Open Access. Powered by Scholars. Published by Universities.®

Medical Specialties Commons™

Open Access. Powered by Scholars. Published by Universities.®

2024

Discipline
Institution
Keyword
Publication
Publication Type
File Type

Articles 4141 - 4170 of 9452

Full-Text Articles in Medical Specialties

The Kat Module Of The Saga Complex Maintains The Oncogenic Gene Expression Program In Mycn- Amplified Neuroblastoma, Clare F Malone, Nathaniel W Mabe, Alexandra B Forman, Gabriela Alexe, Kathleen L Engel, Ying-Jiun C Chen, Melinda Soeung, Silvi Salhotra, Allen Basanthakumar, Bin Liu, Sharon Y R Dent, Kimberly Stegmaier May 2024

The Kat Module Of The Saga Complex Maintains The Oncogenic Gene Expression Program In Mycn- Amplified Neuroblastoma, Clare F Malone, Nathaniel W Mabe, Alexandra B Forman, Gabriela Alexe, Kathleen L Engel, Ying-Jiun C Chen, Melinda Soeung, Silvi Salhotra, Allen Basanthakumar, Bin Liu, Sharon Y R Dent, Kimberly Stegmaier

Faculty, Staff and Student Publications

Pediatric cancers are frequently driven by genomic alterations that result in aberrant transcription factor activity. Here, we used functional genomic screens to identify multiple genes within the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex as selective dependencies for MYCN-amplified neuroblastoma, a disease of dysregulated development driven by an aberrant oncogenic transcriptional program. We characterized the DNA recruitment sites of the SAGA complex in neuroblastoma and the consequences of loss of SAGA complex lysine acetyltransferase (KAT) activity on histone acetylation and gene expression. We demonstrate that loss of SAGA complex KAT activity is associated with reduced MYCN binding on chromatin, suppression of …


Using Patient-Specific 3d Modeling And Simulations To Optimize Microwave Ablation Therapy For Liver Cancer, Amirreza Heshmat, Caleb S O'Connor, Jessica Albuquerque Marques Silva, Iwan Paolucci, Aaron Kyle Jones, Bruno C Odisio, Kristy K Brock May 2024

Using Patient-Specific 3d Modeling And Simulations To Optimize Microwave Ablation Therapy For Liver Cancer, Amirreza Heshmat, Caleb S O'Connor, Jessica Albuquerque Marques Silva, Iwan Paolucci, Aaron Kyle Jones, Bruno C Odisio, Kristy K Brock

Faculty, Staff and Student Publications

Microwave ablation (MWA) of liver tumors presents challenges like under- and over-ablation, potentially leading to inadequate tumor destruction and damage to healthy tissue. This study aims to develop personalized three-dimensional (3D) models to simulate MWA for liver tumors, incorporating patient-specific characteristics. The primary objective is to validate the predicted ablation zones compared to clinical outcomes, offering insights into MWA before therapy to facilitate accurate treatment planning. Contrast-enhanced CT images from three patients were used to create 3D models. The simulations used coupled electromagnetic wave propagation and bioheat transfer to estimate the temperature distribution, predicting tumor destruction and ablation margins. The …


Nivolumab Plus Relatlimab In Patients With Previously Treated Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase Ii Checkmate 142 Study, Michael J Overman, Fabio Gelsomino, Massimo Aglietta, Mark Wong, Maria Luisa Limon Miron, Gregory Leonard, Pilar García-Alfonso, Andrew G Hill, Antonio Cubillo Gracian, Eric Van Cutsem, Bassel El-Rayes, Stephen M Mccraith, Beilei He, Ming Lei, Sara Lonardi May 2024

Nivolumab Plus Relatlimab In Patients With Previously Treated Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase Ii Checkmate 142 Study, Michael J Overman, Fabio Gelsomino, Massimo Aglietta, Mark Wong, Maria Luisa Limon Miron, Gregory Leonard, Pilar García-Alfonso, Andrew G Hill, Antonio Cubillo Gracian, Eric Van Cutsem, Bassel El-Rayes, Stephen M Mccraith, Beilei He, Ming Lei, Sara Lonardi

Faculty, Staff and Student Publications

BACKGROUND: Programmed death-1 (PD-1) inhibitors, including nivolumab, have demonstrated long-term survival benefit in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (CRC). PD-1 and lymphocyte-activation gene 3 (LAG-3) are distinct immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes and contribute to tumor-mediated T-cell dysfunction. Relatlimab is a LAG-3 inhibitor that has demonstrated efficacy in combination with nivolumab in patients with melanoma. Here, we present the results from patients with MSI-H/dMMR metastatic CRC treated with nivolumab plus relatlimab in the CheckMate 142 study.

METHODS: In this open-label, phase II study, previously treated patients with MSI-H/dMMR metastatic CRC …


Systematic Review And Dosage Analysis: Hyperbaric Oxygen Therapy Efficacy In The Treatment Of Posttraumatic Stress Disorder, Susan R. Andrews, Paul G. Harch May 2024

Systematic Review And Dosage Analysis: Hyperbaric Oxygen Therapy Efficacy In The Treatment Of Posttraumatic Stress Disorder, Susan R. Andrews, Paul G. Harch

School of Medicine Faculty Publications

Background: Studies of hyperbaric oxygen therapy (HBOT) treatment of mild traumatic brain injury persistent postconcussion syndrome in military and civilian subjects have shown simultaneous improvement in posttraumatic stress disorder (PTSD) or PTSD symptoms, suggesting that HBOT may be an effective treatment for PTSD. This is a systematic review and dosage analysis of HBOT treatment of patients with PTSD symptoms. Methods: PubMed, CINAHL, and the Cochrane Systematic Review Database were searched from September 18 to November 23, 2023, for all adult clinical studies published in English on HBOT and PTSD. Randomized trials and studies with symptomatic outcomes were selected for final …


Design And Evaluation Of Scancap: A Low-Cost, Reusable Tethered Capsule Endoscope With Blue-Green Illumination Imaging For Unsedated Screening And Early Detection Of Barrett's Esophagus, Cheima Hicheri, Ahad M Azimuddin, Alex Kortum, Joseph Bailey, Yubo Tang, Richard A Schwarz, Daniel Rosen, Shilpa Jain, Nabil M Mansour, Shawn Groth, Shaleen Vasavada, Ashwin Rao, Adrianna Maliga, Leslie Gallego, Jennifer Carns, Sharmila Anandasabapathy, Rebecca Richards-Kortum May 2024

Design And Evaluation Of Scancap: A Low-Cost, Reusable Tethered Capsule Endoscope With Blue-Green Illumination Imaging For Unsedated Screening And Early Detection Of Barrett's Esophagus, Cheima Hicheri, Ahad M Azimuddin, Alex Kortum, Joseph Bailey, Yubo Tang, Richard A Schwarz, Daniel Rosen, Shilpa Jain, Nabil M Mansour, Shawn Groth, Shaleen Vasavada, Ashwin Rao, Adrianna Maliga, Leslie Gallego, Jennifer Carns, Sharmila Anandasabapathy, Rebecca Richards-Kortum

Faculty, Staff and Students Publications

Esophageal carcinoma is the sixth-leading cause of cancer death worldwide. A precursor to esophageal adenocarcinoma (EAC) is Barrett's Esophagus (BE). Early-stage diagnosis and treatment of esophageal neoplasia (Barrett's with high-grade dysplasia/intramucosal cancer) increase the five-year survival rate from 10% to 98%. BE is a global challenge; however, current endoscopes for early BE detection are costly and require extensive infrastructure for patient examination and sedation. We describe the design and evaluation of the first prototype of ScanCap, a high-resolution optical endoscopy system with a reusable, low-cost tethered capsule, designed to provide high-definition, blue-green illumination imaging for the early detection of BE …


Presynaptic Nanoscale Components Of Retrograde Synaptic Signaling, Benjámin Barti, Barna Dudok, Kata Kenesei, Miklós Zöldi, Vivien Miczán, Gyula Y Balla, Diana Zala, Mariana Tasso, Claudia Sagheddu, Máté Kisfali, Blanka Tóth, Marco Ledri, E Sylvester Vizi, Miriam Melis, László Barna, Zsolt Lenkei, Iván Soltész, István Katona May 2024

Presynaptic Nanoscale Components Of Retrograde Synaptic Signaling, Benjámin Barti, Barna Dudok, Kata Kenesei, Miklós Zöldi, Vivien Miczán, Gyula Y Balla, Diana Zala, Mariana Tasso, Claudia Sagheddu, Máté Kisfali, Blanka Tóth, Marco Ledri, E Sylvester Vizi, Miriam Melis, László Barna, Zsolt Lenkei, Iván Soltész, István Katona

Faculty, Staff and Students Publications

While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell–dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes. Instead, by developing a workflow for physiological, anatomical, and molecular measurements at the same unitary synapse, we demonstrate that the nanoscale stoichiometric ratio of type 1 cannabinoid receptors (CB1Rs) to the release machinery is sufficient to predict synapse-specific release probability. Accordingly, …


Rebuilding The Health Sector In Gaza: Alternative Humanitarian Voices, Karl Blanchet, Martine Najem, Lina Shadid, Rouba Ali Fehmi, Fawzi Al Hammouri, Ghassan Saed, Khaled J Saleh, Mosab Nasser, Nidal Moukaddam, Jonathan Polonsky, Omar Lattouf May 2024

Rebuilding The Health Sector In Gaza: Alternative Humanitarian Voices, Karl Blanchet, Martine Najem, Lina Shadid, Rouba Ali Fehmi, Fawzi Al Hammouri, Ghassan Saed, Khaled J Saleh, Mosab Nasser, Nidal Moukaddam, Jonathan Polonsky, Omar Lattouf

Faculty, Staff and Students Publications

In November 2023, a variety of disparate health organizations formed an international coalition to consolidate efforts and develop collaborative strategies in response to the increasing critical healthcare challenges caused by the recent war in Gaza. The coalition includes medical and public health experts, humanitarian practitioners, academics, and health policy-makers from across the world. Their membership has not much to do with mainstream humanitarian organisations. It is lead by the diaspora from the region. Their vision is the long-term reconstruction of the health system in Gaza while responding the most urgent needs. This collective effort will require explicit efforts to speak …


Multifactoral Immune Modulation Potentiates Durable Remission In Multiple Models Of Aggressive Malignancy, Matthew M Halpert, Briana A Burns, Spencer R Rosario, Henry G Withers, Akshar J Trivedi, Colby J Hofferek, Benjamin D Gephart, Haotong Wang, Jonathan Vazquez-Perez, Sharon B Amanya, Sean T Hyslop, Jianhua Yang, Jan O Kemnade, Vlad C Sandulache, Vanaja Konduri, William K Decker May 2024

Multifactoral Immune Modulation Potentiates Durable Remission In Multiple Models Of Aggressive Malignancy, Matthew M Halpert, Briana A Burns, Spencer R Rosario, Henry G Withers, Akshar J Trivedi, Colby J Hofferek, Benjamin D Gephart, Haotong Wang, Jonathan Vazquez-Perez, Sharon B Amanya, Sean T Hyslop, Jianhua Yang, Jan O Kemnade, Vlad C Sandulache, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

Tumors typically lack canonical danger signals required to activate adaptive immunity and also frequently employ substantial immunomodulatory mechanisms that downregulate adaptive responses and contribute to escape from immune surveillance. Given the variety of mechanisms involved in shielding tumors from immune recognition, it is not surprising that single-agent immunomodulatory approaches have been largely unsuccessful in generating durable antitumor responses. Here we report a unique combination of immunomodulatory and cytostatic agents that recondition the tumor microenvironment and eliminate complex and/or poor-prognosis tumor types including the non-immunogenic 4T-1 model of TNBC, the aggressive MOC-2 model of HNSCC, and the high-risk MYCN-amplified model of …


A Qualitative Exploration Of Well-Being In Cancer Survivorship: Implications For Counselors, Hallie M. Sylvestro, Lindsey K. Umstead, Heather Delgado, Christopher Lawrence, Keith Mobley, Kelly L. Wester, Andrew Wood May 2024

A Qualitative Exploration Of Well-Being In Cancer Survivorship: Implications For Counselors, Hallie M. Sylvestro, Lindsey K. Umstead, Heather Delgado, Christopher Lawrence, Keith Mobley, Kelly L. Wester, Andrew Wood

Adultspan Journal

Adult cancer survivors represent an important–and growing–population that could benefit from counseling services. This study employed consensual qualitative research to examine the well-being experiences of eight cancer survivors. Findings suggest a broad range of changes to individual well-being following cancer diagnosis and treatment, and indicate counseling can provide an ideal setting for processing such changes. Recommendations for counseling practice and future research are provided.


The Effect Of A Dynamic Lighting Schedule On Neurobehavioral Performance During A 45-Day Simulated Space Mission, Leilah Grant, Brianne Kent, Shadab Rahman, Melissa St Hilaire, Crystal Kirkley, Kevin Gregory, Toni Clark, John Hanifin, Laura Barger, Charles Czeisler, George Brainard, Steven Lockley, Erin Flynn-Evans May 2024

The Effect Of A Dynamic Lighting Schedule On Neurobehavioral Performance During A 45-Day Simulated Space Mission, Leilah Grant, Brianne Kent, Shadab Rahman, Melissa St Hilaire, Crystal Kirkley, Kevin Gregory, Toni Clark, John Hanifin, Laura Barger, Charles Czeisler, George Brainard, Steven Lockley, Erin Flynn-Evans

Department of Neurology Faculty Papers

Study Objective: We previously reported that during a 45-day simulated space mission, a dynamic lighting schedule (DLS) improved circadian phase alignment and performance assessed once on selected days. This study aimed to evaluate how DLS affected performance on a 5-minute psychomotor vigilance task (PVT) administered multiple times per day on selected days.

Methods: Sixteen crewmembers (37.4 ± 6.7 years; 5F) underwent six cycles of 2 × 8-hour/night followed by 5 × 5-hour/night sleep opportunities. During the DLS (n = 8), daytime white light exposure was blue-enriched (∼6000 K; Level 1: 1079, Level 2: 76 melanopic equivalent daytime illuminance (melEDI) lux) …


Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales May 2024

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …


Molecular Classification And Biomarkers Of Outcome With Immunotherapy In Extensive-Stage Small-Cell Lung Cancer: Analyses Of The Caspian Phase 3 Study, Mingchao Xie, Miljenka Vuko, Jaime Rodriguez-Canales, Johannes Zimmermann, Markus Schick, Cathy O'Brien, Luis Paz-Ares, Jonathan W Goldman, Marina Chiara Garassino, Carl M Gay, John V Heymach, Haiyi Jiang, J Carl Barrett, Ross A Stewart, Zhongwu Lai, Lauren A Byers, Charles M Rudin, Yashaswi Shrestha May 2024

Molecular Classification And Biomarkers Of Outcome With Immunotherapy In Extensive-Stage Small-Cell Lung Cancer: Analyses Of The Caspian Phase 3 Study, Mingchao Xie, Miljenka Vuko, Jaime Rodriguez-Canales, Johannes Zimmermann, Markus Schick, Cathy O'Brien, Luis Paz-Ares, Jonathan W Goldman, Marina Chiara Garassino, Carl M Gay, John V Heymach, Haiyi Jiang, J Carl Barrett, Ross A Stewart, Zhongwu Lai, Lauren A Byers, Charles M Rudin, Yashaswi Shrestha

Faculty, Staff and Student Publications

BACKGROUND: We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial.

METHODS: 805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue …


Multiomics Analysis Of The Phlda Gene Family In Different Cancers And Their Clinical Prognostic Value, Safia Iqbal, Md Rezaul Karim, Shahnawaz Mohammad, Ramya Mathiyalagan, Md Niaj Morshed, Deok-Chun Yang, Hyocheol Bae, Esrat Jahan Rupa, Dong Uk Yang May 2024

Multiomics Analysis Of The Phlda Gene Family In Different Cancers And Their Clinical Prognostic Value, Safia Iqbal, Md Rezaul Karim, Shahnawaz Mohammad, Ramya Mathiyalagan, Md Niaj Morshed, Deok-Chun Yang, Hyocheol Bae, Esrat Jahan Rupa, Dong Uk Yang

Faculty, Staff and Student Publications

The PHLDA (pleckstrin homology-like domain family) gene family is popularly known as a potential biomarker for cancer identification, and members of the PHLDA family have become considered potentially viable targets for cancer treatments. The PHLDA gene family consists of PHLDA1, PHLDA2, and PHLDA3. The predictive significance of PHLDA genes in cancer remains unclear. To determine the role of pleckstrin as a prognostic biomarker in human cancers, we conducted a systematic multiomics investigation. Through various survival analyses, pleckstrin expression was evaluated, and their predictive significance in human tumors was discovered using a variety of online platforms. By analyzing the protein-protein interactions, …


Blunt Cerebrovascular Injury (Bcvi): Universal Cta Neck Screening At Level 2 Trauma Center, Tamine Gogel May 2024

Blunt Cerebrovascular Injury (Bcvi): Universal Cta Neck Screening At Level 2 Trauma Center, Tamine Gogel

Doctor of Nursing Practice Projects

Blunt Cerebrovascular Injury (BCVI) refers to injuries to the vessels supplying blood to the brain, primarily carotid and vertebral arteries, and can result from trauma, resulting in stroke by vessel dissection, thrombus formation, embolization, and hemorrhage. Timely identification is crucial for effective intervention and improved outcomes. This doctoral project proposes the implementation of universal screening using Computed Tomography Angiography (CTA) of the neck during initial workup for blunt force trauma at a Level II ACS-verified trauma center. The primary objective is to mitigate potential delays in diagnosing and treating BCVI, thereby reducing the likelihood of complications. Patients ≥ 15 years …


Infection-Related Readmissions Are Rising Among Patients With Hepatorenal Syndrome: A Nationwide Analysis, Umer Farooq, Zahid I. Tarar, Ammad J. Chaudhary, Abdallah E. Alayli, Faisal Kamal, Chengdu Niu, Kamran Qureshi May 2024

Infection-Related Readmissions Are Rising Among Patients With Hepatorenal Syndrome: A Nationwide Analysis, Umer Farooq, Zahid I. Tarar, Ammad J. Chaudhary, Abdallah E. Alayli, Faisal Kamal, Chengdu Niu, Kamran Qureshi

Division of Gastroenterology and Hepatology Faculty Papers

Hepatorenal syndrome (HRS) is a unique form of renal dysfunction that results from circulatory hemodynamic dysfunction in advanced liver disease. We aimed to determine longitu- dinal trends in both all-cause and cause-specific readmissions for HRS in the United States. Using the National Readmission Database (2010–2018), we identified adult HRS patients during index admission via ICD codes. Fisher’s exact test and Cox regression analysis were used to compare pro- portions and compute adjusted p-values, respectively. Regression models were adjusted for gender, age, the Charlson comorbidity index, median household income, and hospital factors. A total of 169,522 HRS patients were included in …


Machine Learning Models For Predicting Blood Pressure Phenotypes By Combining Multiple Polygenic Risk Scores, Yana Hrytsenko, Benjamin Shea, Michael Elgart, Nuzulul Kurniansyah, Genevieve Lyons, Alanna C Morrison, April P Carson, Bernhard Haring, Braxton D Mitchell, Bruce M Psaty, Byron C Jaeger, C Charles Gu, Charles Kooperberg, Daniel Levy, Donald Lloyd-Jones, Eunhee Choi, Jennifer A Brody, Jennifer A Smith, Jerome I Rotter, Matthew Moll, Myriam Fornage, Noah Simon, Peter Castaldi, Ramon Casanova, Ren-Hua Chung, Robert Kaplan, Ruth J F Loos, Sharon L R Kardia, Stephen S Rich, Susan Redline, Tanika Kelly, Timothy O'Connor, Wei Zhao, Wonji Kim, Xiuqing Guo, Yii-Der Ida Chen, Trans-Omics In Precision Medicine Consortium, Tamar Sofer May 2024

Machine Learning Models For Predicting Blood Pressure Phenotypes By Combining Multiple Polygenic Risk Scores, Yana Hrytsenko, Benjamin Shea, Michael Elgart, Nuzulul Kurniansyah, Genevieve Lyons, Alanna C Morrison, April P Carson, Bernhard Haring, Braxton D Mitchell, Bruce M Psaty, Byron C Jaeger, C Charles Gu, Charles Kooperberg, Daniel Levy, Donald Lloyd-Jones, Eunhee Choi, Jennifer A Brody, Jennifer A Smith, Jerome I Rotter, Matthew Moll, Myriam Fornage, Noah Simon, Peter Castaldi, Ramon Casanova, Ren-Hua Chung, Robert Kaplan, Ruth J F Loos, Sharon L R Kardia, Stephen S Rich, Susan Redline, Tanika Kelly, Timothy O'Connor, Wei Zhao, Wonji Kim, Xiuqing Guo, Yii-Der Ida Chen, Trans-Omics In Precision Medicine Consortium, Tamar Sofer

Faculty, Staff and Student Publications

We construct non-linear machine learning (ML) prediction models for systolic and diastolic blood pressure (SBP, DBP) using demographic and clinical variables and polygenic risk scores (PRSs). We developed a two-model ensemble, consisting of a baseline model, where prediction is based on demographic and clinical variables only, and a genetic model, where we also include PRSs. We evaluate the use of a linear versus a non-linear model at both the baseline and the genetic model levels and assess the improvement in performance when incorporating multiple PRSs. We report the ensemble model's performance as percentage variance explained (PVE) on a held-out test …


Neurorehabilitation With Vagus Nerve Stimulation: A Systematic Review, Radha Korupolu, Alyssa Miller, Andrew Park, Nuray Yozbatiran May 2024

Neurorehabilitation With Vagus Nerve Stimulation: A Systematic Review, Radha Korupolu, Alyssa Miller, Andrew Park, Nuray Yozbatiran

Faculty, Staff and Student Publications

OBJECTIVE: To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI).

METHODS: Data sources: PubMed, EMBASE, SCOPUS, and Cochrane.

STUDY SELECTION: Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery.

DATA EXTRACTION: Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically.

DATA SYNTHESIS: Twenty-nine studies were included; 11 were animal models of stroke, TBI, and …


Validation Of A Blood-Based Protein Biomarker Panel For A Risk Assessment Of Lethal Lung Cancer In The Physicians' Health Study, Lulu Song, Ehsan Irajizad, Andrew Rundle, Howard D Sesso, John Michael Gaziano, Jody V Vykoukal, Kim-Anh Do, Jennifer B Dennison, Edwin J Ostrin, Johannes F Fahrmann, Frederica Perera, Samir Hanash May 2024

Validation Of A Blood-Based Protein Biomarker Panel For A Risk Assessment Of Lethal Lung Cancer In The Physicians' Health Study, Lulu Song, Ehsan Irajizad, Andrew Rundle, Howard D Sesso, John Michael Gaziano, Jody V Vykoukal, Kim-Anh Do, Jennifer B Dennison, Edwin J Ostrin, Johannes F Fahrmann, Frederica Perera, Samir Hanash

Faculty, Staff and Student Publications

This study aimed to assess a four-marker protein panel (4MP)'s performance, including the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19, for predicting lung cancer in a cohort enriched with never- and ever-smokers. Blinded pre-diagnostic plasma samples collected within 2 years prior to a lung cancer diagnosis from 25 cases and 100 sex-, age-, and smoking-matched controls were obtained from the Physicians' Health Study (PHS). The 4MP yielded AUC performance estimates of 0.76 (95% CI: 0.61-0.92) and 0.69 (95% CI: 0.56-0.82) for predicting lung cancer within one year and within two years of diagnosis, respectively. …


Transport Of Non-Classical Light Mediated By Topological Domain Walls In A Ssh Photonic Lattice, Gabriel O'Ryan Pérez, Joaquín Medina Dueñas, Diego Guzmán-Silva, Luis E F Foa Torres, Carla Hermann-Avigliano May 2024

Transport Of Non-Classical Light Mediated By Topological Domain Walls In A Ssh Photonic Lattice, Gabriel O'Ryan Pérez, Joaquín Medina Dueñas, Diego Guzmán-Silva, Luis E F Foa Torres, Carla Hermann-Avigliano

Faculty, Staff and Student Publications

Advancements in photonics technologies have significantly enhanced their capability to facilitate experiments involving quantum light, even at room temperature. Nevertheless, fully integrating photonic chips that include quantum light sources, effective manipulation and transport of light minimizing losses, and appropriate detection systems remains an ongoing challenge. Topological photonic systems have emerged as promising platforms to protect quantum light properties during propagation, beyond merely preserving light intensity. In this work, we delve into the dynamics of non-classical light traversing a Su-Schrieffer-Heeger photonic lattice with topological domain walls. Our focus centers on how topology influences the quantum properties of light as it moves …


Homologous Recombination Deficiency Should Be Tested For In Patients With Advanced Stage High-Grade Serous Ovarian Cancer Aged 70 Years And Over, Omali Pitiyarachchi, Peter J. Ansell, Robert L. Coleman, Minh H. Dinh, Laura Holman, Charles A. Leath, Theresa Werner, Paul Disilvestro, Mark Morgan, William Tew, Christine Lee, Mary Cunningham, Meredith Newton, Babak Edraki, Peter Lim, Joyce Barlin, Nicola M. Spirtos, Krishnansu S. Tewari, Mitchell I. Edelson, Thomas Reid, Jay Carlson, Michael Friedlander May 2024

Homologous Recombination Deficiency Should Be Tested For In Patients With Advanced Stage High-Grade Serous Ovarian Cancer Aged 70 Years And Over, Omali Pitiyarachchi, Peter J. Ansell, Robert L. Coleman, Minh H. Dinh, Laura Holman, Charles A. Leath, Theresa Werner, Paul Disilvestro, Mark Morgan, William Tew, Christine Lee, Mary Cunningham, Meredith Newton, Babak Edraki, Peter Lim, Joyce Barlin, Nicola M. Spirtos, Krishnansu S. Tewari, Mitchell I. Edelson, Thomas Reid, Jay Carlson, Michael Friedlander

Abington Jefferson Health Papers

OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group.

METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed).

RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). …


Variant-Specific Pathophysiological Mechanisms Of Aff3 Differently Influence Transcriptome Profiles, Sissy Bassani, Jacqueline Chrast, Giovanna Ambrosini, Norine Voisin, Frédéric Schütz, Alfredo Brusco, Fabio Sirchia, Lydia Turban, Susanna Schubert, Rami Abou Jamra, Jan-Ulrich Schlump, Desiree Demille, Pinar Bayrak-Toydemir, Gary Rex Nelson, Kristen Nicole Wong, Laura Duncan, Mackenzie Mosera, Christian Gilissen, Lisenka E L M Vissers, Rolph Pfundt, Rogier Kersseboom, Hilde Yttervik, Geir Åsmund Myge Hansen, Marie Falkenberg Smeland, Kameryn M Butler, Michael J Lyons, Claudia M B Carvalho, Chaofan Zhang, James R Lupski, Lorraine Potocki, Leticia Flores-Gallegos, Rodrigo Morales-Toquero, Florence Petit, Binnaz Yalcin, Annabelle Tuttle, Houda Zghal Elloumi, Lane Mccormick, Mary Kukolich, Oliver Klaas, Judit Horvath, Marcello Scala, Michele Iacomino, Francesca Operto, Federico Zara, Karin Writzl, Aleš Maver, Maria K Haanpää, Pia Pohjola, Harri Arikka, Anneke J A Kievit, Camilla Calandrini, Christian Iseli, Nicolas Guex, Alexandre Reymond May 2024

Variant-Specific Pathophysiological Mechanisms Of Aff3 Differently Influence Transcriptome Profiles, Sissy Bassani, Jacqueline Chrast, Giovanna Ambrosini, Norine Voisin, Frédéric Schütz, Alfredo Brusco, Fabio Sirchia, Lydia Turban, Susanna Schubert, Rami Abou Jamra, Jan-Ulrich Schlump, Desiree Demille, Pinar Bayrak-Toydemir, Gary Rex Nelson, Kristen Nicole Wong, Laura Duncan, Mackenzie Mosera, Christian Gilissen, Lisenka E L M Vissers, Rolph Pfundt, Rogier Kersseboom, Hilde Yttervik, Geir Åsmund Myge Hansen, Marie Falkenberg Smeland, Kameryn M Butler, Michael J Lyons, Claudia M B Carvalho, Chaofan Zhang, James R Lupski, Lorraine Potocki, Leticia Flores-Gallegos, Rodrigo Morales-Toquero, Florence Petit, Binnaz Yalcin, Annabelle Tuttle, Houda Zghal Elloumi, Lane Mccormick, Mary Kukolich, Oliver Klaas, Judit Horvath, Marcello Scala, Michele Iacomino, Francesca Operto, Federico Zara, Karin Writzl, Aleš Maver, Maria K Haanpää, Pia Pohjola, Harri Arikka, Anneke J A Kievit, Camilla Calandrini, Christian Iseli, Nicolas Guex, Alexandre Reymond

Faculty, Staff and Students Publications

BACKGROUND: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects.

METHODS: Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants.

RESULTS: We identified …


Abdominal Congestion As A Predictor Of Worsening Renal Function In Patients With Acute Decompensated Heart Failure, Hossameldin Rezk, Ghada (Sayed) Youssef, Karim Said, Iman (Atef) Mandour, Magdy Abdelhamid May 2024

Abdominal Congestion As A Predictor Of Worsening Renal Function In Patients With Acute Decompensated Heart Failure, Hossameldin Rezk, Ghada (Sayed) Youssef, Karim Said, Iman (Atef) Mandour, Magdy Abdelhamid

Journal of the Saudi Heart Association

Objective: Worsening renal function (WRF) is a frequent finding in patients with acute decompensated heart failure (ADHF) and is a powerful independent prognostic factor for adverse outcomes. The link between abdominal congestion and worsening renal function in such patients is not yet fully addressed. The aim of this study was to evaluate the role of abdominal congestion in the early prediction of worsening renal function in hospitalized patients with acute decompensated heart failure. Methods: This was a prospective study that enrolled 100 patients with a diagnosis of ADHF and received intravenous diuretic therapy. Intra-abdominal pressure (IAP), splenic Doppler impedance indices …


Unveiling The Influence Of Hyponatremia On Morbidity, Mortality, And Resource Utilization In Colorectal Carcinoma: Insights From A 5-Year Nationwide Study., Priya Hotwani Md, Vikash Kumar, Bhavyakumar Vachhani, Mrunanjali Gaddam, Jayalekshmi Jayakumar, Manasa Ginjupalli, Ankushi Sanghvi, Jincy Clement, Dhairya Nanavaty May 2024

Unveiling The Influence Of Hyponatremia On Morbidity, Mortality, And Resource Utilization In Colorectal Carcinoma: Insights From A 5-Year Nationwide Study., Priya Hotwani Md, Vikash Kumar, Bhavyakumar Vachhani, Mrunanjali Gaddam, Jayalekshmi Jayakumar, Manasa Ginjupalli, Ankushi Sanghvi, Jincy Clement, Dhairya Nanavaty

Internal Medicine Residency

Meeting Abstract: 2024 ASCO Annual Meeting

Background: Historically, Hyponatremia has been associated with higher mortality rates and longer hospital stays in patients with solid tumors. The existing literature contains limited information on the connection between hyponatremia and Colorectal cancer (CRC). Thus, our study aimed to assess the impact of hyponatremia on mortality, morbidity, and resource usage in patients with CRC.

Methods: A retrospective analysis using the National Inpatient Sample database and International Classification of Diseases, Tenth Revision codes was conducted to examine the impact of hyponatremia on mortality, morbidity, and resource utilization in patients with CRC. Categorical variables were compared …


Early Outcomes Of Mr-Guided Sbrt For Patients With Recurrent Pancreatic Adenocarcinoma, Spencer Poiset, Sophia Shah, Louis Cappelli, Rani Anné, Karen Mooney, Maria Werner-Wasik, Talya Laufer, James Posey, Daniel Lin, Atrayee Mallick, Harish Lavu, Babar Bashir, Charles Yeo, Adam Mueller May 2024

Early Outcomes Of Mr-Guided Sbrt For Patients With Recurrent Pancreatic Adenocarcinoma, Spencer Poiset, Sophia Shah, Louis Cappelli, Rani Anné, Karen Mooney, Maria Werner-Wasik, Talya Laufer, James Posey, Daniel Lin, Atrayee Mallick, Harish Lavu, Babar Bashir, Charles Yeo, Adam Mueller

Kimmel Cancer Center Faculty Papers

BACKGROUND: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC.

METHODS: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local …


Socioeconomic Factors Influencing Hematological Health In Latin America, Lina M. Barrios, Ms May 2024

Socioeconomic Factors Influencing Hematological Health In Latin America, Lina M. Barrios, Ms

Student Papers, Posters & Projects

Hematological malignancies, also known as blood cancers, such as leukemia, lymphomas, and myelomas, are a significant health concern globally. The incidence of these malignancies has dramatically increased over time, leukemias being the leading cause. The incidence of blood cancers in Latin America exhibits regional variability, with leukemia being the emerging cause as the most prevalent type in children and young adults. However, the overall incidences are oddly lower than in developed countries, potentially due to the underreporting of the cases and the lack of cancer registries. This situation implies a critical need for improving surveillance and data collection methods to …


Efficacy And Safety Of Atezolizumab And Bevacizumab In Appendiceal Adenocarcinoma, Nicholas J Hornstein, Mohammad A Zeineddine, Betul B Gunes, Andrew J Pellatt, Mark Knafl, Haifeng Zhu, Anneleis F Willett, Abdelrahman Yousef, Suyu Liu, Ryan Sun, Andrew Futreal, Scott E Woodman, Melissa W Taggart, Michael J Overman, Daniel M Halperin, Kanwal P Raghav, John Paul Shen May 2024

Efficacy And Safety Of Atezolizumab And Bevacizumab In Appendiceal Adenocarcinoma, Nicholas J Hornstein, Mohammad A Zeineddine, Betul B Gunes, Andrew J Pellatt, Mark Knafl, Haifeng Zhu, Anneleis F Willett, Abdelrahman Yousef, Suyu Liu, Ryan Sun, Andrew Futreal, Scott E Woodman, Melissa W Taggart, Michael J Overman, Daniel M Halperin, Kanwal P Raghav, John Paul Shen

Faculty, Staff and Student Publications

PURPOSE: Appendiceal adenocarcinoma (AA) remains an orphan disease with limited treatment options for patients unable to undergo surgical resection. Evidence supporting the efficacy of combined VEGF and PD-1 inhibition in other tumor types provided a compelling rationale for investigating this combination in AA, where immune checkpoint inhibitors have not been explored previously.

EXPERIMENTAL DESIGN: We conducted a prospective, single-arm phase II study evaluating efficacy and safety of atezolizumab in conjunction with bevacizumab (Atezo+Bev) in advanced, unresectable AA.

RESULTS: Patients treated with the Atezo+Bev combination had 100% disease control rate (1 partial response, 15 stable disease) with progression-free survival (PFS) of …


A Framework And Process For Community‑Engaged, Mixed‑Methods Cancer Needs Assessments, Todd Burus, Jessica R. Thompson, Caree R. Mcafee, Lovoria B. Williams, Jennifer R. Knight, Bin Huang, Sarojini Kanotra, Natalie P. Wilhite, Elaine Russell, Melinda Rogers, Connie L. Sorrell, Christine Stroebel, Rachael King, Pamela C. Hull May 2024

A Framework And Process For Community‑Engaged, Mixed‑Methods Cancer Needs Assessments, Todd Burus, Jessica R. Thompson, Caree R. Mcafee, Lovoria B. Williams, Jennifer R. Knight, Bin Huang, Sarojini Kanotra, Natalie P. Wilhite, Elaine Russell, Melinda Rogers, Connie L. Sorrell, Christine Stroebel, Rachael King, Pamela C. Hull

Markey Cancer Center Faculty Publications

Purpose

Community health needs assessments are required for most state and local public health agencies and non-profit hospitals. Typically based on community health improvement planning models, these assessments encompass overall com- munity health and multiple diseases to inform program planning. National Cancer Institute (NCI)-designated Cancer Centers and community-based cancer-focused programs share the goal of reducing cancer burden in the catchment areas they serve. However, to date, no published models exist to guide cancer-specific needs assessments for a determined geographic area that can inform both public health and research initiatives. The purpose of this article is to outline a cancer needs …


Small-Molecule Disruptors Of The Interaction Between Calcium- And Integrin-Binding Protein 1 And Integrin Α, Kalyan Golla, Adam Yasgar, Manjuprasanna Voddarahally Nagaraju, Meghna U. Naik, Bolormaa Baljinnyam, Alexey V. Zakharov, Sankalp Jain, Ganesha Rai, Ajit Jadhav, Anton Simeonov, Ulhas P. Naik May 2024

Small-Molecule Disruptors Of The Interaction Between Calcium- And Integrin-Binding Protein 1 And Integrin Α, Kalyan Golla, Adam Yasgar, Manjuprasanna Voddarahally Nagaraju, Meghna U. Naik, Bolormaa Baljinnyam, Alexey V. Zakharov, Sankalp Jain, Ganesha Rai, Ajit Jadhav, Anton Simeonov, Ulhas P. Naik

Cardeza Foundation for Hematologic Research

Thrombosis, a key factor in most cardiovascular diseases, is a major contributor to human mortality. Existing antithrombotic agents carry a risk of bleeding. Consequently, there is a keen interest in discovering innovative antithrombotic agents that can prevent thrombosis without negatively impacting hemostasis. Platelets play crucial roles in both hemostasis and thrombosis. We have previously characterized calcium- and integrin-binding protein 1 (CIB1) as a key regulatory molecule that regulates platelet function. CIB1 interacts with several platelet proteins including integrin αIIbβ3, the major glycoprotein receptor for fibrinogen on platelets. Given that CIB1 regulates platelet function through its interaction with αIIbβ3, we developed …


Metabolic Alterations And Cellular Responses To Β-Hydroxybutyrate Treatment In Breast Cancer Cells, Hadas Fulman-Levy, Raichel Cohen-Harazi, Bar Levi, Lital Argaev-Frenkel, Ifat Abramovich, Eyal Gottlieb, Sarah Hofmann, Igor Koman, Elimelech Nesher May 2024

Metabolic Alterations And Cellular Responses To Β-Hydroxybutyrate Treatment In Breast Cancer Cells, Hadas Fulman-Levy, Raichel Cohen-Harazi, Bar Levi, Lital Argaev-Frenkel, Ifat Abramovich, Eyal Gottlieb, Sarah Hofmann, Igor Koman, Elimelech Nesher

Faculty, Staff and Student Publications

BACKGROUND: The ketogenic diet (KD), based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Under KD and starvation conditions, the lack of carbohydrates promotes the production of ketone bodies (KB) from fats by the liver as an alternative source of metabolic energy. KD and starvation may affect the metabolism in cancer cells, as well as tumor characteristics. The aim of this study is to evaluate the effect of KD conditions on a wide variety of aspects of breast cancer cells …


Vascular Risk Profile And Changes Of Arterial Hypertension After Surgical Revascularization In Adult Moyamoya Patients, Patrick Haas, Lucas Moritz Wiggenhauser, Jonas Tellermann, Helene Hurth, Daniel Feucht, Marcos Tatagiba, Nadia Khan, Constantin Roder May 2024

Vascular Risk Profile And Changes Of Arterial Hypertension After Surgical Revascularization In Adult Moyamoya Patients, Patrick Haas, Lucas Moritz Wiggenhauser, Jonas Tellermann, Helene Hurth, Daniel Feucht, Marcos Tatagiba, Nadia Khan, Constantin Roder

Faculty, Staff and Student Publications

Moyamoya disease (MMD) is a rare stenoocclusive cerebral vasculopathy often treated by neurosurgical revascularization using extracranial-intracranial bypasses to prevent ischemic or hemorrhagic events. Little is known about the vascular risk profile of adult MMD patients compared to the general population. We therefore analyzed 133 adult MMD patients and compared them with data from more than 22,000 patients from the German Health Update database. Patients with MMD showed an age- and sex-adjusted increased prevalence of arterial hypertension, especially in women between 30 and 44 years and in patients of both sexes between 45 and 64 years. Diabetes mellitus was diagnosed significantly …