Medical Specialties Commons^™

Effect Of Medicaid Expansion On Cancer Treatment And Survival Among Medicaid Beneficiaries And The Uninsured, Kristin M Primm, Hui Zhao, Naomi N Adjei, Charlotte C Sun, Alen Haas, Larissa A Meyer, Shine Chang

Faculty, Staff and Student Publications

BACKGROUND: The Affordable Care Act expanded Medicaid coverage for people with low income in the United States. Expanded insurance coverage could promote more timely access to cancer treatment, which could improve overall survival (OS), yet the long-term effects of Medicaid expansion (ME) remain unknown. We evaluated whether ME was associated with improved timely treatment initiation (TTI) and 3-year OS among patients with breast, cervical, colon, and lung cancers who were affected by the policy.

METHODS: Medicaid-insured or uninsured patients aged 40-64 with stage I-III breast, cervical, colon, or non-small cell lung cancer within the National Cancer Database (NCDB). A difference-in-differences …

Identification Of Immune-Associated Biomarkers Of Diabetes Nephropathy Tubulointerstitial Injury Based On Machine Learning: A Bioinformatics Multi-Chip Integrated Analysis, Lin Wang, Jiaming Su, Zhongjie Liu, Shaowei Ding, Yaotan Li, Baoluo Hou, Yuxin Hu, Zhaoxi Dong, Jingyi Tang, Hongfang Liu, Weijing Liu

Faculty, Staff and Student Publications

BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN.

METHODS: The …

A Deep Catalogue Of Protein-Coding Variation In 983,578 Individuals, Kathie Y Sun, Xiaodong Bai, Siying Chen, Suying Bao, Chuanyi Zhang, Manav Kapoor, Joshua Backman, Tyler Joseph, Evan Maxwell, George Mitra, Alexander Gorovits, Adam Mansfield, Boris Boutkov, Sujit Gokhale, Lukas Habegger, Anthony Marcketta, Adam E Locke, Liron Ganel, Alicia Hawes, Michael D Kessler, Deepika Sharma, Jeffrey Staples, Jonas Bovijn, Sahar Gelfman, Alessandro Di Gioia, Veera M Rajagopal, Alexander Lopez, Jennifer Rico Varela, Jesús Alegre-Díaz, Jaime Berumen, Roberto Tapia-Conyer, Pablo Kuri-Morales, Jason Torres, Jonathan Emberson, Rory Collins, Regeneron Genetics Center, Rgc-Me Cohort Partners; Michael Cantor, Michael Cantor, Timothy Thornton, Hyun Min Kang, John D Overton, Alan R Shuldiner, M Laura Cremona, Mona Nafde, Aris Baras, Gonçalo Abecasis, Jonathan Marchini, Jeffrey G Reid, William Salerno, Suganthi Balasubramanian

Faculty, Staff and Student Publications

Rare coding variants that substantially affect function provide insights into the biology of a gene1-3. However, ascertaining the frequency of such variants requires large sample sizes4-8. Here we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. In total, 23% of the Regeneron Genetics Center Million Exome (RGC-ME) data come from individuals of African, East Asian, Indigenous American, Middle Eastern and South Asian ancestry. The catalogue includes more than 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants. We identify individuals with rare biallelic pLOF variants in 4,848 genes, 1,751 of …

Targeting Of Cyp2e1 By Mirnas In Alcohol-Induced Intestine Injury, Hyejin Mun, Sungyul Lee, Suyoung Choi, Ji-Hoon Jeong, Seungbeom Ko, Yoo Lim Chun, Benjamin Deaton, Clay T Yeager, Audrey Boyette, Juliana Palmera, London Newman, Ping Zhou, Soona Shin, Dong-Chan Kim, Cari A Sagum, Mark T Bedford, Young-Kook Kim, Jaeyul Kwon, Junyang Jung, Jeong Ho Chang, Je-Hyun Yoon

Faculty, Staff and Student Publications

Although binge alcohol-induced gut leakage has been studied extensively in the context of reactive oxygen species-mediated signaling, it was recently revealed that post-transcriptional regulation plays an essential role as well. Ethanol (EtOH)-inducible cytochrome P450-2E1 (CYP2E1), a key enzyme in EtOH metabolism, promotes alcohol-induced hepatic steatosis and inflammatory liver disease, at least in part by mediating changes in intestinal permeability. For instance, gut leakage and elevated intestinal permeability to endotoxins have been shown to be regulated by enhancing CYP2E1 mRNA and CYP2E1 protein levels. Although it is understood that EtOH promotes CYP2E1 induction and activation, the mechanisms that regulate CYP2E1 expression …

Change In Trust In Us Government Health Agencies For Cancer Information In The Covid-19 Era, Onyema G Chido-Amajuoyi, Rajesh Talluri, Henry K Onyeaka, Itunu Sokale, Gideon T Dosunmu, Noelle Loconte, Sanjay Shete

Faculty, Staff and Student Publications

This cross-sectional study assesses changes in levels of public trust in US government health agencies providing cancer information.

Machine Learning Identifies Prognostic Subtypes Of The Tumor Microenvironment Of Nsclc, Duo Yu, Michael J Kane, Eugene J Koay, Ignacio I Wistuba, Brian P Hobbs

Faculty, Staff and Student Publications

The tumor microenvironment (TME) plays a fundamental role in tumorigenesis, tumor progression, and anti-cancer immunity potential of emerging cancer therapeutics. Understanding inter-patient TME heterogeneity, however, remains a challenge to efficient drug development. This article applies recent advances in machine learning (ML) for survival analysis to a retrospective study of NSCLC patients who received definitive surgical resection and immune pathology following surgery. ML methods are compared for their effectiveness in identifying prognostic subtypes. Six survival models, including Cox regression and five survival machine learning methods, were calibrated and applied to predict survival for NSCLC patients based on PD-L1 expression, CD3 expression, …

Mutation Order In Acute Myeloid Leukemia Identifies Uncommon Patterns Of Evolution And Illuminates Phenotypic Heterogeneity, Matthew Schwede, Katharina Jahn, Jack Kuipers, Linde A Miles, Robert L Bowman, Troy Robinson, Ken Furudate, Hidetaka Uryu, Tomoyuki Tanaka, Yuya Sasaki, Asiri Ediriwickrema, Brooks Benard, Andrew J Gentles, Ross Levine, Niko Beerenwinkel, Koichi Takahashi, Ravindra Majeti

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) has a poor prognosis and a heterogeneous mutation landscape. Although common mutations are well-studied, little research has characterized how the sequence of mutations relates to clinical features. Using published, single-cell DNA sequencing data from three institutions, we compared clonal evolution patterns in AML to patient characteristics, disease phenotype, and outcomes. Mutation trees, which represent the order of select mutations, were created for 207 patients from targeted panel sequencing data using 1 639 162 cells, 823 mutations, and 275 samples. In 224 distinct orderings of mutated genes, mutations related to DNA methylation typically preceded those related to …

Epigenetic Regulation Of Heart Failure, Manisha Deogharia, Priyatansh Gurha

Faculty, Staff and Student Publications

Purpose of review: The studies on chromatin-modifying enzymes and how they respond to different stimuli within the cell have revolutionized our understanding of epigenetics. In this review, we provide an overview of the recent studies on epigenetic mechanisms implicated in heart failure.

Recent findings: We focus on the major mechanisms and the conceptual advances in epigenetics as evidenced by studies in humans and mouse models of heart failure. The significance of epigenetic modifications and the enzymes that catalyze them is also discussed. New findings from the studies of histone lysine demethylases demonstrate their significance in regulating fetal gene expression, as …

Provider Experiences With Daily Use Of Elastomeric Half-Mask Respirators In Health Care, Morgan Lane, Lisa Pompeii, Janelle Rios, Elisa Benavides, Marie Kasbaum, Scott Patlovich, Luis Ostrosky-Zeichner, Adam Hornbeck, Caitlin Mcclain, Rohan Fernando, Margaret Sietsema, Colleen Kraft

Faculty, Staff and Student Publications

Background: During public health emergencies, demand for N95 filtering facepiece respirators (N95 FFRs) can outpace supply. Elastomeric half-mask respirators (EHMRs) are a potential alternative that are reusable and provide the same or higher levels of protection. This study sought to examine the practical aspects of EHMR use among health care personnel (HCP).

Methods: Between September and December 2021, 183 HCPs at 2 tertiary referral centers participated in this 3-month EHMR deployment, wearing the EHMR whenever respiratory protection was required according to hospital protocols (ie, when an N95 FFR would typically be worn) and responding to surveys about their experience.

Results: …

Understanding The Genetic Complexity Of Puberty Timing Across The Allele Frequency Spectrum, Katherine A Kentistou, Lena R Kaisinger, Stasa Stankovic, Marc Vaudel, Edson Mendes De Oliveira, Andrea Messina, Robin G Walters, Xiaoxi Liu, Alexander S Busch, Hannes Helgason, Deborah J Thompson, Federico Santoni, Konstantin M Petricek, Yassine Zouaghi, Isabel Huang-Doran, Daniel F Gudbjartsson, Eirik Bratland, Kuang Lin, Eugene J Gardner, Yajie Zhao, Raina Y Jia, Chikashi Terao, Marjorie J Riggan, Manjeet K Bolla, Mojgan Yazdanpanah, Nahid Yazdanpanah, Jonathan P Bradfield, Linda Broer, Archie Campbell, Daniel I Chasman, Diana L Cousminer, Nora Franceschini, Lude H Franke, Giorgia Girotto, Chunyan He, Marjo-Riitta Järvelin, Peter K Joshi, Yoichiro Kamatani, Robert Karlsson, Jian'an Luan, Kathryn L Lunetta, Reedik Mägi, Massimo Mangino, Sarah E Medland, Christa Meisinger, Raymond Noordam, Teresa Nutile, Maria Pina Concas, Ozren Polašek, Eleonora Porcu, Susan M Ring, Cinzia Sala, Albert V Smith, Toshiko Tanaka, Peter J Van Der Most, Veronique Vitart, Carol A Wang, Gonneke Willemsen, Marek Zygmunt, Thomas U Ahearn, Irene L Andrulis, Hoda Anton-Culver, Antonis C Antoniou, Paul L Auer, Catriona L K Barnes, Matthias W Beckmann, Amy Berrington De Gonzalez, Natalia V Bogdanova, Stig E Bojesen, Hermann Brenner, Julie E Buring, Federico Canzian, Jenny Chang-Claude, Fergus J Couch, Angela Cox, Laura Crisponi, Kamila Czene, Mary B Daly, Ellen W Demerath, Joe Dennis, Peter Devilee, Immaculata De Vivo, Thilo Dörk, Alison M Dunning, Miriam Dwek, Johan G Eriksson, Peter A Fasching, Lindsay Fernandez-Rhodes, Liana Ferreli, Olivia Fletcher, Manuela Gago-Dominguez, Montserrat García-Closas, José A García-Sáenz, Anna González-Neira, Harald Grallert, Pascal Guénel, Christopher A Haiman, Per Hall, Ute Hamann, Hakon Hakonarson, Roger J Hart, Martha Hickey, Maartje J Hooning, Reiner Hoppe, John L Hopper, Jouke-Jan Hottenga, Frank B Hu, Hanna Huebner, David J Hunter, Helena Jernström, Esther M John, David Karasik, Elza K Khusnutdinova, Vessela N Kristensen, James V Lacey, Diether Lambrechts, Lenore J Launer, Penelope A Lind, Annika Lindblom, Patrik K E Magnusson, Arto Mannermaa, Mark I Mccarthy, Thomas Meitinger, Cristina Menni, Kyriaki Michailidou, Iona Y Millwood, Roger L Milne, Grant W Montgomery, Heli Nevanlinna, Ilja M Nolte, Dale R Nyholt, Nadia Obi, Katie M O'Brien, Kenneth Offit, Albertine J Oldehinkel, Sisse R Ostrowski, Aarno Palotie, Ole B Pedersen, Annette Peters, Giulia Pianigiani, Dijana Plaseska-Karanfilska, Anneli Pouta, Alfred Pozarickij, Paolo Radice, Gad Rennert, Frits R Rosendaal, Daniela Ruggiero, Emmanouil Saloustros, Dale P Sandler, Sabine Schipf, Carsten O Schmidt, Marjanka K Schmidt, Kerrin Small, Beatrice Spedicati, Meir Stampfer, Jennifer Stone, Rulla M Tamimi, Lauren R Teras, Emmi Tikkanen, Constance Turman, Celine M Vachon, Qin Wang, Robert Winqvist, Alicja Wolk, Babette S Zemel, Wei Zheng, Ko W Van Dijk, Behrooz Z Alizadeh, Stefania Bandinelli, Eric Boerwinkle, Dorret I Boomsma, Marina Ciullo, Georgia Chenevix-Trench, Francesco Cucca, Tõnu Esko, Christian Gieger, Struan F A Grant, Vilmundur Gudnason, Caroline Hayward, Ivana Kolčić, Peter Kraft, Deborah A Lawlor, Nicholas G Martin, Ellen A Nøhr, Nancy L Pedersen, Craig E Pennell, Paul M Ridker, Antonietta Robino, Harold Snieder, Ulla Sovio, Tim D Spector, Doris Stöckl, Cathie Sudlow, Nic J Timpson, Daniela Toniolo, André Uitterlinden, Sheila Ulivi, Henry Völzke, Nicholas J Wareham, Elisabeth Widen, James F Wilson, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Paul D P Pharoah, Liming Li, Douglas F Easton, Pål R Njølstad, Patrick Sulem, Joanne M Murabito, Anna Murray, Despoina Manousaki, Anders Juul, Christian Erikstrup, Kari Stefansson, Momoko Horikoshi, Zhengming Chen, I Sadaf Farooqi, Nelly Pitteloud, Stefan Johansson, Felix R Day, John R B Perry, Ken K Ong

Faculty, Staff and Student Publications

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, …

High Throughput Plasma Proteomics And Risk Of Heart Failure And Frailty In Late Life, Diego Ramonfaur, Leo F Buckley, Victoria Arthur, Yimin Yang, Brian L Claggett, Chiadi E Ndumele, Keenan A Walker, Thomas Austin, Michelle C Odden, James S Floyd, Sandra Sanders-Van Wijk, Joyce Njoroge, Jorge R Kizer, Dalane Kitzman, Suma H Konety, Jennifer Schrack, Fangyu Liu, B Gwen Windham, Priya Palta, Josef Coresh, Bing Yu, Amil M Shah

Faculty, Staff and Student Publications

Importance: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions.

Objective: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics.

Design, setting, and participants: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants …

50-Nm Gas-Filled Protein Nanostructures To Enable The Access Of Lymphatic Cells By Ultrasound Technologies, Qionghua Shen, Zongru Li, Yixian Wang, Matthew D Meyer, Marc T De Guzman, Janie C Lim, Han Xiao, Richard R Bouchard, George J Lu

Faculty, Staff and Student Publications

Ultrasound imaging and ultrasound-mediated gene and drug delivery are rapidly advancing diagnostic and therapeutic methods; however, their use is often limited by the need for microbubbles, which cannot transverse many biological barriers due to their large size. Here, the authors introduce 50-nm gas-filled protein nanostructures derived from genetically engineered gas vesicles(GVs) that are referred to as

Neighborhood-Level Social Determinants Of Health Burden Among Adolescent And Young Adult Cancer Patients And Impact On Overall Survival, Elizabeth R Rodriguez, Tori Tonn, Midhat Jafry, Sairah Ahmed, Branko Cuglievan, J Andrew Livingston, Christopher R Flowers, Gregory J Aune, Karen H Albritton, Michael E Roth, Qian Xiao, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

BACKGROUND: Neighborhood socioeconomic deprivation has been linked to adverse health outcomes, yet it is unclear whether neighborhood-level social determinants of health (SDOH) measures affect overall survival in adolescent and young adult patients with cancer.

METHODS: This study used a diverse cohort of adolescent and young adult patients with cancer (N = 10 261) seen at MD Anderson Cancer Center. Zip codes were linked to Area Deprivation Index (ADI) values, a validated neighborhood-level SDOH measure, with higher ADI values representing worse SDOH.

RESULTS: ADI was statistically significantly worse (P < .050) for Black (61.7) and Hispanic (65.3) patients than for White patients (51.2). Analysis of ADI by cancer type showed statistically significant differences, mainly driven by worse ADI in patients with cervical cancer (62.3) than with other cancers. In multivariable models including sex, age at diagnosis, cancer diagnosis, and race and ethnicity, risk of shorter survival for people residing in neighborhoods with the least favorable ADI quartile was greater than for individuals in the most favorable ADI quartile (hazard ratio = 1.09, 95% confidence interval = 1.00 to 1.19, P = .043).

CONCLUSION: Adolescent and young adult patients with cancer and the worst ADI …

The Impact Of Ribosome Biogenesis In Cancer: From Proliferation To Metastasis, Nitish Mittal, Faisal S Ali, Antonio Pizuorno Machado, Sean Ngo, Malek Shatila, Tomas Davee, Nirav Thosani, Vaibhav Wadhwa

Faculty, Staff and Student Publications

A proportion of patients who undergo intraoperative cholangiogram (IOC) do not have bile duct stones at the time of endoscopic retrograde cholangiopancreatography (ERCP), either due to the spontaneous passage of stones or a false-positive IOC. Glucagon has been utilized as an inexpensive tool to allow the passage of micro-choledocholithiasis to the duodenum and resolve filling defects caused by stones or air bubbles. The purpose of our study is to understand the change in diagnostic accuracy of IOC to detect choledocholithiasis with intraoperative glucagon. We conducted a retrospective study at a tertiary care center on adult patients who underwent laparoscopic cholecystectomy …

Personal Light Exposure Patterns And Incidence Of Type 2 Diabetes: Analysis Of 13 Million Hours Of Light Sensor Data And 670,000 Person-Years Of Prospective Observation, Daniel P Windred, Angus C Burns, Martin K Rutter, Chris Ho Ching Yeung, Jacqueline M Lane, Qian Xiao, Richa Saxena, Sean W Cain, Andrew J K Phillips

Faculty, Staff and Student Publications

BACKGROUND: Light at night disrupts circadian rhythms, and circadian disruption is a risk factor for type 2 diabetes. Whether personal light exposure predicts diabetes risk has not been demonstrated in a large prospective cohort. We therefore assessed whether personal light exposure patterns predicted risk of incident type 2 diabetes in UK Biobank participants, using ∼13 million hours of light sensor data.

METHODS: Participants (N = 84,790, age (M ± SD) = 62.3 ± 7.9 years, 58% female) wore light sensors for one week, recording day and night light exposure. Circadian amplitude and phase were modeled from weekly light data. Incident …

Long-Term Immune Response To Sars-Cov-2 Infection And Vaccination In Children And Adolescents, Sarah E Messiah, Yashar Talebi, Michael D Swartz, Rachit Sabharwal, Haoting Han, Emma Bergqvist, Harold W Kohl, Melissa Valerio-Shewmaker, Stacia M Desantis, Ashraf Yaseen, Steven H Kelder, Jessica Ross, Lindsay N Padilla, Michael O Gonzalez, Leqing Wu, David Lakey, Jennifer A Shuford, Stephen J Pont, Eric Boerwinkle

Faculty, Staff and Student Publications

BACKGROUND: This analysis examined the durability of antibodies present after SARS-CoV-2 infection and vaccination in children and adolescents.

METHODS: Data were collected over 4 time points between October 2020-November 2022 as part of a prospective population-based cohort aged 5-to-19 years (N = 810). Results of the (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test); and (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test); and (3) self-reported antigen/PCR COVID-19 test results, vaccination and symptom status were analyzed.

RESULTS: N antibody levels reached a …

Association Between Participation And Satisfaction With Life Over Time In Older Adults With Traumatic Brain Injury: A Tbi Model Systems Study, Zinat Taiwo, Angelle M Sander, Shannon B Juengst, Xiangyi Liu, Luis Leon Novelo, Flora M Hammond, Therese M O'Neil-Pirozzi, Paul B Perrin, Nicholas Gut

Faculty, Staff and Student Publications

Objective: To examine the association between participation and satisfaction with life at 1, 2, 5, and 10 years after traumatic brain injury (TBI) in older adults.

Setting: Community.

Participants: Participants ( N = 2362) who sustained complicated mild to severe TBI, requiring inpatient rehabilitation, at age 60 years or older and had follow-up data on participation and satisfaction with life for at least 1 follow-up time point across 1, 2, 5, and 10 years. Age at each time period was categorized as 60 to 64 years, 65 to 75 years, and 75 years or older.

Design: Secondary data analysis of …

Evaluating Automatically Generated Normal Tissue Contours For Safe Use In Head And Neck And Cervical Cancer Treatment Planning, Raphael Douglas, Adenike Olanrewaju, Raymond Mumme, Lifei Zhang, Beth M Beadle, Laurence Edward Court

Faculty, Staff and Student Publications

Purpose: Volumetric-modulated arc therapy (VMAT) is a widely accepted treatment method for head and neck (HN) and cervical cancers; however, creating contours and plan optimization for VMAT plans is a time-consuming process. Our group has created an automated treatment planning tool, the Radiation Planning Assistant (RPA), that uses deep learning models to generate organs at risk (OARs), planning structures and automates plan optimization. This study quantitatively evaluates the quality of contours generated by the RPA tool.

Methods: For patients with HN (54) and cervical (39) cancers, we retrospectively generated autoplans using the RPA. Autoplans were generated using deep-learning and RapidPlan …

Autocontouring Of Primary Lung Lesions And Nodal Disease For Radiotherapy Based Only On Computed Tomography Images, Stephen Skett, Tina Patel, Didier Duprez, Sunnia Gupta, Tucker Netherton, Christoph Trauernicht, Sarah Aldridge, David Eaton, Carlos Cardenas, Laurence E Court, Daniel Smith, Ajay Aggarwal

Faculty, Staff and Student Publications

Background and purpose: In many clinics, positron-emission tomography is unavailable and clinician time extremely limited. Here we describe a deep-learning model for autocontouring gross disease for patients undergoing palliative radiotherapy for primary lung lesions and/or hilar/mediastinal nodal disease, based only on computed tomography (CT) images.

Materials and methods: An autocontouring model (nnU-Net) was trained to contour gross disease in 379 cases (352 training, 27 test); 11 further test cases from an external centre were also included. Anchor-point-based post-processing was applied to remove extraneous autocontoured regions. The autocontours were evaluated quantitatively in terms of volume similarity (Dice similarity coefficient [DSC], surface …

Dynamic Stem-Loop Extension By Pol Θ And Templated Insertion During Dna Repair, Denisse Carvajal-Maldonado, Yuzhen Li, Mark Returan, April M Averill, Sylvie Doublié, Richard D Wood

Faculty, Staff and Student Publications

Theta-mediated end joining (TMEJ) is critical for survival of cancer cells when other DNA double-stranded break repair pathways are impaired. Human DNA polymerase theta (Pol θ) can extend ssDNA oligonucleotides, but little is known about preferred substrates and mechanism. We show that Pol θ can extend both ssDNA and RNA substrates by unimolecular stem-loop synthesis initiated by only two 3' terminal base pairs. Given sufficient time, Pol θ uses alternative pairing configurations that greatly expand the repertoire of sequence outcomes. Further primer-template adjustments yield low-fidelity outcomes when the nucleotide pool is imbalanced. Unimolecular stem-loop synthesis competes with bimolecular end joining, …

Combination Therapy With Novel Agents For Acute Myeloid Leukaemia: Insights Into Treatment Of A Heterogenous Disease, Wei-Ying Jen, Hagop Kantarjian, Tapan M Kadia, Courtney D Dinardo, Ghayas C Issa, Nicholas J Short, Musa Yilmaz, Gautam Borthakur, Farhad Ravandi, Naval G Daver

Faculty, Staff and Student Publications

The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets or triplets with targeted or immune therapies is the focus of numerous ongoing trials. The development of mutation-targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed/refractory (RR) AML, and menin inhibitors showing efficacy in RR NPM1

Radiation Dose Attenuation Using Radpad In Cath Lab For Primary And Secondary Operators – Radar-Cath Study, Sandeepan Saha, Aditya Kapoor, Kamlesh Raut, Arpita Katheria, Harshit Khare, Ankit Sahu, Roopali Khanna, Sudeep Kumar, Naveen Garg, Satyendra Tewari

Faculty, Staff and Student Publications

BACKGROUND: Radiation injury is an important concern for interventional cardiologists and needs to be addressed. RADPAD is a radiation protection drape that has been shown to reduce the radiation exposure of the primary operator (PO). While Indian data on radiation exposure of the PO in the cath lab are scarce, the exposure of the secondary operator (SO) is even less well studied.

AIMS: The aim of this study was to evaluate the efficacy of RADPAD drapes in reducing radiation doses in the cath lab for the primary as well as the secondary operator.

METHODS: A total of 160 patients (40 …

Eus-Guided Hydrogel Injection To Separate Pancreatic Head Carcinoma From Duodenum For Enhanced Radiotherapy: Multi-Site Feasibility Study, Manoop S Bhutani, Amol K Narang, Kai Ding, Brenna Casey, Kumar Krishnan, Eugene J Koay, Theodore S Hong, Joseph M Herman, Kristen H Griffin, Eun Ji Shin

Faculty, Staff and Student Publications

Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum.

Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity.

Results …

Sequencing Of Kaposi’S Sarcoma Herpesvirus (Kshv) Genomes From Persons Of Diverse Ethnicities And Provenances With Kshv-Associated Diseases Demonstrate Multiple Infections, Novel Polymorphisms, And Low Intra-Host Variance, Vickie A Marshall, Elena M Cornejo Castro, Charles A Goodman, Nazzarena Labo, Isabella Liu, Nicholas C Fisher, Kyle N Moore, Ananthakrishnan Nair, Taina Immonen, Brandon F Keele, Mark N Polizzotto, Thomas S Uldrick, Yunxiang Mu, Tanuja Saswat, Laurie T Krug, Kevin M Mcbride, Kathryn Lurain, Ramya Ramaswami, Robert Yarchoan, Denise Whitby

Faculty, Staff and Student Publications

Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. …

Ccr2+ Monocytes Promote White Matter Injury And Cognitive Dysfunction After Myocardial Infarction, Edward B Thorp, Mallory Filipp, Maria Dima, Chunfeng Tan, Matthew Feinstein, Brian Popko, Matthew Deberge

Faculty, Staff and Student Publications

Survivors of myocardial infarction are at increased risk for vascular dementia. Neuroinflammation has been implicated in the pathogenesis of vascular dementia, yet little is known about the cellular and molecular mediators of neuroinflammation after myocardial infarction. Using a mouse model of myocardial infarction coupled with flow cytometric analyses and immunohistochemistry, we discovered increased monocyte abundance in the brain after myocardial infarction, which was associated with increases in brain-resident perivascular macrophages and microglia. Myeloid cell recruitment and activation was also observed in post-mortem brains of humans that died after myocardial infarction. Spatial and single cell transcriptomic profiling of brain-resident myeloid cells …

The Beneficial Role Of Sunitinib In Tumor Immune Surveillance By Regulating Tumor Pd-L1, Vivian L Rose, Anaga Ajoy, Craig A Johnston, Gloria R Gogola, Pranav J Parikh

Faculty, Staff and Student Publications

Importance: There is a need for a pediatric hand function test that can be used to objectively assess movement quality. We have developed a toy-based test, the Bead Maze Hand Function (BMHF) test, to quantify how well a child performs an activity. This is achieved by assessing the control of forces applied while drawing a bead over wires of different complexity.

Objective: To study the psychometric properties of the BMHF test and understand the influence of age and task complexity on test measures.

Design: A cross-sectional, observational study performed in a single visit.

Setting: Clinical research laboratory.

Participants: Twenty-three participants …

Exploring The Landscape Of Somatic Asxl2 Mutations In Myeloid Neoplasms: Frequency And Clinical Implications, Tareq Abuasab, Gautam Borthakur, Rashmi Kanagal-Shamanna, Lucia Masarova, Keyur Patel, Koichi Takahashi, Prithviraj Bose, John Villarreal, Sherry Pierce, Tapan Kadia, Guillermo Garcia-Manero, Nicholas J Short, Courtney Dinardo, Naval Daver, Farhad Ravandi, Hagop Kantarjian, Srdan Verstovsek, Musa Yilmaz

Faculty, Staff and Student Publications

No abstract provided.

Endovascular Versus Medical Therapy In Posterior Cerebral Artery Stroke: Role Of Baseline Nihss Score And Occlusion Site, Davide Strambo, Patrik Michel, Thanh N Nguyen, Mohamad Abdalkader, Muhammad M Qureshi, Daniel Strbian, Christian Herweh, Markus A Möhlenbruch, Silja Räty, Marta Olivé-Gadea, Marc Ribo, Marios Psychogios, Urs Fischer, Anh Nguyen, Joji B Kuramatsu, David Haupenthal, Martin Köhrmann, Cornelius Deuschl, Jordi Kühne Escolà, Jelle Demeestere, Robin Lemmens, Lieselotte Vandewalle, Shadi Yaghi, Liqi Shu, Volker Puetz, Daniel P O Kaiser, Johannes Kaesmacher, Adnan Mujanovic, Dominique Cornelius Marterstock, Tobias Engelhorn, Manuel Requena, Hormuzdiyar H Dasenbrock, Piers Klein, Diogo C Haussen, Mahmoud H Mohammaden, Hend Abdelhamid, Lorena Souza Viana, Bruno Cunha, Isabel Fragata, Michele Romoli, Francesco Diana, Wei Hu, Chao Zhang, Pekka Virtanen, Riikka Lauha, Jessica Jesser, Judith Clark, Stavros Matsoukas, Johanna T Fifi, Sunil A Sheth, Sergio Salazar-Marioni, João Pedro Marto, João Nuno Ramos, Milena Miszczuk, Christoph Riegler, Sven Poli, Khouloud Poli, Ashutosh P Jadhav, Shashvat M Desai, Volker Maus, Maximilian Kaeder, Adnan H Siddiqui, Andre Monteiro, Hesham E Masoud, Neil Suryadareva, Maxim Mokin, Shail Thanki, Kemal Alpay, Pauli Ylikotila, James E Siegler, Italo Linfante, Guilherme Dabus, Negar Asdaghi, Vasu Saini, Christian H Nolte, Eberhard Siebert, Bettina L Serrallach, Charlotte S Weyland, Uta Hanning, Lukas Meyer, Anne Berberich, Peter A Ringleb, Raul G Nogueira, Simon Nagel

Faculty, Staff and Student Publications

Background: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site.

Methods: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site …

The Role Of Occipital Condyle And Atlas Anomalies On Occipital Cervical Fusion Outcomes In Chiari Malformation Type I With Syringomyelia: A Study From The Park-Reeves Syringomyelia Research Consortium, Alexander T Yahanda, Joyce Koueik, Laurie L Ackerman, P David Adelson, Gregory W Albert, Philipp R Aldana, Tord D Alden, Richard C E Anderson, David F Bauer, Tammy Bethel-Anderson, Karin Bierbrauer, Douglas L Brockmeyer, Joshua J Chern, Daniel E Couture, David J Daniels, Brian J Dlouhy, Susan R Durham, Richard G Ellenbogen, Ramin Eskandari, Herbert E Fuchs, Gerald A Grant, Patrick C Graupman, Stephanie Greene, Jeffrey P Greenfield, Naina L Gross, Daniel J Guillaume, Todd C Hankinson, Gregory G Heuer, Mark Iantosca, Bermans J Iskandar, Eric M Jackson, George I Jallo, James M Johnston, Bruce A Kaufman, Robert F Keating, Nickalus R Khan, Mark D Krieger, Jeffrey R Leonard, Cormac O Maher, Francesco T Mangano, Jonathan Martin, J Gordon Mccomb, Sean D Mcevoy, Thanda Meehan, Arnold H Menezes, Michael S Muhlbauer, Brent R O'Neill, Greg Olavarria, John Ragheb, Nathan R Selden, Manish N Shah, Chevis N Shannon, Joshua S Shimony, Matthew D Smyth, Scellig S D Stone, Jennifer M Strahle, Mandeep S Tamber, James C Torner, Gerald F Tuite, Elizabeth C Tyler-Kabara, Scott D Wait, John C Wellons, William E Whitehead, Tae Sung Park, David D Limbrick, Raheel Ahmed

Faculty, Staff and Student Publications

Objective: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF).

Methods: The authors analyzed the prevalence of condylar …

The Time-Dependent Association Between Irritable Bowel Syndrome And All-Cause And Cause-Specific Mortality: A Prospective Cohort Study Within The Uk Biobank, Fangyu Li, Yukiko Yano, Lola Étiévant, Carrie R Daniel, Shreela V Sharma, Eric L Brown, Ruosha Li, Erikka Loftfield, Qing Lan, Rashmi Sinha, Baharak Moshiree, Maki Inoue-Choi, Emily Vogtmann

Faculty, Staff and Student Publications

Introduction: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but few studies have evaluated mortality risks among individuals with IBS. We explored the association between IBS and all-cause and cause-specific mortality in the UK Biobank.

Methods: We included 502,369 participants from the UK Biobank with mortality data through 2022. IBS was defined using baseline self-report and linkage to primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models within partitioned follow-up time categories (0-5, >5-10, and >10 …