Digital Commons Network^™

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

Faculty, Staff and Student Publications

Spetzler-Martin Grade IV arteriovenous malformations (AVMs) are challenging due to high risks associated with both treatment and natural progression. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) in high-grade AVMs, analyzing obliteration rates, complications, and functional outcomes. A retrospective cohort of 96 patients treated with either microsurgical resection (33 patients) or SRS (63 patients) was analyzed. Propensity-score matching was employed to account for baseline variables such as AVM size (cm), preoperative embolization and rupture status. Primary endpoints included AVM obliteration, complication rates, and modified Rankin Scale (mRS) scores. After matching, 31 patients per group were analyzed. …

Histone Acetylation Modulators In Breast Cancer, Xueying Yuan, Jeffrey M Rosen

Faculty, Staff and Students Publications

Breast cancer is the most prevalent cancer in women worldwide. Aberrant epigenetic reprogramming such as dysregulation of histone acetylation has been associated with the development of breast cancer. Histone acetylation modulators have been targeted as potential treatments for breast cancer. This review comprehensively discusses the roles of these modulators and the effects of their inhibitors on breast cancer. In addition, epigenetic reprogramming not only affects breast cancer cells but also the immunosuppressive myeloid cells, which can facilitate breast cancer progression. Therefore, the review also highlights the roles of these immunosuppressive myeloid cells and summarizes how histone acetylation modulators affect their …

Social Determinants Of Health And Health Literacy In Emergency Patients With Diabetic Ketoacidosis, Daniel F Suarez, Ryan M Schneider, Margo Girardi, Gina Larossa, Julianne Yeary, Taylor Kaser, Rachel Ancona, Paulina Cruz Bravo, Richard T Griffey

2020-Current year OA Pubs

INTRODUCTION: Social determinants of health (SDoH) and health literacy have been demonstrated to significantly impact health outcomes. As part of a study of diabetic ketoacidosis (DKA) treatment from the emergency department (ED), we assessed the burden of SDoH and health literacy among patients with DKA to identify potentially modifiable risk factors in the development of DKA.

METHODS: This was an exploratory, prospective, cross-sectional study of adult patients with DKA in a large urban academic ED from March 2023-March 2024. We administered the Centers for Medicare & Medicaid Services Accountable Health Communities Health-Related Social Needs Screening Tool (SNST) and the Brief …

O The Places Rural Children Will Go…To Get Physical Activity: A Cross Sectional Analysis., Bethany Forseth, Jordan A. Carlson, Adrian Ortega, Chelsea Steel, Brittany Lancaster, Lauren Fitzpatrick, Qianxia Jiang, Ann M. Davis

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Youth living in rural areas have higher risk for overweight/obesity. It is important to understand where these children engage in moderate-to-vigorous physical activity (MVPA) and sedentary time to encourage or intervene on activity in specific locations. This study compared MVPA and sedentary time across locations among children with overweight/obesity in the rural Midwest of the U.S.

METHODS: Participants wore an accelerometer and Global Positioning System tracker over 7-days to collect data on MVPA, sedentary time, and location. Locations were categorized as Home, Home Neighborhood, School, School Neighborhood, and 'Other'. Differences based on school and non-school days were examined.

RESULTS: …

Dissemination And Implementation Approach To Increasing Access To Local Pre-Exposure Prophylaxis (Prep) Resources With Black Cisgender Women: Intervention Study With Vlogs Shared On Social Media, Mandy J Hill, Laurenia Mangum, Sandra J Coker, Tristen Sutton, Diane M Santa Maria

Faculty, Staff and Student Publications

Background: Black cisgender women account for only 2% of pre-exposure prophylaxis (PrEP)-eligible people in the United States who use PrEP to prevent HIV. Owing to the low PrEP use, Black cisgender women continue to contract HIV more frequently than women from every other racial group. Intervention efforts that can bridge the link between knowing that PrEP prevents HIV and support with access to PrEP are necessary for Black cisgender women.

Objective: The purposes of the vlogs through the campaign were to share information about ways to prevent HIV using PrEP and fact-based education and provide access to PrEP resources with …

Cigarette Smoke Induces Angiogenic Activation In The Cancer Field Through Dysregulation Of An Endothelial Microrna, Asawari Korde, Anuradha Ramaswamy, Seth Anderson, Lei Jin, Jian-Ge Zhang, Buqu Hu, Walter V Velasco, Lixia Diao, Jing Wang, Margaret A Pisani, Maor Sauler, Daniel J Boffa, Jonathan T Puchalski, Xiting Yan, Seyed Javad Moghaddam, Shervin S Takyar

Faculty, Staff and Student Publications

Cigarette smoke (CS) creates a "cancer field" in the lung that promotes malignant transformation. The molecular changes within this field are not fully characterized. We examined the significance of microRNA-1 (miR-1) downregulation as one of these changes. We found that tumor miR-1 levels in three non-small cell lung cancer cohorts show inverse correlations with the smoking burden. Lung MiR-1 levels follow a spatial gradient, have prognostic significance, and correlate inversely with the molecular markers of injury. In CS-exposed lungs, miR-1 is specifically downregulated in the endothelium. Exposure to CS induces angiogenesis by selectively degrading mature miR-1 via a vascular endothelial …

Bridging Gaps In Cancer Care: Utilizing Large Language Models For Accessible Dietary Recommendations, Julia A. Logan, Sriya Sadhu, Cameo Hazlewood, Melissa Denton, Sara Burke, Christina A. Simone-Soule, Caroline Black, Corey Ciaverelli, Jacqueline Stulb, Hamidreza Nourzadeh, Yevgeniy Vinogradskiy, Amy Leader, Adam Dicker, Wookjin Choi, Nicole L Simone

Department of Radiation Oncology Faculty Papers

Background/Objectives: Weight management is directly linked to cancer recurrence and survival, but unfortunately, nutritional oncology counseling is not typically covered by insurance, creating a disparity for patients without nutritional education and food access. Novel ways of imparting personalized nutrition advice are needed to address this issue. Large language models (LLMs) offer a promising path toward tailoring dietary advice to individual patients. This study aimed to assess the capacity of LLMs to offer personalized dietary advice to patients with breast cancer. Methods: Thirty-one prompt templates were designed to evaluate dietary recommendations generated by ChatGPT and Gemini with variations within …

Effects Of Prebiotic Phytocompound Administration In Gestational Diabetic Dams And Its Influence On Offspring Cognitive Outcomes, Gayathri Jagadeesan, Tushar K Das, Jennifer M Mendoza, Ghalya Alrousan, Maria P Blasco-Conesa, Parimelazhagan Thangaraj, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Gestational diabetes mellitus (GD)-induced gut dysbiosis in pregnant mothers may increase the risk of cognitive impairment and neurological disorders in both the mother and offspring as they age. Restoring gut balance could improve cognitive outcomes for both. Despite advancements in GD treatment, side effects have increased, and long-term neurocognitive impacts on offspring born to GD mothers remain underexplored. This study uses a GD mouse model, inducing pancreatic dysfunction in 3-month-old pregnant C57BL/6J mice with Streptozotocin. The efficacy and mechanism of the prebiotic phytocompound green leaf extract (

Dock2 Deficiency And Gata2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (Covid-19) Pneumonia, Sajjad Biglari, Leila Youssefian, Mohammad Amin Tabatabaiefar, Amir Hossein Saeidian, Bahareh Abtahi-Naeini, Erfan Khorram, Roya Sherkat, Atefeh Sohanforooshan Moghaddam, Fatemeh Mohaghegh, Maziyar Rahimi, Hamid Rahimi, Sharareh Babaei, Mohammad Shahrooei, Nikoo Mozafari, Shirin Zaresharifi, Fatemeh Vahidnezhad, Vida Homayouni, Lam C Tsoi, Johann E Gudjonsson, Hakon Hakonarson, Jean-Laurent Casanova, Emmanuelle Jouanguy, Vivien Béziat, Qian Zhang, Aurélie Cobat, Hassan Vahidnezhad

Faculty, Staff and Students Publications

The life-threatening coronavirus disease 2019 (COVID-19) affects about 1 in 1,000 healthy people under 50 without underlying conditions. Among patients with critical COVID-19 pneumonia, rare germline variants at genes controlling type I IFN immunity have been reported in up to 5% of patients. Causal etiologies in 80-85% of cases are still unknown. We analyzed two families with hypoxemic COVID-19 pneumonia for known single-gene inborn errors of immunity. In Family 1, two siblings with critical COVID-19 were homozygous for a DOCK2 variant, c.3624+5G>A. DOCK2 deficiency is a known T-cell disorder underlying severe viral diseases. The variant resulted in skipping exon …

Amniotic Fluid-Derived Mesenchymal Stem Cells As A Therapeutic Tool Against Cytokine Storm: A Comparison With Umbilical Cord Counterparts, Salvatore Vaiasicca, David W James, Gianmarco Melone, Omar Saeed, Lewis W Francis, Bruna Corradetti

Faculty, Staff and Students Publications

Background: Several immunosuppressive therapies have been proposed as key treatment options for critically ill patients since the first appearance of severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) from different sources have been considered for their potential to attenuate the cytokine storm associated to COVID-19 and the consequent multi-organ failure, providing evidence for safe and efficacious treatments. Among them, administration of umbilical cord-derived MSCs (UC-MSCs) has demonstrated a significant increase in survival rates, largely due to their potent immunosuppressive properties.

Methods: We applied next-generation sequencing (NGS) analysis to compare the transcriptomic profiles of MSCs isolated from two gestational …

An In Vivo Screen Identifies Nat10 As A Master Regulator Of Brain Metastasis, Jocelyn F Chen, Peng Xu, Wesley L Cai, Huacui Chen, Emily Wingrove, Xiaojian Shi, Wenxue Li, Giulia Biancon, Meiling Zhang, Amer Balabaki, Ethan D Krop, Elianna Asare, Yangyi Zhang, Mingzhu Yin, Toma Tebaldi, Jordan L Meier, Thomas F Westbrook, Stephanie Halene, Yansheng Liu, Hongying Shen, Don X Nguyen, Qin Yan

Faculty, Staff and Students Publications

Emerging evidence has shown that epigenetic regulation plays a fundamental role in cancer metastasis, the major cause of cancer-related deaths. Here, we conducted an in vivo screen for vulnerabilities of brain metastasis and identified N-acetyltransferase 10 (NAT10) as a driver of brain metastasis. Knockdown of NAT10 restrains cancer cell proliferation and migration in vitro and tumor growth and brain metastasis in vivo. The poorly characterized RNA helicase domain of NAT10 is critical for cell growth in vitro, while both RNA helicase and NAT domains are essential for primary tumor growth and brain metastasis in vivo. Mechanically, NAT10 promotes the …

Association Of Parental Oral Health Knowledge And Self-Efficacy With Early Childhood Caries And Oral Health Quality Of Life In Texas Schoolchildren, Shreela V Sharma, Jeanette E Deason, Mengxi Wang, Alejandra Garcia-Quintana, Ru-Jye Chuang, Kila Johnson, Shalisa Garner, Steven Kelder, Jose-Miguel Yamal

Faculty, Staff and Student Publications

Improving children's oral health is a national priority. Parental knowledge and self-efficacy influence children's health behaviors; however, the relationship between parental oral health-related knowledge, self-efficacy, child oral health-related quality of life (OHQoL), and dental caries remains unclear, especially among low-income, ethnically diverse U.S. families. This study assesses the relationship between parental oral health-related knowledge, self-efficacy, child dental caries, and OHQoL. This cross-sectional seco ndary analysis uses baseline data from a school-based cluster-randomized controlled trial among children (kindergarten-second grade). Dental assessments were conducted using the International Caries Detection and Assessment System (ICDAS) on site in schools at baseline (n = 34 …

Lifespan Of Male And Female App/Ps1 And Appnl-F/Nl-F Mouse Models Of Alzheimer's Disease, Hannah Roberts, Yimin Fang, Kathleen Quinn, Tiarra Hill, Mackenzie R Peck, Andrzej Bartke, Kevin N Hascup, Erin R Hascup

Articles

Alzheimer's disease (AD) disproportionately affects women, yet most preclinical research studies are male-centric. We performed lifespan analyses of male and female AD mouse models (APP/PS1 and APP^NL-F/NL-F) and their shared genetic background control (C57BL/6). Survival curves support significant sex differences between genotypes. Minimal longevity revealed increased age in male APP/PS1, and decreased age in male APP^NL-F/NL-F mice. Maximal longevity revealed an increased average age in males. Furthermore, median lifespan differed between sex and genotype. This study supports dimorphic survival in two mouse models of AD, emphasizing the need to examine mechanisms and treatments in both sexes.

Effectiveness Of Intrapartum Azithromycin To Prevent Infections In Planned Vaginal Births In Low-Income And Middle-Income Countries: A Post-Hoc Analysis Of Data From A Multicentre, Randomised, Double-Blind Placebo-Controlled Trial, Waldemar A. Carlo, Alan T.N. Tita, Janet L. Moore, Musaku Mwenechanya, Elwyn Chomba, Jennifer J. Hemingway-Foday, Avinash Kavi, Mrityunjay C. Metgud, Shivaprasad S. Goudar, Richard J. Derman, Adrien Lokangaka, Antoinette Tshefu, Melissa Bauserman, Jackie K. Patterson, Poonam Shivkumar, Manju Waikar, Archana Patel, Patricia L. Hibberd, Paul Nyongesa, Fabian Esamai, Osayame Austine Ekhaguere, Sherri Bucher, Saleem Jessani, Shiyam Sunder Tikmani, Sarah Saleem, Robert L. Goldenberg, Sk Masum Billah, Ruth Lennox, Rashidul Haque, William Petri, Manolo Mazariegos, Nancy F. Krebs, Denise C. Babineau, Elizabeth M. Mcclure, Marion Koso-Thomas, A-Plus Trial Group

Global Health Articles

Background

In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin reduces maternal sepsis or death in women with planned vaginal delivery in low-resource settings, but whether it reduces maternal infection is unknown. We aimed to evaluate the effectiveness of intrapartum azithromycin in reducing maternal infection.

Methods

We performed a post-hoc analysis of the multicentre, facility-based, randomised, double-blind, placebo-controlled A-PLUS trial. This trial compared prophylactic intrapartum single oral dose of 2 g azithromycin versus placebo on maternal morbidity and mortality in low-resource settings in southeast Asia and Africa from Sept 9, 2020, to Aug 18, 2022. The …

Cost-Effectiveness Of Intrapartum Azithromycin To Prevent Maternal Infection, Sepsis, Or Death In Low-Income And Middle-Income Countries: A Modelling Analysis Of Data From A Randomised, Multicentre, Placebo-Controlled Trial, Jackie K. Patterson, Simon Neuwahl, Sydney Kirsch, Janet L. Moore, Alan T.N. Tita, Waldemar A. Carlo, Adrien Lokangaka, Antoinette Tshefu, Musaku Mwenechanya, Elwyn Chomba, Avinash Kavi, Mrityunjay C. Metgud, Shivaprasad S. Goudar, Richard J. Derman, Poonam Shivkumar, Manju Waikar, Archana Patel, Patricia L. Hibberd, Paul Nyongesa, Fabian Esamai, Osa A. Ekhaguere, Sherri Bucher, Saleem Jessani, Shiyam S. Tikmani, Sarah Saleem, Blair J. Wylie, Robert L. Goldenberg, Sk Masum Billah, Ruth Lennox, Rashidul Haque, William A. Petri, Manolo Mazariegos, Nancy F. Krebs, Jennifer J. Hemingway-Foday, Denise Babineau, Marion Koso-Thomas, Elizabeth M. Mcclure, Melissa Bauserman

Global Health Articles

BACKGROUND: Sepsis is one of the leading causes of maternal mortality globally. In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin for women planning a vaginal birth reduced the risk of maternal sepsis or death and infection. We aimed to evaluate the cost-effectiveness of intrapartum azithromycin for pregnant people planning a vaginal birth in low-income and middle-income countries (LMICs) using A-PLUS trial data.

METHODS: We compared the benefits and costs of intrapartum azithromycin versus standard care across 100 000 model simulations using data from the A-PLUS trial and a probabilistic decision tree model that included 24 …

Distinct Patterns Of Pv And Sst Gabaergic Neuronal Activity In The Basal Forebrain During Olfactory-Guided Behavior In Mice, Elizabeth H Moss, Evelyne K Tantry, Elaine Le, Pey-Shyuan Chin, Priscilla Ambrosi, Katie L Brandel-Ankrapp, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Sensory perception relies on the flexible detection and interpretation of stimuli across variable contexts, conditions, and behavioral states. The basal forebrain (BF) is a hub for behavioral state regulation, supplying dense cholinergic and GABAergic projections to various brain regions involved in sensory processing. Of GABAergic neurons in the BF, parvalbumin (PV) and somatostatin (SST) subtypes serve opposing roles toward regulating behavioral states. To elucidate the role of BF circuits in sensory-guided behavior, we investigated GABAergic signaling dynamics during odor-guided decision-making in male and female mice. We used fiber photometry to record cell type-specific BF activity during an odor discrimination task …

Tumor Treating Fields Therapy In Platinum-Resistant Ovarian Cancer: Results Of The Engot-Ov50/Gog-3029/Innovate-3 Pivotal Phase 3 Randomized Study, Ignace Vergote, Premal H Thaker, Et Al.

2020-Current year OA Pubs

PURPOSE: Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability and tumor progression. The pivotal, phase 3 ENGOT-ov50/GOG-3029/INNOVATE-3 study evaluated efficacy and safety of TTFields therapy with paclitaxel (PTX) vs PTX in patients with platinum-resistant ovarian cancer (PROC).

PATIENTS AND METHODS: Adult patients with PROC with ≤ 5 total prior lines of therapy (LOT), including ≤ 2 prior LOT for platinum-resistant disease, and ECOG PS of 0-1 were randomized 1:1 to receive TTFields (200 kHz; ≥ 18 h/day) + PTX (80 mg/m

RESULTS: Between March 2019 and November 2021, 558 patients (ECOG PS 0, …

Pmp2+ Schwann Cells Maintain The Survival Of Large-Caliber Motor Axons, Mikolaj M Kozlowski, Amy Strickland, Ana Morales Benitez, Robert E Schmidt, A Joseph Bloom, Jeffrey Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

Neurodegenerative diseases of both the central and peripheral nervous system are characterized by selective neuronal vulnerability, i.e., pathology that affects particular types of neurons. While much of this cell type selectivity may be driven by intrinsic differences among the neuron subpopulations, neuron-extrinsic mechanisms such as the selective malfunction of glial support cells may also play a role. Recently, we identified a population of Schwann cells (SCs) expressing

Pediatric Relapsed/Refractory Alk-Positive Anaplastic Large Cell Lymphoma Treatment And Outcomes In The Targeted-Drug Era., Lianna J. Marks, Victor Ritter, Jennifer E. Agrusa, Kala Y. Kamdar, Julie Rivers, Rebecca Gardner, Matthew J. Ehrhardt, Kaitlin J. Devine, Charles A. Phillips, Anne Reilly, Keith August, Joanna Weinstein, Prakash Satwani, Christopher J. Forlenza, Christine Moore Smith, Chelsee Greer, Zeinab Afify, Carol H. Lin, Jennifer A. Belsky, Hilda Ding, David Hoogstra, Keri Toner, Michael P. Link, Liora M. Schultz, Eric J. Lowe, Catherine Aftandilian

Manuscripts, Articles, Book Chapters and Other Papers

Treatment options for patients with relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and anaplastic lymphoma kinase (ALK) inhibitors. However, there is no standard treatment and published data evaluating their use are limited. The goal of this retrospective study was to describe current real-world treatment and outcomes of pediatric, adolescent, and young adult patients with R/R ALK-positive ALCL. We conducted a retrospective, multi-institutional study identifying 81 patients with R/R ALK-positive ALCL aged ≤21 years at initial diagnosis treated between 2011 and 2022 across 18 institutions. Median …

Carotid Peak Flow Velocity Variation As A Surrogate Of Aortic Peak Flow Velocity Variation In A Pediatric Population, Federico Cristiani, Juan Pablo Bouchacourt, Juan Riva, Pablo Motta

Faculty, Staff and Students Publications

Background: Carotid peak velocity variation (ΔVpeakCar) is an alternative to aortic peak velocity variation (ΔVpeakAo) and has been used in the pediatric population. Children's physiology and anatomy are heterogeneous throughout their growth. For this reason, the predictive value of ΔVpeakCar as a surrogate of ΔVpeakAo can vary at different ages. We hypothesize that the ability of ΔVpeakCar as a surrogate of ΔVpeakAo changes throughout childhood.

Aim: Analyze the concordance and the tracking ability of ΔVpeakCar and the ΔVpeakAo at different stages of development.

Methods: Patients from 0 to 12 years were included. Three groups were defined: under 12 months (G1), …

Prevalence Of Psychiatric And Sleep Disorders And Their Impact On Quality Of Life In Children With Hypermobile Ehlers-Danlos Syndrome: An Observational Study., Amanda K. Hertel, Jordan T. Jones, Ashley Lytch, Emily Cramer, Ariana Schroeder, William R. Black

Manuscripts, Articles, Book Chapters and Other Papers

Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common connective tissue disorder. However, few studies exist on psychiatric and sleep disorders in pediatric patients with hEDS. This study aims to describe psychiatric and sleep disorders and evaluate their impact on health-related quality of life (HRQoL) in pediatric patients with hEDS. As part of a longitudinal study, a convenience sample of 123 pediatric patients with hEDS, were recruited at a hEDS multidisciplinary clinic in sequential order over a seven-month period. Patient-reported outcomes were completed (Patient Reported Outcomes Measurement Information System Pediatric Profile Version 2 [PROMIS], Generalized Anxiety Disorder-7 [GAD-7], Adolescent Sleep Wake …

Haploinsufficiency Of Itsn1 Is Associated With A Substantial Increased Risk Of Parkinson’S Disease, Thomas P Spargo, Chloe F Sands, Isabella R Juan, Jonathan Mitchell, Vida Ravanmehr, Jessica C Butts, Ruth B De-Paula, Youngdoo Kim, Fengyuan Hu, Quanli Wang, Dimitrios Vitsios, Manik Garg, Lawrence Middleton, Michal Tyrlik, Mirko Messa, Guillermo Del Angel, Daniel G Calame, Hiba Saade, Laurie Robak, Ben Hollis, Vishnu A Cuddapah, Huda Y Zoghbi, Joshua M Shulman, Slavé Petrovski, Ismael Al-Ramahi, Ioanna Tachmazidou, Ryan S Dhindsa

Faculty, Staff and Students Publications

Despite its significant heritability, the genetic basis of Parkinson's disease (PD) remains incompletely understood. Here, in analyzing whole-genome sequence data from 3,809 PD cases and 247,101 controls in the UK Biobank, we discover that protein-truncating variants in ITSN1 confer a substantially increased risk of PD (p = 6.1 × 10

Care Guided By Tissue Oxygenation And Haemodynamic Monitoring In Off-Pump Coronary Artery Bypass Grafting (Bottomline-Cs): Assessor Blind, Single Centre, Randomised Controlled Trial, Jiange Han, Wenqian Zhai, Zhenhua Wu, Zhao Zhang, Tao Wang, Min Ren, Ziyue Liu, Daniel I Sessler, Zhigang Guo, Lingzhong Meng

Faculty, Staff and Student Publications

Objective: To assess whether perioperative management guided by near-infrared spectroscopy to determine tissue oxygen saturation and haemodynamic monitoring reduces postoperative complications after off-pump coronary artery bypass grafting.

Design: Assessor blinded, single centre, randomised controlled trial (Bottomline-CS trial).

Setting: A tertiary teaching hospital in China.

Participants: 1960 patients aged 60 years or older who were scheduled for elective off-pump coronary artery bypass grafting.

Interventions: All patients had multisite monitoring of tissue oxygen saturation (bilateral forehead and unilateral forearm brachioradialis) and haemodynamic monitoring. Both groups received usual care, including arterial blood pressure, central venous pressure, electrocardiography, and transoesophageal echocardiography when indicated. Guided …

Ovarian-Specific Cyp17a1 Overexpression In Female Mice: A Novel Model Of Endogenous Testosterone Excess, Serene Joseph, Vaibhave Ubba, Zhiqiang Wang, Mingxiao Feng, Milan K Dsilva, Sofia Suero, Danielle Waheed, Nathaniel W Snyder, Xiaofeng Yang, Hong Wang, Joanne S Richards, Chemyong J Ko, Sheng Wu

Faculty, Staff and Students Publications

Excessive androgen levels can severely affect female health. However, most existing models of androgen excess rely on exogenous androgen administration, which does not fully capture the effect of elevated local ovarian testosterone on reproductive and metabolic functions. Here, we report the development of a novel hyperandrogenic mouse model, Cyp17TM-625, generated by combining CRISPR-Cas9 and a Tet-On doxycycline system to induce Cyp17A1 overexpression in ovarian theca-interstitial cells. As a result, Cyp17TM-625 mice exhibited significantly elevated Cyp17A1 messenger RNA and protein levels, accompanied by increased testosterone concentrations without alterations in basal levels of estradiol, progesterone, luteinizing hormone, or follicle-stimulating hormone. These mice …

A Generalized Epilepsy Network Derived From Brain Abnormalities And Deep Brain Stimulation, Gong-Jun Ji, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Idiopathic generalized epilepsy (IGE) is a brain network disease, but the location of this network and its relevance for treatment remain unclear. We combine the locations of brain abnormalities in IGE (131 coordinates from 21 studies) with the human connectome to identify an IGE network. We validate this network by showing alignment with structural brain abnormalities previously identified in IGE and brain areas activated by generalized epileptiform discharges in simultaneous electroencephalogram-functional magnetic resonance imaging. The topography of the IGE network aligns with brain networks involved in motor control and loss of consciousness consistent with generalized seizure semiology. To investigate therapeutic …

Metagenomic Signatures Of Extraintestinal Bacterial Infection In The Febrile Term Infant Gut Microbiome, Anna L Deveaux, Carla Hall-Moore, Nurmohammad Shaikh, Meghan Wallace, Carey-Ann D Burnham, David Schnadower, Nathan Kuppermann, Prashant Mahajan, Octavio Ramilo, Phillip I Tarr, Gautam Dantas, Drew J Schwartz

2020-Current year OA Pubs

BACKGROUND: Extraintestinal bacterial infections (EBIs), e.g., urinary tract infection, bacteremia, and meningitis, occur in approximately 10% of febrile infants younger than 60 days. Although many EBI-causing species commonly reside in the infant gut, proof that the digestive system is a pre-infection habitat remains unestablished.

RESULTS: We studied a cohort of febrile term infants <  60 days old who presented to one of thirteen US emergency departments in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Forty EBI cases and 74 febrile controls matched for age, sex, and race without documented EBIs were selected for analysis. Shotgun sequencing was performed of the gut microbiome and of strains cultured from the gut and extraintestinal site(s) of EBI cases, including blood, urine, and/or cerebrospinal fluid. Using a combination of EBI isolate genomics and fecal metagenomics, we detected an intestinal strain presumptively isogenic to the EBI pathogen (> 99.999% average nucleotide identity) in 63% of infants with EBIs. Although there was no difference in gut microbiome diversity between cases and controls, we observed significantly increased Escherichia coli relative abundance in the gut microbiome of infants with EBIs caused by E. coli. Infants with E. coli …

Prediction Of Persistent Incomplete Occlusion Of Intracranial Aneurysms Treated With Woven Endobridge Device, Muhammed Amir Essibayi, Mohamed Sobhi Jabal, Hasan Jamil, Hamza Adel Salim, Basel Musmar, Nimer Adeeb, Mahmoud Dibas, Nicole M Cancelliere, Jose Danilo Bengzon, Oktay Algin, Sherief Ghozy, Sovann V Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed M Salem, Ivan Lylyk, Paul M Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U Hafeez, Joshua Catapano, Muhammad Waqas, Muhammed Said Besler, Yasin Celal Gunes, James D Rabinov, Julian Maingard, Clemens M Schirmer, Mariangela Piano, Anna L Kühn, Caterina Michelozzi, Robert M Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie T Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Sunil A Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit S Puri, Guglielmo Pero, Eytan Raz, Christoph J Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad I Levy, Deepak Khatri, Neil Haranhalli, Andrew F Ducruet, Felipe C Albuquerque, Robert W Regenhardt, Christopher J Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula I Tjoumakaris, Hugo H Cuellar-Saenz, Pascal M Jabbour, Frédéric Clarençon, Nicola Limbucci, Vitor Mendes Pereira, Aman B Patel, David J Altschul, Adam A Dmytriw, Worldwideweb Consortium Collaborators

Faculty, Staff and Student Publications

While the Woven EndoBridge (WEB) device has transformed the treatment of wide-neck intracranial aneurysms, incomplete occlusion remains a significant challenge requiring better understanding of contributing factors. A retrospective analysis was conducted on multicenter data from patients who underwent WEB device treatment for intracranial aneurysms between January 2011 and December 2022. Using machine learning models, Cox regression, and time-stratified analyses, we evaluated factors associated with persistent incomplete occlusion, defined as non-improving Raymond-Roy Occlusion Classification grade 2 or 3 at final follow-up. Among 813 patients (607 with <  24 months follow-up, 206 with ≥ 24 months), machine learning analysis identified aneurysm height, Acom location, neck diameter, and pretreatment mRS as predictors of persistent incomplete occlusion. On Cox regression. larger aneurysm neck diameter (HR 1.13, 95% CI 1.01-1.27, p = 0.027) and height (HR 1.14, 95% CI 1.02-1.26, p = 0.017), and radial access (HR 2.68, 95% CI 1.76-4.07, p <  0.001) increased, while posterior circulation location (HR 0.56, 95% CI 0.37-0.84, p = 0.005) decreased the risk of persistent incomplete occlusion. Time-stratified analysis revealed that in short-term follow-up (<  24 months), larger aneurysm neck diameter (OR 1.28, 95% CI 1.08-1.52, p = 0.004) increased the risk of incomplete occlusion. In long-term follow-up (≥ 24 months), smoking (OR 2.69, 95% CI 1.04-7.00, p = 0.04), higher pre-treatment mRS (OR 1.78, 95% CI 1.15-2.76, p = 0.009), and immediate flow stagnation (OR 0.33, 95% CI 0.11-0.96, p = 0.04) increased, while older age (OR 0.94, 95% CI 0.90-0.98, p = 0.002) and WEB-DL (OR 0.06, p <  0.001) and SLS devices (OR 0.02, p = 0.003) decreased the risk of persistent incomplete occlusion. Aneurysm characteristics and device type significantly influence long-term WEB treatment outcomes.

Radial Glia Integrin Avb8 Regulates Cell Autonomous Microglial Tgfβ1 Signaling That Is Necessary For Microglial Identity, Gabriel Mckinsey, Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Lauren Tran, Aditya Katewa, Kaylynn Conant, Matthew Barraza, Kian Waddell, Carlos Lizama, Marie La Russa, Ji Hyun Koo, Hyunji Lee, Dibyanti Mukherjee, Helena Paidassi, E. S. Anton, Kamran Atabai, Dean Sheppard, Oleg Butovsky, Thomas Arnold

Department of Medicine Faculty Papers

Microglial diversity arises from the interplay between inherent genetic programs and external environmental signals. However, the mechanisms by which these processes develop and interact within the growing brain are not yet fully understood. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) activates microglia-expressed TGFβ1 to drive microglial development. Domain-restricted deletion of Itgb8 in these progenitors results in regionally restricted and developmentally arrested microglia that persist into adulthood. In the absence of autocrine TGFβ1 signaling, microglia adopt a similar phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the canonical TGFβ signal transducers …

Prediction Of Persistent Incomplete Occlusion Of Intracranial Aneurysms Treated With Woven Endobridge Device, Muhammed Amir Essibayi, Mohamed Sobhi Jabal, Hasan Jamil, Hamza Adel Salim, Basel Musmar, Nimer Adeeb, Mahmoud Dibas, Nicole M. Cancelliere, Jose Danilo Bengzon, Oktay Algin, Sherief Ghozy, Sovann V. Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed M. Salem, Ivan Lylyk, Paul M. Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U. Hafeez, Joshua Catapano, Muhammad Waqas, Muhammed Said Besler, Yasin Celal Gunes, James D. Rabinov, Julian Maingard, Clemens M. Schirmer, Mariangela Piano, Anna L. Kühn, Caterina Michelozzi, Robert M. Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie T. Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Sunil A. Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit S. Puri, Guglielmo Pero, Eytan Raz, Christoph J. Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad I. Levy, Deepak Khatri, Neil Haranhalli, Andrew F. Ducruet, Felipe C. Albuquerque, Robert W. Regenhardt, Christopher J. Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula I. Tjoumakaris, Hugo H. Cuellar-Saenz, Pascal Jabbour, Frédéric Clarençon, Nicola Limbucci, Vitor Mendes Pereira, Aman B. Patel, David J. Altschul, Adam A. Dmytriw, Worldwideweb Consortium Collaborators

Department of Neurosurgery Faculty Papers

While the Woven EndoBridge (WEB) device has transformed the treatment of wide-neck intracranial aneurysms, incomplete occlusion remains a significant challenge requiring better understanding of contributing factors. A retrospective analysis was conducted on multicenter data from patients who underwent WEB device treatment for intracranial aneurysms between January 2011 and December 2022. Using machine learning models, Cox regression, and time-stratified analyses, we evaluated factors associated with persistent incomplete occlusion, defined as non-improving Raymond-Roy Occlusion Classification grade 2 or 3 at final follow-up. Among 813 patients (607 with < 24 months follow-up, 206 with ≥ 24 months), machine learning analysis identified aneurysm height, Acom location, neck diameter, and pretreatment mRS as predictors of persistent incomplete occlusion. On Cox regression. larger aneurysm neck diameter (HR 1.13, 95% CI 1.01-1.27, p = 0.027) and height (HR 1.14, 95% CI 1.02-1.26, p = 0.017), and radial …

Experiences And Perceptions Of Conditional Cash Incentive Provision And Cessation Among People With Hiv For Care Engagement: A Qualitative Study, Julia Giordano, Jayne Lewis-Kulzer, Lina Montoya, Eliud Akama, Harriet Fridah Adhiambo, Everlyne Nyadieka, Sarah Iguna, Elizabeth A Bukusi, Thomas Odeny, Carol S Camlin, Harsha Thirumurthy, Maya Petersen, Elvin Geng

2020-Current year OA Pubs

BACKGROUND: Conditional cash transfers (CCTs) have been shown to improve retention in HIV care while they are provided, but their long-term effectiveness remains uncertain and effects may be time-limited, with cessation resulting in HIV care engagement deterioration. We explored CCT experiences, perceptions, and effects after cessation to investigate potential mechanisms of this observation and better understand the psychological mechanisms behind CCTs.

METHODS: This qualitative study was nested within a larger trial, AdaPT-R (NCT02338739), focused on HIV care engagement in western Kenya. A subset of participants were purposively sampled from AdaPT-R participants: adults with HIV who had recently started ART, received …