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Articles 8251 - 8280 of 76847
Full-Text Articles in Medical Specialties
Unveiling The Intercompartmental Signaling Axis: Mitochondrial To Er Stress Response (Mersr) And Its Impact On Proteostasis, Jeson J Li, Nan Xin, Chunxia Yang, Bo G Kim, Larissa A Tavizon, Ruth Hong, Jina Park, Travis I Moore, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim
Unveiling The Intercompartmental Signaling Axis: Mitochondrial To Er Stress Response (Mersr) And Its Impact On Proteostasis, Jeson J Li, Nan Xin, Chunxia Yang, Bo G Kim, Larissa A Tavizon, Ruth Hong, Jina Park, Travis I Moore, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim
Faculty, Staff and Student Publications
Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and …
Summary Of Research: Efficacy Of Trastuzumab Deruxtecan In Her2-Expressing Solid Tumors By Enrollment Her2 Ihc Status: Post Hoc Analysis Of Destiny-Pantumor02, Ana Oaknin, Jung-Yun Lee, Vicky Makker, Do-Youn Oh, Susana Banerjee, Antonio González-Martín, Kyung Hae Jung, Iwona Ługowska, Luis Manso, Aránzazu Manzano, Bohuslav Melichar, Salvatore Siena, Daniil Stroyakovskiy, Anitra Fielding, Soham Puvvada, Ann Smith, Funda Meric-Bernstam
Summary Of Research: Efficacy Of Trastuzumab Deruxtecan In Her2-Expressing Solid Tumors By Enrollment Her2 Ihc Status: Post Hoc Analysis Of Destiny-Pantumor02, Ana Oaknin, Jung-Yun Lee, Vicky Makker, Do-Youn Oh, Susana Banerjee, Antonio González-Martín, Kyung Hae Jung, Iwona Ługowska, Luis Manso, Aránzazu Manzano, Bohuslav Melichar, Salvatore Siena, Daniil Stroyakovskiy, Anitra Fielding, Soham Puvvada, Ann Smith, Funda Meric-Bernstam
Faculty, Staff and Student Publications
of the original article, 'Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02'. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate, which is a chemotherapy with a linker (deruxtecan) joined to an antibody (trastuzumab). Trastuzumab binds to the human epidermal growth factor receptor 2 (HER2) protein on cancer cells, where it releases the chemotherapy to kill these cells. The DESTINY-PanTumor02 clinical study tested the effectiveness of T-DXd for people with various HER2-expressing cancers and the safety of treatment. Previous results from DESTINY-PanTumor02 showed that T-DXd had antitumor activity, and the greatest effects …
What Rankings, Ratings, And Utilities Do Breast Cancer Patients Place On Tissue- And Implant-Based Breast Reconstruction?, Haoqi Wang, Nsikak M Jackson, Danmeng Huang, Rachel E Alexander, Mary Catherine Bordes, Jun Liu, Tzuan A Chen, Fatima Merchant, Summer E Hanson, Mark Schaverien, Mia K Markey, Gregory P Reece, Scott B Cantor, Aubri S Hoffman
What Rankings, Ratings, And Utilities Do Breast Cancer Patients Place On Tissue- And Implant-Based Breast Reconstruction?, Haoqi Wang, Nsikak M Jackson, Danmeng Huang, Rachel E Alexander, Mary Catherine Bordes, Jun Liu, Tzuan A Chen, Fatima Merchant, Summer E Hanson, Mark Schaverien, Mia K Markey, Gregory P Reece, Scott B Cantor, Aubri S Hoffman
Faculty, Staff and Student Publications
Background: Utility analysis is well-established for comparing treatment options but challenging to assess with patients in clinical care. Preference assessment may be more feasible, but it is not yet known whether it correlates with utilities. The aims of this study were to (1) assess women's rankings, ratings, and utilities for tissue-based, implant-based, and no reconstruction after total mastectomy; and (2) explore assessment methods and correlations with clinical and psychosocial factors.
Methods: Forty patients considering or undergoing breast reconstruction completed 3 assessments-card ranking, visual analog scale, and standard gamble-and psychosocial questionnaires. Each woman rated 9 health states with case-matched images: 4 …
A Biomarker Signature-Guided Clinical Trial Design For Precision Medicine, Yuan Li, Dejian Lai, Ruosha Li, Han Chen, Xuelin Huang, Jing Ning
A Biomarker Signature-Guided Clinical Trial Design For Precision Medicine, Yuan Li, Dejian Lai, Ruosha Li, Han Chen, Xuelin Huang, Jing Ning
Faculty, Staff and Student Publications
Targeted cancer therapies aim to effectively treat patients with specific biomarker profiles. Nevertheless, these therapies may not always precisely hit their intended targets, leading to uncertainty about the specific subset of patients who will benefit. To address this uncertainty, the identification of sensitive patient subsets in clinical trials becomes crucial. Our proposed phase IIB/III clinical trial design seeks to pinpoint a biomarker signature with precision, ensuring the accurate identification of patients who will respond to a specific treatment. This approach allows for the selective enrollment of sensitive patients to maximize benefits for trial participants. We incorporate Bayesian methodology to facilitate …
A Phase 2 Study Of Decitabine With Or Without Carboplatin And Arsenic Trioxide In Patients With Mds And Aml, Patricia L Kropf, Woonbok Chung, Raji Shameem, Lianchun Xiao, Curt Balch, Xuelin Huang, Jean-Pierre J Issa
A Phase 2 Study Of Decitabine With Or Without Carboplatin And Arsenic Trioxide In Patients With Mds And Aml, Patricia L Kropf, Woonbok Chung, Raji Shameem, Lianchun Xiao, Curt Balch, Xuelin Huang, Jean-Pierre J Issa
Faculty, Staff and Student Publications
Although decitabine (DAC) shows activity against myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), patient responses are limited, and prognoses remain poor. Preclinical studies have indicated that arsenic trioxide (ATO) and carboplatin (Carbo) enhance DAC's epigenetic gene derepression. Consequently, we initiated a randomized phase 2 clinical trial evaluating DAC alone, or with Carbo or ATO, in patients with MDS/AML. Thirty patients were initially randomized to receive DAC alone (20 mg/m2, days 1-5), DAC plus Carbo (AUC 5, day 8), or DAC plus ATO (0.15 mg/kg, days 1-5), followed by adaptive randomization of 61 patients, based on response rates, for at …
The Multilayered Transcriptional Architecture Of Glioblastoma Ecosystems, Masashi Nomura, Avishay Spitzer, Kevin C Johnson, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhfury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Roel G W Verhaak, Antonio Iavarone, Mario L Suvà, Itay Tirosh
The Multilayered Transcriptional Architecture Of Glioblastoma Ecosystems, Masashi Nomura, Avishay Spitzer, Kevin C Johnson, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhfury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Roel G W Verhaak, Antonio Iavarone, Mario L Suvà, Itay Tirosh
Faculty, Staff and Student Publications
In isocitrate dehydrogenase wildtype glioblastoma (GBM), cellular heterogeneity across and within tumors may drive therapeutic resistance. Here we analyzed 121 primary and recurrent GBM samples from 59 patients using single-nucleus RNA sequencing and bulk tumor DNA sequencing to characterize GBM transcriptional heterogeneity. First, GBMs can be classified by their broad cellular composition, encompassing malignant and nonmalignant cell types. Second, in each cell type we describe the diversity of cellular states and their pathway activation, particularly an expanded set of malignant cell states, including glial progenitor cell-like, neuronal-like and cilia-like. Third, the remaining variation between GBMs highlights three baseline gene expression …
Deciphering The Longitudinal Trajectories Of Glioblastoma Ecosystems By Integrative Single-Cell Genomics, Avishay Spitzer, Kevin C Johnson, Masashi Nomura, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo-Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Antonio Iavarone, Roel G W Verhaak, Itay Tirosh, Mario L Suvà
Deciphering The Longitudinal Trajectories Of Glioblastoma Ecosystems By Integrative Single-Cell Genomics, Avishay Spitzer, Kevin C Johnson, Masashi Nomura, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo-Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Antonio Iavarone, Roel G W Verhaak, Itay Tirosh, Mario L Suvà
Faculty, Staff and Student Publications
The evolution of isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) after standard-of-care therapy remains poorly understood. Here we analyzed matched primary and recurrent GBMs from 59 patients using single-nucleus RNA sequencing and bulk DNA sequencing, assessing the longitudinal evolution of the GBM ecosystem across layers of cellular and molecular heterogeneity. The most consistent change was a lower malignant cell fraction at recurrence and a reciprocal increase in glial and neuronal cell types in the tumor microenvironment (TME). The predominant malignant cell state differed between most matched pairs, but no states were exclusive or highly enriched in either time point, nor was there …
Prospective Clinical Trials Of Venetoclax And Hypomethylating Agents For Relapsed Bpdcn, Naveen Pemmaraju, Luan Hai Phan, Geoffrey Fell, Marlise R Luskin, Mahesh Swaminathan, Sherry Pierce, Courtney Dinardo, Abhishek Maiti, Marina Konopleva, Andrew A Lane
Prospective Clinical Trials Of Venetoclax And Hypomethylating Agents For Relapsed Bpdcn, Naveen Pemmaraju, Luan Hai Phan, Geoffrey Fell, Marlise R Luskin, Mahesh Swaminathan, Sherry Pierce, Courtney Dinardo, Abhishek Maiti, Marina Konopleva, Andrew A Lane
Faculty, Staff and Student Publications
No abstract provided.
Further Delineation Of The Scaf4-Associated Neurodevelopmental Disorder, Cosima M Schmid, Anne Gregor, Anna Ruiz, Carmen Manso Bazús, Isabella Herman, Farah Ammouri, Urania Kotzaeridou, Vanda Mcniven, Lucie Dupuis, Katharina Steindl, Anaïs Begemann, Anita Rauch, Aude-Annick Suter, Bertrand Isidor, Sandra Mercier, Mathilde Nizon, Benjamin Cogné, Wallid Deb, Thomas Besnard, Tobias B Haack, Ruth J Falb, Amelie J Müller, Tobias Linden, Chad R Haldeman-Englert, Charlotte W Ockeloen, Francesca Mattioli, Alexandre Reymond, Nazia Ibrahim, Shagufta Naz, Elodie Lacaze, Jennifer A Bassetti, Julia Hoefele, Theresa Brunet, Korbinian M Riedhammer, Houda Z Elloumi, Richard Person, Fanggeng Zou, Juliette J Kahle, Kirsten Cremer, Axel Schmidt, Marie-Ange Delrue, Pedro M Almeida, Fabiana Ramos, Siddharth Srivastava, Aisling Quinlan, Stephen Robertson, Eva Manka, Alma Kuechler, Stephanie Spranger, Malgorzata J M Nowaczyk, Reem M Elshafie, Hind Alsharhan, Paul R Hillman, Leslie A Dunnington, Hilde M H Braakman, Shane Mckee, Angelica Moresco, Andrea-Diana Ignat, Ruth Newbury-Ecob, Guillaume Banneau, Olivier Patat, Jeffrey Kuerbitz, Susan Rzucidlo, Susan S Sell, Patricia Gordon, Sarah Schuhmann, André Reis, Yosra Halleb, Radka Stoeva, Boris Keren, Zainab Al Masseri, Zeynep Tümer, Sophia Hammer-Hansen, Sofus Krüger Sølyst, Connolly G Steigerwald, Nicolas J Abreu, Helene Faust, Amica Müller-Nedebock, Frédéric Tran Mau-Them, Heinrich Sticht, Christiane Zweier
Further Delineation Of The Scaf4-Associated Neurodevelopmental Disorder, Cosima M Schmid, Anne Gregor, Anna Ruiz, Carmen Manso Bazús, Isabella Herman, Farah Ammouri, Urania Kotzaeridou, Vanda Mcniven, Lucie Dupuis, Katharina Steindl, Anaïs Begemann, Anita Rauch, Aude-Annick Suter, Bertrand Isidor, Sandra Mercier, Mathilde Nizon, Benjamin Cogné, Wallid Deb, Thomas Besnard, Tobias B Haack, Ruth J Falb, Amelie J Müller, Tobias Linden, Chad R Haldeman-Englert, Charlotte W Ockeloen, Francesca Mattioli, Alexandre Reymond, Nazia Ibrahim, Shagufta Naz, Elodie Lacaze, Jennifer A Bassetti, Julia Hoefele, Theresa Brunet, Korbinian M Riedhammer, Houda Z Elloumi, Richard Person, Fanggeng Zou, Juliette J Kahle, Kirsten Cremer, Axel Schmidt, Marie-Ange Delrue, Pedro M Almeida, Fabiana Ramos, Siddharth Srivastava, Aisling Quinlan, Stephen Robertson, Eva Manka, Alma Kuechler, Stephanie Spranger, Malgorzata J M Nowaczyk, Reem M Elshafie, Hind Alsharhan, Paul R Hillman, Leslie A Dunnington, Hilde M H Braakman, Shane Mckee, Angelica Moresco, Andrea-Diana Ignat, Ruth Newbury-Ecob, Guillaume Banneau, Olivier Patat, Jeffrey Kuerbitz, Susan Rzucidlo, Susan S Sell, Patricia Gordon, Sarah Schuhmann, André Reis, Yosra Halleb, Radka Stoeva, Boris Keren, Zainab Al Masseri, Zeynep Tümer, Sophia Hammer-Hansen, Sofus Krüger Sølyst, Connolly G Steigerwald, Nicolas J Abreu, Helene Faust, Amica Müller-Nedebock, Frédéric Tran Mau-Them, Heinrich Sticht, Christiane Zweier
Faculty, Staff and Student Publications
While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder. The molecular spectrum comprises 25 truncating, eight splice-site and five missense variants. While all other truncating variants were classified as pathogenic/likely pathogenic, significance of one C-terminal truncating variant, one …
Oral Microbiome Profile Of The Us Population, Anil K Chaturvedi, Emily Vogtmann, Jianxin Shi, Yukiko Yano, Martin J Blaser, Nicholas A Bokulich, J Gregory Caporaso, Maura L Gillison, Barry I Graubard, Xing Hua, Autumn G Hullings, Lisa Kahle, Rob Knight, Shilan Li, Jody Mclean, Vaishnavi Purandare, Yunhu Wan, Neal D Freedman, Christian C Abnet
Oral Microbiome Profile Of The Us Population, Anil K Chaturvedi, Emily Vogtmann, Jianxin Shi, Yukiko Yano, Martin J Blaser, Nicholas A Bokulich, J Gregory Caporaso, Maura L Gillison, Barry I Graubard, Xing Hua, Autumn G Hullings, Lisa Kahle, Rob Knight, Shilan Li, Jody Mclean, Vaishnavi Purandare, Yunhu Wan, Neal D Freedman, Christian C Abnet
Faculty, Staff and Student Publications
Importance: The oral microbiome likely plays key roles in human health. Yet, population-representative characterizations are lacking.
Objective: To characterize the composition, diversity, and correlates of the oral microbiome in US adults.
Design, setting, and participants: This cross-sectional study analyzed data from the population-representative National Health and Nutrition Examination Survey (NHANES) from 2009 to 2012. Microbiome data were made publicly available in 2024. NHANES participants were aged 18 to 69 years and provided oral rinse samples in 1 of 2 consecutive NHANES cycles (2009-2010 and 2011-2012).
Exposures: Demographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics.
Main outcomes and measures: Oral microbiome …
Concerns About The Paper, “Benefits Of Targeted Vibration For Bone Strength And Bone Density In Postmenopausal Women With Osteopenia: A Randomized, Sham-Controlled Trial”, Douglas P Kiel, Theresa A Guise, Maya Styner, Janet Rubin
Concerns About The Paper, “Benefits Of Targeted Vibration For Bone Strength And Bone Density In Postmenopausal Women With Osteopenia: A Randomized, Sham-Controlled Trial”, Douglas P Kiel, Theresa A Guise, Maya Styner, Janet Rubin
Faculty, Staff and Student Publications
No abstract provided.
Pd-L1 Testing, Treatment Patterns, And Clinical Outcomes Among Patients With Metastatic Nsclc At An Academic Medical Center, 2017-2021, Mehmet Altan, Dawen Sui, Cai Xu, George R Simon, Saliha T Sulihem, Donna Malveaux, Darcy Ponce, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Melissa L Santorelli, Thomas Burke, Loretta A Williams
Pd-L1 Testing, Treatment Patterns, And Clinical Outcomes Among Patients With Metastatic Nsclc At An Academic Medical Center, 2017-2021, Mehmet Altan, Dawen Sui, Cai Xu, George R Simon, Saliha T Sulihem, Donna Malveaux, Darcy Ponce, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Melissa L Santorelli, Thomas Burke, Loretta A Williams
Faculty, Staff and Student Publications
Introduction: Targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic non-small cell lung cancer (NSCLC) over the past decade.
Methods: This single-center observational study was conducted to describe programmed death-ligand 1 (PD-L1) testing, choice of therapy, and outcomes for adult patients with stage IV NSCLC initiating first-line therapy from 2017 through 2020, with follow-up through June 2021. Patient characteristics and study assessments were described according to four histomolecular subtypes, defined by histologic characteristics and availability of standard-of-care therapies for molecular subgroups at the time of study conduct.
Results: Of 507 eligible patients with metastatic NSCLC, 85 …
Fecal Immunochemical Test Positivity Thresholds: An International Survey Of Population-Based Screening Programs, Graeme P Young, Sally C Benton, Robert S Bresalier, Han-Mo Chiu, Evelien Dekker, Callum G Fraser, Marieke A M Frasa, Stephen P Halloran, Michael Hoffmeister, Susan Parry, Kevin Selby, Carlo Senore, Harminder Singh, Erin L Symonds
Fecal Immunochemical Test Positivity Thresholds: An International Survey Of Population-Based Screening Programs, Graeme P Young, Sally C Benton, Robert S Bresalier, Han-Mo Chiu, Evelien Dekker, Callum G Fraser, Marieke A M Frasa, Stephen P Halloran, Michael Hoffmeister, Susan Parry, Kevin Selby, Carlo Senore, Harminder Singh, Erin L Symonds
Faculty, Staff and Student Publications
Background: The fecal immunochemical test for hemoglobin (FIT) is now a widely used non-invasive test in population-based organized screening programs for colorectal neoplasia. The positivity thresholds of tests currently in use are based on the fecal hemoglobin concentration (f-Hb), but the rationale for the adopted thresholds are not well documented. To understand current global usage of FIT in screening programs we conducted an international survey of the brands of FIT used, the f-Hb positivity threshold applied and the rationale for the choice.
Methods: All members of the World Endoscopy Organization CRC Screening Committee were invited to complete an eight-element initial …
Chd1 Loss Reprograms Srebp2-Driven Cholesterol Synthesis To Fuel Androgen-Responsive Growth And Castration Resistance In Spop-Mutated Prostate Tumors, Feiyu Chen, Haoyan Li, Yin Wang, Ximing Tang, Kevin Lin, Qidong Li, Chenling Meng, Wei Shi, Javier Leo, Xin Liang, Jie Zhang, Vivien Van, Iqbal Mahmud, Bo Wei, Philip L Lorenzi, Maria G Raso, Ana Aparicio, Yue Lu, Daniel E Frigo, Boyi Gan, Di Zhao
Chd1 Loss Reprograms Srebp2-Driven Cholesterol Synthesis To Fuel Androgen-Responsive Growth And Castration Resistance In Spop-Mutated Prostate Tumors, Feiyu Chen, Haoyan Li, Yin Wang, Ximing Tang, Kevin Lin, Qidong Li, Chenling Meng, Wei Shi, Javier Leo, Xin Liang, Jie Zhang, Vivien Van, Iqbal Mahmud, Bo Wei, Philip L Lorenzi, Maria G Raso, Ana Aparicio, Yue Lu, Daniel E Frigo, Boyi Gan, Di Zhao
Faculty, Staff and Student Publications
Despite undergoing castration, most individuals with prostate cancer (PCa) experience progression to castration-resistant PCa (CRPC), in which the androgen receptor (AR) remains an important driver. Concurrent genetic alterations in SPOP and CHD1 define a unique subtype of PCa, but their interactions in tumor progression and therapy response remain unclear. Here, we provide genetic evidence supporting that CHD1 loss accelerates disease progression and confers resistance to castration in males with SPOP-mutated PCa. By leveraging genetic engineering and multiomics, we uncovered a noncanonical function of CHD1 in lipid metabolism reprogramming via repressing the SREBP2 transcriptome. Loss of CHD1 induces cholesterol production, supplies …
Treatment Of C-Met Antibody-Drug Conjugate Asymptomatic Pneumonitis With A Novel Steroid Regimen In Non-Small Cell Lung Cancer: A Case Report, Daniel A Fox, Christine Tran, Vincent Blot, David S Hong
Treatment Of C-Met Antibody-Drug Conjugate Asymptomatic Pneumonitis With A Novel Steroid Regimen In Non-Small Cell Lung Cancer: A Case Report, Daniel A Fox, Christine Tran, Vincent Blot, David S Hong
Faculty, Staff and Student Publications
Antibody-drug conjugates (ADCs) are a potent class of antineoplastic drugs that deliver cytotoxic agents via targeting with monoclonal antibodies; however, ADCs are associated with high rates of lung toxicities, limiting the therapeutic potential in many patients. We report a case of a patient with metastatic non-small cell lung cancer taking the ADC telisotuzumab vedotin (Teliso V) plus osimtertinib who developed ADC-induced pneumonitis despite clinical benefit. This patient was able to tolerate treatment for a prolonged period on a novel steroid regimen, using steroids when pneumonitis was asymptomatic but radiologically evident and as a daily suppressant. This treatment strategy may have …
From Epithelium To Therapy: Transitional Cells In Lung Fibrosis, Sarah Y Shin, Jichao Chen, Irit Milman Krentsis, Yair Reisner, Rodeo Abrencillo, Rahat Hussain, Danielle Wu, Harry Karmouty-Quintana
From Epithelium To Therapy: Transitional Cells In Lung Fibrosis, Sarah Y Shin, Jichao Chen, Irit Milman Krentsis, Yair Reisner, Rodeo Abrencillo, Rahat Hussain, Danielle Wu, Harry Karmouty-Quintana
Faculty, Staff and Student Publications
Patients with idiopathic pulmonary fibrosis and lung fibrosis secondary to infections such as influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have limited treatment options outside of supportive therapy and lung transplantation. Multiple lung stem cell populations have been implicated in the pathogenesis of lung fibrosis, and more progenitor cell populations continue to be discovered and characterized. In this review, we summarize the functions and differentiation pathways of various cells that constitute the lung epithelium. We then focus on two subpopulations of KRT5
Oculomics: Current Concepts And Evidence, Zhuoting Zhu, Yueye Wang, Ziyi Qi, Wenyi Hu, Xiayin Zhang, Siegfried K Wagner, Yujie Wang, An Ran Ran, Joshua Ong, Ethan Waisberg, Mouayad Masalkhi, Alex Suh, Yih Chung Tham, Carol Y Cheung, Xiaohong Yang, Honghua Yu, Zongyuan Ge, Wei Wang, Bin Sheng, Yun Liu, Andrew G Lee, Alastair K Denniston, Peter Van Wijngaarden, Pearse A Keane, Ching-Yu Cheng, Mingguang He, Tien Yin Wong
Oculomics: Current Concepts And Evidence, Zhuoting Zhu, Yueye Wang, Ziyi Qi, Wenyi Hu, Xiayin Zhang, Siegfried K Wagner, Yujie Wang, An Ran Ran, Joshua Ong, Ethan Waisberg, Mouayad Masalkhi, Alex Suh, Yih Chung Tham, Carol Y Cheung, Xiaohong Yang, Honghua Yu, Zongyuan Ge, Wei Wang, Bin Sheng, Yun Liu, Andrew G Lee, Alastair K Denniston, Peter Van Wijngaarden, Pearse A Keane, Ching-Yu Cheng, Mingguang He, Tien Yin Wong
Faculty, Staff and Student Publications
The eye provides novel insights into general health, as well as pathogenesis and development of systemic diseases. In the past decade, growing evidence has demonstrated that the eye's structure and function mirror multiple systemic health conditions, especially in cardiovascular diseases, neurodegenerative disorders, and kidney impairments. This has given rise to the field of oculomics-the application of ophthalmic biomarkers to understand mechanisms, detect and predict disease. The development of this field has been accelerated by three major advances: 1) the availability and widespread clinical adoption of high-resolution and non-invasive ophthalmic imaging ("hardware"); 2) the availability of large studies to interrogate associations …
Comic: A Bayesian Dose Optimization Design For Drug Combination In Multiple Indications With Application To Car-T Therapies, Kai Chen, Kentaro Takeda, Ying Yuan
Comic: A Bayesian Dose Optimization Design For Drug Combination In Multiple Indications With Application To Car-T Therapies, Kai Chen, Kentaro Takeda, Ying Yuan
Faculty, Staff and Student Publications
Project Optimus, initiated by the US Food and Drug Administration (FDA), seeks to shift the focus of dose finding and selection from the maximum tolerated dose to the optimal dose that offers the most favorable risk-benefit balance. However, applying this paradigm shift to drug combination trials presents challenges, particularly due to limited sample sizes and a large two-dimensional dose exploration space. These challenges are amplified when trials involve multiple indications. To address this, we developed a two-stage Bayesian dose optimization design, called COMIC (Combination Optimization in Multiple IndiCations), to efficiently identify Optimal Biological Dose Combinations (OBDC) for multiple indications. The …
Safety, Efficacy, And Adjacent-Level Fracture Risk Following Vertebral Augmentation And Radiofrequency Ablation For The Treatment Of Spine Metastases In Patients With Cancer, Jeremiah Stringam, Koustav Pal, Andrew Niekamp, Rahim Jiwani, Iwan Paolucci, Joshua D Kuban, Zeyad Metwalli, Steven Huang, Peiman Habibollahi, Stephen Chen, Steven Yevich, Milan Patel, Sumit K Subudhi, Matthew Campbell, Amol Ghia, Claudio Tatsui, Rahul A Sheth
Safety, Efficacy, And Adjacent-Level Fracture Risk Following Vertebral Augmentation And Radiofrequency Ablation For The Treatment Of Spine Metastases In Patients With Cancer, Jeremiah Stringam, Koustav Pal, Andrew Niekamp, Rahim Jiwani, Iwan Paolucci, Joshua D Kuban, Zeyad Metwalli, Steven Huang, Peiman Habibollahi, Stephen Chen, Steven Yevich, Milan Patel, Sumit K Subudhi, Matthew Campbell, Amol Ghia, Claudio Tatsui, Rahul A Sheth
Faculty, Staff and Student Publications
Purpose: To evaluate the safety and efficacy of vertebral augmentation (VA) and radiofrequency ablation (RFA) for treating pathologic spinal fractures in patients with cancer and adjacent fracture risk following treatment.
Materials and Methods: This single-institution retrospective study, conducted from January 2017 to September 2020, included patients with cancer who underwent percutaneous VA with or without spine RFA for pathologic spine compression fractures. The primary outcome was pain reduction, assessed using the 10-point visual analog scale before the procedure, at first follow-up, and 2–4 weeks after the procedure. Logistic regression was performed to identify factors associated with epidural cement leak.
Results: …
Todo: A Triple-Outcome Double-Criterion Optimal Design For Dose Monitoring-And-Optimization In Multi-Dose Randomized Trials, Jingyi Zhang, Heng Zhou, Nolan A Wages, Zifang Guo, Fang Liu, Thomas Jemielita, Fangrong Yan, Ruitao Lin
Todo: A Triple-Outcome Double-Criterion Optimal Design For Dose Monitoring-And-Optimization In Multi-Dose Randomized Trials, Jingyi Zhang, Heng Zhou, Nolan A Wages, Zifang Guo, Fang Liu, Thomas Jemielita, Fangrong Yan, Ruitao Lin
Faculty, Staff and Student Publications
Detecting the efficacy signal and determining the optimal dose are critical steps to increase the probability of success and expedite the drug development in cancer treatment. After identifying a safe dose range through phase I studies, conducting a multidose randomized trial becomes an effective approach to achieve this objective. However, there have been limited formal statistical designs for such multidose trials, and dose selection in practice is often ad hoc, relying on descriptive statistics. We propose a Bayesian optimal two-stage design to facilitate rigorous dose monitoring and optimization. Utilizing a flexible Bayesian dynamic linear model for the dose-response relationship, we …
Rna Sculpting By The Primordial Helix-Clasp-Helix-Strand-Loop (Hch-Sl) Motif Enforces Chemical Recognition Enabling Diverse Kh Domain Functions, John A Tainer, Susan E Tsutakawa
Rna Sculpting By The Primordial Helix-Clasp-Helix-Strand-Loop (Hch-Sl) Motif Enforces Chemical Recognition Enabling Diverse Kh Domain Functions, John A Tainer, Susan E Tsutakawa
Faculty, Staff and Student Publications
In all domains of life, the ancient K homology (KH) domain superfamily is central to RNA processes including splicing, transcription, posttranscriptional gene regulation, signaling, and translation. Proteins with 1 to 15 KH domains bind single-strand (ss) RNA or DNA with base sequence specificity. Here, we examine over 40 KH domain experimental structures in complex with nucleic acid (NA) and define a novel Helix-clasp-Helix-Strand-Loop (HcH-SL) NA recognition motif binding 4 to 5 nucleotides using 10 to 18 residues. HcH-SL includes and extends the Gly-X-X-Gly (GXXG) signature sequence "clasp" that brings together two helices as an ∼90° helical corner. The first helix …
Air Embolism After Percutaneous Lung Biopsy Or Ablation: A Report Of Six Cases, Rebecca Choi, Haylie Kieu-Mi Phan, Varshana Gurusamy, Rahul A Sheth, Bruno C Odisio, Kelvin Hong, Alda L Tam
Air Embolism After Percutaneous Lung Biopsy Or Ablation: A Report Of Six Cases, Rebecca Choi, Haylie Kieu-Mi Phan, Varshana Gurusamy, Rahul A Sheth, Bruno C Odisio, Kelvin Hong, Alda L Tam
Faculty, Staff and Student Publications
Systemic air embolism is a rare but potentially life-threatening complication of percutaneous lung biopsy and ablation. This report describes six patients (four male, two female) with air embolism following CT-guided lung interventions at two institutions between January 2021 and March 2024. Air embolisms were identified in locations such as the pulmonary vein, left ventricle, and coronary arteries, with clinical presentations ranging from asymptomatic to life-threatening events. Prompt intervention, including oxygen therapy, patient repositioning, and intravenous administration of epinephrine in cases of cardiac arrest, resulted in favorable outcomes. This series highlights the importance of early detection of systemic air embolism and …
A Comparison Of Carbon Ions Versus Protons For Integrated Mode Ion Imaging, Mikaël Simard, Ryan Fullarton, Lennart Volz, Christoph Schuy, Daniel G Robertson, Allison Toltz, Colin Baker, Sam Beddar, Christian Graeff, Charles-Antoine Collins Fekete
A Comparison Of Carbon Ions Versus Protons For Integrated Mode Ion Imaging, Mikaël Simard, Ryan Fullarton, Lennart Volz, Christoph Schuy, Daniel G Robertson, Allison Toltz, Colin Baker, Sam Beddar, Christian Graeff, Charles-Antoine Collins Fekete
Faculty, Staff and Student Publications
Background: Incorporating image guidance into ion beam therapy is critical for minimizing beam range uncertainties and realizing the modality's potential. One promising avenue for image guidance is to capture transmission ion radiographs (iRads) before and/or during treatment. iRad image quality is typically maximized using a single-event imaging system, which involves tracking individual ions, albeit the approach is generally not suited to clinical beam settings. An alternative faster and clinically compatible method is integrated mode imaging, where individual pencil beam data is acquired, rather than single ion data. To evaluate the usefulness of transmission ion imaging for image guidance, it is …
Addressing Structural Violence In School Policies: A Call To Protect Children's Safety And Well-Being., Daniela Brissett, Jacquelin Rankine, Lisa Mihaly, Romina Barral, Maria Veronica Svetaz, Alison Culyba, Marissa Raymond-Flesch
Addressing Structural Violence In School Policies: A Call To Protect Children's Safety And Well-Being., Daniela Brissett, Jacquelin Rankine, Lisa Mihaly, Romina Barral, Maria Veronica Svetaz, Alison Culyba, Marissa Raymond-Flesch
Manuscripts, Articles, Book Chapters and Other Papers
No abstract provided.
Development Of A Treatment Decision Aid For Patients With Dysplastic Nevi Who Are Candidates For Re-Excision, Jaclyn N Roland-Mcgowan, Steven Caleb Freeman, Wenelia Baghoomian, Bryan T Carroll, Caroline Choi Kim, Clara Curiel-Lewandrowski, Emily Y Chu, Erin L Foster, Kelly Carter Nelson, Kevin P White, Michael E Ming, Rebecca I Hartman, Sancy A Leachman, Stephanie Mengden-Koon, Suephy C Chen, Susan M Swetter, Victor G Prieto, Elizabeth Berry, Wesley Y Yu
Development Of A Treatment Decision Aid For Patients With Dysplastic Nevi Who Are Candidates For Re-Excision, Jaclyn N Roland-Mcgowan, Steven Caleb Freeman, Wenelia Baghoomian, Bryan T Carroll, Caroline Choi Kim, Clara Curiel-Lewandrowski, Emily Y Chu, Erin L Foster, Kelly Carter Nelson, Kevin P White, Michael E Ming, Rebecca I Hartman, Sancy A Leachman, Stephanie Mengden-Koon, Suephy C Chen, Susan M Swetter, Victor G Prieto, Elizabeth Berry, Wesley Y Yu
Faculty, Staff and Student Publications
No abstract provided.
Blood Pressure Misclassification Among Stroke Survivors Followed In A Comprehensive Stroke Prevention Clinic, M Carter Denny, Maha Almohamad, Emmanuel Ebirim, Adriana Morell, Munachi Okpala, Kevin O Hwang, Sean Savitz, Anjail Sharrief
Blood Pressure Misclassification Among Stroke Survivors Followed In A Comprehensive Stroke Prevention Clinic, M Carter Denny, Maha Almohamad, Emmanuel Ebirim, Adriana Morell, Munachi Okpala, Kevin O Hwang, Sean Savitz, Anjail Sharrief
Faculty, Staff and Student Publications
Background: Hypertension is the most important modifiable risk factor for secondary stroke prevention; however, blood pressure (BP) remains uncontrolled for at least 50 % of stroke survivors following an incident stroke. Accurate in-clinic assessment of BP is important for appropriate medication titration. We evaluated misclassification of clinic BP control in a racially diverse stroke clinic population using two BP measurement methods.
Observations: We followed ischemic stroke, intracerebral hemorrhage, and transient ischemic attack patients after hospital discharge in a comprehensive stroke clinic. Casual BP was obtained using a standard office automated machine, attended by a medical assistant. BP was also measured …
Longevity Humans Have Youthful Erythrocyte Function And Metabolic Signatures, Fang Yu, Changhan Chen, Wuping Liu, Zhixiang Zhao, Yuhua Fan, Zhenjiang Li, Weilun Huang, Tingting Xie, Cheng Luo, Zhouzhou Yao, Qi Guo, Zhiyu Yang, Juan Liu, Yujin Zhang, Rodney E Kellems, Jian Xia, Ji Li, Yang Xia
Longevity Humans Have Youthful Erythrocyte Function And Metabolic Signatures, Fang Yu, Changhan Chen, Wuping Liu, Zhixiang Zhao, Yuhua Fan, Zhenjiang Li, Weilun Huang, Tingting Xie, Cheng Luo, Zhouzhou Yao, Qi Guo, Zhiyu Yang, Juan Liu, Yujin Zhang, Rodney E Kellems, Jian Xia, Ji Li, Yang Xia
Faculty, Staff and Student Publications
Longevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging-related diseases. It has long been speculated that "rejuvenation molecules" exist in their blood to promote extended lifespan. We unexpectedly discovered that longevity individuals exhibit erythrocyte oxygen release function similar to young individuals, whereas most elderly show reduced oxygen release capacity. Untargeted erythrocyte metabolomics profiling revealed that longevity individuals are characterized by youth-like metabolic reprogramming and these metabolites effectively differentiate the longevity from the elderly. Quantification analyses led us to identify multiple novel longevity-related metabolites within erythrocytes including adenosine, sphingosine-1-phosphate (S1P), and glutathione (GSH) related amino acids. Mechanistically, …
Donor Age Matters For Haploidentical Hct Patients Even After Adjusting For Hla Factors: A Machine Learning Approach, Rohtesh S Mehta, Rodney Sparapani, Tao Wang, Stephen Spellman, Stephanie J Lee, Effie W Petersdorf
Donor Age Matters For Haploidentical Hct Patients Even After Adjusting For Hla Factors: A Machine Learning Approach, Rohtesh S Mehta, Rodney Sparapani, Tao Wang, Stephen Spellman, Stephanie J Lee, Effie W Petersdorf
Faculty, Staff and Student Publications
No abstract provided.
Successful Flexible Bronchoscopic Extraction Of A Dental Foreign Body Aspirated Into The Left Mainstem Bronchus, Alexys Bolden, Hayden Cooper, Lynnetta Payne, Mark Coomes, Mark Cooper
Successful Flexible Bronchoscopic Extraction Of A Dental Foreign Body Aspirated Into The Left Mainstem Bronchus, Alexys Bolden, Hayden Cooper, Lynnetta Payne, Mark Coomes, Mark Cooper
Marshall Journal of Medicine
Foreign body aspiration (FBA) is a potentially life-threatening emergency that commonly occurs in children but varies widely in clinical presentation. Rapid diagnosis and intervention are of the utmost importance to prevent complications such as airway obstruction, infection, and lung injury. While uncommon in adults, most encountered causes occur in the setting of intoxication, neuromuscular weakness, or iatrogenic dental work. Those with dental prostheses are especially susceptible due to the partially attached nature, rendering the risk of accidental dislodgement. This report discusses an uncommon case wherein an 82-year-old male aspirated a dental bridge into his left mainstem bronchus during routine dental …
From Molars To Bronchus; The Tale Of An Aspirated Dental Instrument, Yisroel Grabie, Sudeep Acharya, Fasih Sami Siddiqui, Gabriel A. Chavez Reyna, Michel Chalhoub
From Molars To Bronchus; The Tale Of An Aspirated Dental Instrument, Yisroel Grabie, Sudeep Acharya, Fasih Sami Siddiqui, Gabriel A. Chavez Reyna, Michel Chalhoub
HCA Healthcare Journal of Medicine
Background
Aspiration of dental instruments is a rare event that carries potentially serious complications when it occurs, especially in older patients, where protective reflexes are diminished. Clinical management may be difficult because of the risk of granulation tissue and different retrieval strategies according to the object’s characteristics. In this report, we describe the case of an 84-year-old man who aspirated a dental bur during a routine dental procedure, necessitating immediate intervention. Timely and precise management was essential to avert severe complications.
Case Presentation
During a routine dental procedure, an 84-year-old man aspirated a bud-shaped cross-cut carbide dental bur. Despite initial …