tbuckley/cabot-search huggingface dataset:
Abstract A022: Novel technology affords real-time PCR the sensitivity required for minimal residual disease monitoring
Authors: Mary Stischer, Nick Allen, Stephanie Barbari, Sarah Kane
Journal: Clinical Cancer Research (2024)

Abstract Monitoring minimal residual disease (MRD) provides invaluable information for disease progression and therapeutic decision making. However, there are many challenges to reliably detect key mutations or biomarkers, such as the accessibility, turnaround time, and sensitivity of current methods. High sensitivity is crucial due to the limited DNA available in certain sample types such as liquid biopsy. Next generation sequencing (NGS) is capable of highly sensitive detection but is dependent on high sample input and read depth, which is not always feasible due to the variable nature of circulating tumor DNA (ctDNA) in blood or plasma. In addition, NGS is not an economical nor rapid option for recurrent longitudinal monitoring. Digital PCR (dPCR) offers the sensitivity required for MRD monitoring but has yet to be widely adopted for this application. While real-time and qPCR are commonly used in oncology research, RT-PCR does not have the sensitivity required for early detection of key MRD mutations. Here, we present novel patent-pending technology that enhances the sensitivity of RT-PCR, allowing this common platform to be used to reliably detect low abundant mutations. We performed comparisons between GT Molecular’s patent-pending technology paired with RT-PCR and commercially available research use only dPCR and NGS assays to assess the sensitivity this new technology provides for RT-PCR. Cell-free DNA (cfDNA) was extracted from real patient or contrived plasma samples using the QIAamp Circulating Nucleic Acid Kit and analyzed using RT-PCR and dPCR assays targeting KRAS or ESR1 mutations. Samples with KRAS or ESR1 mutations were tested at variant allele frequencies (VAFs) varying between 1%-0.01% to evaluate the ability of GT Molecular’s new technology to detect low abundant mutations using RT-PCR. KRAS and ESR1 mutations were reliably detected with RT-PCR at VAFs as low as 0.01%, demonstrating sensitivity comparable to dPCR. Samples demonstrating positivity for KRAS or ESR1 mutations via dPCR were also positive via RT-PCR. With this patent-pending technology, RT-PCR is now capable of achieving the sensitivity required for MRD monitoring, providing critical information from liquid biopsy samples at a fraction of the cost. Citation Format: Mary Stischer, Nick Allen, Stephanie Barbari, Sarah Kane. Novel technology affords real-time PCR the sensitivity required for minimal residual disease monitoring [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A022.
Antibiotic consumption patterns in older adults: a comparative study of people 65 years and older in and outside nursing homes, Belgium, 2016 to 2022
Authors: Moira Kelly, Marc de Falleur, El Maati Allaoui, Laura Bonacini, Boudewijn Catry, Katrien Latour, Lucy Catteau
Journal: Eurosurveillance (2024)

BackgroundInappropriate antimicrobial consumption (AMC) drives the emergence of antimicrobial resistance. Institutionalised, older populations are associated with antimicrobial treatments of longer duration and broader spectrum than recommended, higher rates of multidrug-resistant infections and poorer outcomes for resistant infections. Yet systematic, national monitoring of AMC in nursing home (NH) residents is lacking.AimTo perform a retrospective analysis of antibiotic consumption in Belgian NHs, we compared analogous populations inside and outside NHs. We aimed to provide a blueprint for establishing surveillance of NH AMC, based on national reimbursement data.MethodsThe National Institute for Health and Disability Insurance supplied reimbursement AMC data for outpatients from 2016 to 2022. Data were classified by the Anatomical Therapeutic Chemical system, expressed as defined daily doses (DDD) and aggregated by prescription month, patient age, sex and residency inside/outside a NH. The number of ensured beneficiaries, aggregated by the same demographic variables, was collected from the Intermutualistic Agency. We compared the DDDs per 1,000 beneficiaries per day, along with secondary metrics for national and international targets for analogous populations inside and outside NHs.ResultsTotal antibiotic consumption decreased in both populations but remained twofold higher in NH residents. Proxy prescription quality metrics were consistently less favourable within NHs and diverged further during the COVID-19 pandemic. Distinct consumption patterns and greater seasonal fluctuations were observed in NH residents.ConclusionGiven the different infection risks and higher antibiotic consumption of NH residents, AMC surveillance and antimicrobial stewardship efforts targeting this fragile population are needed.
An in-depth analysis of antimicrobial prescription quality in 10 non-university hospitals, in southwest Germany, 2021
Authors: Gesche Först, Roland Giesen, Geertje Fink, Matthias Sehlbrede, Nicole Wimmesberger, Rebekka Allen, Kerstin Meyer, Sabine Müller, Hanna Niese, Sina Polk, Barbara Reistle, Carolin Schuhmacher, Andreas von Ameln-Meyerhofer, Kim Winter, Dave Wirth, Winfried V Kern, Erik Farin-Glattacker, Siegbert Rieg
Journal: Eurosurveillance (2024)

BackgroundNon-university hospitals are the major provider of inpatient care in Germany, serving 89% of acute care hospital beds. Although surveillance data on antimicrobial use in hospitals are widely available, data on prescription quality are rare.AimWe aimed to provide an in-depth analysis of antimicrobial prescribing patterns and quality in southwest German non-university hospitals.MethodsDuring 2021, we performed three point prevalence surveys (PPS) in 10 non-university hospitals, representing ca 10% of hospital beds in the federal state of Baden-Württemberg (11 million inhabitants). Demographic and clinical information were collected. We assessed the overall performance of 14 validated process quality indicators (QI) covering infection diagnostics, antimicrobial therapy and documentation.ResultsOf 8,560 patients analysed, 2,861 (33%) received at least one antimicrobial. Most (2,789, 80%) antimicrobial prescriptions were for therapeutic indications. Most frequently prescribed agents were beta-lactam/beta-lactamase inhibitors (1,120, 40%) in therapeutic and cefuroxime (269, 37%) in prophylactic indications. According to the World Health Organization's Access, Watch, Reserve classification, the Access-to-Watch ratio was 0.73. Overall adherence to QIs was low and varied substantially (27-93%), with documentation, possible streamlining and switching to oral therapy exhibiting the lowest fulfilment rates (< 50%).ConclusionThe results indicate a need to improve antimicrobial prescribing quality in non-university hospitals. The high prevalence of antimicrobial use in our setting underlines the demand for sustainable antimicrobial stewardship programmes in this sector. Our QI-based PPS approach can be used to identify key targets for future antimicrobial stewardship interventions. The results indicate a need for further legislation on antimicrobial stewardship.
Multinational investigation of a Salmonella Umbilo outbreak reveals rocket salad and baby spinach as the likely infection vehicles, Europe, 2024
Authors: Bettina M Rosner, Sandra Simon, Stine Nielsen, Sandra Köberl-Jelovcan, Pernille Gymoese, Dirk Werber, Anika Meinen, Michael Pietsch, Antje Flieger, Jennie Fischer, Marina C Lamparter, Felix Küffel, Fiona Költringer, Christian Kornschober, Luise Müller, Gerhard Falkenhorst, Sabine Maritschnik
Journal: Eurosurveillance (2024)

A food-borne outbreak with about 200
Epidemiology of invasive meningococcal disease, Japan, 2013 to 2023
Authors: Miho Kobayashi, Hajime Kamiya, Munehisa Fukusumi, Hideyuki Takahashi, Yukihiro Akeda, Motoi Suzuki, Tomimasa Sunagawa
Journal: Eurosurveillance (2024)

BackgroundThe National Surveillance for Invasive Meningococcal Disease (IMD) initiative started in Japan in April 2013. Multiple international mass gathering events have since been held in Japan, and the COVID-19 pandemic has occurred.AimWe summarised 10 years of national surveillance data for IMD in Japan to describe epidemiological characteristics of IMD and evaluate the influence of mass gatherings and the COVID-19 pandemic on IMD.MethodsUpon diagnosis of IMD, patient information and specimens were collected and reported to local health centres. We analysed the epidemiology of IMD cases reported between 1 April 2013 and 31 March 2023.ResultsAmong 274 cases reported (median age: 55 years; 55% male), no outbreaks related to mass gathering events were identified. The annual reported incidence of IMD was 0.001-0.039 cases per 100,000 individuals between 2014 and 2022, with a notable decrease after 2020. The overall case fatality rate was 12% (33/274). The most frequent serogroups were Y and B (46 and 17%). Multilocus sequence typing revealed a predominance of clonal complex (cc) 23, followed by cc2057, while cc11 was detected in eight cases.ConclusionThe reported incidence of IMD in Japan is low compared with high-endemic countries and decreased further during the COVID-19 pandemic. This unique epidemiology of IMD in Japan lacks a clear explanation. However, distribution of meningococcal strains, such as predominance of serogroup Y, could be a contributing factor. Maintaining high-quality surveillance, including of serogroups and sequence types, is crucial to manage and prevent future IMD cases in Japan effectively.
Treatment uptake among notified cases of hepatitis C virus infection in Norway, 1990 to 2022: a registry-based study to monitor progress towards elimination
Authors: Robert Whittaker, Håvard Midgard, Olav Dalgard, Hilde Kløvstad
Journal: Eurosurveillance (2024)

BackgroundHepatitis C virus (HCV) infection is targeted for elimination as a public health threat by 2030. The World Health Organization goal for treatment uptake is ≥ 80% among cases diagnosed with an active HCV infection (RNA- or core antigen-positive), maintained for 2 years.AimTo calculate treatment uptake, time from diagnosis to treatment start and complete treatment dispensation among notified cases of HCV infection in Norway.MethodWe linked national data on notified cases diagnosed from 1990-2022 to dispensed prescriptions for HCV treatment from January 2004-February 2023 and data on residence status at the end of 2022. We described treatment uptake by demographic and epidemiological characteristics. We calculated the median number of months from diagnosis to treatment start by year. For direct-acting antiviral treatment periods, complete dispensation was based on the treatment and number of defined daily doses.ResultsAmong 12,178 notified cases that had an active infection at diagnosis and were still resident, 10,091 (83%) had received treatment. Uptake among resident cases was > 80% in 2021 and 2022. The median number of months from diagnosis to treatment decreased over time to 3 (interquartile range: 1-5) among cases diagnosed in 2021 and 2022. From 2015-22, 89-93% of direct-acting antiviral treatment periods annually had complete treatment dispensed.ConclusionNorway has achieved the elimination goal for treatment uptake among notified cases diagnosed with an active HCV infection. This highlights the benefit of a strategy that includes unrestricted, simplified and integrated treatment options.
Human Milk Microbiome Is Associated With Allergic Diseases in Early Childhood
Authors: Jie Ma, Debra J. Palmer, Donna Geddes, Ching Tat Lai, Susan L. Prescott, Nina D'Vaz, Philip Vlaskovsky, Lisa F. Stinson
Journal: Allergy (2024)

The data that supports the findings of this study are available in the Supporting Information of this article. Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Genomic reconstruction of an azole-resistant Candida parapsilosis outbreak and the creation of a multi-locus sequence typing scheme: a retrospective observational and genomic epidemiology study
Authors: Phillip J T Brassington, Frank-Rainer Klefisch, Barbara Graf, Roland Pfüller, Oliver Kurzai, Grit Walther, Amelia E Barber
Journal: The Lancet Microbe (2024)

Fluconazole-resistant Candida parapsilosis has emerged as a significant health-care-associated pathogen with a propensity to spread patient to patient and cause nosocomial outbreaks, similar to Candida auris. This study investigates a long-lasting outbreak of fluconazole-resistant C parapsilosis that was initially detected in December, 2018, and January, 2019, and officially declared in November, 2019; lasted multiple years; and involved several health-care centres in Berlin, Germany.
Bioinspired hierarchical porous tough adhesive to promote sealing of high-pressure bleeding
Authors: Yinghao Li, Dongling Xiao, Weixi Yan, Meilin Jiang, Ju Tan, Zhongliang Qin, Jingting Zhou, Yue Sun, Mingcan Yang, Guanyuan Yang, Yawei Gu, Yong Liu, Chuhong Zhu
Journal: Bioactive Materials (2024)
Measuring hospital antibiotic consumption in EU/EEA countries: comparison of different metrics, 2017 to 2021
Authors: Igor Rubinić, Vivian H Leung, Liselotte Diaz Högberg, Dominique L Monnet, Vera Vlahović-Palčevski
Journal: Eurosurveillance (2024)

BackgroundAntibiotic resistance poses a considerable public health threat, with data-driven stewardship a main prevention measure. While quantifying antibiotic consumption is a key component of antibiotic stewardship programmes, the choice of denominator for calculating this metric can impact comparative analyses and trend evaluations substantially, influencing targeted stewardship interventions.AimWe aim to evaluate how using hospital sector-specific antibiotic consumption rate denominators at country level impacts country rankings and trends, addressing the limitations of the commonly used 'defined daily doses (DDD) per 1,000 inhabitants per day' metric.MethodsHospital antibiotic consumption data from ESAC-Net and denominator data from Eurostat ('inhabitants,' 'bed-days' and 'discharges') for 2017-2021 were used to calculate hospital antibiotic consumption rates for 24 reporting European Union/ European Economic Area (EU/EEA) countries. Countries were ranked by their consumption rates and trends were analysed to assess the effects of using different denominators.ResultsCountry rankings and 5-year trend analyses varied depending on the denominator used. Antibiotic consumption rates were more similar when using hospital activity-based denominators 'bed-days' and 'discharges' compared with the population-based 'inhabitants' denominator. Differences in country rankings and trends were also seen among rates derived using 'bed-days' and 'discharges'.ConclusionThe study underscores the importance of using hospital activity-based denominators such as 'bed-days' and 'discharges' when evaluating hospital antibiotic consumption. ESAC-Net's historical reliance on only 'DDD per 1,000 inhabitants per day' is challenged, advocating for the use of multiple hospital activity-based denominators. Corresponding hospital activity denominators for ESAC-Net data will more effectively inform national hospital antibiotic stewardship interventions.
Early Heart Failure Outcomes and Medical Therapy Use in a Virtually Managed Hospital-at-Home Setting
Authors: Trejeeve Martyn, Harsh Patolia, Nicholas Platek, Ryan Tang, Nancy M Albert, Danielle Crow, Amanda R Vest, Samir Kapadia, Raed Dweik, Lars G Svensson, Jerry D Estep, Conor P Delaney, Richard D Rothman, Jessica Hohman
Journal: JACC Heart Failure (2024)
Human Tendon‐on‐a‐Chip for Modeling the Myofibroblast Microenvironment in Peritendinous Fibrosis
Authors: Raquel E. Ajalik, Isabelle Linares, Rahul G. Alenchery, Victor Z. Zhang, Terry W. Wright, Benjamin L. Miller, James L. McGrath, Hani A. Awad
Journal: Advanced Healthcare Materials (2024)

Understanding the myofibroblast microenvironment is critical to developing therapies for fibrotic diseases. Here the development of a novel human tendon-on-a-chip (hToC) is reported to model this crosstalk in peritendinous adhesions, which currently lacks biological therapies. The hToC facilitates cellular and paracrine interactions between a vascular component, which contains endothelial cells and monocytes, and a tissue hydrogel component that houses tendon cells and macrophages. It is found that the hToC replicates some aspects of in vivo inflammatory and fibrotic phenotypes in preclinical and clinical samples, including activated mTOR signaling, vascular inflammation, tissue contraction induced by myofibroblast activation, inflammatory cytokines secretion, and transendothelial migration of monocytes to the tissue hydrogel. Transcriptional analysis demonstrates significant overlap in enriched pathways in the hToC with human tenolysis samples, including the activation of mTOR signaling. Rapamycin suppresses the vascular inflammation and fibrotic phenotype in the hToC, which provides proof-of-concept of its utility as an in vitro tool for investigating multicellular crosstalk in fibrosis and testing therapeutics to mitigate it.
Post-hoc analysis of the CARES trial suggests delayed progression of chronic kidney disease in patients with gout during urate-lowering therapy.
Authors: Byeongzu Ghang, Jino Park, Ji Sung Lee, Joon Seo Lim, Hyunwoo Kim, David F L Liew, Jinseok Kim, Duk-Hee Kang, Bin Yoo
Journal: Kidney International (2024)
Identification of Candidates for MASLD Treatment with Indeterminate Vibration-Controlled Transient Elastography
Authors: David Marti-Aguado, José Miguel Carot-Sierra, Aida Villalba-Ortiz, Harris Siddiqi, Rose Marie Vallejo-Vigo, Carmen Lara-Romero, Marta Martín-Fernández, Matías Fernández-Patón, Clara Alfaro-Cervello, Ana Crespo, Elena Coello, Víctor Merino-Murgui, Egbert Madamba, Salvador Benlloch, Judith Pérez-Rojas, Víctor Puglia, Antonio Ferrández, Victoria Aguilera, Cristina Monton, Desamparados Escudero-García, Paloma Lluch, Rocío Aller, Rohit Loomba, Manuel Romero-Gomez, Luis Marti-Bonmati
Journal: Clinical Gastroenterology and Hepatology (2024)

A noteworthy proportion of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have an indeterminate vibration-controlled transient elastography (VCTE). Among these patients, we aimed to identify candidates for MASLD treatment by diagnosing significant fibrosis.
VI-VS: calibrated identification of feature dependencies in single-cell multiomics
Authors: Pierre Boyeau, Stephen Bates, Can Ergen, Michael I. Jordan, Nir Yosef
Journal: Genome biology (2024)

Abstract Unveiling functional relationships between various molecular cell phenotypes from data using machine learning models is a key promise of multiomics. Existing methods either use flexible but hard-to-interpret models or simpler, misspecified models. (Variational Inference for Variable Selection) balances flexibility and interpretability to identify relevant feature relationships in multiomic data. It uses deep generative models to identify conditionally dependent features, with false discovery rate control. is available as an open-source Python package, providing a robust solution to identify features more likely representing genuine causal relationships.
Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma
Authors: Jason C. Klein, Lei Wang, Douglas Strand, Chewlan Lastufka, Gregory A. Hosler, Gary C. Hon
Journal: Molecular Cancer (2024)

Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS.
Impact of TP53 mutation on genetic and cellular hierarchy profile in complex karyotype AML/MDS with increased blasts
Authors: Jinha Hwang, Ha Nui Kim, Jung Ah Kwon, Soo-Young Yoon, Min Ji Jeon, Eun Sang Yu, Dae Sik Kim, Chul Won Choi, Jung Yoon
Journal: Blood Cancer Journal (2024)
Prebiotics in food and dietary supplements: a roadmap to EU health claims
Authors: Kieran Tuohy, Elaine E. Vaughan, Lucien F. Harthoorn, Ellen E. Blaak, Philip W. J. Burnet, Alessandro Busetti, Anirikh Chakrabarti, Nathalie Delzenne, Paul de Vos, Louise Dye, Damien Guillemet, Lesley A. Houghton, Alwine F. M. Kardinaal, Cath Mersh, Kathy Musa-Veloso, Annegret Nielsen, Justyna Palasinska, Seppo Salminen, Gemma Walton, Naomi Venlet, Charlotte Hubermont, Philip C. Calder
Journal: Gut Microbes (2024)

Numerous studies have established that prebiotic ingredients in foods and dietary supplements may play a role in supporting human health. Over the three decades that have passed since prebiotics were first defined as a concept, research has revealed a complex universe of prebiotic-induced changes to the human microbiota. There are strong indications of a direct link between these prebiotic-induced changes and specific health benefits. However, at the present time, the EU has not permitted use of the term 'prebiotic' in connection with an approved health claim. This paper is the outcome of a workshop organized on the 25th October 2023 by the European branch of the International Life Science Institute (ILSI). It provides an overview of the regulatory requirements for authorized health claims in the EU, key areas of prebiotic research, and findings to date in relation to prebiotics and digestive, immune, metabolic and cognitive health. Research gaps and documentation challenges are then explored and a roadmap proposed for achieving authorization of 'prebiotic' in the wording of future EU health claims.
Editor’s Note: Low-Dose Paclitaxel Reduces S100A4 Nuclear Import to Inhibit Invasion and Hematogenous Metastasis of Cholangiocarcinoma
Authors: Massimiliano Cadamuro, Gaia Spagnuolo, Luisa Sambado, Stefano Indraccolo, Giorgia Nardo, Antonio Rosato, Simone Brivio, Chiara Caslini, Tommaso Stecca, Marco Massani, Nicolò Bassi, Eugenio Novelli, Carlo Spirli, Luca Fabris, Mario Strazzabosco
Journal: Cancer Research (2024)