tbuckley/cabot-search huggingface dataset:
Inhibition of tumor progression and M2 microglial polarization by extracellular vesicle-mediated microRNA-124 in a 3D microfluidic glioblastoma microenvironment
Authors: Soohyun Hong, Jae Young You, Kyurim Paek, Jubin Park, Su Jin Kang, Eun Hee Han, Nakwon Choi, Seok Chung, Won Jong Rhee, Jeong Ah Kim
Journal: Theranostics (2021)

Background: Glioblastoma (GBM) is one of the most aggressive types of brain cancer. GBM progression is closely associated with microglia activation; therefore, understanding the regulation of the crosstalk between human GBM and microglia may help develop effective therapeutic strategies. Elucidation of efficient delivery of microRNA (miRNA) via extracellular vesicles (EVs) and their intracellular communications is required for therapeutic applications in GBM treatment. Methods: We used human GBM cells (U373MG) and human microglia. MiRNA-124 was loaded into HEK293T-derived EVs (miR-124 EVs). Various anti-tumor effects (proliferation, metastasis, chemosensitivity, M1/M2 microglial polarization, and cytokine profile) were investigated in U373MG and microglia. Anti-tumor effect of miR-124 EVs was also investigated in five different patient-derived GBM cell lines (SNU-201, SNU-466, SNU-489, SNU-626, and SNU-1105). A three-dimensional (3D) microfluidic device was used to investigate the interactive microenvironment of the tumor and microglia. Results: MiR-124 EVs showed highly efficient anti-tumor effects both in GBM cells and microglia. The mRNA expression levels of tumor progression and M2 microglial polarization markers were decreased in response to miR-124 EVs. The events were closely related to signal transducer and activator of transcription (STAT) 3 signaling in both GBM and microglia. In 3D microfluidic experiments, both U373MG and microglia migrated to a lesser extent and showed less-elongated morphology in the presence of miR-124 EVs compared to the control. Analyses of changes in cytokine levels in the microfluidic GBM-microglia environment showed that the treatment with miR-124 EVs led to tumor suppression and anti-cancer immunity, thereby recruiting natural killer (NK) cells into the tumor. Conclusions: In this study, we demonstrated that EV-mediated miR-124 delivery exerted synergistic anti-tumor effects by suppressing the growth of human GBM cells and inhibiting M2 microglial polarization. These findings provide new insights toward a better understanding of the GBM microenvironment and provide substantial evidence for the development of potential therapeutic strategies using miRNA-loaded EVs.
892 COPPER AVAILABILITY CONTRIBUTES TO IRON PERTUBATIONS IN HUMAN NON-ALCOHOLIC FATTY LIVER DISEASE
Authors: E. Aigner, I. Theurl, H. Haufe, M. Seifert, F. Hohla, L. Scharinger, F. Stickel, G. Weiss, C. Datz
Journal: Journal of Hepatology (2008)
What Matters Most
Authors: Jonathan C. Yeh
Journal: Annals of Internal Medicine (2021)

Ad LibitumOctober 2021What Matters MostJonathan C. Yeh, MDJonathan C. Yeh, MDBeth Israel Deaconess Medical Center, Boston, MassachusettsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-7506 Audio Reading - “What Matters Most” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “What Matters Most” by Jonathan C. Yeh, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail “Just knowing that ... Author, Article, and Disclosure InformationAffiliations: Beth Israel Deaconess Medical Center, Boston, MassachusettsCurrent Author Address: Jonathan C. Yeh, MD, 330 Brookline Avenue, Yamins 100, Boston, MA 02215; e-mail, [email protected]harvard.edu. PreviousarticleNextarticle Advertisement Audio Reading - “What Matters Most” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “What Matters Most” by Jonathan C. Yeh, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics October 2021Volume 174, Issue 10Page: 1492 ePublished: 19 October 2021 Issue Published: October 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Helen Salisbury: Continuity saves lives
Authors: Helen Salisbury
Journal: BMJ (2021)

A new research paper tells us (again) about the benefits of continuity of care. It shows that patients who stayed registered with the same GP over many years had fewer out-of-hours appointments and acute hospital admissions, as well as a reduced risk of death.1 These benefits were significant, and they increased the longer the relationship continued. In 2018, people who had kept the same GP for more than 15 years had a 25% lower chance of dying than those with a GP relationship lasting a year or less.

We spend a lot of our time prescribing …
PL02.05 IMpower010: Characterization of Stage IB-IIIA NSCLC Patients by Type and Extent of Therapy Prior to Adjuvant Atezolizumab
Authors: N. Altorki, E. Felip, C. Zhou, E. Vallieres, V. Moiseyenko, A. Smolin, A. Rittmeyer, R. Vereshchako, M. Perol, W. Schutte, J. Fang, M. Tao, E. Teixeira, Y. Kim, B. Gitlitz, E. Bennett, V. Mcnally, F. Wu, Y. Deng, H. Wakelee
Journal: Journal of Thoracic Oncology (2021)
Therapeutic potential of garlic chive-derived vesicle-like nanoparticles in NLRP3 inflammasome-mediated inflammatory diseases
Authors: Baolong Liu, Xingzhi Li, Han Yu, Xuan Shi, You Zhou, Sophie Alvarez, Michael J Naldrett, Stephen D Kachman, Seung-Hyun Ro, Xinghui Sun, Soonkyu Chung, Lili Jing, Jiujiu Yu
Journal: Theranostics (2021)

Aberrant activation of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome drives the development of many complex inflammatory diseases, such as obesity, Alzheimer's disease, and atherosclerosis. However, no medications specifically targeting the NLRP3 inflammasome have become clinically available. Therefore, we aim to identify new inhibitors of the NLRP3 inflammasome in this study. Methods: Vesicle-like nanoparticles (VLNs) were extracted from garlic chives and other Allium vegetables and their effects on the NLRP3 inflammasome were evaluated in primary macrophages. After garlic chive-derived VLNs (GC-VLNs) were found to exhibit potent anti-NLRP3 inflammasome activity in cell culture, such function was further assessed in a murine acute liver injury disease model, as well as in diet-induced obesity. Finally, GC-VLNs were subjected to omics analysis to identify the active components with anti-NLRP3 inflammasome function. Results: GC-VLNs are membrane-enclosed nanoparticles containing lipids, proteins, and RNAs. They dose-dependently inhibit pathways downstream of NLRP3 inflammasome activation, including caspase-1 autocleavage, cytokine release, and pyroptotic cell death in primary macrophages. The inhibitory effects of GC-VLNs on the NLRP3 inflammasome are specific, considering their marginal impact on activation of other inflammasomes. Local administration of GC-VLNs in mice alleviates NLRP3 inflammasome-mediated inflammation in chemical-induced acute liver injury. When administered orally or intravenously, GC-VLNs accumulate in specific tissues and suppress activation of the NLRP3 inflammasome and chronic inflammation in diet-induced obese mice. The phospholipid 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) in GC-VLNs has been identified to inhibit NLRP3 inflammasome activation. Conclusions: Identification of GC-VLNs and their active component DLPC as potent inflammasome inhibitors provides new therapeutic candidates in the treatment of NLRP3 inflammasome-driven diseases.
Relationship of Mechanical Dyssynchrony and LV Remodeling With Improvement of Mitral Regurgitation After CRT
Authors: Blazej Michalski, Ivan Stankovic, Efstathios Pagourelias, Agnieszka Ciarka, Marit Aarones, Stefan Winter, Lothar Faber, Svend Aakhus, Wolfgang Fehske, Marta Cvijic, Jens-Uwe Voigt
Journal: JACC. Cardiovascular imaging (2021)
Management of Amyloid Cardiomyopathy in Resource-Constrained Settings
Authors: Suvir Singh, Rohit Tandon, Bishav Mohan
Journal: JACC CardioOncology (2021)

A myloid cardiomyopathy (AC) is characterized by extracellular deposition of amyloid fibrils and is an aggressive form of heart disease, often resistant to conventional heart failure (HF) therapies.Data regarding AC from resourceconstrained settings such as India are sparse, although it is clear that most patients present late with symptomatic HF and without access to a full diagnostic workup.We provide a snapshot of the current clinical landscape of AC in India and highlight existing challenges and potential opportunities in this context.The discussion presented below is applicable to most resource-limited settings worldwide.The incidence of myeloma in India ranges from 0.97 to 1.26 per 100,000 population, indicating approximately 15,000 new patients diagnosed every year.Of these patients, approximately 12%-15% are expected to have light-chain (AL) amyloidosis, with 50% having cardiac involvement (1).By this estimate, India should have approximately 900-1,200 newly diagnosed patients with AC per year.However, literature searches (PubMed with the terms "cardiac amyloid AND India" or "amyloid cardiomyopathy
Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomised, double-blind crossover trial
Authors: Antonio Uccelli, Alice Laroni, Rehiana Ali, Mario Alberto Battaglia, Morten Blinkenberg, Lou Brundin, Michel Clanet, Oscar Fernandez, James Marriott, Paolo Muraro, Seyed Massood Nabavi, Roberto S Oliveri, Ernst Radue, Cristina Ramo Tello, Irene Schiavetti, Johann Sellner, Per Soelberg Sorensen, Maria Pia Sormani, Jens Thomas Wuerfel, Mark S Freedman, Naser Aghdami, Eduardo Agüera-Morales, Rehiana Ali, David Allan, Leila Arab, Mario Battaglia, Isabelle Berry, Morten Blinkenberg, Bruno Bonetti, Lou Brundin, Chiara Capelli, Lucio Castellan, Maria Cellerino, Maria Teresa Cencioni, Michel Clanet, Giancarlo Comi, David Courtman, Francesco Dazzi, Anne Fischer-Nielsen, Oscar Fernandez, Victoria Fernandez, Mark S. Freedman, Roberto Furlan, Mario Gimona, Francesca Gualandi, Qingdong Guan, Ellen Iacobaeus, Matilde Inglese, Martino Introna, Guillermo Izquierdo, Shahedeh Karimi, Alice Laroni, Katarina Le Blanc, Sandra Loaiza, Shahrukh Mallik, Stephen Marley, Ruth Ann Marrie, James Marriot, Gianvito Martino, Seyed Massood Nabavi, David Miller, Paolo A. Muraro, Richard Nicholas, Roberto S Oliveri, Giovanni Orengo, Renuka Palanicawande, Matteo Pardini, Ernst W Radue, Cristina Ramo Tello, Carolina Rush, Irene Schiavetti, Johann Sellner, Luc Sensebe, Per Soelberg Sorensen, Maria Pia Sormani, Dirk Strunk, David Szwajcer, Claire Thalamas, Antonio Uccelli, Jens Thomas Wuerfel
Journal: The Lancet Neurology (2021)
Abstract 16742: Early Recurrence of Ventricular Tachycardia is Associated With Greater One-Year Mortality Among Patients With Severe Heart Failure
Authors: Natalie M Beck, Peter J Sauer, Alexis Z Tumolo, Amneet Sandhu, Matthew M Zipse, Ryan T Borne, Duy T Nguyen, Joseph L Schuller, Ryan G Aleong, Christine Tompkins, Paul D Varosy, Michael Rosenberg, Prateeti Khazanie, Natasha Altman, Andreas Brieke, William Cornwell, Eugene Wolfel, Amrut Ambardekar, Larry Allen, Wendy S Tzou
Journal: Circulation (2018)

Background: Ventricular tachycardia (VT) is common in patients with severe heart failure (HF). Objective: We sought to determine whether early recurrence of VT is associated with worse survival. Methods: We performed retrospective analysis of patients presenting to a tertiary referral hospital between 2006-2017 with VT and severe HF (defined as New York Heart Association functional Class IV or any Interagency Registry for Mechanically Assisted Circulatory Support score) for whom electrophysiology consultation was requested. A comparison was made in baseline characteristics and outcomes between those with early VT recurrence (within 30 days of initial consult) and those without early VT recurrence. Results: Of 129 patients, 47% underwent ablation while 53% were managed medically. Mean age was 60±12 years, 84% were males, ischemic cardiomyopathy was present in 55%, mean LVEF was 24±12%, and 77% had a preexisting ICD. Early recurrence of VT was observed in 25 patients (19%). Those with early recurrence had lower mean LVEF (20±7% vs 25±12%, p =0.032), were less likely to have an ICD prior to presentation (56% vs 82%, p =0.015), were more likely to have been treated with only medications (80% vs 20%, p =0.003), had greater in-hospital mortality (28% vs 5%, p =0.002) and experienced a longer hospitalization (23±19 vs 17±16 days), compared to those without early recurrence. There was no significant difference in other baseline characteristics between groups. Patients with early recurrence had significantly worse 1-year survival 56% vs 82% (Figure), with OR 3.5, 95% CI [1.3,8.9]. Conclusion: Early VT recurrence among patients with severe heart failure is associated with increased mortality within the year following presentation. VT ablation should be considered to help mitigate risk of early recurrence and associated morbidity in such patients.
Cardiovascular Magnetic Resonance for Patients With COVID-19
Authors: Steffen E. Petersen, Matthias G. Friedrich, Tim Leiner, Matthew D. Elias, Vanessa M. Ferreira, Maximilian Fenski, Scott D. Flamm, Mark Fogel, Ria Garg, Marc K. Halushka, Allison G. Hays, Nadine Kawel-Boehm, Christopher M. Kramer, Eike Nagel, Ntobeko A.B. Ntusi, Ellen Ostenfeld, Dudley J. Pennell, Zahra Raisi-Estabragh, Scott B. Reeder, Carlos E. Rochitte, Jitka Starekova, Dominika Suchá, Qian Tao, Jeanette Schulz-Menger, David A. Bluemke
Journal: JACC. Cardiovascular imaging (2021)
P45.06 Overall Survival From a Phase 2 Study of Crizotinib in East Asian Patients With ROS1+ Advanced Non-Small-Cell Lung Cancer
Authors: Y. Wu, S. Lu, J.C. Yang, J. Zhou, T. Seto, M. Ahn, W. Su, N. Yamamoto, D. Kim, J. Paolini, T. Usari, K. Wilner, K. Goto
Journal: Journal of Thoracic Oncology (2021)
19P Predictors of osimertinib response at second-line treatment in EGFR mutant non-small cell lung cancer patients with acquired T790M resistance mutation
Authors: I. Dogan, M. Gürbüz, N. Paksoy, N. Khanmamadov, S. Vatansever, P. Saip, A. Demirkazik, A. Aydiner
Journal: Annals of Oncology (2021)
In vitro recovery of FIX clotting activity as a marker of highly functional hepatocytes in a hemophilia B iPSC model
Authors: Eléanor Luce, Clara Steichen, Mickaël Allouche, Antonietta Messina, Jean‐Marie Heslan, Thierry Lambert, Anne Weber, Tuan Huy Nguyen, Olivier Christophe, Anne Dubart‐Kupperschmitt
Journal: Hepatology (2021)

Abstract Background and Aims Pluripotent stem cell–derived hepatocytes differentiated in monolayer culture are known to have more fetal than adult hepatocyte characteristics. If numerous studies tend to show that this immature phenotype might not necessarily be an obstacle to their use in transplantation, other applications such as drug screening, toxicological studies, or bioartificial livers are reliant on hepatocyte functionality and require full differentiation of hepatocytes. New technologies have been used to improve the differentiation process in recent years, usually evaluated by measuring the albumin production and CYP450 activity. Here we used the complex production and most importantly the activity of the coagulation factor IX (FIX) produced by mature hepatocytes to assess the differentiation of hemophilia B (HB) patient’s induced pluripotent stem cells (iPSCs) in both monolayer culture and organoids. Approach and Results Indeed, HB is an X‐linked monogenic disease due to an impaired activity of FIX synthesized by hepatocytes in the liver. We have developed an in vitro model of HB hepatocytes using iPSCs generated from fibroblasts of a severe HB patient. We used CRISPR/Cas9 technology to target the genomic insertion of a coagulation factor 9 minigene bearing the Padua mutation to enhance FIX activity. Noncorrected and corrected iPSCs were differentiated into hepatocytes under both two‐dimensional and three‐dimensional differentiation protocols and deciphered the production of active FIX in vitro. Finally, we assessed the therapeutic efficacy of this approach in vivo using a mouse model of HB. Conclusions Functional FIX, whose post‐translational modifications only occur in fully mature hepatocytes, was only produced in corrected iPSCs differentiated in organoids. Immunohistochemistry analyses of mouse livers indicated a good cell engraftment, and the FIX activity detected in the plasma of transplanted animals confirmed rescue of the bleeding phenotype.
Predictive regulatory and metabolic network models for systems analysis of Clostridioides difficile
Authors: Mario L Arrieta-Ortiz, Selva Rupa Christinal Immanuel, Serdar Turkarslan, Wei-Ju Wu, Brintha P Girinathan, Jay N Worley, Nicholas DiBenedetto, Olga Soutourina, Johann Peltier, Bruno Dupuy, Lynn Bry, Nitin S Baliga
Journal: Cell Host & Microbe (2021)
Correction to: Hyperkalemia in Chronic Kidney Disease in the New Era of Kidney Protection Therapies
Authors: José M. Valdivielso, Olga Balafa, Robert Ekart, Charles J. Ferro, Francesca Mallamaci, Patrick B. Mark, Patrick Rossignol, Pantelis Sarafidis, Lucia Del Vecchio, Alberto Ortiz
Journal: Drugs (2021)
John Studd: a towering figure in gynaecology
Authors: John Illman
Journal: BMJ (2021)

Photo credit: Mark Large/Daily Mail/Shutterstock

One of the most forthright doctors of his age, John Studd fired controversy in both the medical and the political arenas. Few other doctors have been driven to the same degree by the uncompromising belief that they were right.

Among the last of the old style, paternalistic consultants, he made enemies for his Thatcherite support of private healthcare, but he stands out as one of the towering figures in women’s medicine. The “Studd curve” features on every woman’s partogram and is one of the foundations of modern labour management. Studd also had a pioneering role in developing hormone replacement therapy (HRT) and launched the in vitro fertilisation unit at London’s Lister Hospital.

Studd may have been at his most outspoken in his contention that once child bearing was complete, the female reproductive organs were redundant. The risk of cancer, he argued, outweighed the benefits of natural but inconsistent oestrogen over HRT. He was found guilty of serious professional misconduct by the General Medical Council in 1997 for removing a woman’s ovaries without her consent.

But he was highly critical of the medical establishment. He is reported …
P57.10 Clinicopathological Analysis of Anti-Tumor Immunology-Related Factors After Chemoradiotherapy for Lung Cancer
Authors: M. Noguchi, H. Date, T. Menju, M. Hamaji, A. Ohsumi, D. Nakajima, Y. Yutaka, Y. Yamada, S. Tanaka, H. Kayawake
Journal: Journal of Thoracic Oncology (2021)
Abstract 16973: Thrombotic and Bleeding Outcomes of Pregnancy in Women With a Fontan Circulation
Authors: Andrea K Girnius, Dominica Zentner, Magalie Ladouceur, Mary Canobbio, Jamil Aboulhosn, Anne Marie Valente, Wendy Book, Elisa Bradley, Jasmine Grewal, Sara Partington, Morgan Venuti, Yonatan Buber, Barbara J Mulder, Berto Bouma, Nicholas Ollberding, Amita Mirani, Michelle Faust, Gruschen Veldtman
Journal: Circulation (2018)

Introduction: Patients with a Fontan circulation are at increased risk of bleeding as well as thrombosis. Current strategies to mitigate this risk during pregnancy are not well studied. Hypothesis: We hypothesize pregnant women with a Fontan circulation would have a higher risk of bleeding at baseline and anticoagulation (AC) therapy would increase this risk compared to antiplatelet (AP) therapy. Methods: This is an international multicenter retrospective cohort study of women with a history of Fontan palliation and pregnancy (2007-2017). Outcomes analyzed include AC/AP therapy and bleeding and thrombosis complications for each pregnancy. Results: There were 97 pregnancies in 74 women (26.9 +/- 4.6 years old, 25(25.5%) ending in miscarriage). Median gestational age at delivery was 35 weeks (IQR 7 weeks), with a birth weight of 2140grams (IQR 898). Bleeding complication occurred in 33 (35.1%) of pregnancies; the majority were from postpartum hemorrhage/PPH (30(88.2%)). 7(18%) patients required transfusion therapy. Of the 33 pregnancies with bleeding complications, 5 (15.2%) were on combination AC/AP therapy, 17 (50%) on isolated AC and 10 (29.4%) on isolated AP therapy. Only 1 patient with a bleeding event was on no therapy. In the non-bleeding complication cohort (n=37), 6 (16.2%) were on AC/AP therapy, 14 (37.8%) on isolated AC and 14 (37.8%) on isolated AP therapy. There were 3(8.1%) who received neither AC nor AP therapy. Thrombosis occurred in 2 patients (intracardiac n=1, thromboembolic event n=1), both of which were on combination AC/AP therapy. Conclusions: Bleeding risk is high in pregnant women with Fontan circulation, especially during the post-partum period. In this analysis, bleeding risk in those on therapy was higher than what is reported in non-Fontan populations receiving similar therapy. Further study is necessary to discern the relative contribution of anti-thrombotic and antiplatelet strategies to this risk. Thrombosis risk seems to have been effectively minimized with the above antithrombotic strategies.
Risk of SARS-CoV-2 transmission from on-field player contacts in amateur, youth and professional football (soccer)
Authors: Sebastian Schreiber, Oliver Faude, Barbara Gärtner, Tim Meyer, Florian Egger
Journal: British Journal of Sports Medicine (2021)

Objective To investigate the risk of transmission among potentially infectious SARS-CoV-2-positive football players while participating in training or matches at amateur, youth and professional levels. Methods Between August 2020 and March 2021, football players who tested positive for SARS-CoV-2 and participated in matches or training during the period of potential contagiousness were identified through media search (professional level) and a nationwide registry in Germany (amateur and youth level) to determine symptoms, source of infection and hygiene measures adopted. The definition of potentially infectious players was based on the time of a positive PCR testing and symptom onset. Transmission-relevant contacts on the pitch were evaluated through doubly reviewed video analysis. Results Out of 1247 identified football matches and training sessions (1071 amateur and youth level, 176 professional level), 104 cases (38 training sessions, 66 matches) with 165 potentially infectious players were detected. Follow-up PCR testing at the professional level (44 cases) revealed no transmission. At the amateur and youth level, the combination of partial PCR testing (31 of 60 cases) and symptom monitoring within 14 days post-exposure (46 of 60 cases) identified 2 of 60 matches in which follow-up infections occurred that were attributed to non-football activities. This is consistent with the video analysis of 21 matches demonstrating frontal contacts were &lt;1 per player-hour (88%, 30 of 34 players), each lasting no longer than 3 s. Conclusion On-field transmission risk of SARS-CoV-2 in football is very low. Sources of infections in football players are most likely not related to activities on the pitch.
MA14.07 EGFR-Mutant NSCLC With de novo or Acquired Squamous Histology: Molecular Features and Clinical Outcomes
Authors: C. Meador, R. Cobb, Y. Hung, M. Banwait, A. Piper-Vallillo, A. Muzikansky, A. Hata, L.V. Sequist, Z. Piotrowska
Journal: Journal of Thoracic Oncology (2021)