Digital Commons Network^™

Improved Allele Frequencies In Gnomad Through Local Ancestry Inference, Pragati Kore, Michael W Wilson, Grace Tiao, Katherine Chao, Philip W Darnowsky, Nicholas A Watts, Jessica Honorato Mauer, Samantha M Baxter, Genome Aggregation Database Consortium, Heidi L Rehm, Mark J Daly, Konrad J Karczewski, Elizabeth G Atkinson

Faculty, Staff and Students Publications

The Genome Aggregation Database (gnomAD) is a foundational resource for allele frequency data, widely used in genomic research and clinical interpretation. However, traditional estimates rely on individual-level genetic ancestry groupings that may obscure variation in recently admixed populations. To improve resolution, we applied local ancestry inference (LAI) to over 27 million variants in two admixed groups: Admixed American (n = 7612) and African/African American (n = 20,250), deriving ancestry-specific allele frequencies. We show that 78.5% and 85.1% of variants in these groups, respectively, exhibit at least a twofold difference in ancestry-specific frequencies. Moreover, 81.49% of variants with LAI information would …

Temporal Trends In The Epidemiology Of Hip Osteoarthritis In The Usa, 1990-2019: A Cross-Sectional Time-Series Study Using Gbd Data., Arsalaan Sayyed, Gabrielle Lucia Dykhouse, Taylor J Manes, Cameron Sabet, Minali Gautami Nemani, Ambrose Loc Ngo, Ayah A Ibrahim, Phillip C Mckegg, Jignesh N Patel

Ambulatory and Primary Care Articles

OBJECTIVES: To evaluate temporal trends in the epidemiology of hip osteoarthritis (OA) in the USA from 1990 to 2019, with stratification by sex and geographic region.

DESIGN: Cross-sectional time-series analysis using secondary data from the Global Burden of Disease (GBD) study.

SETTING: US population-based analysis, stratified by the four US Census Bureau regions: Northeast, Midwest, South and West.

PARTICIPANTS: De-identified, aggregate population-level data representing all adults in the USA from 1990 to 2019, drawn from the GBD database.

PRIMARY AND SECONDARY OUTCOME MEASURES: Age-standardised rates per 100 000 population for years lived with disability (YLDs), prevalence and incidence of hip …

Causal Ai-Based Clinical And Radiomic Analysis For Optimizing Patient Selection In Combined Immunotherapy And Sabr In Early-Stage Nsclc: A Secondary Analysis Of The Phase Ii I-Sabr Trial, Maliazurina B Saad, Eman Showkatian, Vivek Verma, Qasem Al-Tashi, Muhammad Aminu, Xinyan Xu, Muhamed Qayati Mohamed, Morteza Salehjahromi, Sheeba J Sujit, Yuliya Kitsel, Steven H Lin, Zhongxing Liao, Saumil Gandhi, David Qian, David Jaffray, Caroline Chung, Natalie I Vokes, Jianjun Zhang, J Jack Lee, John V Heymach, Jia Wu, Joe Y Chang

Faculty, Staff and Student Publications

Background: The recent phase II randomized stereotactic ablative radiotherapy with and without immunotherapy (I-SABR) trial has shown improved event-free survival (EFS) when adding immunotherapy to stereotactic ablative radiotherapy (SABR) for early-stage inoperable non-small cell lung cancer (NSCLC). However, optimizing patient selection thereof is critical, because not every patient benefits from immunotherapy. Leveraging the powerful use of artificial intelligence, this secondary analysis of the I-SABR trial developed a modeling system (named "I-SABR-SELECT") based on clinical and radiomic factors to address which patients should receive additional immunotherapy.

Methods: The discovery/validation cohorts were from the I-SABR trial, with external validation from the single-arm …

Robotic Ureteral Reconstruction For Endometriosis-Induced Strictures: Insights From A Multi-Institutional Experience, Matthew Lee, Sonam Saxena, Kelley Zhao, Cameron Dodd, Randall Lee, Michael Stifelman, Lee Zhao, Daniel D. Eun

Department of Surgery Faculty Papers

PURPOSE: To investigate outcomes of robotic ureteral reconstruction (RUR) in female patients with ureteral strictures caused by peri-ureteral endometriosis lesions.

METHODS: We retrospectively reviewed our multi-institutional Collaborative of Reconstructive Robotic Ureteral Surgery (CORRUS) database to identify all consecutive patients undergoing RUR for surgical management of endometriosis-induced ureteral strictures between 2017 and 2022. Indications for surgery included female patients with radiographic evidence of ureteral strictures and/or decreasing renal function on renal scan. We performed a descriptives analysis of perioperative outcomes in patients who met inclusion criteria. Surgical success was defined as freedom from additional interventions for recurrent ureteral stenosis.

RESULTS: Overall, …

Perioperative Repercussions Of Cannabis Use-Implications For Gi Endoscopy Sedation, Basavana Goudra, Michael Green

Department of Anesthesiology Faculty Papers

The legalization of cannabis in multiple U.S. states and several other countries, along with its increasing social acceptance across diverse demographic and socioeconomic groups, has led to a growing number of patients presenting for interventional procedures with a history of cannabis use. Although anesthetic and sedation-related implications may be less pronounced than in major surgery, they remain clinically relevant and warrant careful consideration. Key factors include acute intoxication, chronic use, and cannabis use disorder. Cannabis users often require higher-and sometimes unpredictable-doses of propofol and other sedatives. Inhalational use is associated with airway hyperreactivity, increasing the risk of bronchospasm and, in …

Advancing Modified Barium Swallow Pre-Sorting With Deep Learning: A New Paradigm For The First Step Analysis In X-Ray Swallowing Study, Shitong Mao, Mohamed A Naser, Sheila Buoy, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Purpose: Modified barium swallow (MBS) exams are pivotal for assessing swallowing function and include diagnostic video segments imaged in various planes, such as anteroposterior (AP or coronal plane) and lateral (or mid-sagittal plane), alongside non-diagnostic 'scout' image segments used for anatomic reference and image set-up that do not include bolus swallows. These variations in imaging files necessitate manual sorting and labeling, complicating the pre-analysis workflow.

Methods: Our study introduces a deep learning approach to automate the categorization of swallow videos in MBS exams, distinguishing between the different types of diagnostic videos and identifying non-diagnostic scout videos to streamline the MBS …

Male Hypogonadism: Recommendations From The Fifth International Consultation On Sexual Medicine (Icsm 2024), Mohit Khera, Luiz Otavio Torres, Ethan D Grober, Abraham Morgentaler, Martin Miner, Thomas Hugh Jones, Jesse N Mills, Andrea Salonia

Faculty, Staff and Students Publications

Introduction: Male hypogonadism is a clinical condition combining low circulating testosterone (T) and specific signs and symptoms associated with impaired hormone production.

Objectives: To provide the 5th International Consultation for Sexual Medicine consensus paper with recommendations concerning management strategies for hypogonadism.

Outcomes: A narrative review combined with expert opinions on major topics concerning diagnosis of male hypogonadism; treatment options; T impact toward cardiovascular, metabolic, sexual, and reproductive health; and prostate cancer (PCa).

Methods: A consensus panel was held with leading Sexual Medicine experts during the 5th ICSM. Relevant English-language peer-reviewed literature was reviewed with a focus on research from but …

Expansion Of Hand Trauma Transfers At A Level 1 Trauma Center Following Integration With The Assh Hand Trauma Center Network, William Delahoussaye, Madeline Gautreaux, Patrick A. Palines, Ramin Shekouhi, Kelly L. Babineaux

School of Medicine Faculty Publications

Purpose: This study sought to evaluate how joining the National Hand Trauma Center Network (NHTCN) affected the volume, demographics, and severity of hand trauma transfers to our institution. Methods: Data for this study were collected retrospectively over a 6-year period from 2016 to 2021 from our institutional trauma registry. Patients were selected based on the criterion of being transferred to our facility because of isolated hand trauma. Analyses of transfer rates, transfer distance, sending facilities, injury patterns, insurance type, path of care, and hospital charges prior to and after joining the NHTCN were performed. Results: There was a total of …

Markers Of Tissue Hypoperfusion And Response To Vasopressors In Patients With Septic Shock, Islam M. El-Desoky, Ahmed A. Abdelaziz, Hossam A. Galbt, Ahmed S. Abdelgawad, Ola S. Mohamed

Journal of Medicine in Scientific Research

Background Patients in the early stage of septic shock require individualized fluid resuscitation and early administration of vasopressors to ensure tissue perfusion. We aimed to assess the performance of tissue perfusion markers in patients with septic shock and assessing its role in predicting the response to vasopressors. Methods This observational study was included 90 patients with septic shock within the first 24 hours of admission to the intensive care. Arterial (a) and central venous (cv) blood samples were obtained before beginning vasopressors (T0), and then at 12 and 24 hours after the initial sampling (T12, 24) for analysis of oxygen …

Post-Rt Head And Neck Dce-Mri: Association Between Mandibular Dose And Ve, Brandon Reber, Renjie He, Moamen R Abdelaal, Abdallah S R Mohamed, Samuel L Mulder, Laia Humbert Vidan, Clifton D Fuller, Stephen Y Lai, Kristy K Brock

Faculty, Staff and Student Publications

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a functional imaging modality that can quantify tissue permeability and blood flow. Due to vasculature changes resulting from radiation therapy (RT), DCE-MRI quantitative parameters should be significantly different in regions receiving a high radiation dose compared to regions receiving a low radiation dose. This study sought to determine whether a significant difference exists in post-head-and-neck-cancer (HNC)-RT DCE-MRI quantitative parameters (Ktrans and ve) between regions of the mandible receiving a high radiation dose and regions of the mandible receiving a low radiation dose.

Methods: DCE-MRI was acquired from HNC subjects post-RT. The DCE-MRI …

Assessing Spatial Variability In Observed Infectious Disease Spread In A Prospective Time-Space Series, Chih-Chieh Wu, Chien-Hsiun Chen, Shann-Rong Wang, Sanjay Shete

Faculty, Staff and Student Publications

Most of the growing prospective analytic methods in space-time disease surveillance and intended functions of disease surveillance systems focus on earlier detection of disease outbreaks, disease clusters, or increased incidence. The spread of the virus such as SARS-CoV-2 has not been spatially and temporally uniform in an outbreak. With the identification of an infectious disease outbreak, recognizing and evaluating anomalies (excess and decline) of disease incidence spread at the time of occurrence during the course of an outbreak is a logical next step. We propose and formulate a hypergeometric probability model that investigates anomalies of infectious disease incidence spread at …

Ambient Fine Particulate Matter, Residential Greenness, And Childhood Cancer Risk By Trimester Of Exposure In Minnesota 2000 To 2014: A Case-Control Study, Cassandra J Clark, David Haynes, Zhanni Lu, Jeannette M Sample, Laura A Mcguinn, Thanh T Hoang, Philip J Lupo, Michael E Scheurer, Erin L Marcotte, Lindsay A Williams

Faculty, Staff and Students Publications

Background: Outdoor air pollution is a suspected risk factor for childhood cancer, and there is some evidence that greenness may reduce cancer risk. We examined relationships between prenatal exposure to ambient fine particle air pollution [particulate matter < 2.5 µg/m3 (PM2.5)], greenness, and childhood cancer risk in Minnesota.

Methods: Cases included individuals born in the state of Minnesota and reported to the Minnesota Cancer Reporting System between 2000 and 2014 (n = 1272, ages 0-14 years at diagnosis) and birth year-matched cancer-free controls (n = 5245). We used Network Common Data Form to estimate monthly PM2.5 exposure and the normalized difference vegetation index for census tract-level greenness. We estimated ORs and …

Vaccine Value Profile For Schistosomiasis, Gavin Yamey, Kaci Kennedy Mcdade, Roy M Anderson, Sarah M Bartsch, Maria Elena Bottazzi, David Diemert, Peter J Hotez, Bruce Y Lee, Donald Mcmanus, Adebayo J Molehin, Meta Roestenberg, David Rollinson, Afzal A Siddiqui, Miriam Tendler, Joanne P Webster, Hong You, Raphaël M Zellweger, Caroline Marshall

Faculty, Staff and Students Publications

Schistosomiasis is caused by parasitic flatworms (Schistosoma). The disease in humans can be caused by seven different species of Schistosoma: S. mansoni, S. japonicum, S. haematobium, S. malayensis, S. mekongi, S. guineensis and S. intercalatum, as well as by hybrids between species, including livestock schistosome species. People are infected when exposed to infested water and the parasite larvae penetrate the skin. Poor and rural communities are typically the most affected, and the general population who lives in affected areas and is exposed to contaminated water is at risk. Areas with poor access to safe water and adequate sanitation are also …

All-Optical Voltage Interrogation For Probing Synaptic Plasticity In Vivo, Jacques Carolan, Michelle A Land, Xiaoyu Lu, Maxime Beau, Dimitar Kostadinov, François St-Pierre, Beverley A Clark, Michael Häusser

Faculty, Staff and Students Publications

Measuring synaptic efficacy and defining the rules for induction of synaptic plasticity at identified connections in the mammalian brain is essential for understanding how synapses contribute to learning and memory. This requires new approaches to selectively evoke presynaptic activity and measure postsynaptic responses with high spatiotemporal resolution and high sensitivity over long periods in vivo. Here we develop an all-optical approach to probe synaptic plasticity at identified cerebellar synapses in awake, behaving mice. We developed and applied JEDI-2Psub, a genetically encoded voltage indicator with increased sensitivity around resting membrane potentials, to record subthreshold and suprathreshold activity in Purkinje cell (PC) …

Cerebral Resistive Indices And Intraventricular Hemorrhage In Premature Neonates < 29 Weeks' Gestation: A Pilot Prospective Cohort Study., Abhinav Pal, Dan Stewart, Kshama Ojha, Vesna Kriss, Craig Ziegler, Hannah Fischer

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In extremely preterm newborns, intraventricular hemorrhage (IVH) greatly influences neurodevelopmental outcomes. Preterm newborns who later develop IVH might have altered cerebral blood flow (CBF) as measured by resistive index (RI) on Doppler ultrasound. Knowledge regarding RI in extremely premature infants remains limited.

OBJECTIVE: This pilot prospective cohort study aimed to evaluate the association between early cerebral RI (within the first 36 h of life) and the occurrence of IVH in preterm infants born at <  29 weeks’ gestation.

METHODS: Prospective cohort study in which cranial Doppler was performed in preterm infants <  29 weeks at <  36 h of age and between 5 and 7 days of age. CBF velocities and RI were measured. Clinical and demographic factors were also assessed. Statistical analyses included Pearson’s chi-square exact test, independent

RESULTS: Of the 30 enrolled infants, 27% developed an IVH. RI and …

Performing Dual Glucose Clamp Experiments In Sedated Farm Swine: A Practical Method, Marc Torjman, Winston Hamilton, Katherine Dillon, Channy Loeum, Jeffrey Joseph

Department of Anesthesiology Faculty Papers

The hyperinsulinemic-euglycemic clamp technique is considered the gold standard for measuring insulin sensitivity in large animals. We developed a practical method for conducting concurrent glucose clamp experiments in a pair of sedated farm swine positioned in a sling. Descriptions of customized equipment and central venous access surgical procedures for blood collection are provided. Personnel functions are described for execution of the clamp protocol. A total of 24 hyperinsulinemic-euglycemic clamp studies were performed over 6 weeks. Infusaports remained functional for 1454 blood samples. There were three CSII catheter occlusions during bolus administration, and the swine showed no signs of infection or …

Dual Membrane Receptor Degradation Via Folate Receptor Targeting Chimera, Zhen Wang, Zhixin Li, Jenny Högström, Hiroyuki Inuzuka, Rui Jing, Peiqiang Yan, Tao Hou, Yihang Qi, Daoyuan Huang, Jingchao Wang, Ting Wu, Xiaoying Shi, Bolin Liu, Taru Muranen, Dingpeng Zhang, Wenyi Wei

School of Medicine Faculty Publications

Cancer drug resistance poses a significant challenge in oncology, often driven by intricate cross-talk among membrane-bound receptors that compromise mono-targeted therapies. We develop a dual membrane receptor degradation strategy leveraging Folate Receptor α (FRα) to address this issue. Folate Receptor α Targeting Chimeras-dual (FolTAC-dual) are engineered degraders designed to selectively and simultaneously degrade distinct receptor pairs: (1) EGFR/HER2 and (2) PD-L1/VISTA. Through modular optimization of modality configurations and geometries, we identify the “string” format as the most effective construct. Mechanistic studies demonstrate an ~85% increase in EGFR-binding affinity compared to the conventional knob-into-hole design, likely contributing to the improved efficiency …

A Mast Cell Receptor Mediates Post-Stroke Brain Inflammation Via A Dural-Brain Axis, Ruchita Kothari, Mostafa W Abdulrahim, Hyun Jong Oh, Daniel H Capuzzi, Collin B Kilgore, Sumil K Nair, Yaowu Zhang, Nathachit Limjunyawong, Sarbjit S Saini, Jennifer E Kim, Justin M Caplan, Fernanado L Gonzalez, Christopher M Jackson, Chetan Bettegowda, Judy Huang, Bhanu P Ganesh, Chunfeng Tan, Raymond C Koehler, Rafael J Tamargo, Louise D Mccullough, Risheng Xu, Xinzhong Dong

Faculty, Staff and Student Publications

The immune environment surrounding the brain plays a fundamental role in monitoring signs of injury. Insults, including ischemic stroke, can disrupt this balance and incite an exaggerated inflammatory response, yet the underlying mechanism remains unclear. Here, we show that the mast-cell-specific receptor Mrgprb2 regulates post-stroke brain inflammation from the meninges. Mrgprb2 causes meningeal mast cell degranulation after stroke, releasing immune mediators. This process recruits skull bone marrow neutrophils into the dura and further promotes neutrophil migration from the dura into the brain by cleaving the chemorepellent semaphorin 3a. We demonstrate that the human ortholog, MRGPRX2, is expressed in human meningeal …

Rare Variants In Prkci Cause Van Der Woude Syndrome And Other Features Of Peridermopathy, Kelsey Robinson, Sunil K Singh, Rachel B Walkup, Dorelle V Fawwal, Kendra M Vilfort, Amanda Koloskee, Azeez Fashina, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, Wendy K Chung, David J Cutler, Michael P Epstein, Brooklynn Gasser, Lord J J Gowans, Jacqueline T Hecht, Anuj Mankad, Lina Moreno Uribe, Daryl A Scott, Gary M Shaw, Mary Ann Thomas, Seth M Weinberg, Eric C Liao, Harrison Brand, Mary L Marazita, Robert J Lipinski, Jeffrey C Murray, Robert A Cornell, Elizabeth J Leslie-Clarkson

Faculty, Staff and Student Publications

Van der Woude syndrome (VWS) is an autosomal dominant disorder characterized by lower lip pits and orofacial clefts (OFCs). With a prevalence of ∼1 in 35,000 live births, it is the most common form of syndromic clefting. Most VWS is attributed to variants in IRF6 (∼70%) or GRHL3 (∼5%), leaving up to 25% of individuals without a molecular diagnosis. Both IRF6 and GRHL3 function in a transcriptional regulatory network (TRN) governing differentiation of periderm, a single epithelial cell layer preventing pathological adhesions during palatogenesis. Periderm disruption can elicit a spectrum of phenotypes, including lip pits and OFCs, pterygia, and severe …

Preclinical Models Of Melanoma Leptomeningeal Disease To Assess Intrathecal Checkpoint Blockade, Renato A Guerrieri, Grant M Fischer, Jacob R Cortez, Barbara G Knighton, Debora A Ledesma, Courtney W Hudgens, Yimmy F Delcid, Qianghua Hu, Christian Y B Onana, Fernando C L Carapeto, Michael T Tezlaff, Jason T Huse, Patrick Hwu, Elizabeth M Burton, Isabella C Glitza Oliva, Michael A Davies, Sherise D Ferguson

Faculty, Staff and Student Publications

Leptomeningeal disease (LMD) is a subtype of central nervous system metastatic disease that is associated with poor patient outcomes and limited treatment options. There is an unmet need to develop preclinical models of LMD to expedite and improve the development of new therapeutics. Here, we describe the development of multiple orthotopic immunocompetent murine models of melanoma LMD, including their use to assess the efficacy of systemic and/or intrathecal immunotherapy. LMD was established by direct intrathecal injection of murine cell lines (B16-F10, BP, D4M, D4M-UV2, MC38-gp100, RMS, YUMM3.1, and YUMMER1.7) into the cisterna magna of C57BL/6 mice. Tumor take rate, distribution, …

Long-Term Outcomes In Flt3-Mutated Acute Myeloid Leukemia After Frontline Hypomethylating Agent, Venetoclax And A Flt3 Inhibitor, Nicholas J Short, Sanam Loghavi, Musa Yilmaz, Omer Karrar, Kunhwa Kim, Courtney D Dinardo, Tapan M Kadia, Manuel Maroun, Gautam Borthakur, Ghayas C Issa, Joseph Jabbour, Betul Oran, Elizabeth J Shpall, Uday Popat, Keyur P Patel, Mark Routbort, Marina Konopleva, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Triplet regimens with a hypomethylating agent, venetoclax and a FLT3 inhibitor yield high rates of response in newly diagnosed FLT3-mutated AML. However, the long-term outcomes and patterns of relapse with these triplet regimens are not well-established. In this retrospective analysis, 73 patients with newly diagnosed FLT3-mutated AML received a frontline FLT3 inhibitor-containing triplet regimen. The composite complete remission (CR) and CR with incomplete hematologic recovery (CRi) rate was 93%. Next-generation sequencing FLT3-ITD MRD negativity (sensitivity: 0.005%) was achieved in 60% of patients after cycle 2 and 90% after cycle 4. The estimated 3-year relapse-free survival (RFS) for FLT3-ITD-mutated and FLT3 …

Reversible Arginine Methylation Of Pi3kc2Α Controls Mitotic Spindle Dynamics, Yena Cho, Jee Won Hwang, Mark T Bedford, Dong Hee Na, Dae-Geun Song, Su-Nam Kim, Yong Kee Kim

Faculty, Staff and Student Publications

Microtubules, composed of αβ-tubulin dimers, undergo dynamic polymerization and are fundamental to cell structure and function. In the current study, we discovered that phosphatidylinositol 3-kinase class 2α (PI3KC2α) acts as a novel regulatory factor in microtubule dynamics. Specifically, asymmetric dimethylation of PI3KC2α at the R175 residue (R175me2a) by coactivator-associated arginine methyltransferase 1 (CARM1) enhances its interaction with α-tubulin, stabilizing microtubule assembly. Furthermore, lysine Demethylase 4 A (KDM4A) serves as an arginine demethylase for PI3KC2α R175me2a. During mitosis, protein kinase C (PKC)-mediated phosphorylation of KDM4A results in its dissociation from PI3KC2α, preventing demethylation and increasing R175me2a levels. This facilitates spindle formation …

Functional Effects Of Heavy Metal Exposures On N6-Methyladenosine (M6a) Methylation And Other Epitranscriptomic Modifications In The Central Nervous System, Niraj Lodhi, Lauren Powell, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Among different RNA methylations, N6-methyladenosine (m6A) is the most abundant in the brain and determines the fate of RNA through reversible processes using methyltransferases, demethylases, and methyl-binding proteins. The reversibility of m6A is an emerging regulatory mechanism for gene expression, regulating many aspects of RNA metabolism and influencing learning and memory processes. Global m6A profiles are dynamically modified via the activity of various writers, readers, and erasers. However, m6A alterations from exposure to heavy metals, including the metals lead (Pb), cadmium (Cd), cobalt (Co), and manganese (Mn) and the metalloid arsenic (As), and the impact on brain function, are not …

Evaluating Anti-Sickling Therapies For Sickle Cell Disease: A Microfluidic Assay For Red Blood Cell-Mediated Microvascular Occlusion Under Hypoxia, Zoe Sekyonda, Yuxuan Du, Solomon Oshabaheebwa, Payam Fadaei, Yusang B. Ley, Calvin Abonga, Michael A. Suster, Pedram Mohseni, Umut A. Gurkan

Faculty Scholarship

Sickle cell disease (SCD) is characterized by the polymerization of hemoglobin S (HbS) upon deoxygenation, leading to the formation of sickled red blood cells (RBCs) with reduced deformability. Under hypoxic conditions, the impaired RBC behavior significantly contributes to vaso-occlusive events, hemolysis, and end-organ damage. Consequently, RBC deformability serves as a pivotal hemorheological biomarker for evaluating disease severity and therapeutic response. The OcclusionChip, a microfluidic assay, measures RBCs deformability through microcapillary occlusion. However, its current hypoxic assay relies on a complex nitrogen gas setup, rendering it bulky, expensive, and unsuitable for point-of-care diagnostic use. Here, we optimized a chemically induced hypoxia …

A Needed Nomenclature For Nucleosomes, Michael-Christopher Keogh, Genevieve Almouzni, Andrew J Andrews, Karim-Jean Armache, Cheryl H Arrowsmith, Sung Hee Baek, Mark T Bedford, Emily Bernstein, Jacques Côté, Yael David, John M Denu, Beat Fierz, Benjamin A Garcia, Karen C Glass, Or Gozani, Kristian Helin, Steven Henikoff, Ole N Jensen, Steven Z Josefowicz, Neil L Kelleher, Tatiana G Kutateladze, Herbert H Lindner, Chao Lu, Karolin Luger, Parag Mallick, Catherine A Musselman, Tom W Muir, Ljiljana Paša-Tolić, Robert Schneider, Xiaobing Shi, Yang Shi, Simone Sidoli, Lloyd M Smith, Jessica K Tyler, Cynthia Wolberger, Jerry L Workman, Brian D Strahl, Nicolas L Young

Faculty, Staff and Student Publications

Histone post-translational modifications (PTMs) are crucial to eukaryotic genome regulation, with a range of reported functions and mechanisms of action. Though often studied individually, it has long been recognized that the modifications function by combinatorial synergy or antagonism. Interplay may involve PTMs on the same histone, within the same nucleosome (containing a histone octamer), or between nucleosomes in higher-order chromatin. Given this, the field must distinguish ever greater complexity, and the context in which it is studied, with brevity and precision. The proteoform was introduced to define individual forms of a protein by sequence and PTMs, followed by the nucleoform …

Educating Future Nurse Practitioners And Physician Associates On Pretreatment Of Swallowing In Head And Neck Cancer, Hannah M. Berk, Erin L. O'Bryan, Imran Musaji, Carly A. Thomas, Jamie Harrington

Teaching and Learning in Communication Sciences & Disorders

Head and neck cancer treatment frequently results in long-term severe swallowing deficits, often requiring feeding tube dependency. Patients who have completed swallowing exercise programs before and during cancer treatment experienced more positive swallowing outcomes, but most patients are not referred for swallowing intervention early enough in their care to prevent long-term deficits. This student research project aimed to measure health profession students’ knowledge of swallowing pretreatment for head and neck cancer patients and to investigate the impact of an educational module developed and presented by a Communication Sciences and Disorders graduate student to improve knowledge and awareness of this clinical …

Erector Spinae Plane Block For Preserving Pulmonary Function In Patients With Traumatic Rib Fractures, Dakoda Farrington

Lynchburg Journal of Medical Science

Rib fractures are frequently seen in trauma patients and are associated with increased mortality, primarily due to pulmonary complications. This study investigates the efficacy of erector spinae plane block (ESPB) in preserving pulmonary function in patients with traumatic rib fractures. A search was conducted in PubMed using the terms "erector spinae plane" AND ("rib fracture" OR "rib fractures") AND trauma. The results were filtered to include studies within the past five years, available full-text articles, and relevancy to this research question. Ultimately, five studies were isolated and included in this review. The methodology for measuring pulmonary function varied between the …

An Analysis Of Mental Health In Menopause, Christy Thozer

Lynchburg Journal of Medical Science

Menopause is a major life transition and is frequently accompanied by significant symptoms. While many complaints are often addressed by healthcare providers, many others are frequently left out of the discussion. While these symptoms are significantly detrimental to quality of life and effective treatments are available, many symptoms of menopause remain under-addressed. Mental health symptomatology such as depression, cognitive changes, and decline in libido are common and frequently distressing in the menopause transition and are well worth focused attention. Depression in menopause is well treated by selective serotonin reuptake inhibitors (SSRIs) but may also benefit from treatment with menopausal hormone …

Orthostatic Hypotension In Older Adults And Its Economic Impact On The Healthcare System: A Systematic Literature Review, Olushola E. Ilogho, Jennifer Broyles, Viet Le, Denise Rizzolo

Lynchburg Journal of Medical Science

ABSTRACT

Orthostatic Hypotension (OH) has been shown to lead to poor quality of life, falls, and death. Literature suggests that falls from OH may be preventable, therefore opportunities to reduce its associated cost to the healthcare system exist. This literature review aims to evaluate the importance of diagnosing and treating OH in older adult patients. OH is the drop in blood pressure upon changing to an upright position. This acute hemodynamic drop in blood pressure causes hypoperfusion in the brain, leading to dizziness, syncope, and falls. An extensive literature search for publications in PubMed and Cumulative Index in Nursing and …

America's Physician Shortage: Look To Pas, Not Abroad, Raquelle Akavan, Laura Juarez

Lynchburg Journal of Medical Science

The United States has long addressed physician shortages by recruiting international medical graduates (IMGs), often from low- and- middle income countries. This "brain drain" deprives already fragile health systems and adds to worldwide health disparities. New state legislation has eased licensing standards for IMGs and generated variable training pathways creating patient safety risk in underserved groups. At the same time, the U.S. has a sustainable, highly trained, and proven ready workforce: physician associates (PA). Created in the 1960s to address physician shortages, PAs undergo intensive graduate-degree education, uniform clinical education, and national certification on par with physicians. Nonetheless, obsolete laws …