Medical Sciences Commons^™

Microbiome Influencers Of Checkpoint Blockade-Associated Toxicity, Yinghong Wang, Robert R Jenq, Jennifer A Wargo, Stephanie S Watowich

Faculty, Staff and Student Publications

Immunotherapy has greatly improved cancer outcomes, yet variability in response and off-target tissue damage can occur with these treatments, including immune checkpoint inhibitors (ICIs). Multiple lines of evidence indicate the host microbiome influences ICI response and risk of immune-related adverse events (irAEs). As the microbiome is modifiable, these advances indicate the potential to manipulate microbiome components to increase ICI success. We discuss microbiome features associated with ICI response, with focus on bacterial taxa and potential immune mechanisms involved in irAEs, and the overall goal of driving novel approaches to manipulate the microbiome to improve ICI efficacy while avoiding irAE risk.

Molecularly Targeted Therapy In Acute Myeloid Leukemia: Current Treatment Landscape And Mechanisms Of Response And Resistance, Curtis A Lachowiez, Courtney D Dinardo, Sanam Loghavi

Faculty, Staff and Student Publications

Treatment for acute myeloid leukemia (AML) has evolved rapidly over the last decade as improved understanding of cytogenetic and molecular drivers of leukemogenesis refined survival prognostication and enabled development of targeted therapeutics. Molecularly targeted therapies are now approved for the treatment of FLT3 and IDH1/2-mutated AML and additional molecularly and cellularly targeted therapeutics are in development for defined patient subgroups. Alongside these welcome therapeutic advancements, increased understanding of leukemic biology and treatment resistance has resulted in clinical trials investigating combinations of cytotoxic, cellular, and molecularly targeted therapeutics resulting in improved response and survival outcomes in patients with AML. Herein, …

Immortalized B Cells Transfected With Mrna Of Antigen Fused To Mitd (Ibmam): An Effective Tool For Antigen-Specific T-Cell Expansion And Tcr Validation, Zhe Wang, Tiantian Zhang, Aaron Anderson, Vincent Lee, Szymon Szymura, Zhenyuan Dong, Benjamin Kuang, Elizabeth Oh, Jingwei Liu, Sattva S Neelapu, Larry Kwak, Soung-Chul Cha

Faculty, Staff and Student Publications

Peripheral mononuclear blood cells (PBMCs) are the most widely used study materials for immunomonitoring and antigen-specific T-cell identification. However, limited patient PBMCs and low-frequency antigen-specific T cells remain as significant technical challenges. To address these limitations, we established a novel platform comprised of optimized HLA-matched immortalized B cells transfected with mRNA of a prototype viral or tumor antigen conjugated to MHC class-I trafficking domain protein (MITD) to increase the efficiency of epitope expression in antigen-presenting cells (APCs) essential to expanding antigen-specific T cells. When applied to CMV as a model, the IBMAM platform could successfully expand CMV-specific T cells from …

Phenotypic Plasticity In Circulating Tumor Cells Is Associated With Poor Response To Therapy In Metastatic Breast Cancer Patients, Evan N Cohen, Gitanjali Jayachandran, Hui Gao, Phillip Peabody, Heather B Mcbride, Franklin D Alvarez, Megumi Kai, Juhee Song, Yu Shen, Jie S Willey, Bora Lim, Vicente Valero, Naoto T Ueno, James M Reuben

Faculty, Staff and Student Publications

Circulating tumor cells (CTCs) are indicators of metastatic spread and progression. In a longitudinal, single-center trial of patients with metastatic breast cancer starting a new line of treatment, a microcavity array was used to enrich CTCs from 184 patients at up to 9 timepoints at 3-month intervals. CTCs were analyzed in parallel samples from the same blood draw by imaging and by gene expression profiling to capture CTC phenotypic plasticity. Enumeration of CTCs by image analysis relying primarily on epithelial markers from samples obtained before therapy or at 3-month follow-up identified the patients at the highest risk of progression. CTC …

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 …

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 …

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 …

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 …

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; …

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 …

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 …

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.

Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism., Archana Kumari, Charlotte M. Mistretta

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sensory receptors across the entire tongue are engaged during eating. However, the tongue has distinctive regions with taste (fungiform and circumvallate) and non-taste (filiform) organs that are composed of specialized epithelia, connective tissues, and innervation. The tissue regions and papillae are adapted in form and function for taste and somatosensation associated with eating. It follows that homeostasis and regeneration of distinctive papillae and taste buds with particular functional roles require tailored molecular pathways. Nonetheless, in the chemosensory field, generalizations are often made between mechanisms that regulate anterior tongue fungiform and posterior circumvallate taste papillae, without a clear distinction that highlights …

Altogether Now! Early Introduction Of Case-Based Learning For Success In Clinical Chemistry, Cristy E. Moss

Faculty Publications

•Differentiate between active & passive learning. •Identify ways early integration of case-based learning is beneficial for the medical laboratory student. •Summarize current methods for Integration of case-based activities into routine lecture / discussion sessions with students.

Prevalence And Management Of Sleep Disturbance In Adults With Primary Brain Tumours And Their Caregivers: A Systematic Review, Jason A. Martin, Nicolas H. Hart, Natalie Bradford, Fiona Naumann, Mark B. Pinkham, Elizabeth P. Pinkham, Justin J. Holland

Research outputs 2022 to 2026

Purpose: The aims of this systematic review were to (1) examine the prevalence, severity, manifestations, and clinical associations/risk factors of sleep disturbance in primary brain tumour (PBT) survivors and their caregivers; and (2) determine whether there are any sleep-focused interventons reported in the literature pertaining to people affected by PBT. Methods: This systematic review was registered with the international register for systematic reviews (PROSPERO: CRD42022299332). PubMed, EMBASE, Scopus, PsychINFO, and CINAHL were electronically searched for relevant articles reporting sleep disturbance and/or interventions for managing sleep disturbance published between September 2015 and May 2022. The search strategy included terms focusing on …

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 …

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.

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. …

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 …

Bi-Allelic Tti1 Variants Cause An Autosomal-Recessive Neurodevelopmental Disorder With Microcephaly, Margaux Serey-Gaut, Marisol Cortes, Periklis Makrythanasis, Mohnish Suri, Alexander M R Taylor, Jennifer A Sullivan, Ayat N Asleh, Jaba Mitra, Mohamad A Dar, Amy Mcnamara, Vandana Shashi, Sarah Dugan, Xiaofei Song, Jill A Rosenfeld, Christelle Cabrol, Justyna Iwaszkiewicz, Vincent Zoete, Davut Pehlivan, Zeynep Coban Akdemir, Elizabeth R Roeder, Rebecca Okashah Littlejohn, Harpreet K Dibra, Philip J Byrd, Grant S Stewart, Bilgen B Geckinli, Jennifer Posey, Rachel Westman, Chelsy Jungbluth, Jacqueline Eason, Rani Sachdev, Carey-Anne Evans, Gabrielle Lemire, Grace E Vannoy, Anne O'Donnell-Luria, Frédéric Tran Mau-Them, Aurélien Juven, Juliette Piard, Cheng Yee Nixon, Ying Zhu, Taekjip Ha, Michael F Buckley, Christel Thauvin, George K Essien Umanah, Lionel Van Maldergem, James R Lupski, Tony Roscioli, Valina L Dawson, Ted M Dawson, Stylianos E Antonarakis

Faculty, Staff and Student Publications

Telomere maintenance 2 (TELO2), Tel2 interacting protein 2 (TTI2), and Tel2 interacting protein 1 (TTI1) are the three components of the conserved Triple T (TTT) complex that modulates activity of phosphatidylinositol 3-kinase-related protein kinases (PIKKs), including mTOR, ATM, and ATR, by regulating the assembly of mTOR complex 1 (mTORC1). The TTT complex is essential for the expression, maturation, and stability of ATM and ATR in response to DNA damage. TELO2- and TTI2-related bi-allelic autosomal-recessive (AR) encephalopathies have been described in individuals with moderate to severe intellectual disability (ID), short stature, postnatal microcephaly, and a movement disorder (in the case of …

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 …

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 …

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 …

Immediate Implant Placement Simultaneously With Ridge Augmentation In The Maxillary Esthetic Region Using Allograft Bone Ring Versus Titanium Mesh Guided Bone Regeneration, Omar M. Khamayseh, Nesma M. Elgohary, Fakhreldin H. Abdel-Rahman, Wael M. Said Ahmed

Mansoura Journal of Dentistry

Objective: The present study aimed to assess ridge augmentation with an allograft bone ring versus GBR with titaniummesh, and immediate implant placement (IIP) in the maxillary esthetic zone. Materials and Methods: The 12 patientswith 14 defective sockets were randomly divided into two groups: three females and four males in the control group(Titanium mesh-GBR), and three females and two males in the study group (Allograft bone ring). Patients had postoperativeclinical examinations each day for the first week, then once a month for the next six months. Results: : At 6months post-surgery, all cases in the control group healed well and showed …

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 …