tbuckley/cabot-search huggingface dataset:
Multiparametric characterization of red blood cell physiology after hypotonic dialysis based drug encapsulation process
Authors: Mélanie Robert, Bastien Laperrousaz, Diana Piedrahita, Emilie-Fleur Gautier, Travis Nemkov, Florian Dupuy, Elie Nader, Virginie Salnot, Patrick Mayeux, Angelo D'Alessandro, Catherine Lavazec, Philippe Joly, Alexander Scheer, Philippe Connes, Agnès Cibiel
Journal: Acta Pharmaceutica Sinica B (2021)

Red blood cells (RBCs) can act as carriers for therapeutic agents and can substantially improve the safety, pharmacokinetics, and pharmacodynamics of many drugs. Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier. We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and integrity. Several parameters were compared between processed RBCs loaded with l-asparaginase ("eryaspase"), processed RBCs without drug and non-processed RBCs. Processed RBCs were less hydrated and displayed a reduction of intracellular content. We observed a change in the metabolomic but not in the proteomic profile of processed RBCs. Encapsulation process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles release. Despite a decrease in deformability, processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic resistance. Processed RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free forms. Our study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function.
Abstract 10545: Tricuspid Valve Regurgitation and Shunt Type in Association With Transplant-free Survival After Norwood: An Analysis of the Single Ventricle Reconstruction Trial Database
Authors: Paul J Devlin, Brian W McCrindle, Kamal Pourmoghadam
Journal: Circulation (2019)

Introduction: The Single Ventricle Reconstruction (SVR) Trial found higher 12 month transplant-free survival in Norwood patients who received right ventricle to pulmonary artery (RVPA) shunts compa...
Long-term use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes
Authors: Sven H Loosen, Karel Kostev, Mark Luedde, Natalia Qvartskhava, Tom Luedde, Christoph Roderburg
Journal: Gut (2021)

We read with great interest the work of Yuan et al 1 providing robust evidence for an association between a regular use of proton pump inhibitors (PPIs) and the risk of type 2 diabetes (T2D). In a retrospective case–control study, we used the Disease Analyser database (IQVIA), which compiles drug prescriptions, diagnoses and basic medical and demographic data obtained from general practitioners (GPs) in Germany,2 to evaluate an association between long-term PPI therapy and diagnosis of T2D. A total of 26 744 patients aged ≥18 years with an initial diagnosis of T2D (index date) between January 2010 and December 2020 from 752 GP practices were included. Inclusion criteria included at least one body mass index (BMI) value at baseline and an observation time of at least 12 months prior to the index date. As a control population, GP patients who fulfilled the inclusion criteria but had no diagnosis of T2D in their entire medical history were matched 1:1 to patients with T2D based on propensity scores delivered from logistic …
The Impact of Alcohol and Other Substance Use Disorders on Mortality in Patients With Eating Disorders: A Nationwide Register-Based Retrospective Cohort Study
Authors: Angelina Isabella Mellentin, Anna Mejldal, Maria Mercedes Guala, René Klinkby Støving, Lene Stryhn Eriksen, Elsebeth Stenager, Lotte Skøt
Journal: American Journal of Psychiatry (2021)

Research is lacking on the contribution of different types of substance use disorders (SUDs) to excess mortality across the full spectrum of eating disorders. The authors assessed the association of alcohol use disorders and other SUDs with mortality in anorexia nervosa, bulimia nervosa, and unspecified eating disorder compared with matched control subjects.
TCT-408 Clinical Predictors of Mortality and Heart Failure Hospitalization in Patients With Severe Tricuspid Regurgitation
Authors: Kris Kumar, Timothy Byrne, Timothy Simpson, Ashraf Samhan, Raj Shah, Jorge Rodriguez, Loren Wagner, Miguel Sotelo, Chris Rogers, Scott Chadderdon, Howard Song, Harsh Golwala, Firas Zahr
Journal: Journal of the American College of Cardiology (2021)
Genomic copy number determination in cancer cells from SNP microarrays based on quantitative genotyping corrected for aneuploidy
Authors: Edward Attiyeh, Sharon Diskin, Marc Attiyeh, Yael Mosse, Cuiping Hou, Eric Jackson, Cecilia Kim, Joseph Glessner, Hakon Hakonarson, Jaclyn Biegel, John Maris
Journal: Cancer Research (2008)

1657  Tumor genomics are important in pediatric cancer diagnostics and prognostication. Copy number (CN) aberrations are associated with clinical outcome in neuroblastoma (NBL) and aneuploidy serves as a prognostic marker in both NBL and acute lymphoblastic leukemia (ALL). Single nucleotide polymorphism (SNP) arrays are increasingly used to profile genome-wide CN aberrations in cancer, but the methods used to derive CN from signal intensity values have been suboptimal when applied to cancer genomes. The complexity of genomic aberrations in cancer makes it more difficult to discriminate between signal and noise, and measuring CN as a discreet variable does not account for tumor heterogeneity. Furthermore, standard normalization approaches detect CN changes relative to the overall DNA content, which is often not diploid in cancer. Here we propose an algorithm that corrects for aneuploidy and integrates the degree of allelic imbalance with the probe intensity for a quantitative CN assessment and scoring of allelic ratios. First, we compute the intensity correction factor needed to adjust for aneuploidy as standard approaches assume an overall diploid genome and erroneously normalize aneuploid genomes to fit that model. Absolute CN is then derived as a function of the degree of allelic imbalance. This yields an accurate accounting of absolute chromosome CN as opposed to CN relative to the DNA index. We profiled 488 NBL and 96 ALL samples on the Illumina HumanHap550 array. Chromosome regions present in two copies in hyperdiploid samples appeared to have intensity values consistent with CN loss. Therefore, we used SNPs where the probe intensity was inconsistent with the genotype (e.g. probe intensity showed loss but the genotype did not show LOH) to compute the intensity correction factor needed to adjust for aneuploidy. The adjusted intensity values resulted in CNs reflecting the number of chromosomes seen in ALL karyotypes, even for significantly hyperdiploid cells. For each SNP, the degree of allelic imbalance dictated the possible CNs. For example, if both alleles were present in equal amounts, the possible CNs were 2, 4, 6, 8, or higher even numbers; similarly, if the minor allele ratio was 0.33, the only possible CNs were multiples of three (3, 6, 9, or greater). The probe intensity values were then applied as a qualitative tool to distinguish between these very different CN states. These absolute CNs were used to estimate DNA index and very closely matched the value derived from flow cytometry in 349/488 (72%) NBL samples. This algorithm results in a more precise definition of allelic aberration in the cancer genome, which is essential for translational efforts focused on molecular diagnostics and the discovery of therapeutic targets.
Development of a Blood-based Transcriptional Risk Score for Chronic Obstructive Pulmonary Disease
Authors: Matthew Moll, Adel Boueiz, Auyon J. Ghosh, Aabida Saferali, Sool Lee, Zhonghui Xu, Jeong H. Yun, Brian D. Hobbs, Craig P. Hersh, Don D. Sin, Ruth Tal-Singer, Edwin K. Silverman, Michael H. Cho, Peter J. Castaldi, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Edwin K. Silverman, Emily S. Wan, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Sharon M. Lutz, Kendra A. Young, Surya P. Bhatt, Jessica Bon, Alejandro A. Diaz, Susan Murray, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

The ability of peripheral blood biomarkers to assess chronic obstructive pulmonary disease (COPD) risk and progression is unknown. Genetics and gene expression may capture important aspects of COPD-related biology that predict disease activity.
Radiation Recall Pneumonitis on FDG PET/CT Triggered by COVID-19 Vaccination
Authors: Nicola M. Hughes, Mark M. Hammer, Mark M. Awad, Heather A. Jacene
Journal: Clinical Nuclear Medicine (2021)

Abstract A 67-year-old man with metastatic lung adenocarcinoma was initially treated with whole-brain radiotherapy for intracranial metastases, followed by chemotherapy and pembrolizumab. After completing 2 years of systemic therapy, the primary right lung lesion was biopsy-proven to have residual adenocarcinoma, which was then treated with radiation (6000 cGy in 15 fractions). Follow-up serial FDG PET/CT showed radiation fibrosis. Eighteen months after radiotherapy, the patient received 2 doses of an mRNA COVID-19 vaccine. FDG PET/CT performed 4 days following his second vaccine dose showed FDG-avid multistation lymphadenopathy and radiation recall pneumonitis, likely vaccination-induced and mimicking recurrent disease. This resolved spontaneously without therapy.
One Year Clinical Result of Optical Coherence Tomography Guided PCI in Small Coronary Vessel Disease with 2.25mm Everolimus-Eluting Platinum Stent
Authors: Kijima Yoichi, Masano Tomoya, Nagoshi Ryoji, Kozuki Amane, Imamura Kimitake, Fujiwara Ryudo, Shibata Hiroyuki, Takeshige Ryo, Tsukiyama Yoshiro, Yanaka Kenichi, Nakano Shinsuke, Fukuyama Yusuke, Kawashima Seinosuke, Shite Junya
Journal: Circulation (2015)
Immune landscape in vulvar cancer-draining lymph nodes indicates distinct immune escape mechanisms in support of metastatic spread and growth
Authors: Anne Marijne Heeren, Jossie Rotman, Sanne Samuels, Henry J M A A Zijlmans, Guus Fons, Koen K van de Vijver, Maaike C G Bleeker, Gemma G Kenter, Ekaterina J Jordanova, Tanja D de Gruijl
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Therapeutic immune intervention is highly dependent on the T-cell priming and boosting capacity of tumor-draining lymph nodes (TDLN). In vulvar cancer, in-depth studies on the immune status of (pre)metastatic TDLN is lacking. Methods We have phenotyped and enumerated various T-cell and myeloid subsets in tumor-free (LN−, n=27) and metastatic TDLN (LN+, n=11) using flow cytometry. Additionally, we studied chemokine and cytokine release profiles and assessed expression of indoleamine 2,3-dioxygenase (IDO) in relation to plasmacytoid dendritic cell (pDC) or myeloid subsets. Results Metastatic involvement of TDLN was accompanied by an inflamed microenvironment with immune suppressive features, marked by hampered activation of migratory DC, increased cytokine/chemokine release, and closely correlated elevations of pDC and LN-resident conventional DC (LNR-cDC) activation state and frequencies, as well as of terminal CD8 + effector-memory T-cell (TemRA) differentiation, regulatory T-cell (Treg) rates, T-cell activation, and expression of cytotoxic T-lymphocyte protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) immune checkpoints. In addition, high indoleamine 2,3-dioxygenase (IDO) expression and increased frequencies of monocytic myeloid-derived suppressor cells (mMDSC) were observed. Correlation analyses with primary and metastatic tumor burden suggested respective roles for Tregs and suppression of inducible T cell costimulator (ICOS) + T helper cells in early metastatic niche formation and for CD14 + LNR-cDC and terminal T-cell differentiation in later stages of metastatic growth. Conclusions Metastatic spread in vulvar TDLN is marked by an inflamed microenvironment with activated effector T cells, which are likely kept in check by an interplay of suppressive feedback mechanisms. Our data support (neoadjuvant) TDLN-targeted therapeutic interventions based on CTLA-4 and PD-1 blockade, to reinvigorate memory T cells and curb early metastatic spread and growth.
Abstract 16018: Genetic variation near HCRTR2 associates with dramatic improvement of heart function in patients with heart failure
Authors: Marco V. Perez, Aleksandra Pavlovic, Matthew T. Wheeler, Frederick E. Dewey, Stephen Pan, Devin Absher, Elizabeth Cretti, Audrey Southwick, Paul Heidenreich, Daniel Sedehi, Jeffrey Brandimarto, David Kao, Heidi Salisbury, Khin Chan, David Rosenthal, Daniel Bernstein, Michael B. Fowler, Robert C. Robbins, Richard M. Myers, Thomas Quertermous, Thomas Cappola, Euan Ashley
Journal: Circulation (2013)

Marco V. Perez, 2013 Finalist and Presenting Author
Vaccinating adolescents against SARS-CoV-2 in England: a risk–benefit analysis
Authors: Deepti Gurdasani, Samir Bhatt, Anthony Costello, Spiros Denaxas, Seth Flaxman, Trisha Greenhalgh, Stephen Griffin, Zoë Hyde, Aris Katzourakis, Martin McKee, Susan Michie, Oliver Ratmann, Stephen Reicher, Gabriel Scally, Christopher Tomlinson, Christian Yates, Hisham Ziauddeen, Christina Pagel
Journal: Journal of the Royal Society of Medicine (2021)

To offer a quantitative risk-benefit analysis of two doses of SARS-CoV-2 vaccination among adolescents in England.England.Following the risk-benefit analysis methodology carried out by the US Centers for Disease Control, we calculated historical rates of hospital admission, Intensive Care Unit admission and death for ascertained SARS-CoV-2 cases in children aged 12-17 in England. We then used these rates alongside a range of estimates for incidence of long COVID, vaccine efficacy and vaccine-induced myocarditis, to estimate hospital and Intensive Care Unit admissions, deaths and cases of long COVID over a period of 16 weeks under assumptions of high and low case incidence.All 12-17 year olds with a record of confirmed SARS-CoV-2 infection in England between 1 July 2020 and 31 March 2021 using national linked electronic health records, accessed through the British Heart Foundation Data Science Centre.Hospitalisations, Intensive Care Unit admissions, deaths and cases of long COVID averted by vaccinating all 12-17 year olds in England over a 16-week period under different estimates of future case incidence.At high future case incidence of 1000/100,000 population/week over 16 weeks, vaccination could avert 4430 hospital admissions and 36 deaths over 16 weeks. At the low incidence of 50/100,000/week, vaccination could avert 70 hospital admissions and two deaths over 16 weeks. The benefit of vaccination in terms of hospitalisations in adolescents outweighs risks unless case rates are sustainably very low (below 30/100,000 teenagers/week). Benefit of vaccination exists at any case rate for the outcomes of death and long COVID, since neither have been associated with vaccination to date.Given the current (as at 15 September 2021) high case rates (680/100,000 population/week in 10-19 year olds) in England, our findings support vaccination of adolescents against SARS-CoV2.
A novel technique of migrated biliary stent retrieval
Authors: Rami Reddy Yalaka, Chandan Kumar Kedarisetty, Santhosh M. Narayankar, Kondal Reddy Mogili, Manjunath T. Shepur, Sasanka Vangara
Journal: Endoscopy (2021)

A 28-year-old man presented for stent removal one year after endoscopic retrograde cholangiogram and biliary stenting for anastomotic stricture after living-donor liver transplantation. On duodenoscopy, two biliary stents were visible at the papilla, and retrieval was attempted with the aid of a snare. However, only one stent could be removed completely and the second biliary stent broke off and migrated proximally.
Adaptive immune cells shape obesity-associated type 2 diabetes mellitus and less prominent comorbidities
Authors: Sara SantaCruz-Calvo, Leena Bharath, Gabriella Pugh, Lucia SantaCruz-Calvo, Raji Rajesh Lenin, Jenny Lutshumba, Rui Liu, Adam D. Bachstetter, Beibei Zhu, Barbara S. Nikolajczyk
Journal: Nature Reviews Endocrinology (2021)
A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma
Authors: Andrew B. Lassman, Patrick Y. Wen, Martin J. van den Bent, Scott R. Plotkin, Annemiek M.E. Walenkamp, Adam L. Green, Kai Li, Christopher J. Walker, Hua Chang, Sharon Tamir, Leah Henegar, Yao Shen, Mariano J. Alvarez, Andrea Califano, Yosef Landesman, Michael G. Kauffman, Sharon Shacham, Morten Mau-Sørensen
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Selinexor is an oral selective inhibitor of exportin-1 (XPO1) with efficacy in various solid and hematologic tumors. We assessed intratumoral penetration, safety, and efficacy of selinexor monotherapy for recurrent glioblastoma. Patients and Methods: Seventy-six adults with Karnofsky Performance Status ≥ 60 were enrolled. Patients undergoing cytoreductive surgery received up to three selinexor doses (twice weekly) preoperatively (Arm A; n = 8 patients). Patients not undergoing surgery received 50 mg/m2 (Arm B, n = 24), or 60 mg (Arm C, n = 14) twice weekly, or 80 mg once weekly (Arm D; n = 30). Primary endpoint was 6-month progression-free survival rate (PFS6). Results: Median selinexor concentrations in resected tumors from patients receiving presurgical selinexor was 105.4 nmol/L (range 39.7–291 nmol/L). In Arms B, C, and D, respectively, the PFS6 was 10% [95% confidence interval (CI), 2.79–35.9], 7.7% (95% CI, 1.17–50.6), and 17% (95% CI, 7.78–38.3). Measurable reduction in tumor size was observed in 19 (28%) and RANO-response rate overall was 8.8% [Arm B, 8.3% (95% CI, 1.0–27.0); C: 7.7% (95% CI, 0.2–36.0); D: 10% (95% CI, 2.1–26.5)], with one complete and two durable partial responses in Arm D. Serious adverse events (AEs) occurred in 26 (34%) patients; 1 (1.3%) was fatal. The most common treatment-related AEs were fatigue (61%), nausea (59%), decreased appetite (43%), and thrombocytopenia (43%), and were manageable by supportive care and dose modification. Molecular studies identified a signature predictive of response (AUC = 0.88). Conclusions: At 80 mg weekly, single-agent selinexor induced responses and clinically relevant PFS6 with manageable side effects requiring dose reductions. Ongoing trials are evaluating safety and efficacy of selinexor in combination with other therapies for newly diagnosed or recurrent glioblastoma.
1335P Updated results from a phase I/II study of anlotinib plus docetaxel vs docetaxel as second-line treatment of advanced non-small cell lung cancer (NSCLC)
Authors: Y. Fang, H. Pan, J. Shou, W. Hong, J. Chen, Y. Wang, Q. Guo, L. Lu, C. Rao, X. Yang, D. Zhu, F. Lan
Journal: Annals of Oncology (2021)
Response to comment on “Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2”
Authors: Michael D. Nicholson, Lukas Endler, Alexandra Popa, Jakob-Wendelin Genger, Christoph Bock, Franziska Michor, Andreas Bergthaler
Journal: Science Translational Medicine (2021)

Further analysis of SARS-CoV-2 genome sequencing data identifies several highly recurrent genetic variants with low allele frequencies, which, if filtered out, provide estimates consistent with tighter transmission bottlenecks.
The Many Roles of Cholesterol in Sepsis: A Review
Authors: Daniel A. Hofmaenner, Anna Kleyman, Adrian Press, Michael Bauer, Mervyn Singer
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

The biological functions of cholesterol are diverse, ranging from cell membrane integrity, cell membrane signaling, and immunity to the synthesis of steroid and sex hormones, vitamin D, bile acids, and oxysterols. Multiple studies have demonstrated hypocholesterolemia in sepsis, the degree of which is an excellent prognosticator of poor outcomes. However, the clinical significance of hypocholesterolemia has been largely unrecognized. We undertook a detailed review of the biological roles of cholesterol, the impact of sepsis, its reliability as a prognosticator in sepsis, and the potential utility of cholesterol as a treatment. Sepsis affects cholesterol synthesis, transport, and metabolism. This likely impacts its biological functions, including immunity, hormone and vitamin production, and cell membrane receptor sensitivity. Early preclinical studies show promise for cholesterol as a pleiotropic therapeutic agent. Hypocholesterolemia is a frequent condition in sepsis and an important early prognosticator. Low plasma concentrations are associated with wider changes in cholesterol metabolism and its functional roles, and these appear to play a significant role in sepsis pathophysiology. The therapeutic impact of cholesterol elevation warrants further investigation.
TCT-218 In-Hospital Outcomes of Massive Pulmonary Embolism With Single or Combined Approach Using Different Treatment Modalities: A Nationwide Comparative Analysis
Authors: Rupak Desai, Akhil Jain, Hee Kong Fong, Bisharah Rizvi, Gautam Kumar, Rajesh Sachdeva
Journal: Journal of the American College of Cardiology (2021)
TCT-325 Ultra-Short-Term Evaluation of Coronary Vessel Wall Changes in Reference Segments Adjacent to Culprit Lesions in ST-Segment Elevation Myocardial Infarction
Authors: Kazuhiro Dan, Hector Manel Garcia-Garcia, Omar Yacob, Kayode Kuku, Miguel Adrian Diaz, Marco Valgimigli
Journal: Journal of the American College of Cardiology (2021)
Targeting IgE polyadenylation signal with antisense oligonucleotides decreases IgE secretion and plasma cell viability
Authors: Anne Marchalot, Catherine Horiot, Jean-Marie Lambert, Claire Carrion, Christelle Oblet, Justine Pollet, Michel Cogné, Jeanne Moreau, Brice Laffleur, Laurent Delpy
Journal: Journal of Allergy and Clinical Immunology (2021)
Differential Diagnosis of Anterior Mediastinal Masses in Children (Literature Review with Their Own Clinical Observations)
Authors: N. A. Kriventsova, G. V. Tereshchenko
Journal: Radiology - Practice (2021)

The article is devoted to the description of the X-ray anatomy of the mediastinum, the evolution of the classification of this anatomical region. As well as systematization of radiological signs of the most common formations of the anterior (prevascular) mediastinum in children. Based on these data, a table of the most characteristic radiographic features of various neoplasms of different groups. Reflected basic criteria differential diagnosis of various tumors of the anterior mediastinum.