tbuckley/cabot-search huggingface dataset:
Particulate matter in aerosols produced by two last generation electronic cigarettes: a comparison in a real-world environment
Authors: A. Borgini, C. Veronese, C. De Marco, R. Boffi, A. Tittarelli, M. Bertoldi, E. Fern..ndez, O. Tigova, S. Gallus, A. Lugo, G. Gorini, G. Carreras, M.J. L..pez, X. Continente, S. Semple, R. Dobson, L. Clancy, S. Keogan, A. Tzortzi, C. Vardavas, ... L..pez Nicol..s, P. Starchenko, J.B. Soriano, A.A. Ruprecht
Journal: Pulmonology (2021)

The design of e-cigarettes (e-cigs) is constantly evolving and the latest models can aerosolize using high-power sub-ohm resistance and hence may produce specific particle concentrations. The aim of this study was to evaluate the aerosol characteristics generated by two different types of electronic cigarette in real-world conditions, such as a sitting room or a small office, in number of particles (particles/cm3). We compared the real time and time-integrated measurements of the aerosol generated by the e-cigarette types Just Fog and JUUL. Real time (10 s average) number of particles (particles/cm3) in 8 different aerodynamic sizes was measured using an optical particle counter (OPC) model Profiler 212-2. Tests were conducted with and without a Heating, Ventilating Air Conditioning System (HVACS) in operation, in order to evaluate the efficiency of air filtration. During the vaping sessions the OPC recorded quite significant increases in number of particles/cm3. The JUUL e-cig produced significantly lower emissions than Just Fog with and without the HVACS in operation. The study demonstrates the rapid volatility or change from liquid or semi-liquid to gaseous status of the e-cig aerosols, with half-life in the order of a few seconds (min. 4.6, max 23.9), even without the HVACS in operation. The e-cig aerosol generated by the JUUL proved significantly lower than that generated by the Just Fog, but this reduction may not be sufficient to eliminate or consistently reduce the health risk for vulnerable non e-cig users exposed to it.
Anti-Müllerian Hormone in Female Reproduction
Authors: Nathalie di Clemente, Chrystèle Racine, Alice Pierre, Joëlle Taieb
Journal: Endocrine Reviews (2021)

Anti-Müllerian hormone (AMH), also called Müllerian inhibiting substance, was shown to be synthesized by the ovary in the 1980s. This article reviews the main findings of the past 20 years on the regulation of the expression of AMH and its specific receptor AMHR2 by granulosa cells, the mechanism of action of AMH, the different roles it plays in the reproductive organs, its clinical utility, and its involvement in the principal pathological conditions affecting women. The findings in respect of regulation tell us that AMH and AMHR2 expression is mainly regulated by bone morphogenetic proteins, gonadotropins, and estrogens. It has now been established that AMH regulates the different steps of folliculogenesis and that it has neuroendocrine effects. On the other hand, the importance of serum AMH as a reliable marker of ovarian reserve and as a useful tool in the prediction of the polycystic ovary syndrome (PCOS) and primary ovarian failure has also been acknowledged. Last but not least, a large body of evidence points to the involvement of AMH in the pathogenesis of PCOS.
AB0011 CLINICAL CHARACTERISTICS AND GENETIC EXPRESSION IN A COHORT OF PATIENTS WITH FAMILY MEDITERRANEAN FEVER
Authors: Lara Mendez, Isabel Madroñal García, Clara Aguilera Cros, Ricardo Juan Gil Velez, Maria Dolores Arcila Duran
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Familial Mediterranean fever (FMF) is the most frequent monogenic periodic fever syndrome and is characterized by recurrent episodes of fever, serositis, arthritis, dermal manifestations and long-term renal complications (amyloidosis is the most important complication). The genetic mutation of the disease is found in the MEFV gene located on the short arm of chromosome 16 and is inherited in an autosomal recessive manner. It affects the populations of the Mediterranean basin and is diagnosed according to the clinical evaluation. <h3>Objectives:</h3> To describe the clinical characteristics of a cohort of patients with FMF and to study the different genetic mutations located in the MEFV gene. <h3>Methods:</h3> Retrospective descriptive study of patients treated in our Hospital (2008-2018), with FMF diagnosis and MEFV gene mutation. The data was obtained through the review of medical records. <h3>Results:</h3> We included 52 patients (29 men), mean age 41 years. The following mutations have been identified in alleles of the MEFV gene: Non-pathogenic in 34 patients (65%) (p 202Q 73%, p148Q 17%, p. 319K 6% and p339F 3%). Pathogenic in 18 patients (34%) (pr 202Q 22%, eg 148Q 27%, pr 653H 5%, pm 694V 16%, pi 159T 5%). In 17% of the patients family history was documented. Elevation of acute phase reactants in 41 patients (79%) (C Reactive Protein 75%, Globular sedimentation rate 65%). Echocardiography was performed in 14 patients, with diagnosis of pericardial effusion in 6 of them. Two patients develop renal amyloidosis, one of them (homozygous for the mutation 148Q) died due to this complication. 54% of patients use colchicine as initial treatment, achieving 50% good response with control of symptoms. 19% undergo treatment with glucocorticoids (0.5-1 mg/kg/day), needing to add methotrexate in 1 patient and hydroxychloroquine in another. Four also use biological therapy (1 tocilizumab, 2 anakinra, 1 canakinumab) and 2 thalidomide to control skin manifestations. <h3>Conclusion:</h3> The genetic study confirms the diagnosis of FMF, allowing it to be differentiated from other SAIs. It also has prognostic value, depending on the mutation detected and if it affects one or both alleles. In our series, the most prevalent symptoms in patients with pathogenic mutations were fever, abdominal pain and arthromyalgia. <h3>Disclosure of Interests:</h3> None declared
Abstract 14863: ADAMTS8 Promotes the Development of Pulmonary Arterial Hypertension and Right Ventricular Failure-A Possible Novel Therapeutic Target
Authors: Junichi Omura, Kimio Satoh, Nobuhiro Kikuchi, Taijyu Satoh, Ryo Kurosawa, Masamichi Nogi, Shinichiro Sunamura, Tomohiro Ohtsuki, Elias Al-Mamun, Mohammad A Siddique, Nobuhiro Yaoita, Satoshi Miyata, Yasushi Hoshikawa, Yoshinori Okada, Hiroaki Shimokawa
Journal: Circulation (2017)

Background: Right ventricular (RV) failure is an important prognostic factor for pulmonary arterial hypertension (PAH). A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8) is...
Optimized polyepitope neoantigen DNA vaccines elicit neoantigen-specific immune responses in preclinical models and in clinical translation
Authors: Lijin Li, Xiuli Zhang, Xiaoli Wang, Samuel W. Kim, John M. Herndon, Michelle K. Becker-Hapak, Beatriz M. Carreno, Nancy B. Myers, Mark A. Sturmoski, Michael D. McLellan, Christopher A. Miller, Tanner M. Johanns, Benjamin R. Tan, Gavin P. Dunn, Timothy P. Fleming, Ted H. Hansen, S. Peter Goedegebuure, William E. Gillanders
Journal: Genome Medicine (2021)

Abstract Background Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation. Methods We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer models through genome sequencing and in silico neoantigen prediction pipelines. Optimized polyepitope neoantigen DNA vaccines specific for the murine breast tumor E0771 and 4T1 were designed and their immunogenicity was tested in vivo. We also tested an optimized polyepitope neoantigen DNA vaccine in a patient with metastatic pancreatic neuroendocrine tumor. Results Our data support an optimized polyepitope neoantigen DNA vaccine design encoding long (≥20-mer) epitopes with a mutant form of ubiquitin (Ub mut ) fused to the N-terminus for antigen processing and presentation. Optimized polyepitope neoantigen DNA vaccines were immunogenic and generated robust neoantigen-specific immune responses in mice. The magnitude of immune responses generated by optimized polyepitope neoantigen DNA vaccines was similar to that of synthetic long peptide vaccines specific for the same neoantigens. When combined with immune checkpoint blockade therapy, optimized polyepitope neoantigen DNA vaccines were capable of inducing antitumor immunity in preclinical models. Immune monitoring data suggest that optimized polyepitope neoantigen DNA vaccines are capable of inducing neoantigen-specific T cell responses in a patient with metastatic pancreatic neuroendocrine tumor. Conclusions We have developed and optimized a novel polyepitope neoantigen DNA vaccine platform that can target multiple neoantigens and induce antitumor immune responses in preclinical models and neoantigen-specific responses in clinical translation.
Inconsistent relationship between depth of sedation and intensive care outcome: systematic review and meta-analysis
Authors: Leanne M Aitken, Kalliopi Kydonaki, Bronagh Blackwood, Laurence G Trahair, Edward Purssell, Mandeep Sekhon, Timothy S Walsh
Journal: Thorax (2021)

Purpose To determine the effect of depth of sedation on intensive care mortality, duration of mechanical ventilation, and other clinically important outcomes. Methods We searched MEDLINE, Embase, Cochrane Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, PsycINFO from 2000 to 2020. Randomised controlled trials (RCTs) and cohort studies that examined the effect of sedation depth were included. Two reviewers independently screened, selected articles, extracted data and appraised quality. Data on study design, population, setting, patient characteristics, study interventions, depth of sedation and relevant outcomes were extracted. Quality was assessed using Critical Appraisal Skills Programme tools. Results We included data from 26 studies (n=7865 patients): 8 RCTs and 18 cohort studies. Heterogeneity of studies was substantial. There was no significant effect of lighter sedation on intensive care mortality. Lighter sedation did not affect duration of mechanical ventilation in RCTs (mean difference (MD): −1.44 days (95% CI −3.79 to 0.91)) but did in cohort studies (MD: −1.52 days (95% CI −2.71 to −0.34)). No statistically significant benefit of lighter sedation was identified in RCTs. In cohort studies, lighter sedation improved time to extubation, intensive care and hospital length of stay and ventilator-associated pneumonia. We found no significant effects for hospital mortality, delirium or adverse events. Conclusion Evidence of benefit from lighter sedation is limited, with inconsistency between observational and randomised studies. Positive effects were mainly limited to low quality evidence from observational studies, which could be attributable to bias and confounding factors.
Abstract PO-097: Selective targeting and imaging of orthotopic glioblastoma after a single systemic dose of a novel hydoxyl dendrimer radionuclide
Authors: Rishi Sharma, Minghao Sun, Santiago Appiani, Richard Coelho, Patrick McConville, Susan Alters, Jeffrey L. Cleland
Journal: Clinical Cancer Research (2021)

Abstract Previous studies have demonstrated hydroxyl dendrimers (HDs) are selectively taken up by tumor associated macrophages (TAMs) after a single administration. HDs have also been observed to cross the blood brain barrier in six animal species including dogs and monkeys. The treatment of brain tumors and metastases is hampered by the inability to deliver radiotherapy or cancer agents selectively to the tumor. HDs of two different generations were prepared (HD4 and HD6; both smaller than antibodies) and DOTA was conjugated to the HD through linker arms attached to the hydroxyls on the dendrimer surface. 111In radiolabeling of HD4- and HD6-DOTA resulted in &amp;gt;95% radiochemical purity in both cases and specific activities of 0.621 mCi/mg and 0.638 mCi/mg, respectively. GL-261-luc cells, a syngeneic glioblastoma, were implanted intracranially in 8 female albino C57.bl/6 mice. Tumors were 15-60 mm3 at time of dosing. Mice received a single administration of HD4-DOTA-111In or HD6-DOTA-111In at a dose of approximately 0.5 mg/mouse and 0.3 mCi/mouse. Whole body SPECT/CT imaging was done over time up to 6 days post-dose in 3 animals per compound. The biodistribution and uptake in the brain tumor and other tissues was quantitatively measured using VivoQuant 4.0 (Invicro, Boston). Both HDs rapidly distributed in the systemic circulation after administration. Clearance appeared to be primarily via the kidneys based upon the fraction of injected dose observed in the bladder over time. The % injected dose (%ID)/g in the brain tumor was 2.67 ± 0.45 and 7.05 ± 0.53 at 24 h post-dose for the HD4 and HD6 compounds, respectively. The %ID/g in the contralateral brain section was 0.37 ± 0.17 and 0.90 ± 0.20 at 24 h post-dose for the HD4 and HD6 compounds, respectively. Tumor associated radioactivity persisted for the duration of the study (last time points: HD4, 96 h, 5.27 ± 2.04 %ID/g; HD6, 144 h, 3.20 ± 1.02 %ID/g). These results confirm previous studies in this model demonstrating selective tumor uptake and persistence with 58 fold greater radioactivity at the last time point in brain tumor compared to contralateral brain. The selectivity and prolonged duration of HDs in TAMs will enable the use of the same HD-DOTA constructs to deliver radiotherapeutic 90Y to brain tumors. The HD radiotherapy approach may eliminate the off-target toxicity of current ligand-based approaches. Citation Format: Rishi Sharma, Minghao Sun, Santiago Appiani, Richard Coelho, Patrick McConville, Susan Alters, Jeffrey L. Cleland. Selective targeting and imaging of orthotopic glioblastoma after a single systemic dose of a novel hydoxyl dendrimer radionuclide [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-097.
Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease
Authors: Gabriele Pollara, Carolin T. Turner, Joshua Rosenheim, Aneesh Chandran, Lucy C. K. Bell, Ayesha Khan, Amit Patel, Luis Felipe Peralta, Anna Folino, Ayse Akarca, Cristina Venturini, Tina Baker, Simone Ecker, Fabio L. M. Ricciardolo, Teresa Marafioti, Cesar Ugarte-Gil, David A. J. Moore, Benjamin M. Chain, Gillian S. Tomlinson, Mahdad Noursadeghi
Journal: Science Translational Medicine (2021)

In vivo IL-17A activity is elevated in active tuberculosis and may be a therapeutic target to attenuate disease-associated immunopathology.
LEISURE-TIME PHYSICAL ACTIVITY ASSOCIATES FAVORABLY WITH THE BIOACTIVE LIPIDOME AND RISK OF INCIDENT CVD EVENTS/ RESULTS FROM THE VITAMIN D AND OMEGA-3 TRIAL (VITAL) AND JUPITER TRIALS
Authors: Rosangela Akemi Hoshi, Yanyan Liu, Heike Luttmann-Gibson, Allen M. Andres, Saumya Tiwari, Jeramie D. Watrous, Nancy R. Cook, Trisha Copeland, Karen H. Costenbader, Olivia I. Okereke, Paul Ridker, JoAnn Manson, I-Min Lee, Mohit Jain, Olga Demler, Samia Mora
Journal: Journal of the American College of Cardiology (2021)
MondoA drives malignancy in B-ALL through enhanced adaptation to metabolic stress
Authors: Alexandra Sipol, Erik Hameister, Busheng Xue, Julia Hofstetter, Maxim Barenboim, Rupert Öllinger, Gaurav Jain, Carolin Prexler, Rebeca Alba Rubio, Michaela C. Baldauf, Davide G. Franchina, Andreas Petry, Juliane Schmäh, Uwe Thiel, Agnes Görlach, Gunnar Cario, Dirk Brenner, Günther H. S. Richter, Thomas G. P. Grünewald, Roland Rad, Elmar Wolf, Jürgen Ruland, Poul H. Sorensen, Stefan E. G. Burdach
Journal: Blood (2021)

Cancer cells are in most instances characterized by rapid proliferation and uncontrolled cell division. Hence, they must adapt to proliferation-induced metabolic stress through intrinsic or acquired antimetabolic stress responses to maintain homeostasis and survival. One mechanism to achieve this is reprogramming gene expression in a metabolism-dependent manner. MondoA (also known as Myc-associated factor X-like protein X-interacting protein [MLXIP]), a member of the MYC interactome, has been described as an example of such a metabolic sensor. However, the role of MondoA in malignancy is not fully understood and the underlying mechanism in metabolic responses remains elusive. By assessing patient data sets, we found that MondoA overexpression is associated with worse survival in pediatric common acute lymphoblastic leukemia (ALL; B-precursor ALL [B-ALL]). Using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and RNA-interference approaches, we observed that MondoA depletion reduces the transformational capacity of B-ALL cells in vitro and dramatically inhibits malignant potential in an in vivo mouse model. Interestingly, reduced expression of MondoA in patient data sets correlated with enrichment in metabolic pathways. The loss of MondoA correlated with increased tricarboxylic acid cycle activity. Mechanistically, MondoA senses metabolic stress in B-ALL cells by restricting oxidative phosphorylation through reduced pyruvate dehydrogenase activity. Glutamine starvation conditions greatly enhance this effect and highlight the inability to mitigate metabolic stress upon loss of MondoA in B-ALL. Our findings give novel insight into the function of MondoA in pediatric B-ALL and support the notion that MondoA inhibition in this entity offers a therapeutic opportunity and should be further explored.
Viable virus shedding during SARS-CoV-2 reinfection
Authors: Andrew G Letizia, Darci R Smith, Yongchao Ge, Irene Ramos, Rachel S G Sealfon, Carl Goforth, Ana S Gonzalez-Reiche, Sindhu Vangeti, Dawn L Weir, Hala Alshammary, Hua Wei Chen, Mary-Catherine George, Alessandra Soares-Schanoski, Rhonda A Lizewski, Stephen E Lizewski, Jan Marayag, Clare M Miller, Edgar Nunez, Chad K Porter, Ernesto Santa Ana, Megan Schilling, Victor A Sugiharto, Peifang Sun, Michael Termini, Adriana van de Guchte, Olga G Troyanskaya, Harm van Bakel, Stuart C Sealfon
Journal: The Lancet Respiratory Medicine (2021)
Adrenergic regulation of the vasculature impairs leukocyte interstitial migration and suppresses immune responses
Authors: Sapna Devi, Yannick O. Alexandre, Joon Keit Loi, Ryan Gillis, Nazanin Ghazanfari, Sarah J. Creed, Lauren E. Holz, David Shackleford, Laura K. Mackay, William R. Heath, Erica K. Sloan, Scott N. Mueller
Journal: Immunity (2021)
IMPACT OF TARGET VESSEL CHOICE ON OUTCOMES FOLLOWING PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH A PRIOR CORONARY ARTERY BYPASS GRAFT
Authors: Frans Beerkens, Ranbir Singh, Davide Cao, Johny Nicolas, Victor Razuk, Brent Jones, Samantha Sartori, Clayton Snyder, Bimmer Claessen, David Power, Anton Camaj, Mauro Chiarito, Matteo Nardin, Prakash Krishnan, Nitin Barman, Usman Baber, Joseph Sweeny, George Dangas, Roxana Mehran, Samin Sharma, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2021)
Disabling the Fanconi Anemia Pathway in Stem Cells Leads to Radioresistance and Genomic Instability
Authors: Xinzhu Deng, Jason Tchieu, Daniel S. Higginson, Kuo-Shun Hsu, Regina Feldman, Lorenz Studer, Shai Shaham, Simon N. Powell, Zvi Fuks, Richard Kolesnick
Journal: Cancer Research (2021)

Abstract Fanconi anemia is an inherited genome instability syndrome characterized by interstrand cross-link hypersensitivity, congenital defects, bone marrow failure, and cancer predisposition. Although DNA repair mediated by Fanconi anemia genes has been extensively studied, how inactivation of these genes leads to specific cellular phenotypic consequences associated with Fanconi anemia is not well understood. Here we report that Fanconi anemia stem cells in the C. elegans germline and in murine embryos display marked nonhomologous end joining (NHEJ)–dependent radiation resistance, leading to survival of progeny cells carrying genetic lesions. In contrast, DNA cross-linking does not induce generational genomic instability in Fanconi anemia stem cells, as widely accepted, but rather drives NHEJ-dependent apoptosis in both species. These findings suggest that Fanconi anemia is a stem cell disease reflecting inappropriate NHEJ, which is mutagenic and carcinogenic as a result of DNA misrepair, while marrow failure represents hematopoietic stem cell apoptosis. Significance: This study finds that Fanconi anemia stem cells preferentially activate error-prone NHEJ-dependent DNA repair to survive irradiation, thereby conferring generational genomic instability that is instrumental in carcinogenesis.
Transesophageal Echocardiography in Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: Thomas S. Metkus, Dylan Thibault, Michael C. Grant, Vinay Badhwar, Jeffrey P. Jacobs, Jennifer Lawton, Sean M. O'Brien, Vinod Thourani, Zachary K. Wegermann, Brittany Zwischenberger, Robert Higgins
Journal: Journal of the American College of Cardiology (2021)
STEREOTACTIC CARDIAC RADIOTHERAPY FOR REFRACTORY VENTRICULAR TACHYCARDIA: A METAANALYSIS
Authors: Farhad Sami, John Anderson, Moghniuddin Mohammed, Habeeb Saleh, David Akhavan, Seth Sheldon, Madhu Reddy, Amit Noheria
Journal: Journal of the American College of Cardiology (2021)
A PATIENT WITH SYMPTOMATIC SEVERE BIOPROSTHETIC MITRAL VALVE STENOSIS AND REGURGITATION, LOW FLOW LOW GRADIENT AORTIC VALVE STENOSIS, MODERATE TO SEVERE TRICUSPID REGURGITATION, AND SEVERE PULMONARY HYPERTENSION
Authors: David Sosa, Kathleen Allen, Gerald Charlton, Stacey Bailey, Carlos Roldan
Journal: Journal of the American College of Cardiology (2021)