Faculty Bibliography

OBJECTIVE/UNASSIGNED:The pathway to cardiothoracic surgery is often obscure for premedical students and aspiring applicants and requires navigating various known and unknown obstacles. Recognizing the challenges encountered on the path to a career in cardiothoracic surgery in the United States, we present this guide for students interested in the field to maximize success in their premedical, preclinical, and preresidency years. METHODS/UNASSIGNED:This is a joint collaboration between the Thoracic Surgery Residents Association and the Thoracic Surgery Medical Student Association. Drawing from firsthand experiences and insights gathered from numerous student applicants and current surgical residents, a comprehensive guide was constructed for students from the point of undergraduate school to advanced training options, including super-fellowship training. RESULTS/UNASSIGNED:Several intricacies to cardiothoracic surgery career planning were discussed, including differences between traditional and integrated/fast-track pathways, college and medical school selection, networking, performing during clinical rotations, extracurricular and research activities, building mentorship relationships, and pursuing alternate career and advanced training opportunities. CONCLUSIONS/UNASSIGNED:For premedical students and aspiring applicants, the road to cardiothoracic surgery requires meticulous planning, grit, and thoughtful dedication. This document consolidates firsthand insights and advice from numerous aspiring and matched applicants to serve as a comprehensive guide for students seeking a career in cardiovascular and thoracic surgery.

Understanding the role of temperature in the dynamic response of composite plates is critical for naval systems operating in extreme environments like the Arctic. Despite the advantages of composite materials in improving corrosion resistance and enabling the customization of material properties to their environment, their behavior at cold temperature, especially under dynamic loading, remains elusive. This research gap hinders the effective use of composite materials in extreme environments. Here, we study the dynamic response of air-backed fiberglass epoxy plates under hydrodynamic loading at room temperature and 4^∘C. By employing digital image correlation and particle image velocimetry, we investigated the interplay between fluid"“structure interactions and cold temperatures. Our findings reveal the critical role of temperature in shaping the dynamic response of air-backed composites through changes in the stiffness and damping properties. At cold temperature, the plate experiences a larger (smaller) deformation in the initial (latter) phase of the dynamic response. Furthermore, we observed a pronounced coupling between the structural response and the flow physics, with peaks of the hydrodynamic loading synchronized with the peak deflections. Our results underscore the importance of considering temperature in the design of naval systems for extreme environments, providing key insights into fluid"“structure interactions at cold temperature.

Covalent kinase inhibitors (CKIs) have recently garnered considerable attention, yet the rational design of CKIs continues to pose a great challenge. In the discovery of CKIs targeting focal adhesion kinase (FAK), it has been observed that the chemical structure of the linkers plays a key role in achieving covalent targeting of FAK. However, the mechanism behind the observation remains elusive. In this work, we employ a comprehensive suite of advanced computational methods to investigate the mechanism of CKIs covalently targeting FAK. We reveal that the linker of an inhibitor influences the contacts between the warhead and residue(s) and the residence time in active conformation, thereby dictating the inhibitor's capability to bind covalently to FAK. This study reflects the complexity of CKI design and underscores the importance of considering the dynamic interactions and residence times for the successful development of covalent drugs.

Despite decades of clinical use and a large body of evidence, the WHO continues to exclude methylphenidate for attention-deficit/hyperactivity disorder (ADHD) from its EML.¹ The exclusion of methylphenidate has dire implications for millions of individuals with ADHD worldwide, especially those living in low and low-middle income countries (LMIC), where governmental decisions to make medicines available are contingent on EML listing.

PURPOSE/OBJECTIVE:Rasmussen syndrome (RS) is marked by progressive unihemispheric atrophy, resulting in hemiparesis, refractory epilepsy, and cognitive/language decline. Detailed diagnostic and treatment algorithms are currently lacking. We aimed to survey medical providers on their current practices in the diagnosis and treatment of RS. METHODS:A steering committee was formed to create the survey, which was disseminated to the international medical community. One hundred twelve surveys were completed. Descriptive statistics, as well as comparisons by level of experience, patient age group cared for, and geographic region using Fisher's exact test, were conducted. RESULTS:Analysis of cerebrospinal fluid (82 %) and serum (78 %) for autoimmune encephalitis (AE) are completed by most, while approximately one-third obtain genetic and metabolic studies in all patients (36 % and 38 %, respectively). Providers in US and Europe more readily pursue serum AE antibody panels (85 % and 85 %, respectively, versus 67 %, p = 0.019) and genetic testing (56 % and 47 %, respectively, versus 14 %, p < 0.001) than the rest of the world. Thirty-six percent proceed to biopsy in patients otherwise meeting diagnostic criteria, and US providers are more likely to suggest this than others (73 % versus 14-41 %, p < 0.001). Opinions differed on the prioritization of hemispherectomy/hemispherotomy versus immunotherapy in 14 clinical scenarios with various neurologic deficit severity provided. Preferred immunotherapy regimens also varied, with US providers more often choosing IVIG as first-line (67 %) compared to others (28 %-32 %, p = 0.030). Surgical standard of care was identified as functional hemispherectomy or hemispherotomy by 90 %. CONCLUSION/CONCLUSIONS:The survey highlights trends but also significant variations in clinical practice that can serve as targets for future research and expert consensus guidelines.

Muscle fatigue represents the most prevalent symptom of long-term COVID, with elusive pathogenic mechanisms. We performed a longitudinal study to characterize histopathological and transcriptional changes in skeletal muscle in a hamster model of respiratory SARS-CoV-2 infection and compared them with influenza A virus (IAV) and mock infections. Histopathological and bulk RNA sequencing analyses of leg muscles derived from infected animals at days 3, 30, and 60 post-infection showed no direct viral invasion but myofiber atrophy in the SARS-CoV-2 group, which was accompanied by persistent downregulation of the genes related to myofibers, ribosomal proteins, fatty acid β-oxidation, tricarboxylic acid cycle, and mitochondrial oxidative phosphorylation complexes. While both SARS-CoV-2 and IAV infections induced acute and transient type I and II interferon responses in muscle, only the SARS-CoV-2 infection upregulated TNF-α/NF-κB but not IL-6 signaling in muscle. Treatment of C2C12 myotubes, a skeletal muscle cell line, with combined IFN-γ and TNF-α but not with IFN-γ or TNF-α alone markedly impaired mitochondrial function. We conclude that a respiratory SARS-CoV-2 infection can cause myofiber atrophy and persistent energy metabolism suppression without direct viral invasion. The effects may be induced by the combined systemic interferon and TNF-α responses at the acute phase and may contribute to post-COVID-19 persistent muscle fatigue.

We leveraged information from more than 1.2 million participants, including 97,383 cases, to investigate the genetics of anxiety disorders across five continental groups. Through ancestry-specific and cross-ancestry genome-wide association studies, we identified 51 anxiety-associated loci, 39 of which were novel. In addition, polygenic risk scores derived from individuals of European descent were associated with anxiety in African, admixed American and East Asian groups. The heritability of anxiety was enriched for genes expressed in the limbic system, cerebral cortex, cerebellum, metencephalon, entorhinal cortex and brain stem. Transcriptome-wide and proteome-wide analyses highlighted 115 genes associated with anxiety through brain-specific and cross-tissue regulation. Anxiety also showed global and local genetic correlations with depression, schizophrenia and bipolar disorder and widespread pleiotropy with several physical health domains. Overall, this study expands our knowledge regarding the genetic risk and pathogenesis of anxiety disorders, highlighting the importance of investigating diverse populations and integrating multi-omics information.

BACKGROUND/UNASSIGNED:Anterior retroperitoneal lumbar spinal exposure has traditionally been performed in the supine position (SUP) to access the L4-L5 and L5-S1 disc spaces where lateral approaches may be unsafe. However, advancements in lateral single position surgery have resulted in advocacy for anterior L4-5 disc access in the lateral decubitus position (LAT). While L5-S1 access in the lateral position is well-described, no series of L4-5 anterior access in the lateral position has been published. The study aims to evaluate the safety of anterior lumbar exposure at the L4-5 disc level in the LAT compared to the SUP. METHODS/UNASSIGNED:A multi-center retrospective study of patients who underwent anterior retroperitoneal lumbar exposure involving the L4-5 disc level were classified according to patient positioning: (I) LAT or (II) SUP. RESULTS/UNASSIGNED:10.70%, P=0.09) were similar between groups. CONCLUSIONS/UNASSIGNED:Anterior lumbar spinal exposure of the L4-5 disc in the LAT is safe compared to supine exposure, despite higher case complexity in the lateral position.

This paper presents the case of a 30-year-old man who was diagnosed with an apical-lateral wall left ventricular aneurysm with scarring, prominent left ventricular trabeculations, and mildly diminished systolic function. Working diagnosis was a congenital left ventricular aneurysm in the setting of left ventricular noncompaction, yet with a questionable defect of the pericardium.