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Articles 23071 - 23100 of 76901

Full-Text Articles in Medical Specialties

The Microtubule Quartet Protein Snap1 In Trypanosoma Brucei Facilitates Flagellum And Cell Division Plane Positioning By Promoting Basal Body Segregation, Martin Carbo-Tano, Mathilde Lapoix, Xinyu Jia, Olivier Thouvenin, Marco Pascucci, François Auclair, Feng B Quan, Shahad Albadri, Vernie Aguda, Younes Farouj, Elizabeth M C Hillman, Ruben Portugues, Filippo Del Bene, Tod R Thiele, Réjean Dubuc, Claire Wyart Oct 2023

The Microtubule Quartet Protein Snap1 In Trypanosoma Brucei Facilitates Flagellum And Cell Division Plane Positioning By Promoting Basal Body Segregation, Martin Carbo-Tano, Mathilde Lapoix, Xinyu Jia, Olivier Thouvenin, Marco Pascucci, François Auclair, Feng B Quan, Shahad Albadri, Vernie Aguda, Younes Farouj, Elizabeth M C Hillman, Ruben Portugues, Filippo Del Bene, Tod R Thiele, Réjean Dubuc, Claire Wyart

Faculty, Staff and Student Publications

The mesencephalic locomotor region (MLR) is a brain stem area whose stimulation triggers graded forward locomotion. How MLR neurons recruit downstream vsx2+ (V2a) reticulospinal neurons (RSNs) is poorly understood. Here, to overcome this challenge, we uncovered the locus of MLR in transparent larval zebrafish and show that the MLR locus is distinct from the nucleus of the medial longitudinal fasciculus. MLR stimulations reliably elicit forward locomotion of controlled duration and frequency. MLR neurons recruit V2a RSNs via projections onto somata in pontine and retropontine areas, and onto dendrites in the medulla. High-speed volumetric imaging of neuronal activity reveals that …


Kras G12c In Advanced Nsclc: Prevalence, Co-Mutations, And Testing, Tony Kiat Hon Lim, Ferdinandos Skoulidis, Keith M Kerr, Myung-Ju Ahn, Joshua R Kapp, Fernando A Soares, Yasushi Yatabe Oct 2023

Kras G12c In Advanced Nsclc: Prevalence, Co-Mutations, And Testing, Tony Kiat Hon Lim, Ferdinandos Skoulidis, Keith M Kerr, Myung-Ju Ahn, Joshua R Kapp, Fernando A Soares, Yasushi Yatabe

Faculty, Staff and Student Publications

KRAS is the most commonly mutated oncogene in advanced, non-squamous, non-small cell lung cancer (NSCLC) in Western countries. Of the various KRAS mutants, KRAS G12C is the most common variant (~40%), representing 10-13% of advanced non-squamous NSCLC. Recent regulatory approvals of the KRASG12C-selective inhibitors sotorasib and adagrasib for patients with advanced or metastatic NSCLC harboring KRASG12C have transformed KRAS into a druggable target. In this review, we explore the evolving role of KRAS from a prognostic to a predictive biomarker in advanced NSCLC, discussing KRAS G12C biology, real-world prevalence, clinical relevance of co-mutations, and approaches to molecular testing. Real-world evidence …


X, But Not Y, Chromosomal Complement Contributes To Stroke Sensitivity In Aged Animals, Shaohua Qi, Conelius Ngwa, Abdullah Al Mamun, Sharmeen Romana, Ting Wu, Sean P Marrelli, Arthur P Arnold, Louise D Mccullough, Fudong Liu Oct 2023

X, But Not Y, Chromosomal Complement Contributes To Stroke Sensitivity In Aged Animals, Shaohua Qi, Conelius Ngwa, Abdullah Al Mamun, Sharmeen Romana, Ting Wu, Sean P Marrelli, Arthur P Arnold, Louise D Mccullough, Fudong Liu

Faculty, Staff and Student Publications

Post-menopausal women become vulnerable to stroke and have poorer outcomes and higher mortality than age-matched men, and previous studies suggested that sex chromosomes play a vital role in mediating stroke sensitivity in the aged. It is unknown if this is due to effects of the X or Y chromosome. The present study used the XY* mouse model (with four genotypes: XX and XO gonadal females and XY and XXY gonadal males) to compare the effect of the X vs. Y chromosome compliment in stroke. Aged (18-20 months) and gonadectomized young (8-12 weeks) mice were subjected to a 60-min middle cerebral …


International Association For The Study Of Lung Cancer Study Of Reproducibility In Assessment Of Pathologic Response In Resected Lung Cancers After Neoadjuvant Therapy, Sanja Dacic, William Travis, Mary Redman, Anjali Saqi, Wendy A Cooper, Alain Borczuk, Jin-Haeng Chung, Carolyn Glass, Javier Martin Lopez, Anja C Roden, Lynette Sholl, Annikka Weissferdt, Juan Posadas, Angela Walker, Hu Zhu, Manuja T Wijeratne, Casey Connolly, Murry Wynes, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridion, J Jack Lee, Sabina Berezowska, Teh-Ying Chou, Keith Kerr, Andrew Nicholson, Claudia Poleri, Kurt A Schalper, Ming-Sound Tsao, David P Carbone, Neal Ready, Tina Cascone, John Heymach, Boris Sepesi, Catherine Shu, Naiyer Rizvi, Josuha Sonett, Nasser Altorki, Mariano Provencio, Paul A Bunn, Mark G Kris, Chandra P Belani, Karen Kelly, Ignacio Wistuba Oct 2023

International Association For The Study Of Lung Cancer Study Of Reproducibility In Assessment Of Pathologic Response In Resected Lung Cancers After Neoadjuvant Therapy, Sanja Dacic, William Travis, Mary Redman, Anjali Saqi, Wendy A Cooper, Alain Borczuk, Jin-Haeng Chung, Carolyn Glass, Javier Martin Lopez, Anja C Roden, Lynette Sholl, Annikka Weissferdt, Juan Posadas, Angela Walker, Hu Zhu, Manuja T Wijeratne, Casey Connolly, Murry Wynes, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridion, J Jack Lee, Sabina Berezowska, Teh-Ying Chou, Keith Kerr, Andrew Nicholson, Claudia Poleri, Kurt A Schalper, Ming-Sound Tsao, David P Carbone, Neal Ready, Tina Cascone, John Heymach, Boris Sepesi, Catherine Shu, Naiyer Rizvi, Josuha Sonett, Nasser Altorki, Mariano Provencio, Paul A Bunn, Mark G Kris, Chandra P Belani, Karen Kelly, Ignacio Wistuba

Faculty, Staff and Student Publications

Introduction: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria.

Methods: An international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin-stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable …


Renal Cell Carcinoma Of Variant Histology: Biology And Therapies, Pavlos Msaouel, Giannicola Genovese, Nizar M Tannir Oct 2023

Renal Cell Carcinoma Of Variant Histology: Biology And Therapies, Pavlos Msaouel, Giannicola Genovese, Nizar M Tannir

Faculty, Staff and Student Publications

The term variant histology renal cell carcinomas (vhRCCs), also known as non-clear cell RCCs, refers to a diverse group of malignancies with distinct biologic and therapeutic considerations. The management of vhRCC subtypes is often based on extrapolating results from the more common clear cell RCC studies or basket trials that are not specific to each histology. The unique management of each vhRCC subtype necessitates accurate pathologic diagnosis and dedicated research efforts. Herein, we discuss tailored recommendations for each vhRCC histology informed by ongoing research and clinical experience.


Bayesian Approach For Design And Analysis Of Medical Device Trials In The Era Of Modern Clinical Studies, Han Cao, Chen Yao, Ying Yuan Oct 2023

Bayesian Approach For Design And Analysis Of Medical Device Trials In The Era Of Modern Clinical Studies, Han Cao, Chen Yao, Ying Yuan

Faculty, Staff and Student Publications

Medical device technology develops rapidly, and the life cycle of a medical device is much shorter than drugs. It is necessary to evaluate the safety and effectiveness of a medical device in a timely manner to keep up with technology flux. Bayesian methods provides an efficient approach to addressing this challenge. In this article, we review the characteristics of the Bayesian approach and some Bayesian designs that were commonly used in medical device regulatory setting, including Bayesian adaptive design, Bayesian diagnostic design, Bayesian multiregional design, and Bayesian label expansion study. We illustrate these designs with medical devices approved by the …


Risk Of Covid-19 After Natural Infection Or Vaccination, Anne-Marie Rick, Matthew B Laurens, Ying Huang, Chenchen Yu, Thomas C S Martin, Carina A Rodriguez, Christina A Rostad, Rebone M Maboa, Lindsey R Baden, Hana M El Sahly, Beatriz Grinsztejn, Glenda E Gray, Cynthia L Gay, Peter B Gilbert, Holly E Janes, James G Kublin, Yunda Huang, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Paul A Goepfert, Stephen R Walsh, Dean Follmann, Karen L Kotloff Oct 2023

Risk Of Covid-19 After Natural Infection Or Vaccination, Anne-Marie Rick, Matthew B Laurens, Ying Huang, Chenchen Yu, Thomas C S Martin, Carina A Rodriguez, Christina A Rostad, Rebone M Maboa, Lindsey R Baden, Hana M El Sahly, Beatriz Grinsztejn, Glenda E Gray, Cynthia L Gay, Peter B Gilbert, Holly E Janes, James G Kublin, Yunda Huang, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Paul A Goepfert, Stephen R Walsh, Dean Follmann, Karen L Kotloff

Faculty, Staff and Student Publications

BACKGROUND: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection.

METHODS: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection …


Medication Reconciliation During Transitions Of Care Across Institutions: A Quantitative Analysis Of Challenges And Opportunities, Alejandro Araya, Logan R Thornton, Deukwoo Kwon, Gayla M Ferguson, Linda D Highfield, Kevin O Hwang, Holly M Holmes, Elmer V Bernstam Oct 2023

Medication Reconciliation During Transitions Of Care Across Institutions: A Quantitative Analysis Of Challenges And Opportunities, Alejandro Araya, Logan R Thornton, Deukwoo Kwon, Gayla M Ferguson, Linda D Highfield, Kevin O Hwang, Holly M Holmes, Elmer V Bernstam

Faculty, Staff and Student Publications

OBJECTIVE: Medication discrepancies between clinical systems may pose a patient safety hazard. In this paper, we identify challenges and quantify medication discrepancies across transitions of care.

METHODS: We used structured clinical data and free-text hospital discharge summaries to compare active medications' lists at four time points: preadmission (outpatient), at-admission (inpatient), at-discharge (inpatient), and postdischarge (outpatient). Medication lists were normalized to RxNorm. RxNorm identifiers were further processed using the RxNav API to identify the ingredient. The specific drugs and ingredients from inpatient and outpatient medication lists were compared.

RESULTS: Using RxNorm drugs, the median percentage intersection when comparing active medication lists …


Hiccups: Nerve Irritation Or Masquerading As Acute Coronary Syndrome, Dessiree Cordero, Patrik Schmidt, Franklin Sosa, Maulin Patel, Eduard Sklyar Oct 2023

Hiccups: Nerve Irritation Or Masquerading As Acute Coronary Syndrome, Dessiree Cordero, Patrik Schmidt, Franklin Sosa, Maulin Patel, Eduard Sklyar

Faculty, Staff and Student Publications

The typical clinical presentation of acute coronary syndrome (ACS) includes chest pain that may radiate to the left arm, shoulder, jaw, and neck, accompanied by diaphoresis, dyspnea, nausea, vomiting, and hiccups, which have been observed as the sole symptom of presentation. The mechanism of hiccups involves the activation of the vagus and phrenic nerves, leading to the activation of the diaphragm and intercostal muscles. Several hypotheses link hiccups to ACS, associating irritation of the left anterior descending artery with activation of sympathetic phrenic and vagal nerves. This case report highlights the occurrence of hiccups in patients with inferior and right …


Dynamics Of The Dynll1-Mre11 Complex Regulate Dna End Resection And Recruitment Of Shieldin To Dsbs, Michelle L Swift, Rui Zhou, Aleem Syed, Lisa A Moreau, Bartłomiej Tomasik, John A Tainer, Panagiotis A Konstantinopoulos, Alan D D'Andrea, Yizhou Joseph He, Dipanjan Chowdhury Oct 2023

Dynamics Of The Dynll1-Mre11 Complex Regulate Dna End Resection And Recruitment Of Shieldin To Dsbs, Michelle L Swift, Rui Zhou, Aleem Syed, Lisa A Moreau, Bartłomiej Tomasik, John A Tainer, Panagiotis A Konstantinopoulos, Alan D D'Andrea, Yizhou Joseph He, Dipanjan Chowdhury

Faculty, Staff and Student Publications

The extent and efficacy of DNA end resection at DNA double-strand breaks (DSB) determine the repair pathway choice. Here we describe how the 53BP1-associated protein DYNLL1 works in tandem with the Shieldin complex to protect DNA ends. DYNLL1 is recruited to DSBs by 53BP1, where it limits end resection by binding and disrupting the MRE11 dimer. The Shieldin complex is recruited to a fraction of 53BP1-positive DSBs hours after DYNLL1, predominantly in G1 cells. Shieldin localization to DSBs depends on MRE11 activity and is regulated by the interaction of DYNLL1 with MRE11. BRCA1-deficient cells rendered resistant to PARP inhibitors by …


Partnering With Patients And Families To Improve Diagnostic Safety Through The Ourdx Tool: Effects Of Race, Ethnicity, And Language Preference, Fabienne C Bourgeois, Nicholas J Hart, Zhiyong Dong, Long H Ngo, Catherine M Desroches, Eric J Thomas, Sigall K Bell Oct 2023

Partnering With Patients And Families To Improve Diagnostic Safety Through The Ourdx Tool: Effects Of Race, Ethnicity, And Language Preference, Fabienne C Bourgeois, Nicholas J Hart, Zhiyong Dong, Long H Ngo, Catherine M Desroches, Eric J Thomas, Sigall K Bell

Faculty, Staff and Student Publications

BACKGROUND: Patients and families at risk for health disparities may also be at higher risk for diagnostic errors but less likely to report them.

OBJECTIVES: This study aimed to explore differences in race, ethnicity, and language preference associated with patient and family contributions and concerns using an electronic previsit tool designed to engage patients and families in the diagnostic process (DxP).

METHODS: Cross-sectional study of 5,731 patients and families presenting to three subspecialty clinics at an urban pediatric hospital May to December 2021 who completed a previsit tool, codeveloped and tested with patients and families. Prior to each visit, patients/families …


Postoperative Pain-Related Outcomes And Perioperative Pain Management In China: A Population-Based Study, Yanhong Liu, Saisong Xiao, Huikai Yang, Xuecai Lv, Aisheng Hou, Yulong Ma, Yandong Jiang, Chongyang Duan, Weidong Mi Oct 2023

Postoperative Pain-Related Outcomes And Perioperative Pain Management In China: A Population-Based Study, Yanhong Liu, Saisong Xiao, Huikai Yang, Xuecai Lv, Aisheng Hou, Yulong Ma, Yandong Jiang, Chongyang Duan, Weidong Mi

Faculty, Staff and Student Publications

Background: Postoperative pain poses a significant challenge to the healthcare system and patient satisfaction and is associated with chronic pain and long-term narcotic use. However, systemic assessment of the quality of postoperative pain management in China remains unavailable.

Methods: In this cross-sectional study, we analyzed data collected from a nationwide registry, China Acute Postoperative Pain Study (CAPOPS), between September 2019 and August 2021. Patients aged 18 years or above were required to complete a self-reported pain outcome questionnaire on the first postoperative day (POD1). Perioperative pain management and pain-related outcomes, including the severity of pain, adverse events caused by pain …


Cytosolic Dna Accumulation Promotes Breast Cancer Immunogenicity Via A Sting-Independent Pathway, Jing Zhang, Hui Dai, Lei Huo, Jared K Burks, Daniel J Mcgrail, Shiaw-Yih Lin Oct 2023

Cytosolic Dna Accumulation Promotes Breast Cancer Immunogenicity Via A Sting-Independent Pathway, Jing Zhang, Hui Dai, Lei Huo, Jared K Burks, Daniel J Mcgrail, Shiaw-Yih Lin

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, ICB alone has demonstrated only benefit in a small subset of patients with breast cancer. Recent studies have shown that agents targeting DNA damage response improve the efficacy of ICB and promote cytosolic DNA accumulation. However, recent clinical trials have shown that these agents are associated with hematological toxicities. More effective therapeutic strategies are urgently needed.

METHODS: Primary triple negative breast cancer tumors were stained for cytosolic single-stranded DNA (ssDNA) using multiplex immunohistochemical staining. To increase cytosolic ssDNA, we genetically silenced TREX1. The role of tumor cytosolic ssDNA in promoting …


Anchors: A Way For Ftsz Filaments To Stay Membrane Bound, Arindam Naha, Daniel P Haeusser, William Margolin Oct 2023

Anchors: A Way For Ftsz Filaments To Stay Membrane Bound, Arindam Naha, Daniel P Haeusser, William Margolin

Faculty, Staff and Student Publications

Most bacteria use the tubulin homolog FtsZ to organize their cell division. FtsZ polymers initially assemble into mobile complexes that circle around a ring-like structure at the cell midpoint, followed by the recruitment of other proteins that will constrict the cytoplasmic membrane and synthesize septal peptidoglycan to divide the cell. Despite the need for FtsZ polymers to associate with the membrane, FtsZ lacks intrinsic membrane binding ability. Consequently, FtsZ polymers have evolved to interact with the membrane through adaptor proteins that both bind FtsZ and the membrane. Here, we discuss recent progress in understanding the functions of these FtsZ membrane …


Automated Contouring And Statistical Process Control For Plan Quality In A Breast Clinical Trial, Hana Baroudi, Callistus I Huy Minh Nguyen, Sean Maroongroge, Benjamin D Smith, Joshua S Niedzielski, Simona F Shaitelman, Adam Melancon, Sanjay Shete, Thomas J Whitaker, Melissa P Mitchell, Isidora Yvonne Arzu, Jack Duryea, Soleil Hernandez, Daniel El Basha, Raymond Mumme, Tucker Netherton, Karen Hoffman, Laurence Court Oct 2023

Automated Contouring And Statistical Process Control For Plan Quality In A Breast Clinical Trial, Hana Baroudi, Callistus I Huy Minh Nguyen, Sean Maroongroge, Benjamin D Smith, Joshua S Niedzielski, Simona F Shaitelman, Adam Melancon, Sanjay Shete, Thomas J Whitaker, Melissa P Mitchell, Isidora Yvonne Arzu, Jack Duryea, Soleil Hernandez, Daniel El Basha, Raymond Mumme, Tucker Netherton, Karen Hoffman, Laurence Court

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Automatic review of breast plan quality for clinical trials is time-consuming and has some unique challenges due to the lack of target contours for some planning techniques. We propose using an auto-contouring model and statistical process control to independently assess planning consistency in retrospective data from a breast radiotherapy clinical trial.

MATERIALS AND METHODS: A deep learning auto-contouring model was created and tested quantitatively and qualitatively on 104 post-lumpectomy patients' computed tomography images (nnUNet; train/test: 80/20). The auto-contouring model was then applied to 127 patients enrolled in a clinical trial. Statistical process control was used to assess …


Basic: A Bayesian Adaptive Synthetic-Control Design For Phase Ii Clinical Trials, Liyun Jiang, Peter F Thall, Fangrong Yan, Scott Kopetz, Ying Yuan Oct 2023

Basic: A Bayesian Adaptive Synthetic-Control Design For Phase Ii Clinical Trials, Liyun Jiang, Peter F Thall, Fangrong Yan, Scott Kopetz, Ying Yuan

Faculty, Staff and Student Publications

Background: Randomized controlled trials are considered the gold standard for evaluating experimental treatments but often require large sample sizes. Single-arm trials require smaller sample sizes but are subject to bias when using historical control data for comparative inferences. This article presents a Bayesian adaptive synthetic-control design that exploits historical control data to create a hybrid of a single-arm trial and a randomized controlled trial.

Methods: The Bayesian adaptive synthetic control design has two stages. In stage 1, a prespecified number of patients are enrolled in a single arm given the experimental treatment. Based on the stage 1 data, applying propensity …


Efficacy And Safety Of Transjugular Intrahepatic Portosystemic Shunt In Patients With Hepatocelluar Carcinoma - A Systematic Review And Meta-Analysis, Marko Kozyk, Suprabhat Giri, Ankit Singh, Akash Roy, Kateryna Strubchevska, Taraprasad Tripathi, Ranjan Kumar Patel Oct 2023

Efficacy And Safety Of Transjugular Intrahepatic Portosystemic Shunt In Patients With Hepatocelluar Carcinoma - A Systematic Review And Meta-Analysis, Marko Kozyk, Suprabhat Giri, Ankit Singh, Akash Roy, Kateryna Strubchevska, Taraprasad Tripathi, Ranjan Kumar Patel

Conference Presentation Abstracts

Background: Patients with hepatocellular carcinoma (HCC) and cirrhosis can present with features of severe portal hypertension, which can be worsened further with associated portal vein tumoral thrombosis (PVTT). Due to the technical difficulties and short survival of these patients, HCC was traditionally considered a relative contraindication for transjugular intrahepatic portosystemic shunt (TIPS). However, there is an increasing body of evidence supporting the use of TIPS in HCC. The present study aimed to analyze the efficacy and safety of TIPS in patients with HCC. Methods: A literature search of MEDLINE, Embase, and Scopus was conducted from 2000 to October 2022 for …


A Translational Blueprint For Developing Intraoperative Imaging Agents Via Radiopharmaceutical-Guided Drug Design, Teresa E Sullivan, Servando Hernandez Vargas, Sukhen C Ghosh, Solmaz Aghaamiri, Naruhiko Ikoma, Ali Azhdarinia Oct 2023

A Translational Blueprint For Developing Intraoperative Imaging Agents Via Radiopharmaceutical-Guided Drug Design, Teresa E Sullivan, Servando Hernandez Vargas, Sukhen C Ghosh, Solmaz Aghaamiri, Naruhiko Ikoma, Ali Azhdarinia

Faculty, Staff and Student Publications

Cancer imaging is a rapidly evolving field due to the discovery of novel molecular targets and the availability of corresponding techniques to detect them with high precision, accuracy, and sensitivity. Nuclear medicine is the most widely used molecular imaging modality and has a growing toolkit of clinically used radiopharmaceuticals that enable whole-body tumor visualization, staging, and treatment monitoring for a variety of tumors in a non-invasive manner. The need for similar imaging capabilities in the operating room has led to the emergence of fluorescence-guided surgery (FGS) as a powerful technique that gives surgeons unprecedented ability to distinguish tumors from healthy …


Pd-1 Blockade In Combination With Dasatinib Potentiates Induction Of Anti-Acute Lymphocytic Leukemia Immunity, Paul Koller, Natalia Baran, Karine Harutyunyan, Antonio Cavazos, Saradhi Mallampati, Renee L Chin, Zhou Jiang, Xian Sun, Heng-Huan Lee, Jennifer L Hsu, Patrick Williams, Xuelin Huang, Michael A Curran, Mien-Chie Hung, Marina Konopleva Oct 2023

Pd-1 Blockade In Combination With Dasatinib Potentiates Induction Of Anti-Acute Lymphocytic Leukemia Immunity, Paul Koller, Natalia Baran, Karine Harutyunyan, Antonio Cavazos, Saradhi Mallampati, Renee L Chin, Zhou Jiang, Xian Sun, Heng-Huan Lee, Jennifer L Hsu, Patrick Williams, Xuelin Huang, Michael A Curran, Mien-Chie Hung, Marina Konopleva

Faculty, Staff and Student Publications

Immunotherapy, in the form of hematopoietic stem cell transplantation (HSCT), has been part of the standard of care in the treatment of acute leukemia for over 40 years. Trials evaluating novel immunotherapeutic approaches, such as targeting the programmed death-1 (PD-1) pathway, have unfortunately not yielded comparable results to those seen in solid tumors. Major histocompatibility complex (MHC) proteins are cell surface proteins essential for the adaptive immune system to recognize self versus non-self. MHC typing is used to determine donor compatibility when evaluating patients for HSCT. Recently, loss of MHC class II (MHC II) was shown to be a mechanism …


Sepsis Exacerbates Alzheimer’S Disease Pathophysiology, Modulates The Gut Microbiome, Increases Neuroinflammation And Amyloid Burden, Vijayasree V Giridharan, Celso S G Catumbela, Carlos Henrique R Catalão, Juneyoung Lee, Bhanu P Ganesh, Fabricia Petronilho, Felipe Dal-Pizzol, Rodrigo Morales, Tatiana Barichello Oct 2023

Sepsis Exacerbates Alzheimer’S Disease Pathophysiology, Modulates The Gut Microbiome, Increases Neuroinflammation And Amyloid Burden, Vijayasree V Giridharan, Celso S G Catumbela, Carlos Henrique R Catalão, Juneyoung Lee, Bhanu P Ganesh, Fabricia Petronilho, Felipe Dal-Pizzol, Rodrigo Morales, Tatiana Barichello

Faculty, Staff and Student Publications

While our understanding of the molecular biology of Alzheimer's disease (AD) has grown, the etiology of the disease, especially the involvement of peripheral infection, remains a challenge. In this study, we hypothesize that peripheral infection represents a risk factor for AD pathology. To test our hypothesis, APP/PS1 mice underwent cecal ligation and puncture (CLP) surgery to develop a polymicrobial infection or non-CLP surgery. Mice were euthanized at 3, 30, and 120 days after surgery to evaluate the inflammatory mediators, glial cell markers, amyloid burden, gut microbiome, gut morphology, and short-chain fatty acids (SCFAs) levels. The novel object recognition (NOR) task …


Rare Variants Found In Clinical Gene Panels Illuminate The Genetic And Allelic Architecture Of Orofacial Clefting, Kimberly K Diaz Perez, Sarah W Curtis, Alba Sanchis-Juan, Xuefang Zhao, Taylor Head, Samantha Ho, Bridget Carter, Toby Mchenry, Madison R Bishop, Luz C Valencia-Ramirez, Claudia Restrepo, Jacqueline T Hecht, Lina M Uribe, George Wehby, Seth M Weinberg, Terri H Beaty, Jeffrey C Murray, Eleanor Feingold, Mary L Marazita, David J Cutler, Michael P Epstein, Harrison Brand, Elizabeth J Leslie Oct 2023

Rare Variants Found In Clinical Gene Panels Illuminate The Genetic And Allelic Architecture Of Orofacial Clefting, Kimberly K Diaz Perez, Sarah W Curtis, Alba Sanchis-Juan, Xuefang Zhao, Taylor Head, Samantha Ho, Bridget Carter, Toby Mchenry, Madison R Bishop, Luz C Valencia-Ramirez, Claudia Restrepo, Jacqueline T Hecht, Lina M Uribe, George Wehby, Seth M Weinberg, Terri H Beaty, Jeffrey C Murray, Eleanor Feingold, Mary L Marazita, David J Cutler, Michael P Epstein, Harrison Brand, Elizabeth J Leslie

Faculty, Staff and Student Publications

PURPOSE: Orofacial clefts (OFCs) are common birth defects including cleft lip, cleft lip and palate, and cleft palate. OFCs have heterogeneous etiologies, complicating clinical diagnostics because it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sporadic OFCs; therefore, we estimated the diagnostic yield for 418 genes in 841 cases and 294 controls.

METHODS: We evaluated 418 genes using genome sequencing and curated variants to assess their pathogenicity using American College of Medical Genetics criteria.

RESULTS: 9.04% of cases and 1.02% of controls had "likely pathogenic" variants (P < .0001), which was almost exclusively driven by heterozygous variants in autosomal genes. Cleft palate (17.6%) and cleft lip and palate (9.09%) cases had the highest yield, whereas cleft lip cases had a 2.80% yield. Out of 39 genes with likely pathogenic variants, 9 genes, including CTNND1 and IRF6, accounted for more than half of the yield (4.64% of cases). Most variants (61.8%) were "variants of uncertain significance", occurring more frequently in cases (P = .004), but no individual gene showed a significant excess of variants of uncertain significance.

CONCLUSION: …


Dietary Intake And Quality Among Stroke Survivors: Nhanes 1999-2018, Erika R Zoellner, Mindy A Patterson, Anjail Z Sharrief, Sean I Savitz, Wesley J Tucker, Derek C Miketinas Oct 2023

Dietary Intake And Quality Among Stroke Survivors: Nhanes 1999-2018, Erika R Zoellner, Mindy A Patterson, Anjail Z Sharrief, Sean I Savitz, Wesley J Tucker, Derek C Miketinas

Faculty, Staff and Student Publications

Background: Nutrition is an important modifiable risk factor for prevention and treatment of stroke. However, examination of nutrient intake and diet quality in stroke survivors is limited.

Objectives: The aim of the study was to estimate usual nutrient intake and diet quality in US adults with and without a history of self-reported stroke.

Methods: Using US National Health and Nutrition Examination Survey (NHANES) 1999-2018, we analyzed demographics, health history, and dietary intake data in 1626 individuals with a history of stroke matched for age, gender, and survey cycle to respective controls (n=1621) with no history of stroke. A minimum of …


Toward Standardization In Reporting Data On Basic Human Semen Examination: A Crucial Step In Advancing The Field Of Andrology And Reproductive Medicine, Marie-Claude Hofmann, Aleksander Giwercman Oct 2023

Toward Standardization In Reporting Data On Basic Human Semen Examination: A Crucial Step In Advancing The Field Of Andrology And Reproductive Medicine, Marie-Claude Hofmann, Aleksander Giwercman

Faculty, Staff and Student Publications

No abstract provided.


Preclinical Development Of 1b7/Cd3, A Novel Anti-Tslpr Bispecific Antibody That Targets Crlf2-Rearranged Ph-Like B-All, Ze Tian, Chunhua Shi, Guojun Yang, Jason K Allen, Qing Shi, Amin Al-Shami, Jill Wardell Olson, Melinda G Smith, Qing Chang, Jasbir Kaur, Junping You, Timothy E Lofton, Michelle A Gonzalez, Qi Zhang, Dongxing Zha, Sarah K Tasian, Nitin Jain, Marina Y Konopleva, Timothy Heffernan, Jeffrey J Molldrem Oct 2023

Preclinical Development Of 1b7/Cd3, A Novel Anti-Tslpr Bispecific Antibody That Targets Crlf2-Rearranged Ph-Like B-All, Ze Tian, Chunhua Shi, Guojun Yang, Jason K Allen, Qing Shi, Amin Al-Shami, Jill Wardell Olson, Melinda G Smith, Qing Chang, Jasbir Kaur, Junping You, Timothy E Lofton, Michelle A Gonzalez, Qi Zhang, Dongxing Zha, Sarah K Tasian, Nitin Jain, Marina Y Konopleva, Timothy Heffernan, Jeffrey J Molldrem

Faculty, Staff and Student Publications

Patients harboring CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL) face a 5-year survival rate as low as 20%. While significant gains have been made to position targeted therapies for B-ALL treatment, continued efforts are needed to develop therapeutic options with improved duration of response. Here, first we have demonstrated that patients with CRLF2-rearranged Ph-like ALL harbor elevated thymic stromal lymphopoietin receptor (TSLPR) expression, which is comparable with CD19. Then we present and evaluate the anti-tumor characteristics of 1B7/CD3, a novel CD3-redirecting bispecific antibody (BsAb) that co-targets TSLPR. In vitro, 1B7/CD3 exhibits optimal binding to both human and cynomolgus CD3 and TSLPR. …


Phenotype And Fate Of Liver-Resident Cd8 T Cells During Acute And Chronic Hepacivirus Infection, Piyush Dravid, Satyapramod Murthy, Zayed Attia, Cole Cassady, Rahul Chandra, Sheetal Trivedi, Ashish Vyas, John Gridley, Brantley Holland, Anuradha Kumari, Arash Grakoui, John M Cullen, Christopher M Walker, Himanshu Sharma, Amit Kapoor Oct 2023

Phenotype And Fate Of Liver-Resident Cd8 T Cells During Acute And Chronic Hepacivirus Infection, Piyush Dravid, Satyapramod Murthy, Zayed Attia, Cole Cassady, Rahul Chandra, Sheetal Trivedi, Ashish Vyas, John Gridley, Brantley Holland, Anuradha Kumari, Arash Grakoui, John M Cullen, Christopher M Walker, Himanshu Sharma, Amit Kapoor

Faculty, Staff and Student Publications

Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and chronic rodent HCV-like virus (RHV) infections in lab mice. Here, we developed MHC class I and class II tetramers to characterize the serial changes in RHV-specific CD8 and CD4 T cells during acute and chronic infection in C57BL/6J mice. RHV infection induced rapid expansion of T cells targeting viral structural and nonstructural proteins. After virus clearance, the virus-specific T cells transitioned from effectors to long-lived liver-resident memory T cells (TRM). The effector and …


Can Craniosynostosis Be Diagnosed On Physical Examination? A Retrospective Review, Carmen A Zavala, Laura A Zima, Matthew R Greives, Stephen A Fletcher, Manish N Shah, Brandon A Miller, David I Sandberg, Phuong D Nguyen Oct 2023

Can Craniosynostosis Be Diagnosed On Physical Examination? A Retrospective Review, Carmen A Zavala, Laura A Zima, Matthew R Greives, Stephen A Fletcher, Manish N Shah, Brandon A Miller, David I Sandberg, Phuong D Nguyen

Faculty, Staff and Student Publications

Craniosynostosis is a developmental craniofacial defect in which one or more sutures of the skull fuse together prematurely. Uncorrected craniosynostosis may have serious complications including elevated intracranial pressure, developmental delay, and blindness. Proper diagnosis of craniosynostosis requires a physical examination of the head with assessment for symmetry and palpation of sutures for prominence. Often, if craniosynostosis is suspected, computed tomography (CT) imaging will be obtained. Recent literature has posited that this is unnecessary. This study aims to address whether physical examination alone is sufficient for the diagnosis and treatment planning of single suture craniosynostosis. Between 2015 and 2022, the Divisions …


A Review Of Magnetic Resonance (Mr) Safety: The Essentials To Patient Safety, Aren Shah, Shima Aran Oct 2023

A Review Of Magnetic Resonance (Mr) Safety: The Essentials To Patient Safety, Aren Shah, Shima Aran

Faculty, Staff and Student Publications

Nearly 40 million magnetic resonance imaging (MRI) scans are performed each year in the United States. MRI has become a relatively safe non-invasive diagnostic tool. To maintain a safe magnetic resonance (MR) environment, specific policies and safety procedures are required. The four zones of an MR site allow MR personnel to closely monitor and restrict the area. Screening patients with a questionnaire asking about implants, allergies to contrast agents, and other relevant medical information is important to safely perform an MRI scan. Providers may need to consider anesthesia for patients with claustrophobia who are unable to remain motionless. Radiologists and …


Examination Of Disparities In Prehospital Encounters For Pediatric Asthma Exacerbations, Lauren Riney, Sam Palmer, Erik Finlay, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David W Ashby, Daniel Ostermayer, Olga Semenova, Benjamin N Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Jennifer N Fishe Oct 2023

Examination Of Disparities In Prehospital Encounters For Pediatric Asthma Exacerbations, Lauren Riney, Sam Palmer, Erik Finlay, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David W Ashby, Daniel Ostermayer, Olga Semenova, Benjamin N Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Jennifer N Fishe

Faculty, Staff and Student Publications

INTRODUCTION: There are disparities in multiple aspects of pediatric asthma care; however, prehospital care disparities are largely undescribed. This study's objective was to examine racial and geographic disparities in emergency medical services (EMS) medication administration to pediatric patients with asthma.

METHODS: This is a substudy of the Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial, which includes data from pediatric asthma patients ages 2-18 years. We examined rates of EMS administration of systemic corticosteroids and inhaled bronchodilators by patient race. We geocoded EMS scene addresses, characterized the locations' neighborhood-based conditions and resources relevant to children using …


Characteristics And Outcomes Of Patients With Chronic Myeloid Leukemia And T315i Mutation Treated In The Pre- And Post-Ponatinib Era, Fadi G Haddad, Koji Sasaki, Aram Bidikian, Ghayas C Issa, Tapan Kadia, Nitin Jain, Yesid Alvarado, Nicholas J Short, Naveen Pemmaraju, Sanam Loghavi, Keyur P Patel, Rashmi Kanagal-Shamanna, Musa Yilmaz, Lucia Masarova, Elias Jabbour, Hagop Kantarjian Oct 2023

Characteristics And Outcomes Of Patients With Chronic Myeloid Leukemia And T315i Mutation Treated In The Pre- And Post-Ponatinib Era, Fadi G Haddad, Koji Sasaki, Aram Bidikian, Ghayas C Issa, Tapan Kadia, Nitin Jain, Yesid Alvarado, Nicholas J Short, Naveen Pemmaraju, Sanam Loghavi, Keyur P Patel, Rashmi Kanagal-Shamanna, Musa Yilmaz, Lucia Masarova, Elias Jabbour, Hagop Kantarjian

Faculty, Staff and Student Publications

Patients with chronic myeloid leukemia (CML) and T315I mutation generally have a poor prognosis. Their outcome in the post-ponatinib era remains unclear. We reviewed patients with CML in chronic (CP) or accelerated phase (AP) who developed a T315I mutation between March 15, 2004, and July 26, 2022. Patients were divided into CP, AP, or blastic phase (BP) at the time of mutation detection. Overall survival (OS) was defined from the time of mutation detection to the date of death or last follow-up. We identified a total of 107 patients: 54 (51%) in CP, 14 (13%) in AP, and 39 (36%) …


Comparisons Of Medical Cost Trajectories Between Non-Hispanic Black And Non-Hispanic White Patients With Newly Diagnosed Localized Prostate Cancer, Yu Liu, Shikun Wang, Liang Li, Ying Xu, Yu Shen, Ya-Chen Tina Shih Oct 2023

Comparisons Of Medical Cost Trajectories Between Non-Hispanic Black And Non-Hispanic White Patients With Newly Diagnosed Localized Prostate Cancer, Yu Liu, Shikun Wang, Liang Li, Ying Xu, Yu Shen, Ya-Chen Tina Shih

Faculty, Staff and Student Publications

Objectives: This study applied a recently developed statistical method to compare the mean cost trajectories between non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients with localized prostate cancer conditioning on patients' survival.

Methods: In this observational study, we modeled cost trajectories of NHW and NHB patients with localized prostate cancer for 3 survival durations: 24, 48, and 72 months. We also compared the cost trajectories between NHW and NHB, stratified by comorbidities scores.

Results: We find that the mean cost trajectories of NHB were significantly higher than the trajectories of NHW in the last 12 months before death, regardless of …