tbuckley/cabot-search huggingface dataset:
Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study
Authors: Tài Pham, Antonio Pesenti, Giacomo Bellani, Gordon Rubenfeld, Eddy Fan, Guillermo Bugedo, José Angel Lorente, Antero do Vale Fernandes, Frank Van Haren, Alejandro Bruhn, Fernando Rios, Andres Esteban, Luciano Gattinoni, Anders Larsson, Daniel F. McAuley, Marco Ranieri, B. Taylor Thompson, Hermann Wrigge, Laurent J. Brochard, John G. Laffey
Journal: European Respiratory Journal (2020)

Current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).An international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.More than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
Abstract 12186: Sleep Blood Pressure, Sleep Glucose Values, and Target Organ Damages in Treated Type 2 Diabetes Patients
Authors: Manabu Hayakawa, Yuichiro Yano, Kazuo Kuroki, Sho-ichi Yamagishi, Masayoshi Takeuchi, Takuma Eto, Naoto Nagata, Masamitsu Nakazato, Kazuyuki Shimada, Kazuomi Kario
Journal: Circulation (2012)

Objective: Due to advances in medical technology, blood pressure (BP) or glucose values in vivo can be evaluated clinically not only during waking, but also sleeping time periods. In the field of B...
Abstract 15700: Targeted Nanoparticle Delivery of a Protein Arginine Deiminase-4 Inhibitor Limits Arterial Intimal Netosis and Preserves Endothelial Integrity in Mouse Arterial Erosion-like Injury
Authors: Roberto Molinaro, Mikyung Yu, Collette A Bichsel, Claudia Corbo, Gha Young Y Lee, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K Sukhova, Frederik Kloss, Kevin Croce, Omid C Farokhzad, Jinjun Shi, Peter Libby
Journal: Circulation (2020)

Introduction: Superficial plaque erosion has emerged as a growing cause of residual thrombotic complications of atherosclerosis in an era of effective lipid lowering, anti-hypertensive therapy, and smoking cessation. The mechanisms of plaque erosion remain poorly understood, and we currently lack validated effective diagnostics or therapeutics for superficial erosion. Lesions complicated by erosion have a rich extracellular matrix, sparse lipid, and few mononuclear cells, but do harbor neutrophil extracellular traps (NETs). We recently reported that NETs amplify and propagate the endothelial damage at the site of arterial lesions that recapitulate in mice elements of superficial erosion. We previously showed that genetic loss of protein arginine deiminase (PAD)-4 function inhibited NETosis and preserved endothelial integrity. Hypothesis: We hypothesized that Col IV-targeted NPs (Col IV-NPs) can deliver PAD4 inhibitors selectively to regions of EC sloughing and collagen IV-rich basement membrane exposure, and attenuate the amplification, persistence, and propagation of superficial erosion and consequent thrombosis. Methods: We developed Col IV-NPs to deliver PAD4 inhibitors selectively to regions of endothelial cell sloughing and collagen IV-rich basement membrane exposure using our validated experimental preparation that reproduces in mice some of the conditions ascribed to lesions associated with superficial erosion. Results and Conclusions: We first demonstrated the binding of the targeting ligand in vitro and evaluated Col IV NP targeting towards areas of denuded endothelium in vivo in this mouse preparation. Delivery of the PAD4 inhibitor GSK484 as cargo in these nanoparticles reduced NETs release at sites of eroded areas. Compared to non-targeted NPs, Col IV NPs showed a 1.8-fold increased accumulation at regions of endothelial injury (p&lt;0.0001). When loaded with the PAD4 inhibitor GSK484, Col IV NPs effectively reduced NET accumulation by 2.5 fold at sites of intimal lesions (p&lt;0.01) and preserved endothelial continuity (a 4-fold increase in endothelial continuity percentage, p&lt;0.001). These results indicate the feasibility of using nanotechnology to address the unmet need of specific therapy for superficial erosion.
On the Origin of Coexisting Species
Authors: Rachel M. Germain, Simon P. Hart, Martin M. Turcotte, Sarah P. Otto, Jawad Sakarchi, Jonathan Rolland, Takuji Usui, Amy L. Angert, Dolph Schluter, Ronald D. Bassar, Mia T. Waters, Francisco Henao-Diaz, Adam M. Siepielski
Journal: Trends in Ecology & Evolution (2020)
Association of Prehospital RAAS Inhibitor Use with AKI and Death in a Cohort of Hospitalized COVID-19-Infected Patients
Authors: Ryan Mocerino, Emad Alahiri, Matthew K. Abramowitz, Ladan Golestaneh
Journal: Journal of the American Society of Nephrology (2020)

Mocerino, Ryan; Alahiri, Emad; Abramowitz, Matthew K.; Golestaneh, Ladan Author Information
TAG—Is It It?: Improving Coronary Computed Tomography Angiography With the Isotemporal Transluminal Contrast Attenuation Gradient⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Andrew J. Einstein
Journal: Journal of the American College of Cardiology (2013)
Altered TGF-β responses in a cell culture model of breast cancer progression
Authors: Naomi S. Yoo, Binwu Tang, Lalage Wakefield
Journal: Cancer Research (2005)

2524  We have previously shown that transforming growth factor-beta (TGF-β) has a dual role in breast cancer, functioning first as a tumor suppressor and then becoming a pro-metastatic factor (Tang et al., J. Clin.Invest., 2003, 112:1116). Our aim in this study was to focus on the late stages of the disease process when TGF-β switches roles, by examining in vitro responses to TGF-β in two closely-related cell lines, both derived from a common progenitor cell line, in which the roles of TGF-β differ. MCF10Ca1h (CA1h) form well-differentiated tumors in vivo, and TGF-β functions as a tumor suppressor in this line. In contrast, MCF10Ca1a.cl1(CA1a) cells, form poorly-differentiated metastatic tumors. In these cells, TGF-β no longer acts as a tumor suppressor, but rather as a pro-metastatic factor. We have compared these cells for a variety of cellular and molecular responses to TGF-β in vitro. Interestingly, CA1h and CA1a cells showed no obvious differences in signaling in response to TGF-β, as Smad2 and Smad3 phosphorylation, and activation of the JNK/ERK pathways by TGF-β are similar in both cell types. However, despite the similarity in these early signaling events, we saw significant differences between the two cell types in terms of their proliferation, apoptosis and invasion responses to TGF-β. We have found that the loss of tumor suppressor effects of TGF-β in CA1a cells is associated with a reduced sensitivity to the growth inhibitory effects of TGF-β, when compared with the strongly growth inhibitory response of the CA1h cells. Conversely, TGF-β did not enhance the apoptotic response of CA1h cells to growth factor and nutrient deprivation, whereas TGF-β promoted the survival of CA1a cells under the same conditions. TGF-β also suppressed cell death induced by detachment (anoikis) in the CA1a cells, but not in the CA1h cells. We further found that TGF-β could significantly stimulate CA1a cells to invade through Matrigel, whereas it had no effect on the invasive ability of CA1h cells. Our preliminary data showed that MMP-2 activity was stimulated by TGF-β treatment in both CA1h and CA1a cells, but the effect on CA1a cells was more profound. Based on these observations, we conclude that the transition from tumor suppressor response (seen in the CA1h cells) to pro-metastatic response (seen in the CA1a cells), is associated with a reduction in the anti-proliferative response to TGF-β, and the acquisition of pro-survival and pro-invasion responses to this molecule. We are currently investigating the underlying molecular mechanisms. Understanding the nature of this “metastatic switch” may allow the design of novel new therapeutic strategies that can prevent or reverse it.
Abstract 10954: The Long-Term Outcomes in Patients With Chronic Renal Failure on Hemodialysis After Aortic Valve/root Replacement With Stentless Bioprosthesis - 23-year Experience
Authors: Aroosa Malik, Linda Farhat, Alexander Makkinejad, Elizabeth Norton, Emma St. Pierre, Mohamed Ali Sareini, Xiaoting Wu, Francis D Pagani, Jonathan Haft, Matthew A Romano, Richard L Prager, Karen Kim, Himanshu J Patel, G. Michael Deeb, Bo Yang
Journal: Circulation (2019)

Introduction: The effect chronic renal failure (CRF) on hemodialysis (HD) on the longevity of a stentless bioprosthesis is unkown Hypothesis: We hypothesize CRF on HD cause more reoperations for st...
Authentication framework for security application developed using a pictorial P300 speller
Authors: Nikhil Rathi, Rajesh Singla, Sheela Tiwari
Journal: Brain-Computer Interfaces (2020)

ABSTRACT With the recent advancement in the field of information technology, online frauds have also been increased and hence password-based systems are no more secure. Therefore need for a more reliable authentication system has been growing rapidly. This study focuses on a P300 based authentication system designing. The proposed study presents a new four-choice oddball paradigm where a conventional 6 × 6 character-based speller is replaced by a novel 2 × 2 pictorial speller. In this study, three classifiers were tested: Quadratic Discriminant Analysis (QDA), K-Nearest Neighbor (KNN), and Quadratic Support Vector Machine (QSVM). Out of these three, QDA performed better. The results showed that the designed visual stimuli obtained significantly higher accuracy (97%) and information transfer rates (37.14 bits/min) as compared to the conventional paradigm. The results also show that reduced matrix size and modified stimulus typically affects the accuracy and communication speed of a P300 based authentication system.
Evaluation of the osteoinductive potential of a bio-inspired scaffold mimicking the osteogenic niche for bone augmentation
Authors: Silvia Minardi, Bruna Corradetti, Francesca Taraballi, Monica Sandri, Jeffrey Van Eps, Fernando J. Cabrera, Bradley K. Weiner, Anna Tampieri, Ennio Tasciotti
Journal: Biomaterials (2015)

Augmentation of regenerative osteogenesis represents a premier clinical need, as hundreds of thousands of patients are left with insufficient healing of bony defects related to a host of insults ranging from congenital abnormalities to traumatic injury to surgically-induced deficits. A synthetic material that closely mimics the composition and structure of the human osteogenic niche represents great potential to successfully address this high demand. In this study, a magnesium-doped hydroxyapatite/type I collagen scaffold was fabricated through a biologically-inspired mineralization process and designed to mimic human trabecular bone. The composition of the scaffold was fully characterized by XRD, FTIR, ICP and TGA, and compared to human bone. Also, the scaffold microstructure was evaluated by SEM, while its nano-structure and nano-mechanical properties were evaluated by AFM. Human bone marrow-derived mesenchymal stem cells were used to test the in vitro capability of the scaffold to promote osteogenic differentiation. The cell/scaffold constructs were cultured up to 7 days and the adhesion, organization and proliferation of the cells were evaluated. The ability of the scaffold to induce osteogenic differentiation of the cells was assessed over 3 weeks and the correlate gene expression for classic genes of osteogenesis was assessed. Finally, when tested in an ectopic model in rabbit, the scaffold produced a large volume of trabecular bone in only two weeks, that subsequently underwent maturation over time as expected, with increased mature cortical bone formation, supporting its ability to promote bone regeneration in clinically-relevant scenarios. Altogether, these results confirm a high level of structural mimicry by the scaffold to the composition and structure of human osteogenic niche that translated to faster and more efficient osteoinduction in vivo--features that suggest such a biomaterial may have great utility in future clinical applications where bone regeneration is required.
<i>Has2</i> deficiency enhances OVA‐induced airway inflammation and hyperresponsiveness in mice
Authors: Yoshiya Tsunoda, Mingma Thsering Sherpa, Takumi Kiwamoto, Masashi Matsuyama, Hajime Osawa, Hirofumi Sakurai, Shigen Hayashi, Yosuke Matsuno, Yuko Morishima, Yukio Ishii, Nobuyuki Hizawa
Journal: Allergy (2020)
Correspondence on ‘Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases’
Authors: Sibel Zehra Aydin, Elliot Hepworth, Peter Tugwell
Journal: Annals of the Rheumatic Diseases (2020)

COVID-19 is the most devastating pandemic in recent history leading to utmost economic and social disruption that will likely require decades for recovery. Due to the rapid spread of the virus globally, there have been more than 70 000 publications in the 10 months since January 2020. This is understandable given the need to collaborate globally, and act on our understanding of the virus as soon as possible. However, the immense data urgently generated within this short period of time may have major limitations given that the researchers have been unable to spend the time that it usually requires to carefully design the study protocol, obtain ethics approval, collect and appropriately analyse the data.

The risk of COVID-19 in the large patient population with autoimmune inflammatory rheumatic diseases is also of major interest. Despite the general elevated risk in rheumatological diseases of serious non-COVID-19 infections, either being linked to the underlying diseases, or to the medications with which they are treated, the risk attributable to COVID-19 in these diseases is not straightforward. One reason is the cytokine release syndrome seen in severe …
Tumor-infiltrating dendritic cell states are conserved across solid human cancers
Authors: Genevieve M. Gerhard, Ruben Bill, Marius Messemaker, Allon M. Klein, Mikael J. Pittet
Journal: The Journal of Experimental Medicine (2020)

Dendritic cells (DCs) contribute a small fraction of the tumor microenvironment but are emerging as an essential antitumor component based on their ability to foster T cell immunity and immunotherapy responses. Here, we discuss our expanding view of DC heterogeneity in human tumors, as revealed with meta-analysis of single-cell transcriptome profiling studies. We further examine tumor-infiltrating DC states that are conserved across patients, cancer types, and species and consider the fundamental and clinical relevance of these findings. Finally, we provide an outlook on research opportunities to further explore mechanisms governing tumor-infiltrating DC behavior and functions.
Inferior Vena Cava Tumor Thrombus From Thyroid Cancer Detected by 68Ga-PSMA-617 PET/CT
Authors: Hui Li, Yanqing Liu, Jie Zang, Zhi Yang, Yansong Lin
Journal: Clinical Nuclear Medicine (2020)

A 61-year-old woman was diagnosed with progressive metastatic radioactive iodine refractory differentiated thyroid cancer and underwent multitargeted tyrosine kinase inhibitor (TKI) Donafenib therapy. After 12 months of therapy, she developed resistance to TKI. Considering the limited treatment options available, a 68Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT was conducted for potential therapeutic target. 68Ga-PSMA-617 PET/CT showed an intense radiotracer uptake in inferior vena cava, which was subsequently confirmed as tumor thrombus. Thus, this patient is a rare case in which the tumor thrombus from thyroid cancer was discovered in inferior vena cava via 68Ga-PSMA-617 PET/CT.
Abstract 17589: Use of a Wearable Cardioverter Defibrillator (WCD) to Protect Patients After ICD Explantation: Results From the National Registry
Authors: Chingping Wan, Kenneth A Ellenbogen, Charles J Love, Sanjay Deshpande, Steven J Szymkiewicz
Journal: Circulation (2015)

Introduction: The WCD is used to treat patients (pts) at high risk of VT/VF until ICD therapy can be implemented as well as for pts with ICDs who undergo device removal and treatment of an underlying infectious process. In non-pacemaker dependent pts for whom an ICD must be removed due to infection, the WCD is now routine therapy, allowing the pt to be managed as an outpatient until the infection is resolved. Re-implantation may be postponed for weeks to months depending upon the nature of the infection being treated. The current study sought to report the outcome of using a WCD in pts who underwent ICD explantation. We report on the time course of re-implantation and the use of the WCD in patients after ICD explantation. Methods: Medical orders from 1/2008 through 12/2013 were reviewed for pts prescribed a WCD after ICD explantation. Demographics and WCD-stored electrocardiogram were assessed. A shockable arrhythmia event was defined as all sustained VT or VF occurring within a single 24-hour period. Duration of WCD use and reason for ending use were also evaluated. Results: A total of 8,058 pts were identified. Mean age was 62 ± 14 years; male pts consisted of 75% of the study population. While wearing the WCD, 280 (3%) pts experienced 334 VT or VF events, of which 328 were successfully treated by the WCD. The 24-hour survival was 93% (310/334). VT or VF occurrence was highest in the initial weeks following ICD removal (0.7, 0.6 and 0.7 per pt-week for weeks 1, 2 and 3 respectively). Two-month cumulative event rate was 4%. Median time to re-implantation was 48 (IQR, 24-82) days. Thirty-nine percent of the pts wore the WCD for more than 2 months (Figure). Conclusion: After ICD explantation, pts were at highest risk of VT or VF during the initial 3 weeks. The WCD demonstrated a high efficacy for resuscitating pts from VT/VF events, with 30-day survival rate being 79% and 90-day being 71%.
Activity and bioavailability of tepotinib for leptomeningeal metastasis of NSCLC with MET exon 14 skipping mutation
Authors: Hisashi Tanaka, Kageaki Taima, Tomonori Makiguchi, Junichi Nakagawa, Takenori Niioka, Sadatomo Tasaka
Journal: Cancer Communications (2021)

Abstract Tepotinib is a key drug for cancer patients with mesenchymal‐epithelial transition receptor tyrosine kinase proto‐oncogene (MET) exon 14 skipping mutation. However, its bioavailability in the cerebrospinal fluid (CSF) in humans has not been fully elucidated. Moreover, information about the efficacy of tepotinib in patients with leptomeningeal metastasis is limited. Here, we present the case of a 56‐year‐old man who was diagnosed with lung adenocarcinoma with MET exon 14 skipping mutation. He was urgently hospitalized due to leptomeningeal metastasis. We administered tepotinib 500 mg/day as the second‐line therapy and observed improvement in leptomeningeal metastasis and performance status. The tepotinib concentrations reached 1,648 ng/mL in the plasma and 30.6 ng/mL in the CSF, with a penetration rate (CSF/plasma) of 1.83%. These demonstrate tepotinib could achieve a high rate of central nervous system transition and could be effective against leptomeningeal metastasis.
Final Results of the Prospective Biomarker Trial PETra: [11C]-MET-Accumulation in Postoperative PET/MRI Predicts Outcome after Radiochemotherapy in Glioblastoma
Authors: Annekatrin Seidlitz, Bettina Beuthien-Baumann, Steffen Löck, Christina Jentsch, Ivan Platzek, Klaus Zöphel, Annett Linge, Jörg Kotzerke, Jan Petr, Jörg van den Hoff, Jörg Steinbach, Dietmar Krex, Gabriele Schmitz-Schackert, Monique Falk, Michael Baumann, Mechthild Krause
Journal: Clinical Cancer Research (2020)

This prospective trial investigates the association of time to recurrence (TTR) in glioblastoma with [11C]methionine (MET) tracer uptake before postoperative radiochemotherapy (RCT) aiming to guide radiotherapy boost regions.Between 2013 and 2016, 102 patients with glioblastoma were recruited. RCT was performed with concurrent and adjuvant temozolomide to a total dose of 60 Gy. Tumor residues in postresection PET and MRI were together defined as gross tumor volumes for radiotherapy treatment planning. [11C]methionine (MET)-PET/MRI was performed before RCT and at each follow-up.The primary hypothesis of a longer TTR for patients without increased tracer accumulation in postoperative MET-PET was confirmed in 89 patients. With 18.9 months (95% confidence interval, 9.3-28.5 months), median TTR was significantly (P < 0.001) longer for patients without (n = 29, 32.6%) as compared with 6.3 months (3.6-8.9) for patients with MET accumulation (n = 60, 67.4%) in pre-RCT PET. Although MRI often did not detect all PET-positive regions, an unfavorable impact of residual tumor in postsurgical MRI (n = 38, 42.7%) on TTR was observed [4.6 (4.2-5.1) vs. 15.5 months (6.0-24.9), P < 0.001]. Significant multivariable predictors for TTR were MRI positivity, PET-positive volume, and O6-methylguanine DNA methyltransferase (MGMT) hypermethylation.Postsurgical amino acid PET has prognostic value for TTR after RCT in glioblastoma. Because of the added value of the metabolic beyond the pure structural information, it should complement MRI in radiotherapy planning if available with reasonable effort, at least in the context of maximal therapy. Furthermore, the spatial correlation of regions of recurrence with PET-positive volumes could provide a bioimaging basis for further trials, for example, testing local radiation dose escalation.