tbuckley/cabot-search huggingface dataset:
GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma
Authors: Zhaowei Wang, Lei He, Weina Li, Chuanyang Xu, Jieyu Zhang, Desheng Wang, Kefeng Dou, Ran Zhuang, Boquan Jin, Wei Zhang, Qiang Hao, Kuo Zhang, Wangqian Zhang, Shuning Wang, Yuan Gao, Jintao Gu, Lei Shang, Zhijun Tan, Haichuan Su, Yingqi Zhang, Cun Zhang, Meng Li
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background A better understanding of the molecular mechanisms that manifest in the immunosuppressive tumor microenvironment (TME) is crucial for developing more efficacious immunotherapies for hepatocellular carcinoma (HCC), which has a poor response to current immunotherapies. Regulatory T (Treg) cells are key mediators of HCC-associated immunosuppression. We investigated the selective mechanism exploited by HCC that lead to Treg cells expansion and to find more efficacious immunotherapies. Methods We used matched tumor tissues and blood samples from 150 patients with HCC to identify key factors of Treg cells expansion. We used mass cytometry (CyTOF) and orthotopic cancer mouse models to analyze overall immunological changes after growth differentiation factor 15 (GDF15) gene ablation in HCC. We used flow cytometry, coimmunoprecipitation, RNA sequencing, mass spectrum, chromatin immunoprecipitation and Gdf15 –/– , OT-I and GFP transgenic mice to demonstrate the effects of GDF15 on Treg cells and related molecular mechanism. We used hybridoma technology to generate monoclonal antibody to block GDF15 and evaluate its effects on HCC-associated immunosuppression. Results GDF15 is positively associated with the elevation of Treg cell frequencies in patients wih HCC. Gene ablation of GDF15 in HCC can convert an immunosuppressive TME to an inflammatory state. GDF15 promotes the generation of peripherally derived inducible Treg (iTreg) cells and enhances the suppressive function of natural Treg (nTreg) cells by interacting with a previously unrecognized receptor CD48 on T cells and thus downregulates STUB1, an E3 ligase that mediates forkhead box P3 (FOXP3) protein degradation. GDF15 neutralizing antibody effectively eradicates HCC and augments the antitumor immunity in mouse. Conclusions Our results reveal the generation and function enhancement of Treg cells induced by GDF15 is a new mechanism for HCC-related immunosuppression. CD48 is the first discovered receptor of GDF15 in the immune system which provide the possibility to solve the molecular mechanism of the immunomodulatory function of GDF15. The therapeutic GDF15 blockade achieves HCC clearance without obvious adverse events.
Hemodynamic Determinants of Activity Measured by Accelerometer in Patients With Stable Heart Failure
Authors: Massar Omar, Jesper Jensen, Peter H. Frederiksen, Lars Videbæk, Mikael Kjær Poulsen, Jan Christian Brønd, Finn Gustafsson, Barry A. Borlaug, Morten Schou, Jacob Eifer Møller
Journal: JACC Heart Failure (2021)
Anti-IL5 mepolizumab minimally influences residual blood eosinophils in severe asthma
Authors: Glenn Van Hulst, Joseph Jorssen, Nathalie Jacobs, Monique Henket, Renaud Louis, Florence Schleich, Fabrice Bureau, Christophe J. Desmet
Journal: European Respiratory Journal (2021)

Neutralising antibodies against the cytokine interleukin (IL)5 have become widely used for the control of severe eosinophilic asthma. Remarkably, patients receiving neutralising anti-IL5 biological therapies retain a very stable population of residual blood eosinophils. Whether these residual eosinophils are endowed with particular biological activity has not yet been studied, but is of importance in predicting potential long-term effects of IL5 neutralisation in patients. To tackle the effect of IL5 depletion on residual eosinophils, we used a comparative RNA-sequencing approach and compared the gene expression programme of eosinophils arising in IL5-depleted or IL5-replete human or murine hosts, at steady-state in vivo and following in vitro stimulation with the eosinophil-activating alarmin IL33. We compared blood eosinophils from patients with severe allergic eosinophilic asthma treated with anti-IL5 mepolizumab therapy to those of healthy controls and matched asthma patients receiving anti-IgE omalizumab therapy. We made similar comparisons on bone marrow eosinophils from mice genetically deficient or not for IL5. We report that restriction of IL5 availability did not elicit any detectable transcriptional response in steady-state residual eosinophils in mepolizumab-treated patients or IL5-deficient mice, and influenced only a handful of genes in their response to IL33. Together, these results support the notion that treatment with IL5 neutralising antibodies spares a pool of circulating residual eosinophils largely resembling those of healthy individuals.
An Artificial Intelligence System for the Detection of Bladder Cancer via Cystoscopy: A Multicenter Diagnostic Study
Authors: Shaoxu Wu, Xiong Chen, Jiexin Pan, Wen Dong, Xiayao Diao, Ruiyun Zhang, Yonghai Zhang, Yuanfeng Zhang, Guang Qian, Hao Chen, Haotian Lin, Shizhong Xu, Zhiwen Chen, Xiaozhou Zhou, Hongbing Mei, Chenglong Wu, Qiang Lv, Baorui Yuan, Zeshi Chen, Wenjian Liao, Xuefan Yang, Haige Chen, Jian Huang, Tianxin Lin
Journal: JNCI Journal of the National Cancer Institute (2021)

Cystoscopy plays an important role in bladder cancer (BCa) diagnosis and treatment, but its sensitivity needs improvement. Artificial intelligence has shown promise in endoscopy, but few cystoscopic applications have been reported. We report a Cystoscopy Artificial Intelligence Diagnostic System (CAIDS) for BCa diagnosis.In total, 69 204 images from 10 729 consecutive patients from 6 hospitals were collected and divided into training, internal validation, and external validation sets. The CAIDS was built using a pyramid scene parsing network and transfer learning. A subset (n = 260) of the validation sets was used for a performance comparison between the CAIDS and urologists for complex lesion detection. The diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values and 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method.The diagnostic accuracies of the CAIDS were 0.977 (95% CI = 0.974 to 0.979) in the internal validation set and 0.990 (95% CI = 0.979 to 0.996), 0.982 (95% CI = 0.974 to 0.988), 0.978 (95% CI = 0.959 to 0.989), and 0.991 (95% CI = 0.987 to 0.994) in different external validation sets. In the CAIDS vs urologists' comparisons, the CAIDS showed high accuracy and sensitivity (accuracy = 0.939, 95% CI = 0.902 to 0.964; sensitivity = 0.954, 95% CI = 0.902 to 0.983) with a short latency of 12 seconds, much more accurate and quicker than the expert urologists.The CAIDS achieved accurate BCa detection with a short latency. The CAIDS may provide many clinical benefits, from increasing the diagnostic accuracy for BCa, even for commonly misdiagnosed cases such as flat cancerous tissue (carcinoma in situ), to reducing the operation time for cystoscopy.
Wireless, Skin‐Interfaced Devices for Pediatric Critical Care: Application to Continuous, Noninvasive Blood Pressure Monitoring (Adv. Healthcare Mater. 17/2021)
Authors: Claire Liu, Jin‐Tae Kim, Sung Soo Kwak, Aurelie Hourlier‐Fargette, Raudel Avila, Jamie Vogl, Andreas Tzavelis, Ha Uk Chung, Jong Yoon Lee, Dong Hyun Kim, Dennis Ryu, Kelsey B. Fields, Joanna L. Ciatti, Shupeng Li, Masahiro Irie, Allison Bradley, Avani Shukla, Jairo Chavez, Emma C. Dunne, Seung Sik Kim, Jungwoo Kim, Jun Bin Park, Han Heul Jo, Joohee Kim, Michael C. Johnson, Jean Won Kwak, Surabhi R. Madhvapathy, Shuai Xu, Casey M. Rand, Lauren E. Marsillio, Sue J. Hong, Yonggang Huang, Debra E. Weese‐Mayer, John A. Rogers
Journal: Advanced Healthcare Materials (2021)

Wireless Wearables The cover associated with article 2100383 by Yonggang Huang, Debra E. Weese-Mayer, John A. Rogers, and co-workers, is a picture of an infant wearing a pair of soft, wireless, and skininterfaced devices that provide continuous, clinical-grade, and noninvasive monitoring of various physiological waveforms. Relevant characteristics of such waveforms can be used to infer key hemodynamic information, including blood pressure. These devices offer a route for continuous tracking of short- and long-term hemodynamic trends, including during periods of pharmacological interventions.
There is nothing holy about agony: religious people and leaders support assisted dying too
Authors: Jonathan Romain, George Carey
Journal: BMJ (2021)

A new alliance of faith leaders has formed to ensure the voice of religious proponents of legalised assisted dying is heard. The former Archbishop of Canterbury<b> George Carey</b> and rabbi <b>Jonathan Romain</b> argue that nothing in the scripture directly prohibits assisting a death to end suffering
Radiotherapy resources in Africa: an International Atomic Energy Agency update and analysis of projected needs
Authors: Shekinah N C Elmore, Alfredo Polo, Jean-Marc Bourque, Yaroslav Pynda, Debbie van der Merwe, Surbhi Grover, Kirsten Hopkins, Eduardo Zubizarreta, May Abdel-Wahab
Journal: The Lancet Oncology (2021)
Integration of imaging and circulating biomarkers in heart failure: a consensus document by the Biomarkers and Imaging Study Groups of the Heart Failure Association of the European Society of Cardiology
Authors: Brenda Moura, Alberto Aimo, Abdallah Al‐Mohammad, Andreas Flammer, Vassilis Barberis, Antoni Bayes‐Genis, Hans‐Peter Brunner‐La Rocca, Ricardo Fontes‐Carvalho, Julia Grapsa, Martin Hülsmann, Nasrien Ibrahim, Christian Knackstedt, James L. Januzzi, Tomas Lapinskas, Axel Sarrias, Simon Matskeplishvili, Wouter C. Meijers, Daniel Messroghli, Christian Mueller, Noemi Pavo, Justas Simonavičius, Arco J. Teske, Roland van Kimmenade, Petar Seferovic, Andrew J.S. Coats, Michele Emdin, A. Mark Richards
Journal: European Journal of Heart Failure (2021)
Current therapeutic strategies for respiratory diseases using mesenchymal stem cells
Authors: Ming‐yao Wang, Ting‐yue Zhou, Zhi‐dong Zhang, Hao‐yang Liu, Zhi‐yao Zheng, Hui‐qi Xie
Journal: MedComm (2021)

Abstract Mesenchymal stromal/stem cells (MSCs) have a great potential to proliferate, undergo multi‐directional differentiation, and exert immunoregulatory effects. There is already much enthusiasm for their therapeutic potentials for respiratory inflammatory diseases. Although the mechanism of MSCs‐based therapy has been well explored, only a few articles have summarized the key advances in this field. We hereby provide a review over the latest progresses made on the MSCs‐based therapies for four types of inflammatory respiratory diseases, including idiopathic pulmonary fibrosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and asthma, and the uncovery of their underlying mechanisms from the perspective of biological characteristics and functions. Furthermore, we have also discussed the advantages and disadvantages of the MSCs‐based therapies and prospects for their optimization.
Correction to: Identification of TBX15 as an adipose master trans regulator of abdominal obesity genes
Authors: David Z. Pan, Zong Miao, Caroline Comenho, Sandhya Rajkumar, Amogha Koka, Seung Hyuk T. Lee, Marcus Alvarez, Dorota Kaminska, Arthur Ko, Janet S. Sinsheimer, Karen L. Mohlke, Nicholas Mancuso, Linda Liliana Muñoz-Hernandez, Miguel Herrera-Hernandez, Maria Teresa Tusié-Luna, Carlos Aguilar-Salinas, Kirsi H. Pietiläinen, Jussi Pihlajamäki, Markku Laakso, Kristina M. Garske, Päivi Pajukanta
Journal: Genome Medicine (2021)
Uncovering cancer vulnerabilities by machine learning prediction of synthetic lethality
Authors: Salvatore Benfatto, Özdemirhan Serçin, Francesca R. Dejure, Amir Abdollahi, Frank T. Zenke, Balca R. Mardin
Journal: Molecular Cancer (2021)

Synthetic lethality describes a genetic interaction between two perturbations, leading to cell death, whereas neither event alone has a significant effect on cell viability. This concept can be exploited to specifically target tumor cells. CRISPR viability screens have been widely employed to identify cancer vulnerabilities. However, an approach to systematically infer genetic interactions from viability screens is missing.Here we describe PAn-canceR Inferred Synthetic lethalities (PARIS), a machine learning approach to identify cancer vulnerabilities. PARIS predicts synthetic lethal (SL) interactions by combining CRISPR viability screens with genomics and transcriptomics data across hundreds of cancer cell lines profiled within the Cancer Dependency Map.Using PARIS, we predicted 15 high confidence SL interactions within 549 DNA damage repair (DDR) genes. We show experimental validation of an SL interaction between the tumor suppressor CDKN2A, thymidine phosphorylase (TYMP) and the thymidylate synthase (TYMS), which may allow stratifying patients for treatment with TYMS inhibitors. Using genome-wide mapping of SL interactions for DDR genes, we unraveled a dependency between the aldehyde dehydrogenase ALDH2 and the BRCA-interacting protein BRIP1. Our results suggest BRIP1 as a potential therapeutic target in ~ 30% of all tumors, which express low levels of ALDH2.PARIS is an unbiased, scalable and easy to adapt platform to identify SL interactions that should aid in improving cancer therapy with increased availability of cancer genomics data.
Fucoidan-functionalized polysaccharide submicroparticles loaded with alteplase for efficient targeted thrombolytic therapy
Authors: Alina Zenych, Charlène Jacqmarcq, Rachida Aid, Louise Fournier, Laura M. Forero Ramirez, Frédéric Chaubet, Thomas Bonnard, Denis Vivien, Didier Letourneur, Cédric Chauvierre
Journal: Biomaterials (2021)
Homologous Recombination Deficiency Alterations in Colorectal Cancer: Clinical, Molecular, and Prognostic Implications
Authors: Roberto Moretto, Andrew Elliott, Jian Zhang, Hiroyuki Arai, Marco Maria Germani, Veronica Conca, Joanne Xiu, Phillip Stafford, Matthew Oberley, Jim Abraham, David Spetzler, Daniele Rossini, Carlotta Antoniotti, John Marshall, Anthony Shields, Gilberto Lopes, Sara Lonardi, Filippo Pietrantonio, Gianluca Tomasello, Alessandro Passardi, Emiliano Tamburini, Daniele Santini, Giuseppe Aprile, Gianluca Masi, Alfredo Falcone, Heinz-Josef Lenz, Michael Korn, Chiara Cremolini
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Tumors with homologous recombination deficiency (HRD) show high sensitivity to platinum salts and poly(ADP-ribose) polymerase–inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown. Methods Next-generation sequencing, whole transcriptome sequencing, and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments certified laboratory. Tumors with pathogenic and/or presumed pathogenic mutations in 33 genes involved in the homologous recombination pathway were considered HRD, the others were homologous recombination proficient (HRP). Furthermore, tumor samples from patients enrolled in the phase III TRIBE2 study comparing upfront FOLFOXIRI+bevacizumab vs FOLFOX+bevacizumab were analyzed with next-generation sequencing. The analyses were separately conducted in microsatellite stable or proficient mismatch repair (MSS/pMMR) and microsatellite instable-high or deficient mismatch repair (MSI-H/dMMR) groups. All statistical tests were 2-sided. Results Of 9321 CRC tumors, 1270 (13.6%) and 8051 (86.4%) were HRD and HRP, respectively. HRD tumors were more frequent among MSI-H/dMMR than MSS/pMMR tumors (73.4% vs 9.5%; P &amp;lt; .001; q &amp;lt; 0.001). In MSS/pMMR group, HRD tumors were more frequently tumor mutational burden high (8.1% vs 2.2%; P &amp;lt; .001; q &amp;lt; 0.001) and PD-L1 positive (5.0% vs 2.4%; P &amp;lt; .001; q = 0.001), enriched in all immune cell and fibroblast populations and genomic loss of heterozygosity-high (16.2% vs 9.5%; P = .03). In the TRIBE2 study, patients with MSS/pMMR and HRD tumors (10.7%) showed longer overall survival compared with MSS/pMMR and HRP tumors (40.2 vs 23.8 months; hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.45 to 0.98; P = .04). Consistent results were reported in the multivariable model (HR = 0.67, 95% CI = 0.45 to 1.02; P = .07). No interaction effect was evident between homologous recombination groups and treatment arm. Conclusions HRD tumors are a distinctive subgroup of MSS/pMMR CRCs with specific molecular and prognostic characteristics. The potential efficacy of agents targeting the homologous recombination system and immune checkpoint inhibitors in this subgroup is worthy of clinical investigation.
Letter to the editor: Sequencing bias for residue 28 of the neuraminidase of the recent highly pathogenic avian influenza virus A(H5N8)
Authors: Jinyue Guo, Congying Wang, Shujian Huang, Feng Wen
Journal: Eurosurveillance (2021)

Preview this article: Letter to the editor: Sequencing bias for residue 28 of the neuraminidase of the recent highly pathogenic avian influenza virus A(H5N8), Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/26/36/eurosurv-26-36-4-1.gif
Lifting dyspnoea invisibility: COVID-19 face masks, the experience of breathing discomfort, and improved lung health perception – a French nationwide survey
Authors: Laure Serresse, Noémie Simon-Tillaux, Maxens Decavèle, Frederick Gay, Nathalie Nion, Sophie Lavault, Antoine Guerder, Antoine Châtelet, Frédéric Dabi, Alexandre Demoule, Capucine Morélot-Panzini, Caroline Moricot, Thomas Similowski
Journal: European Respiratory Journal (2021)

In contrast with pain, dyspnoea is not visible to the general public, who lack the corresponding experiential baggage. We tested the hypothesis that the generalised use of face masks to fight severe acute respiratory syndrome coronavirus 2 dissemination could change this and sensitise people to respiratory health.General population polling (1012-person panel demographically representative of the adult French population, quota sampling method; 517 (51%) female). 860 (85%) answered "no" to "treated for a chronic respiratory disease" ("respiratory healthy"), and 152 answered "yes" ("respiratory disease"). 14% of respiratory healthy respondents reported having a close family member treated for a chronic respiratory disease (RH-family+ ). Respondents described mask-related attitudes, beliefs, inconveniencies, dyspnoea and changes in their respiratory health vision . RESULTS: Compliance with masks was high (94.7%). Dyspnoea ranked first among mask inconveniencies (respiratory disease 79.3%, respiratory healthy 67.3%; p=0.013). "Air hunger" was the main sensory dyspnoea descriptor. Mask-related dyspnoea was independently associated with belonging to RH-family+ (OR 1.85, 95% CI 1.16-2.98) and removing masks to improve breathing (OR 5.21, 95% CI 3.73-7.28). It was negatively associated with considering masks effective to protect others (OR 0.42, 95% CI 0.25-0.75). Half the respondents were more concerned with their respiratory health since wearing masks; 41% reported better understanding patients' experiences.Wearing protective face masks leads to the mass discovery of breathing discomfort. It raises public awareness of what respiratory diseases involve and sensitivity to the importance of breathing. These data should be used as the fulcrum of respiratory health oriented communication actions.
P14.85 Impact of the neuro-radiologist and neuro-surgeon in contouring with the neuro-oncologist on local relapse rates for brain metastases treated with stereotactic radiosurgery
Authors: M Robinson, K Sayal, C Tunstall, S Padmanaban, R Watson, P Pretorius, R Joseph, S Jeyaretna, C Hobbs
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The audit evaluates the value of MDT, including neuro-radiologist and neuro-surgeon, review of contouring carried out by a clinical oncologist in stereotactic radiosurgery (SRS). MATERIAL AND METHODS A sequential audit was conducted of all patients receiving intracranial SRS at our local institution for the first 22 months of a new SRS service. Lesions were contoured first by clinical oncologist then reviewed/edited by the MDT. The initial contour was compared with final contour using Jaccard conformity and geographical miss indices. The dosimetric impact of a contouring change was assessed using plan metrics to both original and final contour. The impact of the contouring review on local relapse, overall survival and radio necrosis rate was evaluated with at least 24 months follow up (24–46 months). RESULTS 113 patients and 142 lesions treated over 22 months were identified. Mean JCI was 0.92 (0.32–1.00) and 38% needed significant editing (JCI&amp;lt;0.95). Mean GMI was 0.03 (0.0–0.65) and 17% showed significant miss (GMI&amp;gt;0.05). Resection cavities showed more changes, with lower JCI and higher GMI (p&amp;lt;0.05). There was no significant improvement on JCI or GMI shown over time. Dosimetric analysis indicated a strong association of conformity metrics with PTV dose metrics; a 0.1 change in GTV conformity metric association with 6–17% change in dose to 95% of resulting PTV. Greater association was seen in resection cavity suggesting the geographical nature of a typical contouring error gives rise to greater potential change in dose. Clinical outcomes compared well with published series. Median survival was 20 months and local relapse free rate in the treated areas of 0.89 (0.8–0.94) at 40 months, and 0.9 (0.83–0.95) radio-necrosis free rate at 40 months with a median 17 months to developing radio-necrosis for those that did. CONCLUSION This work highlights that a MDT contour review adds significant value to SRS and the approach translates into reduced local recurrence rates at our local institution compared with previously published data. Radio-necrosis rates are below 10%. No improvement in clinical oncologist contouring over time was shown indicating a collaborative approach is needed regardless of experience of clinical oncologist. MDT input is recommended in particular in contouring of resection cavities.
It’s a no brainer: combat sports should be ground zero for research on concussion
Authors: Bruno Follmer, E Paul Zehr
Journal: British Journal of Sports Medicine (2021)

Many combat sports have as their overt goal the incapacitation of the opponent which is often achieved by blows to the head. While head impact in contact sports like football, rugby and hockey is accidental and susceptible to sanctioning, strikes directly to the head are intentional and determinants of success in combat sports like Muay Thai, kickboxing, boxing and mixed martial arts (MMA).1 2 Yet, combat modalities are often not mentioned among the sports identified with the highest concussion rates. Boxing is found ‘far behind’ equestrian events, rugby union, cricket, soccer and other organised college sports (eg, football and hockey).3 Data remain limited or unavailable for fighting arts.4

Fighting has been a sport since at least 648 BC in ancient Greece with pankration, a discipline that combined wrestling and boxing. Almost a century ago, ‘dementia pugilistica’ and ‘punch drunk’ described neurological impairments manifested in long-time boxers. Neuropathological reports on the long-term effects of boxing predate those in football.5

The popularity and financial power of combat sports have grown exponentially in recent years. Karate joined boxing, wrestling and taekwondo as an Olympic modality, while kickboxing …
NHS funding: £5.4bn boost must be first of many, say health leaders
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The NHS in England will get an extra £5.4bn (€6.3bn; $7.5bn) in funding over the next six months to help tackle lengthening waiting lists and manage the immediate pressures of the covid pandemic, the government has announced.

The £5.4bn comprises:

England’s health secretary, Sajid Javid, …