Digital Commons Network^™

Endovascular Therapy In Patients With Acute Ischemic Stroke With Large Infarct: A Guideline From The Society Of Vascular And Interventional Neurology, Maxim Mokin, Tudor G Jovin, Sunil A Sheth, Thanh N Nguyen, Kaiz S Asif, Ameer E Hassan, Ashutosh P Jadhav, Cynthia Kenmuir, David S Liebeskind, Ossama Mansour, Raul G Nogueira, Robin Novakovic, Santiago Ortega-Gutierrez, Albert J Yoo, Waldo R Guerrero, Amer M Malik

Faculty, Staff and Student Publications

Background: Recent randomized clinical trials of endovascular therapy in patients with large infarct provided new evidence in support of endovascular interventions in patients with acute ischemic stroke. The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee aims to provide up-to-date recommendations on focused relevant clinical questions. Here, we review current evidence and provide recommendations for the selection and endovascular treatment of patients with anterior circulation large vessel occlusion and large infarct.

Methods: The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee assembled a writing group and recruited interdisciplinary experts to review and evaluate the …

Multiethnic Growth Standards For Fetal Body Composition And Organ Volumes Derived From 3d Ultrasonography, Katherine L Grantz, Wesley Lee, Lauren M Mack, Magdalena Sanz Cortes, Luis F Goncalves, Jimmy Espinoza, Roger B Newman, William A Grobman, Ronald J Wapner, Karin Fuchs, Mary E D'Alton, Daniel W Skupski, John Owen, Anthony Sciscione, Deborah A Wing, Michael P Nageotte, Angela C Ranzini, Edward K Chien, Sabrina Craigo, Seth Sherman, Robert E Gore-Langton, Dian He, Fasil Tekola-Ayele, Cuilin Zhang, Jagteshwar Grewal, Zhen Chen

Faculty, Staff and Student Publications

Background: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort.

Objective: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with …

Nulliparous With Class Iii Obesity At Term: Labor Induction Or Cesarean Delivery Without Labor, Yossi Bart, Rachel L Wiley, Ipsita Ghose, Michal Fishel Bartal, Khalil M Chahine, Suneet P Chauhan, Sean Blackwell, Baha M Sibai

Faculty, Staff and Student Publications

Objective: This study aimed to compare maternal and neonatal outcomes between labor induction versus cesarean delivery (CD) without labor among nulliparous individuals with class III obesity (body mass index [BMI] ≥40 kg/m2).

Study design: A retrospective cohort study of all nulliparous singleton deliveries at ≥37 weeks with a BMI of ≥40 kg/m2 at delivery between March 2020 and February 2022. We excluded individuals with spontaneous labor, fetal malformations, and stillbirths. The primary outcome was a composite of maternal mortality and morbidity, including infectious and hemorrhagic morbidity. The secondary outcome was a neonatal composite. A subgroup analysis evaluated patients with a …

Intra- And Postoperative Complications In 4565 Vnotes Hysterectomies: International Registry Cohort Study., Andrea Stuart, Johanna Wagenius, Levon Badiglian-Filho, Jens Schnabel, Alvaro Montealegre, Sophia Ehrström, Michael Hartmann, Jona Vercammen, Daniela Huber, Anna Lingström, Jan Baekelandt

Faculty, Staff and Student Publications

Objective: To present the rates of intra- and postoperative complications and conversions in a large cohort of unselected vNOTES hysterectomies, performed by surgeons with different levels of expertise.

Design: International register-based cohort study.

Setting: Hysterectomies in the iNOTESs registry, 2015 to January 2024, performed by 201 surgeons from multiple countries.

Population: 4565 patients undergoing vNOTES hysterectomy.

Methods: Descriptive data are presented in frequencies (n) and percent (%).

Main outcome measure: Intra- and postoperative complications. Conversions.

Results: Intraoperative and postoperative complication rates were 3.2% (n = 144) and 2.5% (n = 115), respectively. Conversions occurred in 1.6% (n = 72), of …

Curq+ With Resveratrol Diminish Joint Pain In A Child With Pseudoachondroplasia: A Case Report, Jacqueline T Hecht, Ana-Coral Barreda-Bonis, Karen L Posey

Faculty, Staff and Student Publications

This case report details the successful use of over-the-counter resveratrol and CurQ+ in a five-year-old with pseudoachondroplasia (PSACH), a severe dwarfing condition caused by mutations in cartilage oligomeric matrix protein (COMP). Disproportionate short stature, abnormal joints, joint deformities, and pain starting in early childhood are characteristic findings. Adult treatments include non-steroidal anti-inflammatory drugs (NSAIDs) and joint replacement to manage joint pain. Childhood pain goes largely untreated given the concern of daily use of NSAIDs in the very young. Recently, resveratrol has been shown to reduce pain and CurQ+ improves growth in a mouse model of PSACH. The use of these …

Liver Involvement In A Large Cohort Of Patients With Erythropoietic Protoporphyria Or X-Linked Protoporphyria, Cynthia Levy, Hetanshi Naik, Jessica Overbey, Karli Hedstrom, Kelly Wang, Catherine Mcdonough, Mary Freeman, Siobán B Keel, Angelika L Erwin, Amy K Dickey, Rebecca K Leaf, John Quigley, Marshall Mazepa, Bruce Wang, John Phillips, Charles Parker, Brendan Mcguire, Mohamed Kazamel, Herbert Bonkovsky, Sean Rudnick, Karl E Anderson, Akshata Moghe, Manish Thapar, Behnam Saberi, Kristen Wheeden, Robert Desnick, Manisha Balwani, Porphyrias Consortium Of The Rare Diseases Clinical Research Network

Faculty, Staff and Student Publications

Background: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by the accumulation of protoporphyrin in the marrow, erythrocytes, plasma, skin, and liver, and present clinically with painful cutaneous phototoxicity. Liver abnormalities have been reported in over 25% of patients with EPP. Further characterization of liver involvement in protoporphyria is needed.

Methods: Patients with EPP or XLP enrolled in the longitudinal studies of the NIH-supported Porphyrias Consortium were included. Medical history, laboratory, and liver histology data were abstracted and described.

Results: A total of 322 patients were enrolled; 28 (8.7%) had XLP, 52% were female, and the median age at …

Assessment Of Skin Fibrosis In A Murine Model Of Systemic Sclerosis With Multifunctional Optical Coherence Tomography, Harshdeep Singh Chawla, Yanping Chen, Minghua Wu, Pavel Nikitin, Jessica Gutierrez, Chandra Mohan, Manmohan Singh, Salavat R Aglyamov, Shervin Assassi, Kirill V Larin

Faculty, Staff and Student Publications

Significance: Systemic sclerosis (SSc) is a chronic idiopathic disease that causes immune dysregulation, vasculopathy, and organ fibrosis that affects more than 3 million people in the US alone. The modified Rodnan skin score (mRSS) is the current gold standard for diagnosing and staging skin fibrosis in SSc. However, mRSS is subjective, requires extensive training, and has high observer variability.

Aim: We aim to provide a quantitative method for the assessment of fibrosis.

Approach: We utilized optical coherence tomography (OCT), its extensions, optical coherence elastography (OCE), and OCT angiography (OCTA) to evaluate SSc-like fibrosis and therapy response in a mouse model. …

Relapsed Acute Myeloid Leukemia With Early Presentation As Leukemia Cutis, Refractory To Second-Line Treatment, Emin Gayibov, Aditi Karambelkar, Virushnee Senthilkumar, Amita J Dsouza, Amit K Correa

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a hematologic malignancy with a poor prognosis, often presenting with systemic and extramedullary manifestations. Leukemia cutis (LC), the infiltration of leukemic cells into the skin, is a rare and clinically significant complication of AML. It often signals extramedullary disease involvement, may precede systemic relapse, and is associated with poor survival outcomes. We report the case of a 36-year-old female with AML who developed recurrent, reddish-brown nodular skin lesions on the face, trunk, and extremities, consistent with LC. Despite achieving initial remission with induction and consolidation chemotherapy, she experienced early LC recurrence, pancytopenia, hepatobiliary dysfunction, and …

Factors Affecting Waiting Times To Enter Opioid Use Disorder Treatment In The United States With A Particular Focus On Potential Biological Sex Disparity, Stanley Nkemjika, Kenneth Oforeh, Connie Olwit, Olaniyi Olayinka, Terence Tumenta

Faculty, Staff and Student Publications

Aim: Opioid use disorder (OUD) is the problematic use of licit or illicit opioids. Thus far, the literature on biological sex differences in accessing treatment is scarce. Hence, we hypothesize that biological sex has a moderating effect on OUD treatment accessibility. We aim to explore biological sex differences in treatment disparities and its role in wait time to enter OUD treatment.

Method: Using the 2018 Treatment Episode Data Set Discharge, the national sample representative of OUD patients in the substance use disorder treatment facilities within the 50 states of the United States was 382,547. Univariate and multivariable logistic analysis of …

[Treatment Adherence For Attention Deficit Hyperactivity Disorder (Adhd) In The Champ Ut-Health Houston Program], Rachitha P Jadala, Hali Temkin, Kerri L Daniel, Cesar A Soutullo

Faculty, Staff and Student Publications

Introduction: ADHD has a safe and effective treatment, but treatment adherence is often low. Several factors contribute to this low adherence, some of which are modifiable.

Methods: We conducted a literature review of recent studies on medication adherence in children and adolescents with ADHD. We gathered data on ADHD treatment adherence from our clinic in the ADHD Program and the Child and Adolescent Mood Disorders Program (ChAMP) at the University of Texas Health-Houston Program. We analyzed factors related to medication adherence, such as patient age, sex, prescription type, release formula, and their association with adherence in 117 patients with ADHD …

A Multilevel Latent Class Analysis Of Adolescent Engagement In Interpersonal Violence: The Role Of Stressful Life Events, School Climate, And School Characteristics, Yu Lu, Sabina Low, Shristi Bhochhibhoya, Adriana Dragicevic, Elizabeth Baumler, Jeff R Temple

Faculty, Staff and Student Publications

Objective: Little is known about the role of school-level factors in adolescent violence. Using multilevel latent class analysis, we identified groups of adolescents and schools based on adolescent involvement in violent behaviors and assessed how these group memberships differed by individual and school characteristics.

Method: We used baseline data from a randomized controlled trial of a school-based violence prevention program. Participants included 2,768 adolescents (Meanage=13 years) enrolled in 7th grade across 24 public schools in southeast Texas.

Results: We identified three classes of adolescents, including a Non-violent class (74.5%), a Moderately Violent class (20.0%), and a Highly Violent class (5.4%). …

Fructose Induces Inflammatory Activation In Macrophages And Microglia Through The Nutrient-Sensing Ghrelin Receptor, Zheng Shen, Zeyu Liu, Hongying Wang, Danilo Landrock, Ji Yeon Noh, Qun Sophia Zang, Chih-Hao Lee, Yuhua Z Farnell, Zheng Chen, Yuxiang Sun

Faculty, Staff and Student Publications

High fructose corn syrup (HFCS) is a commonly used sweetener in soft drinks and processed foods, and HFCS exacerbates inflammation when consumed in excess. Fructose, a primary component of HFCS; however, it is unclear whether fructose directly activates inflammatory signaling. Growth hormone secretagogue receptor (GHSR) is a receptor of the nutrient‐sensing hormone ghrelin. We previously reported that GHSR ablation mitigates HFCS‐induced inflammation in adipose tissue and liver, shifting macrophages toward an anti‐inflammatory spectrum. Since inflammation is primarily governed by innate immune cells, such as macrophages in the peripheral tissues and microglia in the brain, this study aims to investigate whether …

Dissolution Of Bovine Palatal Tissue With Degassed Sodium Hypochlorite, Justin Fang, Zhen Shen, Ransome Van Der Hoeven, David E Jaramillo

Faculty, Staff and Student Publications

Objective: To investigate the tissue dissolution efficacy of different concentrations of sodium hypochlorite (NaOCl) using the GentleWave® technology (GW) and compare it with that of passive ultrasonic irrigation. This study will provide a novel in vitro model used to evaluate the tissue dissolution efficacy of different concentrations of NaOCl using the GentleWave® procedure.

Materials and Methods: Palatal bovine tissue was standardized by weight at 70-75 mg (average of 74.4 mg). The samples were divided into three groups of n = 10, Group 1: GW + 0.5% NaOCl, Group 2: GW + 3% NaOCl, and Group 3: ultrasonic group (US) + …

New Onset Diabetes Predicts Clinical Outcomes In Patients With Pancreatic Adenocarcinoma, Chirayu Mohindroo, Paul S Dy, Suraj P Hande, Christopher R D'Adamo, Arun Mavanur, Asha Thomas, Florencia Mcallister, Ana De Jesus-Acosta

Faculty, Staff and Student Publications

Background: One percent of pancreatic adenocarcinoma (PDAC) patients are diagnosed with new onset diabetes (NOD) over the age of 50 years within 3 years. Therefore, NOD is a major factor for early diagnosis of PDAC. Research has focused on understanding the differences between NOD and type 2 diabetes, particularly in relation to PDAC. However, conflicting data exists regarding their impact on survival outcomes in PDAC patients. We performed this multi-center study to assess the prevalence and influence of NOD on clinical outcomes in patients with PDAC within a community-based hospital system.

Methods: We conducted a retrospective cohort study of 138 …

Muscle-Specific Errγ Activation Mitigates Muscle Atrophy After Acl Injury, Aiping Lu, Katie J Sikes, Ping Guo, Matthieu Huard, Shelbi Green, Kelly Santangelo, Jacob Singer, Ashley Groesbeck, Scott Tashman, Vihang A Narkar, Johnny Huard

Faculty, Staff and Student Publications

Anterior cruciate ligament (ACL) injury adversely affects skeletal muscle, leading to muscle atrophy and weakness, significantly impacting clinical outcomes. This study aimed to determine if estrogen-related receptor gamma (ERRγ) overexpression in skeletal muscle could mitigate muscle atrophy after ACL injury. An animal model with selective overexpression of ERRγ in skeletal muscle (ERR-gamma transgenic mice, TG) and WT control mice were used for this study. All the mice received a mechanical ACL rupture and were euthanized at 4- and 8-week post-injury. Muscle histology, atrophy, and function were evaluated and compared between the TG and WT mice. Muscle-specific ERRγ activation in TG …

Chemogenetic Activation Of Microglial Gi Signaling Decreases Microglial Surveillance And Impairs Neuronal Synchronization, Shunyi Zhao, Lingxiao Wang, Dimitrios Kleidonas, Fangfang Qi, Yue Liang, Jiaying Zheng, Anthony D Umpierre, Long-Jun Wu

Faculty, Staff and Student Publications

Microglia actively survey the brain and dynamically interact with neurons to maintain brain homeostasis. Microglial Gi protein-coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, the impact of temporally activating microglial Gi signaling on microglial dynamics and neuronal activity in the homeostatic brain remains largely unknown. In this study, we used Gi-based designer receptors exclusively activated by designer drugs (Gi-DREADD) to selectively and temporally modulate microglial Gi signaling pathway. By integrating this chemogenetic approach with in vivo two-photon imaging, we observed that exogenous activation of microglial Gi signaling transiently inhibited microglial process dynamics, reduced neuronal activity, and impaired …

Spetzler-Martin Grade I And Ii Cerebral Arteriovenous Malformations: A Propensity-Score Matched Analysis Of Resection And Stereotactic Radiosurgery In Adult Patients, Salem M Tos, Mahmoud Osama, Georgios Mantziaris, Bardia Hajikarimloo, Nimer Adeeb, Sandeep Kandregula, Adam A Dmytriw, Hamza Adel Salim, Basel Musmar, Kareem El Naamani, Christopher Ogilvy, Douglas Kondziolka, Ahmed Abdelsalam, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Ufuk Erginoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Howard Riina, Arwin Rezai, Johannes Pöppe, Rajeev D Sen, Omar Alwakaa, Christoph J Griessenauer, Pascal Jabbour, Stavropoula I Tjoumakaris, Jan-Karl Burkhardt, Robert M Starke, Mustafa Baskaya, Laligam N Sekhar, Michael R Levitt, David J Altschul, Neil Haranhalli, Malia Mcavoy, Assala Aslan, Abdallah Abushehab, Christian Swaid, Adib Abla, Christopher Stapleton, Matthew Koch, Visish M Srinivasan, Peng R Chen, Spiros Blackburn, Mark J Dannenbaum, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Markus Möhlenbruch, Ali Alaraj, Ali Aziz-Sultan, Aman B Patel, Hugo H Cuellar, Michael Lawton, Jacques Morcos, Bharat Guthikonda, Jason Sheehan

Faculty, Staff and Student Publications

Cerebral arteriovenous malformations (AVMs) are congenital vascular anomalies that can lead to severe complications, including hemorrhage and neurological deficits. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) for SM grade I and II AVMs. Out of a large multicenter registry, we identified 180 matched patients with SM grade I and II AVMs treated with either microsurgical resection or SRS between 2010 and 2023. The primary outcomes were AVM obliteration rates and complications; secondary outcomes included neurological status and functional outcomes measured by the modified Rankin Scale (mRS). Propensity score matching (PSM) was utilized to ensure comparability …

Kedrec-Lm: A Knowledge-Distilled Explainable Drug Recommendation Large Language Model, Kai Zhang, Rui Zhu, Shutian Ma, Jingwei Xong, Yejin Kim, Fabricio Murai, Xiaozhong Liu

Faculty, Staff and Student Publications

Drug discovery is a critical task in biomedical natural language processing (NLP), yet explainable drug discovery remains underexplored. Meanwhile, large language models (LLMs) have shown remarkable abilities in natural language understanding and generation. Leveraging LLMs for explainable drug discovery has the potential to improve downstream tasks and real-world applications. In this study, we utilize open-source drug knowledge graphs, clinical trial data, and PubMed publications to construct a comprehensive dataset for the explainable drug discovery task, named \textbf{expRxRec}. Furthermore, we introduce \textbf{KEDRec-LM}, an instruction-tuned LLM which distills knowledge from rich medical knowledge corpus for drug recommendation and rationale generation. To encourage …

Is The Pendulum Slowly Starting To Swing Back?, Michael S Ewer, Jay Herson

Faculty, Staff and Student Publications

No abstract provided.

Complement Activity And Autophagy Are Dysregulated In The Lungs Of Patients With Nonresolvable Covid-19 Requiring Lung Transplantation, Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N Lefebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) pandemic has challenged the current understanding of the complement cascade mechanisms of host immune responses during infection-induced nonresolvable lung disease. While the complement system is involved in opsonization and phagocytosis of the invading pathogens, uncontrolled complement activation also leads to aberrant autophagic response and tissue damage. Our recent study revealed unique pathologic and fibrotic signature genes associated with epithelial bronchiolization in the lung tissues of patients with nonresolvable COVID-19 (NR-COVID-19) requiring lung transplantation. However, there is a knowledge gap if complement components are modulated to contribute to tissue …

The Transition To Adulthood: A Qualitative Study Of Autism Spectrum Disorder From Military And Veteran Parents And Military-Dependent Young Adults, Antonio F Pagán, Mara C Montenegro, Mark Ahlenius, Ana C Ramirez, Miriam Ortiz, Estefani Bernal, Cecilia Montiel-Nava, Jennifer Bittner, Katherine A Loveland, Ron E Acierno

Faculty, Staff and Student Publications

Introduction: Given the unique experiences of military service members and their families, military-dependent young adults (18-25 years old) with autism spectrum disorder (ASD) and their military or veteran families experience unique barriers to accessing quality mental health care during the transition to adulthood. In fact, developing services to address ASD challenges for military families is a burgeoning area of interest for the department of defense. However, there is a limited knowledge on the specific needs of military families as the young adult's transition outside of high school and lose supports.

Materials and methods: The present study conducted 3 focus groups …

Intersect Between Brain Mechanisms Of Conditioned Threat, Active Avoidance, And Reward, Muhammad Badarnee, Zhenfu Wen, Mira Z Hammoud, Paul Glimcher, Christopher K Cain, Mohammed R Milad

Faculty, Staff and Student Publications

Active avoidance is a core behavior for human coping, and its excess is common across psychiatric diseases. The decision to actively avoid a threat is influenced by cost and reward. Yet, threat, avoidance, and reward have been studied in silos. We discuss behavioral and brain circuits of active avoidance and the interactions with fear and threat. In addition, we present a neural toggle switch model enabling fear-to-anxiety transition and approaching reward vs. avoiding harm decision. To fully comprehend how threat, active avoidance, and reward intersect, it is paramount to develop one shared experimental approach across phenomena and behaviors, which will …

Inhibition Of Il-6 Trans-Signaling Promotes Post-Stroke Functional Recovery In A Sex And Dose-Dependent Manner, Cassandra Hall, Dustin T Nguyen, Kate Mendoza, Chunfeng Tan, Anjali Chauhan

Faculty, Staff and Student Publications

Introduction: Elevated circulating IL-6 levels are associated with poorer outcomes after stroke, and increased serum IL-6 levels are linked to a higher risk of stroke. IL-6 binds to soluble IL-6 receptors (sIL-6R) and subsequently to ubiquitously expressed gp130, initiating proinflammatory trans-signaling. This study tested the hypothesis that inhibiting IL-6 trans-signaling by administering soluble (s) gp130 improves long-term functional outcomes in young mice after stroke.

Methods: Recombinant mouse gp130Fc chimera (sgp130) was administered one hour after middle cerebral artery occlusion (MCAO) followed by twice-weekly administration for 2 weeks in mice (8-15 weeks old). Behavioral assessments were done on days 7 and …

Impact Of Measurable Residual Disease Clearance Kinetics In Patients With Aml Undergoing Intensive Chemotherapy, Wei-Ying Jen, Koji Sasaki, Farhad Ravandi, Tapan M Kadia, Sa A Wang, Wei Wang, Sanam Loghavi, Naval G Daver, Courtney D Dinardo, Ghayas C Issa, Hussein A Abbas, Cedric Nasnas, Alex Bataller, Samuel Urrutia, Omer S Karrar, Sherry Pierce, Hagop M Kantarjian, Nicholas J Short

Faculty, Staff and Student Publications

The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal time point for achieving undetectable MRD is unclear. We retrospectively studied patients with newly diagnosed (ND) AML who achieved remission with frontline intensive chemotherapy and had MRD assessed by flow cytometry after induction (time point 1 [TP1]) and after cycles 2 or 3 (TP2). Cases were grouped into MRD negative (Neg)/Neg, positive (Pos)/Neg, or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met the inclusion criteria and were included in this analysis. The median relapse-free survival (RFS) …

The Spatial Landscape Of Cancer Hallmarks Reveals Patterns Of Tumor Ecological Dynamics And Drug Sensitivity, Mustafa Sibai, Sergi Cervilla, Daniela Grases, Eva Musulen, Rossana Lazcano, Chia-Kuei Mo, Veronica Davalos, Arola Fortian, Adrià Bernat, Margarita Romeo, Collin Tokheim, Jordi Barretina, Alexander J Lazar, Li Ding, Dutreneo Study Investigators, Enrique Grande, Francisco X Real, Manel Esteller, Matthew H Bailey, Eduard Porta-Pardo

Faculty, Staff and Student Publications

Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics. We show that hallmark activity is spatially organized, with the cancer compartment contributing to the activity of seven out of 13 hallmarks, while the tumor microenvironment (TME) contributes to the activity of the rest. Additionally, we discover that genomic distance between tumor subclones correlates with differences in hallmark activity, even leading to clone-hallmark specialization. Finally, we …

Immunological Biomarkers Of Response And Resistance To Treatment With Cabozantinib And Nivolumab In Recurrent Endometrial Cancer, Vladimir Roudko, Diane Marie Del Valle, Emir Radkevich, Geoffrey Kelly, Xie Hui, Manishkumar Patel, Edgar Gonzalez-Kozlova, Kevin Tuballes, Howard Streicher, Swati Atale, Lisa Wang, Benito Czinczin, Seunghee Kim-Schulze, Ignacio I Wistuba, Cara L Haymaker, Gheath Al-Atrash, Ganiraju Manyam, Jianjun Zhang, Ryan Thompson, Mayte Suarez-Farinas, Stephanie Lheureux, Sacha Gnjatic

Faculty, Staff and Student Publications

Background: Antiangiogenics combined with immune checkpoint blockade have become standard of care for recurrent endometrial cancer after standard platinum-based chemotherapy. To dissect mechanisms and define biomarkers associated with clinical outcomes to these combinations, we applied multidimensional immune monitoring to peripheral blood specimens collected from a randomized phase 2 trial of nivolumab with or without cabozantinib in 75 evaluable patients with recurrent endometrial cancer (NCI ETCTN 10104, NCT03367741). This trial demonstrated superiority of the combination to nivolumab alone.

Methods and results: Using Olink proteomics, mass cytometry, tumor antigen-specific ELISA, and whole exome tumor sequencing, we identified longitudinal immune signatures specific …

Characterization Of Factors Associated With Death In Deceased Patients With Mitochondrial Disorders: A Multicenter Cross-Sectional Survey, Alina Ivaniuk, Irina A Anselm, Aaron Bowen, Bruce H Cohen, Fatma Tuba Eminoglu, Jane Estrella, Renata C Gallagher, Rebecca D Ganetzky, Jennifer Gannon, Grainne S Gorman, Carol Greene, Andrea L Gropman, Richard H Haas, Michio Hirano, Seema Kapoor, Amel Karaa, Mary Kay Koenig, Cornelia Kornblum, Engin Kose, Austin Larson, Uta Lichter-Konecki, Piervito Lopriore, Michelangelo Mancuso, Robert Mcfarland, Aye Myat Moe, Eva Morava, Yi Shiau Ng, Russell P Saneto, Fernando Scaglia, Carolyn M Sue, Mark Tarnopolsky, Melissa A Walker, Sumit Parikh, Fung Cheuk-Wing, Tsz-Sum Wong, Kiran Belaramani, Chun-Kong Chan, Wing-Ki Chan, Wai-Lun Larry Chan, Hon-Wing Cheung, Ka-Yin Cheung, Shek-Kwan Chang, Sing-Ngai Cheung, Tsz-Fung Cheung, Yuk-Fai Cheung, Shuk-Ching Josephine Chong, Chi-Kwan Jasmine Chow, Hon-Yin B Chung, Sin-Ying Florence Fan, Wai-Ming Joshua Fok, Ka-Wing Fong, Tsui-Hang Sharon Fung, Kwok-Fai Hui, Ting-Hin Hui, Joannie Hui, Chun Hung Ko, Min-Chung Kwan, Mei-Kwan Anne Kwok, Sung-Shing Jeffrey Kwok, Moon-Sing Lai, Yau-On Lam, Ching-Wan Lam, Ming-Chung Lau, Chun-Yiu Eric Law, Hiu-Fung Law, Wing-Cheong Lee, Han-Chih Hencher Lee, Kin-Hang Leung, Kit-Yan Leung, Siu-Hung Li, Tsz-Ki Jacky Ling, Kam-Tim Timothy Liu, Fai-Man Lo, Colin Lui, Ching-On Luk, Ho-Ming Luk, Che-Kwan Ma, Karen Ma, Kam-Hung Ma, Yuen-Ni Mew, Alex Mo, Sui-Fun Hg, Wing-Kit Grace Poon, Bun Sheng, Cheuk-Ling Charing Szeto, Shuk-Mui Tai, Jing-Liang Tang, Choi-Ting Alan Tse, Li-Yan Lilian Tsung, Ho-Ming June Wong, Wing-Yin Winnie Wong, Kwok-Kui Wong, Suet-Na Sheila Wong, Chun-Nei Virginia Wong, Wai-Shan Sammy Wong, Chi-Kin Felix Wong, Shun-Ping Wu, Hiu-Fung Jerome Wu, Man-Mut Yau, Kin-Cheong Eric Yau, Wai-Lan Yeung, Hon-Ming Jonas Yeung, Kin-Keung Edwin Yip, Hui-Jun Wu, Pui-Hong Terence Young, Gao Yuan, Yuet-Ping Liz Yuen, Chi-Lap Yuen

Faculty, Staff and Student Publications

Background and objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.

Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023. Individuals with genetically confirmed mitochondrial disorders were included, along with patients with clinically or genetically diagnosed Leigh syndrome. Collected data included demographic and genetic diagnosis variables, clinical phenotype, involvement of organs and systems, conditions leading to death, and supportive care. We defined pediatric and adult groups based …

Efficacy And Safety Of Mechanical Transvenous Lead Extraction: Median Follow-Up Analysis And Development Of An Experimental Model For Predicting Survival Post-Extraction, Shima Nasri, Sahar Samimi, Masoud Eslami, Khashayar Hematpour, Morteza Eslami, Hirad Yarmohammadi, Reza Mollazadeh, Mehrzad Rahmanian

Faculty, Staff and Student Publications

Background: Cardiac implantable electronic device (CIED) implantation is on the rise, accompanied by an increase in its inevitable complications such as different types of CIED infections that require further therapy and potential device extraction. Ensuring efficacy and safety remains paramount in transvenous lead extraction (TLE), given the complex nature of the procedure. The purpose of this study is to assess the outcomes of relatively low-cost mechanical TLE, including mid-term clinical follow-up, and to develop a predictive model for post-TLE survival. This study included all consecutive patients admitted for TLE at two tertiary medical centers between 2016 and 2021. Baseline characteristics, …

Non-Invasive Real-Time Pulsed Doppler Assessment Of Blood Flow In Mouse Ophthalmic Artery, Iraida Sharina, Radwa Awad, Soren Cobb, Emil Martin, Sean P Marrelli, Anilkumar K Reddy

Faculty, Staff and Student Publications

Non-invasive and high-temporal resolution methods for characterizing blood flow in mouse cranial arteries, such as the ophthalmic artery (OphA), are lacking. We present an application of pulsed Doppler ultrasound to provide real-time, non-invasive measurement of blood flow velocity in the OphA through an identified soft tissue window in the mouse head. We confirmed the identity of the artery and mapped its origin from the internal carotid artery by a combination of microcomputed tomography (microCT) vascular imaging and transient occlusion of the internal carotid artery. Application of our approach demonstrated sex differences in the OphA vasodilative response to agonists. We also …

Openmmdl - Simplifying The Complex: Building, Simulating, And Analyzing Protein-Ligand Systems In Openmm, Valerij Talagayev, Yu Chen, Niklas Piet Doering, Leon Obendorf, Katrin Denzinger, Kristina Puls, Kevin Lam, Sijie Liu, Clemens Alexander Wolf, Theresa Noonan, Marko Breznik, Petra Knaus, Gerhard Wolber

Faculty, Staff and Student Publications

Molecular dynamics (MD) simulations have become an essential tool for studying the dynamics of biological systems and exploring protein–ligand interactions. OpenMM is a modern, open-source software toolkit designed for MD simulations. Until now, it has lacked a module dedicated to building receptor–ligand systems, which is highly useful for investigating protein–ligand interactions for drug discovery. We therefore introduce OpenMMDL, an open-source toolkit that enables the preparation and simulation of protein–ligand complexes in OpenMM, along with the subsequent analysis of protein–ligand interactions. OpenMMDL consists of three main components: OpenMMDL Setup, a graphical user interface based on Python Flask to …