tbuckley/cabot-search huggingface dataset:
Exosome-inflammasome crosstalk and their roles in inflammatory responses
Authors: Chadanat Noonin, Visith Thongboonkerd
Journal: Theranostics (2021)

Inflammasome is a complex of multiple proteins found in cytoplasm of the cells activated by infectious and/or non-infectious stimuli. This complex involves caspase-1 activation, leading to unconventional secretion of interleukin-1β (IL-1β) and IL-18 and inflammatory cascade. Exosome is the nanoscale membrane-bound extracellular vesicle that plays significant roles in intercellular communications by carrying bioactive molecules, e.g., proteins, RNAs, microRNAs (miRNAs), DNAs, from one cell to the others. In this review, we provide the update information on the crosstalk between exosome and inflammasome and their roles in inflammatory responses. The effects of inflammasome activation on exosomal secretion are summarized. On the other hand, the (dual) effects of exosomes on inhibiting and promoting inflammasome activation are discussed. Finally, perspectives on therapeutic roles of exosomes in human diseases and future direction of the research on exosome-inflammasome crosstalk are provided.
Factors Contributing to Missing COVID-19 Cases During Contact Tracing—Reply
Authors: Darpun D. Sachdev, Stephanie E. Cohen, Susan Scheer
Journal: JAMA Internal Medicine (2021)

Darpun D. Sachdev, MD; Hannah K. Brosnan, MPH; Michael J. A. Reid, MD, MPH; Michelle Kirian, MPH; Stephanie E. Cohen, MD, MPH; Trang Q. Nguyen, PhD, MPH; Susan Scheer, PhD, MPH
Abstract 13368: Clinical Impact of Heart Rate Change in Early Phase in Patients With Acute Decompensated Heart Failure
Authors: shingo kazama, Toru Kondo, Yuki Kimura, Naoki Shibata, Hideo Oishi, Takashi Araki, Takashi Mizutani, Tasuku Kuwayama, Hiroaki Hiraiwa, Ryota Morimoto, TAKAHIRO OKUMURA, Akinori Sawamura, Kiyokazu Shimizu, Toshiaki Kato, Toyoaki Murohara
Journal: Circulation (2020)

Introduction: Several studies have evaluated prognostic value of heart rate (HR) change during hospitalization in patients with acute heart failure (AHF). However, the relationship between HR change in early phase after admission and prognosis have not been fully elucidated. Hypothesis: The aim of this study was to evaluate the prognostic value of HR change in early phase in patients with AHF. Methods: We used a data of multicenter retrospective registry for the consecutive hospitalized patients due to AHF since January 2012 to March 2019. Patients were divided into three groups according to tertiles of HR at admission: lower tertile, HR &lt;85 bpm; middle tertile, HR 85-108 bpm; higher tertile, HR &gt;108 bpm. And, (HR [at admission] - HR [at 12 hour after admission]) * 100 / HR [at admission] was calculated as HR change (%). Results: Total of 1625 patients were analyzed. The median HR at admission was 96 bpm, and HR decreased to 81 bpm at 12 hours after admission (p &lt; 0.001). Larger HR change was observed according to increase in HR at admission (HR change; lower tertile, 1.0%; middle tertile, 12.5%, higher tertile, 38.0%, p &lt; 0.001). In Kaplan-Meier analysis, the cumulative event-free rates in the composite endpoint of death and re-hospitalization due to AHF showed better according to higher HR at admission (p &lt; 0.001, log-rank) (Figure). After dividing the patient into two groups in each tertiles based on the median HR change, the cumulative event-free rates were comparable between higher HR change group and lower HR change group in all tertiles (Figure). Cox proportional hazards analysis showed that HR change was not the independent predictors of composite endpoint adjusted by covariates in each tertile (lower tertile, p = 0.81; middle tertile, p = 0.78; higher tertile, p = 0.90). Conclusions: HR decreased significantly until 12 hours after admission. However, HR change in early phase did not have prognostic value in patients with AHF.
MA05.08 Impact of Low-Dose CT Screening for Primary Lung Cancer on Subsequent Risk of Brain Metastasis: Secondary Analysis of NLST
Authors: C.C. Su, J. Wu, J. Neal, R. Popat, L. Backhus, A. Leung, S. Nagpal, H.A. Wakelee, S. Han
Journal: Journal of Thoracic Oncology (2021)
Development and validation of the Brigham Eyelash Tool for Alopecia (BELA): A measure of eyelash alopecia areata
Authors: Priya Manjaly, Sara J. Li, Elizabeth Tkachenko, Justin M. Ko, Kristina J. Liu, Deborah A. Scott, Maryanne M. Senna, Cara J. Joyce, Arash Mostaghimi, Kathie P. Huang
Journal: Journal of the American Academy of Dermatology (2021)
Short-Term sequelae of Multisystem Inflammatory Syndrome in Children Assessed by CMR
Authors: Ivan Altamar Bermejo, Carles Bautista-Rodriguez, Alain Fraisse, Inga Voges, Peter Gatehouse, Heechan Kang, Enrico Piccinelli, Giselle Rowlinson, Mary Lane, Thomas Semple, Sara Moscatelli, Maria Dwornik, Amrit Lota, Giovanni Di Salvo, Ricardo Wage, Sanjay K. Prasad, Raad Mohiaddin, Dudley J. Pennell, Sylvia Krupickova
Journal: JACC. Cardiovascular imaging (2021)
Characterization of drug-induced human mitochondrial ADP/ATP carrier inhibition
Authors: Stephany Jaiquel Baron, Martin S. King, Edmund R.S. Kunji, Tom J.J. Schirris
Journal: Theranostics (2021)

An increasing number of commonly prescribed drugs are known to interfere with mitochondrial function, causing cellular toxicity, but the underlying mechanisms are largely unknown.Although often not considered, mitochondrial transport proteins form a significant class of potential mitochondrial off-targets.So far, most drug interactions have been reported for the mitochondrial ADP/ATP carrier (AAC), which exchanges cytosolic ADP for mitochondrial ATP.Here, we show inhibition of cellular respiratory capacity by only a subset of the 18 published AAC inhibitors, which questions whether all compound do indeed inhibit such a central metabolic process.This could be explained by the lack of a simple, direct model system to evaluate and compare drug-induced AAC inhibition.Methods: For its development, we have expressed and purified human AAC1 (hAAC1) and applied two approaches.In the first, thermostability shift assays were carried out to investigate the binding of these compounds to human AAC1.In the second, the effect of these compounds on transport was assessed in proteoliposomes with reconstituted human AAC1, enabling characterization of their inhibition kinetics.Results: Of the proposed inhibitors, chebulinic acid, CD-437 and suramin are the most potent with IC50-values in the low micromolar range, whereas another six are effective at a concentration of 100 µM.Remarkably, half of all previously published AAC inhibitors do not show significant inhibition in our assays, indicating that they are false positives.Finally, we show that inhibitor strength correlates with a negatively charged surface area of the inhibitor, matching the positively charged surface of the substrate binding site.Conclusion: Consequently, we have provided a straightforward model system to investigate AAC inhibition and have gained new insights into the chemical compound features important for inhibition.Better evaluation methods of drug-induced inhibition of mitochondrial transport proteins will contribute to the development of drugs with an enhanced safety profile.
Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes Insipidus
Authors: Federica Petrillo, Anna Iervolino, Tiziana Angrisano, Sabina Jelen, Vincenzo Costanzo, Mariavittoria D’Acierno, Lei Cheng, Qi Wu, Ilaria Guerriero, Maria Cristina Mazzarella, Alfonso De Falco, Fulvio D’Angelo, Michele Ceccarelli, Michele Caraglia, Giovambattista Capasso, Robert A. Fenton, Francesco Trepiccione
Journal: Journal of the American Society of Nephrology (2021)

MicroRNAs (miRNAs), formed by cleavage of pre-microRNA by the endoribonuclease Dicer, are critical modulators of cell function by post-transcriptionally regulating gene expression.Selective ablation of Dicer in AQP2-expressing cells (DicerAQP2Cre+ mice) was used to investigate the role of miRNAs in the kidney collecting duct of mice.The mice had severe polyuria and nephrogenic diabetes insipidus, potentially due to greatly reduced AQP2 and AQP4 levels. Although epithelial sodium channel levels were decreased in cortex and increased in inner medulla, amiloride-sensitive sodium reabsorption was equivalent in DicerAQP2Cre+ mice and controls. Small-RNA sequencing and proteomic analysis revealed 31 and 178 significantly regulated miRNAs and proteins, respectively. Integrated bioinformatic analysis of the miRNAome and proteome suggested alterations in the epigenetic machinery and various transcription factors regulating AQP2 expression in DicerAQP2Cre+ mice. The expression profile and function of three miRNAs (miR-7688-5p, miR-8114, and miR-409-3p) whose predicted targets were involved in epigenetic control (Phf2, Kdm5c, and Kdm4a) or transcriptional regulation (GATA3, GATA2, and ELF3) of AQP2 were validated. Luciferase assays could not demonstrate direct interaction of AQP2 or the three potential transcription factors with miR-7688-5p, miR-8114, and miR-409-3p. However, transfection of respective miRNA mimics reduced AQP2 expression. Chromatin immunoprecipitation assays demonstrated decreased Phf2 and significantly increased Kdm5c interactions at the Aqp2 gene promoter in DicerAQP2Cre+ mice, resulting in decreased RNA Pol II association.Novel evidence indicates miRNA-mediated epigenetic regulation of AQP2 expression.
Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial
Authors: Antonio M Risitano, Alexander Röth, Juliette Soret, Camilla Frieri, Flore Sicre de Fontbrune, Luana Marano, Ferras Alashkar, Lina Benajiba, Serena Marotta, Izabela Rozenberg, Julie Milojevic, Peter End, Prasanna K Nidamarthy, Guido Junge, Régis Peffault de Latour
Journal: The Lancet Haematology (2021)
Hyaluronan is a natural and effective immunological adjuvant for protein-based vaccines
Authors: Anna Dalla Pietà, Debora Carpanese, Antonella Grigoletto, Anna Tosi, Silvia Dalla Santa, Gabriel Kristian Pedersen, Dennis Christensen, Laura Meléndez-Alafort, Vito Barbieri, Paola De Benedictis, Gianfranco Pasut, Isabella Monia Montagner, Antonio Rosato
Journal: Cellular and Molecular Immunology (2021)

Abstract One of the main goals of vaccine research is the development of adjuvants that can enhance immune responses and are both safe and biocompatible. We explored the application of the natural polymer hyaluronan (HA) as a promising immunological adjuvant for protein-based vaccines. Chemical conjugation of HA to antigens strongly increased their immunogenicity, reduced booster requirements, and allowed antigen dose sparing. HA-based bioconjugates stimulated robust and long-lasting humoral responses without the addition of other immunostimulatory compounds and proved highly efficient when compared to other adjuvants. Due to its intrinsic biocompatibility, HA allowed the exploitation of different injection routes and did not induce inflammation at the inoculation site. This polymer promoted rapid translocation of the antigen to draining lymph nodes, thus facilitating encounters with antigen-presenting cells. Overall, HA can be regarded as an effective and biocompatible adjuvant to be exploited for the design of a wide variety of vaccines.
Sleep quality and daytime sleepiness in epilepsy: Systematic review and meta-analysis of 25 studies including 8,196 individuals
Authors: Melanie Bergmann, Lena Tschiderer, Ambra Stefani, Anna Heidbreder, Peter Willeit, Birgit Högl
Journal: Sleep Medicine Reviews (2021)

We sought to gain a better understanding of the relationship between epilepsy and sleep quality and daytime sleepiness by performing a literature search of PubMed for case–control studies that compared patients with epilepsy to controls and reported the Pittsburgh sleep quality index (PSQI) and/or the Epworth sleepiness scale (ESS). Study-specific mean differences in the PSQI and ESS between cases and controls were extracted from the publications and pooled using random-effects meta-analysis. Twenty-five studies (2964 cases, 5232 controls) were included. Fifteen studies reported the PSQI and 24 the ESS. Mean age was 40 years; 50.4% were women. When comparing cases to controls, the pooled mean differences in the PSQI and ESS were 1.27 (95% confidence interval (CI): 0.76, 1.78; P < 0.001; I2: 81.4%) and 0.38 (95% CI: −0.07, 0.84; P = 0.099; I2: 81.0%). Subgroup analyses revealed that mean differences in the ESS were significantly lower in studies with a higher proportion of patients with focal epilepsy (P = 0.004). In this large-scale meta-analysis patients with epilepsy had a higher PSQI, close to the pathological cut-off, compared to controls, but a similar and unremarkable ESS. Further studies are needed to investigate potential effect modifiers, such as specific antiepileptic drugs or seizure frequency.
Directed Evolution of an Enhanced POU Reprogramming Factor for Cell Fate Engineering
Authors: Daisylyn Senna Tan, Yanpu Chen, Ya Gao, Anastasia Bednarz, Yuanjie Wei, Vikas Malik, Derek Hoi-Hang Ho, Mingxi Weng, Sik Yin Ho, Yogesh Srivastava, Sergiy Velychko, Xiaoxiao Yang, Ligang Fan, Johnny Kim, Johannes Graumann, Gary D. Stormo, Thomas Braun, Jian Yan, Hans R. Schöler, Ralf Jauch
Journal: Molecular Biology and Evolution (2021)

Transcription factor-driven cell fate engineering in pluripotency induction, transdifferentiation, and forward reprogramming requires efficiency, speed, and maturity for widespread adoption and clinical translation. Here, we used Oct4, Sox2, Klf4, and c-Myc driven pluripotency reprogramming to evaluate methods for enhancing and tailoring cell fate transitions, through directed evolution with iterative screening of pooled mutant libraries and phenotypic selection. We identified an artificially evolved and enhanced POU factor (ePOU) that substantially outperforms wild-type Oct4 in terms of reprogramming speed and efficiency. In contrast to Oct4, not only can ePOU induce pluripotency with Sox2 alone, but it can also do so in the absence of Sox2 in a three-factor ePOU/Klf4/c-Myc cocktail. Biochemical assays combined with genome-wide analyses showed that ePOU possesses a new preference to dimerize on palindromic DNA elements. Yet, the moderate capacity of Oct4 to function as a pioneer factor, its preference to bind octamer DNA and its capability to dimerize with Sox2 and Sox17 proteins remain unchanged in ePOU. Compared with Oct4, ePOU is thermodynamically stabilized and persists longer in reprogramming cells. In consequence, ePOU: 1) differentially activates several genes hitherto not implicated in reprogramming, 2) reveals an unappreciated role of thyrotropin-releasing hormone signaling, and 3) binds a distinct class of retrotransposons. Collectively, these features enable ePOU to accelerate the establishment of the pluripotency network. This demonstrates that the phenotypic selection of novel factor variants from mammalian cells with desired properties is key to advancing cell fate conversions with artificially evolved biomolecules.
P14.09 Early Expansion of M-MDSCs and High Plasma TSLP levels as Predictors of Primary Resistance to PD1 Inhibitors in Metastatic NSCLC
Authors: S. Lau, S. Wong, B. Wang, D. Patel, A. Fares, M. Tsao, P. Bradbury, G. Liu, F. Shepherd, N. Leighl, T. Mcgaha, P. Ohashi, A. Sacher
Journal: Journal of Thoracic Oncology (2021)
P38.14 Demographic and Molecular Epidemiologic Profile of Primary Lung Cancer in Eastern India
Authors: P. Mohapatra, S. Bhuniya, M. Panigrahi, S. Bal, S. Patra, S. Das Majumdar, P. Mishra, S. Mohakud, S. Naik, M. Kar, D. Muduly, S. Padmaja, M.K. K, S. Ghosh, S. Panigrahi, G. Durgeshwar, V.R. Acharyulu, D. Parida
Journal: Journal of Thoracic Oncology (2021)
Recent Randomized Trials of Antithrombotic Therapy for Patients With COVID-19
Authors: Azita H. Talasaz, Parham Sadeghipour, Hessam Kakavand, Maryam Aghakouchakzadeh, Elaheh Kordzadeh-Kermani, Benjamin W. Van Tassell, Azin Gheymati, Hamid Ariannejad, Seyed Hossein Hosseini, Sepehr Jamalkhani, Michelle Sholzberg, Manuel Monreal, David Jimenez, Gregory Piazza, Sahil A. Parikh, Ajay J. Kirtane, John W. Eikelboom, Jean M. Connors, Beverley J. Hunt, Stavros V. Konstantinides, Mary Cushman, Jeffrey I. Weitz, Gregg W. Stone, Harlan M. Krumholz, Gregory Y.H. Lip, Samuel Z. Goldhaber, Behnood Bikdeli
Journal: Journal of the American College of Cardiology (2021)
Large fuzzy biodegradable polyester microspheres with dopamine deposition enhance cell adhesion and bone regeneration in vivo
Authors: Deteng Zhang, Honghao Zheng, Keyu Geng, Jianhua Shen, Xue Feng, Peifang Xu, Yiyuan Duan, Yifan Li, Ronghuan Wu, Zhongru Gou, Changyou Gao
Journal: Biomaterials (2021)
NHS backlog: Realism is needed about how far £8.1bn will stretch, say health leaders
Authors: Jacqui Wise
Journal: BMJ (2021)

NHS England has set out an £8.1bn (€9.5bn; $11.2bn) plan to tackle the backlog of care caused by the covid-19 pandemic and to provide more support for burnt out healthcare workers. The plan has been welcomed for providing clarity for the year ahead, but professional organisations have warned that the government must be realistic about how far the funding will stretch. The NHS’s operational planning guidance outlines how the NHS will operate in 2021-22.1 The government has agreed an additional £8.1bn for the first six months of the year, and the financial settlement for the second half will be agreed later. The sum includes £1.5bn allocated for elective recovery, mental health, and workforce development. The plan includes:
The dark side of daylight: photoaging and the tumor microenvironment in melanoma progression
Authors: Asurayya Worrede, Stephen M. Douglass, Ashani T. Weeraratna
Journal: Journal of Clinical Investigation (2021)

Continued thinning of the atmospheric ozone, which protects the earth from damaging ultraviolet radiation (UVR), will result in elevated levels of UVR reaching the earth’s surface, leading to a drastic increase in the incidence of skin cancer. In addition to promoting carcinogenesis in skin cells, UVR is a potent extrinsic driver of age-related changes in the skin known as “photoaging.” We are in the preliminary stages of understanding of the role of intrinsic aging in melanoma, and the tumor-permissive effects of photoaging on the skin microenvironment remain largely unexplored. In this Review, we provide an overview of the impact of UVR on the skin microenvironment, addressing changes that converge or diverge with those observed in intrinsic aging. Intrinsic and extrinsic aging promote phenotypic changes to skin cell populations that alter fundamental processes such as melanogenesis, extracellular matrix deposition, inflammation, and immune response. Given the relevance of these processes in cancer, we discuss how photoaging might render the skin microenvironment permissive to melanoma progression.
P19.04 Effect of Local Therapy on Survival in Oligometastatic Epidermal Growth Factor Receptor (EGFR) Mutated Non-Small Cell Lung Cancer (NSCLC)
Authors: Y.Y. Soon, C.C. Lee, W.Y. Koh, C.N. Leong, J. Tey
Journal: Journal of Thoracic Oncology (2021)
Effectiveness of the Pfizer-BioNTech COVID-19 Vaccine Among Residents of Two Skilled Nursing Facilities Experiencing COVID-19 Outbreaks — Connecticut, December 2020–February 2021
Authors: Amadea Britton, Kara M. Jacobs Slifka, Chris Edens, Srinivas Acharya Nanduri, Stephen M. Bart, Nong Shang, Adora Harizaj, Jillian Armstrong, Kerui Xu, Hanna Y. Ehrlich, Elizabeth Soda, Gordana Derado, Jennifer R. Verani, Stephanie J. Schrag, John A. Jernigan, Vivian H. Leung, Sunil Parikh
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

This report describes an analysis of two Connecticut skilled nursing facilities that found partial vaccination, >14 days after the first dose through 7 days after the second dose, with the Pfizer-BioNTech COVID-19 vaccine 63% effective against SARS-CoV-2 infection.
The Prognostic Role of Magnetic Resonance Imaging Biomarkers in Mild Traumatic Injury
Authors: Elie Massaad, John H. Shin, Wende N. Gibbs
Journal: JAMA Network Open (2021)

Sophie Richter, MD; Stefan Winzeck, MSc; Evgenios N. Kornaropoulos, PhD; Tilak Das, MD, PhD; Thijs Vande Vyvere, PhD; Jan Verheyden, MSc; Guy B. Williams, PhD; Marta M. Correia, PhD; David K. Menon, MD, PhD; Virginia F. J. Newcombe, MD, PhD; Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Magnetic Resonance Imaging (CENTER-TBI MRI) Substudy Participants and Investigators
P79.06 CHIO3: ChEmotherapy Combined with Immune Checkpoint Inhibitor for Operable Stage IIIA/B Non-Small Cell Lung Cancer (AFT-46)
Authors: L. Martin, X. Wang, J. Patel, D. Kozono, C. Crocker, J. Urbanic, E. Vokes, T. Stinchcombe
Journal: Journal of Thoracic Oncology (2021)
LncRNA PRADX-mediated recruitment of PRC2/DDX5 complex suppresses UBXN1 expression and activates NF-κB activity, promoting tumorigenesis
Authors: Yansheng Li, Xing Liu, Xiaoteng Cui, Yanli Tan, Qixue Wang, Yunfei Wang, Can Xu, Chuan Fang, Chunsheng Kang
Journal: Theranostics (2021)

Rationale: Accumulating evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in cancer progression; however, only few have been characterized in detail. The current study aimed to identify a novel cancer driver lncRNA in glioblastoma and colon adenocarcinoma. Methods: We performed whole transcriptome analysis of TCGA pan-cancer datasets to compare the lncRNA expression profiles of tumor and paired normal tissues. In situ hybridization of tissue sections was performed to validate the expression data and determine the localization of lncRNAs that may be linked to glioblastoma and colon adenocarcinoma. Chromatin isolation by RNA purification (ChIRP), chromatin immunoprecipitation (ChIP), and Co-immunoprecipitation (Co-IP) assays were performed to assess the interaction between lncRNA, proteins, and chromatin. The functional significance of the identified lncRNAs was verified in vitro and in vivo by knockdown or exogenous expression experiments. Results: We found a lncRNA ENST00000449248.1 termed PRC2 and DDX5 associated lncRNA (PRADX) that is highly expressed in glioblastoma and colon adenocarcinoma cells and tissues. PRADX, mainly located in the nucleus of tumor cells, could bind to EZH2 protein via the 5' terminal sequence. Moreover, PRADX increased the trimethylation of H3K27 in the UBXN1 gene promoter via PRC2/DDX5 complex recruitment and promoted NF-κB activity through UBXN1 suppression. Knockdown of PRADX significantly inhibited tumor cell viability and clonogenic growth in vitro. In xenograft models, PRADX knockdown suppressed tumor growth and tumorigenesis and prolonged the survival of tumor-bearing mice. Conclusions: PRADX acts as a cancer driver and may serve as a potential therapeutic target for glioblastoma and colon adenocarcinoma.
P42.06 Automatic Lung Nodule Detection by a Deep Learning-Based CAD System: The Value of Slab Thickness in the Maximum Intensity Projection Technique
Authors: S. Zheng, X. Cui, M. Vonder, R. Veldhuis, M. Dorrius, Z. Ye, R. Vliegenthart, M. Oudkerk, P. Van Ooijen
Journal: Journal of Thoracic Oncology (2021)
Endoscopic removal of a fractured esophageal stent from the mediastinum and leak closure with endoscopic vacuum therapy
Authors: Seung-Hun Chon, Eleonora Ramadori, Daniel Pinto dos Santos, Florian Lorenz, Hakan Alakus, Tobias Goeser, Christiane Josephine Bruns
Journal: Endoscopy (2021)

Self-expanding metal stents (SEMSs) are effective and safe for the treatment of esophageal leaks [1] [2]. However, optimal timing of stent removal is vital, as hyperplasia of the tissue can make it challenging [3] [4]. Complications range from bleeding and stent overgrowth requiring multiple endoscopic procedures to perforation requiring surgical repair [5].