tbuckley/cabot-search huggingface dataset:
Early Changes in Tumor-Naive Cell-Free Methylomes and Fragmentomes Predict Outcomes in Pembrolizumab-Treated Solid Tumors
Authors: Eric Y. Stutheit-Zhao, Enrique Sanz-Garcia, Zhihui (Amy) Liu, Derek Wong, Kayla Marsh, Albiruni R. Abdul Razak, Anna Spreafico, Philippe L. Bedard, Aaron R. Hansen, Stephanie Lheureux, Dax Torti, Bernard Lam, Shih Yu Cindy Yang, Justin Burgener, Ping Luo, Yong Zeng, Nicholas Cheng, Philip Awadalla, Scott V. Bratman, Pamela S. Ohashi, Trevor J. Pugh, Lillian L. Siu
Journal: Cancer Discovery (2024)

Abstract Early kinetics of circulating tumor DNA (ctDNA) in plasma predict response to pembrolizumab but typically requires sequencing of matched tumor tissue or fixed gene panels. We analyzed genome-wide methylation and fragment-length profiles using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq) in 204 plasma samples from 87 patients before and during treatment with pembrolizumab from a pan-cancer phase II investigator-initiated trial (INSPIRE). We trained a pan-cancer methylation signature using independent methylation array data from The Cancer Genome Atlas to quantify cancer-specific methylation (CSM) and fragment-length score (FLS) for each sample. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. Early kinetics of CSM predict overall survival and progression-free survival, independently of tumor type, PD-L1, and tumor mutation burden. Early kinetics of FLS are associated with overall survival independently of CSM. Our tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab. Significance: Analysis of methylation and fragment length in plasma using cfMeDIP-seq provides a tumor-naive approach to measure ctDNA with results comparable with a tumor-informed bespoke ctDNA. Early kinetics within the first weeks of treatment in methylation and fragment quantity can predict outcomes with pembrolizumab in patients with various advanced solid tumors. This article is featured in Selected Articles from This Issue, p. 897
The evolution of preclinical models for myelodysplastic neoplasms
Authors: Alain Mina, Steven Pavletic, Peter D. Aplan
Journal: Leukemia (2024)

Myelodysplastic Neoplasms (MDS) are a group of clonal disorders characterized by ineffective hematopoiesis and morphologic dysplasia. Clinical manifestations of MDS vary widely and are dictated in large part by a range of genetic aberrations. The lack of robust in vitro models for MDS has limited the ability to conduct high throughput drug screens, which in turn has hampered the development of novel therapies for MDS. There are very few well-characterized MDS cell lines, and the available cell lines expand poorly in vitro. Conventional xenograft mouse models can provide an in vivo vessel to provide growth of cancer cells, but human MDS cells engraft poorly. Three-dimensional (3D) scaffold models that form human "ossicles" represent a promising new approach and can reproduce the intricate communication between hematopoietic stem and progenitor cells and their environment. Genetically engineered mice utilize specific mutations and may not represent the entire array of human MDS; however, genetically engineered mice provided in vivo proof of principle for novel agents such as luspatercept, demonstrating the clinical utility of this approach. This review offers an overview of available preclinical MDS models and potential approaches to accelerate accurate clinical translation.
Mouse eosinophil‐associated ribonuclease‐2 exacerbates the allergic response
Authors: Linh Manh Nguyen, Akira Kanda, Yuji Kamioka, Keizo Tokuhiro, Yoshiki Kobayashi, Yasutaka Yun, Dan Van Bui, Hanh Hong Chu, Nhi Kieu Thi Le, Kensuke Suzuki, Akitoshi Mitani, Akihiro Shimamura, Kenta Fukui, David Dombrowicz, Hiroshi Iwai
Journal: Allergy (2024)

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Rita Colwell: Use your voice to bring about positive change
Authors: Lucie Van Emmenis
Journal: The Journal of Experimental Medicine (2024)

Rita Colwell is a Distinguished University Professor at the University of Maryland at College Park and at Johns Hopkins University Bloomberg School of Public Health, senior advisor and chairman emeritus at Canon US Life Sciences, Inc., founder and chairman of CosmosID, Inc., and president of the Rosalind Franklin Society. She has authored or co-authored 20 books and more than 800 scientific publications, and throughout her career has focused on improving health outcomes across the world and highlighting the impacts of infectious diseases in drinking/bathing water. We recently spoke to Rita about her career and her thoughts about the future for women in science.
CXCL12+ dermal fibroblasts promote neutrophil recruitment and host defense by recognition of IL-17
Authors: Kellen J. Cavagnero, Fengwu Li, Tatsuya Dokoshi, Teruaki Nakatsuji, Alan M. O’Neill, Carlos Aguilera, Edward Liu, Michael Shia, Olive Osuoji, Tissa Hata, Richard L. Gallo
Journal: The Journal of Experimental Medicine (2024)

The skin provides an essential barrier for host defense through rapid action of multiple resident and recruited cell types, but the complex communication network governing these processes is incompletely understood. To define these cell–cell interactions more clearly, we performed an unbiased network analysis of mouse skin during invasive S. aureus infection and revealed a dominant role for CXCL12+ fibroblast subsets in neutrophil communication. These subsets predominantly reside in the reticular dermis, express adipocyte lineage markers, detect IL-17 and TNFα, and promote robust neutrophil recruitment through NFKBIZ-dependent release of CXCR2 ligands and CXCL12. Targeted deletion of Il17ra in mouse fibroblasts resulted in greatly reduced neutrophil recruitment and increased infection by S. aureus. Analogous human CXCL12+ fibroblast subsets abundantly express neutrophil chemotactic factors in psoriatic skin that are subsequently decreased upon therapeutic targeting of IL-17. These findings show that CXCL12+ dermal immune acting fibroblast subsets play a critical role in cutaneous neutrophil recruitment and host defense.
Systematic review of the association between short‐chain fatty acids and allergic diseases
Authors: Mari Sasaki, Noor H. A. Suaini, Jamie Afghani, Kristina N. Heye, Liam O'Mahony, Carina Venter, Roger Lauener, Remo Frei, Caroline Roduit
Journal: Allergy (2024)

Abstract We performed a systematic review to investigate the current evidence on the association between allergic diseases and short chain fatty acids (SCFAs), which are microbially produced and suggested as one mechanism on how gut microbiome affects the risk of allergic diseases. Medline, Embase and Web of Science were searched from data inception until September 2022. We identified 37 papers, of which 17 investigated prenatal or early childhood SCFAs and the development of allergic diseases in childhood, and 20 assessed SCFAs in patients with pre‐existing allergic diseases. Study design, study populations, outcome definition, analysis method and reporting of the results varied between papers. Overall, there was some evidence showing that the three main SCFAs (acetate, propionate and butyrate) in the first few years of life had a protective effect against allergic diseases, especially for atopic dermatitis, wheeze or asthma and IgE‐mediated food allergy in childhood. The association between each SCFA and allergic disease appeared to be different by disease and the age of assessment. Further research that can determine the potentially timing specific effect of each SCFA will be useful to investigate how SCFAs can be used in treatment or in prevention against allergic diseases.
Why do we distinguish between virus-positive and virus-negative Merkel cell carcinoma?
Authors: Furkan Bahar, James A DeCaprio
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Why do we distinguish between virus-positive and virus-negative Merkel cell carcinoma? Get access Furkan Bahar, Furkan Bahar Writing - original draft, Writing - review & editing Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Search for other works by this author on: Oxford Academic Google Scholar James A DeCaprio James A DeCaprio Writing - review & editing Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Correspondence: James A. DeCaprio. Email: james_decaprio@dfci.harvard.edu https://orcid.org/0000-0002-0896-167X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae086, https://doi.org/10.1093/bjd/ljae086 Published: 23 February 2024 Article history Received: 17 February 2024 Accepted: 20 February 2024 Published: 23 February 2024 Corrected and typeset: 16 March 2024
The triple A model (age, absolute neutrophil count, absolute lymphocyte count‐<scp>AAA</scp>) predicts survival and thrombosis in polycythemia vera
Authors: Ivan Krecak, Danijela Lekovic, Isidora Arsenovic, Hrvoje Holik, Ivan Zekanovic, Martina Moric Peric, Marko Lucijanic
Journal: American Journal of Hematology (2024)
CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis
Authors: Simon Rauber, Hashem Mohammadian, Christian Schmidkonz, Armin Atzinger, Alina Soare, Christoph Treutlein, Samuel Kemble, Christopher B. Mahony, Manuel Geisthoff, Mario R. Angeli, Maria G. Raimondo, Cong Xu, Kai-Ting Yang, Le Lu, Hannah Labinsky, Mina S. A. Saad, Charles A. Gwellem, Jiyang Chang, Kaiyue Huang, Eleni Kampylafka, Johannes Knitza, Rostyslav Bilyy, Jörg H. W. Distler, Megan M. Hanlon, Ursula Fearon, Douglas J. Veale, Frank W. Roemer, Tobias Bäuerle, Hans M. Maric, Simone Maschauer, Arif B. Ekici, Christopher D. Buckley, Adam P. Croft, Torsten Kuwert, Olaf Prante, Juan D. Cañete, Georg Schett, Andreas Ramming
Journal: Nature Immunology (2024)
Dopamine projections to the basolateral amygdala drive the encoding of identity-specific reward memories
Authors: Ana C. Sias, Yousif Jafar, Caitlin M. Goodpaster, Kathia Ramírez-Armenta, Tyler M. Wrenn, Nicholas K. Griffin, Keshav Patel, Alexander C. Lamparelli, Melissa J. Sharpe, Kate M. Wassum
Journal: Nature Neuroscience (2024)
Wastewater-based reproduction numbers and projections of COVID-19 cases in three areas in Japan, November 2021 to December 2022
Authors: Shogo Miyazawa, Ting Sam Wong, Genta Ito, Ryo Iwamoto, Kozo Watanabe, Michiel van Boven, Jacco Wallinga, Fuminari Miura
Journal: Eurosurveillance (2024)

Background Wastewater surveillance has expanded globally as a means to monitor spread of infectious diseases. An inherent challenge is substantial noise and bias in wastewater data because of the sampling and quantification process, limiting the applicability of wastewater surveillance as a monitoring tool. Aim To present an analytical framework for capturing the growth trend of circulating infections from wastewater data and conducting scenario analyses to guide policy decisions. Methods We developed a mathematical model for translating the observed SARS-CoV-2 viral load in wastewater into effective reproduction numbers. We used an extended Kalman filter to infer underlying transmissions by smoothing out observational noise. We also illustrated the impact of different countermeasures such as expanded vaccinations and non-pharmaceutical interventions on the projected number of cases using three study areas in Japan during 2021–22 as an example. Results Observed notified cases were matched with the range of cases estimated by our approach with wastewater data only, across different study areas and virus quantification methods, especially when the disease prevalence was high. Estimated reproduction numbers derived from wastewater data were consistent with notification-based reproduction numbers. Our projections showed that a 10–20% increase in vaccination coverage or a 10% reduction in contact rate may suffice to initiate a declining trend in study areas. Conclusion Our study demonstrates how wastewater data can be used to track reproduction numbers and perform scenario modelling to inform policy decisions. The proposed framework complements conventional clinical surveillance, especially when reliable and timely epidemiological data are not available.
Application of the screening method for estimating COVID-19 vaccine effectiveness using routine surveillance data: Germany’s experience during the COVID-19 pandemic, July 2021 to March 2023
Authors: Nita Perumal, Viktoria Schönfeld, Ole Wichmann
Journal: Eurosurveillance (2024)

The screening method represents a simple, quick, and practical tool for estimating vaccine effectiveness (VE) using routine disease surveillance and vaccine coverage data, even if these data cannot be linked. In Germany, where notification data, laboratory testing data, and vaccine coverage data cannot be linked due to strict data protection requirements, the screening method was used to assess COVID-19 VE continuously between July 2021 and March 2023. During this period, when Delta and Omicron variants circulated, VE estimates were produced in real-time for different age groups and clinical outcomes. Here we describe the country’s overall positive experience using the screening method, including its strengths and limitations, and provide practical guidance regarding a few issues, such as case definition stringency, testing behaviour, and data stratification, that require careful consideration during data analysis and the interpretation of the results.
Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024
Authors: Marine Maurel, Jennifer Howard, Esther Kissling, Francisco Pozo, Gloria Pérez-Gimeno, Silke Buda, Noémie Sève, Adele McKenna, Adam Meijer, Ana Paula Rodrigues, Iván Martínez-Baz, Ivan Mlinarić, Neus Latorre-Margalef, Gergő Túri, Mihaela Lazăr, Clara Mazagatos, Aitziber Echeverria, Stephen Abela, Marc Bourgeois, Ausenda Machado, Ralf Dürrwald, Goranka Petrović, Beatrix Oroszi, Ligita Jancoriene, Alexandru Marin, Petr Husa, Roisin Duffy, Frederika Dijkstra, Virtudes Gallardo García, Luise Goerlitz, Vincent Enouf, Charlene Bennett, Mariëtte Hooiveld, Raquel Guiomar, Camino Trobajo-Sanmartín, Vesna Višekruna Vučina, Tove Samuelsson Hagey, Ana Sofía Lameiras Azevedo, Jesús Castilla, Gerd Xuereb, Bénédicte Delaere, Verónica Gómez, Kristin Tolksdorf, Sabrina Bacci, Nathalie Nicolay, Marlena Kaczmarek, Angela MC Rose
Journal: Eurosurveillance (2024)

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: −3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: −32 to 43), respectively.
Clinical isolates of ST131 blaOXA-244-positive Escherichia coli, Italy, December 2022 to July 2023
Authors: Aurora Piazza, Marta Corbella, Vittoria Mattioni Marchetti, Cristina Merla, Irene Mileto, Angela Kuka, Greta Petazzoni, Stefano Gaiarsa, Roberta Migliavacca, Fausto Baldanti, Patrizia Cambieri
Journal: Eurosurveillance (2024)

The dissemination of carbapenemase-producing Escherichia coli, although still at low level, should be continuously monitored. OXA-244 is emerging in Europe, mainly in E. coli . In Italy, this carbapenemase was reported from an environmental river sample in 2019. We report clinical isolates of OXA-244-producing ST131 E. coli in four patients admitted to an acute care hospital in Pavia, Italy. The association of this difficult-to-detect determinant with a globally circulating high-risk clone, ST131 E. coli, is of clinical relevance.
Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19
Authors: Hannah Chung, Michael A Campitelli, Sarah A Buchan, Aaron Campigotto, Natasha S Crowcroft, Jonathan B Gubbay, James KH Jung, Timothy Karnauchow, Kevin Katz, Allison J McGeer, J Dayre McNally, David C Richardson, Susan E Richardson, Laura C Rosella, Margaret L Russell, Kevin L Schwartz, Andrew Simor, Marek Smieja, Maria E Sundaram, Bryna F Warshawsky, George Zahariadis, Jeffrey C Kwong
Journal: Eurosurveillance (2024)

Background Waning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases. Aim We examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time. Methods Using linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days. Results There were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91–1.22) at 42–69 days after vaccination and peaked at 1.27 (95% CI: 1.04–1.55) at 126–153 days when compared with the reference interval (14–41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04–1.15). Individuals aged 18–64 years showed the greatest decline in protection against influenza A(H1N1) (aOR per 28 days = 1.26; 95% CI: 0.97–1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aOR per 28 days = 1.20; 95% CI: 1.08–1.33). We did not observe evidence of waning vaccine protection for individuals aged &lt; 18 years. Conclusions Influenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.
Authors’ correction for Euro Surveill. 2024;29(3)
Journal: Eurosurveillance (2024)

© This work is licensed under a Creative Commons Attribution 4.0 International License. Closure This is a corrected article applying to the following content: Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023
SHARE-Topic: Bayesian interpretable modeling of single-cell multi-omic data
Authors: Nour El Kazwini, Guido Sanguinetti
Journal: Genome biology (2024)

Abstract Multi-omic single-cell technologies, which simultaneously measure the transcriptional and epigenomic state of the same cell, enable understanding epigenetic mechanisms of gene regulation. However, noisy and sparse data pose fundamental statistical challenges to extract biological knowledge from complex datasets. SHARE-Topic, a Bayesian generative model of multi-omic single cell data using topic models, aims to address these challenges. SHARE-Topic identifies common patterns of co-variation between different omic layers, providing interpretable explanations for the data complexity. Tested on data from different technological platforms, SHARE-Topic provides low dimensional representations recapitulating known biology and defines associations between genes and distal regulators in individual cells.
Monitoring Dual-Cancer Treatment in a Patient With Prostate and Hepatocellular Carcinoma Using Prostate-Specific Membrane Antigen-Directed PET/CT
Authors: Florian P. Reiter, Alexander Weich, Takahiro Higuchi, Sebastian E. Serfling, Ralph Kickuth, Rudolf A. Werner
Journal: Clinical Nuclear Medicine (2024)

Abstract We report on a 70-year-old man affected with prostate carcinoma (PC) scheduled for prostate-specific membrane antigen (PSMA) PET/CT using 18 F-PSMA1007. Because of uptake in the liver and corresponding findings on magnetic resonance, diagnosis of hepatocellular carcinoma (HCC, G1) was established. The patient was then scheduled for antihormonal treatment for PC and locoregional therapy due to HCC. On follow-up PSMA-targeted PET/CT, we observed durable response to PC-associated therapy, whereas hepatic lesions showed progressive disease. As such, we herein report on a dual-cancer targeting molecular imaging strategy to determine disease extent in a patient affected with both PC and HCC, along with potential of monitoring both systemic and locoregional treatment.
Prostate-Specific Membrane Antigen PET/CT Detection of Prostate Cancer Metastasis to Thyroid and Cricoid Cartilages
Authors: Joshua Eichhorn, Nadia Nelson, Surbhi Raichandani, Aaron Sesler, Fathima Fijula Palot Manzil
Journal: Clinical Nuclear Medicine (2024)

Prostate-specific membrane antigen (PSMA) PET/CT has revolutionized the imaging of prostate cancer. Historically, prostate cancer metastasis to thyroid and cricoid cartilages was thought to be exceedingly rare, with only a few reported cases in the literature. Prostate cancer metastasis to the laryngeal cartilages was detected in 4 of 221 patients who underwent imaging with 18 F-PSMA (Pylarify) or 68 Ga-PSMA (Illuccix) PET/CT for initial staging of high-risk prostate cancer or restaging evaluation in the setting of biochemical recurrence from April 2022 through October 2023. The increased sensitivity and specificity of PSMA PET/CT allow for the detection of previously occult metastatic disease.
A Hangover Under 177Lu-PSMA-617 Therapy
Authors: Nathan Poterszman, Laura Somme, Caroline Bund, Emilie Hutt, François Somme
Journal: Clinical Nuclear Medicine (2024)

Abstract Leptomeningeal carcinomatosis in prostate cancer is extremely rare. Because of the low overall penetration of drugs into the brain and the prolonged survival of castration-resistant prostate cancer (CRPC) patients, a special attention should be paid to the appearance of neurological symptoms in long-term CRPC survivors. A patient suffering from a CRPC with bone metastases underwent 4 cycles of 177 Lu-PSMA (prostate-specific membrane antigen)-617. Starting from the third cycle, he reported an increasing feeling of a permanent hangover. A 68 Ga-PSMA-11 brain PET/MRI was carried out after the fourth cycle. It revealed intraparenchymatous brain metastases with intense uptake and evidences of leptomeningeal carcinomatosis.
Extensive Cutaneous-Mucosal and Muscular Involvement of Gamma/Delta Cutaneous T-Cell Lymphoma on 18F-FDG PET/CT
Authors: Hugo Peslier, Julien Reichart, Charles Boursot, Kevin Cohen-Tannugi, Franck Lacoeuille
Journal: Clinical Nuclear Medicine (2024)

Abstract Gamma/delta T-cell lymphoma is a rare and aggressive subtype of primary cutaneous lymphoma. Clinical manifestations typically include the development of subcutaneous nodules and ulcerated plaques. Some forms present as panniculitis with hemophagocytic syndrome. Prognosis is bleak, with a 10% 5-year survival rate. In this report, we present the case of a 20-year-old man from French Polynesia, referred for 18 F-FDG PET/CT because of the progressive worsening of febrile cutaneous-mucosal infiltration on the face persisting for 1 month. PET examination guided a biopsy from the right deltoid muscle, and expert histological analysis confirmed a CD8 + not otherwise specified T-cell lymphoma, granzyme+ and TCR gamma/delta.