New York University Florence

ABSTRACTThe basal ganglia and midbrain dopaminergic systems are critical for motor control, reward processing, and reinforcement learning, with dysfunction in these systems implicated in numerous neurodegenerative and neuropsychiatric disorders. To enable precise genetic targeting of key neuronal populations, we generated and characterized five knock-in mouse lines:Drd1-Cre, Adora2a-Cre, Drd1-FlpO, Adora2a-FlpO, andDAT-FlpO. These lines allow for Cre-or FlpO-mediated recombination in dopamine D1 receptor-expressing spiny projection neurons (SPNs), adenosine A2a receptor-expressing SPNs, and dopamine transporter (DAT)-expressing neurons in the midbrain. Histological analyses confirmed recombinase activity in expected brain regions, and whole-cell electrophysiological recordings validated the intrinsic excitability profiles of each neuronal subpopulation. These tools provide high specificity and reliability for studying basal ganglia circuitry and dopaminergic neurons. By enabling targeted manipulations, these openly available knock-in lines will advance research into the neural mechanisms underlying motor control, reward, and neuropsychiatric diseases.

Objectives/Goals: NIH requires researchers submit Data Management and Sharing (DMS) Plans with their grant applications. Librarians developed an assessment tool for the plans and completed a pilot assessment in order to leverage the plans and understand current institutional research data management and sharing. Methods/Study Population: The assessment tool includes questions related to evaluations of DMS Plans as well as questions related to the content of the plans. Evaluation questions were adapted from the Federation of American Societies for Experimental Biology evaluation rubric developed for the DataWorks! Data Management Plan (DMP) Challenge. Fields were added to collect information on the content of DMS Plans, including data type, institutional resources, data repositories, data standards, and data dissemination timelines. The assessment tool was tested in a pilot implementation. Seven library workers were trained and completed paired review samples of 27 DMS Plans (54 evaluations total) in order to test for tool reliability. Results/Anticipated Results: Results include findings on the reliability of the tool as well as preliminary results from an assessment of DMS Plans. Findings on the reliability of the tool include assessments of the paired reviewers for each question included in the tool. Paired reviewers generally agreed, but tended to differ on specific questions, including questions pertaining to the data types generated or used in a research project. Questions with high levels of agreement included subjects of study and code sharing practices. Results on the content of the DMS Plans include information such as data repositories used, data oversight responsibilities, and data and metadata standards employed. Discussion/Significance of Impact: DMS Plans present an opportunity to better understand data management and sharing practices, and good data management supports high-quality, reproducible research. Developing and testing assessment tools for these plans is a key step toward understanding and improving current research data management practices.

PurposeNumerous clinical practice guidelines and consensus statements have been published in hernia surgery, however, there is still a need for high-quality evidence to address remaining unanswered questions. The aim of this study was to conduct research priority setting through a modified Delphi process to identify a list of top research priorities in hernia surgery.MethodsA structured literature review of clinical practice guidelines was performed by the steering committee. Topics considered clinically significant, practical to study and lacking strong evidence were extracted and refined into a comprehensive list, then entered into a two-round Delphi survey for prioritization at the Abdominal Core Health Quality Collaborative (ACHQC) Quality Improvement Summit. In round 1, participants were instructed to select any topic that should be prioritized for future research. Topics were ranked according to the proportion of votes and the 25 highest-ranking topics were included in the second round. In round 2, participants were instructed to select only the top 10 topics for research prioritization.ResultsEleven clinical practice guidelines were reviewed. Eighty-seven topics were extracted by the steering committee and submitted for prioritization. After the first round, 25 of the highest-ranking topics were determined and included in the second round. A final list of 11 research questions was identified. The hernia types with the most research interest were inguinal and epigastric/umbilical hernias. Other topics of high interest were the management of diastasis recti, primary versus mesh repairs and expectant management versus surgical repair.ConclusionOur study provides a research agenda generated through expert consensus that may be used in the prioritization of the design and funding of clinical trials in hernia surgery.

Lenalidomide maintenance is associated with a significantly improved progression-free in patients with newly diagnosed multiple myeloma. Maintenance with lenalidomide is generally well tolerated; however, lenalidomide associated diarrhea is a common side effect and bile acid malabsorption has been suggested as an underlying mechanism. We conducted a single arm phase 2 trial of colesevelam, a bile acid binder, for lenalidomide-associated diarrhea in multiple myeloma. Patients were treated with colesevelam daily starting at 1250 mg (2 tablets 625 mg) for 12 weeks. The trial included 25 patients, 1 patient with grade 3 diarrhea, 14 with grade 2, and 10 with grade 1 diarrhea. All patients were on treatment with single agent lenalidomide maintenance and no patient progressed during the trial.Colesevelam treatment was highly effective for treatment of lenalidomide-associated diarrhea; 22 (88%) of the 25 patients responded where 17 patients (68%) had complete resolution of diarrhea, and 5 patients (20%) had improvement by 1 grade of diarrhea. The responses to colesevelam were seen within the first two weeks of treatment. These findings support the conclusion that lenalidomide-associated diarrhea is driven by bile acid malabsorption. Five patients reported mild gastrointestinal side effects including constipation. Importantly, the pharmacokinetics of lenalidomide were not affected by concomitant colesevelam treatment. The stool microbiome composition was not significantly different before and after colesevelam treatment. Patients reported improved diarrhea, fewer gastrointestinal symptoms, and less interference with their daily life after starting colesevelam. In summary, colesevelam was safe and highly effective for treatment of lenalidomide-associated diarrhea in multiple myeloma and does not reduce the clinical effect of lenalidomide.

Differentiating between real transit events and false positive signals in photometric time series data is a bottleneck in the identification of transiting exoplanets, particularly long-period planets. This differentiation typically requires visual inspection of a large number of transit-like signals to rule out instrumental and astrophysical false positives that mimic planetary transit signals. We build a one-dimensional convolutional neural network (CNN) to separate eclipsing binaries and other false positives from potential planet candidates, reducing the number of light curves that require human vetting. Our CNN is trained using the TESS light curves that were identified by Planet Hunters citizen scientists as likely containing a transit. We also include the background flux and centroid information. The light curves are visually inspected and labeled by project scientists and are minimally pre-processed, with only normalization and data augmentation taking place before training. The median percentage of contaminants flagged across the test sectors is 18% with a maximum of 37% and a minimum of 10%. Our model keeps 100% of the planets for 16 of the 18 test sectors, while incorrectly flagging one planet candidate (0.3%) for one sector and two (0.6%) for the remaining sector. Our method shows potential to reduce the number of light curves requiring manual vetting by up to a third with minimal misclassification of planet candidates.

To present a case of a 52-year-old female with relapsing progressive bilateral optic neuritis over 5 years in the absence of systemic symptoms and serum and CSF markers suggestive of sarcoidosis, ultimately found to have neurosarcoidosis.

To provide an overview of the procedural and clinical outcomes of patients who underwent stenting for symptomatic ICAS.