Medicine and Health Sciences Commons^™

Tumor-Intrinsic Sirpa Promotes Sensitivity To Checkpoint Inhibition Immunotherapy In Melanoma, Zhicheng Zhou, Mei-Ju May Chen, Yikai Luo, Kamalika Mojumdar, Xin Peng, Hu Chen, Shweta V Kumar, Rehan Akbani, Yiling Lu, Han Liang

Faculty, Staff and Student Publications

Checkpoint inhibition immunotherapy has revolutionized cancer treatment, but many patients show resistance. Here we perform integrative transcriptomic and proteomic analyses on emerging immuno-oncology targets across multiple clinical cohorts of melanoma under anti-PD-1 treatment, on both bulk and single-cell levels. We reveal a surprising role of tumor-intrinsic SIRPA in enhancing antitumor immunity, in contrast to its well-established role as a major inhibitory immune modulator in macrophages. The loss of SIRPA expression is a marker of melanoma dedifferentiation, a key phenotype linked to immunotherapy efficacy. Inhibition of SIRPA in melanoma cells abrogates tumor killing by activated CD8+ T cells in a co-culture …

Medicc2: Whole-Genome Doubling Aware Copy-Number Phylogenies For Cancer Evolution, Tom L Kaufmann, Marina Petkovic, Thomas B K Watkins, Emma C Colliver, Sofya Laskina, Nisha Thapa, Darlan C Minussi, Nicholas Navin, Charles Swanton, Peter Van Loo, Kerstin Haase, Maxime Tarabichi, Roland F Schwarz

Faculty, Staff and Student Publications

Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution and provide information for the complex task of phylogenetic inference. We present MEDICC2, a method for inferring evolutionary trees and WGD using haplotype-specific somatic copy-number alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as the infinite sites assumption, allowing multiple mutations and parallel evolution, and does not treat adjacent loci as independent, allowing overlapping copy-number events. Using simulations and multiple data types from 2780 tumors, we use MEDICC2 to demonstrate accurate inference of phylogenies, clonal and subclonal WGD, and ancestral copy-number states.

Tumor Suppressor Dear1 Regulates Mammary Epithelial Cell Fate And Predicts Early Onset And Metastasis In Triple Negative Breast Cancer, Uyen Q Le, Nanyue Chen, Seetharaman Balasenthil, Eugene Lurie, Fei Yang, Suyu Liu, Laura Rubin, Luisa Maren Solis Soto, Maria Gabriela Raso, Harsh Batra, Aysegul A Sahin, Ignacio I Wistuba, Ann Mcneill Killary

Faculty, Staff and Student Publications

Triple negative breast cancer (TNBC) is a disease of poor prognosis, with the majority classified as the basal-like subtype associated with epithelial-mesenchymal transition and metastasis. Because basal breast cancers originate from proliferative luminal progenitor-like cells upon dysregulation of proper luminal differentiation, genes regulating luminal-basal transition are critical to elucidate novel therapeutic targets to improve TNBC outcomes. Herein we demonstrate that the tumor suppressor DEAR1/TRIM62 is a critical regulator of luminal cell fate. DEAR1 loss in human mammary epithelial cells results in significantly enhanced mammosphere formation that is accelerated in the presence of TGF-β/SMAD3 signaling. Mammospheres formed following DEAR1 loss are …

Gating Intermediates Reveal Inhibitory Role Of The Voltage Sensor In A Cyclic Nucleotide-Modulated Ion Channel, Xiaolong Gao, Philipp A M Schmidpeter, Vladimir Berka, Ryan J Durham, Chen Fan, Vasanthi Jayaraman, Crina M Nimigean

Faculty, Staff and Student Publications

Understanding how ion channels gate is important for elucidating their physiological roles and targeting them in pathophysiological states. Here, we used SthK, a cyclic nucleotide-modulated channel from Spirochaeta thermophila, to define a ligand-gating trajectory that includes multiple on-pathway intermediates. cAMP is a poor partial agonist for SthK and depolarization increases SthK activity. Tuning the energy landscape by gain-of-function mutations in the voltage sensor domain (VSD) allowed us to capture multiple intermediates along the ligand-activation pathway, highlighting the allosteric linkage between VSD, cyclic nucleotide-binding (CNBD) and pore domains. Small, lateral displacements of the VSD S4 segment were necessary to open the …

I-Climate: A “Clinical Climate Informatics” Action Framework To Reduce Environmental Pollution From Healthcare, Dean F Sittig, Jodi D Sherman, Matthew J Eckelman, Andrew Draper, Hardeep Singh

Faculty, Staff and Student Publications

Addressing environmental pollution and climate change is one of the biggest sociotechnical challenges of our time. While information technology has led to improvements in healthcare, it has also contributed to increased energy usage, destructive natural resource extraction, piles of e-waste, and increased greenhouse gases. We introduce a framework "Information technology-enabled Clinical cLimate InforMAtics acTions for the Environment" (i-CLIMATE) to illustrate how clinical informatics can help reduce healthcare's environmental pollution and climate-related impacts using 5 actionable components: (1) create a circular economy for health IT, (2) reduce energy consumption through smarter use of health IT, (3) support more environmentally friendly decision-making …

Dual Optical Nanosensor Based On Ormosil Nanoparticles For Monitoring O2 And Ph, Reham Ali

Faculty, Staff and Student Publications

Monitoring O2 and pH has excellent potential in different sensing applications, especially in biological and clinical applications. This report presents a protocol for synthesizing an optical dual nanosensor for those two parameters. The organically modified silica (ormosil) nanoparticles were prepared based on phenytrimethoxysilane in an aqueous solution using an acid-base one-pot strategy. Ormosil was selected as a lipophilic matrix for loading fluorescent O2-sensitive dye platinum(II)-tetrakis-(pentafluorophenyl) porphyrin (Pt-TPFPP), which was quenched in the presence of O2 gas and exhibited a considerable detection proficiency within a percentage range of (0-100%) O2. Commercially available drug ingredient salicylamide was labeled on the surface of …

Dual-Channel P-Type Ternary Dntt-Graphene Barristor, Yongsu Lee, Seung-Mo Kim, Kiyung Kim, So-Young Kim, Ho-In Lee, Heejin Kwon, Hae-Won Lee, Chaeeun Kim, Surajit Some, Hyeon Jun Hwang, Byoung Hun Lee

Faculty, Staff and Student Publications

P-type ternary switch devices are crucial elements for the practical implementation of complementary ternary circuits. This report demonstrates a p-type ternary device showing three distinct electrical output states with controllable threshold voltage values using a dual-channel dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]-thiophene-graphene barristor structure. to obtain transfer characteristics with distinctively separated ternary states, novel structures called contact-resistive and contact-doping layers were developed. The feasibility of a complementary standard ternary inverter design around 1 V was demonstrated using the experimentally calibrated ternary device model.

Ontology-Based Feature Engineering In Machine Learning Workflows For Heterogeneous Epilepsy Patient Records, Satya S Sahoo, Katja Kobow, Jianzhe Zhang, Jeffrey Buchhalter, Mojtaba Dayyani, Dipak P Upadhyaya, Katrina Prantzalos, Meenakshi Bhattacharjee, Ingmar Blumcke, Samuel Wiebe, Samden D Lhatoo

Faculty, Staff and Student Publications

Biomedical ontologies are widely used to harmonize heterogeneous data and integrate large volumes of clinical data from multiple sources. This study analyzed the utility of ontologies beyond their traditional roles, that is, in addressing a challenging and currently underserved field of feature engineering in machine learning workflows. Machine learning workflows are being increasingly used to analyze medical records with heterogeneous phenotypic, genotypic, and related medical terms to improve patient care. We performed a retrospective study using neuropathology reports from the German Neuropathology Reference Center for Epilepsy Surgery at Erlangen, Germany. This cohort included 312 patients who underwent epilepsy surgery and …

Challenges Associated With The Integration Of Immuno-Oncology Agents In Clinical Practice, Patrice Lazure, Aparna R Parikh, Neal E Ready, Marianne J Davies, Sophie Péloquin, Jeffrey M Caterino, Robert Lewandowski, Alexander J Lazar, Suzanne Murray

Faculty, Staff and Student Publications

Background: The availability of new immuno-oncology therapeutics markedly impacts oncology clinicians' treatment decision-making. To effectively support healthcare professionals (HCPs) in their practice, it is important to better understand the challenges and barriers that can accompany the introduction of these agents. This study aimed to establish the types and causes of clinical challenges posed by the introduction of new immuno-oncology agents.

Methods: The mixed-methods design included qualitative in-depth interviews and group discussions with HCPs, in which participants discussed clinical challenges and potential underlying reasons for these challenges. Qualitative findings informed a quantitative survey. This survey investigated the extent and distribution of …

Self-Guided Smartphone Application To Manage Chronic Musculoskeletal Pain: A Randomized, Controlled Pilot Trial, Chao Hsing Yeh, Jennifer Kawi, Lauren Grant, Xinran Huang, Hulin Wu, Robin L Hardwicke, Paul J Christo

Faculty, Staff and Student Publications

Objective: The goal of this study is to evaluate the feasibility and efficacy of an auricular point acupressure smartphone app (mAPA) to self-manage chronic musculoskeletal pain. Methods: A prospective, longitudinal, randomized, controlled pilot trial was conducted using a three-group design (self-guided mAPA (n = 14); in-person mAPA (n = 12); and control (n = 11)). The primary outcomes included physical function and pain intensity. Results: After a 4-week APA intervention, participants in the in-person mAPA group had improved physical function of 32% immediately post-intervention and 29% at the 1M follow-up. Participants in the self-guided mAPA group had …

Pancreatic Tumor Microenvironmental Acidosis And Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles For Potent Radiosensitization, Pradipta Ranjan Rauta, Yuri Mackeyev, Keith Sanders, Joseph B K Kim, Valeria V Gonzalez, Yasmin Zahra, Muhammad A Shohayeb, Belal Abousaida, Geraldine V Vijay, Okan Tezcan, Paul Derry, Anton V Liopo, Eugene R Zubarev, Rickey Carter, Pankaj Singh, Sunil Krishnan

Faculty, Staff and Student Publications

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate …

Pancreatic Tumor Microenvironmental Acidosis And Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles For Potent Radiosensitization, Pradipta Ranjan Rauta, Yuri Mackeyev, Keith Sanders, Joseph B K Kim, Valeria V Gonzalez, Yasmin Zahra, Muhammad A Shohayeb, Belal Abousaida, Geraldine V Vijay, Okan Tezcan, Paul Derry, Anton V Liopo, Eugene R Zubarev, Rickey Carter, Pankaj Singh, Sunil Krishnan

Faculty, Staff and Student Publications

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate …

Impact Of Molecular Sequence Data Completeness On Hiv Cluster Detection And A Network Science Approach To Enhance Detection, Sepideh Mazrouee, Camden J Hallmark, Ricardo Mora, Natascha Del Vecchio, Rocio Carrasco Hernandez, Michelle Carr, Marlene Mcneese, Kayo Fujimoto, Joel O Wertheim

Faculty, Staff and Student Publications

Detection of viral transmission clusters using molecular epidemiology is critical to the response pillar of the Ending the HIV Epidemic initiative. Here, we studied whether inference with an incomplete dataset would influence the accuracy of the reconstructed molecular transmission network. We analyzed viral sequence data available from ~ 13,000 individuals with diagnosed HIV (2012-2019) from Houston Health Department surveillance data with 53% completeness (n = 6852 individuals with sequences). We extracted random subsamples and compared the resulting reconstructed networks versus the full-size network. Increasing simulated completeness was associated with an increase in the number of detected clusters. We also subsampled …

Targeting The Mdm2-P53 Pathway In Dedifferentiated Liposarcoma, Raymond S Traweek, Brandon M Cope, Christina L Roland, Emily Z Keung, Elise F Nassif, Derek J Erstad

Faculty, Staff and Student Publications

Dedifferentiated liposarcoma (DDLPS) is an aggressive adipogenic cancer with poor prognosis. DDLPS tumors are only modestly sensitive to chemotherapy and radiation, and there is a need for more effective therapies. Genetically, DDLPS is characterized by a low tumor mutational burden and frequent chromosomal structural abnormalities including amplification of the 12q13-15 chromosomal region and the MDM2 gene, which are defining features of DDLPS. The MDM2 protein is an E3 ubiquitin ligase that targets the tumor suppressor, p53, for proteasomal degradation. MDM2 amplification or overexpression in human malignancies is associated with cell-cycle progression and worse prognosis. The MDM2-p53 interaction has thus garnered …

A Comprehensive Artificial Intelligence Framework For Dental Diagnosis And Charting, Tanjida Kabir, Chun-Teh Lee, Luyao Chen, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

BACKGROUND: The aim of this study was to develop artificial intelligence (AI) guided framework to recognize tooth numbers in panoramic and intraoral radiographs (periapical and bitewing) without prior domain knowledge and arrange the intraoral radiographs into a full mouth series (FMS) arrangement template. This model can be integrated with different diseases diagnosis models, such as periodontitis or caries, to facilitate clinical examinations and diagnoses.

METHODS: The framework utilized image segmentation models to generate the masks of bone area, tooth, and cementoenamel junction (CEJ) lines from intraoral radiographs. These masks were used to detect and extract teeth bounding boxes utilizing several …

Sars-Cov-2 Incubation Period According To Vaccination Status During The Fifth Covid-19 Wave In A Tertiary-Care Center In Spain: A Cohort Study, Jordi Cortés Martínez, Daewoo Pak, Gabriela Abelenda-Alonso, Klaus Langohr, Jing Ning, Alexander Rombauts, Mireia Colom, Yu Shen, Guadalupe Gómez Melis

Faculty, Staff and Student Publications

Background: The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period.

Methods: We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The …

Envenomation By The Green Bush Viper Atheris Squamigera, Sam T Ontiveros, Priya Srihari, Garret A Winkler, Jake Del Rosso, Julia Sobel, Richard F Clark, Alicia B Minns

Faculty, Staff and Student Publications

The Green Bush Viper, Atheris squamigera, is native to West and Central Africa and has few well reported envenomations. Bite victims experience dizziness, nausea, headache, regional lymphadenopathy, and localized edema. Most reports also detail severe effects including thrombocytopenia, coagulopathy, hemolysis, hemorrhage, or renal failure. Fatalities are reported, but poorly described. There is no specific antivenom for A. squamigera, but non-species specific antivenom has been reported helpful in several cases. We report the case of a 36-year-old woman who was bitten by a green bush viper and was treated with several non-species specific antivenoms. There were no complications to antivenom administration …

Multi-Organ Segmentation Of Abdominal Structures From Non-Contrast And Contrast Enhanced Ct Images, Cenji Yu, Chidinma P Anakwenze, Yao Zhao, Rachael M Martin, Ethan B Ludmir, Joshua S Niedzielski, Asad Qureshi, Prajnan Das, Emma B Holliday, Ann C Raldow, Callistus M Nguyen, Raymond P Mumme, Tucker J Netherton, Dong Joo Rhee, Skylar S Gay, Jinzhong Yang, Laurence E Court, Carlos E Cardenas

Faculty, Staff and Student Publications

Manually delineating upper abdominal organs at risk (OARs) is a time-consuming task. To develop a deep-learning-based tool for accurate and robust auto-segmentation of these OARs, forty pancreatic cancer patients with contrast-enhanced breath-hold computed tomographic (CT) images were selected. We trained a three-dimensional (3D) U-Net ensemble that automatically segments all organ contours concurrently with the self-configuring nnU-Net framework. Our tool's performance was assessed on a held-out test set of 30 patients quantitatively. Five radiation oncologists from three different institutions assessed the performance of the tool using a 5-point Likert scale on an additional 75 randomly selected test patients. The mean (± …

Atomistic Measurement And Modeling Of Intrinsic Fracture Toughness Of Two-Dimensional Materials, Xu Zhang, Hoang Nguyen, Xiang Zhang, Pulickel M Ajayan, Jianguo Wen, Horacio D Espinosa

Faculty, Staff and Student Publications

Quantifying the intrinsic mechanical properties of two-dimensional (2D) materials is essential to predict the long-term reliability of materials and systems in emerging applications ranging from energy to health to next-generation sensors and electronics. Currently, measurements of fracture toughness and identification of associated atomistic mechanisms remain challenging. Herein, we report an integrated experimental-computational framework in which in-situ high-resolution transmission electron microscopy (HRTEM) measurements of the intrinsic fracture energy of monolayer MoS

Body Mass Index And Survival After Cancer Diagnosis: A Pan-Cancer Cohort Study Of 114 430 Patients With Cancer, Huakang Tu, Jennifer L Mcquade, Michael A Davies, Maosheng Huang, Kunlin Xie, Yuanqing Ye, Wong-Ho Chow, Alma Rodriguez, Xifeng Wu

Faculty, Staff and Student Publications

The recommendation encouraging patients with cancer to keep a normal body mass index (BMI) is largely extrapolated from data on risk of developing cancer. We tested the prospective association between peri-diagnostic (within 1 year post-diagnosis) BMI and all-cause mortality in patients with incident cancers. During 7.2 years of follow-up, 42% (48,340) of the 114 430 patients with cancer died. Spline analysis revealed that compared with a BMI of 22.5, a BMI lower than 22.5 was associated with increased risk of all-cause mortality across 24 cancer types. A BMI higher than 22.5 was associated with reduced all-cause mortality, while a non-linear …

Omics Analyses Of A Somatic Trp53r245w/+ Breast Cancer Model Identify Cooperating Driver Events Activating Pi3k/Akt/Mtor Signaling, Xiaojie Yu, Yun Zhang, Shunbin Xiong, Joy M Mcdaniel, Chang Sun, Gilda P Chau, Jovanka Gencel-Augusto, Dhruv Chachad, Rhiannon L Morrissey, Xiayu Rao, Jing Wang, Guillermina Lozano

Faculty, Staff and Student Publications

Alterations of the tumor suppressor

Antibody-Drug Conjugates For The Treatment Of Her2-Positive Breast Cancer, Mariana K Najjar, Sara G Manore, Angelina T Regua, Hui-Wen Lo

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20–30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted …

A High-Resolution 3d Atlas Of The Spectrum Of Tuberculous Andcovid-19 Lung Lesions, Gordon Wells, Joel N Glasgow, Kievershen Nargan, Kapongo Lumamba, Rajhmun Madansein, Kameel Maharaj, Leon Y Perumal, Malcolm Matthew, Robert L Hunter, Hayden Pacl, Jacelyn E Peabody Lever, Denise D Stanford, Satinder P Singh, Prachi Bajpai, Upender Manne, Paul V Benson, Steven M Rowe, Stephan Le Roux, Alex Sigal, Muofhe Tshibalanganda, Carlyn Wells, Anton Du Plessis, Mpumelelo Msimang, Threnesan Naidoo, Adrie J C Steyn

Faculty, Staff and Student Publications

Our current understanding of the spectrum of TB and COVID-19 lesions in the human lung is limited by a reliance on low-resolution imaging platforms that cannot provide accurate 3D representations of lesion types within the context of the whole lung. To characterize TB and COVID-19 lesions in 3D, we applied micro/nanocomputed tomography to surgically resected, postmortem, and paraffin-embedded human lung tissue. We define a spectrum of TB pathologies, including cavitary lesions, calcium deposits outside and inside necrotic granulomas and mycetomas, and vascular rearrangement. We identified an unusual spatial arrangement of vasculature within an entire COVID-19 lobe, and 3D segmentation of …

A Randomized Pilot Study Of Oncology Massage To Treat Chemotherapy-Induced Peripheral Neuropathy, Gabriel Lopez, Cathy Eng, Michael Overman, David Ramirez, Wenli Liu, Curtiss Beinhorn, Pamela Sumler, Sarah Prinsloo, Yisheng Li, Minxing Chen, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

This pilot randomized controlled trial investigated massage therapy for symptomatic relief of chemotherapy-induced peripheral neuropathy (CIPN) to determine the ideal weekly frequency and number of weeks of providing massage. We evaluated the feasibility and initial efficacy of a Swedish massage protocol to treat lower extremity (LE) CIPN. Inclusion criteria: LE neuropathy attributed to oxaliplatin, paclitaxel, or docetaxel, with no other attributable causes; ≥ 6 months since last chemotherapy; self-reported neuropathy score ≥ 3, 0-10 scale; age ≥ 18. Participant randomization (2:2:1:1) to one of four groups: LE (2) or head/neck/shoulder (control; 1) massage 3 times (3X) a week for 4 …

Prevalence Of Sleep-Related Problems And Risks In A Community-Dwelling Older Adult Population: A Cross-Sectional Survey-Based Study, Nancy P Gordon, Jimmy H Yao, Leslea A Brickner, Joan C Lo

Faculty, Staff and Student Publications

BACKGROUND: Despite evidence of adverse health consequences of inadequate restorative sleep for older adults, assessment of sleep quantity, quality, and use of sleep aids is not routinely done. We aimed to characterize sleep problems, sleep risks, and advice received about sleep in a community-dwelling older adult population, overall and in subgroups with health conditions and functional difficulties.

METHODS: This cross-sectional study used weighted self-report data for 5074 Kaiser Permanente Northern California members aged 65-79y who responded to a 2017 or 2020 Member Health Survey. We estimated usual amount of sleep (< 6, 6 to < 7, ≥7 hours) and prevalence of sleep problems (frequent insomnia, frequent daytime fatigue, poor quality sleep, and potential sleep apnea (OSA) symptoms (frequent very loud snoring, apnea episodes)) for older adults overall, by self-rated health, and in subgroups reporting hypertension, diabetes, heart disease, frequent problems with balance/walking, and frequent memory problems. We also estimated percentages who regularly used sleep aids and had discussed sleep adequacy with a healthcare professional in the past year.

RESULTS: Approximately 30% of older adults usually got less …

Polygenic Risk Score Improves The Accuracy Of A Clinical Risk Score For Coronary Artery Disease, Austin King, Lang Wu, Hong-Wen Deng, Hui Shen, Chong Wu

Faculty, Staff and Student Publications

BACKGROUND: The value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves the prediction of CAD beyond pooled cohort equations. METHODS: An observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case-control sample of 9499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine …

Radiation Therapy Induces Immunosenescence Mediated By P90rsk, Masaki Imanishi, Haizi Cheng, Sivareddy Kotla, Anita Deswal, Nhat-Tu Le, Eduardo Chini, Kyung Ae Ko, Venkata S K Samanthapudi, Ling-Ling Lee, Joerg Herrmann, Xiaolei Xu, Cielito Reyes-Gibby, Sai-Ching J Yeung, Keri L Schadler, Syed Wamique Yusuf, Zhongxing Liao, Roza Nurieva, El-Ad David Amir, Jared K Burks, Nicolas L Palaskas, John P Cooke, Steven H Lin, Michihiro Kobayashi, Momoko Yoshimoto, Jun-Ichi Abe

Faculty, Staff and Student Publications

Radiation therapy (RT) to the chest increases the patients’ risk of cardiovascular disease (CVD). A complete understanding of the mechanisms by which RT induces CVD could lead to specific preventive, therapeutic approaches. It is becoming evident that both genotoxic chemotherapy agents and radiation induce mitochondrial dysfunction and cellular senescence. Notably, one of the common phenotypes observed in cancer survivors is accelerated senescence, and immunosenescence is closely related to both cancer risk and CVD development. Therefore, suppression of immunosenescence can be an ideal target to prevent cancer treatment-induced CVD. However, the mechanism(s) by which cancer treatments induce immunosenescence are incompletely characterized. …

High-Contrast Detection Of Somatostatin Receptor Subtype-2 For Fluorescence-Guided Surgery, Servando Hernandez Vargas, Solmaz Aghaamiri, Sukhen C Ghosh, Michael P Luciano, Luis C Borbon, Po Hien Ear, James R Howe, Jennifer M Bailey-Lundberg, Gregory D Simonek, Daniel M Halperin, Hop S Tran Cao, Naruhiko Ikoma, Martin J Schnermann, Ali Azhdarinia

Faculty, Staff and Student Publications

Dye design can influence the ability of fluorescently labeled imaging agents to generate tumor contrast and has become an area of significant interest in the field of fluorescence-guided surgery (FGS). Here, we show that the charge-balanced near-infrared fluorescent (NIRF) dye FNIR-Tag enhances the imaging properties of a fluorescently labeled somatostatin analogue.

New Non-Fullerene Acceptor With Extended Conjugation Of Cyclopenta [2,1-B:3,4-B’] Dithiophene For Organic Solar Cells, Cheng Sun, Sanseong Lee, Changeun Choi, Soyeong Jeong, Juhui Oh, Ju-Hyeon Kim, Jaeyoung Kim, Ho Eon Baek, Hongkyu Kang, Soo-Young Jang, Hyun Ho Choi, Kwanghee Lee, Yun-Hi Kim

Faculty, Staff and Student Publications

Herein, we design and characterize 9-heterocyclic ring non-fullerene acceptors (NFAs) with the extended backbone of indacenodithiophene by cyclopenta [2,1-b:3,4-b'] dithiophene (CPDT). The planar conjugated CPDT donor enhances absorption by reducing vibronic transition and charge transport. Developed NFAs with different end groups shows maximum absorption at approximately 790-850 nm in film. Because of the electronegative nature of the end-group, the corresponding acceptors showed deeper LUMO energy levels and red-shifted ultraviolet absorption. We investigate the crystallinity, film morphology, surface energy, and electronic as well as photovoltaic performance. The organic photovoltaic cells using novel NFAs with the halogen end groups fluorine or chlorine …

Elective Surgery System Strengthening: Development, Measurement, And Validation Of The Surgical Preparedness Index Across 1632 Hospitals In 119 Countries, Nihr Global Health Unit On Global Surgery, Covidsurg Collaborative

Faculty, Staff and Student Publications

BACKGROUND: The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs.

METHODS: First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), …