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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
#2
JOURNAL ARTICLE
Karuna Mittal, Garrett W Cooper, Benjamin P Lee, Yongdong Su, Katie T Skinner, Jenny Shim, Hunter C Jonus, Won Jun Kim, Mihir Doshi, Diego Almanza, Bryan D Kynnap, Amanda L Christie, Xiaoping Yang, Glenn S Cowley, Brittaney A Leeper, Christopher L Morton, Bhakti Dwivedi, Taylor Lawrence, Manali Rupji, Paula Keskula, Stephanie Meyer, Catherine M Clinton, Manoj Bhasin, Brian D Crompton, Yuen-Yi Tseng, Jesse S Boehm, Keith L Ligon, David E Root, Andrew J Murphy, David M Weinstock, Prafulla C Gokhale, Jennifer M Spangle, Miguel N Rivera, Elizabeth A Mullen, Kimberly Stegmaier, Kelly C Goldsmith, William C Hahn, Andrew L Hong
Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies remains challenging in part due to the lack of faithful preclinical in vitro models. Here we establish twelve patient-derived WT cell lines and demonstrate that these models faithfully recapitulate WT biology using genomic and transcriptomic techniques...
April 8, 2024: Communications Biology
#3
JOURNAL ARTICLE
David M Fairlamb, Kinga Szepeshazi, David Goldsmith, Peter Danos, Hadar Lev-Tov, Nathan Young, Jason Hanft, Charles Zelen
We report the first clinical evaluation of a new enzymatic wound debridement product containing tarumase in venous leg ulcer patients. As a first-in-human study, this was a prospective, open-label, multi-centre, dose escalation study across five dose cohorts and involving a total of 43 patients treated three times weekly for up to 4 weeks (12 applications). The primary and secondary endpoints of the study were to assess the systemic safety, local tolerability, and early proof of concept both for wound debridement and healing...
March 2024: International Wound Journal
#4
JOURNAL ARTICLE
Sanat Vibhas Modak, Daniel Pert, Jessica L Tami, Wanggang Shen, Ibrahim Abdullahi, Xun Huan, Anne J McNeil, Bryan R Goldsmith, David G Kwabi
Aqueous redox flow batteries (RFBs) are attractive candidates for low-cost, grid-scale storage of energy from renewable sources. Quinoxaline derivatives represent a promising but underexplored class of charge-storing materials on account of poor chemical stability in prior studies (with capacity fade rates >20%/day). Here, we establish that 2,3-dimethylquinoxaline-6-carboxylic acid (DMeQUIC) is vulnerable to tautomerization in its reduced form under alkaline conditions. We obtain kinetic rate constants for tautomerization by applying Bayesian inference to ultraviolet-visible spectroscopic data from operating flow cells and show that these rate constants quantitatively account for capacity fade measured in cycled cells...
February 15, 2024: Journal of the American Chemical Society
#5
JOURNAL ARTICLE
David J Collier, Mike Taylor, Thomas Godec, Julian Shiel, Rebecca James, Yasmin Chowdury, Patrizia Ebano, Vivienne Monk, Mital Patel, Jane Pheby, Ruby Pheby, Amanda Foubister, Clovel David, Manish Saxena, Leanne Richardson, James Siddle, Gregor Timlin, Paul Goldsmith, Nicholas Deeming, Neil R Poulter, Rhian Gabe, Richard J McManus, Mark J Caulfield
BACKGROUND: The objective of the PERSONAL-CovidBP (Personalised Electronic Record Supported Optimisation When Alone for Patients With Hypertension: Pilot Study for Remote Medical Management of Hypertension During the COVID-19 Pandemic) trial was to assess the efficacy and safety of smartphone-enabled remote precision dosing of amlodipine to control blood pressure (BP) in participants with primary hypertension during the COVID-19 pandemic. METHODS AND RESULTS: This was an open-label, remote, dose titration trial using daily home self-monitoring of BP, drug dose, and side effects with linked smartphone app and telemonitoring...
February 7, 2024: Journal of the American Heart Association
#6
Steve Gillard, Katie Anderson, Geraldine Clarke, Chloe Crowe, Lucy Goldsmith, Heather Jarman, Sonia Johnson, Jo Lomani, David McDaid, Paris Pariza, A-La Park, Jared Smith, Kati Turner, Heather Yoeli
BACKGROUND: People experiencing mental health crises in the community often present to emergency departments and are admitted to a psychiatric hospital. Because of the demands on emergency department and inpatient care, psychiatric decision units have emerged to provide a more suitable environment for assessment and signposting to appropriate care. OBJECTIVES: The study aimed to ascertain the structure and activities of psychiatric decision units in England and to provide an evidence base for their effectiveness, costs and benefits, and optimal configuration...
December 2023: Health Soc Care Deliv Res
#7
JOURNAL ARTICLE
Jerome Henry Taylor, Julieta Bermudez-Gomez, Marina Zhou, Oscar Gomez, Casey Ganz-Leary, Cesar Palacios, Zeeshan M Huque, Ran Barzilay, David R Goldsmith, Raquel E Gur
OBJECTIVE: While genetic and cohort studies suggest immune and reduction/oxidation (redox) alterations occur in psychosis, less is known about potential alterations in children and adolescents. METHODS: We conducted a systematic review to identify immune and redox biomarker studies in children and adolescents (mean age ≤ 18 years old) across the psychosis spectrum: from psychotic like experiences, which are common in children, to threshold psychotic disorders like schizophrenia...
December 21, 2023: Brain, Behavior, and Immunity
#8
JOURNAL ARTICLE
Dimosthenis Tsapekos, Rebecca Strawbridge, Matteo Cella, Kimberley Goldsmith, Michail Kalfas, Rosie H Taylor, Samuel Swidzinski, Steven Marwaha, Libby Grey, Elizabeth Newton, Julie Shackleton, Paul J Harrison, Michael Browning, Catherine Harmer, Hannah Hartland, David Cousins, Stephen Barton, Til Wykes, Allan H Young
BACKGROUND: A substantial proportion of people with bipolar disorder (BD) experience persistent cognitive difficulties associated with impairments in psychosocial functioning and a poorer disorder course. Emerging evidence suggests that cognitive remediation (CR), a psychological intervention with established efficacy in people with schizophrenia, can also benefit people with BD. Following a proof-of-concept trial showing that CR is feasible and potentially beneficial for people with BD, we are conducting an adequately powered trial in euthymic people with BD to 1) determine whether an individual, therapist-supported, computerised CR can reduce cognitive difficulties and improve functional outcomes; and 2) explore how CR exerts its effects...
November 15, 2023: BMC Psychiatry
#9
JOURNAL ARTICLE
Agnes Grudniewicz, Ellen Randall, M Ruth Lavergne, Emily Gard Marshall, Lori Jones, David Rudoler, Kathleen Horrey, Maria Mathews, Madeleine McKay, Goldis Mitra, Ian Scott, David Snadden, Sabrina T Wong, Laurie J Goldsmith
BACKGROUND: Comprehensiveness of primary care has been declining, and much of the blame has been placed on early-career family physicians and their practice choices. To better understand early-career family physicians' practice choices in Canada, we sought to identify the factors that most influence their decisions about how to practice. METHODS: We conducted a qualitative study using framework analysis. Family physicians in their first 10 years of practice were recruited from three Canadian provinces: British Columbia, Ontario, and Nova Scotia...
October 26, 2023: Human Resources for Health
#10
JOURNAL ARTICLE
Hagar Fox, Shifra Ben-Dor, Adi Doron-Faigenboim, Moshe Goldsmith, Tamir Klein, Rakefet David-Schwartz
In trees, nonstructural carbohydrates (NSCs) serve as long-term carbon storage and long-distance carbon transport from source to sink. NSC management in response to drought stress is key to our understanding of drought acclimation. However, the molecular mechanisms underlying these processes remain unclear. By combining a transcriptomic approach with NSC quantification in the leaves, stems, and roots of Populus alba under drought stress, we analyzed genes from 29 gene families related to NSC signaling, translocation, and metabolism...
2023: Physiologia Plantarum
#11
JOURNAL ARTICLE
Victoria H Ng, Zachary Spencer, Leif R Neitzel, Anmada Nayak, Matthew A Loberg, Chen Shen, Sara N Kassel, Heather K Kroh, Zhenyi An, Christin C Anthony, Jamal M Bryant, Amanda Lawson, Lily Goldsmith, Hassina Benchabane, Amanda G Hansen, Jingjing Li, Starina D'Souza, Andres M Lebensohn, Rajat Rohatgi, William A Weiss, Vivian L Weiss, Charles Williams, Charles C Hong, David J Robbins, Yashi Ahmed, Ethan Lee
The relative abundance of Wnt receptors plays a crucial role in controlling Wnt signaling in tissue homeostasis and human disease. While the ubiquitin ligases that ubiquitylate Wnt receptors are well-characterized, the deubiquitylase that reverses these reactions remains unclear. Herein, we identify USP46, UAF1, and WDR20 (USP46 complex) as positive regulators of Wnt signaling in cultured human cells. We find that the USP46 complex is similarly required for Wnt signaling in Xenopus and zebrafish embryos. We demonstrate that Wnt signaling promotes the association between the USP46 complex and cell surface Wnt coreceptor, LRP6...
October 5, 2023: Nature Communications
#12
JOURNAL ARTICLE
Benjamin Lebwohl, Christopher Ma, Stephen M Lagana, Rish K Pai, K Adam Baker, Alexa Zayadi, Malcolm Hogan, Gerd Bouma, Christophe Cellier, Jeffrey D Goldsmith, Knut E A Lundin, Maria I Pinto-Sanchez, Marie E Robert, Alberto Rubio-Tapia, David S Sanders, David F Schaeffer, Carol E Semrad, Jocelyn A Silvester, Elena F Verdú, Ritu Verma, Tsung-Teh Wu, Brian G Feagan, Eileen Crowley, Vipul Jairath, Joseph A Murray
BACKGROUND & AIMS: There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. METHODS: A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes...
September 11, 2023: Gastroenterology
#13
JOURNAL ARTICLE
Katarzyna Kostyrka-Allchorne, Petrina Chu, Claire Ballard, Nancy Lean, Blandine French, Ellen Hedstrom, Sarah Byford, Samuele Cortese, David Daley, Johnny Downs, Cristine Glazebrook, Kimberley Goldsmith, Charlotte L Hall, Hanna Kovshoff, Jana Kreppner, Kapil Sayal, James Shearer, Emily Simonoff, Margaret Thompson, Edmund J S Sonuga-Barke
BACKGROUND: The Structured E-Parenting Support (STEPS) app provides support for parents of children with elevated hyperactivity, impulsivity, inattention, and conduct problems who are awaiting clinical assessment. STEPS will be evaluated in a randomized controlled trial (RCT) within the Online Parent Training for the Initial Management of ADHD Referrals (OPTIMA) research program in the United Kingdom. Phase 1 of the OPTIMA tested the feasibility of participants' recruitment and the app's usability...
September 11, 2023: JMIR Pediatrics and Parenting
#14
JOURNAL ARTICLE
Anjali Chandra, Brian J Miller, David R Goldsmith
Given evidence pointing toward a role for immune dysregulation in the pathogenesis of schizophrenia, anti-inflammatory agents are promising adjunctive treatments that have potential to support a causal relationship for inflammation and psychopathology and lead to novel treatments for individuals. Indeed, previous meta-analyses have demonstrated small-to-medium effect sizes (ES) in favor of various anti-inflammatory agents, though there is significant heterogeneity and challenges in the interpretation of this literature...
August 20, 2023: Brain, Behavior, and Immunity
#15
REVIEW
David S White, Mackinsey A Smith, Baron Chanda, Randall H Goldsmith
Fluorescence-based single-molecule approaches have helped revolutionize our understanding of chemical and biological mechanisms. Unfortunately, these methods are only suitable at low concentrations of fluorescent molecules so that single fluorescent species of interest can be successfully resolved beyond background signal. The application of these techniques has therefore been limited to high-affinity interactions despite most biological and chemical processes occurring at much higher reactant concentrations...
August 16, 2023: ACS Meas Sci Au
#16
JOURNAL ARTICLE
M Ruth Lavergne, David Rudoler, Sandra Peterson, David Stock, Carole Taylor, Andrew S Wilton, Sabrina T Wong, Ian Scott, Kimberlyn M McGrail, Rita K McCracken, Emily Gard Marshall, Adrian MacKenzie, Alan Katz, Margaret Jamieson, Lindsay Hedden, Agnes Grudniewicz, Laurie J Goldsmith, Richard H Glazier, Fred Burge, Doug Blackie
OBJECTIVE: To describe changes in the comprehensiveness of services delivered by family physicians across service settings and service areas in 4 Canadian provinces, to identify which settings and areas have changed the most, and to compare the magnitude of changes by physician characteristics. DESIGN: Descriptive analysis of province-wide, population-based billing data linked to population and physician registries. SETTING: British Columbia, Manitoba, Ontario, and Nova Scotia...
August 2023: Canadian Family Physician Médecin de Famille Canadien
#17
JOURNAL ARTICLE
David I Suster, John M Gross, Laura Fayad, Cornelia Wenokor, Jeffrey D Goldsmith, Ashley Ward, Caroline Early, Santiago Lazano-Calderon, Michael J Klein
Sclerosing epithelioid fibrosarcoma (SEF) occurring as a primary bone tumor is exceptionally uncommon. Even more rare are cases of SEF that show morphologic overlap with low-grade fibromyxoid sarcoma (LGFMS). Such hybrid lesions arising within the bone have only rarely been reported in the literature. Due to their variegated histomorphology and non-specific radiologic features, these tumors may pose diagnostic difficulties. Herein we describe three molecularly confirmed primary bone cases of sclerosing epithelioid fibrosarcoma that demonstrated prominent areas showing the features of LGFMS and with areas resembling so-called hyalinizing spindle cell tumor with giant rosettes (HSCTGR)...
July 31, 2023: Skeletal Radiology
#18
RANDOMIZED CONTROLLED TRIAL
Douglas J Robertson, Jason A Dominitz, Alexander Beed, Kathy D Boardman, Barbara J Del Curto, Peter D Guarino, Thomas F Imperiale, Andrew LaCasse, Meaghan F Larson, Samir Gupta, David Lieberman, Beata Planeta, Aasma Shaukat, Shanaz Sultan, Stacy B Menees, Sameer D Saini, Philip Schoenfeld, Stephan Goebel, Erik C von Rosenvinge, Gyorgy Baffy, Ildiko Halasz, Marcos C Pedrosa, Lyn Sue Kahng, Riaz Cassim, Katarina B Greer, Margaret F Kinnard, Divya B Bhatt, Kerry B Dunbar, William V Harford, John A Mengshol, Jed E Olson, Swati G Patel, Fadi Antaki, Deborah A Fisher, Brian A Sullivan, Christopher Lenza, Devang N Prajapati, Helen Wong, Rebecca Beyth, John G Lieb, Joseph Manlolo, Fernando V Ona, Rhonda A Cole, Natalia Khalaf, Charles J Kahi, Divyanshoo Rai Kohli, Tarun Rai, Prateek Sharma, Jiannis Anastasiou, Curt Hagedorn, Ronald S Fernando, Christian S Jackson, M Mazen Jamal, Robert H Lee, Farrukh Merchant, Folasade P May, Joseph R Pisegna, Endashaw Omer, Dipendra Parajuli, Adnan Said, Toan D Nguyen, Claudio Ruben Tombazzi, Paul A Feldman, Leslie Jacob, Rachel N Koppelman, Kyle P Lehenbauer, Deepak S Desai, Mohammad F Madhoun, William M Tierney, Minh Q Ho, Heather J Hockman, Christopher Lopez, Emily Carter Paulson, Martin Tobi, Hugo L Pinillos, Michele Young, Nancy C Ho, Ranjan Mascarenhas, Kirrichai Promrat, Pritesh R Mutha, William M Pandak, Tilak Shah, Mitchell Schubert, Frank S Pancotto, Andrew J Gawron, Amelia E Underwood, Samuel B Ho, Priscilla Magno-Pagatzaurtundua, Doris H Toro, Charles H Beymer, Andrew M Kaz, Jill Elwing, Jeffrey A Gill, Susan F Goldsmith, Michael D Yao, Petr Protiva, Heiko Pohl, Tassos Kyriakides
IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors...
July 3, 2023: JAMA Network Open
#19
JOURNAL ARTICLE
Adriana Osickova, Sarka Knoblochova, Ladislav Bumba, Petr Man, Zuzana Kalaninova, Anna Lepesheva, David Jurnecka, Monika Cizkova, Lada Biedermannova, Jory A Goldsmith, Jennifer A Maynard, Jason S McLellan, Radim Osicka, Peter Sebo, Jiri Masin
The acylated Repeats in ToXins (RTX) leukotoxins, the adenylate cyclase toxin (CyaA) or α-hemolysin (HlyA), bind β2 integrins of leukocytes but also penetrate cells lacking these receptors. We show that the indole of conserved tryptophans in the acylated segments, e.g. W876 of CyaA and W579 of HlyA, is crucial for β2 -integrin-independent membrane penetration. Substitutions of W876 by aliphatic or aromatic residues did not affect acylation, folding or the activities of CyaA W876L/F/Y variants on cells expressing high amounts of the β2 integrin CR3...
June 28, 2023: Journal of Biological Chemistry
#20
JOURNAL ARTICLE
Sanat Vibhas Modak, Wanggang Shen, Siddhant Singh, Dylan Herrera, Fairooz Oudeif, Bryan R Goldsmith, Xun Huan, David G Kwabi
Organic redox-active molecules are attractive as redox-flow battery (RFB) reactants because of their low anticipated costs and widely tunable properties. Unfortunately, many lab-scale flow cells experience rapid material degradation (from chemical and electrochemical decay mechanisms) and capacity fade during cycling (>0.1%/day) hindering their commercial deployment. In this work, we combine ultraviolet-visible spectrophotometry and statistical inference techniques to elucidate the Michael attack decay mechanism for 4,5-dihydroxy-1,3-benzenedisulfonic acid (BQDS), a once-promising positive electrolyte reactant for aqueous organic redox-flow batteries...
June 16, 2023: Nature Communications
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