Digital Commons Network^™

Anything But Endo: Diagnostic Buck-Passing In Endometriosis Diagnosis, Rita Dexter, Megan Kitts, Heather Welty, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

People living with endometriosis, a disease in which tissue similar to the lining of the uterus grows elsewhere in the body, often experience prolonged diagnostic journeys because of symptom variability, normalisation of period pain and other symptoms, and lack of awareness of the condition. In this article, we analyse the endometriosis diagnostic journey through the lens of epistemic injustice. Drawing on in-depth interviews with 52 people living with endometriosis in the United States, we introduce the concept of diagnostic buck-passing to characterise the phenomenon wherein individuals who seek treatment for their symptoms end up stuck in a cycle of seeing …

Access To Digital Health Technologies: Personalized Framework And Global Perspectives, Sanjiv M Narayan, Mina K Chung, Demilade Adedinsewo, Luisa C C Brant, Leslie L Davis, David Duncker, Jennifer L Hall, Janet K Han, Carolyn S P Lam, Eldrin Lewis, Joseph Loscalzo, Manlio F Márquez, Vasiliki Rahimzadeh, Fatima Rodriguez, Prashanthan Sanders, Emma Svennberg, Kenneth Stein, Mintu Turakhia, Clyde Yancy, Antonis A Armoundas

Center for Medical Ethics and Health Policy Staff Publications

The emergence and rapid adoption of digital health technologies (DHT) present unprecedented opportunities to democratize and reduce disparities in health care by monitoring health and disease at the point of care in all patients. However, limited access to DHT is becoming a major obstacle to realizing these goals. Access to DHT is influenced not only by well-recognized social determinants of health, but also by digital determinants of health, such as digital literacy and the need for broad access to digital infrastructure, as well as commercial and economic factors. Addressing these challenges and designing unbiased systems of care are essential to …

Toward Ethical Provenance Tracking: The Ga4gh Model Data Access Agreement (Daa), Alexander Bernier, Bartha Maria Knoppers, Jonathan Lawson, Robyn Mcdougall, Maili Raven-Adams, Vasiliki Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Standardizing contractual clauses that govern data access enables research institutions to responsibly steward genomic and related health data while enabling its efficient downstream reuse.

Methods: We describe a document analysis study using both qualitative and comparative law analytical approaches to identify the most common categories of clauses from 29 different data access agreements used by human biomedical research consortia globally. We furthermore characterized the legal positions and standard practices for each common element of the agreement and synthesized across them to develop model clauses. A total of 3 discussion sessions were organized virtually to refine the clauses among members …

Psychometric Properties Of A Novel Affective Bias Task And Its Application In Clinical And Nonclinical Populations, Prathik Kalva, Kourtney Kanja, Brian A Metzger, Xiaoxu Fan, Brian Cui, Bailey Pascuzzi, John Magnotti, Madaline Mocchi, Raissa Mathura, Kelly R Bijanki

Faculty, Staff and Students Publications

To mitigate limitations in self-reported mood assessments, we introduce a novel affective bias task (ABT). The task quantifies instantaneous emotional state by leveraging the phenomenon of affective bias, in which people interpret external emotional stimuli in a manner consistent with their current emotional state. This study establishes task stability in measuring and tracking depressive symptoms in clinical and non-clinical populations. Initial assessment in a large non-clinical sample established normative ratings. Depressive symptoms were tracked relative to task performance in a non-clinical sample, as well as in a clinical cohort undergoing surgical evaluation for severe epilepsy. In both cohorts, a stronger …

Prevalence Of Clinically Relevant Nightmares And Their Differences By Sex And Diagnosis In Psychiatric Inpatients, Katrina A Rufino, Michelle A Patriquin, Courtney B Worley, Michael R Nadorff

Faculty, Staff and Students Publications

Nightmares have been shown to be associated with numerous forms of psychopathology, but the vast majority of this research has taken place in the general population and very little is known about their relation with psychopathology in those requiring inpatient hospitalization. In a sample of 1170 voluntarily admitted psychiatric inpatients, this study explores the frequency of reported nightmares in psychiatric inpatients with the aim of examining the prevalence of psychiatric diagnosis in those with and without clinically relevant nightmares. Participants completed the Disturbing Dream and Nightmare Severity Index (DDNSI) and the Structured Clinical Interview for DSM Disorders (SCID-5) at admission. …

Gallbladder Decompression And Hydrodissection As Adjuncts For Ablation Of Pericholecystic Hepatocellular Carcinomas, Taylor Hoffman, Arta Kasaeian, Johnathon Chung, Ashkan Berenji, David Wynne, Mohammad Ghasemi-Rad, David Léon

Faculty, Staff and Students Publications

Microwave ablation is an effective treatment for hepatocellular carcinoma, but tumors adjacent to extrahepatic organs carry a higher risk for thermal injury. Thermoprotective techniques such as hydrodissection and gallbladder decompression can reduce this risk and expand the range of lesions amenable to percutaneous treatment. We present a case of a 68-year-old woman with hepatocellular carcinoma in hepatic segment V, with partial treatment response from prior transarterial chemoembolization. Due to the lesion's proximity to the gallbladder and transverse colon, microwave ablation was performed with concurrent ultrasound- and CT-guided gallbladder decompression and hydrodissection. The ablation was technically successful without post-procedural complications. At …

Tau In Alzheimer’S Disease: Shaping The Future Patient Journey, Catherine J Mummery, Christopher Chen Li-Hsian, Cristian A Lasagna-Reeves, Rik Ossenkoppele, Christopher C Rowe, Douglas W Scharre, Huali Wang, Simon Kyaga, Jeffrey L Cummings

Faculty, Staff and Students Publications

Alzheimer's disease is a complex and multifactorial disease characterized by two key pathological hallmarks: amyloid-beta plaques and tau neurofibrillary tangles. Recent progress has led to the development and approval of disease-targeted therapies for Alzheimer's disease in the form of anti-amyloid-beta monoclonal antibodies. However, findings suggest that amelioration of multiple pathological drivers may be required to maximize clinical effect. An increasing body of evidence suggests that tau is a critical player in Alzheimer's disease pathophysiology, contributing significantly to neurodegeneration and cognitive decline. There are now several tau-targeting drugs in clinical development. In this review, we build on research and advancements in …

Cerebellar Deep Brain Stimulation Rescues Purkinje Cell Mitochondrial Density In A Genetic Mouse Model Of Cerebellar Ataxia, Lauren N Miterko-Myers, Lauren E Peacoe, Lita Duraine, Zhongyuan Zuo, Roy V Sillitoe

Faculty, Staff and Students Publications

Deep brain stimulation (DBS) improves motor function in a growing list of movement diseases including Parkinson's disease, dystonia, and tremor. There is evidence that DBS may also be effective in ataxia. It is not known why DBS is effective, but modulating cell activity and conferring neuroprotection are hypothesized to underlie its benefits. Understanding the effects of DBS on neurons is paramount to extending its clinical use in the treatment of various motor and non-motor diseases. Here, we stimulated the cerebellum of Car8 waddles (Car8wdl) mice, given the cerebellum's important role in ataxia pathophysiology. Using transmission electron microscopy, we tested the …

Senolytic-Resistant Senescent Cells Have A Distinct Sasp Profile And Functional Impact: The Path To Developing Senosensitizers, Utkarsh Tripathi, Masayoshi Suda, Vagisha Kulshreshtha, Bryan T Piatkowski, Allyson K Palmer, Nino Giorgadze, Christina Inman, Nathan Gasek, Ming Xu, Kurt O Johnson, Tamar Pirtskhalava, Selim Chaib, Larissa P G Langhi Prata, Yi Zhu, Renuka Kandhaya-Pillai, Stefan G Tullius, Saranya P Wyles, Rambabu Majji, Hari Krishna Yalamanchili, David B Allison, Tamar Tchkonia, James L Kirkland

Faculty, Staff and Students Publications

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant". Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro-inflammatory. In cell cultures, the 30%-70% of human senescent preadipocytes or human umbilical …

Unraveling Posttranslational Modification Complexity: Advances In Quantitative Histone Proteoform Mass Spectrometry, Karl F Poncha, Alyssa T Paparella, Nicolas L Young

Faculty, Staff and Students Publications

Histone proteins and their posttranslational modifications are central to chromatin structure and function. These modifications often occur in combinations, generating a diverse array of histone proteoforms that contribute to the dynamic regulation of chromatin architecture. Advancements in mass spectrometry-based proteomics, particularly top-down and middle-down approaches, have significantly enhanced our ability to characterize these proteoforms and elucidate PTM crosstalk. This review provides an analysis of the epigenetic machinery involved in the addition, recognition, and removal of histone PTMs, emphasizing the complexity introduced by histone variants and combinatorial PTM patterns. We examine the challenges and limitations of traditional antibody-based methods for PTM …

Clinical Factors And Diagnoses Associated With Inappropriate Urine Culture Ordering In Primary Care, Marissa Valentine-King, Barbara W Trautner, Michael A Hansen, Roger Zoorob, Lisa C K Danek, Kenneth Muldrew, Forrest Hudson, Robert L Atmar, Larissa Grigoryan

Faculty, Staff and Students Publications

Objective: Evaluate the prevalence and risk factors for inappropriately ordered urine cultures in primary care.

Design: Cross-sectional study using chart reviews.

Setting: Two primary care, safety-net clinics in Houston, Texas.

Patients: Non-pregnant adults without a urinary catheter who had a urine culture and a primary care visit between 11/2018 and 3/2020.

Methods: We classified patients lacking physician documentation of the following symptoms as having an inappropriately ordered urine culture: dysuria, frequency, urgency, hematuria, fever, chills, costovertebral angle tenderness, nephrolithiasis, and pain (suprapubic, pelvic, or flank). We extracted patient demographics, visit-related diagnostic codes, past medical history, and urine culture results. Diagnostic …

In Vivo Volumetric Visualization And Quantification Of Cumulus Expansion In Mice With Intravital Optical Coherence Tomography, Kohei Umezu, Frank J Brooks, Irina Larina

Faculty, Staff and Students Publications

Ovulation is preceded by a critical physiological process known as cumulus expansion, during which the cumulus cell layer surrounding the oocyte undergoes structural remodeling. Despite the recognized importance of this process for reproductive success, live quantitative imaging of cumulus expansion has not been previously achieved due to limitations of current imaging technologies for deeply located ovaries. In this study, we employed intravital optical coherence tomography for three-dimensional visualization of mouse follicles containing cumulus-oocyte complexes (COC) within the physiological context of the ovary, both ex vivo and in vivo. This method enabled time-lapse measurement of cumulus layer thickness and COC …

Evolving Burden Of Metabolic Dysfunction-Associated Steatotic Liver Disease And Its Complications In A Us Nationwide Healthcare System, Basim Ali, Ronald Samuel, Jennifer R Kramer, Liang Li, Xian Yu, Yumei Cao, Roxanne Desiderio, George Cholankeril, Steven M Asch, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health problem. Measuring the burden of cirrhosis and its complications in people with MASLD is important to inform health care delivery.

Methods: We aimed to quantify the changes in the burden of MASLD-related cirrhosis and hepatocellular carcinoma (HCC) in a nationwide U.S. healthcare system. We used data from the Veterans Health Administration to examine temporal trends between 2010 and 2021 in the annual incidence and prevalence of cirrhosis and HCC in a large cohort of patients with MASLD, and to compare them to those in patients with hepatitis C …

Platelet Extravasation In The Microvasculature: An Under-Appreciated Role For Platelets, Justin A Courson, Vahid Afshar-Kharghan, Alan R Burns, Rolando E Rumbaut

Faculty, Staff and Students Publications

In recent years, evidence has accumulated highlighting the presence and role of platelet extravasation - wherein platelets accumulate in tissue parenchyma - at a variety of sites throughout the body. While platelets are traditionally known for their roles in hemostasis and thrombosis, it is evident that platelets are potent mediators of inflammation across an array of physiological and pathological contexts. While anucleate and small in size, platelets contain a rich diversity of molecules in their granules capable of modulating cell proliferation, tissue repair, and a host of immune responses. There is growing evidence that platelet extravasation out of the vascular …

Executive Summary Of The Kdigo 2026 Clinical Practice Guideline For The Management Of Anemia In Chronic Kidney Disease (Ckd), Jodie L Babitt, Jeffrey S Berns, Biykem Bozkurt, Rebecca S Cheung Khedairy, Yarieli Cuevas, Emmanuel E Effa, Michele F Eisenga, Steven Fishbane, Yelena Z Ginzburg, Volker H Haase, S Susan Hedayati, Siah Kim, José A Moura-Neto, Evi V Nagler, Patrick Rossignol, Manisha Sahay, Tetsuhiro Tanaka, Angela Yee-Moon Wang, David C Wheeler, Karen A Robinson, Lisa M Wilson, Renee F Wilson, Amy Earley, Elie A Akl, Marcello Tonelli

Faculty, Staff and Students Publications

The Kidney Disease: Improving Global Outcomes (KDIGO) 2026 Clinical Practice Guideline for the Management of Anemia in Chronic Kidney Disease (CKD) represents an update to the guideline published in 2012. Its scope includes diagnosis and evaluation of anemia; use of iron to treat iron deficiency and anemia in CKD; use of erythropoiesis-stimulating agents and hypoxia-inducible factor-prolyl hydroxylase inhibitors to treat anemia in CKD; and red blood cell transfusions to treat anemia in CKD. The guideline has been developed with patient partners, healthcare providers, and researchers around the world, with the goal to generate a useful resource for healthcare providers and …

Gould Edu: Cluster-Randomized Trial Of An Educational Intervention To Improve Lipid-Lowering Guideline Adherence, Christopher P Cannon, Christie M Ballantyne, Deepak L Bhatt, James A De Lemos, Qi Gao, Naishu Kui, Robert S Rosenson, Katherine E Mues, Jason Exter, Shushama Alam, Mikhail N Kosiborod

Faculty, Staff and Students Publications

Background: Adherence to lipid-lowering therapy (LLT) guidelines is suboptimal, leading to poor achievement of low-density lipoprotein cholesterol (LDL-C) goals and elevated risk for atherosclerotic cardiovascular disease (ASCVD) events.

Objectives: The purpose of this study was to determine whether an educational intervention targeting physicians improves optimization of LLT over 1 year for patients with ASCVD.

Methods: GOULD (Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management) EDU (Education) was a 1-year extension in a subset of sites in the GOULD prospective, observational registry of United States patients with ASCVD. In a cluster-randomized, stepped-wedge design, sites were randomized to …

Esophageal Myotomy And Risk Of Esophageal Cancer And Mortality In Achalasia: Real-World Cohort Study, Fouad Jaber, Mohamad Ali Ibrahim, Mohammed Jaber, Youssef Soliman, Mai A Khalaf, Tara Keihanian, Fares Ayoub, Mohamed O Othman, Salmaan Jawaid

Faculty, Staff and Students Publications

Background and study aims: Achalasia is associated with increased risk of esophageal cancer, particularly squamous cell carcinoma. Although esophageal myotomy improves dysphagia, its impact on cancer risk and mortality remains unclear.

Patients and methods: We conducted a retrospective cohort study using the TriNetX research network, including adults (≥ 18 years) with achalasia confirmed by esophageal manometry. Patients were categorized based on treatment of those undergoing esophageal myotomy (peroral endoscopic myotomy [POEM] or laparoscopic Heller myotomy [LHM]) and those managed without myotomy. Patients with prior esophagectomy or malignancies associated with increased esophageal cancer risk were excluded. The primary outcome was incident …

Predictors Of Inpatient Rn Turnover In Rural And Urban Vha Hospitals, Katherine G Bay, Chase S Eck, Melissa K Knox, Paras Mehta, Laura A Petersen

Faculty, Staff and Students Publications

Background: The rising demand for health care delivery and an aging workforce is of particular concern in rural areas, where health care access depends upon an adequate nursing workforce. To address this shortage and optimize care, it is essential to measure when registered nurses (RN) leave inpatient direct care positions (ie, inpatient RN turnover) and identify modifiable factors correlated with RN turnover.

Objectives: Apply a novel method for characterizing inpatient RN turnover to understand factors associated with variation in RNs leaving inpatient positions at rural and urban Veterans Health Administration (VHA) hospitals.

Project design: Retrospective cohort study.

Subjects: Direct care …

Findings And Recommendations From The State Of The Art (Sota) Conference On Nursing Research To Improve Veteran Outcomes, Amelia E Schlak, Sarah Krein, Laura A Petersen, David Atkins, Catherine Battaglia, Elizabeth Burkhart, Renee Colsch, Marguerite Daus, Heather Gilmartin, Nipa Kamdar, Melissa Knox, Ann Kutney-Lee, Christine M Olney, Kathryn Rugen, Tracy Weistreich, Sheila Cox Sullivan, On Behalf The Nursing Sota Planning Committee

Faculty, Staff and Students Publications

The Veterans Health Administration (VHA), the largest employer of nurses in the United States, has more than 120,000 nursing personnel providing care to over 9 million Veterans across diverse settings. Despite nursing's central role in delivering and sustaining care, research on strengthening the nursing workforce and optimizing nursing practice has remained underdeveloped in VHA. To address this gap, VHA's Office of Research and Development, in partnership with the Office of Nursing Services, convened a State of the Art (SOTA) conference in November 2023 focused on nursing. The Nursing SOTA brought together nurses, researchers, operational leaders, and other stakeholders to review …

Relationship Between Number Of Assigned Patients And Rn Time To Administer Medications During The Peak-Time Medication Pass, Chase S Eck, Melissa K Knox, Paras D Mehta, Christine Yang, Laura A Petersen

Faculty, Staff and Students Publications

Background: Inpatient nurse staffing affects patient outcomes. Less is known about the mechanism of this relationship and how lower overall staffing in a unit affects individual RN activities at the bedside.

Objectives: Estimate the relationship between the number of patients assigned to an RN and time spent on medication administration at the peak-time medication pass (PTM), a common nursing task.

Research design: Estimate the association using multivariable linear regression to adjust for patient severity and staff and unit fixed effects.

Subjects: All 9272 RNs administering medications during the PTM on 243 inpatient units in 113 VHA hospitals in 2019.

Measures: …

Long Covid And Cardiovascular Diseases Among U.S. Adults: Results From The U.S. Medical Expenditure Panel Survey, Geoffrey Y Zhang, John C Lin, Dang Nguyen, Sameed Ahmed M Khatana, Thomas P Giordano

Faculty, Staff and Students Publications

Objective: Long COVID is associated with persistent symptoms including cardiovascular complications; however, the epidemiology and directionality of this association remain unclear.

Methods: Utilizing a retrospective cohort study design with cross-sectional analyses, 8,332 respondents aged 18 and older from the 2022 Medical Expenditure Panel Survey (MEPS) who had a prior COVID-19 infection, were analyzed to determine the temporal association between long COVID and cardiovascular disease (CVD), modeling each as both outcome and exposure in separate analyses.

Results: Long COVID was associated with any CVD diagnosis (OR 1.37; 95% CI: 1.05-1.80), specifically angina (OR 1.81; 95% CI: 1.18-2.77) and myocardial infarction (OR …

Hypothyroidism Is Associated With Higher Healthcare Utilisation And Higher Need For Blood Transfusion After Primary Total Knee Arthroplasty (Tka) In Patients With Osteoarthritis: A National Inpatient Sample Analysis, Sumanth R Chandrupatla, Kranti C Rumalla, Jasvinder A Singh

Faculty, Staff and Students Publications

Purpose: To examine the association of hypothyroidism with primary total knee arthroplasty (TKA) outcomes in adults with primary underlying diagnosis of osteoarthritis (OA).

Methods: We identified a prospective cohort of patients in the 2016-2020 national inpatient sample (NIS) that received primary TKA with an underlying diagnosis of OA, identified using International Classification of Diseases, Tenth Revision, Common Modification (ICD-10-CM) and Procedure Coding System (ICD-10-PCS) codes in the primary procedure and diagnosis positions, respectively. We performed multivariable-adjusted regression analyses for healthcare utilisation (length of hospital stay, hospital charges and discharge destination) and clinical outcomes (blood transfusion; prosthetic fracture, dislocation or infection; …

Healthcare Transition In Spina Bifida: A National Mixed Method Study, Betsy Hopson, Kathy H Huen, Molly B Richardson, Rhonda G Cady, Jennifer T Queally, Judy Thibadeau, Ellen Fremion

Faculty, Staff and Students Publications

Introduction: Adolescents and young adults (AYA) with spina bifida (SB) face substantial challenges during the transition from pediatric to adult healthcare, including fragmented systems, limited adult provider availability, and gaps in self-management readiness. Despite national guidelines, little is known about how transition practices are implemented across the Spina Bifida Association (SBA) Clinical Care Partner (CCP) network. This study examined clinician perspectives on current practices, barriers, facilitators, and definitions of successful healthcare transition (HCT).

Methods: Using an explanatory sequential mixed methods design, we first conducted a 47-item survey with clinicians from SBA CCP clinics (n = 20/32; 62.5 % response rate). …

Safety And Efficacy Of Vadadustat Versus Darbepoetin Alfa For Chronic Kidney Disease-Related Anemia In Patients Receiving Dialysis By Baseline Erythropoiesis-Stimulating Agent Dose, Alan Jardine, Steven K Burke, Wenli Luo, Todd Minga, Mark J Sarnak, Wolfgang C Winkelmayer, Rajiv Agarwal, Glenn M Chertow, Kai-Uwe Eckardt, Mark J Koury

Faculty, Staff and Students Publications

Introduction: Erythropoiesis-stimulating agents (ESAs) and iron supplementation are standard treatments for chronic kidney disease (CKD)-related anemia. Targeting higher hemoglobin values in CKD increases cardiovascular risk. Whether the increased risk is from higher ESA doses or higher hemoglobin levels is uncertain, but alternative therapies are sought for patients requiring high ESA doses. Phase 3 INNO2VATE trials in patients with dialysis-dependent CKD (DD-CKD) demonstrated vadadustat's noninferiority compared with darbepoetin alfa. To determine vadadustat's potential to treat anemia, including in patients requiring high ESA doses, its safety and efficacy were compared with those of darbepoetin alfa across prespecified baseline ESA dose subgroups in …

Ptpn1 Regulation Via Ybx1-Ptbp1 Interaction Promotes Fibroblast Activation And Fibrotic Remodeling In The Lung, Huibing Liu, Cong Xia, Yingying Zhang, Yulong Gan, Lianhui Cheng, Xuqian Wang, Airu Chang, Wenyu Zhao, Bin Li, Yaxuan Wang, Yajun Li, Ivan Rosas, Juntang Yang, Guoying Yu, Lan Wang

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial pneumonia of unknown etiology. Its pathogenesis involves complex multicellular interactions and signaling pathways, with fibroblast-to-myofibroblast transition (FMT) being critical for fibrogenesis. Although the transcription factor Y-box binding protein 1 (YBX1) regulates processes such as cell proliferation, transcription, translation, and DNA repair, its role in IPF remains undefined. Here, we demonstrate that YBX1 overexpression significantly promotes transforming growth factor-β1 (TGF-β1)-induced pulmonary FMT, leading to substantially increased extracellular matrix (ECM) deposition in primary human (PHLFs) and mouse (PMLFs) lung fibroblasts. Conversely, YBX1 inhibition markedly suppresses TGF-β1-driven aberrant fibroblast migration and activation. Mechanistically, YBX1 …

Correction: Establishing Standardized Transthoracic Echocardiography Reference Ranges For Mouse Models: Insights Into The Impact Of Anesthesia, Sex, And Age, Manuela A Oestereicher, Christopher S Ward, Elida Schneltzer, Susan Marschall, Helmut Fuchs, Valerie Gailus-Durner, Ghina Bou About, Mohammed Selloum, Hamid Meziane, Michelle Stewart, Lydia Teboul, Clare Norris, Dale Pimm, Marina Kan, Federico López Gómez, Robert Wilson, Mayra Monroy, Sheraz Pasha, Eva Zabrodska, Jan Prochazka, David Pajuelo Reguera, Zuzana Nichtova, Yann Herault, Sara Wells, Helen Parkinson, Jason D Heaney, Radislav Sedlacek, Xiang Gao, Martin Hrabe De Angelis, Nadine Spielmann

Faculty, Staff and Students Publications

This corrects the article "Establishing standardized transthoracic echocardiography reference ranges for mouse models: insights into the impact of anesthesia, sex, and age" in volume 12, 1695034.

Case Series Of Nizon-Isidor Syndrome By Heterozygous Variants In Med12l With Further Evidence Of Mitotic Instability In One Case With Diploid-Triploid Mosaicism, Russell Stewart, Kimberly M Ezell, Deanna S Bell, Brian Corner, Ashley Mcminn, Joy D Cogan, Rizwan Hamid, Lynette Rives, John A Phillips, Nina Paddu, Gitanjali Srivastava, Ronit Marom, Farah A Ladha, Claudia Soler-Alfonso, Rachel Franciskovich, Mary Koziura, Sumit Pruthi, Gabriele Richard, Christina B Sheedy, Undiagnosed Diseases Network, Thomas Cassini

Faculty, Staff and Students Publications

Nizon-Isidor syndrome is a rare disorder caused by heterozygous variants in MED12L, with only eight documented cases in the literature. Here, we present three additional cases of this syndrome. Proband 1 was a 7-year-old female who presented with developmental delay, right-leg hemihypertrophy, laryngeal cleft, esotropia, abnormal skin pigmentation, sectoral iris hypopigmentation, dysphagia, periventricular nodular heterotopia, seizures, morbid obesity, and a pelvic kidney. Genome sequencing (GS) revealed a MED12L variant, NM_053002.5:c.3559+2T>G. Both computational models and transcriptomic analysis confirmed that this variant induced splice loss of MED12L exon 25. Probands 2 and 3 presented with overlapping phenotypes of developmental delay; sequencing …

Efficacy And Safety Of Pyrimidine Nucleos(T)Ide Therapy In Thymidine Kinase 2 Deficiency, Michio Hirano, Caterina Garone, Richard Haas, Carmen Paradas, Fernando Scaglia, Irene Rebollo Mesa, Carl Chiang, Anny-Odile Colson, Susan Vanmeter, Cristina Domínguez-González

Faculty, Staff and Students Publications

Thymidine kinase 2 deficiency (TK2d) (MIM 609560) is an ultra-rare, autosomal recessive mitochondrial myopathy caused by TK2 variants, leading to mitochondrial DNA depletion and/or multiple deletions. People with thymidine kinase 2 deficiency experience progressive myopathy, bulbar weakness and respiratory insufficiency, often losing the ability to walk, eat and breathe independently. Doxecitine and doxribtimine represents the first approved treatment for patients with thymidine kinase 2 deficiency with age of symptom onset ≤12 years by the US Food and Drug Administration and the European Medicines Agency; previously, disease management was limited to supportive care. We investigated the efficacy and safety of pyrimidine …

Rare But Relevant? Assessing Variants In Dystonia-Linked Genes In Parkinson's Disease, Lara M Lange, Zih-Hua Fang, Laurel Screven, Ai Huey Tan, Roy N Alcalay, Rim Amouri, Roberta Bovenzi, Matilda Fenn, Joshua L I Frost, Joseph Jankovic, Simona Jasaityte, Zane Jaunmuktane, Beomseok Jeon, Ignacio Juan Keller Sarmiento, Rejko Krüger, Gregor Kuhlenbäumer, Chin-Hsien Lin, Lukas Pavelka, Maria Teresa Periñan, Samia Ben Sassi, Tommaso Schirinzi, Jung Hwan Shin, Joshua M Shulman, Yi Wen Tay, Ryan Uitti, Tom Warner, Zbigniew K Wszolek, Lesley Wu, Ruey-Meei Wu, Kirsten E Zeuner, Cornelis Blauwendraat, Andrew Singleton, Niccolò E Mencacci, Huw R Morris, Shen-Yang Lim, Katja Lohmann, Christine Klein

Faculty, Staff and Students Publications

Background: Dystonia and Parkinson's disease (PD) exhibit clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear.

Objective: The aim was to assess the frequency of dystonia-linked pathogenic variants in PD.

Methods: We screened sequencing data from 15,684 individuals (8272 PD, 3200 atypical parkinsonism, and 4212 unaffected) from the Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) for variants in genes linked to isolated dystonia, dystonia-parkinsonism, and myoclonus-dystonia.

Results: Pathogenic variants were identified only in PD patients. Forty-five PD individuals (0.54%) carried 26 distinct (likely) pathogenic variants in nine dystonia-linked genes, most …

The Words Community Dwelling, Spanish-Preferring Mexican/Mexican American Adults Use To Talk About Alzheimer’S Disease And Genetic Testing: Implications For Education And Outreach, Jamie C Fong, Fatima I Chavez, Karla Silos, Mirna L Arroyo-Miranda, Gabriela Castro Castro, Mark E Kunik, Joshua M Shulman, Luis D Medina

Faculty, Staff and Students Publications

Introduction: Hispanic/Latino (H/L) adults are more likely than non-Hispanic White individuals to have Alzheimer's disease (AD), yet fewer than one in five H/L adults has apolipoprotein E (APOE) Ɛ4, underscoring gaps in understanding genetic risk across H/L heritage groups. H/L adults remain underrepresented in AD research that uses genetic data for participant stratification. To inform culturally appropriate educational materials for 16 million U.S. Spanish speakers, we identified culturally salient words Spanish-preferring H/L adults use to describe AD and genetic testing beyond APOE.

Methods: Community-residing, Spanish-preferring Mexican/Mexican American adults (n = 14) completed freelisting interviews, a method eliciting …