tbuckley/cabot-search huggingface dataset:
Core-shell hydrogel microfiber-expanded pluripotent stem cell-derived lung progenitors applicable to lung reconstruction in vivo
Authors: Satoshi Ikeo, Yuki Yamamoto, Kazuhiro Ikeda, Naoyuki Sone, Yohei Korogi, Lucia Tomiyama, Hisako Matsumoto, Toyohiro Hirai, Masatoshi Hagiwara, Shimpei Gotoh
Journal: Biomaterials (2021)

Lung transplantation is the only treatment available for end-stage lung diseases; however, donor shortage is a global issue. The use of human pluripotent stem cells (hPSCs) for organ regeneration is a promising approach. Nevertheless, methods for the expansion of isolated hPSC-derived lung progenitors (hLPs) for transplantation purposes have not yet been reported. Herein, we established an expansion system of hLPs based on their three-dimensional culture in core-shell hydrogel microfibers, that ensures the maintenance of their bipotency for differentiation into alveolar and airway epithelial cells including alveolar type II (AT2) cells. Further, we developed an efficient in vivo transplantation method using an endoscope-assisted transtracheal administration system; the successful engraftment and in vivo differentiation of hLPs into alveolar epithelial cells (incorporated into the alveoli) was observed. Importantly, expanded hLPs in the context of microfibers were successfully transplanted into the murine lungs, opening avenues for cell-based therapies of lung diseases. Therefore, our novel method has potential regenerative medicine applications; additionally, the high-quality hLPs and AT2 cells generated via the microfiber-based technology are valuable for drug discovery purposes.
Regaining the Tumor Control in Relapsed/Refractory Hodgkin Lymphoma after Nivolumab Failure with Addition of Another Antineoplastic Agent
Authors: Nataliia Mikhailova, Kirill Lepik, Elena Kondakova, Evgeniya Borzenkova, Yuri Zalaylov, Andrey Kozlov, Vadim Baykov, Lilia Stelmakh, Luibov Tsvetkova, Olesya Smykova, Axel R Zander, Boris Afanasyev
Journal: Blood (2017)
Extrapolating Survival From Randomized Clinical Trial Data—Possibilities and Caution
Authors: Laine Elliott Thomas, Ann Marie Navar, Michael J. Pencina
Journal: JAMA Cardiology (2021)

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MYC suppresses STING-dependent innate immunity by transcriptionally upregulating DNMT1 in triple-negative breast cancer
Authors: Si-Yu Wu, Yi Xiao, Jin-Li Wei, Xiao-En Xu, Xi Jin, Xin Hu, Da-Qiang Li, Yi-Zhou Jiang, Zhi-Ming Shao
Journal: Journal for ImmunoTherapy of Cancer (2021)

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and lacks definite treatment targets. Tumor immune microenvironment (TIME) heterogeneity has a profound impact on the immunotherapy response. Tumors with non-inflamed TIME derive limited benefit from immunotherapy. However, what drives the formation of the non-inflamed TIME in TNBC remains unclear.Using our multiomics database of TNBC, we conducted an analysis to explore the key genomic events driving the formation of the non-inflamed TIME in TNBC. In vitro and in vivo studies further revealed potential mechanisms and the efficacy of combination treatment with immunotherapy.With transcriptomic and genomic data, we systematically analyzed the TIME of TNBC and revealed that the classical basal-like subtype of TNBC consisted of two distinct microenvironment phenotypes, defined as the 'inflamed' and 'non-inflamed' subtypes. We performed further screening and demonstrated that MYC amplification and overexpression led to low immune infiltration and cytolytic activity in TIME. Mechanistically, MYC bound to DNMT1 promoter and activated DNMT1 transcription in TNBC cells, thus suppressing the Cyclic GMP-AMP synthase (cGAS)-STING pathway via an epigenetic regulatory way. In MYC-overexpressing TNBC, decitabine, an Food and Drug Administration (FDA)-approved DNA methyltransferase inhibitor, converted tumors from non-inflamed to inflamed tumors by enhancing T cell infiltration. Furthermore, the combination of decitabine with programmed cell death protein 1 (PD-1) inhibitor reversed T cell exhaustion and improved T cell function in mouse models, which elicited potent antitumor activity in MYC-overexpressing TNBC.Our work elucidates that the classic oncogene MYC induces immune evasion by repressing innate immunity. Furthermore, we provide a rationale for combining DNA methyltransferase inhibition with immunotherapy for the treatment of MYC-overexpressing TNBC.
Sequential activation of heterogeneous macrophage phenotypes is essential for biomaterials-induced bone regeneration
Authors: Wei Qiao, Huizhi Xie, Jinghan Fang, Jie Shen, Wenting Li, Danni Shen, Jun Wu, Shuilin Wu, Xuanyong Liu, Yufeng Zheng, Kenneth M.C. Cheung, Kelvin W.K. Yeung
Journal: Biomaterials (2021)
Comparative Secretome Analysis of <i>Magnaporthe oryzae</i> Identified Proteins Involved in Virulence and Cell Wall Integrity
Authors: Ning Liu, Linlu Qi, Manna Huang, Deng Chen, Changfa Yin, Yiying Zhang, Xingbin Wang, Guixin Yuan, Rui-Jin Wang, Jun Yang, You-Liang Peng, Xunli Lu
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Plant fungal pathogens secrete numerous proteins into the apoplast at the plant–fungus contact sites to facilitate colonization. However, only a few secretory proteins were functionally characterized in Magnaporthe oryzae, the fungal pathogen causing rice blast disease worldwide. Asparagine-linked glycosylation 3 (Alg3) is an α-1,3-mannosyltransferase functioning in the N-glycan synthesis of N-glycosylated secretory proteins. Fungal pathogenicity and cell wall integrity are impaired in Δalg3 mutants, but the secreted proteins affected in Δalg3 mutants are largely unknown. In this study, we compared the secretome s of the wild-type strain and the Δalg3 mutant and identified 51 proteins that require Alg3 for proper secretion. These proteins were predicted to be involved in metabolic processes, interspecies interactions, cell wall organization, and response to chemicals. Nine proteins were selected for further validation. We found that these proteins were localized at the apoplastic region surrounding the fungal infection hyphae. Moreover, the N-glycosylation of these proteins was significantly changed in the Δalg3 mutant, leading to the decreased protein secretion and abnormal protein localization. Furthermore, we tested the biological functions of two genes, INV1 (encoding invertase 1, a secreted invertase) and AMCase (encoding acid mammalian chinitase, a secreted chitinase). The fungal virulence was significantly reduced, and the cell wall integrity was altered in the Δinv1 and Δamcase mutant strains. Moreover, the N-glycosylation was essential for the function and secretion of AMCase. Taken together, our study provides new insight into the role of N-glycosylated secretory proteins in fungal virulence and cell wall integrity.
Improved Sézary cell detection and novel insights into immunophenotypic and molecular heterogeneity in Sézary syndrome
Authors: Safa Najidh, Cornelis P. Tensen, Alita J. van der Sluijs-Gelling, Cristina Teodosio, Davy Cats, Hailiang Mei, Thomas B. Kuipers, Jacoba J. Out-Luijting, Willem H. Zoutman, Thorbald van Hall, Alberto Orfao, Julia Almeida, Jacques J. M. van Dongen, Maarten H. Vermeer
Journal: Blood (2021)
血液透析患者におけるPTCRA(経皮的経管腔的冠状動脈回転性血管形成術)の中期結果
Authors: Aoki J, Ikari Y, Nakajima H, Iijima R, Minatoya Y, Nakayama T, Miyazawa A, Kyouno H, Hara K
Journal: Circulation (2002)
ChAdOx1 nCoV-19 Vaccine Efficacy against the B.1.351 Variant
Authors: Shabir A Madhi, Alane Izu, Andrew J Pollard
Journal: New England Journal of Medicine (2021)

To the Editor: Madhi et al. (May 20 issue) 1 report on the efficacy of vaccination with the recombinant adenoviral vector encoding the spike protein antigen of SARS-CoV-2 (ChAdOx1 nCoV-19) against the SARS-CoV-2 B.1.351(or beta) variant lineage.They commented that in the ENSEMBLE study evaluating the efficacy of the Ad26.COV2.S vaccine, only patients with infection that was confirmed by polymerase-chain-reaction assay who had at least three signs or symptoms of Covid-19 were approved for end-point adjudication.The authors incorrectly concluded that the vaccine efficacy analyses excluded the majority of mild Covid-19 cases.However, all patients with mild or moderate cases of Covid-19 who had one or two symptoms did not require adjudication for confirmation as a case and were included in primary or secondary efficacy analyses, as detailed in the protocol.The Clinical Severity Adjudication Committee was established to independently assess, in a blinded manner, potential severe or critical cases of Covid-19, adjudicating all cases meeting the criteria for severe-critical disease and all cases meeting the criteria for moderate disease with at least three signs or symptoms to determine whether the case was severe-critical in their judgment. 2This focused process yielded blinded, independent confirmation of severecritical cases by clinical infectious disease experts and pulmonologists, ensuring the robustness and clinical relevance of this important end point.
<scp>COVID</scp>‐19 severity, <scp>miR</scp>‐21 targets, and common human genetic variation. Letter regarding the article ‘Circulating cardiovascular <scp>microRNAs</scp> in critically ill <scp>COVID</scp>‐19 patients’
Authors: Simon A. Dingsdag, Oliver K. Clay, Gustavo A. Quintero
Journal: European Journal of Heart Failure (2021)
Associations between Exposure to Organochlorine Chemicals and Endometriosis: A Systematic Review of Experimental Studies and Integration of Epidemiological Evidence
Authors: Komodo Matta, Meriem Koual, Stéphane Ploteau, Xavier Coumoul, Karine Audouze, Bruno Le Bizec, Jean-Philippe Antignac, Germán Cano-Sancho
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Growing epidemiological evidence suggests that organochlorine chemicals (OCCs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play a role in the pathogenesis of endometriosis.OBJECTIVES: We aimed to systematically review the experimental evidence (in vivo and in vitro) on the associations between exposure to OCCs and endometriosis-related end points.METHODS: A systematic review protocol was developed following the National Toxicology Program /Office of Health Assessment and Translation (NTP/OHAT) framework and managed within a web-based interface.In vivo studies designed to evaluate the impact of OCCs on the onset or progression of endometriosis and proliferation of induced endometriotic lesions were eligible.Eligible in vitro studies included single-cell and co-culture models to evaluate the proliferation, migration, and/or invasion of endometrial cells.We applied the search strings to PubMed, Web of Science, and Scopus ® .A final search was performed on 24 June 2020.Assessment of risk of bias and the level of evidence and integration of preevaluated epidemiological evidence was conducted using NTP/OHAT framework RESULTS: Out of 812 total studies, 39 met the predetermined eligibility criteria (15 in vivo, 23 in vitro, and 1 both).Most studies (n = 27) tested TCDD and other dioxin-like chemicals.In vivo evidence supported TCDD's promotion of endometriosis onset and lesion growth.In vitro evidence supported TCDD's promotion of cell migration and invasion, but there was insufficient evidence for cell proliferation.In vitro evidence further supported the roles of the aryl hydrocarbon receptor and matrix metalloproteinases in mediating steroidogenic disruption and inflammatory responses.Estrogen interactions were found across studies and end points.CONCLUSION: Based on the integration of a high level of animal evidence with a moderate level of epidemiological evidence, we concluded that TCDD was a known hazard for endometriosis in humans and the conclusion is supported by mechanistic in vitro evidence.Nonetheless, there is need for further research to fill in our gaps in understanding of the relationship between OCCs and their mixtures and endometriosis, beyond the prototypical TCDD.
MO38-3 Clinical update with genomic analyses in expansion part of phase 1 study of selective FGFR inhibitor E7090
Authors: Makoto Ueno, Chigusa Morizane, Tatsuya Ioka, Masahiro Tajika, Masafumi Ikeda, Kensei Yamaguchi, Hiroki Hara, Hiroshi Yabusaki, Atsushi Miyamoto, Satoru Iwasa, Manabu Muto, Tsutomu Takashima, Keiko Minashi, Yoshito Komatsu, Tomohiro Nishina, Takako Nakajima, Takatoshi Sahara, Taisuke Uehara, Setsuo Funasaka, Masakazu Yashiro, Junji Furuse
Journal: Annals of Oncology (2021)
FLT3 ITD AML Outcomes Are Impacted By Exposure to One Cycle of Cytarabine Based Consolidation, Pre- and Post-Transplant TKI Therapy, and Presence of Minimal Residual Disease (MRD) Prior to Allogeneic Blood or Marrow Transplant
Authors: Melanie Rebechi, Amy E. DeZern, Amanda Kagan, B. Douglas Smith, Ivana Gojo, Margaret M. Showel, Gabrielle T. Prince, Gabriel Ghiaur, Lukasz P. Gondek, William Matsui, Ephraim J. Fuchs, Leo Luznik, Shannon R. McCurdy, Carol Ann Huff, Lode J. Swinnen, Ivan M. Borrello, Douglas E. Gladstone, Javier Bolanos-Meade, Richard F Ambinder, Richard J. Jones, Mark J. Levis, Keith Pratz
Journal: Blood (2017)
Endoscopic closure of tracheoesophageal fistula with a novel dumbbell-shaped occluder
Authors: Chang Zhu, Lurong Li, Yun Wang, Weifeng Zhang, Wenjie Li, Xuan Li, Guoxin Zhang
Journal: Endoscopy (2021)

Tracheoesophageal fistula (TEF) is a challenging condition that is difficult to treat. Several reports have described successful TEF treatment with an Amplatzer occluder (AGA Medical Corporation, Plymouth, Minnesota, USA) [1] [2]. However, Daniel et al. reported the case of a benign gastrobronchial fistula patient who underwent treatment with the Amplatzer device and died of fatal hemoptysis [3]. Inspired by this case, we developed a new dumbbell-shaped occluder device [4]. Compared with the Amplatzer occluder, this device has no protrusions, which reduces the risk of bleeding; even if the patient coughs, it will not increase airway damage.
Interpreting post-colonoscopy colorectal cancer rates in inflammatory bowel disease
Authors: Nicholas Ewin Burr
Journal: Endoscopy (2021)

People with colonic inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Colonoscopic surveillance is advocated in this population, with the aim of preventing death from CRC. This seems intuitive for a high risk group, but there is only limited observational evidence for the efficacy of surveillance [1]. A randomized controlled trial would now be extremely difficult to conduct as one group would be randomized to no colonoscopy surveillance. Furthermore, the absolute risk of CRC is low and it can take years for CRC to develop.
P31-7 Clinical outcomes of cerebral infarction associated with Trousseau’s syndrome in advanced pancreatic cancer patients
Authors: Tomoyo Oguri, Hiroyuki Takeda, Kumiko Umemoto, Ayako Doi, Hiroyuki Arai, Yoshiki Horie, Takuro Mizukami, Naoki Izawa, Takashi Ogura, Yu Sunakawa
Journal: Annals of Oncology (2021)
TGFβ promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis
Authors: Paôline Laurent, Benoit Allard, Pauline Manicki, Valérie Jolivel, Emeline Levionnois, Mohamed Jeljeli, Pauline Henrot, Julien Izotte, Damien Leleu, Alexis Groppi, Julien Seneschal, Joel Constans, Carlo Chizzolini, Christophe Richez, Pierre Duffau, Estibaliz Lazaro, Edouard Forcade, Thierry Schaeverbeke, Thomas Pradeu, Frédéric Batteux, Patrick Blanco, Cécile Contin-Bordes, Marie-Elise Truchetet
Journal: Annals of the Rheumatic Diseases (2021)

Objective Innate lymphoid cells-2 (ILC2) were shown to be involved in the development of lung or hepatic fibrosis. We sought to explore the functional and phenotypic heterogeneity of ILC2 in skin fibrosis within systemic sclerosis (SSc). Methods Blood samples and skin biopsies from healthy donor or patients with SSc were analysed by immunostaining techniques. The fibrotic role of sorted ILC2 was studied in vitro on dermal fibroblast and further explored by transcriptomic approach. Finally, the efficacy of a new treatment against fibrosis was assessed with a mouse model of SSc. Results We found that ILC2 numbers were increased in the skin of patients with SSc and correlated with the extent of skin fibrosis. In SSc skin, KLRG1 − ILC2 (natural ILC2) were dominating over KLRG1 + ILC2 (inflammatory ILC2). The cytokine transforming growth factor-β (TGFβ), whose activity is increased in SSc, favoured the expansion of KLRG1 - ILC2 simultaneously decreasing their production of interleukin 10 (IL10), which regulates negatively collagen production by dermal fibroblasts. TGFβ-stimulated ILC2 also increased myofibroblast differentiation. Thus, human KLRG1 - ILC2 had an enhanced profibrotic activity. In a mouse model of SSc, therapeutic intervention-combining pirfenidone with the administration of IL10 was required to reduce the numbers of skin infiltrating ILC2, enhancing their expression of KLRG1 and strongly alleviating skin fibrosis. Conclusion Our results demonstrate a novel role for natural ILC2 and highlight their inter-relationships with TGFβ and IL10 in the development of skin fibrosis, thereby opening up new therapeutic approaches in SSc.
Interventions Using Wearable Physical Activity Trackers Among Adults With Cardiometabolic Conditions
Authors: Alexander Hodkinson, Evangelos Kontopantelis, Charles Adeniji, Harm van Marwijk, Brian McMillian, Peter Bower, Maria Panagioti
Journal: JAMA Network Open (2021)

Wearable physical activity (PA) trackers, such as accelerometers, fitness trackers, and pedometers, are accessible technologies that may encourage increased PA levels in line with current recommendations. However, whether their use is associated with improvements in PA levels in participants who experience 1 or more cardiometabolic conditions, such as diabetes, prediabetes, obesity, and cardiovascular disease, is unknown.
How to Perform Pericardiocentesis in Cancer Patients With Thrombocytopenia
Authors: Robin Jacob, Nicolas L. Palaskas, Juan Lopez-Mattei, Saamir Hassan, Peter Kim, Teodora Donisan, Dinu Valentin Balanescu, Mehmet Cilingiroglu, Konstantinos Marmagkiolis, Cezar Iliescu
Journal: JACC CardioOncology (2021)
Covid-19: Fully vaccinated NHS staff may not need to self-isolate
Authors: Gareth Iacobucci
Journal: BMJ (2021)

NHS and care staff in England who have been told to self-isolate will be permitted to attend work in “exceptional circumstances” if they are fully vaccinated and return a negative PCR test, the government has announced.

The measure is being introduced to alleviate pressure on services after a sharp rise in absences of staff who have been told to self-isolate. The change in policy covers staff who have been contacted as a close contact of a case of covid-19 by NHS Test and Trace or who have been advised to self-isolate by the NHS covid-19 app.

To qualify, staff must have received two doses of covid-19 vaccine and a negative PCR test …
Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures
Authors: Maria Arechederra, María Rullán, Irene Amat, Daniel Oyon, Lucia Zabalza, Maria Elizalde, M Ujue Latasa, Maria R Mercado, David Ruiz-Clavijo, Cristina Saldaña, Ignacio Fernández-Urién, Juan Carrascosa, Vanesa Jusué, David Guerrero-Setas, Cruz Zazpe, Iranzu González-Borja, Bruno Sangro, Jose M Herranz, Ana Purroy, Isabel Gil, Leonard J Nelson, Juan J Vila, Marcin Krawczyk, Krzysztof Zieniewicz, Waldemar Patkowski, Piotr Milkiewicz, Francisco Javier Cubero, Gorka Alkorta-Aranburu, Maite G Fernandez-Barrena, Jesus M Urman, Carmen Berasain, Matias A Avila
Journal: Gut (2021)

Objective Despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). Design A prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. Results An initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. Conclusion Implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.