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JOURNAL ARTICLE
Arielle Elkrief, Igor Odintsov, Vladimir Markov, Rebecca Caeser, Pawel Sobczuk, Sam E Tischfield, Umesh Bhanot, Chad M Vanderbilt, Emily H Cheng, Alexander Drilon, Gregory J Riely, William W Lockwood, Elisa de Stanchina, Vijaya G Tirunagaru, Robert C Doebele, Álvaro Quintanal-Villalonga, Charles M Rudin, Romel Somwar, Marc Ladanyi
INTRODUCTION: Although targeted therapies have revolutionized the therapeutic landscape of lung adenocarcinomas (LUADs), disease progression on single-agent targeted therapy against known oncogenic drivers is common, and therapeutic options after disease progression are limited. In patients with MDM2 amplification (MDM2amp) and a concurrent oncogenic driver alteration, we hypothesized that targeting of the tumor-suppressor pathway (by means of restoration of p53 using MDM2 inhibition) and simultaneous targeting of co-occurring MAPK oncogenic pathway might represent a more durably effective therapeutic strategy...
September 2023: Journal of Thoracic Oncology
#22
JOURNAL ARTICLE
Sam E Williams, Catherine R Back, Eleanor Best, Judith Mantell, James E M Stach, Tom A Williams, Paul R Race, Paul Curnow
The deep sea is known to host novel bacteria with the potential to produce a diverse array of undiscovered natural products. Thus, understanding these bacteria is of broad interest in ecology and could also underpin applied drug discovery, specifically in the area of antimicrobials. Here, we isolate a new strain of Streptomyces from the tissue of the deep-sea sponge Polymastia corticata collected at a depth of 1869 m from the Gramberg Seamount in the Atlantic Ocean. This strain, which was given the initial designation A15ISP2-DRY2T , has a genome size of 9...
May 2023: Microbial Genomics
#23
JOURNAL ARTICLE
James L Alexander, Joram M Posma, Alasdair Scott, Liam Poynter, Sam E Mason, M Luisa Doria, Lili Herendi, Lauren Roberts, Julie A K McDonald, Simon Cameron, David J Hughes, Vaclav Liska, Simona Susova, Pavel Soucek, Verena Horneffer-van der Sluis, Maria Gomez-Romero, Matthew R Lewis, Lesley Hoyles, Andrew Woolston, David Cunningham, Ara Darzi, Marco Gerlinger, Robert Goldin, Zoltan Takats, Julian R Marchesi, Julian Teare, James Kinross
BACKGROUND AND AIMS: The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes. METHODS: A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing...
May 8, 2023: Microbiome
#24
JOURNAL ARTICLE
Andrew D Hoffmann, Sam E Weinberg, Suchitra Swaminathan, Shuvam Chaudhuri, Hannah Faisal Mubarak, Matthew J Schipma, Chengsheng Mao, Xinkun Wang, Lamiaa El-Shennawy, Nurmaa K Dashzeveg, Juncheng Wei, Paul J Mehl, Laura J Shihadah, Ching Man Wai, Carolina Ostiguin, Yuzhi Jia, Paolo D'Amico, Neale R Wang, Yuan Luo, Alexis R Demonbreun, Michael G Ison, Huiping Liu, Deyu Fang
Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is critical to advance our understanding SARS-CoV-2 and COVID-19-associated long-term complications, remains largely unknown. Herein, we characterized single-cell profiles of circulating immune cells in the peripheral blood of 100 patients, including convalescent COVID-19 and sero-negative controls. Flow cytometry analyses revealed reduced frequencies of both short-lived monocytes and long-lived regulatory T (Treg) cells within the patients who have recovered from severe COVID-19...
May 5, 2023: Clinical Immunology: the Official Journal of the Clinical Immunology Society
#25
Catherine R Back, Henry L Stennett, Sam E Williams, Luoyi Wang, Jorge Ojeda Gomez, Omar M Abdulle, Thomas Duffy, Christopher Neal, Judith Mantell, Mark A Jepson, Katharine R Hendry, David Powell, James E M Stach, Angela E Essex-Lopresti, Christine L Willis, Paul Curnow, Paul R Race
After publication of this article [...].
March 28, 2023: Marine Drugs
#26
Adam L Smoulder, Patrick J Marino, Emily R Oby, Sam E Snyder, Hiroo Miyata, Nick P Pavlovsky, William E Bishop, Byron M Yu, Steven M Chase, Aaron P Batista
UNLABELLED: Incentives tend to drive improvements in performance. But when incentives get too high, we can "choke under pressure" and underperform when it matters most. What neural processes might lead to choking under pressure? We studied Rhesus monkeys performing a challenging reaching task in which they underperform when an unusually large "jackpot" reward is at stake. We observed a collapse in neural information about upcoming movements for jackpot rewards: in the motor cortex, neural planning signals became less distinguishable for different reach directions when a jackpot reward was made available...
April 16, 2023: bioRxiv
#27
Niels Banhos Danneskiold-Sams E, Deniz Kavi, Kevin M Jude, Silas Boye Nissen, Lianna W Wat, Laetitia Coassolo, Meng Zhao, Galia Asae Santana-Oikawa, Beatrice Blythe Broido, K Christopher Garcia, Katrin J Svensson
Secreted proteins are extracellular ligands that play key roles in paracrine and endocrine signaling, classically by binding cell surface receptors. Experimental assays to identify new extracellular ligand-receptor interactions are challenging, which has hampered the rate of novel ligand discovery. Here, using AlphaFold-multimer, we developed and applied an approach for extracellular ligand-binding prediction to a structural library of 1,108 single-pass transmembrane receptors. We demonstrate high discriminatory power and a success rate of close to 90 % for known ligand-receptor pairs where no a priori structural information is required...
March 17, 2023: bioRxiv
#28
EDITORIAL
Zezhong Ye, Sam E Gary
No abstract text is available yet for this article.
March 28, 2023: Journal of Magnetic Resonance Imaging: JMRI
#29
JOURNAL ARTICLE
Minos Kritikos, Erica D Diminich, Jaymie Meliker, Michelle Mielke, David A Bennett, Caleb E Finch, Sam E Gandy, Melissa A Carr, Xiaohua Yang, Roman Kotov, Pei-Fen Kuan, Evelyn J Bromet, Sean A P Clouston, Benjamin J Luft
INTRODUCTION: World Trade Center (WTC) responders are experiencing a high risk of mild cognitive impairment (MCI) and dementia, though the etiology remains inadequately characterized. This study investigated whether WTC exposures and chronic post-traumatic stress disorder (PTSD) were correlated with plasma biomarkers characteristic of Alzheimer's disease (AD) neuropathology. METHODS: Eligible participants included WTC-exposed individuals with a baseline cognitive assessment and available plasma sample...
2023: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
#30
JOURNAL ARTICLE
Frank D Mann, Sean A P Clouston, Adolfo Cuevas, Monika A Waszczuk, Pei-Fen Kuan, Melissa A Carr, Anna R Docherty, Andrea A Shabalin, Sam E Gandy, Benjamin J Luft
BACKGROUND: There is a high incidence of cognitive impairment among World Trade Center (WTC) responders, comorbid with post-traumatic stress disorder (PTSD). Yet, it remains unknown whether genetic liability for Alzheimer's disease, PTSD, educational attainment, or for a combination of these phenotypes, is associated with cognitive impairment in this high-risk population. Similarly, whether the effects of genetic liability are comparable to PTSD and indicators of exposure severity remains unknown...
February 10, 2023: Journal of Alzheimer's Disease: JAD
#31
JOURNAL ARTICLE
Andrew D Barr, Sam E Rigby, Sam D Clarke, Dain Farrimond, Andy Tyas
The design of blast-resistant structures and protective systems requires a firm understanding of the loadings imparted to structures by blast waves. While empirical methods can reliably predict these loadings in the far field, there is currently a lack of understanding on the pressures experienced in the very near field, where physics-based numerical modelling and semi-empirical fast-running engineering model predictions can vary by an order of magnitude. In this paper, we present the design of an experimental facility capable of providing definitive spatially and temporally resolved reflected pressure data in the extreme near field (Z<0...
January 14, 2023: Sensors
#32
JOURNAL ARTICLE
JingYang Liu, David B Grayden, Janet R Keast, Sam E John
OBJECTIVE: Endovascular neuromodulation has attracted substantial interest in recent years as a minimally invasive approach to treat neurological disorders. In this study, we investigated with a computational model the feasibility of stimulating peripheral nerves with an endovascular stent-mounted electrode array. APPROACH: Anatomically realistic FEM models were constructed for the pudendal and vagal neurovascular bundles. The electromagnetic fields generated from electrical stimuli was computed using Sim4Life NEURON models to predict dynamic axonal responses...
November 28, 2022: Journal of Neural Engineering
#33
JOURNAL ARTICLE
Andrew Chow, Fathema Z Uddin, Michael Liu, Anton Dobrin, Barzin Y Nabet, Levi Mangarin, Yonit Lavin, Hira Rizvi, Sam E Tischfield, Alvaro Quintanal-Villalonga, Joseph M Chan, Nisargbhai Shah, Viola Allaj, Parvathy Manoj, Marissa Mattar, Maximiliano Meneses, Rebecca Landau, Mariana Ward, Amanda Kulick, Charlene Kwong, Matthew Wierzbicki, Jessica Yavner, Jacklynn Egger, Shweta S Chavan, Abigail Farillas, Aliya Holland, Harsha Sridhar, Metamia Ciampricotti, Daniel Hirschhorn, Xiangnan Guan, Allison L Richards, Glenn Heller, Jorge Mansilla-Soto, Michel Sadelain, Christopher A Klebanoff, Matthew D Hellmann, Triparna Sen, Elisa de Stanchina, Jedd D Wolchok, Taha Merghoub, Charles M Rudin
Improved identification of anti-tumor T cells is needed to advance cancer immunotherapies. CD39 expression is a promising surrogate of tumor-reactive CD8+ T cells. Here, we comprehensively profiled CD39 expression in human lung cancer. CD39 expression enriched for CD8+ T cells with features of exhaustion, tumor reactivity, and clonal expansion. Flow cytometry of 440 lung cancer biospecimens revealed weak association between CD39+ CD8+ T cells and tumoral features, such as programmed death-ligand 1 (PD-L1), tumor mutation burden, and driver mutations...
January 10, 2023: Immunity
#34
JOURNAL ARTICLE
Alisa M Higgins, Lindsay R Berry, Elizabeth Lorenzi, Srinivas Murthy, Zoe McQuilten, Paul R Mouncey, Farah Al-Beidh, Djillali Annane, Yaseen M Arabi, Abi Beane, Wilma van Bentum-Puijk, Zahra Bhimani, Marc J M Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Aidan Burrell, Adrian Buzgau, Meredith Buxton, Walton N Charles, Matthew Cove, Michelle A Detry, Lise J Estcourt, Elizabeth O Fagbodun, Mark Fitzgerald, Timothy D Girard, Ewan C Goligher, Herman Goossens, Rashan Haniffa, Thomas Hills, Christopher M Horvat, David T Huang, Nao Ichihara, Francois Lamontagne, John C Marshall, Daniel F McAuley, Anna McGlothlin, Shay P McGuinness, Bryan J McVerry, Matthew D Neal, Alistair D Nichol, Rachael L Parke, Jane C Parker, Karen Parry-Billings, Sam E C Peters, Luis F Reyes, Kathryn M Rowan, Hiroki Saito, Marlene S Santos, Christina T Saunders, Ary Serpa-Neto, Christopher W Seymour, Manu Shankar-Hari, Lucy M Stronach, Alexis F Turgeon, Anne M Turner, Frank L van de Veerdonk, Ryan Zarychanski, Cameron Green, Roger J Lewis, Derek C Angus, Colin J McArthur, Scott Berry, Lennie P G Derde, Anthony C Gordon, Steve A Webb, Patrick R Lawler
IMPORTANCE: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. OBJECTIVE: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries...
January 3, 2023: JAMA
#35
JOURNAL ARTICLE
Robert S Redman, Scott R Diehl, Trina Jones-Richardson, Rebeka G Silva, Chih-Ko Yeh, Kevin J Malley, Sam E Farish, Mary B Duffy, Robert M Craig, Deborah M Winn
OBJECTIVES: This analysis examined the clinical and histopathological characteristics of white and red oral mucosal lesions and patient lifestyle behaviors to understand how the lesions changed over 19-23 years, including among patients who developed oral and pharyngeal cancer. MATERIALS AND METHODS: Seventy-five individuals with red and/or white oral mucosal lesions with clinical diagnoses of smokeless tobacco lesions, leukoplakia, erythroplakia, lichen planus, ulcer, and virus-associated lesions were identified in six Veterans Affairs Medical Center Dental Clinics (VAMC) from 1996 to 2001...
December 12, 2022: Clinical and Experimental Dental Research
#36
JOURNAL ARTICLE
Barbara R Terlouw, Kai Blin, Jorge C Navarro-Muñoz, Nicole E Avalon, Marc G Chevrette, Susan Egbert, Sanghoon Lee, David Meijer, Michael J J Recchia, Zachary L Reitz, Jeffrey A van Santen, Nelly Selem-Mojica, Thomas Tørring, Liana Zaroubi, Mohammad Alanjary, Gajender Aleti, César Aguilar, Suhad A A Al-Salihi, Hannah E Augustijn, J Abraham Avelar-Rivas, Luis A Avitia-Domínguez, Francisco Barona-Gómez, Jordan Bernaldo-Agüero, Vincent A Bielinski, Friederike Biermann, Thomas J Booth, Victor J Carrion Bravo, Raquel Castelo-Branco, Fernanda O Chagas, Pablo Cruz-Morales, Chao Du, Katherine R Duncan, Athina Gavriilidou, Damien Gayrard, Karina Gutiérrez-García, Kristina Haslinger, Eric J N Helfrich, Justin J J van der Hooft, Afif P Jati, Edward Kalkreuter, Nikolaos Kalyvas, Kyo B Kang, Satria Kautsar, Wonyong Kim, Aditya M Kunjapur, Yong-Xin Li, Geng-Min Lin, Catarina Loureiro, Joris J R Louwen, Nico L L Louwen, George Lund, Jonathan Parra, Benjamin Philmus, Bita Pourmohsenin, Lotte J U Pronk, Adriana Rego, Devasahayam Arokia Balaya Rex, Serina Robinson, L Rodrigo Rosas-Becerra, Eve T Roxborough, Michelle A Schorn, Darren J Scobie, Kumar Saurabh Singh, Nika Sokolova, Xiaoyu Tang, Daniel Udwary, Aruna Vigneshwari, Kristiina Vind, Sophie P J M Vromans, Valentin Waschulin, Sam E Williams, Jaclyn M Winter, Thomas E Witte, Huali Xie, Dong Yang, Jingwei Yu, Mitja Zdouc, Zheng Zhong, Jérôme Collemare, Roger G Linington, Tilmann Weber, Marnix H Medema
With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC...
November 18, 2022: Nucleic Acids Research
#37
JOURNAL ARTICLE
Sam E Wing, Marta M Jankowska, Xiaoke Zou, Ernesto Sosa, Jiue-An Yang, Tarik Benmarhnia, Susan L Neuhausen, Rebecca Nelson, Ravi Salgia, Stacy W Gray, Loretta Erhunmwunsee
PURPOSE: It remains unclear why individuals living in disadvantaged neighborhoods have shorter non-small cell lung cancer (NSCLC) survival. It is possible that living in these deprived areas is linked with increased risk of developing aggressive NSCLC biology. Here, we explored the association of somatic KRAS mutations, which are associated with shorter survival in NSCLC patients, and 11 definitions of neighborhood disadvantage spanning socioeconomic and structural environmental elements...
November 16, 2022: Journal of Cancer Research and Clinical Oncology
#38
JOURNAL ARTICLE
Michael Offin, Jennifer L Sauter, Sam E Tischfield, Jacklynn V Egger, Shweta Chavan, Nisargbhai S Shah, Parvathy Manoj, Katia Ventura, Viola Allaj, Elisa de Stanchina, William Travis, Marc Ladanyi, Andreas Rimner, Valerie W Rusch, Prasad S Adusumilli, John T Poirier, Marjorie G Zauderer, Charles M Rudin, Triparna Sen
BACKGROUND: Diffuse pleural mesothelioma (DPM) is an aggressive malignancy that, despite recent treatment advances, has unacceptably poor outcomes. Therapeutic research in DPM is inhibited by a paucity of preclinical models that faithfully recapitulate the human disease. METHODS: We established 22 patient-derived xenografts (PDX) from 22 patients with DPM and performed multi-omic analyses to deconvolute the mutational landscapes, global expression profiles, and molecular subtypes of these PDX models and compared features to those of the matched primary patient tumors...
November 15, 2022: Genome Medicine
#39
JOURNAL ARTICLE
Xiao Zang, Sam E Bessey, Maxwell S Krieger, Benjamin D Hallowell, Jennifer A Koziol, Shayla Nolen, Czarina N Behrends, Sean M Murphy, Alexander Y Walley, Benjamin P Linas, Bruce R Schackman, Brandon D L Marshall
Importance: In 2021, the state of Rhode Island distributed 10 000 additional naloxone kits compared with the prior year through partnerships with community-based organizations. Objective: To compare various strategies to increase naloxone distribution through community-based programs in Rhode Island to identify one most effective and efficient strategy in preventing opioid overdose deaths (OODs). Design, Setting, and Participants: In this decision analytical model study conducted from January 2016 to December 2022, a spatial microsimulation model with an integrated decision tree was developed and calibrated to compare the outcomes of alternative strategies for distributing 10 000 additional naloxone kits annually among all individuals at risk for opioid overdose in Rhode Island...
November 1, 2022: JAMA Network Open
#40
JOURNAL ARTICLE
Sam E John, Sam Donegan, Theodore C Scordas, Weijie Qi, Prayshita Sharma, Kishan Liyanage, Stefan Wilson, Ian Birchall, Andrew Ooi, Thomas J Oxley, Clive N May, David B Grayden, Nicholas L Opie
Objective. The aim of this work was to assess vascular remodeling after the placement of an endovascular neural interface (ENI) in the superior sagittal sinus (SSS) of sheep. We also assessed the efficacy of neural recording using an ENI. Approach. The study used histological analysis to assess the composition of the foreign body response. Micro-CT images were analyzed to assess the profiles of the foreign body response and create a model of a blood vessel. Computational fluid dynamic modeling was performed on a reconstructed blood vessel to evaluate the blood flow within the vessel...
October 28, 2022: Journal of Neural Engineering
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