Digital Commons Network^™

Churning The Tides Of Care: When Nurse Turnover Makes Waves In Patient Access To Primary Care, Kelley Arredondo, Ashley M Hughes, Houston F Lester, Trang N D Pham, Laura A Petersen, Lechauncy Woodard, Richard Sorelle, Cheng Rebecca Jiang, Frederick L Oswald, Daniel R Murphy, Hilary N Touchett, Joshua Hamer, Sylvia J Hysong

Faculty, Staff and Students Publications

BACKGROUND: Team-based primary care (PC) enhances the quality of and access to health care. The Veterans Health Administration (VHA) implements team-based care through Patient Aligned Care Teams (PACTs), consisting of four core members: a primary care provider, registered nurse (RN) care manager, licensed vocational nurse, and scheduling clerk. RNs play a central role: they coordinate patient care, manage operational needs, and serve as a patient point of contact. Currently, it is not known how varying levels of RN staffing on primary care teams impact patient outcomes.

OBJECTIVE: This study aims to empirically assess how the stability of RN staffing within …

Larp1 Haploinsufficiency Is Associated With An Autosomal Dominant Neurodevelopmental Disorder, James Chettle, Raymond J Louie, Olivia Larner, Robert Best, Kevin Chen, Josephine Morris, Zinaida Dedeic, Anna Childers, R Curtis Rogers, Barbara R Dupont, Cindy Skinner, Sébastien Küry, Kevin Uguen, Marc Planes, Danielle Monteil, Megan Li, Aviva Eliyahu, Lior Greenbaum, Nofar Mor, Thomas Besnard, Bertrand Isidor, Benjamin Cogné, Alyssa Blesson, Anne Comi, Ingrid M Wentzensen, Blake Vuocolo, Seema R Lalani, Roberta Sierra, Lori Berry, Kent Carter, Stephan J Sanders, Sarah P Blagden

Faculty, Staff and Students Publications

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and …

Forecasting The Effects Of Smoking Prevalence Scenarios On Years Of Life Lost And Life Expectancy From 2022 To 2050: A Systematic Analysis For The Global Burden Of Disease Study 2021, Gbd 2021 Tobacco Forecasting Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Smoking is the leading behavioural risk factor for mortality globally, accounting for more than 175 million deaths and nearly 4·30 billion years of life lost (YLLs) from 1990 to 2021. The pace of decline in smoking prevalence has slowed in recent years for many countries, and although strategies have recently been proposed to achieve tobacco-free generations, none have been implemented to date. Assessing what could happen if current trends in smoking prevalence persist, and what could happen if additional smoking prevalence reductions occur, is important for communicating the effect of potential smoking policies.

METHODS: In this analysis, we use …

Single-Cell Somatic Copy Number Variants In Brain Using Different Amplification Methods And Reference Genomes, Ester Kalef-Ezra, Zeliha Gozde Turan, Diego Perez-Rodriguez, Ida Bomann, Sairam Behera, Caoimhe Morley, Sonja W Scholz, Zane Jaunmuktane, Jonas Demeulemeester, Fritz J Sedlazeck, Christos Proukakis

Faculty, Staff and Students Publications

The presence of somatic mutations, including copy number variants (CNVs), in the brain is well recognized. Comprehensive study requires single-cell whole genome amplification, with several methods available, prior to sequencing. Here we compare PicoPLEX with two recent adaptations of multiple displacement amplification (MDA): primary template-directed amplification (PTA) and droplet MDA, across 93 human brain cortical nuclei. We demonstrate different properties for each, with PTA providing the broadest amplification, PicoPLEX the most even, and distinct chimeric profiles. Furthermore, we perform CNV calling on two brains with multiple system atrophy and one control brain using different reference genomes. We find that 20.6% …

Personalized Brachytherapy: Applications And Future Directions, Piyush Pathak, Justin J Thomas, Arjit Baghwala, Chengfeng Li, Bin S Teh, Edward B Butler, Andrew M Farach

Faculty, Staff and Students Publications

Brachytherapy offers a highly conformal and adaptive approach to radiation therapy for various oncologic conditions. This review explores the rationale, applications, technological advances, and future directions of personalized brachytherapy. Integration of advanced imaging techniques, 3D-printed applicators, and artificial intelligence are rapidly enhancing brachytherapy delivery and efficiency, while genomic tests and molecular biomarkers are refining patient and dose selection. Emerging research on combining brachytherapy with immunotherapy offers unique synergistic potential, and technologies such as intensity-modulated and shielded brachytherapy applicators present novel opportunities to further optimize dose distributions. Despite these promising advances, the field faces challenges including a need to train more …

Whole Genomes Of Amazonian Uakari Monkeys Reveal Complex Connectivity And Fast Differentiation Driven By High Environmental Dynamism, Núria Hermosilla-Albala, Felipe Ennes Silva, Sebastián Cuadros-Espinoza, Claudia Fontsere, Alejandro Valenzuela-Seba, Harvinder Pawar, Marta Gut, Joanna L Kelley, Sandra Ruibal-Puertas, Pol Alentorn-Moron, Armida Faella, Esther Lizano, Izeni Farias, Tomas Hrbek, Joao Valsecchi, Ivo G Gut, Jeffrey Rogers, Kyle Kai-How Farh, Lukas F K Kuderna, Tomas Marques-Bonet, Jean P Boubli

Faculty, Staff and Students Publications

Despite showing the greatest primate diversity on the planet, genomic studies on Amazonian primates show very little representation in the literature. With 48 geolocalized high coverage whole genomes from wild uakari monkeys, we present the first population-level study on platyrrhines using whole genome data. In a very restricted range of the Amazon rainforest, eight uakari species (Cacajao genus) have been described and categorized into the bald and black uakari groups, based on phenotypic and ecological differences. Despite a slight habitat overlap, we show that posterior to their split 0.92 Mya, bald and black uakaris have remained independent, without gene flow. …

Tca Metabolism Regulates Dna Hypermethylation In Lps And Mycobacterium Tuberculosis–Induced Immune Tolerance, Abhimanyu, Santiago Carrero Longlax, Tomoki Nishiguchi, Malik Ladki, Daanish Sheikh, Amera L Martinez, Emily M Mace, Sandra L Grimm, Thaleia Caldwell, Alexandra Portillo Varela, Rajagopal V Sekhar, Anna M Mandalakas, Mandla Mlotshwa, Sibuse Ginidza, Jeffrey D Cirillo, Robert S Wallis, Mihai G Netea, Reinout Van Crevel, Cristian Coarfa, Andrew R Dinardo

Faculty, Staff and Students Publications

Severe and chronic infections, including pneumonia, sepsis, and tuberculosis (TB), induce long-lasting epigenetic changes that are associated with an increase in all-cause postinfectious morbidity and mortality. Oncology studies identified metabolic drivers of the epigenetic landscape, with the tricarboxylic acid (TCA) cycle acting as a central hub. It is unknown if the TCA cycle also regulates epigenetics, specifically DNA methylation, after infection-induced immune tolerance. The following studies demonstrate that lipopolysaccharide and Mycobacterium tuberculosis induce changes in DNA methylation that are mediated by the TCA cycle. Infection-induced DNA hypermethylation is mitigated by inhibitors of cellular metabolism (rapamycin, everolimus, metformin) and the TCA …

Gender And Sexuality Awareness In Medical Education And Practice: Mixed Methods Study, Rola Khamisy-Farah, Eden Biras, Rabie Shehadeh, Ruba Tuma, Hisham Atwan, Anna Siri, Manlio Converti, Francesco Chirico, Łukasz Szarpak, Carlo Biz, Raymond Farah, Nicola Bragazzi

Faculty, Staff and Students Publications

BACKGROUND: The integration of gender and sexuality awareness in health care is increasingly recognized as vital for patient outcomes. Despite this, there is a notable lack of comprehensive data on the current state of physicians' training and perceptions in these areas, leading to a gap in targeted educational interventions and optimal health care delivery.

OBJECTIVE: The study's aim was to explore the experiences and perceptions of attending and resident physicians regarding the inclusion of gender and sexuality content in medical school curricula and professional practice in Israel.

METHODS: This cross-sectional survey targeted a diverse group of physicians across various specializations …

The Fundamentals Of Antiseizure Medications: A Through Z, Timothy E Welty, Jeannine M Conway, Jacquelyn Bainbridge, Kristen Park, David G Vossler, Archana A Patel, Alica Goldman

Faculty, Staff and Students Publications

Since bromides were first used in 1857 to treat epilepsy, numerous antiseizure medications (ASM) have been developed. Many of these are available for the treatment of epilepsy and status epilepticus today. With so many ASM available, questions arise as to whether all of these medications are needed and when should they be used. As precision medicine begins to play a larger role in determining targeted treatments for specific types of epilepsy, a complete understanding of various medications is needed. Additionally, access to several of these medications can be limited in the United States and are especially limited globally. All these …

Genomics Of Natural Populations: Gene Conversion Events Reveal Selected Genes Within The Inversions Of Drosophila Pseudoobscura, Stephen W Schaeffer, Stephen Richards, Zachary L Fuller

Faculty, Staff and Students Publications

When adaptive phenotypic variation or quantitative trait loci map within an inverted segment of a chromosome, researchers often despair because the suppression of crossing over will prevent the discovery of selective target genes that established the rearrangement. If an inversion polymorphism is old enough, then the accumulation of gene conversion tracts offers the promise that quantitative trait loci or selected loci within inversions can be mapped. The inversion polymorphism of Drosophila pseudoobscura is a model system to show that gene conversion analysis is a useful tool for mapping selected loci within inversions. D. pseudoobscura has over 30 different chromosomal arrangements …

Trβ Activation Confers At2-To-At1 Cell Differentiation And Anti-Fibrosis During Lung Repair Via Klf2 And Cebpa, Xin Pan, Lan Wang, Juntang Yang, Yingge Li, Min Xu, Chenxi Liang, Lulu Liu, Zhongzheng Li, Cong Xia, Jiaojiao Pang, Mengyuan Wang, Meng Li, Saiya Guo, Peishuo Yan, Chen Ding, Ivan O Rosas, Guoying Yu

Faculty, Staff and Students Publications

Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is essential for lung regeneration. Moreover, thyroid hormone receptor α (TRα) promotes cell proliferation, while TRβ fuels cell maturation in lung regeneration. Using a specific TRβ agonist, sobetirome, we demonstrate that the anti-fibrotic effects of thyroid hormone mainly rely on TRβ in mice. Cellularly, TRβ activation enhances alveolar type-2 (AT2) cell differentiation into AT1 cell and constrains AT2 cell hyperplasia. Molecularly, TRβ activation directly regulates the …

Rescue Of Scn5a Mis-Splicing Does Not Improve The Structural And Functional Heart Defects Of A Dm1 Heart Mouse Model, Larissa Nitschke, Rong-Chi Hu, Andrew N Miller, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant multisystemic disorder for which cardiac features, including conduction delays and arrhythmias, are the second leading cause of disease mortality. DM1 is caused by expanded CTG repeats in the 3' untranslated region of the DMPK gene. Transcription of the expanded DMPK allele produces mRNAs containing long tracts of CUG repeats, which sequester the Muscleblind-Like family of RNA binding proteins, leading to their loss-of-function and the dysregulation of alternative splicing. A well-characterized mis-regulated splicing event in the DM1 heart is the increased inclusion of SCN5A exon 6A rather than the mutually exclusive exon …

Terminal Differentiation Precedes Functional Circuit Integration In The Peduncle Neurons In Regenerating Hydra Vulgaris, Alondra Escobar, Soonyoung Kim, Abby S Primack, Guillaume Duret, Celina E Juliano, Jacob T Robinson

Faculty, Staff and Students Publications

Understanding how neural circuits are regenerated following injury is a fundamental question in neuroscience. Hydra is a powerful model for studying this process because it has a simple neural circuit structure, significant and reproducible regenerative abilities, and established methods for creating transgenics with cell-type-specific expression. While Hydra is a long-standing model for regeneration and development, little is known about how neural activity and behavior is restored following significant injury. In this study, we ask if regenerating neurons terminally differentiate prior to reforming functional neural circuits, or if neural circuits regenerate first and then guide the constituent naive cells toward their …

Identification Of An Ionic Mechanism For Erα-Mediated Rapid Excitation In Neurons, Meng Yu, Na Yin, Bing Feng, Peiyu Gao, Kaifan Yu, Hesong Liu, Hailan Liu, Yongxiang Li, Olivia Z Ginnard, Kristine M Conde, Mengjie Wang, Xing Fang, Longlong Tu, Jonathan C Bean, Qingzhuo Liu, Yue Deng, Yuxue Yang, Junying Han, Sanika V Jossy, Megan L Burt, Huey Zhong Wong, Yongjie Yang, Benjamin R Arenkiel, Yang He, Shaodong Guo, Pierre Gourdy, Jean-Francois Arnal, Francoise Lenfant, Zhao Wang, Chunmei Wang, Yanlin He, Yong Xu

Faculty, Staff and Students Publications

The major female ovarian hormone, 17β-estradiol (E2), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E2, but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα. Clic1-mediated currents can be enhanced by E2 and reduced by its depletion. In addition, Clic1 currents are required to mediate the E2-induced rapid excitations in multiple brain ERα …

2024 Clinical Practice Guideline Update By The Infectious Diseases Society Of America On Complicated Intra-Abdominal Infections: Diagnostic Imaging Of Suspected Acute Intra-Abdominal Abscess In Adults, Children, And Pregnant People, Robert A Bonomo, Pranita D Tamma, Fredrick M Abrahamian, Mary Bessesen, Anthony W Chow, E Patchen Dellinger, Morven S Edwards, Ellie Goldstein, Mary K Hayden, Romney Humphries, Keith S Kaye, Brian A Potoski, Jesús Rodríguez-Baño, Robert Sawyer, Marion Skalweit, David R Snydman, Katelyn Donnelly, Jennifer Loveless

Faculty, Staff and Students Publications

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this article, the panel provides recommendations for diagnostic imaging of suspected acute intra-abdominal abscess. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

2024 Clinical Practice Guideline Update By The Infectious Diseases Society Of America On Complicated Intra-Abdominal Infections: Risk Assessment, Diagnostic Imaging, And Microbiological Evaluation In Adults, Children, And Pregnant People, Robert A Bonomo, Anthony W Chow, Morven S Edwards, Romney Humphries, Pranita D Tamma, Fredrick M Abrahamian, Mary Bessesen, E Patchen Dellinger, Ellie Goldstein, Mary K Hayden, Keith S Kaye, Brian A Potoski, Jesús Rodríguez-Baño, Robert Sawyer, Marion Skalweit, David R Snydman, Sarah Pahlke, Katelyn Donnelly, Jennifer Loveless

Faculty, Staff and Students Publications

As the first part of an update to the clinical practice guideline on the diagnosis and management of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America, the panel presents 21 updated recommendations. These recommendations span risk assessment, diagnostic imaging, and microbiological evaluation. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.

2024 Clinical Practice Guideline Update By The Infectious Diseases Society Of America On Complicated Intraabdominal Infections: Diagnostic Imaging Of Suspected Acute Cholecystitis And Acute Cholangitis In Adults, Children, And Pregnant People, Robert A Bonomo, Morven S Edwards, Fredrick M Abrahamian, Mary Bessesen, Anthony W Chow, E Patchen Dellinger, Ellie Goldstein, Mary K Hayden, Romney Humphries, Kaye, Brian A Potoski, Rodríguez-Baño, Robert Sawyer, Marion Skalweit, David R Snydman, Pranita D Tamma, Katelyn Donnelly, Jennifer Loveless

Faculty, Staff and Students Publications

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intraabdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this article, the panel provides recommendations for diagnostic imaging of suspected acute cholecystitis and acute cholangitis. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

2024 Clinical Practice Guideline Update By The Infectious Diseases Society Of America On Complicated Intra-Abdominal Infections: Diagnostic Imaging Of Suspected Acute Appendicitis In Adults, Children, And Pregnant People, Robert A Bonomo, Pranita D Tamma, Fredrick M Abrahamian, Mary Bessesen, Anthony W Chow, E Patchen Dellinger, Morven S Edwards, Ellie Goldstein, Mary K Hayden, Romney Humphries, Keith S Kaye, Brian A Potoski, Jesús Rodríguez-Baño, Robert Sawyer, Marion Skalweit, David R Snydman, Katelyn Donnelly, Jennifer Loveless

Faculty, Staff and Students Publications

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America (IDSA). In this paper, the panel provides recommendations for diagnostic imaging of suspected acute appendicitis. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

2024 Clinical Practice Guideline Update By The Infectious Diseases Society Of America On Complicated Intra-Abdominal Infections: Utility Of Blood Cultures In Adults, Children, And Pregnant People, Robert A Bonomo, Romney Humphries, Fredrick M Abrahamian, Mary Bessesen, Anthony W Chow, E Patchen Dellinger, Morven S Edwards, Ellie Goldstein, Mary K Hayden, Keith S Kaye, Brian A Potoski, Jesús Rodríguez-Baño, Robert Sawyer, Marion Skalweit, David R Snydman, Pranita D Tamma, Sarah Pahlke, Katelyn Donnelly, Jennifer Loveless

Faculty, Staff and Students Publications

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this guideline, the panel provides recommendations for obtaining blood cultures in patients with known or suspected intra-abdominal infection. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

2024 Clinical Practice Guideline Update By The Infectious Diseases Society Of America On Complicated Intra-Abdominal Infections: Diagnostic Imaging Of Suspected Acute Diverticulitis In Adults And Pregnant People, Robert A Bonomo, Pranita D Tamma, Fredrick M Abrahamian, Mary Bessesen, Anthony W Chow, E Patchen Dellinger, Morven S Edwards, Ellie Goldstein, Mary K Hayden, Romney Humphries, Keith S Kaye, Brian A Potoski, Jesús Rodríguez-Baño, Robert Sawyer, Marion Skalweit, David R Snydman, Katelyn Donnelly, Jennifer Loveless

Faculty, Staff and Students Publications

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute diverticulitis. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

2024 Clinical Practice Guideline Update By The Infectious Diseases Society Of America On Complicated Intra-Abdominal Infections: Risk Assessment In Adults And Children, Robert A Bonomo, Anthony W Chow, Fredrick M Abrahamian, Mary Bessesen, E Patchen Dellinger, Morven S Edwards, Ellie Goldstein, Mary K Hayden, Romney Humphries, Keith S Kaye, Brian A Potoski, Jesús Rodríguez-Baño, Robert Sawyer, Marion Skalweit, David R Snydman, Pranita D Tamma, Katelyn Donnelly, Dipleen Kaur, Jennifer Loveless

Faculty, Staff and Students Publications

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides a recommendation for risk stratification according to severity of illness score. The panel's recommendation is based on evidence derived from systematic literature reviews and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.

2024 Clinical Practice Guideline Update By The Infectious Diseases Society Of America On Complicated Intra-Abdominal Infections: Utility Of Intra-Abdominal Fluid Cultures In Adults, Children, And Pregnant People, Robert A Bonomo, Romney Humphries, Fredrick M Abrahamian, Mary Bessesen, Anthony W Chow, E Patchen Dellinger, Morven S Edwards, Ellie Goldstein, Mary K Hayden, Keith S Kaye, Brian A Potoski, Jesús Rodríguez-Baño, Robert Sawyer, Marion Skalweit, David R Snydman, Pranita D Tamma, Katelyn Donnelly, Jennifer Loveless

Faculty, Staff and Students Publications

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining cultures of intra-abdominal fluid in patients with known or suspected intra-abdominal infection. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Default Mode Network Electrophysiological Dynamics And Causal Role In Creative Thinking, Eleonora Bartoli, Ethan Devara, Huy Q Dang, Rikki Rabinovich, Raissa K Mathura, Adrish Anand, Bailey R Pascuzzi, Joshua Adkinson, Yoed N Kenett, Kelly R Bijanki, Sameer A Sheth, Ben Shofty

Faculty, Staff and Students Publications

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by …

Leptomeningeal Metastases From Solid Tumors: A Society For Neuro-Oncology And American Society Of Clinical Oncology Consensus Review On Clinical Management And Future Directions, Jessica A Wilcox, Ugonma N Chukwueke, Myung-Ju Ahn, Ayal A Aizer, Tejus A Bale, Dieta Brandsma, Priscilla K Brastianos, Susan Chang, Mariza Daras, Peter Forsyth, Livia Garzia, Michael Glantz, Isabella C Glitza Oliva, Priya Kumthekar, Emilie Le Rhun, Seema Nagpal, Barbara O'Brien, Elena Pentsova, Eudocia Quant Lee, Jan Remsik, Roberta Rudà, Inna Smalley, Michael D Taylor, Michael Weller, Jeffrey Wefel, Jonathan T Yang, Robert J Young, Patrick Y Wen, Adrienne A Boire

Faculty, Staff and Students Publications

Leptomeningeal metastases (LM) are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options, and clinical research protocols for patients with LM from solid tumors have similarly evolved to improve survival within specific populations. Recent expansions in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions. These include leptomeningeal metastasis biology and preferred animal modeling, epidemiology in the modern cancer population, ensuring validation and accessibility of newer leptomeningeal metastasis diagnostics, …

Penicillin Susceptibility Among Staphylococcus Aureus Skin And Soft Tissue Infections At A Children’S Hospital, J Chase Mcneil, Lauren M Sommer, Marritta Joseph, Kristina G Hulten, Sheldon L Kaplan

Faculty, Staff and Students Publications

Shortly after its introduction into clinical practice, Staphylococcus aureus isolates gained resistance to penicillin via the acquisition of β-lactamases. A number of centers have recently described an increase in the proportion of invasive methicillin-susceptible S. aureus (MSSA), which are also susceptible to penicillin (PSSA). Little data are available regarding the prevalence or impact of PSSA in skin and soft tissue infections (SSTI). Community-acquired MSSA SSTI isolates were obtained through a surveillance study at Texas Children’s Hospital from January 2017 to December 2021. A total of 200 random isolates underwent PCR for blaZ β-lactamase; blaZ-negative isolates then underwent penicillin susceptibility …

Inflammation-Induced Epigenetic Imprinting Regulates Intestinal Stem Cells, Dongchang Zhao, Visweswaran Ravikumar, Tyler J Leach, Daniel Kraushaar, Emma Lauder, Lu Li, Yaping Sun, Katherine Oravecz-Wilson, Evan T Keller, Fengju Chen, Laure Maneix, Robert R Jenq, Robert Britton, Katherine Y King, Ana E Santibanez, Chad J Creighton, Arvind Rao, Pavan Reddy

Faculty, Staff and Students Publications

It remains unknown whether, and how intestinal stem cells (ISC) adapt to inflammatory exposure, and if the adaptation leaves scars will affect their subsequent regeneration. We investigated the consequences of inflammation on Lgr5+ISCs in well-defined clinically relevant models of gastrointestinal acute graft-versus-host disease (GI GVHD). Utilizing single cell transcriptomics, organoid, metabolic, epigenomic and in vivo models we found that Lgr5+ISCs undergo metabolic changes that lead to accumulation of succinate, which reprograms its epigenome. These changes reduced the ability of ISCs to differentiate and regenerate ex vivo in serial organoid cultures and also in vivo following serial transplantation. Furthermore, ISCs demonstrated …

In Acute Severe Ulcerative Colitis Patients Who Receive Rescue Therapy, Prior Maintenance Therapy And Day 3 C-Reactive Protein After Rescue Therapy Are Associated With 12-Month Colectomy Risk, Jared A Sninsky, Ana-Maria Staicu, Edward L Barnes

Faculty, Staff and Students Publications

No abstract provided.

A Ligation-Independent Sequencing Method Reveals Trna-Derived Rnas With Blocked 3′ Termini, Alessandro Scacchetti, Emily J Shields, Natalie A Trigg, Grace S Lee, Jeremy E Wilusz, Colin C Conine, Roberto Bonasio

Faculty, Staff and Students Publications

Despite the numerous sequencing methods available, the diversity in RNA size and chemical modification makes it difficult to capture all RNAs in a cell. We developed a method that combines quasi-random priming with template switching to construct sequencing libraries from RNA molecules of any length and with any type of 3' modifications, allowing for the sequencing of virtually all RNA species. Our ligation-independent detection of all types of RNA (LIDAR) is a simple, effective tool to identify and quantify all classes of coding and non-coding RNAs. With LIDAR, we comprehensively characterized the transcriptomes of mouse embryonic stem cells, neural progenitor …

Structural Proteomics Defines A Sequential Priming Mechanism For The Progesterone Receptor, Matthew D Mann, Min Wang, Josephine C Ferreon, Michael P Suess, Antrix Jain, Anna Malovannaya, Roberto Vera Alvarez, Bruce D Pascal, Raj Kumar, Dean P Edwards, Patrick R Griffin

Faculty, Staff and Students Publications

The progesterone receptor (PR) is a steroid-responsive nuclear receptor with two isoforms: PR-A and PR-B. Disruption of PR-A:PR-B signaling is associated with breast cancer through interactions with oncogenic co-regulatory proteins (CoRs). However, molecular details of isoform-specific PR-CoR interactions remain poorly understood. Using structural mass spectrometry, we investigate the sequential binding mechanism of purified full-length PR and intact CoRs, steroid receptor coactivator 3 (SRC3) and p300, as complexes on target DNA. Our findings reveal selective CoR NR-box binding by PR and unique interaction surfaces between PR and CoRs during complex assembly, providing a structural basis for CoR sequential binding on PR. …

Pulse Oximetry Accuracy In Children With Dark Skin Tones: Relevance To Acute Lower Respiratory Infection Care In Low- And Middle-Income Countries, Shubhada Hooli, Tim Colbourn, Manish I Shah, Kristy Murray, Anna Mandalakas, Eric D Mccollum

Faculty, Staff and Students Publications

Acute lower respiratory infections (ALRI) are the leading post-neonatal cause of death in children under 5 years old. There is a high prevalence of pediatric ALRI-related hypoxemia in low- and middle-income countries. The WHO defines clinically meaningful hypoxemia in children as a SpO2 (peripheral oxygen saturation) < 90%. Multiple studies put this convention into question and found SpO2 of 90% to 92% to be associated with child ALRI mortality. An evolving body of evidence suggests that pulse oximeters systematically overestimate oxygen saturation in individuals with dark skin tones. We conducted a narrative review of pediatric studies evaluating pulse oximeter accuracy in children without COVID-19. Four studies, one prospective, examined pulse oximeter accuracy in children of varying ages with dark skin tones. All studies had limitations that affect their generalizability. There is evidence that certain pulse oximeters may overestimate oxygen saturation in children with dark skin tones. Further prospective research is urgently needed to identify affected populations and clinical implications. Despite recognized challenges, we strongly urge continued and expanded use of pulse oximetry as its use will save lives.