Biomedical Informatics Commons^™

Pet Image Denoising Based On Denoising Diffusion Probabilistic Model, Kuang Gong, Keith Johnson, Georges El Fakhri, Quanzheng Li, Tinsu Pan

Faculty, Staff and Student Publications

Purpose: Due to various physical degradation factors and limited counts received, PET image quality needs further improvements. The denoising diffusion probabilistic model (DDPM) was a distribution learning-based model, which tried to transform a normal distribution into a specific data distribution based on iterative refinements. In this work, we proposed and evaluated different DDPM-based methods for PET image denoising.

Methods: Under the DDPM framework, one way to perform PET image denoising was to provide the PET image and/or the prior image as the input. Another way was to supply the prior image as the network input with the PET image included …

Transcriptomics Analysis Reveals Potential Mechanisms Underlying Mitochondrial Dysfunction And T Cell Exhaustion In Astronauts’ Blood Cells In Space, Maria Moreno-Villanueva, Luis E Jimenez-Chavez, Stephanie Krieger, Liang-Hao Ding, Ye Zhang, Adriana Babiak-Vazquez, Mark Berres, Sandra Splinter, Kristen E Pauken, Brian C Schaefer, Brian E Crucian, Honglu Wu

Faculty, Staff and Student Publications

Introduction: The impact of spaceflight on the immune system and mitochondria has been investigated for decades. However, the molecular mechanisms underlying spaceflight-induced immune dysregulations are still unclear.

Methods: In this study, blood from eleven crewmembers was collected before and during International Space Station (ISS) missions. Transcriptomic analysis was performed in isolated peripheral blood mononuclear cells (PBMCs) using RNA-sequencing. Differentially expresses genes (DEG) in space were determined by comparing of the inflight to the preflight samples. Pathways and statistical analyses of these DEG were performed using the Ingenuity Pathway Analysis (IPA) tool.

Results: In comparison to pre-flight, a total of 2030 …

Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar

Honors Undergraduate Theses

Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …

Xuebijing Improves Intestinal Microcirculation Dysfunction In Septic Rats By Regulating The Vegf-A/Pi3k/Akt Signaling Pathway, A-Ling Tang, Yan Li, Li-Chao Sun, Xiao-Yu Liu, Nan Gao, Sheng-Tao Yan, Guo-Qiang Zhang

Faculty, Staff and Student Publications

BACKGROUND: This study aims to explore whether Xuebijing (XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.

METHODS: A rat model of sepsis was established by cecal ligation and puncture (CLP). A total of 30 male SD rats were divided into four groups: sham group, CLP group, XBJ + axitinib group, and XBJ group. XBJ was intraperitoneally injected 2 h before CLP. Hemodynamic data (blood pressure and heart rate) were recorded. The intestinal microcirculation data of the rats were analyzed via microcirculation imaging. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum levels of interleukin-6 (IL-6), …

Predicting Endothelium-Dependent Diastolic Function (Fmd)And Its Correlation With The Degree Of Coronary Artery Disease (Cad) And Plaque Vulnerability For Cardiovascular Events, Guangming Zhang, Jing Yang, Hanghang Xing, Hongning Yin, Guoqing Gu

Faculty, Staff and Student Publications

OBJECTIVE: This study aims to investigate the correlation between vascular endothelium-dependent diastolic function (FMD) and the degree of coronary artery disease (CAD), plaque vulnerability, and its predictive value for cardiovascular events.

METHODS: Initially, patients (n=100) who were admitted from January 2020 to January 2021 and intended to undergo percutaneous coronary intervention (PCI) were selected. Further, FMD in all patients was determined before the procedure and divided into a high-FMD group (≥4.2%) and a low-FMD group (

RESULTS: No significant differences were observed concerning general information, number of coronary arteries-associated branches, lesion type, involvement of the left main stem (LM), the …

Protein-Centric Omics Analysis Reveals Circulating Complements Linked To Non-Viral Liver Diseases As Potential Therapeutic Targets, Yingzhou Shi, Hang Dong, Shiwei Sun, Xiaoqin Wu, Jiansong Fang, Jianbo Zhao, Junming Han, Zongyue Li, Huixiao Wu, Luna Liu, Wanhong Wu, Yang Tian, Guandou Yuan, Xiude Fan, Chao Xu

Faculty, Staff and Student Publications

BACKGROUND/AIMS: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.

METHODS: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.

RESULTS: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018-1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk …

Statins Are Rarely Prescribed For Incidentally Discovered Covert Cerebrovascular Disease: A Retrospective Cohort In A Large Electronic Health Record (Ehr) Identified Using Natural Language Processing, Lester Y Leung, Eric Puttock, David F Kallmes, Patrick Luetmer, Sunyang Fu, Chengyi X Zheng, Hongfang Liu, Wansu Chen, David M Kent

Faculty, Staff and Student Publications

Introduction: While incidentally discovered covert cerebrovascular diseases (id-CCD) are associated with future stroke, it is not known if patients with id-CCD are prescribed statins.

Methods: Patients age ≥50 with id-CCD on neuroimaging from 2009 to 2019 with no prior ischaemic stroke, transient ischaemic attack or dementia were identified using natural language processing in a large real-world cohort. Robust Poisson multivariable regression was used to assess statin prescription among patients without prior statins.

Results: Among 2 41 050 patients, 74 975 patients (31.1%; 4.7% with covert brain infarcts (CBI); 29.0% with white matter disease (WMD)) had id-CCD. 53.5% (95% CI 53.2 …

Feasible Diet And Circadian Interventions Reduce In Vivo Progression Of Flt3-Itd-Positive Acute Myeloid Leukemia, Megan Rodriguez, Baharan Fekry, Brianna Murphy, Mary Figueroa, Tiewei Cheng, Margaret Raber, Lisa Wartenberg, Donna Bell, Lisa Triche, Karla Crawford, Huaxian Ma, Kendra Allton, Ruwaida Ahmed, Jaime Tran, Christine Ranieri, Marina Konopleva, Michelle Barton, Cesar Nunez, Kristin Eckel-Mahan, Joya Chandra

Faculty, Staff and Student Publications

BACKGROUND: Acute myeloid leukemia (AML) with an internal tandem duplication in the fms-like tyrosine kinase receptor 3 gene (FLT3-ITD) is associated with poor survival, and few studies have examined the impact of modifiable behaviors, such as nutrient quality and timing, in this subset of acute leukemia.

METHODS: The influence of diet composition (low-sucrose and/or low-fat diets) and timing of diet were tested in tandem with anthracycline treatment in orthotopic xenograft mouse models. A pilot clinical study to test receptivity of pediatric leukemia patients to macronutrient matched foods was conducted. A role for the circadian protein, BMAL1 (brain and muscle ARNT-like …

Prioritizing Clinically Significant Lung Cancer Somatic Mutations For Targeted Therapy Through Efficient Ngs Data Filtering System, Jinlian Wang, Hui Li, Hongfang Liu

Faculty, Staff and Student Publications

In the realm of lung cancer treatment, where genetic heterogeneity presents formidable challenges, precision oncology demands an exacting approach to identify and hierarchically sort clinically significant somatic mutations. Current Next-Generation Sequencing (NGS) data filtering pipelines, while utilizing various external databases for mutation screening, often fall short in comprehensive integration and flexibility needed to keep pace with the evolving landscape of clinical data. Our study introduces a sophisticated NGS data filtering system, which not only aggregates but effectively synergizes diverse data sources, encompassing genetic variants, gene functions, clinical evidence, and an extensive body of literature. This system is distinguished by a …

New-Onset Diabetes Is A Predictive Risk Factor For Pancreatic Lesions In High-Risk Individuals: An Observational Cohort Study, Seyda Baydogan, Chirayu Mohindroo, Merve Hasanov, Maria F Montiel, Pompeyo Quesada, Irina M Cazacu, Adrianna A Luzuriaga Chavez, Maureen E Mork, Wenli Dong, Lei Feng, Y Nancy You, Banu Arun, Eduardo Vilar, Powel Brown, Matthew H G Katz, Suresh T Chari, Anirban Maitra, Eric P Tamm, Michael P Kim, Manoop S Bhutani, Florencia Mcallister

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Pancreatic cancer (PC) is the third cause of cancer-related deaths. Early detection and interception of premalignant pancreatic lesions represent a promising strategy to improve outcomes. We evaluated risk factors of focal pancreatic lesions (FPLs) in asymptomatic individuals at hereditary high risk for PC.

METHODS: This is an observational single-institution cohort study conducted over a period of 5 years. Surveillance was performed through imaging studies (EUS or magnetic resonance imaging/magnetic resonance cholangiopancreatography) and serum biomarkers. We collected demographic characteristics and used univariate and multivariate logistic regression models to evaluate associations between potential risk factors and odd ratios (ORs) …

Systemic Treatment Of Patients With Metastatic Breast Cancer: Asco Resource-Stratified Guideline Q And A, Sana Al Sukhun, Bogda Koczwara, Sarah Temin, Banu K Arun

Faculty, Staff and Student Publications

The Systemic Treatment of Patients with Metastatic Breast Cancer: @ASCO Resource-Stratified Guideline Q and A presents takeways, rationale, and key recommendations based on #JCOGO full guideline for patients by menopausal and marker status.

Developing Medical Genetics In A Low-Income Country: Unveiling The Journey Of The Pakistani Society Of Medical Genetics And Genomics (Psmg), Aisha Furqan, Syed A Ahmed, Rizwan Naeem, Myla Ashfaq

Faculty, Staff and Student Publications

No abstract provided.

Mouse Models Of Chronic Lymphocytic Leukemia And Richter Transformation: What We Have Learnt And What We Are Missing, Maria Teresa Sabrina Bertilaccio, Shih-Shih Chen

Faculty, Staff and Student Publications

Although the chronic lymphocytic leukemia (CLL) treatment landscape has changed dramatically, unmet clinical needs are emerging, as CLL in many patients does not respond, becomes resistant to treatment, relapses during treatment, or transforms into Richter. In the majority of cases, transformation evolves the original leukemia clone into a diffuse large B-cell lymphoma (DLBCL). Richter transformation (RT) represents a dreadful clinical challenge with limited therapeutic opportunities and scarce preclinical tools. CLL cells are well known to highly depend on survival signals provided by the tumor microenvironment (TME). These signals enhance the frequency of immunosuppressive cells with protumor function, including regulatory CD4

Comprehensive Analysis Of Craniopharyngioma: Epidemiology, Clinical Characteristics, Management Strategies, And Role Of Radiotherapy, Amir Mushtaq, Mohsin Fayaz, Abdul Rashid Bhat, Abbas F Abdul Hussein, Gianluca Ferini, Giuseppe Emmanuele Umana, Gianluca Scalia, Feroze Ahmad Mir, Aizul Khursheed, Bipin Chaurasia

Faculty, Staff and Student Publications

BACKGROUND/AIM: Craniopharyngiomas pose challenges in diagnosis and management due to their rare occurrence and diverse clinical manifestations. This study aimed to provide a comprehensive analysis of cranio-pharyngioma, including its epidemiological trends, clinical presentations, radiological characteristics, surgical interventions, and the role of radiotherapy.

PATIENTS AND METHODS: A retrospective observational study was conducted on 23 patients diagnosed with craniopharyngioma at our hospital from August 2017 to July 2019. Data regarding demographics, clinical presentation, radiological findings, surgical interventions, and adjuvant therapies were collected and analyzed.

RESULTS: Craniopharyngiomas exhibited a bimodal age distribution, with peaks in childhood and late adulthood. Clinical presentations varied between …

A Relay Velocity Model Infers Cell-Dependent Rna Velocity, Shengyu Li, Pengzhi Zhang, Weiqing Chen, Lingqun Ye, Kristopher W Brannan, Nhat-Tu Le, Jun-Ichi Abe, John P Cooke, Guangyu Wang

Faculty, Staff and Student Publications

RNA velocity provides an approach for inferring cellular state transitions from single-cell RNA sequencing (scRNA-seq) data. Conventional RNA velocity models infer universal kinetics from all cells in an scRNA-seq experiment, resulting in unpredictable performance in experiments with multi-stage and/or multi-lineage transition of cell states where the assumption of the same kinetic rates for all cells no longer holds. Here we present cellDancer, a scalable deep neural network that locally infers velocity for each cell from its neighbors and then relays a series of local velocities to provide single-cell resolution inference of velocity kinetics. In the simulation benchmark, cellDancer shows robust …

Linking Artificial Sweetener Intake With Kidney Function: Insights From Nhanes 2003-2006 And Findings From Mendelian Randomization Research, Zhuoling Ran, Yuxuan Zheng, Lin Yu, Yuxian Zhang, Zhenjiang Zhang, Huijie Li, Xuhan Li, Jing Song, Li Zhang, Ran Zhang, Chang Lu, Yang Gong, Jian Gong

Faculty, Staff and Student Publications

BACKGROUND: The current investigation examines the association between artificial sweetener (AS) consumption and the likelihood of developing chronic kidney disease (CKD), along with its impact on kidney function.

METHODS: We utilized data from the National Health and Nutrition Examination Survey from 2003-2006 to conduct covariance analysis and weighted adjusted logistic regression, aiming to assess the association between artificial sweetener intake and CKD risk, as well as kidney function indicators. Subsequently, we employed Mendelian randomization methods to validate the causal relationship between the intake of artificial sweeteners, CKD risk, and kidney function indicators. Instrumental variable analysis using inverse-variance weighting and Robust …

Intermittent Theta Burst Stimulation And Functional Connectivity In People Living With Hiv/Aids Who Smoke Tobacco Cigarettes: A Preliminary Pilot Study, Gopalkumar Rakesh, Thomas G Adams, Rajendra A Morey, Joseph L Alcorn, Rebika Khanal, Amanda E Su, Seth S Himelhoch, Craig R Rush

Faculty, Staff and Student Publications

BACKGROUND: People living with HIV (PLWHA) smoke at three times the rate of the general population and respond poorly to cessation strategies. Previous studies examined repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (L. dlPFC) to reduce craving, but no studies have explored rTMS among PLWHA who smoke. The current pilot study compared the effects of active and sham intermittent theta-burst stimulation (iTBS) on resting state functional connectivity (rsFC), cigarette cue attentional bias, and cigarette craving in PLWHA who smoke.

METHODS: Eight PLWHA were recruited (single-blind, within-subject design) to receive one session of iTBS (n=8) over the L. …

Modernizing And Harmonizing Regulatory Data Requirements For Genetically Modified Crops-Perspectives From A Workshop, Nicholas P Storer, Abigail R Simmons, Jordan Sottosanto, Jennifer A Anderson, Ming Hua Huang, Debbie Mahadeo, Carey A Mathesius, Mitscheli Sanches Da Rocha, Shuang Song, Ewa Urbanczyk-Wochniak

Faculty, Staff and Student Publications

Genetically modified (GM) crops that have been engineered to express transgenes have been in commercial use since 1995 and are annually grown on 200 million hectares globally. These crops have provided documented benefits to food security, rural economies, and the environment, with no substantiated case of food, feed, or environmental harm attributable to cultivation or consumption. Despite this extensive history of advantages and safety, the level of regulatory scrutiny has continually increased, placing undue burdens on regulators, developers, and society, while reinforcing consumer distrust of the technology. CropLife International held a workshop at the 16th International Society of Biosafety Research …

Vagus Nerve Stimulation For The Therapy Of Dravet Syndrome: A Systematic Review And Meta-Analysis, Shuang Chen, Man Li, Ming Huang

Faculty, Staff and Student Publications

OBJECTIVE: Dravet syndrome (DS) is a refractory developmental and epileptic encephalopathy characterized by seizures, developmental delay and cognitive impairment with a variety of comorbidities, including autism-like behavior, speech dysfunction, and ataxia. Vagus nerve stimulation (VNS) is one of the common therapies for DS. Here, we aim to perform a meta-analysis and systematic review of the efficacy of VNS in DS patients.

METHODS: We systematically searched four databases (PubMed, Embase, Cochrane and CNKI) to identify potentially eligible studies from their inception to January 2024. These studies provided the effective rate of VNS in treating patients with DS. The proportions of DS …

Fc Gamma Receptors Promote Antibody-Induced Lilrb4 Internalization And Immune Regulation Of Monocytic Aml, Joshua W Morse, Xun Gui, Mi Deng, Ryan Huang, Xiaohua Ye, Peng Zhao, Xuejun Fan, Wei Xiong, Chengcheng Zhang, Ningyan Zhang, Zhiqiang An

Faculty, Staff and Student Publications

The immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4) is found specifically on the cell surface of acute monocytic leukemia (monocytic AML), an aggressive and common subtype of AML. We have developed a humanized monoclonal IgG1 LILRB4-blocking antibody (h128-3), which improved immune regulation but reduced cell surface expression of LILRB4 in monocytic AML models by 40–60%. Interestingly, most of this effect was neutralized by mutation of the Fc region of the antibody (h128-3/N297A), which prevents interaction with Fc gamma receptors (FcγRs). This suggested that there is FcγR-dependent antigenic modulation underlying h128-3’s effects, a mechanism known to alter the function of antibodies …

Neuromuscular Polytrauma Pain Is Resolved By Macrophage Cox-2 Nanoimmunomodulation, Ibdanelo Cortez, Caitlyn M Gaffney, Riddhi Vichare, Caitlin V Crelli, Lu Liu, Eric Lee, Jules Edralin, James M Nichols, Hoang Vu Pham, Syed Mehdi, Jelena M Janjic, Andrew J Shepherd

Faculty, Staff and Student Publications

Soft tissue injuries often involve muscle and peripheral nerves and are qualitatively distinct from single-tissue injuries. Prior research suggests that damaged innervation compromises wound healing. To test this in a traumatic injury context, we developed a novel mouse model of nerve and lower limb polytrauma, which features greater pain hypersensitivity and more sustained macrophage infiltration than either injury in isolation. We also show that macrophages are crucial mediators of pain hypersensitivity in this model by delivering macrophage-targeted nanoemulsions laden with the cyclooxygenase-2 (COX-2) inhibitor celecoxib. This treatment was more effective in males than females, and more effective when delivered 3 …

Approaches To Estimate Bidirectional Causal Effects Using Mendelian Randomization With Application To Body Mass Index And Fasting Glucose, Jinhao Zou, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Mendelian randomization (MR) is an epidemiological framework using genetic variants as instrumental variables (IVs) to examine the causal effect of exposures on outcomes. Statistical methods based on unidirectional MR (UMR) are widely used to estimate the causal effects of exposures on outcomes in observational studies. To estimate the bidirectional causal effects between two phenotypes, investigators have naively applied UMR methods separately in each direction. However, bidirectional causal effects between two phenotypes create a feedback loop that biases the estimation when UMR methods are naively applied. To overcome this limitation, we proposed two novel approaches to estimate bidirectional causal effects using …

Hpv Vaccination In Africa In The Covid-19 Era: A Cross-Sectional Survey Of Healthcare Providers' Knowledge, Training, And Recommendation Practices, Joel Fokom Domgue, Issimouha Dille, Sharon Kapambwe, Robert Yu, Freddy Gnangnon, Lameck Chinula, Gad Murenzi, Nomonde Mbatani, Mala Pande, Fatoumata Sidibe, Joseph Kamgno, Bangaly Traore, Hicham El Fazazi, Mamadou Diop, Pierre-Marie Tebeu, Mohenou Isidore Diomande, Fabrice Lecuru, Isaac Adewole, Marie Plante, Partha Basu, Jean-Marie Dangou, Sanjay Shete

Faculty, Staff and Student Publications

INTRODUCTION: Although the burden of cervical cancer in Africa is highest, HPV vaccination coverage remains alarmingly low in this region. Providers' knowledge and recommendation are key drivers of HPV vaccination uptake. Yet, evidence about providers' knowledge and recommendation practices about the HPV vaccine against a backdrop of emerging vaccine hesitancy fueled by the COVID-19 pandemic is lacking in Africa.

METHODS: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior training, the availability of the HPV vaccine in their practice, whether they recommended the HPV vaccine, …

Secondhand Tobacco Smoke Exposure In Homes And Vehicles In Youth: Disparities Among Racial, And Sexual And Gender Minorities, Rajesh Talluri, Sahil S Shete, Surendra S Shastri, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: Secondhand smoke exposure (SHSe) among youth is a serious public health concern, leading to an increased risk of conditions such as asthma and respiratory infections. However, there is little research on SHSe among vulnerable populations, such as racial and sexual minorities. Understanding the factors associated with youth SHSe in homes and vehicles is crucial to developing better protective policies.

METHODS: This study utilized 2020 data from the National Youth Tobacco Survey, a representative sample of middle- and high-school students in the US. The primary outcomes were youth SHSe at home and while riding in a vehicle. Multinomial regression models …

Immune-Related Adverse Event In The Emergency Department: Methodology Of The Immune-Related Emergency Disposition Index (Iredi), Cielito C Reyes-Gibby, Jeffrey M Caterino, Christopher J Coyne, Demetrios N Kyriacou, Aiham Qdaisat, Jennifer Mcquade, Dwight H Owen, Jason J Bischof, Sanjay Shete, Sai-Ching Jim Yeung

Faculty, Staff and Student Publications

For many cancer patients, immune checkpoint inhibitors (ICIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICIs can be debilitating and can quickly become severe or even be fatal. Often, irAEs will precipitate visits to the emergency department (ED). Therefore, early recognition and the decision to admit, observe, or discharge these patients from the ED can be key to a cancer patient's morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe, or discharge) within 2-6 h from their patient's ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the …

Sdha Secondary Findings In Germline Testing: Counseling And Surveillance Considerations, Catherine M Skefos, Pamela L Brock, Erica Blouch, Samantha E Greenberg

Faculty, Staff and Student Publications

This commentary explores the complexities faced by clinicians when encountering a secondary SDHA pathogenic variant (PV) in patients without a personal or family history of SDHA-related tumors. The increasing use of germline multi-gene panel testing has led to a rise in such secondary findings, necessitating a nuanced approach to counseling, surveillance, and decision-making. We aim to discuss the current data surrounding the penetrance of SDHA PVs, the spectrum of screening guidelines, recommendations for educating individuals and families about their secondary findings, and the need for future research to optimize care for these individuals. Practical recommendations for clinicians dealing with …

A Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Diseasea Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Disease, Ofir Sade, Daphna Fischel, Noa Barak-Broner, Shir Halevi, Irit Gottfried, Dana Bar-On, Stefan Sachs, Anat Mirelman, Avner Thaler, Aviv Gour, Meir Kestenbaum, Mali Gana Weisz, Saar Anis, Claudio Soto, Melanie Shanie Roitman, Shimon Shahar, Kathrin Doppler, Markus Sauer, Nir Giladi, Nirit Lev, Roy N Alcalay, Sharon Hassin-Baer, Uri Ashery

Faculty, Staff and Student Publications

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson’s disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, …

Combining Egfr And Kras G12c Inhibitors For Kras G12c Mutated Advanced Colorectal Cancer, Hirotaka Miyashita, David S Hong

Faculty, Staff and Student Publications

KRAS is a commonly mutated gene in advanced colorectal cancer (CRC). Recently, inhibitors of KRAS G12C were developed and have shown promising efficacy for KRAS G12C mutated non-small cell lung cancer. However, KRAS G12C inhibitor monotherapy has not demonstrated excellent efficacy for KRAS G12C mutated advanced CRC due to multiple resistance mechanisms, especially receptor tyrosine kinase (RTK) signaling activation. To overcome this resistance mechanism, various combinations of epithelial growth factor receptor (EGFR) and KRAS G12C inhibitors, including panitumumab plus sotorasib, have been investigated in clinical trials. The combination of EGFR and KRAS G12C inhibitors for KRAS G12C mutated CRC demonstrated …

Sotorasib With Panitumumab In Chemotherapy-Refractory Kras G12c-Mutated Colorectal Cancer: A Phase 1b Trial, Yasutoshi Kuboki, Marwan Fakih, John Strickler, Rona Yaeger, Toshiki Masuishi, Edward J Kim, Christine M Bestvina, Scott Kopetz, Gerald S Falchook, Corey Langer, John Krauss, Sonam Puri, Panli Cardona, Emily Chan, Tracy Varrieur, Lata Mukundan, Abraham Anderson, Qui Tran, David S Hong

Faculty, Staff and Student Publications

The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, and panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, was hypothesized to overcome treatment-induced resistance. This phase 1b substudy of the CodeBreaK 101 master protocol evaluated sotorasib plus panitumumab in patients with chemotherapy-refractory KRAS

A Phase 2, Multicenter, Open-Label Study Of Anti-Lag-3 Ieramilimab In Combination With Anti-Pd-1 Spartalizumab In Patients With Advanced Solid Malignancies, Chia-Chi Lin, Elena Garralda, Patrick Schöffski, David S Hong, Lillian L Siu, Miguel Martin, Michela Maur, Rina Hui, Ross A Soo, Joanne Chiu, Tian Zhang, Brigette Ma, Chrisann Kyi, Daniel Sw Tan, Philippe A Cassier, John Sarantopoulos, Andrew Weickhardt, Richard D Carvajal, Jennifer Spratlin, Taito Esaki, Fréderic Rolland, Wallace Akerley, Barbara Deschler-Baier, Lawrence Rispoli, Tanay S Samant, Niladri Roy Chowdhury, Daniel Gusenleitner, Eunice L Kwak, Vasileios Askoxylakis, Filippo De Braud

Faculty, Staff and Student Publications

Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated). Patients received ieramilimab (400 mg) followed by spartalizumab (300 mg) every 3 weeks. The primary endpoint was objective response rate (ORR), along …