Digital Commons Network^™

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 …

Ghcu, A Molecular Chaperone, Regulates Leaf Curling By Modulating The Distribution Of Kngh1 In Cotton, Yihao Zang, Chenyu Xu, Lishan Yu, Longen Ma, Lisha Xuan, Sunyi Yan, Yayao Zhang, Yiwen Cao, Xiaoran Li, Zhanfeng Si, Jieqiong Deng, Tianzhen Zhang, Yan Hu

Faculty, Staff and Student Publications

Leaf shape is considered to be one of the most significant agronomic traits in crop breeding. However, the molecular basis underlying leaf morphogenesis in cotton is still largely unknown. In this study, through genetic mapping and molecular investigation using a natural cotton mutant cu with leaves curling upward, the causal gene GHCU is successfully identified as the key regulator of leaf flattening. Knockout of GHCU or its homolog in cotton and tobacco using CRISPR results in abnormal leaf shape. It is further discovered that GHCU facilitates the transport of the HD protein KNOTTED1-like (KNGH1) from the adaxial to the abaxial …

Genetic Analysis Of Seven Patients With Inherited Ichthyosis And Nagashima-Type Palmoplantar Keratoderma, Jing Zhang, Yue Yao, Ya Tan, Hua-Ying Hu, Lin-Xi Zeng, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Inherited ichthyosis comprises a series of heterogeneous dermal conditions; it mainly manifests as widespread hyperkeratosis, xerosis and scaling of the skin. At times, overlapping symptoms require differential diagnosis between ichthyosis and several other similar disorders. The present study reports seven patients with confirmed or suspected to be associated with ichthyosis by conducting a thorough clinical and genetic investigation. Genetic testing was conducted using whole-exome sequencing, with Sanger sequencing as the validation method. The MEGA7 program was used to analyze the conservation of amino acid residues affected by the detected missense variants. The enrolled patients exhibited ichthyosis-like but distinct clinical manifestations. …

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 …

Fc Engineering By Monoclonal Mammalian Cell Display For Improved Affinity And Selectivity Towards Fcγrs, Zening Wang, Minhyo Kang, Afshin Ebrahimpour, Chuan Chen, Xin Ge

Faculty, Staff and Student Publications

Fc optimization can significantly enhance therapeutic efficacy of monoclonal antibodies. However, existing Fc engineering approaches are sub-optimal with noted limitations, such as inappropriate glycosylation, polyclonal libraries, and utilizing fragment but not full-length IgG display. Applying cell cycle arrested recombinase-mediated cassette exchange, this study constructed high-quality monoclonal Fc libraries in CHO cells, displayed full-length IgG on cell surface, and preformed ratiometric fluorescence activated cell sorting (FACS) with the antigen and individual FcγRs. Identified Fc variants were quantitatively evaluated by flow cytometry, ELISA, kinetic and steady-state binding affinity measurements, and cytotoxicity assays. An error-prone Fc library focusing on the hinge-CH2 region was …

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: …

Health Care Workers’ Comfort Ratings For Elastomeric Half-Mask Respirators Versus N95® Filtering Facepiece Respirators During The Covid-19 Pandemic, Lisa Pompeii, Janelle Rios, Colleen S Kraft, Marie Kasbaum, Elisa Benavides, Scott J Patlovich, Luis Ostrosky-Zeichner, Adam Hornbeck, Caitlin Mcclain, Rohan D Fernando, Margaret Sietsema, Morgan Lane

Faculty, Staff and Student Publications

BACKGROUND: Reusable elastomeric half-mask respirators (EHMR) are an alternative to address shortages of disposable respirators. While respirator discomfort has been noted as a barrier to adherence to wearing an N95 filtering facepiece respirator (FFR) among health care personnel (HCP), few have examined EHMR comfort while providing patient care, which was the purpose of this study.

METHOD: Among a cohort of 183 HCP, we prospectively examined how HCP rated EHMR tolerability using the Respirator Comfort, Wearing Experience, and Function Instrument (R-COMFI) questionnaire at Study Week 2 and Week 10. At the completion of the study (Week-12), HCP compared EHMR comfort with …

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 …

Transgender Women With Suppressed Testosterone Display Lower Burden Of Coronary Disease Than Matched Cisgender Men, Jordan E Lake, Han Feng, Ana N Hyatt, Hongyu Miao, Paula Debroy, Nicholas Funderburg, Kate Ailstock, Adrian Dobs, Sabina Haberlen, Jared W Magnani, Joseph B Margolick, Kate Mcgowan, Frank J Palella, Mallory D Witt, Shalender Bhasin, Matthew J Budoff, Wendy S Post, Todd T Brown

Faculty, Staff and Student Publications

Context: Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls.

Objective: We compared CVD burden and biomarker profiles between TW and matched cisgender men (CM).

Methods: Adult TW on GAHT (n = 29) were recruited for a cross-sectional study (2018-2020). CM (n = 48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary …

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 …

Genetic Correlations Between Liver Fat Content, Metabolic Health, And Adiposity Distribution In The Fels Longitudinal Study, Ariana L Garza, Miryoung Lee, John Blangero, Cici X Bauer, Stefan A Czerwinski, Audrey C Choh

Faculty, Staff and Student Publications

Background and aims: Hepatic steatosis is known to be heritable, but its genetic basis is mostly uncharacterized. Steatosis is associated with metabolic and adiposity features; recent studies hypothesize that shared genetic effects between these traits could account for some of the unexplained heritability. This study aimed to quantify these genetic associations in a family-based sample of non-Hispanic white adults.

Methods and results: 704 participants (18-95 years, 55.8% female) from the Fels Longitudinal Study with an MRI assessment of liver fat were included. Quantitative genetic analyses estimated the age- and sex-adjusted heritability of individual traits and the genetic correlations within trait …

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 …

Dermoscopy Of A Solitary Circumscribed Neuroma Of The Lip Vermillion, Cody M Atack, Victoria A Mañón, Arthur L Taguchi, Nadarajah Vigneswaran, Jose M Marchena

Faculty, Staff and Student Publications

No abstract provided.

A Cytomics-On-A-Chip Platform And Diagnostic Model Stratifies Risk For Oral Lichenoid Conditions, Michael P Mcrae, Kritika Srinivasan Rajsri, A Ross Kerr, Nadarajah Vigneswaran, Spencer W Redding, Malvin Janal, Stella K Kang, Leena Palomo, Nicolaos J Christodoulides, Meena Singh, Jeffery Johnston, John T Mcdevitt

Faculty, Staff and Student Publications

Objective: A small fraction of oral lichenoid conditions (OLC) have potential for malignant transformation. Distinguishing OLCs from other oral potentially malignant disorders (OPMDs) can help prevent unnecessary concern or testing, but accurate identification by nonexpert clinicians is challenging due to overlapping clinical features. In this study, the authors developed a 'cytomics-on-a-chip' tool and integrated predictive model for aiding the identification of OLCs.

Study design: All study subjects underwent both scalpel biopsy for histopathology and brush cytology. A predictive model and OLC Index comprising clinical, demographic, and cytologic features was generated to discriminate between subjects with lichenoid (OLC+) (N = 94) …

Financial Incentives For Smoking Cessation Among Socioeconomically Disadvantaged Adults: A Randomized Clinical Trial, Darla E Kendzor, Michael S Businelle, Summer G Frank-Pearce, Joseph J C Waring, Sixia Chen, Emily T Hébert, Michael D Swartz, Adam C Alexander, Munjireen S Sifat, Laili Kharazi Boozary, David W Wetter

Faculty, Staff and Student Publications

IMPORTANCE: Socioeconomically disadvantaged individuals (ie, those with low socioeconomic status [SES]) have difficulty quitting smoking and may benefit from incentive-based cessation interventions.

OBJECTIVES: To evaluate the impact of incentivizing smoking abstinence on smoking cessation among adults with low SES.

DESIGN, SETTING, AND PARTICIPANTS: This study used a 2-group randomized clinical trial design. Data collection occurred between January 30, 2017, and February 7, 2022. Participants included adults with low SES who were willing to undergo smoking cessation treatment. Data were analyzed from April 18, 2023, to April 19, 2024.

INTERVENTIONS: Participants were randomized to usual care (UC) for smoking cessation (counseling …

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

Uldp-Fl: Federated Learning With Across-Silo User-Level Differential Privacy, Fumiyuki Kato, Li Xiong, Shun Takagi, Yang Cao, Masatoshi Yoshikawa

Faculty, Staff and Student Publications

Differentially Private Federated Learning (DP-FL) has garnered attention as a collaborative machine learning approach that ensures formal privacy. Most DP-FL approaches ensure DP at the record-level within each silo for cross-silo FL. However, a single user's data may extend across multiple silos, and the desired user-level DP guarantee for such a setting remains unknown. In this study, we present Uldp-FL, a novel FL framework designed to guarantee user-level DP in cross-silo FL where a single user's data may belong to multiple silos. Our proposed algorithm directly ensures user-level DP through per-user weighted clipping, departing from group-privacy approaches. We provide a …

Does Differential Privacy Prevent Backdoor Attacks In Practice?, Fereshteh Razmi, Jian Lou, Li Xiong

Faculty, Staff and Student Publications

Differential Privacy (DP) was originally developed to protect privacy. However, it has recently been utilized to secure machine learning (ML) models from poisoning attacks, with DP-SGD receiving substantial attention. Nevertheless, a thorough investigation is required to assess the effectiveness of different DP techniques in preventing backdoor attacks in practice. In this paper, we investigate the effectiveness of DP-SGD and, for the first time, examine PATE and Label-DP in the context of backdoor attacks. We also explore the role of different components of DP algorithms in defending against backdoor attacks and will show that PATE is effective against these attacks due …

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 …