Digital Commons Network^™

Tourette Syndrome Research Highlights From 2023 [Version 2; Peer Review: 3 Approved], Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Nanette Mol Debes, Simon Morand-Beaulieu, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Kevin J Black

2020-Current year OA Pubs

In this, the tenth annual update for the F1000Research Tics collection, we summarize research reports from 2023 on Gilles de la Tourette syndrome and other tic disorders. The authors welcome article suggestions and thoughtful feedback from readers.

Analyses Of Patients Who Self-Administered Diazepam Nasal Spray For Acute Treatment Of Seizure Clusters, Sunita N Misra, Michael R Sperling, Vikram R Rao, Jurriaan M Peters, Patricia Penovich, James Wheless, R Edward Hogan, Charles S Davis, Enrique Carrazana, Adrian L Rabinowicz

2020-Current year OA Pubs

For acute treatment of seizure clusters in patients with epilepsy, intranasal administration of acute seizure therapies has been shown to provide accessibility and ease of use to care partners as well as the potential for self-administration by patients. Diazepam nasal spray (Valtoco®) was approved by the US Food and Drug Administration for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Self-administration consistent with the prescribing information is feasible and was reported by a subgroup of patients (n = 27 of 163) in a long-term phase …

Tract-Based Analyses Of White Matter In Schizophrenia, Bipolar Disorder, Aging, And Dementia Using High Spatial And Directional Resolution Diffusion Imaging: A Pilot Study, Daniel Mamah, Shingshiun Chen, Joshua S Shimony, Michael P Harms

2020-Current year OA Pubs

INTRODUCTION: Structural brain connectivity abnormalities have been associated with several psychiatric disorders. Schizophrenia (SCZ) is a chronic disabling disorder associated with accelerated aging and increased risk of dementia, though brain findings in the disorder have rarely been directly compared to those that occur with aging.

METHODS: We used an automated approach to reconstruct key white matter tracts and assessed tract integrity in five participant groups. We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n =28), bipolar disorder (BPD, n =21), and SCZ (n =22) participants aged 18-30, and healthy elderly (ELD, n =15) and dementia (DEM, n …

Systematic Computer-Aided Disulfide Design As A General Strategy To Stabilize Prefusion Class I Fusion Proteins, Karen J Gonzalez, Kevin C Yim, Jorge C G Blanco, Marina S Boukhvalova, Eva-Maria Strauch

2020-Current year OA Pubs

Numerous enveloped viruses, such as coronaviruses, influenza, and respiratory syncytial virus (RSV), utilize class I fusion proteins for cell entry. During this process, the proteins transition from a prefusion to a postfusion state, undergoing substantial and irreversible conformational changes. The prefusion conformation has repeatedly shown significant potential in vaccine development. However, the instability of this state poses challenges for its practical application in vaccines. While non-native disulfides have been effective in maintaining the prefusion structure, identifying stabilizing disulfide bonds remains an intricate task. Here, we present a general computational approach to systematically identify prefusion-stabilizing disulfides. Our method assesses the geometric …

Negligence In Biomedical Research: An Anti-Racist Approach For Substance Use Researchers, Jonathan Lehman, Danniella Balangoy, Angie P Mejia, Carlos Cardenas-Iniguez, Scott Marek, Anita C Randolph

2020-Current year OA Pubs

Racism is embedded in the fabric of society at structural, disciplinary, hegemonic, and interpersonal levels, working as a mechanism that drives health disparities. In particular, stigmatized views of substance use get entangled with racialization, serving as a tool to uphold oppressive systems. While national health institutions have made commitments to dismantle these systems in the United States, anti-racism has not been integrated into biomedical research practice. The ways in which substance use researchers use and interpret race data-without engaging in structural racism as a mechanism of health inequity-can only be described as inadequate. Drawing upon concepts from the Public Health …

Classification Of Ipsc-Derived Cultures Using Convolutional Neural Networks To Identify Single Differentiated Neurons For Isolation Or Measurement, Purva Patel, Lina K. Mohammad Ali, Uma Kaushik, Malllory Wright, Kaylee Green, Jason E. Waligorski, Colin L. Kremitzki, Graham W. Bachman, Serena N. Elia, William J. Buchser

2020-Current year OA Pubs

No abstract provided.

Co-Occurring Autism, Adhd, And Gender Dysphoria In Children, Adolescents, And Young Adults With Eating Disorders: An Examination Of Pre- Vs. Post-Covid Pandemic Outbreak Trends With Real-Time Electronic Health Record Data, Tashalee R Brown, Madeline O Jansen, A Ning Zhou, Dominic Moog, Hui Xie, Katherine V Liebesny, Kevin Y Xu, Binx Y Lin, Wisteria Y Deng

2020-Current year OA Pubs

BACKGROUND: Incidence rates of autism, attention-deficit/hyperactivity disorder (ADHD), and gender dysphoria (GD) are rising not only in the general population, but particularly among children, adolescents, and young adults with eating disorders (EDs). While ED rates have risen during the COVID pandemic, trends in co-occurring autism, ADHD, and GD have yet to be investigated in detail or at scale by way of large electronic medical record data.

OBJECTIVES: To investigate trends in rates of co-occurring autism, ADHD, and GD among children, adolescents, and young adults with EDs in years prior to and during the COVID-19 pandemic.

METHODS: We utilized a de-identified …

Case Report: Deep Sequencing And Long-Read Genome Sequencing Refine Prior Genetic Analyses In Families With Apparent Gonadal Mosaicism In Pik3cd-Related Activated Pi3k Delta Syndrome, Halyn Orellana, Alex Paul, Nermina Saucier, Megan Cooper, Et Al.

2020-Current year OA Pubs

Gonadal and gonosomal mosaicism describe phenomena in which a seemingly healthy individual carries a genetic variant in a subset of their gonadal tissue or gonadal and somatic tissue(s), respectively, with risk of transmitting the variant to their offspring. In families with one or more affected offspring, occurrence of the same apparently

Changing Hearts And Minds: Theorizing How, When, And Under What Conditions Three Social Influence Implementation Strategies Work, Bryan J Weiner, Rosemary D Meza, Predrag Klasnja, Rebecca Lengnick-Hall, Gretchen J Buchanan, Aaron R Lyon, Kayne D Mettert, Marcella H Boynton, Byron J Powell, Cara C Lewis

2020-Current year OA Pubs

BACKGROUND: Opinion leadership, educational outreach visiting, and innovation championing are commonly used strategies to address barriers to implementing innovations and evidence-based practices in healthcare settings. Despite voluminous research, ambiguities persist in how these strategies work and under what conditions they work well, work poorly, or work at all. The current paper develops middle-range theories to address this gap.

METHODS: Conceptual articles, systematic reviews, and empirical studies informed the development of causal pathway diagrams (CPDs). CPDs are visualization tools for depicting and theorizing about the causal process through which strategies operate, including the mechanisms they activate, the barriers they address, and …

Molecular Characterization Of Gliomas And Glioneuronal Tumors Amid Noonan Syndrome: Cancer Predisposition Examined, Margaret Shatara, Mohamed S Abdelbaki, Et Al

2020-Current year OA Pubs

INTRODUCTION: In the setting of pediatric and adolescent young adult cancer, increased access to genomic profiling has enhanced the detection of genetic variation associated with cancer predisposition, including germline syndromic conditions. Noonan syndrome (NS) is associated with the germline RAS pathway activating alterations and increased risk of cancer. Herein, we describe our comprehensive molecular profiling approach, the association of NS with glioma and glioneuronal tumors, and the clinical and histopathologic characteristics associated with the disease.

METHODS: Within an institutional pediatric cancer cohort (n = 314), molecular profiling comprised of paired somatic disease-germline comparator exome analysis, RNA sequencing, and tumor classification …

Characterization And Z-Score Calculation Of Cardiovascular Magnetic Resonance Imaging Parameters In Patients After The Fontan Operation: A Fontan Outcome Registry Using Cardiovascular Magnetic Resonance Examinations Study, Tarek Alsaied, Manish Aggarwal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cardiac magnetic resonance (CMR) offers valuable hemodynamic insights post-Fontan, but is limited by the absence of normative single ventricle data. The Fontan Outcomes Registry using CMR Examinations (FORCE) is a large international Fontan-specific CMR registry. This study used FORCE registry data to evaluate expected CMR ventricular size/function and create Fontan-specific z-scores adjusting for ventricular morphology (VM) in healthier Fontan patients.

METHODS: "Healthier" Fontan patients were defined as patients free of adverse outcomes, who are New York Heart Association class I, have mild or less valve disease, and < 30% aortopulmonary collateral burden. General linear modeling was performed on 70% of the dataset to create z-scores for volumes and function. Models were tested using the remainder (30%) of the data. The z-scores were compared between children and adults. The z-scores were also compared between "healthier" Fontan and patients with adverse outcomes (death, listing for transplantation, or multiorgan disease).

RESULTS: The "healthier" Fontan population included 885 patients (15.0 ± 7.6 years) …

Community-Level Knowledge, Attitudes, And Practices Regarding Cardiovascular Diseases And Modifiable Risk Factors In India, Kavita Singh, Dimple Kondal, Deepa Mohan, Mareesha Gandral, Sheril Rajan, Viswanathan Mohan, Mohammed K Ali, Km Venkat Narayan, Mark D Huffman, Dorairaj Prabhakaran, Nikhil Tandon

2020-Current year OA Pubs

BACKGROUND: Assessment of knowledge, attitudes, and practices regarding cardiovascular diseases (CVD) and cardiovascular risk factors (CVRF) is critical to inform CVD prevention strategies, but limited community-level data exist from developing countries.

OBJECTIVE: To assess the knowledge, attitudes, and practices regarding CVD and CVRF and acceptability of non-physician health workers and text-message based reminders to guide CVD prevention strategies in India.

METHODS: We conducted a telephone-based survey nested in the on-going Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) cohort in Delhi and Chennai, India between January 2021 to February 2021. We randomly selected people with CVRF, but no established …

The Association Of Dementia Risk Symptoms And Functional Activity In Adults With Down Syndrome, Selena E Washington, Amy E Bodde, Brian C Helsel, Rebecca M Bollinger, Nora Smith, Lauren T Ptomey, Beau Ances, Susan L Stark

2020-Current year OA Pubs

INTRODUCTION: Adults with Down syndrome (DS) have an increased risk of Alzheimer's disease (AD) dementia, often showing neuropathological indicators by age 40. Physical function and activities of daily living (ADLs) are understudied areas of function that may inform dementia risk. We investigated associations among age, physical function (gait/balance, grip strength, and lower extremity strength), ADLs, and dementia risk symptoms in adults with DS. We hypothesized that compromised physical function and lower independence with ADLs would be associated with an informant/caregiver-reported measure of dementia risk symptoms.

METHODS: A secondary analysis for this cross-sectional study was completed using data from two academic …

Persistent Elevation Of Plasma Markers Of Cellular Senescence After Hip Fracture: A Pilot Longitudinal Study, Eric J Lenze, Ginger E Nicol, George A Kuchel, Michael S Avidan, Breno S Diniz

2020-Current year OA Pubs

INTRODUCTION: Hip fractures may result from and contribute to accelerated biological aging. We aimed to evaluate the impact of hip fracture and its surgery on the senescence-associated secretory phenotype (SASP) index, a composite of peripheral protein markers where higher scores are thought to indicate greater levels of cellular senescence and accelerated aging.

METHODS: We examined the SASP index in plasma over 12 weeks post-surgery and its prediction of long-term post-surgical functional outcomes. We included 60 older adults: 20 recruited immediately after hip fracture surgery, and 40 comparison individuals who were either healthy or suffering chronic psychosocial stress (caregiving). We assessed …

Unraveling The Role Of Hif And Epigenetic Regulation In Pulmonary Arterial Hypertension: Implications For Clinical Research And Its Therapeutic Approach, Ankita Mitra, Dan Yi, Zhiyu Dai, Vinicio De Jesus Perez

2020-Current year OA Pubs

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling with high pulmonary pressure, which ultimately leads to right heart failure and premature death. Emerging evidence suggests that both hypoxia and epigenetics play a pivotal role in the pathogenesis of PAH development. In this review article, we summarize the current developments in regulation of hypoxia inducible factor (HIF) isoforms in PAH vascular remodeling and the development of suitable animal models for discovery and testing of HIF pathway-targeting PAH therapeutics. In addition, we also discuss the epigenetic regulation of HIF-dependent isoforms in PAH and its therapeutic potential from a new perspective …

Lipin1 As A Therapeutic Target For Respiratory Insufficiency Of Duchenne Muscular Dystrophy, Alexandra Brown, Brooklyn Morris, John Karanja Kamau, Ryan J Rakoczy, Brian N Finck, Christopher N Wyatt, Hongmei Ren

2020-Current year OA Pubs

In Duchenne muscular dystrophy (DMD), diaphragm muscle dysfunction results in respiratory insufficiency which is a leading cause of death in patients. Mutations to the dystrophin gene result in myocyte membrane instability, contributing to the structural deterioration of the diaphragm muscle tissues. With previous works suggesting the importance of lipin1 for maintaining skeletal muscle membrane integrity, we explored the roles of lipin1 in the dystrophic diaphragm. We found that the protein expression levels of lipin1 were reduced by 60% in the dystrophic diaphragm. While further knockdown of lipin1 in the dystrophic diaphragm leads to increased necroptosis, restoration of lipin1 in the …

The Risks Of Unconcern: Low Sensitivity To Threat Can Have Unfortunate Consequences, Stephen L Ristvedt

2020-Current year OA Pubs

Each one of us is confronted with warnings of danger or threats to wellbeing in our everyday life, whether in the form of certain road signs, Public Service Announcements, ominous changes in bodily functioning, or cautionary tales heard from family or friends. There is great inter-individual variation in how people respond to such threats, with some people habitually tending to ignore or dismiss them, often to their peril. The first purpose of the present paper is to review several studies showing that individuals-most often men-who score very low on measures of trait anxiety are more likely to engage in behaviors …

Protein Quality Malnutrition, Mark J Manary, Donna R Wegner, Kenneth Maleta

2020-Current year OA Pubs

Protein quality refers to the evaluation of a food or a diet based on its amino acid composition, protein digestibility, and protein bioavailability. When these parameters are specified, either through direct measurement or estimation, the amino acids provided by the diet are compared to those required by a healthy individual, and based on this comparison, an adequacy ratio or score is assigned. Two widely used protein quality scoring systems are the protein digestibility-corrected amino acid score (PDCAAS) and the digestible indispensable amino acid score (DIAAS), neither of which account for the dietary source of the protein. In malnourished children, metabolic …

Case Report: Targeted Treatment By Fluoxetine/Norfluoxetine Of A Kcnc2 Variant Causing Developmental And Epileptic Encephalopathy, Ping Li, Alice Butler, Yu Zhou, Karl L Magleby, Christina A Gurnett, Lawrence Salkoff

2020-Current year OA Pubs

The Kv3.2 subfamily of voltage activated potassium channels encoded by the

Awareness, Use, Motivations And Methods Of Accessing Genetic Testing In 2022 In The United States, Sukh Makhnoon, Minjae Lee, Tanushree Prasad, Alexa Badalamenti, Tami Gurley, Erika A Waters, Celette Sugg Skinner

2020-Current year OA Pubs

INTRODUCTION: Awareness, access, and use of clinical and direct-to-consumer (DTC) genetic tests has increased in recent years with documented disparities in these services. We provide updated data on test awareness and use, and report novel data on motivations and methods for accessing genetic tests.

METHODS: Nationally representative data from the 2022 Health Information National Trends Survey (HINTS 6) were used to assess awareness and use of ancestry, personal trait, specific disease, and carrier testing by sociodemographic characteristics, examine reasons for undergoing tests, and methods of accessing them.

RESULTS: Overall, 81.4% of respondents were aware and 40.0% had undergone testing. Only …

Campylobacter Colonization And Undernutrition In Infants In Rural Eastern Ethiopia — A Longitudinal Community-Based Birth Cohort Study, Dehao Chen, Nurmohammad Shaik, Mark J Manary, Et Al.

2020-Current year OA Pubs

BACKGROUND:

METHODS: We followed a birth cohort of 106 infants in rural smallholder households in eastern Ethiopia up to 13 months of age. We measured anthropometry, surveyed sociodemographic determinants, and collected stool and urine samples. A short survey was conducted during monthly visits, infant stool samples were collected, and

RESULTS: The

CONCLUSION: This study found that most determinants associated with increased

Beta Cell Primary Cilia Mediate Somatostatin Responsiveness Via Sstr3, Samantha E Adamson, Zipeng A Li, Jing W Hughes

2020-Current year OA Pubs

Somatostatin is a paracrine modulator of insulin secretion and beta cell function with pleotropic effects on glucose homeostasis. The mechanism of somatostatin-mediated communication between delta and beta cells is not well-understood, which we address in this study via the ciliary somatostatin receptor 3 (SSTR3). Primary cilia are membrane organelles that act as signaling hubs in islets by virtue of their subcellular location and enrichment in signaling proteins such as G-protein coupled receptors (GPCRs). We show that SSTR3, a ciliary GPCR, mediates somatostatin suppression of insulin secretion in mouse islets. Quantitative analysis of calcium flux using a mouse model of genetically …

Inhaled Medications For Chronic Obstructive Pulmonary Disease Predict Surgical Complications And Survival In Stage I Non-Small Cell Lung Cancer, Steven Tohmasi, Daniel B. Eaton, Brendan T Heiden, Nikki E. Rossetti, Valerio Rasi, Su-Hsin Chang, Yan Yan, Deepika Gopukumar, Mayank R. Patel, Bryan F. Meyers, Benjamin D. Kozower, Varun Puri, Martin W. Schoen

2020-Current year OA Pubs

BACKGROUND: Lung function is routinely assessed prior to surgical resection for non-small cell lung cancer (NSCLC). Further assessment of chronic obstructive pulmonary disease (COPD) using inhaled COPD medications to determine disease severity, a readily available metric of disease burden, may predict postoperative outcomes and overall survival (OS) in lung cancer patients undergoing surgery.

METHODS: We retrospectively evaluated clinical stage I NSCLC patients receiving surgical treatment within the Veterans Health Administration from 2006-2016 to determine the relationship between number and type of inhaled COPD medications (short- and long-acting beta2-agonists, muscarinic antagonists, or corticosteroids prescribed within 1 year before surgery) and postoperative …

Surgical Approaches For Thoracic Outlet Decompression In The Treatment Of Thoracic Outlet Syndrome, Stijn B. J. Teijink, Jens Goeteyn, Niels Pesser, Bart F. L. Van Nuenen, Robert W. Thompson, Joep A. W. Teijink

2020-Current year OA Pubs

Thoracic outlet syndrome (TOS) is a controversial and uncommon syndrome. Three different diagnoses can be made based on the compressed structure: arterial TOS, venous TOS, and neurogenic TOS. Diagnosing TOS, especially neurogenic TOS, remains difficult since a single diagnostic tool does not exist. Although this resulted in a lot of confusion, standardization of care and outcome improved daily care practice measures in the last decade. Current treatment algorithms consist of both conservative and surgical treatment approaches, which should be chosen depending on the type of TOS and extend of the complaints. Surgical treatment of TOS is performed via thoracic outlet …

A Real-World Study Of Pneumonitis In Non-Small Cell Lung Cancer Patients Receiving Durvalumab Following Concurrent Chemoradiation, Neha Akkad, Theodore S. Thomas, Suhong Luo, Eric Knoche, Kristen M. Sanfilippo, Jesse W. Keller

2020-Current year OA Pubs

BACKGROUND: Locally advanced non-small cell lung cancer (LA-NSCLC) treated with the programmed death-ligand 1 inhibitor durvalumab has been associated with significant rates of pneumonitis, which has led to higher rates of discontinuation of therapy in real-world populations. Thus far there has been no consensus in the literature on the impact of pneumonitis on survival.

METHODS: This is a retrospective cohort study of veterans receiving durvalumab between 12/5/2017 and 4/15/2020. Participants were identified using VINCI data services. Patients were followed through 9/14/2021. Development of clinical pneumonitis was assessed through review of documentation and graded using CTCAE 4.0 criteria. Univariate logistic regression …

Viral Targeting Of Importin Alpha-Mediated Nuclear Import To Block Innate Immunity, Olivia A Vogel, Jade K Forwood, Daisy W Leung, Gaya K Amarasinghe, Christopher F Basler

2020-Current year OA Pubs

Cellular nucleocytoplasmic trafficking is mediated by the importin family of nuclear transport proteins. The well-characterized importin alpha (IMPA) and importin beta (IMPB) nuclear import pathway plays a crucial role in the innate immune response to viral infection by mediating the nuclear import of transcription factors such as IRF3, NFκB, and STAT1. The nuclear transport of these transcription factors ultimately leads to the upregulation of a wide range of antiviral genes, including IFN and IFN-stimulated genes (ISGs). To replicate efficiently in cells, viruses have developed mechanisms to block these signaling pathways. One strategy to evade host innate immune responses involves blocking …

Single-Pulse Electrical Stimulation Artifact Removal Using The Novel Matching Pursuit-Based Artifact Reconstruction And Removal Method (Mparrm), Tao Xie, Thomas J Foutz, Markus Adamek, James R Swift, Cory S Inman, Joseph R Manns, Eric C Leuthardt, Jon T Willie, Peter Brunner

2020-Current year OA Pubs

No abstract provided.

Using Long-Read Cage Sequencing To Profile Cryptic-Promoter-Derived Transcripts And Their Contribution To The Immunopeptidome, Ju Heon Maeng, H Josh Jang, Alan Y Du, Shin-Cheng Tzeng, Ting Wang

2020-Current year OA Pubs

Recent studies have shown that the noncoding genome can produce unannotated proteins as antigens that induce immune response. One major source of this activity is the aberrant epigenetic reactivation of transposable elements (TEs). In tumors, TEs often provide cryptic or alternate promoters, which can generate transcripts that encode tumor-specific unannotated proteins. Thus, TE-derived transcripts (TE transcripts) have the potential to produce tumor-specific, but recurrent, antigens shared among many tumors. Identification of TE-derived tumor antigens holds the promise to improve cancer immunotherapy approaches; however, current genomics and computational tools are not optimized for their detection. Here we combined CAGE technology with …

Mecp2 Represses The Activity Of Topoisomerase Iiβ In Long Neuronal Genes, Sabin A Nettles, Yoshiho Ikeuchi, Katheryn B Lefton, Ladan Abbasi, Alyssa Erickson, Chibueze Agwu, Thomas Papouin, Azad Bonni, Harrison W Gabel

2020-Current year OA Pubs

A unique signature of neurons is the high expression of the longest genes in the genome. These genes have essential neuronal functions, and disruption of their expression has been implicated in neurological disorders. DNA topoisomerases resolve DNA topological constraints and facilitate neuronal long gene expression. Conversely, the Rett syndrome protein, methyl-CpG-binding protein 2 (MeCP2), can transcriptionally repress long genes. How these factors regulate long genes is not well understood, and whether they interact is not known. Here, we identify and map a functional interaction between MeCP2 and topoisomerase IIβ (TOP2β) in mouse neurons. We profile neuronal TOP2β activity genome wide, …

Development Of White Matter Fiber Covariance Networks Supports Executive Function In Youth, Joëlle Bagautdinova, Aristeidis Sotiras, Et Al.

2020-Current year OA Pubs

During adolescence, the brain undergoes extensive changes in white matter structure that support cognition. Data-driven approaches applied to cortical surface properties have led the field to understand brain development as a spatially and temporally coordinated mechanism that follows hierarchically organized gradients of change. Although white matter development also appears asynchronous, previous studies have relied largely on anatomical tract-based atlases, precluding a direct assessment of how white matter structure is spatially and temporally coordinated. Harnessing advances in diffusion modeling and machine learning, we identified 14 data-driven patterns of covarying white matter structure in a large sample of youth. Fiber covariance networks …