Medical Specialties Commons^™

Mechanosensitive Membrane Proteins: Usual And Unusual Suspects In Mediating Mechanotransduction, Miriam B Goodman, Elizabeth S Haswell, Valeria Vásquez

Faculty, Staff and Student Publications

This Viewpoint, which accompanies a Special Issue focusing on membrane mechanosensors, discusses unifying and unique features of both established and emerging mechanosensitive (MS) membrane proteins, their distribution across protein families and phyla, and current and future challenges in the study of these important proteins and their partners. MS membrane proteins are essential for tissue development, cellular motion, osmotic homeostasis, and sensing external and self-generated mechanical cues like those responsible for touch and proprioception. Though researchers' attention and this Viewpoint focus on a few famous ion channels that are considered the usual suspects as MS mechanosensors, we also discuss some of …

Whole-Exome Sequencing Study Identifies Four Novel Gene Loci Associated With Diabetic Kidney Disease, Yang Pan, Xiao Sun, Xuenan Mi, Zhijie Huang, Yenchih Hsu, James E Hixson, Donna Munzy, Ginger Metcalf, Nora Franceschini, Adrienne Tin, Anna Köttgen, Michael Francis, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium Topmed Kidney Function Working Group, Jennifer A Brody, Bryan Kestenbaum, Colleen M Sitlani, Josyf C Mychaleckyj, Holly Kramer, Leslie A Lange, Xiuqing Guo, Shih-Jen Hwang, Marguerite R Irvin, Jennifer A Smith, Lisa R Yanek, Dhananjay Vaidya, Yii-Der Ida Chen, Myriam Fornage, Donald M Lloyd-Jones, Lifang Hou, Rasika A Mathias, Braxton D Mitchell, Patricia A Peyser, Sharon L R Kardia, Donna K Arnett, Adolfo Correa, Laura M Raffield, Ramachandran S Vasan, L Adrienne Cupple, Daniel Levy, Robert C Kaplan, Kari E North, Jerome I Rotter, Charles Kooperberg, Alexander P Reiner, Bruce M Psaty, Russell P Tracy, Richard A Gibbs, Alanna C Morrison, Harold Feldman, Eric Boerwinkle, Jiang He, Tanika N Kelly, Cric Study Investigators

Faculty, Staff and Students Publications

Diabetic kidney disease (DKD) is recognized as an important public health challenge. However, its genomic mechanisms are poorly understood. To identify rare variants for DKD, we conducted a whole-exome sequencing (WES) study leveraging large cohorts well-phenotyped for chronic kidney disease and diabetes. Our two-stage WES study included 4372 European and African ancestry participants from the Chronic Renal Insufficiency Cohort and Atherosclerosis Risk in Communities studies (stage 1) and 11 487 multi-ancestry Trans-Omics for Precision Medicine participants (stage 2). Generalized linear mixed models, which accounted for genetic relatedness and adjusted for age, sex and ancestry, were used to test associations between …

The Fly Homolog Of Supt16h, A Gene Associated With Neurodevelopmental Disorders, Is Required In A Cell-Autonomous Fashion For Cell Survival, Mengqi Ma, Xi Zhang, Yiming Zheng, Shenzhao Lu, Xueyang Pan, Xiao Mao, Hongling Pan, Hyung-Lok Chung, Hua Wang, Hong Guo, Hugo J Bellen

Faculty, Staff and Students Publications

SUPT16H encodes the large subunit of the FAcilitate Chromatin Transcription (FACT) complex, which functions as a nucleosome organizer during transcription. We identified two individuals from unrelated families carrying de novo missense variants in SUPT16H. The probands exhibit global developmental delay, intellectual disability, epilepsy, facial dysmorphism and brain structural abnormalities. We used Drosophila to characterize two variants: p.T171I and p.G808R. Loss of the fly ortholog, dre4, causes lethality at an early developmental stage. RNAi-mediated knockdown of dre4 in either glia or neurons causes severely reduced eclosion and longevity. Tissue-specific knockdown of dre4 in the eye or wing leads to the loss …

Assigning Pathogenicity For Tab2 Variants Using A Novel Scalable Functional Assay And Expanding Tab2 Disease Spectrum, Weiyi Xu, Andrea Graves, Monika Weisz-Hubshman, Lamees Hegazy, Christina Magyar, Zian Liu, Eleni Nasiotis, Md Abul Hassan Samee, Thomas Burris, Seema Lalani, Lilei Zhang

Faculty, Staff and Students Publications

Haploinsufficiency of TGF-beta-activated kinase 1 (MAP3K7) binding protein 2 (TAB2) has been associated with congenital heart disease and more recently multiorgan structural abnormalities. Missense variant represents a major proportion of non-synonymous TAB2 variants reported in gnomAD (295/576) and Clinvar (16/73), most of which are variants of uncertain significance (VUSs). However, interpretation of TAB2 missense variants remains challenging because of lack of functional assays. To address this issue, we established a cell-based luciferase assay that enables high-throughput screening of TAB2 variants to assess the functional consequence for predicting variant pathogenicity. Using this platform, we screened 47 TAB2 variants including five pathogenic …

Child Weight Status: The Role Of Feeding Styles And Highly Motivated Eating In Children, Maria A Papaioannou, Thomas G Power, Teresia M O'Connor, Jennifer O Fisher, Nilda E Micheli, Sheryl O Hughes

Children’s Nutrition Research Center Staff Publications

Although parental feeding plays an important role in child eating and weight status, high food motivation among children may also be a factor shaping how feeding impacts child weight. This study explored whether individual differences in preschool children’s food motivation interacted with mothers’ feeding styles in predicting subsequent child weight status. Participants included 129 Hispanic Head Start mother/child dyads. Data were collected at ages 4–5 years (Time 1) and 7–9 (Time 3). Staff measured heights/weights and observed children in an eating in the absence of hunger task. Mothers reported on feeding styles/practices and children’s eating behaviors. A principal components analysis …

Clinically Adjudicated Reference Standards For Evaluation Of Infectious Diseases Diagnostics, Robin Patel, Ephraim L Tsalik, Scott Evans, Vance G Fowler, Sarah B Doernberg, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

Lack of a gold standard can present a challenge for evaluation of diagnostic test accuracy of some infectious diseases tests, particularly when the test's accuracy potentially exceeds that of its predecessors. This approach may measure agreement with an imperfect reference, rather than correctness, because the right answer is unknown. Solutions consist of multitest comparators, including those that involve a test under evaluation if multiple new tests are being evaluated together, using latent class modeling, and clinically adjudicated reference standards. Clinically adjudicated reference standards may be considered as comparator methods when no predefined test or composite of tests is sufficiently accurate; …

Child Weight Status: The Role Of Feeding Styles And Highly Motivated Eating In Children, Maria A Papaioannou, Thomas G Power, Teresia M O'Connor, Jennifer O Fisher, Nilda E Micheli, Sheryl O Hughes

Faculty, Staff and Students Publications

Although parental feeding plays an important role in child eating and weight status, high food motivation among children may also be a factor shaping how feeding impacts child weight. This study explored whether individual differences in preschool children’s food motivation interacted with mothers’ feeding styles in predicting subsequent child weight status. Participants included 129 Hispanic Head Start mother/child dyads. Data were collected at ages 4–5 years (Time 1) and 7–9 (Time 3). Staff measured heights/weights and observed children in an eating in the absence of hunger task. Mothers reported on feeding styles/practices and children’s eating behaviors. A principal components analysis …

The Ipdgc/Gp2 Hackathon - An Open Science Event For Training In Data Science, Genomics, And Collaboration Using Parkinson's Disease Data, Hampton L Leonard, Ruqaya Murtadha, Alejandro Martinez-Carrasco, Alina Jama, Amica Corda Müller-Nedebock, Ana-Luisa Gil-Martinez, Anastasia Illarionova, Anni Moore, Bernabe I Bustos, Bharati Jadhav, Brook Huxford, Catherine Storm, Clodagh Towns, Dan Vitale, Devina Chetty, Eric Yu, Francis P Grenn, Gabriela Salazar, Geoffrey Rateau, Hirotaka Iwaki, Inas Elsayed, Isabelle Francesca Foote, Zuné Jansen Van Rensburg, Jonggeol Jeff Kim, Jie Yuan, Julie Lake, Kajsa Brolin, Konstantin Senkevich, Lesley Wu, Manuela M X Tan, María Teresa Periñán, Mary B Makarious, Michael Ta, Nikita Simone Pillay, Oswaldo Lorenzo Betancor, Paula R Reyes-Pérez, Pilar Alvarez Jerez, Prabhjyot Saini, Rami Al-Ouran, Ramiya Sivakumar, Raquel Real, Regina H Reynolds, Ruifneg Hu, Shameemah Abrahams, Shilpa C Rao, Tarek Antar, Thiago Peixoto Leal, Vassilena Iankova, William J Scotton, Yeajin Song, Andrew Singleton, Mike A Nalls, Sumit Dey, Sara Bandres-Ciga, Cornelis Blauwendraat, Alastair J Noyce, The International Parkinson Disease Genomics Consortium (Ipdgc) And The Global Parkinson’S Genetics Program (Gp2)

Faculty, Staff and Students Publications

Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of …

Consensus Recommendations For The Use Of Automated Insulin Delivery Technologies In Clinical Practice, Moshe Phillip, Revital Nimri, Richard M Bergenstal, Katharine Barnard-Kelly, Thomas Danne, Roman Hovorka, Boris P Kovatchev, Laurel H Messer, Christopher G Parkin, Louise Ambler-Osborn, Stephanie A Amiel, Lia Bally, Roy W Beck, Sarah Biester, Torben Biester, Julia E Blanchette, Emanuele Bosi, Charlotte K Boughton, Marc D Breton, Sue A Brown, Bruce A Buckingham, Albert Cai, Anders L Carlson, Jessica R Castle, Pratik Choudhary, Kelly L Close, Claudio Cobelli, Amy B Criego, Elizabeth Davis, Carine De Beaufort, Martin I De Bock, Daniel J Desalvo, J Hans Devries, Klemen Dovc, Francis J Doyle, Laya Ekhlaspour, Naama Fisch Shvalb, Gregory P Forlenza, Geraldine Gallen, Satish K Garg, Dana C Gershenoff, Linda A Gonder-Frederick, Ahmad Haidar, Sara Hartnell, Lutz Heinemann, Simon Heller, Irl B Hirsch, Korey K Hood, Diana Isaacs, David C Klonoff, Olga Kordonouri, Aaron Kowalski, Lori Laffel, Julia Lawton, Rayhan A Lal, Lalantha Leelarathna, David M Maahs, Helen R Murphy, Kirsten Nørgaard, David O'Neal, Sean Oser, Tamara Oser, Eric Renard, Michael C Riddell, David Rodbard, Steven J Russell, Desmond A Schatz, Viral N Shah, Jennifer L Sherr, Gregg D Simonson, R Paul Wadwa, Candice Ward, Stuart A Weinzimer, Emma G Wilmot, Tadej Battelino

Faculty, Staff and Students Publications

The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems …

Srtsim: Spatial Pattern Preserving Simulations For Spatially Resolved Transcriptomics, Jiaqiang Zhu, Lulu Shang, Xiang Zhou

Faculty, Staff and Student Publications

Spatially resolved transcriptomics (SRT)-specific computational methods are often developed, tested, validated, and evaluated in silico using simulated data. Unfortunately, existing simulated SRT data are often poorly documented, hard to reproduce, or unrealistic. Single-cell simulators are not directly applicable for SRT simulation as they cannot incorporate spatial information. We present SRTsim, an SRT-specific simulator for scalable, reproducible, and realistic SRT simulations. SRTsim not only maintains various expression characteristics of SRT data but also preserves spatial patterns. We illustrate the benefits of SRTsim in benchmarking methods for spatial clustering, spatial expression pattern detection, and cell-cell communication identification.

Maize/Peanut Intercropping Has Greater Synergistic Effects And Home-Field Advantages Than Maize/Soybean On Straw Decomposition, Surigaoge Surigaoge, Hao Yang, Ye Su, Yu-He Du, Su-Xian Ren, Dario Fornara, Peter Christie, Wei-Ping Zhang, Long Li

Faculty, Staff and Student Publications

INTRODUCTION: The decomposition of plant litter mass is responsible for substantial carbon fluxes and remains a key process regulating nutrient cycling in natural and managed ecosystems. Litter decomposition has been addressed in agricultural monoculture systems, but not in intercropping systems, which produce species-diverse litter mass mixtures. The aim here is to quantify how straw type, the soil environment and their combined effects may influence straw decomposition in widely practiced maize/legume intercropping systems.

METHODS: Three decomposition experiments were conducted over 341 days within a long-term intercropping field experiment which included two nitrogen (N) addition levels (i.e. no-N and N-addition) and five …

Umbilical Cord Blood Transplantation: Connecting Its Origin To Its Future, Gabriela Sanchez-Petitto, Katayoun Rezvani, May Daher, Hind Rafei, Partow Kebriaei, Elizabeth J Shpall, Amanda Olson

Faculty, Staff and Student Publications

Transplantation of umbilical cord blood (UCB) is an attractive alternative source of hematopoietic stem cells (HSCs). The unique properties of cord blood and its distinct immune tolerance and engraftment kinetics compared to bone marrow (BM) and peripheral blood progenitor cells, permit a wider disparity in human leukocyte antigen levels between a cord blood donor and recipient after an unrelated umbilical cord blood transplant (UCBT). In addition, it is readily available and has a lowered risk of graft-versus-host disease (GvHD), with similar long-term clinical outcomes, compared to BM transplants. However, the relatively low number of cells administered by UCB units, as …

Results Of Duet: A Web-Based Weight Loss Randomized Controlled Feasibility Trial Among Cancer Survivors And Their Chosen Partners, Wendy Demark-Wahnefried, Robert A Oster, Tracy E Crane, Laura Q Rogers, W Walker Cole, Harleen Kaur, David Farrell, Kelsey B Parrish, Hoda J Badr, Kathleen Y Wolin, Dori W Pekmezi

Faculty, Staff and Students Publications

Simple Summary

Effective and scalable diet, exercise, and weight management interventions are needed for primary cancer prevention in the general public, as well as for cancer control and tertiary prevention among the growing population of cancer survivors. A 6-month online intervention, entitled “Daughters, dUdes, mothErs, and others Together” (DUET), was designed to promote weight loss, a healthful diet, and increased physical activity among cancer survivors and their chosen partners. Fifty-six cancer survivor-partner dyads (n = 112 participants in total) were recruited into a randomized controlled trial that compared DUET to a waitlist control. The trial surpassed all feasibility endpoints …

Combining Targeted Dna Repair Inhibition And Immune-Oncology Approaches For Enhanced Tumor Control, Kyle Concannon, Benjamin B Morris, Carl M Gay, Lauren A Byers

Faculty, Staff and Student Publications

Targeted therapy and immunotherapy have revolutionized cancer treatment. However, the ability of cancer to evade the immune system remains a major barrier for effective treatment. Related to this, several targeted DNA-damage response inhibitors (DDRis) are being tested in the clinic and have been shown to potentiate anti-tumor immune responses. Seminal studies have shown that these agents are highly effective in a pan-cancer class of tumors with genetic defects in key DNA repair genes such as BRCA1/2, BRCA-related genes, ataxia telangiectasia mutated (ATM), and others. Here, we review the molecular consequences of targeted DDR inhibition, from tumor cell death to increased …

Non-Invasive Neuromodulation Methods To Alleviate Symptoms Of Huntington's Disease: A Systematic Review Of The Literature, Lijin Jose, Lais Bhering Martins, Thiago M Cordeiro, Keya Lee, Alexandre Paim Diaz, Hyochol Ahn, Antonio L Teixeira

Faculty, Staff and Student Publications

Huntington's disease (HD) is a progressive and debilitating neurodegenerative disease. There is growing evidence for non-invasive neuromodulation tools as therapeutic strategies in neurodegenerative diseases. This systematic review aims to investigate the effectiveness of noninvasive neuromodulation in HD-associated motor, cognitive, and behavioral symptoms. A comprehensive literature search was conducted in Ovid MEDLINE, Cochrane Central Register of Clinical Trials, Embase, and PsycINFO from inception to 13 July 2021. Case reports, case series, and clinical trials were included while screening/diagnostic tests involving non-invasive neuromodulation, review papers, experimental studies on animal models, other systematic reviews, and meta-analyses were excluded. We have identified 19 studies …

Neoadjuvant-Adjuvant Or Adjuvant-Only Pembrolizumab In Advanced Melanoma, Sapna P Patel, Megan Othus, Yuanbin Chen, G Paul Wright, Kathleen J Yost, John R Hyngstrom, Siwen Hu-Lieskovan, Christopher D Lao, Leslie A Fecher, Thach-Giao Truong, Jennifer L Eisenstein, Sunandana Chandra, Jeffrey A Sosman, Kari L Kendra, Richard C Wu, Craig E Devoe, Gary B Deutsch, Aparna Hegde, Maya Khalil, Ankit Mangla, Amy M Reese, Merrick I Ross, Andrew S Poklepovic, Giao Q Phan, Adedayo A Onitilo, Demet G Yasar, Benjamin C Powers, Gary C Doolittle, Gino K In, Niels Kokot, Geoffrey T Gibney, Michael B Atkins, Montaser Shaheen, James A Warneke, Alexandra Ikeguchi, Jose E Najera, Bartosz Chmielowski, Joseph G Crompton, Justin D Floyd, Eddy Hsueh, Kim A Margolin, Warren A Chow, Kenneth F Grossmann, Eliana Dietrich, Victor G Prieto, Michael C Lowe, Elizabeth I Buchbinder, John M Kirkwood, Larissa Korde, James Moon, Elad Sharon, Vernon K Sondak, Antoni Ribas

Faculty, Staff and Student Publications

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown.

METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year …

Association Of Qaca/B And Smr Carriage With Staphylococcus Aureus Survival Following Exposure To Antiseptics In An Ex Vivo Venous Catheter Disinfection Model, J Chase Mcneil, Lauren M Sommer, Jesus G Vallejo, Kristina G Hulten, Sheldon L Kaplan

Faculty, Staff and Students Publications

Many health care centers have reported an association between Staphylococcus aureus isolates bearing efflux pump genes and an elevated MIC/minimal bactericidal concentration (MBC) to chlorhexidine gluconate (CHG) and other antiseptics. The significance of these organisms is uncertain, given that their MIC/MBC is typically far lower than the CHG concentration in most commercial preparations. We sought to evaluate the relationship between carriage of the efflux pump genes qacA/B and smr in S. aureus and the efficacy of CHG-based antisepsis in a venous catheter disinfection model. S. aureus isolates with and without smr and/or qacA/B were utilized. The CHG MICs were determined. …

Epigenetic-Metabolic Interplay In The Dna Damage Response And Therapeutic Resistance Of Breast Cancer, Chandrima Das, Swagata Adhikari, Apoorva Bhattacharya, Sanjukta Chakraborty, Payel Mondal, Shalini S Yadav, Santanu Adhikary, Clayton R Hunt, Kamlesh K Yadav, Shruti Pandita, Siddhartha Roy, John A Tainer, Zamal Ahmed, Tej K Pandita

Faculty, Staff and Student Publications

Therapy resistance is imposing a daunting challenge on effective clinical management of breast cancer. Although the development of resistance to drugs is multifaceted, reprogramming of energy metabolism pathways is emerging as a central but heterogenous regulator of this therapeutic challenge. Metabolic heterogeneity in cancer cells is intricately associated with alterations of different signaling networks and activation of DNA damage response pathways. Here we consider how the dynamic metabolic milieu of cancer cells regulates their DNA damage repair ability to ultimately contribute to development of therapy resistance. Diverse epigenetic regulators are crucial in remodeling the metabolic landscape of cancer. This epigenetic-metabolic …

Taking A Load Off: User Perceptions Of Smart Offloading Walkers For Diabetic Foot Ulcers Using The Technology Acceptance Model, M G Finco, Gozde Cay, Myeounggon Lee, Jason Garcia, Elia Salazar, Tze-Woei Tan, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

People with diabetic foot ulcers (DFUs) are commonly prescribed offloading walkers, but inadequate adherence to prescribed use can be a barrier to ulcer healing. This study examined user perspectives of offloading walkers to provide insight on ways to help promote adherence. Participants were randomized to wear: (1) irremovable, (2) removable, or (3) smart removable walkers (smart boot) that provided feedback on adherence and daily walking. Participants completed a 15-item questionnaire based on the Technology Acceptance Model (TAM). Spearman correlations assessed associations between TAM ratings with participant characteristics. Chi-squared tests compared TAM ratings between ethnicities, as well as 12-month retrospective fall …

Adenoviral Gene Therapy For Bladder Cancer, Roland W Herzog, Masataka Suzuki

Faculty, Staff and Students Publications

Enhanced by polyamide surfactant Syn3, intravesical administration of rAd-IFNα2b results in transduction of the virus into the bladder epithelium, resulting in the synthesis and expression of local IFNα2b cytokine. Upon secretion, IFNα2b binds to the IFNα receptor on bladder cancer and other cells, resulting in signaling via the JAK-STAT pathway. A plethora of induced IFN-stimulated genes containing IFN-sensitive response elements that contribute to activation of pathways restrict cancer growth.

Hyperoxia Disrupts Lung Lymphatic Homeostasis In Neonatal Mice, Nithyapriya Shankar, Shyam Thapa, Amrit Kumar Shrestha, Poonam Sarkar, M Waleed Gaber, Roberto Barrios, Binoy Shivanna

Faculty, Staff and Students Publications

Inflammation causes bronchopulmonary dysplasia (BPD), a common lung disease of preterm infants. One reason this disease lacks specific therapies is the paucity of information on the mechanisms regulating inflammation in developing lungs. We address this gap by characterizing the lymphatic phenotype in an experimental BPD model because lymphatics are major regulators of immune homeostasis. We hypothesized that hyperoxia (HO), a major risk factor for experimental and human BPD, disrupts lymphatic endothelial homeostasis using neonatal mice and human dermal lymphatic endothelial cells (HDLECs). Exposure to 70% O2 for 24–72 h decreased the expression of prospero homeobox 1 (Prox1) and …

Effects Of Protein-Coding Variants On Blood Metabolite Measurements And Clinical Biomarkers In The Uk Biobank, Abhishek Nag, Ryan S Dhindsa, Lawrence Middleton, Xiao Jiang, Dimitrios Vitsios, Eleanor Wigmore, Erik L Allman, Anna Reznichenko, Keren Carss, Katherine R Smith, Quanli Wang, Benjamin Challis, Dirk S Paul, Andrew R Harper, Slavé Petrovski

Faculty, Staff and Students Publications

Genome-wide association studies (GWASs) have established the contribution of common and low-frequency variants to metabolic blood measurements in the UK Biobank (UKB). To complement existing GWAS findings, we assessed the contribution of rare protein-coding variants in relation to 355 metabolic blood measurements-including 325 predominantly lipid-related nuclear magnetic resonance (NMR)-derived blood metabolite measurements (Nightingale Health Plc) and 30 clinical blood biomarkers-using 412,393 exome sequences from four genetically diverse ancestries in the UKB. Gene-level collapsing analyses were conducted to evaluate a diverse range of rare-variant architectures for the metabolic blood measurements. Altogether, we identified significant associations (p < 1 × 10

Integrating Palliative Care In A Family Nurse Practitioner Curricula - Post Survey Data, Betty Lang, Susan Montgomery, Ellen P. Moore, Amanda Townsend

MSN Project Data

There is a growing need to integrate Palliative Care in Family Nurse Practitioner (FNP) curricula. Due to increasing costs in an already overstretched healthcare system, a large portion of primary care is delivered by FNPs, often to older or sicker patients. Therefore, it is imperative that FNPs receive formal educational and professional preparation regarding palliative care resources. One of the Core concepts presented by The American Association of Colleges of Nursing's Essentials: Core Concepts for Professional Nursing Education (2021) is palliative care, as are hospice and supportive care. Graduate Competencies and Recommendations for Educating nursing Students (G-CARES) further describe advanced-level …

Gibbon Surgical Review, Volume 6, Issue 1, 2023

Gibbon Surgical Review

Table of Contents

6 - Dr. Thomas Mütter’s Legacy: The Mütter Museum

8 - The History and Progression of Laparoscopic Surgery

10 - An Interview with Dr. Andrew Morgan

12 - A Surgical Perspective of the Effects of the COVID-19 Pandemic on Healthcare

14 - An Interview with Dr. Deviney Rattigan

16 - The Importance of Mentorship in Improving the Outlook and Perception of General Surgery Among Medical Students

18 - Surgical Fellow Spotlight: An Interview with Dr. Steve Gurien

20 - Point of Care Ultrasound in General Surgery Training

22 - Surgical Resident Spotlight: An Interview with Hamza Rshaidat …

Mitochondrial Structure And Function Adaptation In Residual Triple Negative Breast Cancer Cells Surviving Chemotherapy Treatment, Mokryun L Baek, Junegoo Lee, Katherine E Pendleton, Mariah J Berner, Emily B Goff, Lin Tan, Sara A Martinez, Iqbal Mahmud, Tao Wang, Matthew D Meyer, Bora Lim, James P Barrish, Weston Porter, Philip L Lorenzi, Gloria V Echeverria

Faculty, Staff and Student Publications

Neoadjuvant chemotherapy (NACT) used for triple negative breast cancer (TNBC) eradicates tumors in ~45% of patients. Unfortunately, TNBC patients with substantial residual cancer burden have poor metastasis free and overall survival rates. We previously demonstrated mitochondrial oxidative phosphorylation (OXPHOS) was elevated and was a unique therapeutic dependency of residual TNBC cells surviving NACT. We sought to investigate the mechanism underlying this enhanced reliance on mitochondrial metabolism. Mitochondria are morphologically plastic organelles that cycle between fission and fusion to maintain mitochondrial integrity and metabolic homeostasis. The functional impact of mitochondrial structure on metabolic output is highly context dependent. Several chemotherapy agents …

Approaches For Optimizing Venous Thromboembolism Prevention In Injured Patients: Findings From The Consensus Conference To Implement Optimal Venous Thromboembolism Prophylaxis In Trauma, Amanda L Teichman, Bryan A Cotton, James Byrne, Navpreet K Dhillon, Allison E Berndtson, Michelle A Price, Tracy J Johns, Eric J Ley, Todd Costantini, Elliott R Haut

Faculty, Staff and Student Publications

Venous thromboembolism (VTE) is a major issue in trauma patients. Without prophylaxis, the rate of deep venous thrombosis approaches 60% and even with chemoprophylaxis may be nearly 30%. Advances in VTE reduction are imperative to reduce the burden of this issue in the trauma population. Novel approaches in VTE prevention may include new medications, dosing regimens, and extending prophylaxis to the postdischarge phase of care. Standard dosing regimens of low-molecular-weight heparin are insufficient in trauma, shifting our focus toward alternative dosing strategies to improve prophylaxis. Mixed data suggest that anti-Xa-guided dosage, weight-based dosing, and thromboelastography are among these potential strategies. …

Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei

Markey Cancer Center Faculty Publications

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation–reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the …

Macrophage-Derived Mlkl In Alcohol-Associated Liver Disease: Regulation Of Phagocytosis, Xiaoqin Wu, Xiude Fan, Megan R Mcmullen, Tatsunori Miyata, Adam Kim, Vai Pathak, Jianguo Wu, Le Z Day, Josiah E Hardesty, Nicole Welch, Jaividhya Dasarathy, Daniela S Allende, Arthur J Mccullough, Jon M Jacobs, Daniel M Rotroff, Srinivasan Dasarathy, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays a role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury in alcohol-associated liver disease (ALD). Although receptor interacting protein kinase 3 (Rip3)-/- mice are completely protected from ethanol-induced liver injury, Mlkl-/- mice are only partially protected. Therefore, we hypothesized that cell-specific functions of MLKL may contribute to ethanol-induced injury.

APPROACH AND RESULTS: Bone marrow transplants between Mlkl-/- mice and littermates were conducted to distinguish the role of myeloid versus nonmyeloid Mlkl in the Gao-binge model of ALD. Ethanol-induced …

A Potent And Broad Neutralization Of Sars-Cov-2 Variants Of Concern By Darpins, Vikas Chonira, Young D Kwon, Jason Gorman, James Brett Case, Zhiqiang Ku, Rudo Simeon, Ryan G Casner, Darcy R Harris, Adam S Olia, Tyler Stephens, Lawrence Shapiro, Michael F Bender, Hannah Boyd, I-Ting Teng, Yaroslav Tsybovsky, Florian Krammer, Ningyan Zhang, Michael S Diamond, Peter D Kwong, Zhiqiang An, Zhilei Chen

Faculty, Staff and Student Publications

We report the engineering and selection of two synthetic proteins-FSR16m and FSR22-for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and FSR22 are trimeric proteins composed of DARPin SR16m or SR22 fused with a T4 foldon. Despite selection by a spike protein from a now historical SARS-CoV-2 strain, FSR16m and FSR22 exhibit broad-spectrum neutralization of SARS-CoV-2 strains, inhibiting authentic B.1.351, B.1.617.2 and BA.1.1 viruses, with respective IC

Neoadjuvant Chemotherapy Plus Nivolumab With Or Without Ipilimumab In Operable Non-Small Cell Lung Cancer: The Phase 2 Platform Neostar Trial, Tina Cascone, Cheuk H Leung, Annikka Weissferdt, Apar Pataer, Brett W Carter, Myrna C B Godoy, Hope Feldman, William N William, Yuanxin Xi, Sreyashi Basu, Jing Jing Sun, Shalini S Yadav, Frank R Rojas Alvarez, Younghee Lee, Aditya K Mishra, Lili Chen, Monika Pradhan, Haiping Guo, Ansam Sinjab, Nicolas Zhou, Marcelo V Negrao, Xiuning Le, Carl M Gay, Anne S Tsao, Lauren Averett Byers, Mehmet Altan, Bonnie S Glisson, Frank V Fossella, Yasir Y Elamin, George Blumenschein, Jianjun Zhang, Ferdinandos Skoulidis, Jia Wu, Reza J Mehran, David C Rice, Garrett L Walsh, Wayne L Hofstetter, Ravi Rajaram, Mara B Antonoff, Junya Fujimoto, Luisa M Solis, Edwin R Parra, Cara Haymaker, Ignacio I Wistuba, Stephen G Swisher, Ara A Vaporciyan, Heather Y Lin, Jing Wang, Don L Gibbons, J Jack Lee, Nadim J Ajami, Jennifer A Wargo, James P Allison, Padmanee Sharma, Humam Kadara, John V Heymach, Boris Sepesi

Faculty, Staff and Student Publications

Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6–61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. …