Publications by authors named "Gerson J"

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.

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  • Bruton tyrosine kinase inhibitors (BTKi) have significantly improved treatment for B-cell malignancies, but many patients stop using them due to side effects, with cardiac issues being the most common reason for discontinuation.* -
  • The BRUIN study tested pirtobrutinib, a new non-covalent BTKi, on 127 patients who were intolerant to previous BTKi treatments, finding that many experienced fewer or no cardiac issues while showing a high overall response rate.* -
  • Results indicated pirtobrutinib had a median time on treatment of 15.3 months, with notable side effects like fatigue and neutropenia; overall, it proved to be a safe and effective alternative for
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Patients 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.

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Introduction: 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.

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Background: 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.

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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.

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Background 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.

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Background: First generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.

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Electrochemical 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.

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Little 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.

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Electrochemical 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.

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Brexucabtagene 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.

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  • A T cell lymphoma (TCL) case was reported occurring three months after a patient received anti-CD19 CAR T cell therapy for non-Hodgkin B cell lymphoma, diagnosed through surgery for lung cancer.
  • The TCL showed a CD8 cytotoxic profile and a JAK3 variant, and it was identified at low levels prior to CAR T infusion and also in the lung cancer samples.
  • An analysis of 449 patients treated with CAR T therapy revealed that 3.6% developed a secondary primary malignancy, with a low overall risk of TCL after such treatment.
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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.

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Lymphodepletion (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.

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Environmental 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.

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  • Mantle cell lymphoma (MCL) varies in prognosis, with blastoid and pleomorphic variants generally having poorer outcomes.
  • A study involving 1029 MCL patients over 15 years focused on the characteristics and survival rates of those with these variants, finding a median progression-free survival (PFS) of 38 months and overall survival (OS) of 68 months.
  • Key factors influencing PFS included receiving autologous hematopoietic transplantation (auto-HCT) and MCL International Prognostic Index (MIPI) scores; however, auto-HCT did not improve OS, indicating its benefits are more related to managing the disease's progression rather than overall survival.
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Electrochemical 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.

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Antibodies 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.

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  • Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) often struggle after failing treatment with covalent BTK inhibitors, prompting the need for new options like pirtobrutinib, a selective noncovalent BTK inhibitor designed to resume BTK inhibition.* -
  • In a phase 1-2 trial involving 317 patients, 73.3% responded positively to pirtobrutinib, with a notable 82.2% response rate when including those showing partial responses with lymphocytosis; the median progression-free survival was reported at 19.6 months.* -
  • Common side effects from pirtobrutinib treatment included infections (71%),
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Patients 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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  • Traditional methods for measuring drug concentrations in the brain lack real-time capabilities and have poor temporal resolution, limiting the understanding of drug effects in behaving subjects.
  • Electrochemical aptamer-based sensors have been developed that allow for real-time, seconds-resolved measurements of drug concentrations, achieving precise detection limits and enabling the study of pharmacokinetics in freely moving rats.
  • The study shows that these sensors can maintain constant drug levels in the brain for extended periods, highlighting their potential for site-specific drug delivery and analysis of concentration-behavior relationships in individual subjects.
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  • Pirtobrutinib is a new, selective Bruton tyrosine kinase inhibitor (BTKi) that shows promise for patients with mantle-cell lymphoma (MCL) who have previously been treated with covalent BTK inhibitors due to a generally poor prognosis.
  • In a phase I/II trial, the drug demonstrated an overall response rate of 57.8% with a median duration of response lasting 21.6 months, indicating effectiveness in this challenging patient group.
  • The treatment was well tolerated, with only a small percentage of patients discontinuing therapy due to adverse events such as fatigue and diarrhea, suggesting it may be a viable option for patients with previously recurRent MCL.
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