tbuckley/cabot-search huggingface dataset:
O12 Macrophages enhance angiogenesis in an induced pluripotent stem cell-derived skin organoid model
Authors: April Rose Foster, Chloe Admane, Diana Adao, Fereshteh Torabi, Nusayhah Hudaa Gopee, Bayanne Olabi, Elena Winheim, Victoria Rowe, Phuong Ahn Le, Sara Serdy, Jin Kim, CiCi Deakin, Jiyoon Lee, Tong Li, Karl Koehler, Laure Gambardella, Muzlifah Haniffa
Journal: British Journal of Dermatology (2024)

Abstract Introduction and aims Hair-bearing skin organoids (SkOs) are a complex three-dimensional (3D) model that faithfully recapitulates human skin as a multicellular organ with appendage structures. The development of such models provides unique potential for investigating human skin development and translational dermatology. Although this model answers many demands of an investigative tool, one obvious limitation is the absence of immune cells in SkOs. Our aim is to generate coculture systems of SkOs with macrophages to investigate how macrophages influence skin development. Methods Our group, and others, generated single-cell (sc)RNA-Seq and spatial transcriptomic datasets to thoroughly characterize human skin cell populations across the human lifespan. We used these datasets to compare the dynamic tempo of induced pluripotent stem cell (iPSC)-derived SkO (n = 84) differentiation with human prenatal (n = 15) and adult skin. For functional assays, we generated 2D angiogenesis coculture assays with macrophages and endothelial cells (n = 3) and 3D coculture of SkOs with macrophages (n = 3). Macrophages, endothelial cells and SkOs were all derived from the same iPSC line following established protocols. SkO vasculature was analysed after immunowholemount staining of CD31+ endothelial cells. Results Analysis of scRNA-Seq data highlighted a paucity in endothelial cell heterogeneity in SkOs compared with prenatal skin. We hypothesized that this could be explained by the absence of immune cells, as spatial transcriptomics microenvironment analysis of prenatal skin demonstrated that endothelial cells collocate with macrophages. With this in mind, we generated functional assays to investigate interactions of macrophages and endothelial cells in skin development. The 2D and 3D assays revealed that presence of macrophages significantly increased endothelial cell sprouting and network formation. Conclusions Our findings suggest a vital role of macrophages in skin morphogenesis, specifically in relation to the guidance of tip cells during angiogenesis. In addition, we present the SkO as an excellent complex model for investigating skin development, cell–cell interactions, and disease modelling for translational research in regenerative medicine and beyond.
O06 Naïve human keratinocytes initiate a chromatin-protective mechanism in response to ultraviolet radiation through the upregulation of histone deacetylase 5
Authors: Yu-Hsuan Tsai, Rachel Watson, Abigail Langton
Journal: British Journal of Dermatology (2024)

Abstract Introduction and aims During normal development and throughout life, epigenetic changes arise in response to an individuals’ behaviour and environmental exposures. Histone deacetylases (HDACs) are chromatin-modifying enzymes that regulate gene expression and their activity and expression in primary human keratinocytes alters with increasing age. Solar ultraviolet radiation (UVR) is a major causative factor of skin ageing, but how this factor affects HDAC expression and activity is largely unknown. We aimed to determine how UVR exposure affects HDAC expression and activity in primary human keratinocytes. Methods Normal human epidermal keratinocytes (NHEKs) from juvenile (aged 1–6 years; n = 3), middle-aged (56–61 years; n = 3) and aged (83–85 years; n = 3) donors were exposed to solar-simulated radiation (SSR) and HDAC abundance and activity were assayed. Results Exposure to SSR significantly increased HDAC activity in primary NHEKs irrespective of donor age (P &amp;lt; 0.05). However, Western blotting for HDAC abundance revealed that there was a differential response to SSR exposure across age groups; juvenile NHEKs expressed significantly more HDAC5 in response to SSR (P &amp;lt; 0.05) than cells from middle-aged or aged donors. Furthermore, following SSR exposure of juvenile NHEKs, the cellular localization of HDAC5 was redistributed to the nucleus from the cytoplasm. Dual immunofluorescence staining revealed that those NHEKs with nuclear HDAC5 expression were also positive for p16INK4a, a robust marker of cellular senescence (P &amp;lt; 0.01). Conclusions Our Results suggest that naïve human keratinocytes are responsive to UVR exposure and appear to initiate a chromatin-protective mechanism through the upregulation of HDAC5 to prevent gene expression of damaged DNA.
O02 Ubiquitomics of CYLD-deficient skin tumours reveals dysregulation of hair follicle keratinocyte processes
Authors: Joseph Inns, Andrew Frey, Neil Rajan
Journal: British Journal of Dermatology (2024)

Abstract Introduction and aims CYLD cutaneous syndrome (CCS) is an inherited hair follicle tumour syndrome where biallelic loss of function of the deubiquitinase enzyme CYLD gives rise to cylindroma skin tumours. The role of CYLD in skin biology is not well characterized but it is known to regulate several cell signalling pathways through deubiquitination of effector proteins. We aimed to determine how loss of CYLD function can lead to CCS skin tumour formation by studying the ubiquitome of CCS tumours and healthy skin. Methods Healthy skin (n = 5) and CCS tumour tissue (n = 5) were collected from flash frozen samples. Lysed homogenates were trypsin-digested and the resulting peptides underwent diglycine immunopurification for subsequent liquid chromatography–tandem mass spectrometry analysis on a Bruker Tims-TOF HT (Billerica, MA, USA) mass spectrometer. We utilized a data-independent acquisition method adapted for diglycine-containing peptides to generate mass spectrometry data. Peptide identification was performed by searching mass spectrometry data against an in silico neural network derived spectral library with diglycine modification. Results We identified 1273 ubiquitination sites across 649 proteins in CCS tumour and control samples. After performing t-tests (P &amp;lt; 0.05), we found 305 ubiquitination sites that were either unique to their respective condition or were differentially regulated. Analysis of ubiquitinated peptide sequences uncovered cell surface receptors with increased ubiquitination in CCS tumour samples including the insulin receptor, which had ubiquitination modifications at its kinase domain, suggesting increased insulin signalling in CCS tumours. Gene set enrichment analysis of CCS tumour ubiquitinated substrates revealed increased ubiquitination of secretory granules and extracellular exosomes, suggesting that loss of CYLD may disrupt regulation of protein secretion processes. Conclusions Our findings describe the ubiquitome of CCS keratinocytes, providing insights into how loss of CYLD function can affect biological processes in skin.
Shape‐Persistent Conductive Nerve Guidance Conduits for Peripheral Nerve Regeneration
Authors: Jiahui Song, Jize Dong, Zhengchao Yuan, Moran Huang, Xiao Yu, Yue Zhao, Yihong Shen, Jinglei Wu, Mohamed EL‐Newehy, Meera Moydeen Abdulhameed, Binbin Sun, Jiwu Chen, Xiumei Mo
Journal: Advanced Healthcare Materials (2024)

To solve the problems of slow regeneration and mismatch of axon regeneration after peripheral nerve injury, nerve guidance conduits (NGCs) have been widely used to promote nerve regeneration. Multichannel NGCs have been widely studied to mimic the structure of natural nerve bundles. However, multichannel conduits are prone to structural instability. Thermo-responsive shape memory polymers (SMPs) can maintain a persistent initial structure over the body temperature range. Electrical stimulation (ES), utilized within nerve NGCs, serves as a biological signal to expedite damaged nerve regeneration. Here, an electrospun shape-persistent conductive NGC is designed to maintain the persistent tubular structure in the physiological temperature range and improve the conductivity. The physicochemical and biocompatibility of these P, P/G, P/G-GO, and P/G-RGO NGCs are conducted in vitro. Meanwhile, to evaluate biocompatibility and peripheral nerve regeneration, NGCs are implanted in subcutaneous parts of the back of rats and sciatic nerves assessed by histology and immunofluorescence analyses. The conductive NGC displays a stable structure, good biocompatibility, and promoted nerve regeneration. Collectively, the shape-persistent conductive NGC (P/G-RGO) is expected to promote peripheral nerve recovery, especially for long-gap and large-diameter nerves.
Anonymizing medical case-based explanations through disentanglement
Authors: Helena Montenegro, Jaime S. Cardoso
Journal: Medical Image Analysis (2024)

Case-based explanations are an intuitive method to gain insight into the decision-making process of deep learning models in clinical contexts. However, medical images cannot be shared as explanations due to privacy concerns. To address this problem, we propose a novel method for disentangling identity and medical characteristics of images and apply it to anonymize medical images. The disentanglement mechanism replaces some feature vectors in an image while ensuring that the remaining features are preserved, obtaining independent feature vectors that encode the images' identity and medical characteristics. We also propose a model to manufacture synthetic privacy-preserving identities to replace the original image's identity and achieve anonymization. The models are applied to medical and biometric datasets, demonstrating their capacity to generate realistic-looking anonymized images that preserve their original medical content. Additionally, the experiments show the network's inherent capacity to generate counterfactual images through the replacement of medical features.
Poly(3,4‐Ethylenedioxythiophene)/Functional Gold Nanoparticle films for Improving the Electrode‐Neural Interface
Authors: Yiyong Wu, Lulu Wang, Mengying Yan, Xufang Wang, Xin Liao, Cheng Zhong, Dingning Ke, Yi Lu
Journal: Advanced Healthcare Materials (2024)

Implantable neural electrodes are indispensable tools for recording neuron activity, playing a crucial role in neuroscience research. However, traditional neural electrodes suffer from limited electrochemical performance, compromised biocompatibility, and tentative stability, posing great challenges for reliable long-term studies in free-moving animals. In this study, a novel approach employing a hybrid film composed of poly(3,4-ethylenedioxythiophene)/functional gold nanoparticles (PEDOT/3-MPA-Au) to improve the electrode-neural interface is presented. The deposited PEDOT/3-MPA-Au demonstrates superior cathodal charge storage capacity, reduced electrochemical impedance, and remarkable electrochemical and mechanical stability. Upon implantation into the cortex of mice for a duration of 12 weeks, the modified electrodes exhibit notably decreased levels of glial fibrillary acidic protein and increased neuronal nuclei immunostaining compared to counterparts utilizing poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate). Additionally, the PEDOT/3-MPA-Au modified electrodes consistently capture high-quality, stable long-term electrophysiological signals in vivo, enabling continuous recording of target neurons for up to 16 weeks. This innovative modification strategy offers a promising solution for fabricating low-impedance, tissue-friendly, and long-term stable neural interfaces, thereby addressing the shortcomings of conventional neural electrodes. These findings mark a significant advancement toward the development of more reliable and efficacious neural interfaces, with broad implications for both research and clinical applications.
Aedes albopictus is a competent vector of five arboviruses affecting human health, greater Paris, France, 2023
Authors: Chloé Bohers, Marie Vazeille, Lydia Bernaoui, Luidji Pascalin, Kevin Meignan, Laurence Mousson, Georges Jakerian, Anaïs Karch, Xavier de Lamballerie, Anna-Bella Failloux
Journal: Eurosurveillance (2024)

Aedes albopictus collected in 2023 in the greater Paris area (Île-de-France) were experimentally able to transmit five arboviruses: West Nile virus from 3 days post-infection (dpi), chikungunya virus and Usutu virus from 7 dpi, dengue virus and Zika virus from 21 dpi. Given the growing number of imported dengue cases reported in early 2024 in France, surveillance of Ae. albopictus should be reinforced during the Paris Olympic Games in July, when many international visitors including from endemic countries are expected.
Autochthonous and imported giardiasis cases: An analysis of two decades of national surveillance data, Germany, 2002 to 2021
Authors: Franziska Hommes, Achim Dörre, Susanne C Behnke, Klaus Stark, Mirko Faber
Journal: Eurosurveillance (2024)

Background Giardia duodenalis is a major cause of gastroenteritis globally, and is the most common food- and waterborne parasitic infection in Europe. Aim To describe the epidemiology of reported acute giardiasis cases in Germany and compare demographic and clinical characteristics between imported and autochthonous cases. Methods We conducted a descriptive analysis of giardiasis cases that fulfilled the national case definition and were reported between January 2002 and December 2021. We defined an imported case as having at least one place of exposure abroad in the 3–25 days before symptom onset. We analysed case numbers and incidence by age, sex, month reported and geographic region, both overall and stratified by autochthonous and imported cases. Results From 2002 to 2021, 72,318 giardiasis cases were reported in Germany, corresponding to a mean annual incidence of 4.4 per 100,000 population. Annual incidence gradually decreased since 2013, declining sharply during the COVID-19 pandemic in 2020–21. Of 69,345 cases reported between 2002 and 2019, 35% were imported. Incidence of autochthonous cases (overall yearly mean: 3.1/100,000) was highest in males and young children (&lt; 5 years); imported cases were predominantly adults aged 20–39 years. We identified seasonal patterns for imported and autochthonous cases. Conclusions Giardiasis in Germany is typically assumed to be imported. Our data, however, underline the importance of autochthonous giardiasis. Travel advice might reduce imported infections, but prevention strategies for autochthonous infections are less clear. Dietary, behavioural and environmental risk factors need to be further investigated to enhance infection prevention measures for autochthonous giardiasis.
Authors’ response: Atypical age distribution and high disease severity in children with RSV infections during two irregular epidemic seasons throughout the COVID-19 pandemic
Authors: Wei Cai, Sophie Köndgen, Kristin Tolksdorf, Ralf Dürrwald, Barbara Biere, Walter Haas, Thorsten Wolff, Silke Buda, Janine Reiche
Journal: Eurosurveillance (2024)

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p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial
Authors: Hayley R C Shanks, Kewei Chen, Eric M Reiman, Kaj Blennow, Jeffrey L Cummings, Stephen M Massa, Frank M Longo, Anne Börjesson-Hanson, Manfred Windisch, Taylor W Schmitz
Journal: Nature Medicine (2024)

Abstract p75 neurotrophin receptor (p75 NTR ) signaling pathways substantially overlap with degenerative networks active in Alzheimer disease (AD). Modulation of p75 NTR with the first-in-class small molecule LM11A-31 mitigates amyloid-induced and pathological tau-induced synaptic loss in preclinical models. Here we conducted a 26-week randomized, placebo-controlled, double-blinded phase 2a safety and exploratory endpoint trial of LM11A-31 in 242 participants with mild to moderate AD with three arms: placebo, 200 mg LM11A-31 and 400 mg LM11A-31, administered twice daily by oral capsules. This trial met its primary endpoint of safety and tolerability. Within the prespecified secondary and exploratory outcome domains (structural magnetic resonance imaging, fluorodeoxyglucose positron-emission tomography and cerebrospinal fluid biomarkers), significant drug–placebo differences were found, consistent with the hypothesis that LM11A-31 slows progression of pathophysiological features of AD; no significant effect of active treatment was observed on cognitive tests. Together, these results suggest that targeting p75 NTR with LM11A-31 warrants further investigation in larger-scale clinical trials of longer duration. EU Clinical Trials registration: 2015-005263-16 ; ClinicalTrials.gov registration: NCT03069014 .
Spatial genomic, biochemical and cellular mechanisms underlying meningioma heterogeneity and evolution
Authors: Calixto-Hope G Lucas, Kanish Mirchia, Kyounghee Seo, Hinda Najem, William C Chen, Naomi Zakimi, Kyla Foster, Charlotte D Eaton, Martha A Cady, Abrar Choudhury, S John Liu, Joanna J Phillips, Stephen T Magill, Craig M Horbinski, David A Solomon, Arie Perry, Harish N Vasudevan, Amy B Heimberger, David R Raleigh
Journal: Nature Genetics (2024)
The gray area of RQ-PCR-based measurable residual disease: subdividing the “positive, below quantitative range” category
Authors: Michaela Kotrova, Eva Fronkova, Michael Svaton, Daniela Drandi, Felix Schön, Patricia Hoogeveen, Jeremy Hancock, Aneta Skotnicova, Anke Schilhabel, Cornelia Eckert, Emmanuelle Clappier, Gianni Cazzaniga, Beat W. Schäfer, Jacques J. M. van Dongen, Matthias Ritgen, Christiane Pott, Vincent H. J. van der Velden, Jan Trka, Monika Brüggemann
Journal: Leukemia (2024)

Detection of measurable residual disease (MRD) in hematological malignancies is crucial for prognostication and treatment decisions.Real-time quantitative PCR (RQ-PCR), which targets immunoglobulin (IG) and T-cell receptor (TR) rearrangements, is deemed the gold-standard method for MRD detection in national and international clinical trials.However, this approach does have some limitations, primarily related to standard curve performance and non-specific background amplification.International guidelines and criteria for interpreting IG/TR RQ-PCR-based MRD data, developed by the EuroMRD Consortium and available since 2007 [1], define two key parameters: sensitivity and quantitative range (QR).To ensure reliable and accurate assessment of MRD, sensitivity and QR are determined for each clone-specific RQ-PCR assay using a standard dilution curve of the patient diagnostic sample in leukocytes from healthy donors (socalled "buffy coat" (BC), mimicking the background of polyclonal lymphoid cells in bone marrow samples from patients in complete remission.To minimize the risk of false-positive results, the definition of the sensitivity and QR, as well as the criteria for sample positivity, consider the possible nonspecific background amplification.Additional and more stringent criteria, including reproducibility within replicates and distance from the background, are required to establish the QR and accurately quantify the sample.However, according to these criteria, certain samples may be considered positive, but not quantifiable, also known as "positive below QR" (PBQR).This category of samples poses a challenge for the interpretation of MRD and subsequent clinical evaluation, potentially leading to an incorrect treatment decision.Previous studies have shown that certain PBQR samples may be false positives, caused
Prediction of DNA methylation-based tumor types from histopathology in central nervous system tumors with deep learning
Authors: Danh-Tai Hoang, Eldad D. Shulman, Rust Turakulov, Zied Abdullaev, Omkar Singh, Emma M. Campagnolo, H. Lalchungnunga, Eric A. Stone, MacLean P. Nasrallah, Eytan Ruppin, Kenneth Aldape
Journal: Nature Medicine (2024)
Increase in invasive group A streptococcal infections (iGAS) in children and older adults, Norway, 2022 to 2024
Authors: Beatriz Valcarcel Salamanca, Pascale Renée Cyr, Yngvild Emblem Bentdal, Sara Viksmoen Watle, Astrid Louise Wester, Åse Marie Wikman Strand, Håkon Bøås
Journal: Eurosurveillance (2024)

At the end of 2022 and most notably during the first half of 2023, the number of invasive group A streptococcus (iGAS) notifications increased in Norway, largely affecting children younger than 10 years, as observed in several other countries. Following this atypical season, a new surge in the number of iGAS notifications began in December 2023 and peaked between January and February 2024, now particularly affecting both children younger than 10 years and older adults (70 years and above).
An outbreak of Legionnaires’ disease linked to a municipal and industrial wastewater treatment plant, The Netherlands, September–October 2022
Authors: Roan Pijnacker, Petra Brandsema, Sjoerd Euser, Ali Vahidnia, Arnold Kuiter, Jesse Limaheluw, Christine Schout, Gaaled Haj Mohammad, Stijn Raven
Journal: Eurosurveillance (2024)

Wastewater treatment plants (WWTPs) are increasingly identified as Legionnaires’ disease (LD) sources. An outbreak investigation was initiated following five LD cases reported in September 2022 in Houten, the Netherlands. Case identification was based on the European LD case definition, with symptom onset from 1 September 2022, residence in or within 5 km of Houten, or visit to Houten within the incubation period, without other likely sources. We sampled potential sources and genotyped environmental and clinical isolates. We identified 15 LD cases with onset between 13 September and 23 October 2022. A spatial source identification and wind direction model suggested an industrial (iWWTP) and a municipal WWTP (mWWTP) as potential sources, with the first discharging water into the latter. Both tested positive for Legionella pneumophila serogroups 1 and 6 with multiple sequence types (ST). We detected L. pneumophila sg1 ST42 in the mWWTP, matching with one of three available clinical isolates. Following control measures at the WWTPs, no further cases were observed. This outbreak underlines that municipal and industrial WWTPs can play an important role in community LD cases and outbreaks, especially those with favourable conditions for Legionella growth and dissemination, or even non-favourable conditions for growth but with the influx of contaminated water.
Letter to the editor: Atypical age distribution and high disease severity in children with RSV infections during two irregular epidemic seasons throughout the COVID-19 pandemic
Authors: Xiangting Liu, Guangting Zeng
Journal: Eurosurveillance (2024)

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