Digital Commons Network^™

The Biology Of Hope: Inflammatory And Neuroendocrine Profiles In Ovarian Cancer Patients, Susan K Lutgendorf, Rachel M Telles, Brendan Whitney, Premal H Thaker, George M Slavich, Michael J Goodheart, Frank J Penedo, Alyssa E Noble, Steven W Cole, Anil K Sood, Benjamin W Corn

Faculty, Staff and Student Publications

INTRODUCTION: Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers.

METHOD: Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey …

Allogeneic Stem Cell Therapy For Acute Ischemic Stroke: The Phase 2/3 Treasure Randomized Clinical Trial, Kiyohiro Houkin, Toshiya Osanai, Shinichiro Uchiyama, Kazuo Minematsu, Akihiko Taguchi, Katsuhiko Maruichi, Yoshimasa Niiya, Katsuyuki Asaoka, Yoshihiro Kuga, Katsumi Takizawa, Koichi Haraguchi, Shinichi Yoshimura, Kazumi Kimura, Koji Tokunaga, Atsuo Aoyama, Fusao Ikawa, Chikanori Inenaga, Tatsuya Abe, Atsushi Tominaga, Shinichi Takahashi, Kohsuke Kudo, Miki Fujimura, Taku Sugiyama, Masaki Ito, Masahito Kawabori, David C Hess, Sean I Savitz, Teruyuki Hirano

Faculty, Staff and Student Publications

IMPORTANCE: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke.

OBJECTIVE: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset.

DESIGN, SETTING, AND PARTICIPANTS: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were …

Weight-Based Enoxaparin Thromboprophylaxis In Young Trauma Patients: Analysis Of The Clott-1 Registry, Sarah Lombardo, Marta Mccrum, M Margaret Knudson, Ernest E Moore, Lucy Kornblith, Scott Brakenridge, Brandon Bruns, Mark D Cipolle, Todd W Costantini, Bruce Crookes, Elliott R Haut, Andrew J Kerwin, Laszlo N Kiraly, Lisa Marie Knowlton, Matthew J Martin, Michelle K Mcnutt, David J Milia, Alicia Mohr, Frederick Rogers, Thomas Scalea, Sherry Sixta, David Spain, Charles E Wade, George C Velmahos, Ram Nirula, Jade Nunez

Faculty, Staff and Student Publications

INTRODUCTION: Optimal venous thromboembolism (VTE) enoxaparin prophylaxis dosing remains elusive. Weight-based (WB) dosing safely increases anti-factor Xa levels without the need for routine monitoring but it is unclear if it leads to lower VTE risk. We hypothesized that WB dosing would decrease VTE risk compared with standard fixed dosing (SFD).

METHODS: Patients from the prospective, observational CLOTT-1 registry receiving prophylactic enoxaparin (n=5539) were categorized as WB (0.45-0.55 mg/kg two times per day) or SFD (30 mg two times per day, 40 mg once a day). Multivariate logistic regression was used to generate a predicted probability of VTE for WB and …

The Artificial Intelligence-Based Model Anorak Improves Histopathological Grading Of Lung Adenocarcinoma, Xiaoxi Pan, Khalid Abduljabbar, Jose Coelho-Lima, Anca-Ioana Grapa, Hanyun Zhang, Alvin Ho Kwan Cheung, Juvenal Baena, Takahiro Karasaki, Claire Rachel Wilson, Marco Sereno, Selvaraju Veeriah, Sarah J Aitken, Allan Hackshaw, Andrew G Nicholson, Mariam Jamal-Hanjani, Charles Swanton, Yinyin Yuan, John Le Quesne, David A Moore

Faculty, Staff and Student Publications

The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant …

Anatomy Of The Female Reproductive Tract Organs Of The Brown Anole (Anolis Sagrei), Bonnie K Kircher, Edward L Stanley, Richard R Behringer

Faculty, Staff and Student Publications

Female reproduction in squamate reptiles (lizards and snakes) is highly diverse and mode of reproduction, clutch size, and reproductive tract morphology all vary widely across this group of ~11,000 species. Recently, CRISPR genome editing techniques that require manipulation of the female reproductive anatomy have been developed in this group, making a more complete understanding of this anatomy essential. We describe the adult female reproductive anatomy of the model reptile the brown anole (Anolis sagrei). We show that the brown anole female reproductive tract has three distinct anterior-to-posterior regions, the infundibulum, the glandular uterus, and the nonglandular uterus. The infundibulum has …

Ex Vivo Expanded Cord Blood Natural Killer Cells Combined With Rituximab And High-Dose Chemotherapy And Autologous Stem Cell Transplantation For B Cell Non-Hodgkin Lymphoma, Yago Nieto, Pinaki Banerjee, Indresh Kaur, Kun Hee Kim, Dexing Fang, Peter F Thall, Lori Griffin, Melissa Barnett, Rafet Basar, Chitra Hosing, Jeremy Ramdial, Samer Srour, May Daher, David Marin, Xianli Jiang, Ken Chen, Richard Champlin, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

Relapse is the major cause of failure of high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) for B cell non-Hodgkin lymphomas (B-NHL). Improvement strategies include use in combination with effective immunotherapies. We hypothesized that the combination of rituximab/HDC/ASCT with expanded cord blood (CB)-derived natural killer (NK) cells is safe and active in B-NHL. Patients with B-NHL age 15 to 70 years and appropriate ASCT candidates were eligible for the study. The CB units were selected without considering HLA match with the recipient. The CB NK cells were expanded from day -19 to day -5. Treatment included rituximab on days …

Association Between Circulating Inflammatory Markers And Adult Cancer Risk: A Mendelian Randomization Analysis, James Yarmolinsky, Jamie W Robinson, Daniela Mariosa, Ville Karhunen, Jian Huang, Niki Dimou, Neil Murphy, Kimberley Burrows, Emmanouil Bouras, Karl Smith-Byrne, Sarah J Lewis, Tessel E Galesloot, Lambertus A Kiemeney, Sita Vermeulen, Paul Martin, Demetrius Albanes, Lifang Hou, Polly A Newcomb, Emily White, Alicja Wolk, Anna H Wu, Loïc Le Marchand, Amanda I Phipps, Daniel D Buchanan, International Lung Cancer Consortium, Practical Consortium, Sizheng Steven Zhao, Dipender Gill, Stephen J Chanock, Mark P Purdue, George Davey Smith, Paul Brennan, Karl-Heinz Herzig, Marjo-Riitta Järvelin, Chris I Amos, Rayjean J Hung, Abbas Dehghan, Mattias Johansson, Marc J Gunter, Kostas K Tsilidis, Richard M Martin

Faculty, Staff and Student Publications

BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were …

Antiviral Potency Of Long-Acting Islatravir Subdermal Implant In Shiv-Infected Macaques, Fernanda P Pons-Faudoa, Nicola Di Trani, Simone Capuani, Ilaria Facchi, Anthony M Wood, Bharti Nehete, Ashley Delise, Suman Sharma, Kathryn A Shelton, Lane R Bushman, Corrine Ying Xuan Chua, Michael M Ittmann, Jason T Kimata, Peter L Anderson, Pramod N Nehete, Roberto C Arduino, Alessandro Grattoni

Faculty, Staff and Student Publications

Treatment nonadherence is a pressing issue in people living with HIV (PLWH), as they require lifelong therapy to maintain viral suppression. Poor adherence leads to antiretroviral (ARV) resistance, transmission to others, AIDS progression, and increased morbidity and mortality. Long-acting (LA) ARV therapy is a promising strategy to combat the clinical drawback of user-dependent dosing. Islatravir (ISL) is a promising candidate for HIV treatment given its long half-life and high potency. Here we show constant ISL release from a subdermal LA nanofluidic implant achieves viral load reduction in SHIV-infected macaques. Specifically, a mean delivery dosage of 0.21 ± 0.07 mg/kg/day yielded …

Implementation And Evaluation Of A Mhealth-Based Community Health Worker Feedback Loop For Hispanics With And At Risk For Diabetes, Elizabeth M Vaughan, Victor J Cardenas, Wenyaw Chan, Amber B Amspoker, Craig A Johnston, Salim S Virani, Christie M Ballantyne, Aanand D Naik

Faculty, Staff and Student Publications

BACKGROUND: Gaps in accessibility and communication hinder diabetes care in poor communities. Combining mobile health (mHealth) and community health workers (CHWs) into models to bridge these gaps has great potential but needs evaluation.

OBJECTIVE: To evaluate a mHealth-based, Participant-CHW-Clinician feedback loop in a real-world setting.

DESIGN: Quasi-experimental feasibility study with intervention and usual care (UC) groups.

PARTICIPANTS: A total of 134 participants (n = 67/group) who were all low-income, uninsured Hispanics with or at-risk for type 2 diabetes.

INTERVENTION: A 15-month study with a weekly to semimonthly mHealth Participant-CHW-Clinician feedback loop to identify participant issues and provide participants monthly diabetes …

Pluripotency Of A Founding Field: Rebranding Developmental Biology, Crystal D Rogers, Chris Amemiya, Swathi Arur, Leslie Babonis, Michael Barresi, Madelaine Bartlett, Richard Behringer, Blair Benham-Pyle, Dominique Bergmann, Ben Blackman, C Titus Brown, Bill Browne, Jasmin Camacho, Chiswili Yves Chabu, Ida Chow, Ondine Cleaver, Jonah Cool, Megan Y Dennis, Alexandra Jazz Dickinson, Stefano Di Talia, Margaret Frank, Stewart Gillmor, Eric S Haag, Iswar Hariharan, Richard Harland, Aman Husbands, Loydie Jerome-Majewska, Kristen Koenig, Carole Labonne, Michael Layden, Chris Lowe, Madhav Mani, Megan Martik, Katelyn Mckown, Cecilia Moens, Christian Mosimann, Joyce Onyenedum, Robert Reed, Ajna Rivera, Dan Rokhsar, Loic Royer, Flora Rutaganira, Rachel Shahan, Neelima Sinha, Billie Swalla, Jaimie M Van Norman, Daniel E Wagner, Athula Wikramanayake, Sophia Zebell, Siobhán M Brady

Faculty, Staff and Student Publications

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional …

Brief Report: Comprehensive Clinicogenomic Profiling Of Small Cell Transformation From Egfr-Mutant Nsclc Informs Potential Therapeutic Targets, Bingnan Zhang, Whitney Lewis, C Allison Stewart, Benjamin B Morris, Luisa M Solis, Alejandra Serrano, Yuanxin Xi, Qi Wang, Elyse R Lopez, Kyle Concannon, Simon Heeke, Ximing Tang, Gabriela Raso, Robert J Cardnell, Natalie Vokes, George Blumenschein, Yasir Elamin, Frank Fosella, Anne Tsao, Ferdinandos Skoulidis, Celyne Bueno Hume, Koji Sasak, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Jack Lee, Hai Tran, Jianjun Zhang, Don Gibbons, Ara Vaporciyan, Jing Wang, Keunchil Park, John V Heymach, Lauren A Byers, Carl M Gay, Xiuning Le

Faculty, Staff and Student Publications

INTRODUCTION: NSCLC transformation to SCLC has been best characterized with

METHODS: In this study, we conducted a single-center retrospective analysis of clinical and genomic characteristics of patients with

RESULTS: A total of 34 patients were identified in our study. Median age at initial diagnosis was 58, and median time to SCLC transformation was 24.2 months. 68% were female and 82% were never smokers. 79% of patients were diagnosed as stage IV disease, and over half had brain metastases at baseline. Median overall survival of the entire cohort was 38.3 months from initial diagnoses and 12.4 months from time of SCLC …

Circulating Immune Signatures Across Clinical Stages Of Chronic Pancreatitis: A Pilot Study, Rasmus Hagn-Meincke, Phil A Hart, Dana K Andersen, Santhi S Vege, Evan L Fogel, Jose Serrano, Melena D Bellin, Mark D Topazian, Darwin L Conwell, Liang Li, Stephen K Van Den Eeden, Asbjørn M Drewes, Stephen J Pandol, Chris E Forsmark, William E Fisher, Dhiraj Yadav, Søren S Olesen, Walter G Park, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Objective: This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP).

Methods: We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to …

Safety, Immunogenicity, And Mechanism Of A Rotavirus Mrna-Lnp Vaccine In Mice, Chenxing Lu, Yan Li, Rong Chen, Xiaoqing Hu, Qingmei Leng, Xiaopeng Song, Xiaochen Lin, Jun Ye, Jinlan Wang, Jinmei Li, Lida Yao, Xianqiong Tang, Xiangjun Kuang, Guangming Zhang, Maosheng Sun, Yan Zhou, Hongjun Li

Faculty, Staff and Student Publications

Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of live attenuated RV vaccines or developing non-replicating RV (e.g., mRNA) vaccines is crucial for reducing the morbidity and mortality from RV infections. Herein, a nucleoside-modified mRNA vaccine encapsulated in lipid nanoparticles (LNP) and encoding the VP7 protein from the G1 type of RV was developed. The 5' untranslated region of an isolated human RV was utilized for the mRNA vaccine. After undergoing quality inspection, the VP7-mRNA vaccine was injected by subcutaneous or intramuscular routes into mice. …

Blood Epigenome-Wide Association Studies Of Suicide Attempt In Adults With Bipolar Disorder, Salahudeen Mirza, Camila N C Lima, Alexandra Del Favero-Campbell, Alexandre Rubinstein, Natasha Topolski, Brenda Cabrera-Mendoza, Emese H C Kovács, Hilary P Blumberg, Jenny Gringer Richards, Aislinn J Williams, John A Wemmie, Vincent A Magnotta, Jess G Fiedorowicz, Marie E Gaine, Consuelo Walss-Bass, Joao Quevedo, Jair C Soares, Gabriel R Fries

Faculty, Staff and Student Publications

Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at >700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related …

Delays In Intervention: A Post-Mortem Of The Uk-Reboa And Cryostat-2 Trials, Bryan A Cotton

Faculty, Staff and Student Publications

No abstract provided.

A Novel Polymer-Encapsulated Multi-Imaging Modality Fiducial Marker With Positive Signal Contrast For Image-Guided Radiation Therapy, Li Wang, Jeremiah Sanders, John F Ward, Stephen R Lee, Falk Poenisch, David Michael Swanson, Narayan Sahoo, Xiaorong Ronald Zhu, Jingfei Ma, Rajat J Kudchadker, Seungtaek L Choi, Quynh-Nhu Nguyen, Lauren L Mayo, Shalin J Shah, Steven J Frank

Faculty, Staff and Student Publications

BACKGROUND: Current fiducial markers (FMs) in external-beam radiotherapy (EBRT) for prostate cancer (PCa) cannot be positively visualized on magnetic resonance imaging (MRI) and create dose perturbation and significant imaging artifacts on computed tomography (CT) and MRI. We report our initial experience with clinical imaging of a novel multimodality FM, NOVA.

METHODS: We tested Gold Anchor [G-FM], BiomarC [carbon, C-FM], and NOVA FMs in phantoms imaged with kilovoltage (kV) X-rays, transrectal ultrasound (TRUS), CT, and MRI. Artifacts of the FMs on CT were quantified by the relative streak artifacts level (rSAL) metric. Proton dose perturbations (PDPs) were measured with Gafchromic EBT3 …

Management Of Infliximab Refractory Immune Checkpoint Inhibitor Gastrointestinal Toxicity: A Multicenter Case Series, Catriona Harvey, Kazi J Nahar, Janet Mckeown, Serigne N Lo, Sheima Farag, Nadia Yousaf, Kate Young, Liselotte Tas, Aafke Meerveld-Eggink, Christian Blank, Austin Thomas, Jennifer Mcquade, Bastian Schilling, Douglas B Johnson, Roberto Martín Huertas, Ana Arance, Joanna Lee, Lisa Zimmer, Georgina V Long, Matteo S Carlino, Yinghong Wang, Alexander Maxwell Menzies

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab, however best management of infliximab-refractory ICI gastrointestinal toxicity (IRIGItox) is unknown.

Methods: We conducted an international multicenter retrospective case series. IRIGItox was defined as failure of symptom resolution ≤grade 1 (Common Terminology Criteria for Adverse Events V.5.0) following ≥2 infliximab doses or failure of symptom resolution ≤grade 2 after one dose. Data were extracted regarding demographics, steroid use, response to treatment, and survival outcomes. Toxicity was graded at symptom onset and time of infliximab failure. …

Cytoskeleton Remodeling Induced By Smyd2 Methyltransferase Drives Breast Cancer Metastasis, Alexandre G Casanova, Gael S Roth, Simone Hausmann, Xiaoyin Lu, Ludivine J M Bischoff, Emilie M Froeliger, Lucid Belmudes, Ekaterina Bourova-Flin, Natasha M Flores, Ana Morales Benitez, Tourkian Chasan, Marcello Caporicci, Jessica Vayr, Sandrine Blanchet, Francesco Ielasi, Sophie Rousseaux, Pierre Hainaut, Or Gozani, Muriel Le Romancer, Yohann Couté, Andres Palencia, Pawel K Mazur, Nicolas Reynoird

Faculty, Staff and Student Publications

Malignant forms of breast cancer refractory to existing therapies remain a major unmet health issue, primarily due to metastatic spread. A better understanding of the mechanisms at play will provide better insights for alternative treatments to prevent breast cancer cell dispersion. Here, we identify the lysine methyltransferase SMYD2 as a clinically actionable master regulator of breast cancer metastasis. While SMYD2 is overexpressed in aggressive breast cancers, we notice that it is not required for primary tumor growth. However, mammary-epithelium specific SMYD2 ablation increases mouse overall survival by blocking the primary tumor cell ability to metastasize. Mechanistically, we identify BCAR3 as …

Measures Of Resting-State Brain Network Segregation And Integration Vary In Relation To Data Quantity: Implications For Within And Between Subject Comparisons Of Functional Brain Network Organization, Liang Han, Micaela Y Chan, Phillip F Agres, Ezra Winter-Nelson, Ziwei Zhang, Gagan S Wig

Faculty, Staff and Student Publications

Measures of functional brain network segregation and integration vary with an individual's age, cognitive ability, and health status. Based on these relationships, these measures are frequently examined to study and quantify large-scale patterns of network organization in both basic and applied research settings. However, there is limited information on the stability and reliability of the network measures as applied to functional time-series; these measurement properties are critical to understand if the measures are to be used for individualized characterization of brain networks. We examine measurement reliability using several human datasets (Midnight Scan Club and Human Connectome Project [both Young Adult …

Development Of A Culinary Medicine Toolkit To Improve Implementation Of Virtual Cooking Classes For Low-Income Adults With Type 2 Diabetes, David Ai, Natalia I Heredia, Vanessa Cruz, Diana C Guevara, Shreela V Sharma, Dolores Woods, Melisa Danho, John Wesley Mcwhorter

Faculty, Staff and Student Publications

Culinary medicine (CM) addresses diseases through nutrition and culinary education. To promote access to educational material for people with diabetes and engagement in virtual classes, we created a virtual culinary medicine toolkit (VCMT) sensitive to literacy levels and language preferences. The VCMT was developed to accompany existing virtual CM programs and help improve participant interaction and retention, offering educational materials for providers and participants. The provider VCMT offers level-setting education to reduce mixed nutrition messaging, including educational resources discussing inclusive nutrition and mindful eating topics. Each handout has a QR code and link to engaging, animated videos that provide further …

Association Between Regulatory T Cells And Ischemic Heart Disease: A Mendelian Randomization Study, Yucheng Hou, Ke Si, Jingyue Yang, Tan Liu, Basel Abdelazeem, Nonthikorn Theerasuwipakorn, Jingwei Zhao, Zhenya Shen

Faculty, Staff and Student Publications

BACKGROUND: An imbalance of innate and acquired immune responses is significantly involved in the pathophysiology of coronary atherosclerosis and the occurrence of ischemic heart disease (IHD). Regulatory T cells (Tregs) play an essential regulatory role in atherosclerotic plaque formation and maintenance; therefore, dysfunction of Tregs triggers the formation of atherosclerotic plaques and accelerates their progression. However, due to the inherent limitations of observational research, clinical evidence is limited concerning the relationship between the variation in peripheral Tregs and the risk of IHD, and the cause-and-effect relationship between these factors is unclear. Mendelian randomization (MR) uses genetic variation as a proxy …

Comprehensive Characterization Of Polyproline Tri-Helix Macrocyclic Nanoscaffolds For Predictive Ligand Positioning, Chia-Lung Tsai, Je-Wei Chang, Kum-Yi Cheng, Yu-Jing Lan, Yi-Cheng Hsu, Qun-Da Lin, Tzu-Yuan Chen, Orion Shih, Chih-Hsun Lin, Po-Hsun Chiang, Mantas Simenas, Vidmantas Kalendra, Yun-Wei Chiang, Chun-Hsien Chen, U-Ser Jeng, Sheng-Kai Wang

Faculty, Staff and Student Publications

Multivalent ligands hold promise for enhancing avidity and selectivity to simultaneously target multimeric proteins, as well as potentially modulating receptor signaling in pharmaceutical applications. Essential for these manipulations are nanosized scaffolds that precisely control ligand display patterns, which can be achieved by using polyproline oligo-helix macrocyclic nanoscaffolds via selective binding to protein oligomers and cell surface receptors. This work focuses on synthesis and structural characterization of different-sized polyproline tri-helix macrocyclic (PP3M) scaffolds. Through combined analysis of circular dichroism (CD), small- and wide-angle X-ray scattering (SWAXS), electron spin resonance (ESR) spectroscopy, and molecular modeling, a non-coplanar tri-helix loop structure with partially …

Short-Term Outcomes And Efficacy Of Percutaneous Deep Vein Arterialization For No-Option Critical Limb Ischemia: A Systematic Review And Meta-Analysis, Roshanak Roustazadeh, Alexander Gombert, Julia Krabbe, Michael Jacobs, Panagiotis Doukas

Faculty, Staff and Student Publications

BACKGROUND: Percutaneous deep vein arterialization (pDVA) is considered a treatment modality in patients with no-option critical limb ischemia. However, there is still a paucity of evidence regarding its safety and efficacy.

DATA SOURCES: MEDLINE (via PubMed), Embase and Web of Science databases as well as the CENTRAL registry up to the end of June 2023.

METHODS: This review adhered to the PRISMA guidelines (PROSPERO registration no. CRD42023445171). The risk of bias was assessed using the methodological index for non-randomized studies (MINORS). Primary endpoints included technical success, overall survival and limb salvage during the follow-up. Amputation-free survival at 30 days, 6 …

Home Blood Pressure Telemonitoring Technology For Patients With Asymptomatic Elevated Blood Pressure Discharged From The Emergency Department: Pilot Study, Karen C Tran, Meagan Mak, Laura M Kuyper, Jesse Bittman, Birinder Mangat, Heather Lindsay, Chad Kim Sing, Liang Xu, Hubert Wong, Martin Dawes, Nadia Khan, Kendall Ho

Faculty, Staff and Student Publications

BACKGROUND: Hypertension affects 1 in 5 Canadians and is the leading cause of morbidity and mortality globally. Hypertension control is declining due to multiple factors including lack of access to primary care. Consequently, patients with hypertension frequently visit the emergency department (ED) due to high blood pressure (BP). Telehealth for Emergency-Community Continuity of Care Connectivity via Home-Telemonitoring Blood Pressure is a pilot project that implements and evaluates a comprehensive home blood pressure telemonitoring (HBPT) and physician case management protocol designed as a postdischarge management strategy to support patients with asymptomatic elevated BP as they transition from the ED to home. …

Myd88 In Myofibroblasts Enhances Nonalcoholic Fatty Liver Disease-Related Hepatocarcinogenesis Via Promoting Macrophage M2 Polarization, Yu Liu, Haiqiang Chen, Xuanxuan Yan, Jie Zhang, Zhenzhong Deng, Maosheng Huang, Jianchun Gu, Jinhua Zhang

Faculty, Staff and Student Publications

Background: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases and has emerged as the leading factor in the pathogenesis of hepatocellular carcinoma (HCC). MyD88 contributes to the development of HCC. However, the underlying mechanism by which MyD88 in myofibroblasts regulates NAFLD-associated liver cancer development remains unknown.

Results: Myofibroblast MyD88-deficient (SMAMyD88-/-) mice were protected from diet-induced obesity and developed fewer and smaller liver tumors. MyD88 deficiency in myofibroblasts attenuated macrophage M2 polarization and fat accumulation in HCC tissues. Mechanistically, MyD88 signaling in myofibroblasts enhanced CCL9 secretion, thereby promoting macrophage M2 polarization. This process may depend on …

Longitudinal Varying Coefficient Single-Index Model With Censored Covariates, Shikun Wang, Jing Ning, Ying Xu, Ya-Chen Tina Shih, Yu Shen, Liang Li

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It is of interest to health policy research to estimate the population-averaged longitudinal medical cost trajectory from initial cancer diagnosis to death, and understand how the trajectory curve is affected by patient characteristics. This research question leads to a number of statistical challenges because the longitudinal cost data are often non-normally distributed with skewness, zero-inflation, and heteroscedasticity. The trajectory is nonlinear, and its length and shape depend on survival, which are subject to censoring. Modeling the association between multiple patient characteristics and nonlinear cost trajectory curves of varying lengths should take into consideration parsimony, flexibility, and interpretation. We propose a …

It's Not That We Care Less: Insights Into Health Care Utilization For Comorbid Diabetes And Depression Among Latinos, Sharon Borja, Miriam G Valdovinos, Kenia M Rivera, Natalia Giraldo-Santiago, Robin E Gearing, Luis R Torres

Faculty, Staff and Student Publications

Despite robust knowledge regarding the socio-economic and cultural factors affecting Latino* access to healthcare, limited research has explored service utilization in the context of comorbid conditions like diabetes and depression. This qualitative study, embedded in a larger mixed-methods project, aimed to investigate perceptions held by Latinos and their social support systems (i.e., family members) regarding comorbid diabetes and depression and to identify barriers and facilitators to their help-seeking behaviors and treatment engagement. Bilingual and bicultural researchers conducted eight focus groups with 94 participants in a large U.S. metropolitan area and were primarily conducted in Spanish. The participants either had a …

Accounting For Network Noise In Graph-Guided Bayesian Modeling Of Structured High-Dimensional Data, Wenrui Li, Changgee Chang, Suprateek Kundu, Qi Long

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There is a growing body of literature on knowledge-guided statistical learning methods for analysis of structured high-dimensional data (such as genomic and transcriptomic data) that can incorporate knowledge of underlying networks derived from functional genomics and functional proteomics. These methods have been shown to improve variable selection and prediction accuracy and yield more interpretable results. However, these methods typically use graphs extracted from existing databases or rely on subject matter expertise, which are known to be incomplete and may contain false edges. To address this gap, we propose a graph-guided Bayesian modeling framework to account for network noise in regression …

Action-Outcome Delays Modulate The Temporal Expansion Of Intended Outcomes, Rohan R Donapati, Anuj Shukla, Raju S Bapi

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The phenomenon of intentional binding pertains to the perceived connection between a voluntary action and its anticipated result. When an individual intends an outcome, it appears to subjectively extend in time due to a pre-activation of the intended result, particularly evident at shorter action-outcome delays. However, there is a concern that the operationalisation of intention might have led to a mixed interpretation of the outcome expansion attributed to the pre-activation of intention, given the sensitivity of time perception and intentional binding to external cues that could accelerate the realisation of expectations. To investigate the expansion dynamics of an intended outcome, …

“My Addiction Doesn’T Define Me”—Experiences Of Stigma Among Mothers With Opioid Use Disorder, Christine Bakos-Block, Andreaa Yaatsco, A Sarah Cohen, Francine Vega, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

Opioid use in women has increased by 300% since 1999, and opioid use disorder among pregnant women has quadrupled. The stigma of substance use disorder is a significant barrier to treatment, especially among women. The purpose of this study was to explore the experiences and perceptions of stigma among mothers and the underlying themes. (1) Background: To understand the stigmatization of women with substance use disorders, we interviewed mothers in recovery from opioid use disorder. (2) Methods: Qualitative methods and descriptive analysis was used to extrapolate themes related to the experienced stigma. (3) Results: A total of 20 mothers in …