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JOURNAL ARTICLE
Sharif Hala, Mohammed Malaikah, Jiayi Huang, Wesam Bahitham, Omniya Fallatah, Samer Zakri, Chakkiath Paul Antony, Mohammed Alshehri, Raeece Naeem Ghazzali, Fathia Ben-Rached, Abdullah Alsahafi, Asim Alsaedi, Ghadeer AlAhmadi, Mai Kaaki, Meshari Alazmi, Baraa AlhajHussein, Muhammad Yaseen, Hosam M Zowawi, Majed F Alghoribi, Abdulhakeem O Althaqafi, Abdulfattah Al-Amri, Danesh Moradigaravand, Arnab Pain
BACKGROUND: Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks...
April 18, 2024: Genome Medicine
#22
JOURNAL ARTICLE
Panagiotis A Konstantinopoulos, Su-Chun Cheng, Elizabeth K Lee, Alexandre André B A da Costa, Doga Gulhan, Andrea E Wahner Hendrickson, Bose Kochupurakkal, David L Kolin, Elise C Kohn, Joyce F Liu, Richard T Penson, Elizabeth H Stover, Jennifer Curtis, Hannah Sawyer, Madeline Polak, Dipanjan Chowdhury, Alan D D'Andrea, Anniina Färkkilä, Geoffrey I Shapiro, Ursula A Matulonis
PURPOSE: The multicenter, open-label, randomized phase 2 NCI-9944 study (NCT02595892) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (hazard ratio [HR]=0.57, one-sided log-rank P = .044, which met the one-sided significance level of 0.1 used for sample size calculation). METHODS: We report here the final overall survival (OS) analysis and biomarker correlations (ATM expression by immunohistochemistry, mutational signature 3 and a genomic biomarker of replication stress) along with post-hoc exploratory analyses to adjust for crossover from gemcitabine to gemcitabine/berzosertib...
April 2024: JCO Precision Oncology
#23
JOURNAL ARTICLE
Masaya Hattori, Victoria Serelli-Lee, Yoichi Naito, Takashi Yamanaka, Hiroyuki Yasojima, Rikiya Nakamura, Takao Fujisawa, Mitsuho Imai, Yoshiaki Nakamura, Hideaki Bando, Tsutomu Kawaguchi, Takayuki Yoshino, Hiroji Iwata
PURPOSE: To understand the mutational landscape of circulating tumor DNA (ctDNA) and tumor tissue of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) treated with abemaciclib + endocrine therapy (ET). METHODS: Blood samples for ctDNA and/or tissue samples were collected from abemaciclib-treated patients with HR+/HER2- MBC enrolled in the SCRUM-Japan MONSTAR-SCREEN project. Blood samples were collected before abemaciclib initiation (baseline) and at disease progression/abemaciclib discontinuation (post abemaciclib treatment)...
April 2024: JCO Precision Oncology
#24
JOURNAL ARTICLE
Ashley E Ross, Kenneth K Iwata, Dina Elsouda, John Hairston, David Russell, Elai Davicioni, James A Proudfoot, Neal D Shore, Edward M Schaeffer
PURPOSE: Few studies have explored the potential for pharmacological interventions to delay disease progression in patients undergoing active surveillance (AS). This preplanned transcriptomic analysis of patient samples from the ENACT trial aims to identify biomarkers in patients on AS who are at increased risk for disease progression or who may derive the greatest benefit from enzalutamide treatment. PATIENTS AND METHODS: In the phase II ENACT (ClinicalTrials.gov identifier: NCT02799745) trial, patients on AS were randomly assigned 1:1 to 160 mg orally once daily enzalutamide monotherapy or continued AS for 1 year...
April 2024: JCO Precision Oncology
#25
JOURNAL ARTICLE
Hye Sook Kim, Jong Kwang Kim, Jeong Hyeon Lee, Young Joo Lee, Geon-Kuk Lee, Ji-Youn Han
PURPOSE: High-grade neuroendocrine carcinoma (HGNEC) of the lung is an aggressive cancer with a complex biology. We aimed to explore the prognostic value of genetic aberrations and poly(ADP-ribose) polymerase-1 (PARP1) expression in HGNEC and to establish a novel prognostic model. MATERIALS AND METHODS: We retrospectively enrolled 191 patients with histologically confirmed HGNEC of the lung. Tumor tissues were analyzed using PARP1 immunohistochemistry (IHC; N = 191) and comprehensive cancer panel sequencing (n = 102)...
April 2024: JCO Precision Oncology
#26
JOURNAL ARTICLE
Yu-Hui Wang, Dina Espinoza Rivera, William Klobasa, Marcé D Lorenzen
The corn planthopper, Peregrinus maidis, is an economically important pest of corn and sorghum. Here we report the initial steps towards developing a CRISPR-based control method, precision guided sterile insect technique (pgSIT), for this hemipteran pest. Specifically, we evaluated the potential of transformer-2 (tra-2) as a target for sterilizing insects. First, we identified tra-2 transcripts within our P. maidis transcriptome database and performed RNA interference (RNAi) to confirm functional conservation...
2024: PloS One
#27
JOURNAL ARTICLE
Mark Roschewski, James D Phelan, Elaine S Jaffe
Diffuse large B-cell lymphoma (DLBCL) encompasses a diverse spectrum of aggressive B-cell lymphomas with remarkable genetic heterogeneity and myriad clinical presentations. Multiplatform genomic analyses of DLBCL have identified oncogenic drivers within genetic subtypes that allow for pathologic subclassification of tumors into discrete entities with shared immunophenotypic, genetic, and clinical features. Robust classification of lymphoid tumors establishes a foundation for precision medicine and enables the identification of novel therapeutic vulnerabilities within biologically homogeneous entities...
April 18, 2024: Blood
#28
JOURNAL ARTICLE
Terese Knoppers, Cassandra E Haley, Sarah Bouhouita-Guermech, Julie Hagan, Jacqueline Bradbury-Jost, Samuel Alarie, Marie Cosquer, Ma'n H Zawati
BACKGROUND: Acute myeloid leukemia (AML), a rapidly progressing cancer of the blood and bone marrow, is the most common and fatal type of adult leukemia. Therapeutic web portals have great potential to facilitate AML research advances and improve health outcomes by increasing the availability of data, the speed and reach of new knowledge, and the communication between researchers and clinicians in the field. However, there is a need for stakeholder research regarding their optimal features, utility, and implementation...
2024: PloS One
#29
JOURNAL ARTICLE
Mohammad A Anwar, Ammar H Keshteli, Haiyan Yang, Windy Wang, Xukun Li, Helen M Messier, Pieter R Cullis, Christoph H Borchers, Robert Fraser, David S Wishart
Over a decade ago, longitudinal multiomics analysis was pioneered for early disease detection and individually tailored precision health interventions. However, high sample processing costs, expansive multiomics measurements along with complex data analysis have made this approach to precision/personalized medicine impractical. Here we describe in a case report, a more practical approach that uses fewer measurements, annual sampling, and faster decision making. We also show how this approach offers promise to detect an exceedingly rare and potentially fatal condition before it fully manifests...
April 17, 2024: Omics: a Journal of Integrative Biology
#30
JOURNAL ARTICLE
J Sebastian Garcia-Medina, Karolina Sienkiewicz, S Anand Narayanan, Eliah G Overbey, Kirill Grigorev, Krista A Ryon, Marissa Burke, Jacqueline Proszynski, Braden Tierney, Caleb M Schmidt, Nuria Mencia-Trinchant, Remi Klotz, Veronica Ortiz, Jonathan Foox, Christopher Chin, Deena Najjar, Irina Matei, Irenaeus Chan, Carlos Cruchaga, Ashley Kleinman, JangKeun Kim, Alexander Lucaci, Conor Loy, Omary Mzava, Iwijn De Vlaminck, Anvita Singaraju, Lynn E Taylor, Julian C Schmidt, Michael A Schmidt, Kelly Blease, Juan Moreno, Andrew Boddicker, Junhua Zhao, Bryan Lajoie, Andrew Altomare, Semyon Kruglyak, Shawn Levy, Min Yu, Duane C Hassane, Susan M Bailey, Kelly Bolton, Jaime Mateus, Christopher E Mason
BACKGROUND: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure. METHODS: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction...
March 2024: Precision Clinical Medicine
#31
REVIEW
Smitesh Padte, Vikramaditya Samala Venkata, Priyal Mehta, Sawsan Tawfeeq, Rahul Kashyap, Salim Surani
Critical care medicine in the 21st century has witnessed remarkable advancements that have significantly improved patient outcomes in intensive care units (ICUs). This abstract provides a concise summary of the latest developments in critical care, highlighting key areas of innovation. Recent advancements in critical care include Precision Medicine: Tailoring treatments based on individual patient characteristics, genomics, and biomarkers to enhance the effectiveness of therapies. The objective is to describe the recent advancements in Critical Care Medicine...
March 9, 2024: World Journal of Critical Care Medicine
#32
JOURNAL ARTICLE
Yifei Cheng, Lang Wu, Junyi Xin, Shuai Ben, Silu Chen, Huiqin Li, Lingyan Zhao, Meilin Wang, Gong Cheng, Mulong Du
BACKGROUND: Early-onset prostate cancer (EOPC, ≤ 55 years) has a unique clinical entity harboring high genetic risk, but the majority of EOPC patients still substantial opportunity to be early-detected thus suffering an unfavorable prognosis. A refined understanding of age-based polygenic risk score (PRS) for prostate cancer (PCa) would be essential for personalized risk stratification. METHODS: We included 167,517 male participants [4882 cases including 205 EOPC and 4677 late-onset PCa (LOPC)] from UK Biobank...
April 17, 2024: Journal of Translational Medicine
#33
JOURNAL ARTICLE
Chihiro Mimura, Rei Takamiya, Shodai Fujimoto, Takafumi Fukui, Atsuhiko Yatani, Jun Yamada, Mizuki Takayasu, Naoya Takata, Hiroki Sato, Kiyoko Fukuda, Koichi Furukawa, Daisuke Hazama, Naoko Katsurada, Masatsugu Yamamoto, Shingo Matsumoto, Koichi Goto, Motoko Tachihara
BACKGROUND: Next-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay. METHODS: We retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine...
April 17, 2024: BMC Cancer
#34
JOURNAL ARTICLE
Janet Vittone, David Gill, Alex Goldsmith, Eric A Klein, Jordan J Karlitz
US Preventive Services Task Force (USPSTF) guidelines recommend single-cancer screening for select cancers (e.g., breast, cervical, colorectal, lung). Advances in genome sequencing and machine learning have facilitated the development of blood-based multi-cancer early detection (MCED) tests intended to complement single-cancer screening. MCED tests can interrogate circulating cell-free DNA to detect a shared cancer signal across multiple tumor types. We report real-world experience with an MCED test that detected cancer signals in three individuals subsequently diagnosed with cancers of the ovary, kidney, and head/neck that lack USPSTF-recommended screening...
April 17, 2024: NPJ Precision Oncology
#35
JOURNAL ARTICLE
Nicola J Wyatt, Hannah Watson, Carl A Anderson, Nicholas A Kennedy, Tim Raine, Tariq Ahmad, Dean Allerton, Michelle Bardgett, Emma Clark, Dawn Clewes, Cristina Cotobal Martin, Mary Doona, Jennifer A Doyle, Katherine Frith, Helen C Hancock, Ailsa L Hart, Victoria Hildreth, Peter M Irving, Sameena Iqbal, Ciara Kennedy, Andrew King, Sarah Lawrence, Charlie W Lees, Robert Lees, Laura Letchford, Trevor Liddle, James O Lindsay, Rebecca H Maier, John C Mansfield, Julian R Marchesi, Naomi McGregor, Rebecca E McIntyre, Jasmin Ostermayer, Tolulope Osunnuyi, Nick Powell, Natalie J Prescott, Jack Satsangi, Shriya Sharma, Tara Shrestha, Ally Speight, Michelle Strickland, James Ms Wason, Kevin Whelan, Ruth Wood, Gregory R Young, Xinyue Zhang, Miles Parkes, Christopher J Stewart, Luke Jostins-Dean, Christopher A Lamb
INTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients...
April 17, 2024: BMJ Open
#36
REVIEW
Claudia Christowitz, Daniel W Olivier, Johann W Schneider, Maritha J Kotze, Anna-Mart Engelbrecht
A pathology-supported genetic testing (PSGT) framework was established in South Africa to improve access to precision medicine for patients with breast carcinomas. Nevertheless, the frequent identification of variants of uncertain significance (VUSs) with the use of genome-scale next-generation sequencing has created a bottleneck in the return of results to patients. This review highlights the importance of incorporating functional genomics into the PSGT framework as a proposed initiative. Here, we explore various model systems and experimental methods available for conducting functional studies in South Africa to enhance both variant classification and clinical interpretation...
April 15, 2024: Mutation Research. Reviews in Mutation Research
#37
JOURNAL ARTICLE
Vaishnavee Thote, Susha Dinesh, Sameer Sharma
MDC1 (Mediator of DNA damage Checkpoint protein 1) functions to facilitate the localization of numerous DNA damage response (DDR) components to DNA double-strand break sites. MDC1 is an integral component in preserving genomic stability and appropriate DDR regulation. There haven't been systematic investigations of MDC1 mutations that induce cancer and genomic instability. Variations in nsSNPs have the potential to modify the protein chemistry and their function. Describing functional SNPs in disease-associated genes presents a significant conundrum for investigators, it is possible to assess potential functional SNPs before conducting larger population examinations...
December 2024: Systems Biology in Reproductive Medicine
#38
JOURNAL ARTICLE
Priscila Radu, Gayathri Kumar, Amanda Cole, Aikaterini Fameli, Mark Guthrie, Lieven Annemans, Jan Geissler, Antoine Italiano, Brian O'Rourke, Entela Xoxi, Lotte Steuten
BACKGROUND: Genomic and molecular alterations are increasingly important in cancer diagnosis, and scientific advances are opening new treatment avenues. Precision oncology (PO) uses a patient's genomic profile to determine optimal treatment, promising fewer side effects and higher success rates. Within PO, tumor-agnostic (TA) therapies target genomic alterations irrespective of tumor location. However, traditional value frameworks and approval pathways pose challenges which may limit patient access to PO therapies...
April 17, 2024: Oncologist
#39
JOURNAL ARTICLE
Imogen R Walpole, Farzana Y Zaman, Peinan Zhao, Vikki M Marshall, Frank P Lin, David M Thomas, Mark Shackleton, Albert A Antolin, Malaka Ameratunga
PURPOSE: Systematic repurposing of approved medicines for another indication may accelerate drug development in oncology. We present a strategy combining biomarker testing with drug repurposing to identify new treatments for patients with advanced cancer. METHODS: Tumours were sequenced with the Illumina TruSight Oncology 500 (TSO-500) platform or the FoundationOne CDx panel. Mutations were screened by two medical oncologists and pathogenic mutations were categorised referencing literature...
April 2024: Clinical and Translational Medicine
#40
REVIEW
Clésio Gomes Mariano, Vanessa Cristina de Oliveira, Carlos Eduardo Ambrósio
The CRISPR/Cas9 system is a simpler and more versatile method compared to other engineered nucleases such as Zinc Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs), and since its discovery, the efficiency of CRISPR-based genome editing has increased to the point that multiple and different types of edits can be made simultaneously. These advances in gene editing have revolutionized biotechnology by enabling precise genome editing with greater simplicity and efficacy than ever before...
2024: Animal Reproduction
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