There can be adverse psychosocial outcomes for children who have negative healthcare experiences. Identifying children's risk for experiencing elevated distress early on when entering the healthcare setting would allow targeted, proactive support to help mitigate negative psychological sequelae. The aim of this retrospective study was to evaluate the psychometric properties of the Pediatric Emotional Safety Screener (PESS), designed to screen for psychosocial distress for pediatric patients.
View Article and Find Full Text PDFPatients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters.
View Article and Find Full Text PDFIntroduction: Dry eye disease (DED) is multifactorial and characterized by a loss of tear film homeostasis that causes a cycle of tear film instability, tear hyperosmolarity, and inflammation. While artificial tears are the traditional mainstay of treatment, addressing the underlying pathophysiology could relieve symptoms and prevent progression. Increasing evidence indicates a role for oral nutritional supplementation in multiple ophthalmic diseases, including DED.
View Article and Find Full Text PDFBackground: Little is known about how the brains of autistic children process language during real-world "social contexts," despite the fact that challenges with language, communication, and social interaction are core features of Autism Spectrum Disorder (ASD).
Methods: We investigated the neural bases of language processing during social and non-social contexts in a sample of =20 autistic and =20 neurotypical (NT) preschool-aged children, 3 to 6 years old. Functional near-infrared spectroscopy (fNIRS) was used to measure children's brain response to "live language" spoken by a live experimenter during an in-person social context (i.
The electrochemical aptamer-based (EAB) sensor platform is the only molecular monitoring approach yet reported that is (1) real time and effectively continuous, (2) selective enough to deploy in the living body, and (3) independent of the chemical or enzymatic reactivity of its target, rendering it adaptable to a wide range of analytes. These attributes suggest the EAB platform will prove to be an important tool in both biomedical research and clinical practice. To advance this possibility, here we have explored the stability of EAB sensors upon storage, using retention of the target recognizing aptamer, the sensor's signal gain, and the affinity of the aptamer as our performance metrics.
View Article and Find Full Text PDFBackground And Purpose: The ability to measure specific molecules at multiple sites within the body simultaneously, and with a time resolution of seconds, could greatly advance our understanding of drug transport and elimination.
Experimental Approach: As a proof-of-principle demonstration, here we describe the use of electrochemical aptamer-based (EAB) sensors to measure transport of the antibiotic vancomycin from the plasma (measured in the jugular vein) to the cerebrospinal fluid (measured in the lateral ventricle) of live rats with temporal resolution of a few seconds.
Key Results: In our first efforts, we made measurements solely in the ventricle.
Background: First generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.
View Article and Find Full Text PDFElectrochemical aptamer-based (EAB) sensors represent the first molecular measurement technology that is both (1) independent of the chemical reactivity of the target, and thus generalizable to many targets and (2) able to function in an accurate, drift-corrected manner in situ in the living body. Signaling in EAB sensors is generated when an electrode-bound aptamer binds to its target ligand, altering the rate of electron transfer from an attached redox reporter and producing an easily detectable change in peak current when the sensor is interrogated using square wave voltammetry. Due to differences in the microscopic surface area of the interrogating electrodes, the baseline peak currents obtained from EAB sensors, however, can be highly variable.
View Article and Find Full Text PDFLittle is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions.
View Article and Find Full Text PDFElectrochemical aptamer-based sensors support the high-frequency, real-time monitoring of molecules-of-interest in vivo. Achieving this requires methods for correcting the sensor drift seen during in vivo placements. While this correction ensures EAB sensor measurements remain accurate, as drift progresses it reduces the signal-to-noise ratio and precision.
View Article and Find Full Text PDFBrexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for treatment of relapsed/refractory mantle cell lymphoma (MCL). During a fludarabine shortage, we used bendamustine as an alternative to standard cyclophosphamide/fludarabine (cy/flu) lymphodepletion (LD) prior to brexu-cel. We assessed MCL patient outcomes as well as CAR T-cell expansion and persistence after brexu-cel following bendamustine or cy/flu LD at our center.
View Article and Find Full Text PDFCold Spring Harb Mol Case Stud
December 2023
We present a unique case of a single patient presenting with two mutationally distinct, PD-L1 diffuse large B-cell lymphomas (DLBCLs). One of these DLBCLs demonstrated exceptionally high mutational burden (eight disease-associated variants and 41 variants of undetermined significance) with microsatellite instability (MSI) and an acquired mutation with loss of PMS2 protein expression, detected postchemotherapy. This report, while highlighting the extent of possible tumor heterogeneity across separate clonal expansions as well as possible syndromic B-cell neoplasia, supports the notion that, although rare, PD-L1 expression and associated states permissive of high mutational burden (such as mismatch repair gene loss of function/MSI) should be more routinely considered in DLBCLs.
View Article and Find Full Text PDFLymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy of bendamustine (Benda) to standard fludarabine/cyclophosphamide (Flu/Cy) LD before CD19-directed, CD28-costimulated CART axicabtagene ciloleucel (axi-cel) for patients with large B-cell lymphoma (LBCL) and follicular lymphoma (FL). We analyzed 59 patients diagnosed with LBCL (n = 48) and FL (n = 11) consecutively treated with axi-cel at the University of Pennsylvania.
View Article and Find Full Text PDFEnvironmental mercury (Hg) contamination of the global tropics outpaces our understanding of its consequences for biodiversity. Knowledge gaps of pollution exposure could obscure conservation threats in the Neotropics: a region that supports over half of the world's species, but faces ongoing land-use change and Hg emission via artisanal and small-scale gold mining (ASGM). Due to their global distribution and sensitivity to pollution, birds provide a valuable opportunity as bioindicators to assess how accelerating Hg emissions impact an ecosystem's ability to support biodiversity, and ultimately, global health.
View Article and Find Full Text PDFElectrochemical aptamer-based (EAB) sensors are capable of measuring the concentrations of specific molecules in vivo, in real time, and with a few-second time resolution. For their signal transduction mechanism, these sensors utilize a binding-induced conformational change in their target-recognizing, redox-reporter-modified aptamer to alter the rate of electron transfer between the reporter and the supporting electrode. While a variety of voltammetric techniques have been used to monitor this change in kinetics, they suffer from various drawbacks, including time resolution limited to several seconds and sensor-to-sensor variation that requires calibration to remove.
View Article and Find Full Text PDFAntibodies that recognize specific protein conformational states are broadly important for research, diagnostic and therapeutic applications, yet they are difficult to generate in a predictable and systematic manner using either immunization or antibody display methods. This problem is particularly severe for conformational antibodies that recognize insoluble antigens such as amyloid fibrils associated with many neurodegenerative disorders. Here we report a quantitative fluorescence-activated cell sorting (FACS) method for directly selecting high-quality conformational antibodies against different types of insoluble (amyloid fibril) antigens using a single, off-the-shelf human library.
View Article and Find Full Text PDFPatients diagnosed with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) or high-grade B cell lymphoma (HGBL) may achieve prolonged survival following receipt of high-dose chemotherapy/autologous stem cell transplantation (HDC/ASCT) or CD19-directed chimeric antigen receptor modified T cell therapy (CART19). Although early results from randomized clinical trials suggest that assignment to CART19 versus salvage immunochemotherapy as second-line therapy results in improved survival, analysis of a large series of patients who actually received HDC/ASCT or CART19 has yet to be performed. Such an analysis may inform future research efforts to optimize the risk stratification of R/R DLBCL/HGBL patients who are candidates for either therapy.
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