversity necessary for deep learning approaches to capture molecular recognition.
View Article and Find Full Text PDFThe engineering of novel protein-ligand binding interactions, particularly for complex drug-like molecules, is an unsolved problem which could enable many practical applications of protein biosensors. In this work, we analyzed two engineer ed biosensors, derived from the plant hormone sensor PYR1, to recognize either the agrochemical mandipropamid or the synthetic cannabinoid WIN55,212-2. Using a combination of quantitative deep mutational scanning experiments and molecular dynamics simulations, we demonstrated that mutations at common positions can promote protein-ligand shape complementarity and revealed prominent differences in the electrostatic networks needed to complement diverse ligands.
View Article and Find Full Text PDFAntibodies are engineerable quantities in medicine. Learning antibody molecular recognition would enable the design of high affinity binders against nearly any proteinaceous surface. Yet, publicly available experiment antibody sequence-binding datasets may not contain the mutagenic, antigenic, or antibody sequence diversity necessary for deep learning approaches to capture molecular recognition.
View Article and Find Full Text PDFDue to a combination of asymptomatic or undiagnosed infections, the proportion of the United States population infected with SARS-CoV-2 was unclear from the beginning of the pandemic. We previously established a platform to screen for SARS-CoV-2 positivity across a representative proportion of the US population, from which we reported that almost 17 million Americans were estimated to have had undocumented infections in the Spring of 2020. Since then, vaccine rollout and prevalence of different SARS-CoV-2 variants have further altered seropositivity trends within the United States population.
View Article and Find Full Text PDFWe report the first direct observation of neutrino interactions at a particle collider experiment. Neutrino candidate events are identified in a 13.6 TeV center-of-mass energy pp collision dataset of 35.
View Article and Find Full Text PDFIntroduction: With the flood of engineered antibodies, there is a heightened need to elucidate the structural features of antibodies that contribute to specificity, stability, and breadth. While antibody flexibility and interface angle have begun to be explored, design rules have yet to emerge, as their impact on the metrics above remains unclear. Furthermore, the purpose of framework mutations in mature antibodies is highly convoluted.
View Article and Find Full Text PDFAims: Our primary objective was to determine whether all-cause rates of mortality and resource utilization were higher during periods of diabetic foot ulceration. In support of this objective, a secondary objective was to develop and validate an episode-of-care model for diabetic foot ulceration.
Methods: We evaluated data from the Medicare Limited Data Set between 2013 and 2019.
Monoclonal antibodies (mAbs) are an important class of therapeutics used to treat cancer, inflammation, and infectious diseases. Identifying highly developable mAb sequences could greatly reduce the time and cost required for therapeutic mAb development. Here, we present position-specific scoring matrices (PSSMs) for antibody framework mutations developed using baseline human antibody repertoire sequences.
View Article and Find Full Text PDFBMJ Open Diabetes Res Care
June 2021
In this study, we determined the reamputation-free survival to both limbs and to the contralateral limb only following an index amputation of any-level and assessed whether reamputation rates have changed over time. We completed a systematic search using PubMed and screened a total of 205 articles for data on reamputation rates. We reported qualitative characteristics of 56 studies that included data on reamputation rates and completed a meta-analysis on 22 of the studies which enrolled exclusively participants with diabetes.
View Article and Find Full Text PDFObjectives: To conduct a scoping review that (1) describes what is known about the relationship between athletic identity and sport-related injury outcomes and (2) describes the relationship that an injury (as an exposure) has on athletic identity (as an outcome) in athletes.
Design: Scoping review.
Participants: A total of n=1852 athletes from various sport backgrounds and levels of competition.
Introduction: We assessed the impact of a diabetic foot ulcer prevention program incorporating once-daily foot temperature monitoring on hospitalizations, emergency department and outpatient visits, and rates of diabetic foot ulcer recurrence and lower extremity amputations for patients with recently healed foot ulcers.
Research Design And Methods: In this retrospective analysis of real-world data, we enrolled 80 participants with a healed diabetic foot ulcer in a year-long foot ulcer recurrence prevention program. Four outpatient centers within a large integrated healthcare system in the USA contributed to enrollment.
Introduction: Foot ulcers are a common and costly complication of diabetes, and delays in treatment can result in impaired healing, infection, hospitalization, and lower extremity amputation.
Research Design And Methods: We aimed to determine whether patterns in plantar diabetic foot ulcer (DFU) recurrence coincided with typical intervals between routine preventive care appointments, which would suggest that delays exist between ulcer development and identification. We completed an analysis of existing data from two multicenter studies in 300 total participants.
Introduction: Diabetic foot ulcers (DFUs) are responsible for considerable morbidity, mortality, and cost. Remote temperature monitoring (RTM) is an evidenced-based and recommended component of standard foot care for at-risk patients. Although previous research has demonstrated the value of RTM for foot ulcer prevention, its benefits related to the early identification of diabetic foot complications may be underappreciated.
View Article and Find Full Text PDFAims: To assess the accuracy of once-daily foot temperature monitoring for predicting foot ulceration in diabetic patients with recent wounds and partial foot amputation, complications previously perceived as challenging.
Methods: We completed a planned analysis of existing data from a recent study in 129 participants with a previously-healed diabetic foot ulcer. We considered four cohorts: all participants, participants with partial foot amputation, participants with a recent wound, and participants without partial foot amputation and without a recent wound.
Background: Developing novel therapeutic agents to treat amyotrophic lateral sclerosis (ALS) has been difficult due to multifactorial pathophysiologic processes at work. Intrathecal drug administration shows promise due to close proximity of cerebrospinal fluid (CSF) to affected tissues. Development of effective intrathecal pharmaceuticals will rely on accurate models of how drugs are dispersed in the CSF.
View Article and Find Full Text PDFBackground: The "cancer analogy" is powerful for communicating risk to and organizing care for patients with diabetic foot syndrome. One potentially underappreciated similarity between cancer and foot ulcers is that both can recur at anatomical locations distinct from the primary occurrence, albeit with different physiological mechanisms. Few studies have characterized the location of diabetic foot ulcer recurrence, and these have been limited by considering only the first recurrent wound following a recent-healed wound.
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