tbuckley/cabot-search huggingface dataset:
A paradigm shift in how we treat pediatric low-grade glioma—Targeting the molecular drivers
Authors: David S Ziegler, Rebecca Lehmann, David D Eisenstat
Journal: Neuro-Oncology (2024)

Journal Article Corrected proof A paradigm shift in how we treat pediatric low-grade glioma—Targeting the molecular drivers Get access David S Ziegler, David S Ziegler Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, AustraliaSchool of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, New South Wales, AustraliaKids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia Corresponding Authors: David S. Ziegler, BSc (Med), MBBS, FRACP, MD, Kids Cancer Centre, Sydney Children's Hospital, High Street, Randwick, NSW 2031, Australia (d.ziegler@unsw.edu.au) https://orcid.org/0000-0001-7451-7916 Search for other works by this author on: Oxford Academic PubMed Google Scholar Rebecca Lehmann, Rebecca Lehmann Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, AustraliaSchool of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, New South Wales, Australia https://orcid.org/0000-0001-6145-5971 Search for other works by this author on: Oxford Academic PubMed Google Scholar David D Eisenstat David D Eisenstat Children's Cancer Centre, Royal Children's Hospital, Parkville, Victoria, AustraliaMurdoch Children's Research Institute, Parkville, Victoria, AustraliaDepartment of Paediatrics, University of Melbourne, Parkville, Victoria, Australia David D. Eisenstat, MD, MA, FRCPC, FRACP, Children's Cancer Centre, The Royal Children's Hospital Melbourne, 50 Flemington Road, Parkville, VIC 3052, Australia (david.eisenstat@rch.org.au). https://orcid.org/0000-0002-5976-0798 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae008, https://doi.org/10.1093/neuonc/noae008 Published: 19 January 2024 Article history Published: 19 January 2024 Corrected and typeset: 17 February 2024
Fluorescein-stained confocal laser endomicroscopy versus conventional frozen section for intraoperative histopathological assessment of intracranial tumors
Authors: Arthur Wagner, Maria Charlotte Brielmaier, Charlotte Kampf, Lea Baumgart, Amir Kaywan Aftahy, Hanno S Meyer, Victoria Kehl, Julius Höhne, Karl-Michael Schebesch, Nils O Schmidt, Saida Zoubaa, Markus J Riemenschneider, Miriam Ratliff, Frederik Enders, Andreas von Deimling, Friederike Liesche-Starnecker, Claire Delbridge, Juergen Schlegel, Bernhard Meyer, Jens Gempt
Journal: Neuro-Oncology (2024)

Abstract Background The aim of this clinical trial was to compare Fluorescein-stained intraoperative confocal laser endomicroscopy (CLE) of intracranial lesions and evaluation by a neuropathologist with routine intraoperative frozen section (FS) assessment by neuropathology. Methods In this phase II noninferiority, prospective, multicenter, nonrandomized, off-label clinical trial (EudraCT: 2019-004512-58), patients above the age of 18 years with any intracranial lesion scheduled for elective resection were included. The diagnostic accuracies of both CLE and FS referenced with the final histopathological diagnosis were statistically compared in a noninferiority analysis, representing the primary endpoint. Secondary endpoints included the safety of the technique and time expedited for CLE and FS. Results A total of 210 patients were included by 3 participating sites between November 2020 and June 2022. Most common entities were high-grade gliomas (37.9%), metastases (24.1%), and meningiomas (22.7%). A total of 6 serious adverse events in 4 (2%) patients were recorded. For the primary endpoint, the diagnostic accuracy for CLE was inferior with 0.87 versus 0.91 for FS, resulting in a difference of 0.04 (95% confidence interval −0.10; 0.02; P = .367). The median time expedited until intraoperative diagnosis was 3 minutes for CLE and 27 minutes for FS, with a mean difference of 27.5 minutes (standard deviation 14.5; P &amp;lt; .001). Conclusions CLE allowed for a safe and time-effective intraoperative histological diagnosis with a diagnostic accuracy of 87% across all intracranial entities included. The technique achieved histological assessments in real time with a 10-fold reduction of processing time compared to FS, which may invariably impact surgical strategy on the fly.
Fighting the scanner effect in brain MRI segmentation with a progressive level-of-detail network trained on multi-site data
Authors: Michele Svanera, Mattia Savardi, Alberto Signoroni, Sergio Benini, Lars Muckli
Journal: Medical Image Analysis (2024)

Many clinical and research studies of the human brain require accurate structural MRI segmentation. While traditional atlas-based methods can be applied to volumes from any acquisition site, recent deep learning algorithms ensure high accuracy only when tested on data from the same sites exploited in training (i.e., internal data). Performance degradation experienced on external data (i.e., unseen volumes from unseen sites) is due to the inter-site variability in intensity distributions, and to unique artefacts caused by different MR scanner models and acquisition parameters. To mitigate this site-dependency, often referred to as the scanner effect, we propose LOD-Brain, a 3D convolutional neural network with progressive levels-of-detail (LOD), able to segment brain data from any site. Coarser network levels are responsible for learning a robust anatomical prior helpful in identifying brain structures and their locations, while finer levels refine the model to handle site-specific intensity distributions and anatomical variations. We ensure robustness across sites by training the model on an unprecedentedly rich dataset aggregating data from open repositories: almost 27,000 T1w volumes from around 160 acquisition sites, at 1.5 - 3T, from a population spanning from 8 to 90 years old. Extensive tests demonstrate that LOD-Brain produces state-of-the-art results, with no significant difference in performance between internal and external sites, and robust to challenging anatomical variations. Its portability paves the way for large-scale applications across different healthcare institutions, patient populations, and imaging technology manufacturers. Code, model, and demo are available on the project website.
Mechanisms of blood-retinal barrier disruption related to intraocular inflammation and malignancy
Authors: Oren Tomkins-Netzer, Rachael Niederer, John Greenwood, Ido Didi Fabian, Yonatan Serlin, Alon Friedman, Sue Lightman
Journal: Progress in Retinal and Eye Research (2024)

Blood-retinal barrier (BRB) disruption is a common accompaniment of intermediate, posterior and panuveitis causing leakage into the retina and macular oedema resulting in vision loss. It is much less common in anterior uveitis or in patients with intraocular lymphoma who may have marked signs of intraocular inflammation. New drugs used for chemotherapy (cytarabine, immune checkpoint inhibitors, BRAF inhibitors, EGFR inhibitors, bispecific anti-EGFR inhibitors, MET receptor inhibitors and Bruton tyrosine kinase inhibitors) can also cause different types of uveitis and BRB disruption. As malignant disease itself can cause uveitis, particularly from breast, lung and gastrointestinal tract cancers, it can be clinically difficult to sort out the cause of BRB disruption. Immunosuppression due to malignant disease and/or chemotherapy can lead to infection which can also cause BRB disruption and intraocular infection. In this paper we address the pathophysiology of BRB disruption related to intraocular inflammation and malignancy, methods for estimating the extent and effect of the disruption and examine why some types of intraocular inflammation and malignancy cause BRB disruption and others do not. Understanding this may help sort and manage these patients, as well as devise future therapeutic approaches.
Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms
Authors: Leire Bejarano, Annamaria Kauzlaric, Eleni Lamprou, Joao Lourenco, Nadine Fournier, Michelle Ballabio, Roberto Colotti, Roeltje Maas, Sabine Galland, Matteo Massara, Klara Soukup, Johanna Lilja, Jean-Philippe Brouland, Andreas F. Hottinger, Roy T. Daniel, Monika E. Hegi, Johanna A. Joyce
Journal: Cancer Cell (2024)

Brain metastasis (BrM) is a common malignancy, predominantly originating from lung, melanoma, and breast cancers. The vasculature is a key component of the BrM tumor microenvironment with critical roles in regulating metastatic seeding and progression. However, the heterogeneity of the major BrM vascular components, namely endothelial and mural cells, is still poorly understood. We perform single-cell and bulk RNA-sequencing of sorted vascular cell types and detect multiple subtypes enriched specifically in BrM compared to non-tumor brain, including previously unrecognized immune regulatory subtypes. We integrate the human data with mouse models, creating a platform to interrogate vascular targets for the treatment of BrM. We find that the CD276 immune checkpoint molecule is significantly upregulated in the BrM vasculature, and anti-CD276 blocking antibodies prolonged survival in preclinical trials. This study provides important insights into the complex interactions between the vasculature, immune cells, and cancer cells, with translational relevance for designing therapeutic interventions.
Proof-of-concept for multiple AON delivery by a single U7snRNA vector to restore splicing defects in ABCA4
Authors: Nuria Suárez-Herrera, Iris B. Riswick, Irene Vázquez-Domínguez, Lonneke Duijkers, Dyah W. Karjosukarso, Davide Piccolo, Miriam Bauwens, Elfride De Baere, Michael E. Cheetham, Alejandro Garanto, Rob W.J. Collin
Journal: Molecular Therapy (2024)
Biomimetic-gasdermin-protein-expressing nanoplatform mediates tumor-specific pyroptosis for cancer immunotherapy
Authors: Xiaoxi Wang, Yan Wang, Wenyan Zhang, Xueqin Zhu, Zimai Liu, Meiyi Liu, Sijia Liu, Bingyu Li, Yalan Chen, Ziyan Wang, Pingping Zhu, Wenshan Zhao, Yongchao Wang, Zhenzhen Chen
Journal: Journal of Controlled Release (2024)
Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior
Authors: Mai-Anh T. Vu, Eleanor H. Brown, Michelle J. Wen, Christian A. Noggle, Zicheng Zhang, Kevin J. Monk, Safa Bouabid, Lydia Mroz, Benjamin M. Graham, Yizhou Zhuo, Yulong Li, Timothy M. Otchy, Lin Tian, Ian G. Davison, David A. Boas, Mark W. Howe
Journal: Neuron (2024)

Neural population dynamics relevant to behavior vary over multiple spatial and temporal scales across three-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice, enabling the investigation of cell-type- and neurotransmitter-specific signals over arbitrary 3D volumes at a spatial resolution and coverage previously inaccessible. We applied this method to resolve rapid dopamine release dynamics across the striatum, revealing distinct, modality-specific spatiotemporal patterns in response to salient sensory stimuli extending over millimeters of tissue. Targeted optogenetics enabled flexible control of neural signaling on multiple spatial scales, better matching endogenous signaling patterns, and the spatial localization of behavioral function across large circuits.
Preclinical evaluation of a novel CAR-T therapy utilizing a scFv antibody highly specific to MAGE-A4p230-239/HLA-A∗02:01 complex
Authors: Linan Wang, Masahiro Matsumoto, Yasushi Akahori, Naohiro Seo, Kazuko Shirakura, Takuma Kato, Yoichi Katsumoto, Yoshihiro Miyahara, Hiroshi Shiku
Journal: Molecular Therapy (2024)

Despite the revolutionary success of chimeric antigen receptor (CAR)-T therapy for hematological malignancies, successful CAR-T therapies for solid tumors remain limited. One major obstacle is the scarcity of tumor-specific cell-surface molecules. One potential solution to overcome this barrier is to utilize antibodies that recognize peptide/major histocompatibility complex (MHCs) in a T cell receptor (TCR)-like fashion, allowing CAR-T cells to recognize intracellular tumor antigens. This study reports a highly specific single-chain variable fragment (scFv) antibody against the MAGE-A4
A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma
Authors: Andres F Espinoza, Roma H Patel, Kalyani R Patel, Andrew A Badachhape, Richard Whitlock, Rohit K Srivastava, Saiabhiroop R Govindu, Ashley Duong, Abhishek Kona, Pavan Kureti, Bryan Armbruster, Dina Kats, Ramakrishnan R Srinivasan, Lacey E Dobrolecki, Xinjian Yu, Mohammad J Najaf Panah, Barry Zorman, Stephen F Sarabia, Martin Urbicain, Angela Major, Karl-Dimiter Bissig, Charles Keller, Michael T Lewis, Andras Heczey, Pavel Sumazin, Dolores H López-Terrada, Sarah E Woodfield, Sanjeev A Vasudevan
Journal: Journal of Hepatology (2024)
Cell-free DNA fragmentomics and second malignant neoplasm risk in patients with PTEN hamartoma tumor syndrome
Authors: Darren Liu, Lamis Yehia, Andrew Dhawan, Ying Ni, Charis Eng
Journal: Cell Reports Medicine (2024)

Individuals with PTEN hamartoma tumor syndrome (PHTS) harbor pathogenic germline PTEN variants that confer a significantly increased lifetime risk of various organ-specific cancers including second primary malignant neoplasms (SMNs). Currently, there are no reliable biomarkers that can predict individual-level cancer risk. Despite the highly promising value of cell-free DNA (cfDNA) as a biomarker for underlying sporadic cancers, the utility of cfDNA in individuals with known cancer-associated germline variants and subclinical cancers remains poorly understood. We perform ultra-low-pass whole-genome sequencing (ULP-WGS) of cfDNA from plasma samples from patients with PHTS and cancer as well as those without cancer. Analysis of cfDNA reveals that patients with PHTS and SMNs have distinct cfDNA size distribution, aberrant genome-wide fragmentation, and differential fragment end motif frequencies. Our work provides evidence that cfDNA profiles may be used as a marker for SMN risk in patients with PHTS.
SARS-CoV-2 Delta and Omicron community transmission networks as added value to contact tracing
Authors: John M. Murray, Daniel D. Murray, Evelyne Schvoerer, Elma H. Akand
Journal: Journal of Infection (2024)

ObjectivesCalculations of SARS-CoV-2 transmission networks at a population level have been limited. Networks that estimate infections between individuals and whether this results in a mutation, can be a way to evaluate fitness of a mutational clone by how much it expands in number as well as determining the likelihood a transmission results in a new variant.MethodsAustralian Delta and Omicron SARS-CoV-2 sequences were downloaded from GISAID. Transmission networks of infection between individuals were estimated using a novel mathematical method.ResultsMany of the sequences were identical, with clone sizes following power law distributions driven by negative binomial probability distributions for both the number of infections per individual and the number of mutations per transmission (median 0.74 nucleotide changes for Delta and 0.71 for Omicron). Using these distributions, an agent-based model was able to replicate the observed clonal network structure, providing a basis for more detailed COVID-19 modelling. Possible recombination events, tracked by insertion/deletion (indel) patterns, were identified for each variant in these outbreaks.ConclusionsThis modelling approach reveals key transmission characteristics of SARS-CoV-2 and may complement traditional contact tracing. This methodology can also be applied to other diseases as genetic sequencing of viruses becomes more commonplace.
Longitudinal study of meningococcal carriage in adolescents and young adults in South Australia 2017-2020
Authors: Mark McMillan, Hassen Mohammed, Jana Bednarz, Lex E.X. Leong, Andrew Lawrence, Thomas R. Sullivan, Martin C.J. Maiden, Helen S. Marshall
Journal: Journal of Infection (2024)

BackgroundThis analysis investigated longitudinal changes in meningococcal carriage in adolescents in South Australia over 4 years.MethodsData from the “B Part of It” study, which included a state-wide cluster randomized controlled trial in secondary-school students (n=34,489 in 2017 and 2018) and serial cross-sectional studies in school leavers aged 17–25 years (n=4,028 in 2019-2020). Individuals had oropharyngeal swabs collected annually. This study included two unique cohorts: (1) individuals enrolled in 2019, with three consecutive annual swabs taken in 2017, 2018 and 2019; and (2) individuals enrolled in 2020, with swabs taken in 2017, 2018, and 2020. Disease-associated N. meningitidis genogroups were identified using PCR and whole genome sequencing. Univariate analysis identified risk factors for recurrent carriage (≥2).ResultsAmong school leavers, 50 (1.7%, total n=2,980) had carriage detected at successive visits. In participants with meningococcal carriage at successive visits, 38/50 (76.0%) had the same genogroup detected by porA PCR. Of those, 19 had the same MLST type and demonstrated minimal variation, indicating they most likely had sustained carriage of the same isolate (range 226 to 490 days, mean duration 352 [SD 51] days). In the 2019 school leaver cohort, 6.7% acquired carriage in their first year out of school compared to 3.3% in their final school year. Compared to single carriage detection, recurrent carriage was potentially more likely in older adolescents (16 compared to ≤ 15 years; OR=1.97 (95%CI 1.0,3.86);p=0.048).ConclusionWhilst carriage is typically transient, some adolescents/young adults may have persistent carriage and are likely to be an important group in the transmission of meningococci.
The effect of computerised decision support alerts tailored to intensive care on the administration of high-risk drug combinations, and their monitoring: a cluster randomised stepped-wedge trial
Authors: Tinka Bakker, Joanna E Klopotowska, Dave A Dongelmans, Saeid Eslami, Wytze J Vermeijden, Stefaan Hendriks, Julia ten Cate, Attila Karakus, Ilse M Purmer, Sjoerd H W van Bree, Peter E Spronk, Martijn Hoeksema, Evert de Jonge, Nicolette F de Keizer, Ameen Abu-Hanna, Dorieke E.M. van Balen, Peter F. Schutte, Marnix J. Sigtermans, Emile M. Kuck, Erik J.M. van Kan, Marijke S. van der Steen, Liesbeth E. Bosma, Ralph O. Nowitzky, Albertus Beishuizen, Kris L.L. Movig, Elsbeth M. Wesselink, Rick J.W. Lammers, Cedric Lau, Joost B. Masselink, Rob J. Bosman, Dylan W. de Lange, Rob J. van Marum, Heleen van der Sijs, Eric J.F. Franssen, Hans Kieft, Walter M. van den Bergh, Wouter Bult, Maurits H. Renes, Peter W. de Feiter, Evert-Jan Wils, Nicole G.M. Hunfeld, Froukje Mulder, Michiel Duyvendak
Journal: The Lancet (2024)
Polyphenol nanocomplex modulats lactate metabolic reprogramming and elicits immune responses to enhance cancer therapeutic effect
Authors: Zhan Zhang, Xinnan Li, Weiqiang Liu, Guanglei Chen, Jinchi Liu, Qingtian Ma, Pengjie Hou, Lu Liang, Caigang Liu
Journal: Drug Resistance Updates (2024)

Cancer lactate metabolic reprogramming induces an elevated level of extracellular lactate and H+, leading to an acidic immunosuppressive tumor microenvironment (TEM). High lactic acid level may affect the metabolic programs of various cells that comprise an antitumor immune response, therefore, restricting immune-mediated tumor destruction, and leading to therapeutic resistance and unsatisfactory prognosis. Here, we report a metal-phenolic coordination-based nanocomplex loaded with a natural polyphenol galloflavin, which inhibits the function of lactate dehydrogenase, reducing the production of lactic acid, and alleviating the acidic immunosuppressive TME. Besides, the co-entrapped natural polyphenol carnosic acid and the synthetic PEG-Ce6 polyphenol derivative (serving as a photosensitizer) could induce immunogenic cancer cell death upon laser irradiation, which further activates immune system and promotes immune cell recruitment and infiltration in tumor tissues. We demonstrated that this nanocomplex-based combinational therapy could reshape the TME and elicit immune responses in a murine breast cancer model, which provides a promising strategy to enhance the therapeutic efficiency of drug-resistant breast cancer.
Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial
Authors: Claire Dahyot-Fizelier, Sigismond Lasocki, Thomas Kerforne, Pierre-Francois Perrigault, Thomas Geeraerts, Karim Asehnoune, Raphaël Cinotti, Yoann Launey, Vincent Cottenceau, Marc Laffon, Thomas Gaillard, Matthieu Boisson, Camille Aleyrat, Denis Frasca, Olivier Mimoz, Claire DAHYOT-FIZELIER, Sigismond LASOCKI, Thomas KERFORNE, Pierre-Francois PERRIGAULT, Thomas GEERAERTS, Karim ASEHNOUNE, Raphaël CINOTTI, Yoann LAUNEY, Vincent COTTENCEAU, Marc LAFFON, Thomas GAILLARD, Matthieu BOISSON, Camille ALEYRAT, Denis FRASCA, Olivier MIMOZ, Clément GUYONNAUD, Rémy BELLIER, Thierry BENARD, Elsa CARISE, Franck PETITPAS, Hodanou NANADOUMGAR, Nadia IMZI, Sabrina SEGUIN, Karine GARNIER, Véronique FERRAND-RIGALLAUD, Séverine CLERJAUD, Soizic GERGAUD, Flora DJANIKIAN, Kevin CHALARD, Ségolène MROZEK, Sylvain PANH, Antoine ROQUILLY, Bertrand ROZEC, Philippe SEGUIN, Yannick MALLEDANT, Djilali ELAROUSSI, Martine FERRANDIERE, Matthieu BIAIS
Journal: The Lancet Respiratory Medicine (2024)
Immunogenicity and safety of concomitant bivalent COVID-19 and quadrivalent influenza vaccination: implications of immune imprinting and interference
Authors: Min Joo Choi, Young Jun Yu, Jae Won Kim, Hea Jeon Ju, So Youn Shin, Yun-Jung Yang, Hee Jin Cheong, Woo Joo Kim, Chulwoo Kim, Hwa Jung Kim, Sun Kyung Yoon, Se-Jin Park, WonSeok Gwak, June-Woo Lee, Byoungguk Kim, Joon Young Song
Journal: Clinical Microbiology and Infection (2024)
Error in Byline
Journal: JAMA Network Open (2024)

Xuantao Li, MPH; Recai Yucel, PhD; Helene Clervius, MD; Kundun Kamalakar, MPH; Henrik Zetterberg, MD, PhD; Kaj Blennow, MD, PhD; Jinbing Zhang, PhD; Adaora Adimora, MD; Lauren F. Collins, MD; Margaret Fischl, MD; Seble Kassaye, MD; Pauline Maki, PhD; Eric Seaberg, PhD; Anjali Sharma, MD; David Vance, PhD; Deborah R. Gustafson, MS, PhD
Imeglimin improves systemic metabolism by targeting brown adipose tissue and gut microbiota in obese model mice
Authors: Motoharu Awazawa, Maya Matsushita, Ikumi Nomura, Naoki Kobayashi, Miwa Tamura-Nakano, Yuriko Sorimachi, Keiyo Takubo, Kohjiro Ueki
Journal: Metabolism (2024)
Expanding the horizons of targeted protein degradation: A non-small molecule perspective
Authors: Xiaowei Huang, Fengbo Wu, Jing Ye, Lian Wang, Xiaoyun Wang, Xiang Li, Gu He
Journal: Acta Pharmaceutica Sinica B (2024)

Targeted protein degradation (TPD) represented by proteolysis targeting chimeras (PROTACs) marks a significant stride in drug discovery. A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond degradation. Non-small-molecule-based approaches play an irreplaceable role in this field. A wide variety of agents spanning a broad chemical spectrum, including peptides, nucleic acids, antibodies, and even vaccines, which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing paradigms. Herein we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs, including three major trajectories, to provide insights for the design strategies based on novel paradigms.