Digital Commons Network^™

Global Blood Pressure Screening During The Covid-19 Pandemic: Results From The May Measurement Month 2021 Campaign, George S Stergiou, Rafael Hernandez-Hernandez, Mohammad Ishaq, Jacek Jozwiak, Nadia Khan, Gaia Kiru, Harsha Mccardle, Augustine Nonso Odili, Wook Bum Pyun, Cesar A Romero, Jiguang Wang, Neil R Poulter, Mmm Investigators

Faculty, Staff and Student Publications

BACKGROUND: Raised blood pressure (BP) remains the biggest risk factor contributing to the global burden of disease and mortality, despite the COVID-19 pandemic. May Measurement Month (MMM), an annual global screening campaign aims to highlight the importance of BP measurement by evaluating global awareness, treatment and control rates among adults with hypertension. In 2021, we assessed the global burden of these rates during the COVID-19 pandemic.

METHODS: Screening sites were set up in 54 countries between May and November 2021 and screenees were recruited by convenience sampling. Three sitting BPs were measured, and a questionnaire completed including demographic, lifestyle and …

Characteristics Of Patients Diagnosed With Pancreatic Cancer Who Access Palliative Care: An Observational Study, Megan Blanchard, Luc Te Marvelde

Faculty, Staff and Student Publications

PURPOSE: Despite the benefits of palliative care (PC) in pancreatic cancer, little is known about patients who access PC. This observational study examines the characteristics of patients with pancreatic cancer at their first episode of PC.

METHODS: First-time, specialist PC episodes captured through the Palliative Care Outcomes Collaboration (PCOC), in Victoria, Australia between 2014 and 2020, for pancreatic cancer, were identified. Multivariable logistic regression analyses examined the impact of patient- and service-level characteristics on symptom burden (measured through patient-reported outcome measures and clinician-rated scores) at first PC episode.

RESULTS: Of 2890 eligible episodes, 45% began when the patient was deteriorating …

Lymphocytic Choriomeningitis Virus In Person Living With Hiv, Connecticut, Usa, 2021, Ketan Patel, Debi Cannon, Mary Choi, Inna Krapiunaya, John D Klena, Trevor Shoemaker

Faculty, Staff and Student Publications

Lymphocytic choriomeningitis virus is an underreported cause of miscarriage and neurologic disease. Surveillance remains challenging because of nonspecific symptomatology, inconsistent case reporting, and difficulties with diagnostic testing. We describe a case of acute lymphocytic choriomeningitis virus disease in a person living with HIV in Connecticut, USA, identified by using quantitative reverse transcription PCR.

Exploring Stakeholders' Perspectives On Implementing Universal Germline Testing For Colorectal Cancer: Findings From A Clinical Practice Survey, Linda Rodgers-Fouche, Sanjeevani Arora, Charité Ricker, Dan Li, Maheen Farooqi, Mev Dominguez-Valentin, Priyanka Kanth, David Liska, Joshua Melson, Kathryn A Mraz, Brian H Shirts, Eduardo Vilar, Bryson W Katona, Rachel Hodan

Faculty, Staff and Student Publications

Purpose: New guidelines recommend considering germline genetic testing for all patients with colorectal cancer (CRC). However, there is a lack of data on stakeholders' perspectives on the advantages and barriers of implementing universal germline testing (UGT). This study assessed the perspectives of members of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) regarding the implementation of UGT for patients with CRC, including readiness, logistics, and barriers.

Methods: A cross-sectional survey was sent to 317 active members of CGA-IGC. The survey included sections on demographics, clinical practice specialty, established institutional practices for testing, and questions pertaining to support …

Greater Male Variability In Daily Energy Expenditure Develops Through Puberty, Lewis G Halsey, Vincent Careau, Philip N Ainslie, Heliodoro Alemán-Mateo, Lene F Andersen, Leonore Arab, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Soren Brage, Maciej S Buchowski, Nancy Butte, Stephan G Camps, Regian Casper, Graeme L Close, Lisa H Colbert, Jamie A Cooper, Richard Cooper, Prasangi Dabare, Sai Krupa Das, Peter S W Davies, Sanjoy Deb, Christine Delisle Nyström, William Dietz, Lara R Dugas, Simon Eaton, Ulf Ekelund, Asmaa El Hamdouchi, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Hinke Haisma, Catherine Hambly, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, Nader Lessan, Marie Löf, Corby Martin, Eric Matsiko, Gerwin A Meijer, James C Morehen, James P Morton, Aviva Must, Marian Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietilainen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto Rabinovich, Susan B Racette, David A Raichen, Eric Ravussin, Leanne Redman, John J Reilly, Rebecca Reynolds, Susan Roberts, Jennifer C Rood, Dulani Samaranayake, Luís B Sardinha, Albertine J Scuitt, Analiza M Silva, Srishti Sinha, Anders M Sjödin, Eric Stice, Albert Stunkard, Samuel S Urlacher, Mauro Eduardo Valencia, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jeanine A Verbunt, Jonathan C K Wells, George Wilson, Brian Wood, Tsukasa Yoshida, Xueying Zhang, Alexia Murphy-Alford, Cornelia Loechl, Amy Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Klaas R Westerterp, William W Wong, Yosuke Yamada, John R Speakman

Faculty, Staff and Student Publications

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at …

Cancer Informatics For Cancer Centers: Sharing Ideas On How To Build An Artificial Intelligence-Ready Informatics Ecosystem For Radiation Oncology, Danielle S Bitterman, Michael F Gensheimer, David Jaffray, Daniel A Pryma, Steve B Jiang, Jorge Barrios Ginart, Katherine A Vallis, John M Buatti, Joseph Deasy, H Timothy Hsiao, Caroline Chung, Clifton D Fuller, Emily Greenspan, Kristy Cloyd-Warwick, Samir Courdy, Allen Mao, Jill Barnholtz-Sloan, Umit Topaloglu, Isaac Hands, Ian Maurer, May Terry, Walter J Curran, Quynh-Thu Le, Sorena Nadaf, Warren Kibbe

Faculty, Staff and Student Publications

In August 2022, the Cancer Informatics for Cancer Centers brought together cancer informatics leaders for its biannual symposium, Precision Medicine Applications in Radiation Oncology, co-chaired by Quynh-Thu Le, MD (Stanford University), and Walter J. Curran, MD (GenesisCare). Over the course of 3 days, presenters discussed a range of topics relevant to radiation oncology and the cancer informatics community more broadly, including biomarker development, decision support algorithms, novel imaging tools, theranostics, and artificial intelligence (AI) for the radiotherapy workflow. Since the symposium, there has been an impressive shift in the promise and potential for integration of AI in clinical care, accelerated …

Evaluation Of The Prognostic Role Of Liver Metastases On Patient Outcomes: Systematic Review And Meta-Analysis, Jessica J Waninger, Vincent T Ma, Zoey Chopra, Ashley N Pearson, Michael D Green

Faculty, Staff and Student Publications

The liver is a common site of metastasis for many primary malignancies, but the quantitative impact on survival is unknown. We performed a systematic review and meta-analysis of 83 studies (604,853 patients) assessing the overall hazard associated with liver metastases by primary tumor type and treatment regimen. The pooled overall survival hazard ratio (HR) for all included studies was 1.77 (95% confidence interval [CI], 1.62-1.93). Patients with breast cancer primaries fared the worst (HR, 2.37; 95% CI, 1.64-3.44), as did patients treated with immunotherapies (HR, 1.86; 95% CI, 1.42-2.42). Liver metastases negatively impact survival, necessitating new approaches to disease management.

Evolving Trends And Outcomes In Older Patients With Acute Myeloid Leukemia Including Allogeneic Stem Cell Transplantation, Alexandre Bazinet, Hagop Kantarjian, Naszrin Arani, Uday Popat, Alex Bataller, Courtney D Dinardo, Musa Yilmaz, Hussein A Abbas, Nicholas J Short, Ghayas Issa, Elias Jabbour, Sherry A Pierce, Julianne Chen, Ricky Garcia, Marina Konopleva, Guillermo Garcia-Manero, Amin Alousi, Elizabeth J Shpall, Richard E Champlin, Gautam Borthakur, Farhad Ravandi, Tapan Kadia

Faculty, Staff and Student Publications

Outcomes in older patients with acute myeloid leukemia (AML) have historically been poor. Given advances in low-intensity therapy (LIT) and stem cell transplantation (SCT), we performed a retrospective single-center study to evaluate the contemporary outcomes of this population. We reviewed all patients ≥60 years with newly diagnosed AML between 2012 and 2021 and analyzed treatment and SCT-related trends and outcomes. We identified 1073 patients with a median age of 71 years. Adverse clinical and cytomolecular findings were frequent within this cohort. In total, 16% of patients were treated with intensive chemotherapy, 51% with LIT alone, and 32% with LIT plus …

Feasibility And Clinical Acceptability Of Automation-Assisted 3d Conformal Radiotherapy Planning For Patients With Cervical Cancer In A Resource-Constrained Setting, Sikudhani Muya, Jerry Ndumbalo, Sarah Kutika Nyagabona, Shaid Yusuf, Dong Joo Rhee, Benjamin Li, Surbhi Grover, Mary Feng, I-Chow Hsu, Elia Mmbaga, Katherine Van Loon, Laurence Court, Melody Xu

Faculty, Staff and Student Publications

Purpose: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system.

Materials and methods: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety …

Making Waves: Integrating Wastewater Surveillance With Dynamic Modeling To Track And Predict Viral Outbreaks, Tin Phan, Samantha Brozak, Bruce Pell, Jeremiah Oghuan, Anna Gitter, Ruy M Ribeiro, Kristina D Mena, Alan S Perelson, Yang Kuang, Fuqing Wu

Faculty, Staff and Student Publications

Wastewater surveillance has proved to be a valuable tool to track the COVID-19 pandemic. However, most studies using wastewater surveillance data revolve around establishing correlations and lead time relative to reported case data. In this perspective, we advocate for the integration of wastewater surveillance data with dynamic within-host and between-host models to better understand, monitor, and predict viral disease outbreaks. Dynamic models overcome emblematic difficulties of using wastewater surveillance data such as establishing the temporal viral shedding profile. Complementarily, wastewater surveillance data bypasses the issues of time lag and underreporting in clinical case report data, thus enhancing the utility and …

A Review Of Pulmonary Neutrophilia And Insights Into The Key Role Of Neutrophils In Particle-Induced Pathogenesis In The Lung From Animal Studies Of Lunar Dusts And Other Poorly Soluble Dust Particles, Chiu-Wing Lam, Vincent Castranova, Kevin Driscoll, David Warheit, Valerie Ryder, Patti Zeidler-Erdely, Robert Scully, William Wallace, John James, Brian Crucian, Mayra Nelman, Richard Mccluskey, Donald Gardner, Roger Renne, Roger Mcclellan

Faculty, Staff and Student Publications

The mechanisms of particle-induced pathogenesis in the lung remain poorly understood. Neutrophilic inflammation and oxidative stress in the lung are hallmarks of toxicity. Some investigators have postulated that oxidative stress from particle surface reactive oxygen species (psROS) on the dust produces the toxicopathology in the lungs of dust-exposed animals. This postulate was tested concurrently with the studies to elucidate the toxicity of lunar dust (LD), which is believed to contain psROS due to high-speed micrometeoroid bombardment that fractured and pulverized lunar surface regolith. Results from studies of rats intratracheally instilled (ITI) with three LDs (prepared from an Apollo-14 lunar regolith), …

Abnormal Motion Capture In Acute Stroke (Bionics): A Low-Cost Tele-Evaluation Tool For Automated Assessment Of Upper Extremity Function In Stroke Patients, Dorothea M Parker, Shayan Shams

Faculty, Staff and Student Publications

BACKGROUND: The incidence of stroke and stroke-related hemiparesis has been steadily increasing and is projected to become a serious social, financial, and physical burden on the aging population. Limited access to outpatient rehabilitation for these stroke survivors further deepens the healthcare issue and estranges the stroke patient demographic in rural areas. However, new advances in motion detection deep learning enable the use of handheld smartphone cameras for body tracking, offering unparalleled levels of accessibility.

METHODS: In this study we want to develop an automated method for evaluation of a shortened variant of the Fugl-Meyer assessment, the standard stroke rehabilitation scale …

Host-Derived Reactive Oxygen Species Trigger Activation Of The Candida Albicans Transcription Regulator Rtg1/3, Joachim Morschhäuser

Faculty, Staff and Student Publications

The signals that denote mammalian host environments and dictate the activation of signaling pathways in human-associated microorganisms are often unknown. The transcription regulator Rtg1/3 in the human fungal pathogen Candida albicans is a crucial determinant of host colonization and pathogenicity. Rtg1/3's activity is controlled, in part, by shuttling the regulator between the cytoplasm and nucleus of the fungus. The host signal(s) that Rtg1/3 respond(s) to, however, have remained unclear. Here we report that neutrophil-derived reactive oxygen species (ROS) direct the subcellular localization of this C. albicans transcription regulator. Upon engulfment of Candida cells by human or mouse neutrophils, the regulator …

New Insights Into Rna Processing By The Eukaryotic Trna Splicing Endonuclease, Simon Trowitzsch

Faculty, Staff and Student Publications

Through its role in intron cleavage, tRNA splicing endonuclease (TSEN) plays a critical function in the maturation of intron-containing pre-tRNAs. The catalytic mechanism and core requirement for this process is conserved between archaea and eukaryotes, but for decades, it has been known that eukaryotic TSENs have evolved additional modes of RNA recognition, which have remained poorly understood. Recent research identified new roles for eukaryotic TSEN, including processing or degradation of additional RNA substrates, and determined the first structures of pre-tRNA-bound human TSEN complexes. These recent discoveries have changed our understanding of how the eukaryotic TSEN targets and recognizes substrates. Here, …

Cancer Patients' Preferences And Perceptions Of Advantages And Disadvantages Of Telehealth Visits During The Covid-19 Pandemic, Deepika Kumar, Nancy Gordon, Constanza Zamani, Tammy Sheehan, Ernesto Martin, Jessica Payne, Elad Neeman, Raymond Liu

Faculty, Staff and Student Publications

PURPOSE: We aimed to ascertain oncology patients' perceptions of telehealth versus in-person (IP) visits for different types of clinical encounters.

METHODS: We surveyed adults undergoing cancer treatment at Kaiser Permanente Northern California infusion centers between November 2021 and May 2022 using a self-administered questionnaire. Patients were asked about visit modality preferences (video, phone, and IP) for six types of clinical discussions, overall advantages and disadvantages of telehealth (video or phone) versus IP modalities, and barriers to video visit use.

RESULTS: The 839 patients who completed surveys in English were 63% female; median age 63 years; 64% White; and 73% college-educated …

Clonal Evolution And Hierarchy In Myeloid Malignancies, Koichi Takahashi, Tomoyuki Tanaka

Faculty, Staff and Student Publications

Myeloid malignancies, a group of hematopoietic disorders that includes acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), are caused by the accumulation of genetic and epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) over time. Despite the relatively low number of genomic drivers compared with other forms of cancer, the process by which these changes shape the genomic architecture of myeloid malignancies remains elusive. Recent advancements in clonal hematopoiesis research and the use of cutting-edge single cell technologies have shed new light on the developmental process of myeloid malignancies. In this review, we delve into the …

Key Genetic Determinants Driving Esophageal Squamous Cell Carcinoma Initiation And Immune Evasion, Kyung-Pil Ko, Yuanjian Huang, Shengzhe Zhang, Gengyi Zou, Bongjun Kim, Sohee Jun, Karen J Dunbar, Gizem Efe, Anil K Rustgi, Hiroshi Nakagawa, Jae-Il Park

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Despite recent progress in identifying aberrant genetic and epigenetic alterations in esophageal squamous cell carcinoma (ESCC), the mechanism of ESCC initiation remains unknown.

METHODS: Using CRISPR/Cas 9-based genetic ablation, we targeted 9 genes (TP53, CDKN2A, NOTCH1, NOTCH3, KMT2D, KMT2C, FAT1, FAT4, and AJUBA) in murine esophageal organoids. Transcriptomic phenotypes of organoids and chemokine released by organoids were analyzed by single-cell RNA sequencing. Tumorigenicity and immune evasion of organoids were monitored by allograft transplantation. Human ESCC single-cell RNA sequencing data sets were analyzed to classify patients and find subsets relevant to organoid models and immune evasion.

RESULTS: We …

Multiplatform Analysis Of Intratumoral Pten Heterogeneity In Melanoma, Sharmeen Chagani, Mariana P De Macedo, Fernando Carapeto, Feng Wang, Diego M Marzese, Lauren E Haydu, Giang T Ong, Sarah E Warren, Joseph M Beechem, Dave S B Hoon, Gordon B Mills, Michael T Tetzlaff, Alexander J Lazar, Lawrence N Kwong, Michael A Davies

Faculty, Staff and Student Publications

Loss of protein expression of the tumor suppressor PTEN is associated with increased cancer aggressiveness, decreased tumor immune infiltration, and resistance to immune and targeted therapies in melanoma. We assessed a unique cohort of eight melanoma samples with focal loss of PTEN protein expression to understand the features and mechanisms of PTEN loss in this disease. We compared the PTEN-negative (PTEN[-]) areas to their adjacent PTEN-positive (PTEN[+]) areas using DNA sequencing, DNA methylation, RNA expression, digital spatial profiling, and immunohistochemical platforms. Variations or homozygous deletions of PTEN were identified in PTEN(-) areas that were not detected in the adjacent PTEN(+) …

Efficacy Of Immune Checkpoint Inhibitors For The Treatment Of Advanced Melanoma In Patients With Concomitant Chronic Lymphocytic Leukemia, S H Cass, J W D Tobin, Y D Seo, G Gener-Ricos, E Z Keung, M A Davies, A J Lazar, R Mason, M Millward, S Sandhu, C Khoo, L Warburton, V Guerra, A Haydon, H Dearden, A M Menzies, M S Carlino, J L Smith, P Mollee, M Burgess, S Mapp, C Keane, V Atkinson, S A Parikh, S N Markovic, W Ding, T G Call, P J Hampel, G V Long, J A Wargo, A Ferrajoli

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses.

PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients …

Incidence Of Major Bleeding In Patients With Chronic Lymphocytic Leukemia Receiving Ibrutinib And Therapeutic Anticoagulation, Laura M Roccograndi, Alexandra R Lovell, Alessandra Ferrajoli, Philip A Thompson, Jan A Burger, Nitin Jain

Faculty, Staff and Student Publications

Increased rates of clinically significant bleeding have been reported with ibrutinib, however, limited data is available on the risk when given with concomitant therapeutic anticoagulation. We analyzed the incidence of major bleeding in 64 patient exposures that received ibrutinib with concomitant therapeutic anticoagulation. Major bleeding was observed in 5/64 (8%) patient exposures. The highest incidence was observed with rivaroxaban (3/17, 18%), followed by apixaban (2/35, 6%). No major bleeding events were seen with enoxaparin (n = 10). A total of 38% of patient exposures received a concomitant antiplatelet agent along with therapeutic anticoagulation. Among these patients, one (4%) experienced …

Adagrasib In Advanced Solid Tumors Harboring A Krasg12c Mutation, Tanios S Bekaii-Saab, Rona Yaeger, Alexander I Spira, Meredith S Pelster, Joshua K Sabari, Minal Barve, Xiaohong Yan, Aditya Shetty, Hirak Der-Torossian, Shubham Pant

Faculty, Staff and Student Publications

Purpose: Adagrasib, a KRASG12C inhibitor, has demonstrated clinical activity in patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRASG12C mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRASG12C mutation.

Methods: In this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C-mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response …

Worth A Pound Of Cure? Emerging Strategies And Challenges In Cancer Immunoprevention, Saurav D Haldar, Eduardo Vilar, Anirban Maitra, Neeha Zaidi

Faculty, Staff and Student Publications

Cancer immunoprevention applies immunologic approaches such as vaccines to prevent, rather than to treat or cure, cancer. Despite limited success in the treatment of advanced disease, the development of cancer vaccines to intercept premalignant states is a promising area of current research. These efforts are supported by the rationale that vaccination in the premalignant setting is less susceptible to mechanisms of immune evasion compared with established cancer. Prophylactic vaccines have already been developed for a minority of cancers mediated by oncogenic viruses (e.g., hepatitis B and human papillomavirus). Extending the use of preventive vaccines to non-virally driven malignancies remains an …

Outcomes Of Transcatheter Aortic Valve Replacement In Patients With Cardiogenic Shock, Anju Bhardwaj, Richard Smalling, Abhijeet Dhoble

Faculty, Staff and Student Publications

AIMS: The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock (CS) remain largely unknown. In this study, the TAVRs performed for CS between June 2015 and September 2022 using SAPIEN 3 and SAPIEN 3 Ultra bioprosthesis from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were analysed.

METHODS AND RESULTS: CS was defined as: (i) coding of CS within 24 h on Transcatheter Valve Therapy Registry form; and/or (ii) pre-procedural use of inotropes or mechanical circulatory support devices and/or (iii) cardiac arrest within 24 …

Interictal Respiratory Variability Predicts Severity Of Hypoxemia After Generalized Convulsive Seizures, Xiaojin Li, George B Richerson, Brian K Gehlbach

Faculty, Staff and Student Publications

Objective: Severe respiratory dysfunction induced by generalized convulsive seizures (GCS) is now thought to be a common mechanism for sudden unexpected death in epilepsy (SUDEP). In a mouse model of seizure-induced death, increased interictal respiratory variability was reported in mice that later died of respiratory arrest after GCS. We studied respiratory variability in epilepsy patients as a predictive tool for severity of postictal hypoxemia, a potential biomarker for SUDEP risk. We then explored the relationship between respiratory variability and central CO2 drive, measured by the hypercapnic ventilatory response (HCVR).

Methods: We reviewed clinical, video-electroencephalography, and respiratory (belts, airflow, pulse oximeter, …

Paradoxes Of Cellular Sumoylation Regulation: A Role Of Biomolecular Condensates?

Faculty, Staff and Student Publications

Protein SUMOylation is a major post-translational modification essential for maintaining cellular homeostasis. SUMOylation has long been associated with stress responses as a diverse array of cellular stress signals are known to trigger rapid alternations in global protein SUMOylation. In addition, while there are large families of ubiquitination enzymes, all small ubiquitin-like modifiers (SUMOs) are conjugated by a set of enzymatic machinery comprising one heterodimeric SUMO-activating enzyme, a single SUMO-conjugating enzyme, and a small number of SUMO protein ligases and SUMO-specific proteases. How a few SUMOylation enzymes specifically modify thousands of functional targets in response to diverse cellular stresses remains an …

Current Curricular Trends After The Covid-19 Pandemic: A National Survey Of Psychiatry Residency Programs, Jeff Wang Jin, Kacy Smith, Amanda Helminiak, Vineeth John, Hanjing Emily Wu

Faculty, Staff and Student Publications

Objectives: During the COVID-19 pandemic, many psychiatry residencies (academic, community, and hybrid programs) have adopted different learning modalities to preserve a high quality of educational training. There is minimal data on specific program adaptations, related change perspectives, and program type stratification. This study sought to examine trends in curriculum changes in accredited psychiatry residency programs in the United States.

Methods: Program directors of accredited general psychiatry programs in the United States were surveyed to assess both general program details and changes in educational content, delivery, and perspectives with regard to program curricula.

Results: A total of 63 program directors out …

Trigeminal Autonomic Cephalalgias And Neuralgias In Children And Adolescents: A Narrative Review, Ankita Ghosh, Leena Varghese, Mark J Burish, Christina L Szperka

Faculty, Staff and Student Publications

Purpose of review: To summarize the available literature as well as the authors' experience on trigeminal autonomic cephalalgias (TACs) and cranial neuralgias in children and adolescents.

Recent findings: While TACs and cranial neuralgias are rare in children, several recent case series have been published. TACs in children share most of the clinical features of TACs in adults. However, there are many reported cases with clinical features which overlap more than one diagnosis, suggesting that TACs may be less differentiated in youth. Indomethacin-responsive cases of cluster headache and SUNCT/SUNA have been reported in children, whereas in adults indomethacin is usually reserved …

Risk Factors For Perinatal Transmission Of Hepatitis C Virus, Mona Prasad, George R Saade, Rebecca G Clifton, Grecio J Sandoval, Brenna L Hughes, Uma M Reddy, Anna Bartholomew, Ashley Salazar, 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, Mobeen Rathore, Rodrigo Diaz-Velasco, Ana M Puga, Andrew Wiznia, Andrea Kovacs, David J Garry, George A Macones, For The 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 estimate the rate of perinatal transmission of hepatitis C virus (HCV) infection, to identify risk factors for perinatal transmission of HCV infection, and to determine the viremic threshold for perinatal transmission.

Methods: This was a prospective, multicenter, observational study of pregnant individuals at less than 24 weeks of gestation screened for HCV infection from 2012 to 2018 in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Individuals found to be HCV antibody-positive were followed throughout pregnancy. Children were followed for evidence of perinatal transmission at 2-6 months (HCV RNA testing) …

Antegrade Fixation Of Distal Metaphyseal Ulnar Shortening Osteotomy, Joanne Y Zhou, Christopher S Frey, Kalpit N Shah, Peter J Ostergaard, Jeffrey Yao

Faculty, Staff and Student Publications

The ulnar shortening osteotomy (USO) is a common procedure used to treat ulnar impaction syndrome secondary to static or dynamic ulnar-positive variance. There are many described techniques for the USO. The distal metaphyseal ulnar shortening osteotomy (DMUSO) with retrograde cannulated screw fixation was described to reduce complications seen with other techniques. Biomechanical analysis of fixation constructs demonstrates 2-screw constructs are significantly stiffer than 1 screw and antegrade constructs have similar or greater stiffness when compared with retrograde constructs. Here, we describe a technique of antegrade cannulated screw fixation for DMUSO that obviates the need for the disruption of the distal …

Reduced Digestion Of Circulating Genomic Dna In Systemic Sclerosis Patients With The Dnase1l3 R206c Variant\, Kay T Pham, Ivan Caiello, Maureen D Mayes, Shervin Assassi

Faculty, Staff and Student Publications

Objectives: Polymorphism in a coding region of deoxyribonuclease I-like III (DNASE1L3), causing amino acid substitution of Arg-206 to Cys (R206C), is a robustly replicated heritable risk factor for SSc and other autoimmune diseases. DNASE1L3 is secreted into the circulation, where it can digest genomic DNA (gDNA) in apoptosis-derived membrane vesicles (AdMVs). We sought to determine the impact of DNASE1L3 R206C on digestion of circulating gDNA in SSc patients and healthy controls (HCs).

Methods: The ability of DNASE1L3 to digest AdMV-associated gDNA was tested in vitro. The effect of R206C substitution on extracellular secretion of DNASE1L3 was determined using a transfected …