Digital Commons Network^™

Edge-Wise Analysis Reveals White Matter Connectivity Associated With Focal To Bilateral Tonic-Clonic Seizures, Sam S. Javidi, Xiaosong He, Ankeeta Ankeeta, Qirui Zhang, Salvatore Citro, Michael R. Sperling, Joseph I. Tracy

Farber Institute for Neuroscience Faculty Papers

OBJECTIVE: Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS.

METHODS: T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs …

Mapping Sca1 Regional Vulnerabilities Reveals Neural And Skeletal Muscle Contributions To Disease, Lisa Duvick, W Michael Southern, Kellie A Benzow, Zoe N Burch, Hillary P Handler, Jason S Mitchell, Hannah Kuivinen, Udaya Gadiparthi, Praseuth Yang, Alyssa Soles, Carrie A Sheeler, Orion Rainwater, Shannah Serres, Erin B Lind, Tessa Nichols-Meade, Yun You, Brennon O'Callaghan, Huda Y Zoghbi, Marija Cvetanovic, Vanessa C Wheeler, James M Ervasti, Michael D Koob, Harry T Orr

Duncan NRI Faculty and Staff Publications

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockin mouse (f-ATXN1146Q/2Q) with mouse Atxn1 coding exons replaced by human ATXN1 exons encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. Central nervous system (CNS) contributions to disease were revealed using f-ATXN1146Q/2Q;Nestin-Cre mice, which showed improved rotarod, open field, and Barnes maze performance by 6-12 weeks of age. In contrast, …

Tumor Treating Fields Suppress Tumor Cell Growth And Neurologic Decline In Models Of Spinal Metastases, Daniel Ledbetter, Romulo Augusto Andrade De Almeida, Xizi Wu, Ariel Naveh, Chirag B Patel, Queena Gonzalez, Thomas H Beckham, Robert North, Laurence Rhines, Jing Li, Amol Ghia, David Aten, Claudio Tatsui, Christopher Alvarez-Breckenridge

Faculty, Staff and Student Publications

Spinal metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesized that bone's dielectric properties will enhance TTFields-mediated suppression of tumor growth in spinal metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts …

Establishment Of Murine Pregnancy Requires The Promyelocytic Leukemia Zinc Finger Transcription Factor, Lan Hai, Vineet K Maurya, Francesco J Demayo, John P Lydon

Faculty, Staff and Students Publications

Using an established human primary cell culture model, we previously demonstrated that the promyelocytic leukemia zinc finger (PLZF) transcription factor is a direct target of the progesterone receptor (PGR) and is essential for progestin-dependent decidualization of human endometrial stromal cells (HESCs). These in vitro findings were supported by immunohistochemical analysis of human endometrial tissue biopsies, which showed that the strongest immunoreactivity for endometrial PLZF is detected during the progesterone (P4)-dominant secretory phase of the menstrual cycle. While these human studies provided critical clinical support for the important role of PLZF in P4-dependent HESC decidualization, functional validation in vivo was not …

Visual Outcome And Ocular Complications In Patients With Lacrimal Gland Carcinoma After Eye-Sparing Surgery And Adjuvant Radiation Therapy, Zhenyang Zhao, Steven Jay Frank, Jing Ning, Jiawei Zhao, Xinyang Jiang, Xin A Wang, Amy C Schefler, Ehab Hanna, Amy Moreno, Brandon Gunn, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Background: We report visual outcomes and ocular complications in patients with lacrimal gland carcinoma who had eye-sparing surgery followed by radiotherapy.

Methods: This review included consecutive patients with lacrimal gland carcinoma who underwent eye-sparing surgery and adjuvant radiotherapy or concurrent chemoradiation therapy between 2007 and 2018. Clinical data, including details of ophthalmological examinations and radiation treatment were reviewed.

Results: The study included 23 patients, 15 males and 8 females, with median age 51 years. Twenty patients (87%) received intensity-modulated proton therapy; 3 (13%) received intensity-modulated radiotherapy. Nineteen patients (83%) received concurrent chemotherapy. After a median follow-up time of 37 months …

What Do Cervical Cancer Patients Know, How Do They Learn, And Who Do They Tell? A Pilot Study, Sharon Larson, Brian Mcanany, Ilene Ladd, Radhika Gogoi

College of Population Health Faculty Papers

BACKGROUND: This study explored what patients identified with cervical cancer know about the link between human papillomavirus (HPV) and cervical cancer and where they learned this information. Patients share a great deal of information with family, friends and colleagues and we were interested in the accuracy and sources of information they are sharing.

METHODS: Patients identified through the EHR of a health system who had a history of cervical cancer were invited to participate in a brief survey of their experience. The sample represents an opportunity sample of patients who responded.

RESULTS: Generally, these patients, drawn from the Geisinger Health …

Outpatient Covid-19 Convalescent Plasma Recipient Antibody Thresholds Correlated To Reduced Hospitalizations Within A Randomized Trial, Han-Sol Park, Anna Yin, Caelan Barranta, John S Lee, Christopher A Caputo, Jaiprasath Sachithanandham, Maggie Li, Steve Yoon, Ioannis Sitaras, Anne Jedlicka, Yolanda Eby, Malathi Ram, Reinaldo E Fernandez, Owen R Baker, Aarthi G Shenoy, Giselle S Mosnaim, Yuriko Fukuta, Bela Patel, Sonya L Heath, Adam C Levine, Barry R Meisenberg, Emily S Spivak, Shweta Anjan, Moises A Huaman, Janis E Blair, Judith S Currier, James H Paxton, Jonathan M Gerber, Joann R Petrini, Patrick B Broderick, William Rausch, Marie Elena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L Hammitt, Catherine G Sutcliffe, Donald N Forthal, Martin S Zand, Edward R Cachay, Jay S Raval, Seble G Kassaye, Christi E Marshall, Anusha Yarava, Karen Lane, Nichol A Mcbee, Amy L Gawad, Nicky Karlen, Atika Singh, Daniel E Ford, Douglas A Jabs, Lawrence J Appel, David M Shade, Bryan Lau, Stephan Ehrhardt, Sheriza N Baksh, Janna R Shapiro, Jiangda Ou, Yu Bin Na, Maria D Knoll, Elysse Ornelas-Gatdula, Netzahualcoyotl Arroyo-Curras, Thomas J Gniadek, Patrizio Caturegli, Jinke Wu, Nelson Ndahiro, Michael J Betenbaugh, Alyssa Ziman, Daniel F Hanley, Arturo Casadevall, Shmuel Shoham, Evan M Bloch, Kelly A Gebo, Aaron Ar Tobian, Oliver Laeyendecker, Andrew Pekosz, Sabra L Klein, David J Sullivan

Faculty, Staff and Students Publications

BACKGROUND

COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.

METHODS

This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization–equivalent anti–Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors …

Strabismus Management In Retinoblastoma Survivors, Babak Masoomian, Carol L. Shields, Hamid Riazi Esfahani, Atefeh Khalili, Fariba Ghassemi, Pukhraj Rishi, Mohammad Reza Akbari, Masoud Khorrami-Nejad

Wills Eye Hospital Papers

PURPOSE: To report the result of strabismus surgery in eye-salvaged retinoblastoma (Rb) patients.

METHODS: A retrospective case series including 18 patients with Rb and strabismus who underwent strabismus surgery after completing tumor treatment by a single pediatric ophthalmologist.

RESULTS: A total of 18 patients (10 females and 8 males) were included with a mean age of 13.3 ± 3.0 (range, 2-39) months at the time tumor presentation and 6.0 ± 1.5 (range, 4-9) years at the time of strabismus surgery. Ten (56%) patients had unilateral and 8(44%) had bilateral involvement and the most common worse eye tumor's group was D …

Pharmacokinetics Of Propofol In Severely Obese Surgical Patients, Martin Rygh Braathen, Ann E. Rigby-Jones, Johan Ræder, Olav Spigset, Tom Heier

Peninsula Medical School

Background: Existing PK models of propofol include sparse data from very obese patients. The aim of this study was to develop a PK model based on standardised surgical conditions and spanning from normal-weight up to, and including, a high number of very obese patients. Methods: Adult patients scheduled for laparoscopic cholecystectomy or bariatric surgery were studied. Anaesthesia was induced with propofol 2 mg/kg adjusted body weight over 2 min followed by 6 mg/kg/h adjusted body weight over 30 min. For the remainder of the operation anaesthesia was maintained with sevoflurane. Remifentanil was dosed according to clinical need. Eight arterial samples …

Mental Health, Chronic And Infectious Conditions Among Pregnant Persons In Us State Prisons And Local Jails 2016-2017., Caitlin A Hendricks, Karissa M Rajagopal, Carolyn B Sufrin, Camille Kramer, Monik C Jiménez

Cooper Medical School of Rowan University Departmental Research

BACKGROUND: Pregnant individuals in incarcerated settings have unique healthcare needs. Rates of mental health, infectious diseases, and chronic disease are higher among nonpregnant incarcerated women compared with those who are not, but the prevalence of these conditions among pregnant people in custody has not been documented.

OBJECTIVES: The objective of this study is to describe the prevalence of metabolic, infectious, and mental health conditions in pregnant people to identify the medical needs of high-risk pregnancies in US state prisons and local jails.

STUDY DESIGN: This was a prospective epidemiologic surveillance of a convenience sample of state prisons (n = …

Variants In Zfx Are Associated With An X-Linked Neurodevelopmental Disorder With Recurrent Facial Gestalt\, James L Shepherdson, Katie Hutchison, Dilan Wellalage Don, George Mcgillivray, Tae-Ik Choi, Carolyn A Allan, David J Amor, Siddharth Banka, Donald G Basel, Laura D Buch, Deanna Alexis Carere, Renée Carroll, Jill Clayton-Smith, Ali Crawford, Morten Dunø, Laurence Faivre, Christopher P Gilfillan, Nina B Gold, Karen W Gripp, Emma Hobson, Alexander M Holtz, A Micheil Innes, Bertrand Isidor, Adam Jackson, Panagiotis Katsonis, Leila Amel Riazat Kesh, Genomics England Research Consortium;, Sébastien Küry, François Lecoquierre, Paul Lockhart, Julien Maraval, Naomichi Matsumoto, Julie Mccarrier, Josephine Mccarthy, Noriko Miyake, Lip Hen Moey, Andrea H Németh, Elsebet Østergaard, Rushina Patel, Kate Pope, Jennifer E Posey, Rhonda E Schnur, Marie Shaw, Elliot Stolerman, Julie P Taylor, Erin Wadman, Emma Wakeling, Susan M White, Lawrence C Wong, James R Lupski, Olivier Lichtarge, Mark A Corbett, Jozef Gecz, Charles M Nicolet, Peggy J Farnham, Cheol-Hee Kim, Marwan Shinawi

Duncan NRI Faculty and Staff Publications

Pathogenic variants in multiple genes on the X chromosome have been implicated in syndromic and non-syndromic intellectual disability disorders. ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not been characterized in association with disease. Here, we present clinical and molecular characterization of 18 individuals with germline ZFX variants. Exome or genome sequencing revealed 11 variants in 18 subjects (14 males and 4 females) from 16 unrelated families. Four missense variants were identified in 11 subjects, with seven truncation variants in the remaining individuals. Clinical findings included …

Endovascular Thrombectomy For Large Ischemic Stroke Across Ischemic Injury And Penumbra Profiles, Amrou Sarraj, Ameer E Hassan, Michael G Abraham, Santiago Ortega-Gutierrez, Scott E Kasner, Muhammad Shazam Hussain, Michael Chen, Leonid Churilov, Hannah Johns, Clark W Sitton, Vignan Yogendrakumar, Felix C Ng, Deep K Pujara, Spiros Blackburn, Sophia Sundararajan, Yin C Hu, Nabeel A Herial, Juan F Arenillas, Jenny P Tsai, Ronald F Budzik, William J Hicks, Osman Kozak, Bernard Yan, Dennis J Cordato, Nathan W Manning, Mark W Parsons, Andrew Cheung, Ricardo A Hanel, Amin N Aghaebrahim, Teddy Y Wu, Pere Cardona Portela, Chirag D Gandhi, Fawaz Al-Mufti, Natalia Pérez De La Ossa, Joanna D Schaafsma, Jordi Blasco, Navdeep Sangha, Steven Warach, Timothy J Kleinig, Faris Shaker, Faisal Al Shaibi, Gabor Toth, Mohammad A Abdulrazzak, Gagan Sharma, Abhishek Ray, Jeffrey Sunshine, Amanda Opaskar, Kelsey R Duncan, Wei Xiong, Edgar A Samaniego, Laith Maali, Colleen G Lechtenberg, Arturo Renú, Nirav Vora, Thanh Nguyen, Johanna T Fifi, Stavropoula I Tjoumakaris, Pascal Jabbour, Georgios Tsivgoulis, Vitor Mendes Pereira, Maarten G Lansberg, Michael Degeorgia, Cathy A Sila, Nicholas Bambakidis, Michael D Hill, Stephen M Davis, Lawrence Wechsler, James C Grotta, Marc Ribo, Greg W Albers, Bruce C Campbell

Faculty, Staff and Student Publications

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.

Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.

Design, setting, and participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 …

Endovascular Thrombectomy For Large Ischemic Stroke Across Ischemic Injury And Penumbra Profiles., Amrou Sarraj, Ameer E Hassan, Michael G Abraham, Santiago Ortega-Gutierrez, Scott E Kasner, Muhammad Shazam Hussain, Michael Chen, Leonid Churilov, Hannah Johns, Clark W Sitton, Vignan Yogendrakumar, Felix C Ng, Deep K Pujara, Spiros Blackburn, Sophia Sundararajan, Yin C Hu, Nabeel A Herial, Juan F Arenillas, Jenny P Tsai, Ronald F Budzik, William J Hicks, Osman Kozak, Bernard Yan, Dennis J Cordato, Nathan W Manning, Mark W Parsons, Andrew Cheung, Ricardo A Hanel, Amin N Aghaebrahim, Teddy Y Wu, Pere Cardona Portela, Chirag D Gandhi, Fawaz Al-Mufti, Natalia Pérez De La Ossa, Joanna D Schaafsma, Jordi Blasco, Navdeep Sangha, Steven Warach, Timothy J Kleinig, Faris Shaker, Faisal Al Shaibi, Gabor Toth, Mohammad A Abdulrazzak, Gagan Sharma, Abhishek Ray, Jeffrey Sunshine, Amanda Opaskar, Kelsey R Duncan, Wei Xiong, Edgar A Samaniego, Laith Maali, Colleen G Lechtenberg, Arturo Renú, Nirav Vora, Thanh Nguyen, Johanna T Fifi, Stavropoula I Tjoumakaris, Pascal Jabbour, Georgios Tsivgoulis, Vitor Mendes Pereira, Maarten G Lansberg, Michael Degeorgia, Cathy A Sila, Nicholas Bambakidis, Michael D Hill, Stephen M Davis, Lawrence Wechsler, James C Grotta, Marc Ribo, Greg W Albers, Bruce C Campbell

Neuroscience Articles

IMPORTANCE: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.

OBJECTIVE: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.

DESIGN, SETTING, AND PARTICIPANTS: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 …

Hippo Cooperates With P53 To Maintain Foregut Homeostasis And Suppress The Malignant Transformation Of Foregut Basal Progenitor Cells, Yu Jiang, Haidi Huang, Jiangying Liu, Dan Luo, Rongzi Mu, Jianghong Yuan, Jihong Lin, Qiyue Chen, Wufan Tao, Ling Yang, Man Zhang, Pingping Zhang, Fengqin Fang, Jianming Xu, Qingqiu Gong, Zhiping Xie, Yongchun Zhang

Faculty, Staff and Students Publications

Basal progenitor cells serve as a stem cell pool to maintain the homeostasis of the epithelium of the foregut, including the esophagus and the forestomach. Aberrant genetic regulation in these cells can lead to carcinogenesis, such as squamous cell carcinoma (SCC). However, the underlying molecular mechanisms regulating the function of basal progenitor cells remain largely unknown. Here, we use mouse models to reveal that Hippo signaling is required for maintaining the homeostasis of the foregut epithelium and cooperates with p53 to repress the initiation of foregut SCC. Deletion of

Intraoperative Evaluation Of Breast Tissues During Breast Cancer Operations Using The Masspec Pen, Kyana Y Garza, Mary E King, Chandandeep Nagi, Rachel J Dehoog, Jialing Zhang, Marta Sans, Anna Krieger, Clara L Feider, Alena V Bensussan, Michael F Keating, John Q Lin, Min Woo Sun, Robert Tibshirani, Christopher Pirko, Kirtan A Brahmbhatt, Ahmed R Al-Fartosi, Alastair M Thompson, Elizabeth Bonefas, James Suliburk, Stacey A Carter, Livia S Eberlin

Faculty, Staff and Students Publications

IMPORTANCE: Surgery with complete tumor resection remains the main treatment option for patients with breast cancer. Yet, current technologies are limited in providing accurate assessment of breast tissue in vivo, warranting development of new technologies for surgical guidance.

OBJECTIVE: To evaluate the performance of the MasSpec Pen for accurate intraoperative assessment of breast tissues and surgical margins based on metabolic and lipid information.

DESIGN, SETTING, AND PARTICIPANTS: In this diagnostic study conducted between February 23, 2017, and August 19, 2021, the mass spectrometry-based device was used to analyze healthy breast and invasive ductal carcinoma (IDC) banked tissue samples from adult …

Postconcussive Symptoms After Early Childhood Concussion, Dominique Dupont, Ken Tang, Cindy Beaudoin, Fanny Dégeilh, Isabelle Gagnon, Keith Owen Yeates, Sean C Rose, Jocelyn Gravel, Brett Burstein, Antonia S Stang, Rachel M Stanley, Roger L Zemek, Miriam H Beauchamp, Perc Koala Study

Faculty, Staff and Student Publications

IMPORTANCE: Research on postconcussive symptoms (PCS) following early childhood concussion has been hindered by a lack of measures suitable for this age group, resulting in a limited understanding of their evolution in young children.

OBJECTIVE: To document PCS in the first 3 months after early childhood concussion using a developmentally appropriate measure.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data collected at 3 Canadian and 1 US urban pediatric emergency departments (EDs) and 8 Canadian daycares from December 2018 to December 2022 as part of the Kids' Outcomes and Long-Term Abilities (KOALA) project, a prospective, multicenter, longitudinal cohort study. …

Germline Genetic Testing And Survival Outcomes Among Children With Rhabdomyosarcoma: A Report From The Children's Oncology Group, Bailey A Martin-Giacalone, He Li, Michael E Scheurer, Dana L Casey, Shannon Dugan-Perez, Deborah A Marquez-Do, Donna Muzny, Richard A Gibbs, Donald A Barkauskas, David Hall, Douglas R Stewart, Joshua D Schiffman, Matthew T Mcevoy, Javed Khan, David Malkin, Corinne M Linardic, Brian D Crompton, Jack F Shern, Stephen X Skapek, Rajkumar Venkatramani, Douglas S Hawkins, Aniko Sabo, Sharon E Plon, Philip J Lupo

Faculty, Staff and Students Publications

IMPORTANCE: Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma.

OBJECTIVE: To assess whether CPVs are associated with outcome among children with rhabdomyosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, data were obtained for individuals, aged 0.01-23.23 years, newly diagnosed with rhabdomyosarcoma who were treated across 171 Children's Oncology Group sites from March 15, 1999, to December 8, 2017. Data analysis was performed from June 16, 2021, to May 15, 2023.

EXPOSURE: The presence of a CPV in 24 rhabdomyosarcoma-associated cancer-predisposition genes (CPGs) or an expanded set …

Physical Activity Patterns Within Dementia Care Dyads, N Farina, R Mcardle, Rg Lowry, S Banerjee

Peninsula Medical School

Previous research has explored the physical activity habits of people with dementia and their family carers separately, with little consideration of how physical habits are associated within dyads. In this observational study, we sought to explore the relationship between people with dementia and their carers' physical activity, at a group level and at a dyadic level. Twenty-six participant dyads (persons with dementia and their carer spouses) were asked to wear an accelerometer for 30 days continuously. Comparisons were made at a group level and a dyadic level. People with dementia did not participate in significantly more moderate to vigorous physical …

The Immunopathological Landscape Of Human Pre-Tcrα Deficiency: From Rare To Common Variants., Marie Materna, Ottavia M Delmonte, Marita Bosticardo, Mana Momenilandi, Peyton E Conrey, Bénédicte Charmeteau-De Muylder, Clotilde Bravetti, Rebecca Bellworthy, Axel Cederholm, Frederik Staels, Christian A Ganoza, Samuel Darko, Samir Sayed, Corentin Le Floc'h, Masato Ogishi, Darawan Rinchai, Andrea Guenoun, Alexandre Bolze, Taushif Khan, Adrian Gervais, Renate Krüger, Mirjam Völler, Boaz Palterer, Mahnaz Sadeghi-Shabestari, Anne Langlois De Septenville, Chaim A Schramm, Sanjana Shah, John J Tello-Cajiao, Francesca Pala, Kayla Amini, Jose S Campos, Noemia Santana Lima, Daniel Eriksson, Romain Lévy, Yoann Seeleuthner, Soma Jyonouchi, Manar Ata, Fatima Al Ali, Anna Stittrich, Caroline Deswarte, Anaïs Pereira, Jérôme Mégret, Tom Le Voyer, Paul Bastard, Laureline Berteloot, Michaël Dussiot, Natasha Vladikine, Paula P Cardenas, Emmanuelle Jouanguy, Mashael Alqahtani, Amal Hasan, Thangavel Alphonse Thanaraj, Jérémie Rosain, Fahd Al Qureshah, Vito Sabato, Marie Alexandra Alyanakian, Marianne Leruez-Ville, Flore Rozenberg, Elie Haddad, Jose R Regueiro, Maria L Toribio, Judith R Kelsen, Mansoor Salehi, Shahram Nasiri, Mehdi Torabizadeh, Hassan Rokni-Zadeh, Majid Changi-Ashtiani, Nasimeh Vatandoost, Hossein Moravej, Seyed Mohammad Akrami, Mohsen Mazloomrezaei, Aurélie Cobat, Isabelle Meyts, Etsushi Toyofuku, Madoka Nishimura, Kunihiko Moriya, Tomoyuki Mizukami, Kohsuke Imai, Laurent Abel, Bernard Malissen, Fahd Al-Mulla, Fowzan Sami Alkuraya, Nima Parvaneh, Horst Von Bernuth, Christian Beetz, Frédéric Davi, Daniel C Douek, Rémi Cheynier, David Langlais, Nils Landegren, Nico Marr, Tomohiro Morio, Mohammad Shahrooei, Rik Schrijvers, Sarah E Henrickson, Hervé Luche, Luigi D Notarangelo, Jean-Laurent Casanova, Vivien Béziat

Faculty Research 2024

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre–a T cell receptor (pre-TCRa) expression. Low circulating naive ab T cell counts at birth persisted over time, with normal memory ab and high gd T cell counts. Their TCRa repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue ab T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive ab T cell …

Retrograde Endocannabinoid Signaling At Inhibitory Synapses In Vivo, Barna Dudok, Linlin Z Fan, Jordan S Farrell, Shreya Malhotra, Jesslyn Homidan, Doo Kyung Kim, Celestine Wenardy, Charu Ramakrishnan, Yulong Li, Karl Deisseroth, Ivan Soltesz

Faculty, Staff and Students Publications

Endocannabinoid (eCB)-mediated suppression of inhibitory synapses has been hypothesized, but this has not yet been demonstrated to occur in vivo because of the difficulty in tracking eCB dynamics and synaptic plasticity during behavior. In mice navigating a linear track, we observed location-specific eCB signaling in hippocampal CA1 place cells, and this was detected both in the postsynaptic membrane and the presynaptic inhibitory axons. All-optical in vivo investigation of synaptic responses revealed that postsynaptic depolarization was followed by a suppression of inhibitory synaptic potentials. Furthermore, interneuron-specific cannabinoid receptor deletion altered place cell tuning. Therefore, rapid, postsynaptic, activity-dependent eCB signaling modulates inhibitory …

Heterozygous Map3k20 Variants Cause Ectodermal Dysplasia, Craniosynostosis, Sensorineural Hearing Loss, And Limb Anomalies, Daniel Brooks, Elizabeth Burke, Sukyeong Lee, Tanya N Eble, Melanie O'Leary, Ikeoluwa Osei-Owusu, Heidi L Rehm, Shweta U Dhar, Lisa Emrick, David Bick, Michelle Nehrebecky, Ellen Macnamara, Dídac Casas-Alba, Judith Armstrong, Carolina Prat, Antonio F Martínez-Monseny, Francesc Palau, Pengfei Liu, David Adams, Undiagnosed Diseases Network, Seema Lalani, Jill A Rosenfeld, Lindsay C Burrage

Faculty, Staff and Students Publications

Biallelic pathogenic variants in MAP3K20, which encodes a mitogen-activated protein kinase, are a rare cause of split-hand foot malformation (SHFM), hearing loss, and nail abnormalities or congenital myopathy. However, heterozygous variants in this gene have not been definitively associated with a phenotype. Here, we describe the phenotypic spectrum associated with heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20. We report five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in this specific region of the gene. …

Self-Sampling For Human Papillomavirus Testing: Acceptability In A Us Safety Net Health System, Susan L Parker, Trisha L Amboree, Shaun Bulsara, Maria Daheri, Matthew L Anderson, Susan G Hilsenbeck, Maria L Jibaja-Weiss, Mohammed Zare, Kathleen M Schmeler, Ashish A Deshmukh, Elizabeth Y Chiao, Michael E Scheurer, Jane R Montealegre

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Self-sampling for human papillomavirus testing is increasingly recognized as a strategy to expand cervical cancer screening access and utilization. Acceptability is a key determinant of uptake. This study assesses the acceptability of and experiences with mailed self-sampling kits for human papillomavirus testing among underscreened patients in a safety net health system.

Methods: A nested telephone survey was administered between 2021 and 2023 to a sample (n=272) of the 2,268 participants enrolled in the Prospective Evaluation of Self-Testing to Increase Screening trial. Trial participants include patients of a safety net health system aged 30-65 years who were not up to …

A Study Of Dietary Patterns Derived By Cluster Analysis And Their Association With Metabolic Dysfunction-Associated Steatotic Liver Disease Severity Among Hispanic Patients, Xiaotao Zhang, Carrie R Daniel, Valeria Soltero, Ximena Vargas, Shilpa Jain, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Student Publications

Introduction: Diet is a modifiable metabolic dysfunction-associated steatotic liver disease (MASLD) risk factor, but few studies have been conducted among Hispanic patients, despite the fact that MASLD prevalence and severity are highest among this ethnic subgroup. We aimed to identify prevalent dietary patterns among Hispanic patients using cluster analysis and to investigate associations with MASLD severity.

Methods: This cross-sectional analysis included 421 Harris County MASLD Cohort participants who self-reported Hispanic ethnicity and completed baseline food frequency questionnaires. All included patients had MASLD, diagnosed per standard clinical criteria. K-means analysis was used to identify clusters of patients sharing similar dietary habits. …

The Conceptual Definition Of Sarcopenia: Delphi Consensus From The Global Leadership Initiative In Sarcopenia (Glis), Ben Kirk, Ellen F Binder, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists.

OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia.

DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of …

Diagnostic Yield Of Exome Sequencing In Prenatal Agenesis Of Corpus Callosum: Systematic Review And Meta-Analysis, H. J. Mustafa, J. P. Barbera, E. V. Sambatur, G. Pagani, Y. Yaron, C. D. Baptiste, R. J. Wapner, C. J. Brewer, A. Khalil

Department of Medicine Faculty Papers

OBJECTIVES: To determine the incremental diagnostic yield of exome sequencing (ES) after negative chromosomal microarray analysis (CMA) in cases of prenatally diagnosed agenesis of the corpus callosum (ACC) and to identify the associated genes and variants.

METHODS: A systematic search was performed to identify relevant studies published up until June 2022 using four databases: PubMed, SCOPUS, Web of Science and The Cochrane Library. Studies in English reporting on the diagnostic yield of ES following negative CMA in prenatally diagnosed partial or complete ACC were included. Authors of cohort studies were contacted for individual participant data and extended cohorts were provided …

Fetoscopic Endoluminal Tracheal Occlusion For Severe, Left-Sided Congenital Diaphragmatic Hernia: The North American Fetal Therapy Network Fetoscopic Endoluminal Tracheal Occlusion Consortium Experience, Eric Bergh, Ahmet A Baschat, Magdalena Sanz Cortes, Holly L Hedrick, Greg Ryan, Foong-Yen Lim, Michael V Zaretsky, Mauro H Schenone, Timothy M Crombleholme, Rodrigo Ruano, Kristen A Gosnell, Anthony Johnson

Faculty, Staff and Students Publications

OBJECTIVE: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed.

METHODS: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic …

Self-Efficacy To Refuse Sex Mediates The Relationship Between Dating Violence Victimization And Sexual Risk Behavior, Briana Edison, Shristi Bhochhibhoya, Elizabeth R Baumler, Christine M Markham, Melissa F Peskin, Ross Shegog, Susan T Emery, Robert C Addy, Jeff R Temple, Dennis E Reidy

Faculty, Staff and Student Publications

Purpose: While cross-sectional studies have shown that teen dating violence (TDV) victimization is linked to sexual risk behavior (SRB), the pathway between these variables is not well-understood. To address this knowledge gap, we explore the mediating role of self-efficacy to refuse sex in the longitudinal relationship between physical TDV victimization and subsequent SRB among adolescents.

Methods: Self-report data from three prior longitudinal studies were harmonized to create a single aggregated sample of primarily racial and ethnic minority adolescents (N = 4,620; 51.4% Hispanic, 38.5% Black, and 58% female) from 44 schools in the southwest U.S. Participants' physical TDV victimization at …

Breastfeeding Initiation, Duration, And Associated Factors Among People With Hepatitis C Virus Infection, Jennifer L Grasch, Jessica A De Voest, George R Saade, Brenna L Hughes, Uma M Reddy, Maged M Costantine, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

OBJECTIVE: To characterize breastfeeding behaviors and identify factors associated with breastfeeding initiation among people with hepatitis C virus (HCV) infection.

METHODS: We conducted a secondary analysis of a multicenter observational cohort of pregnant people with singleton gestations and HCV seropositivity. This analysis includes individuals with data on breastfeeding initiation and excludes those with human immunodeficiency virus (HIV) co-infection. The primary outcome was self-reported initiation of breastfeeding or provision of expressed breast milk. Secondary outcomes included duration of breastfeeding. Demographic and obstetric characteristics were compared between those who initiated breastfeeding and those who did not to identify associated factors. Univariable and …

Examining Full-Time Academic General Pediatric Faculty Compensation By Gender, Race, And Ethnicity: 2020-2021, Emma A Omoruyi, Callie L Brown, Colin J Orr, Kimberly Montez

Faculty, Staff and Student Publications

Objective: In medicine, women have lower lifetime earnings than men. To our knowledge, an in-depth examination of academic general pediatric faculty compensation by gender, race, and ethnicity has not been conducted. We aimed to 1) explore full-time academic general pediatric faculty salary differences by race and ethnicity; 2) explore these differences among all full-time pediatric faculty.

Methods: We performed a cross-sectional study using data on median full-time academic general pediatric faculty compensation for the academic year of 2020-2021 from the Association of American Medical Colleges Medical School Faculty Salary Survey report. Pearson's chi-square tests were used to evaluate the association …

Estrogen-Induced Glial Il-1Β Mediates Extrinsic Retinal Ganglion Cell Vulnerability In Murine Nf1 Optic Glioma, Yunshuo Tang, Jit Chatterjee, Ngan Wagoner, Stephanie Bozeman, David H Gutmann

2020-Current year OA Pubs

Optic pathway gliomas (OPGs) arising in children with neurofibromatosis type 1 (NF1) can cause retinal ganglion cell (RGC) dysfunction and vision loss, which occurs more frequently in girls. While our previous studies demonstrated that estrogen was partly responsible for this sexually dimorphic visual impairment, herein we elucidate the underlying mechanism. In contrast to their male counterparts, female Nf1