Medical Specialties Commons^™

Expansion Of The Genotypic And Phenotypic Spectrum Of Ctcf-Related Disorder Guides Clinical Management: 43 New Subjects And A Comprehensive Literature Review, Hannah Gabriela Valverde De Morales, Hsiao-Lin V Wang, Kathryn Garber, Xiaodong Cheng, Victor G Corces, Hong Li

Faculty, Staff and Student Publications

Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF-related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed. Here, we examined the clinical features, including facial profiles, and genotypic spectrum of 107 subjects with identified CTCF variants, including 43 new and 64 previously described subjects. Among the 43 new subjects, 23 novel variants were reported. The cardinal clinical features in subjects with …

Hereditary Angioedema And Covid-19 During Pregnancy: Two Case Reports, Amanda Salih, Aaron Chin, Manisha Gandhi, Amir Shamshirsaz, Hennie Lombaard, Joud Hajjar

Faculty, Staff and Students Publications

No abstract provided.

Brain Ageing In Schizophrenia: Evidence From 26 International Cohorts Via The Enigma Schizophrenia Consortium, Constantinos Constantinides, Laura K M Han, Clara Alloza, Linda Antonella Antonucci, Celso Arango, Rosa Ayesa-Arriola, Nerisa Banaj, Alessandro Bertolino, Stefan Borgwardt, Jason Bruggemann, Juan Bustillo, Oleg Bykhovski, Vince Calhoun, Vaughan Carr, Stanley Catts, Young-Chul Chung, Benedicto Crespo-Facorro, Covadonga M Díaz-Caneja, Gary Donohoe, Stefan Du Plessis, Jesse Edmond, Stefan Ehrlich, Robin Emsley, Lisa T Eyler, Paola Fuentes-Claramonte, Foivos Georgiadis, Melissa Green, Amalia Guerrero-Pedraza, Minji Ha, Tim Hahn, Frans A Henskens, Laurena Holleran, Stephanie Homan, Philipp Homan, Neda Jahanshad, Joost Janssen, Ellen Ji, Stefan Kaiser, Vasily Kaleda, Minah Kim, Woo-Sung Kim, Matthias Kirschner, Peter Kochunov, Yoo Bin Kwak, Jun Soo Kwon, Irina Lebedeva, Jingyu Liu, Patricia Mitchie, Stijn Michielse, David Mothersill, Bryan Mowry, Víctor Ortiz-García De La Foz, Christos Pantelis, Giulio Pergola, Fabrizio Piras, Edith Pomarol-Clotet, Adrian Preda, Yann Quidé, Paul E Rasser, Kelly Rootes-Murdy, Raymond Salvador, Marina Sangiuliano, Salvador Sarró, Ulrich Schall, André Schmidt, Rodney J Scott, Pierluigi Selvaggi, Kang Sim, Antonin Skoch, Gianfranco Spalletta, Filip Spaniel, Sophia I Thomopoulos, David Tomecek, Alexander S Tomyshev, Diana Tordesillas-Gutiérrez, Therese Van Amelsvoort, Javier Vázquez-Bourgon, Daniela Vecchio, Aristotle Voineskos, Cynthia S Weickert, Thomas Weickert, Paul M Thompson, Lianne Schmaal, Theo G M Van Erp, Jessica Turner, James H Cole, Enigma Schizophrenia Consortium, Danai Dima, Esther Walton

Faculty, Staff and Students Publications

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on …

Response To: A True Point-Of-Care Molecular Testing Method For Tailored Therapy For Helicobacter Pylori Eradication, David Y Graham, Theodore Rokkas

Faculty, Staff and Students Publications

No abstract provided.

Affinity Purification Of Serum-Derived Anti-Ia-2 Autoantibodies In Type 1 Diabetes Using A Novel Mbp-Ia-2 Fusion Protein, Thilini Mendis, Barbora Filipova, Jing Jing Wang, Massimo Pietropaolo, Michael W Jackson

Faculty, Staff and Students Publications

Autoantibodies targeting epitopes contained within the intracellular domain (IC) of the protein phosphatase-like islet antigen 2 (IA-2) are a common marker of autoimmune type 1 diabetes (T1D), however the isolation of genuine, serum derived anti-IA-2 autoantibodies has proven challenging due to a lack of suitable bioassays. In the current study, an ELISA format was developed for affinity purification of human anti-IA-2ic autoantibodies utilizing a fusion protein (FP) incorporating maltose binding protein and the full-length IA-2IC domain. Using a T1D patient cohort validated for anti-IA-2ic autoantibodies by commercial ELISA, we demonstrate the MBP-IA-2ic FP ELISA detects serum anti-IA-2IC autoantibodies from 3 …

Systemic Inflammatory Markers And Eeg Features Of Children With Fires Receiving Anakinra, Yi-Chen Lai, Gabriella Abou-El-Kheir, Thao Nguyen, Margo Hanerhoff, James J Riviello, Eyal Muscal

Faculty, Staff and Students Publications

In a retrospective case series of 10 children with cryptogenic FIRES, we sought to describe the early clinical course and potential biomarkers following anakinra initiation. Six children achieved anesthetic withdrawal within 3 weeks of therapy and one in week four. Of the available cEEG (six children), CRP (10 children), and serum cytokine (six children) studies, there were temporal changes in highly epileptiform bursts (observed in three children), CRP, IL-6, and IL-10 levels that might parallel clinical progression. These observations may represent candidate biomarkers for monitoring clinical progression and therapeutic interventions including anakinra, which merits further investigation in future studies.

Driving Impairment In Movement Disorders, Karim Makhoul, Joseph Jankovic

Faculty, Staff and Students Publications

BACKGROUND: Driving may be adversely affected by any movement disorder, but has been mostly studied in Parkinson's disease (PD). Few studies have addressed driving impairment in patients with Huntington's disease (HD); driving in other movement disorders such as dystonia, blepharospasm and Tourette syndrome (TS) has not been adequately evaluated.

OBJECTIVES: The aim of this review is to summarize the findings of driving impairment in movement disorders and evaluate the usefulness of clinical tools in guiding clinicians whether to refer patients for driving assessment.

METHODS: A review of literature was performed on PubMed and articles on driving and movement disorders were …

Initial Evidence For Reliable And Valid Use Of Scores On The 8-Item Econ-Qol Short Form To Measure Economic Quality Of Life In Caregivers Of Persons With Traumatic Brain Injury, Noelle E Carlozzi, Christopher Graves, Jonathan P Troost, Michael A Kallen, David S Tulsky, Robin A Hanks, Phillip A Ianni, Jennifer A Miner, Angelle M Sander

Faculty, Staff and Students Publications

OBJECTIVE: To provide reliability and validity data to support the clinical utility of Economic Quality of Life Measure (Econ-QOL) scores in caregivers of civilians and service members/veterans with traumatic brain injury (TBI).

DESIGN: Cross-sectional survey study.

SETTING: Three academic medical centers and a Veterans Affairs treatment facility.

PARTICIPANTS: 376 caregivers of civilians (n=213) and service members/veterans (n=163) with TBI (N=376).

INTERVENTIONS: N/A.

MAIN OUTCOME MEASURES: Econ-QOL and several patient-reported outcome measures (Traumatic Brain Injury Caregiver Quality of Life Caregiver-Specific Anxiety and Caregiver Strain, Patient-Reported Outcomes Measurement Information System sleep-related impairment, Neurological Quality of Life Measurement System positive affect and well-being) …

Risk Factors For Hcc In Contemporary Cohorts Of Patients With Cirrhosis, Fasiha Kanwal, Saira Khaderi, Amit G Singal, Jorge A Marrero, Nicole Loo, Sumeet K Asrani, Christopher I Amos, Aaron P Thrift, Xiangjun Gu, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed HCC risk.

APPROACH AND RESULTS: We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven US centers and followed until HCC diagnosis, transplant, death, or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on …

Validation Of The Entrainment Signal Regularity Index And Associations With Children’S Changes In Bmi, Jennette P Moreno, Kevin M Hannay, Amy R Goetz, Olivia Walch, Philip Cheng

Children’s Nutrition Research Center Staff Publications

Objective: This study examined the validity of a novel metric of circadian health, the Entrainment Signal Regularity Index (ESRI), and its relationship to changes in BMI during the school year and summer.

Methods: In a longitudinal observational data set, this study examined the relationship between ESRI score and children's (n = 119, 5- to 8-year-olds) sleep and physical activity levels during the school year and summer, differences in ESRI score during the school year and summer, and the association of ESRI score during the school year and summer with changes in BMI across those time periods.

Results: The ESRI score …

Mitochondrial Structure And Function Adaptation In Residual Triple Negative Breast Cancer Cells Surviving Chemotherapy Treatment, Mokryun L Baek, Junegoo Lee, Katherine E Pendleton, Mariah J Berner, Emily B Goff, Lin Tan, Sara A Martinez, Iqbal Mahmud, Tao Wang, Matthew D Meyer, Bora Lim, James P Barrish, Weston Porter, Philip L Lorenzi, Gloria V Echeverria

Faculty, Staff and Student Publications

Neoadjuvant chemotherapy (NACT) used for triple negative breast cancer (TNBC) eradicates tumors in ~45% of patients. Unfortunately, TNBC patients with substantial residual cancer burden have poor metastasis free and overall survival rates. We previously demonstrated mitochondrial oxidative phosphorylation (OXPHOS) was elevated and was a unique therapeutic dependency of residual TNBC cells surviving NACT. We sought to investigate the mechanism underlying this enhanced reliance on mitochondrial metabolism. Mitochondria are morphologically plastic organelles that cycle between fission and fusion to maintain mitochondrial integrity and metabolic homeostasis. The functional impact of mitochondrial structure on metabolic output is highly context dependent. Several chemotherapy agents …

In Utero Exposure To Antiemetic And Risk Of Adult-Onset Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s.

METHODS: We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 …

Delphi Initiative For Early-Onset Colorectal Cancer (Direct) International Management Guidelines, Giulia Martina Cavestro, Alessandro Mannucci, Francesc Balaguer, Heather Hampel, Sonia S Kupfer, Alessandro Repici, Andrea Sartore-Bianchi, Toni T Seppälä, Vincenzo Valentini, Clement Richard Boland, Randall E Brand, Tineke E Buffart, Carol A Burke, Riccardo Caccialanza, Renato Cannizzaro, Stefano Cascinu, Andrea Cercek, Emma J Crosbie, Silvio Danese, Evelien Dekker, Maria Daca-Alvarez, Francesco Deni, Mev Dominguez-Valentin, Cathy Eng, Ajay Goel, Josè G Guillem, Britt B S L Houwen, Charles Kahi, Matthew F Kalady, Fay Kastrinos, Florian Kühn, Luigi Laghi, Andrew Latchford, David Liska, Patrick Lynch, Alberto Malesci, Gianluca Mauri, Elisa Meldolesi, Pål Møller, Kevin J Monahan, Gabriela Möslein, Caitlin C Murphy, Karlijn Nass, Kimmie Ng, Cristina Oliani, Enrico Papaleo, Swati G Patel, Marta Puzzono, Andrea Remo, Luigi Ricciardiello, Carla Ida Ripamonti, Salvatore Siena, Satish K Singh, Zsofia K Stadler, Peter P Stanich, Sapna Syngal, Stefano Turi, Emanuele Damiano Urso, Laura Valle, Valeria Stella Vanni, Eduardo Vilar, Marco Vitellaro, Yi-Qian Nancy You, Matthew B Yurgelun, Raffaella Alessia Zuppardo, Elena M Stoffel, Associazione Italiana Familiarità Ereditarietà Tumori, Collaborative Group Of The Americas On Inherited Gastrointestinal Cancer, European Hereditary Tumour Group, And The International Society For Gastrointestinal Hereditary Tumours

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC.

METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%.

RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that …

Use Of Contrast Media During Ct-Guided Thermal Ablation Of Colorectal Liver Metastasis For Procedure Planning Is Associated With Improved Immediate Outcomes, Iwan Paolucci, Yuan-Mao Lin, A Kyle Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to analyze the impact of using intra-procedural pre-ablation contrast-enhanced CT prior to percutaneous thermal ablation (pre-ablation CECT) of colorectal liver metastases (CLM) on local outcomes.

MATERIALS AND METHODS: This retrospective analysis of a prospectively collected liver ablation registry included 144 consecutive patients (median age 57 years IQR [49, 65], 60% men) who underwent 173 CT-guided ablation sessions for 250 CLM between October 2015 and March 2020. In addition to oncologic outcomes, technical success was retrospectively evaluated using a biomechanical deformable image registration software for 3D-minimal ablative margin (3D-MAM) quantification. Bayesian regression was used …

Metabolomic Markers Of Ultra-Processed Food And Incident Ckd, Donghan Su, Jingsha Chen, Shutong Du, Hyunju Kim, Bing Yu, Kari E Wong, Eric Boerwinkle, Casey M Rebholz

Faculty, Staff and Student Publications

BACKGROUND: High ultra-processed food consumption is associated with higher risk of CKD. However, there is no biomarker for ultra-processed food, and the mechanism through which ultra-processed food is associated with CKD is not clear. Metabolomics can provide objective biomarkers of ultra-processed food and provide important insights into the mechanisms by which ultra-processed food is associated with risk of incident CKD. Our objective was to identify serum metabolites associated with ultra-processed food consumption and investigate whether ultra-processed food-associated metabolites are prospectively associated with incident CKD.

METHODS: We used data from 3751 Black and White men and women (aged 45-64 years) in …

Prospective Study Of Pain Outcomes Associated With Breast Surgery In Women With Nonhereditary Breast Cancer, Demetria J Smith-Graziani, Patricia A Parker, Susan K Peterson, Isabelle Bedrosian, Y Shen, Dalliah M Black, Sarah M Desnyder, Kelly K Hunt, Wenli Dong, Abenaa M Brewster

Faculty, Staff and Student Publications

Objective: To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes.

Summary of background data: Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo different types of breast surgery.

Methods: Women with nonhereditary breast cancer completed the brief pain inventory before surgery and at 1, 6, 12, and 18 months postsurgery. We assessed associations between pain outcomes and CPM status and mastectomy status using multivariable repeated measures models. We assessed associations between pain outcome and …

Recent Advances In Centrifugal Spinning And Their Applications In Tissue Engineering, Shaik Merkatur Hakim Marjuban, Musfira Rahman, Syeda Sharmin Duza, Mohammad Boshir Ahmed, Dinesh K Patel, Md Saifur Rahman, Karen Lozano

Faculty, Staff and Student Publications

Over the last decade, researchers have investigated the potential of nano and microfiber scaffolds to promote wound healing, tissue regeneration, and skin protection. The centrifugal spinning technique is favored over others due to its relatively straightforward mechanism for producing large quantities of fiber. Many polymeric materials have yet to be investigated in search of those with multifunctional properties that would make them attractive in tissue applications. This literature presents the fundamental process of fiber generation, and the effects of fabrication parameters (machine, solution) on the morphologies such as fiber diameter, distribution, alignment, porous features, and mechanical properties. Additionally, a brief …

Customizable Landmark-Based Field Aperture Design For Automated Whole-Brain Radiotherapy Treatment Planning, Yao Xiao, Carlos Cardenas, Dong Joo Rhee, Tucker Netherton, Lifei Zhang, Callistus Nguyen, Raphael Douglas, Raymond Mumme, Stephen Skett, Tina Patel, Chris Trauernicht, Caroline Chung, Hannah Simonds, Ajay Aggarwal, Laurence Court

Faculty, Staff and Student Publications

Purpose: To develop and evaluate an automated whole-brain radiotherapy (WBRT) treatment planning pipeline with a deep learning-based auto-contouring and customizable landmark-based field aperture design.

Methods: The pipeline consisted of the following steps: (1) Auto-contour normal structures on computed tomography scans and digitally reconstructed radiographs using deep learning techniques, (2) locate the landmark structures using the beam's-eye-view, (3) generate field apertures based on eight different landmark rules addressing different clinical purposes and physician preferences. Two parallel approaches for generating field apertures were developed for quality control. The performance of the generated field shapes and dose distributions were compared with the original …

Clinical Outcomes Of Combined Cervical And Transthoracic Surgical Approaches In Patients With Advanced Thyroid Cancer, Jared A Shenson, Mark E Zafereo, Mark Lee, Kevin J Contrera, Lei Feng, Mongkol Boonsripitayanon, Neil Gross, Ryan Goepfert, Anastasios Maniakas, Jennifer Rui Wang, Libby Grubbs, Ara Vaporciyan, Wayne Hofstetter, Stephen Swisher, Reza Mehran, David Rice, Boris Sepesi, Mara Antonoff, Maria Cabanillas, Naifa Busaidy, Ramona Dadu, Natalie L Silver

Faculty, Staff and Student Publications

Background: Advanced thyroid disease involving the mediastinum may be managed surgically with a combined transcervical and transthoracic approach. Contemporary analysis of this infrequently encountered cohort will aid the multidisciplinary team in personalizing treatment approaches.

Methods: Retrospective review of patients undergoing combined transcervical and transthoracic surgery for thyroid cancer at a single high-volume institution from 1994 to 2015.

Results: Thirty-eight patients with median age 59 years (range 28-76) underwent surgery without perioperative mortality. Most patients had primary disease. A majority had distant metastases outside the mediastinum but had locoregionally curable disease. Common complications were temporary (39%) and permanent (18%) hypoparathyroidism, and …

Dysregulated Amino Acid Sensing Drives Colorectal Cancer Growth And Metabolic Reprogramming Leading To Chemoresistance, Sumeet Solanki, Katherine Sanchez, Varun Ponnusamy, Vasudha Kota, Hannah N Bell, Chun-Seok Cho, Allison H Kowalsky, Michael Green, Jun Hee Lee, Yatrik M Shah

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Colorectal cancer (CRC) is a devastating disease that is highly modulated by dietary nutrients. Mechanistic target of rapamycin complex 1 (mTORC1) contributes to tumor growth and limits therapy responses. Growth factor signaling is a major mechanism of mTORC1 activation. However, compensatory pathways exist to sustain mTORC1 activity after therapies that target oncogenic growth factor signaling. Amino acids potently activate mTORC1 via amino acid-sensing GTPase activity towards Rags (GATOR). The role of amino acid-sensing pathways in CRC is unclear.

METHODS: Human colon cancer cell lines, preclinical intestinal epithelial-specific GATOR1 and GATOR2 knockout mice subjected to colitis-induced or sporadic …

An Extension Of Estimating Equations To Model Longitudinal Medical Cost Trajectory With Medicare Claims Data Linked To Seer Cancer Registry, Shikun Wang, Jing Ning, Ying Xu, Ya-Chen Tina Shih, Y U Shen, Liang Li

Faculty, Staff and Student Publications

Insurance claims data is an increasingly important health policy research resource, given its longitudinal assessment of cancer care clinical outcomes. Population-level information on medical cost trajectory from disease diagnosis to terminal events, such as death, specifically interests policy makers. Estimating the mean cost trajectory has statistical challenges. The shape of the trajectory is usually highly nonlinear with varying durations, depending on the diagnosis-to-death population time distribution. The terminal event may be right censored, resulting in missing subsequent costs. Medical costs often have skewed distributions with zero-inflation and heteroscedasticity, which may not fit well with the commonly used parametric family of …

Adding The X-Ray Bragg Reflection Physical Process In Crystal To The Geant4 Monte Carlo Simulation Toolkit, Part I: Reflection From A Crystal Slab, Fada Guan, Makoto Asai, Dirk A Bartkoski, Michael Kleckner, Ze'ev Harel, Mohammad Salehpour

Faculty, Staff and Student Publications

X-ray diffraction from a solid crystal shows the wave nature of photons. It is an important electromagnetic (EM) physics process when X-ray photons interact with a crystal. Bragg diffraction, often called Bragg reflection, is a special case of the general form of X-ray diffraction, known as Laue diffraction. When the Bragg's law is met, the incident photon beam is reflected from the crystal plane behaving as a specular reflection at the Bragg angle. However, the Bragg reflection physical process has not been integrated into the general-purpose Monte Carlo simulation toolkit Geant4 for particle physics. In the current study, we developed …

Surgical Results Of The Lung Cancer Mutation Consortium 3 Trial: A Phase Ii Multicenter Single-Arm Study To Investigate The Efficacy And Safety Of Atezolizumab As Neoadjuvant Therapy In Patients With Stages Ib-Select Iiib Resectable Non-Small Cell Lung Cancer, Valerie W Rusch, Alan Nicholas, G Alexander Patterson, Salama N Waqar, Eric M Toloza, Eric B Haura, Dan J Raz, Karen L Reckamp, Robert E Merritt, Dwight H Owen, David J Finley, Ciaran J Mcnamee, Justin D Blasberg, Edward B Garon, John D Mitchell, Robert C Doebele, Frank Baciewicz, Misako Nagasaka, Harvey I Pass, Katja Schulze, Ann Johnson, Paul A Bunn, Bruce E Johnson, Mark G Kris, David J Kwiatkowski, Ignacio I Wistuba, Jamie E Chaft, David P Carbone, Jay M Lee

Faculty, Staff and Student Publications

Objective: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery.

Methods: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was …

Actin Cytoskeleton Vulnerability To Disulfide Stress Mediates Disulfidptosi, Xiaoguang Liu, Litong Nie, Yilei Zhang, Yuelong Yan, Chao Wang, Medina Colic, Kellen Olszewski, Amber Horbath, Xiong Chen, Guang Lei, Chao Mao, Shiqi Wu, Li Zhuang, Masha V Poyurovsky, M James You, Traver Hart, Daniel D Billadeau, Junjie Chen, Boyi Gan

Faculty, Staff and Student Publications

SLC7A11-mediated cystine uptake suppresses ferroptosis yet promotes cell death under glucose starvation; the nature of the latter cell death remains unknown. Here, we show that aberrant accumulation of intracellular disulfides in SLC7A11high cells under glucose starvation induces a previously uncharacterized form of cell death distinct from apoptosis or ferroptosis. We term this cell death disulfidptosis. Chemical proteomics and cell biological analyses showed that glucose starvation in SLC7A11high cells induces aberrant disulfide bonds in actin cytoskeleton proteins and F-actin collapse in a SLC7A11-dependent manner. CRISPR screens and functional studies revealed that inactivation of the WAVE regulatory complex (WRC, which promotes actin …

Highly Synchronized Cortical Circuit Dynamics Mediate Spontaneous Pain In Mice, Weihua Ding, Lukas Fischer, Qian Chen, Ziyi Li, Liuyue Yang, Zerong You, Kun Hu, Xinbo Wu, Xue Zhou, Wei Chao, Peter Hu, Tewodros Mulugeta Dagnew, Daniel M Dubreuil, Shiyu Wang, Suyun Xia, Caroline Bao, Shengmei Zhu, Lucy Chen, Changning Wang, Brian Wainger, Peng Jin, Jianren Mao, Guoping Feng, Mark T Harnett, Shiqian Shen

Faculty, Staff and Student Publications

Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a "normal" operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain-like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized …

Integrative Bioinformatic Analysis Of P53 And Pathway Alterations In Two Different Lung Cancer Subtypes, Yun Zhang, Abie Williams-Villalobo, Jyotsna D Godavarthi, Faith Shakoor, Shunbin Xiong, Bin Liu

Faculty, Staff and Student Publications

Whether p53, either wild type (WT) or mutant, plays cell-specific or uniform role remains controversial. Using The Cancer Genome Atlas, we examined p53 in the lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), two lung cancers with different cellular origins and frequent p53 mutation (52% and 83%, respectively). Mutant p53 more strongly correlates with different genomic alteration and protein expression profiles in LUAD than in LUSC. p53 mutation in LUAD and LUSC is associated with multiple exacerbated clinical outcomes. Although the presence of p53 mutation does not change the survival of LUAD patients, LUSC patients containing p53 mutation exhibit …

A Look At The Global Impact Of Covid-19 Pandemic On Neurosurgical Services And Residency Training, Cathleen C Kuo, Alexander O Aguirre, Andrea Kassay, Brianna M Donnelly, Hebatalla Bakr, Mohamed Aly, Ahmed A M Ezzat, Mohamed A R Soliman

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has left an indelible effect on healthcare delivery and education system, including residency training. Particularly, neurosurgical departments worldwide had to adapt their operating model to the constantly changing pandemic landscape. This review aimed to quantify the reduction in neurosurgical operative volume and describe the impact of these trends on neurosurgical residency training.

METHODS: We performed a comprehensive search of PubMed and EMBASE between December 2019 and October 2022 to identify studies comparing pre-pandemic and pandemic neurosurgical caseloads as well as articles detailing the impact of COVID-19 on neurosurgery residency training. Statistical analysis of quantitative data was …

Defining The Role Of Ab Externo Xen Gel Stent In Glaucomatous Eyes With Prior Failed Surgical Intervention, Lillian K To, Rupak K Dhoot, Alice Z Chuang, Sam Karimaghaei, Francisco Guevara-Abadia, Ruchi D Shah, Robert M Feldman

Faculty, Staff and Student Publications

PURPOSE: To evaluate the safety and efficacy of Xen45 Gel stent (Xen; Allergan) in eyes that have failed prior surgical intervention, compared to traditional glaucoma drainage device (GDD) or continuous-wave cyclophotocoagulation (CPC). Since this population has low expected success rates with additional surgery, it is vital to compare to standard-of-care surgical options.

METHODS: Retrospective, single-center, case-control study of ab externo transconjunctival Xen shunt in eyes that have previously undergone trabeculectomy and/or GDD surgery. Postoperative data were collected for 18 months. Failure was defined as no light perception, additional glaucoma surgery required, or intraocular pressure (IOP) of < 6 mmHg after 6 weeks postoperatively.

RESULTS: Eighteen Xen eyes …

Common Kinase Mutations Do Not Impact Optimal Molecular Responses In Core Binding Factor Acute Myeloid Leukemia Treated With Fludarabine, Cytarabine, And G-Csf Based Regimens, Jayastu Senapati, Tareq Abuasab, Fadi G Haddad, Farhad Ravandi, Tapan Kadia, Courtney Dinardo, Naval Daver, Naveen Pemmaraju, Yesid Alvarado, Mark A Brandt, Hagop Kantarjian, Gautam Borthakur

Faculty, Staff and Student Publications

No abstract provided.

New Developments In Allergic Fungal Rhinosinusitis Pathophysiology And Treatment, Brian H Cameron, Amber U Luong

Faculty, Staff and Student Publications

Background: Allergic fungal rhinosinusitis (AFRS) is an endotype of chronic rhinosinusitis (CRS) with nasal polyps characterized by eosinophilic mucin laden with fungal hyphae entrapped in expanded sinus cavities with an exaggerated hypersensitivity to fungal elements. The last decade has elucidated fungi-driven inflammatory pathways contributing to the pathophysiology of chronic inflammatory respiratory diseases. In addition, novel therapeutic biologic options have become available for CRS over the last several years.

Objective: To review the current literature examining AFRS, focusing on recent developments in our understanding of its pathophysiology and implications for treatment options.

Methods: Review article.

Results: Fungi-driven respiratory inflammation has been …