tbuckley/cabot-search huggingface dataset:
JAK2-Inhibitor Therapy Associated Lymphomas in Myelofibrosis: Distinct Clinico-Pathological Features Recapitulated in a Mouse Model
Authors: Sabrina Tripolt, Edit Anna Porpaczy, Andrea Hoelbl-Kovacic, Bettina Gisslinger, Zsuzanna Bago-Horvath, Emilio Casanova, Thomas Decker, Daniela Fux, Gerwin Heller, Harald Herkner, Thomas Kolbe, Christoph Kornauth, Mathias Mueller, Michaela Prchal-Murphy, Ana Iris Schiefer, Christine Schneckenleithner, Cathrin Skrabs, Wolfgang R. Sperr, Philipp Bernhard Staber, Birgit Strobl, Peter Valent, Ingrid Simonitsch-Klupp, Gregor Hoermann, Jean-Jacques Kiladjian, Robert Kralovics, Maria-Theresa Krauth, Ulrich Jaeger, Veronika Sexl, Heinz Gisslinger
Journal: Blood (2017)
Association of Prehospital Oxygen Saturation to Inspired Oxygen Ratio With 1-, 2-, and 7-Day Mortality
Authors: Francisco Martín-Rodríguez, Raúl López-Izquierdo, Carlos del Pozo Vegas, Juan F. Delgado-Benito, Guillermo J. Ortega, Miguel A. Castro Villamor, Ancor Sanz-García
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The early identification of patients at high risk of clinical deterioration represents one of the greatest challenges for emergency medical services (EMS). <h3>Objective</h3> To assess whether use of the ratio of prehospital oxygen saturation measured by pulse oximetry (Spo<sub>2</sub>) to fraction of inspired oxygen (Fio<sub>2</sub>) measured during initial contact by EMS with the patient (ie, the first Spo<sub>2</sub>to Fio<sub>2</sub>ratio) and 5 minutes before the patient's arrival at the hospital (ie, the second Spo<sub>2</sub>to Fio<sub>2</sub>ratio) can predict the risk of early in-hospital deterioration. <h3>Design, Setting, and Participants</h3> A prospective, derivation-validation prognostic cohort study of 3606 adults with acute diseases referred to 5 tertiary care hospitals in Spain was conducted between October 26, 2018, and June 30, 2020. Eligible patients were recruited from among all telephone requests for EMS assistance for adults who were later evacuated with priority in advanced life support units to the referral hospitals during the study period. <h3>Main Outcomes and Measures</h3> The primary outcome was hospital mortality from any cause within the first, second, third, or seventh day after EMS transport to the hospital. The main measure was the Spo<sub>2</sub>to Fio<sub>2</sub>ratio. <h3>Results</h3> A total of 3606 participants comprised 2 separate cohorts: the derivation cohort (3081 patients) and the validation cohort (525 patients). The median age was 69 years (interquartile range, 54-81 years), and 2122 patients (58.8%) were men. The overall mortality rate of the patients in the study cohort ranged from 3.6% for 1-day mortality (131 patients) to 7.1% for 7-day mortality (256 patients). The best model performance was for 2-day mortality with the second Spo<sub>2</sub>to Fio<sub>2</sub>ratio with an area under the curve of 0.890 (95% CI, 0.829-0.950;<i>P</i> &lt; .001), although the other outcomes also presented good results. In addition, a risk-stratification model was generated. The optimal cutoff resulted in the following ranges of Spo<sub>2</sub>to Fio<sub>2</sub>ratios: 50 to 100 for high risk of mortality, 101 to 426 for intermediate risk, and 427 to 476 for low risk. <h3>Conclusions and Relevance</h3> This study suggests that use of the prehospital Spo<sub>2</sub>to Fio<sub>2</sub>ratio was associated with improved management of patients with acute disease because it accurately predicts short-term mortality.
Curcumin down-regulates neuropilin-1, semaphorin 3a, ccl2 and ccr2 mRNA expression in PC-3 cells
Authors: Jeffery Herman, Charles Roselli
Journal: Cancer Research (2008)

2753  Curcumin is the active phytochemical ingredient of turmeric (Curcuma longa). Turmeric is used frequently as a spice in India and Asia, leading to about 80-200 mg of curcumin ingested daily. The ingestion of high levels of curcumin could be one reason for the lower incidence of prostate cancer (PCa) in these regions compared to the United States. It has been reported that curcumin decreases cell viability and invasion of PCa cell lines; however, the underlying mechanism of curcumin in PCa has not yet been fully elucidated. With this study, we hypothesized that curcumin can regulate the expression of important mediators of proliferation and cell motility in PC-3 cells, a bone-derived metastatic androgen-independent prostate cancer cell line. PC-3 cells were exposed to curcumin (30 μM, 18 hrs), dose and time points that are below the threshold levels at which curcumin decreases cell viability, allowing for a better understanding of the mechanistic effects of curcumin that are separate from any cytotoxic effects. Using inventoried Taqman primers in the 7500 FAST Real-Time PCR system (Applied Biosystems), we found that curcumin suppressed the mRNA expression of important mediators of PCa progression and invasion when compared to an ETOH vehicle control. Curcumin significantly decreased(-68% ± 8% SEM) the expression of neuropilin-1 (NP-1), an important receptor of vascular endothelial growth factor (VEGF) isoform 165 signaling. When highly expressed, NP-1 increases invasion and proliferation of PCa. Curcumin also significantly down-regulated (-74% ± 8% SEM) the mRNA expression of semaphorin 3A, another binding partner of NP-1, which can, depending on various cellular cues, lead to very different yet important changes in cellular invasion and adhesion. Furthermore, we found that curcumin significantly decreased (-86% ± 8.1% SEM) the mRNA expression of chemokine CCL2 (chemokine ligand-2 or monocyte chemotactic protein-1) as well as the small membrane bound G-protein CCL2 receptor, CCR2 (-86% ± 4% SEM). Recent evidence demonstrated that CCL2 is a potent chemoattractant of PC-3 cells and CCR2 levels increase with increased PCa progression. We also observed, using a human CCL2 ELISA kit from Ebiosicences, that PC-3 cells exposed to curcumin, exhibited decreased levels of secreted CCL2 (-61% ± 4% SEM). The effects of curcumin were specific to PC-3 and were not uniformly exhibited when other cell lines (DU145, LNCaP and RWPE1) were studied. These data suggest that exposure of bone-derived PC-3 cells to curcumin results in the suppression of important mediators of PCa progression, and indicate novel mechanisms by which curcumin may decrease PCa growth and metastasis.
The prevention and treatment of Plasmodium vivax malaria
Authors: Cindy S. Chu, Nicholas J. White
Journal: PLoS Medicine (2021)

points• The worldwide burden of Plasmodium vivax malaria has more than halved from an estimated 17.3 to 6.5 million cases between 2010 and 2019.This resulted from increased deployment of conventional malaria control measures (rapid diagnostic tests, effective antimalarial treatment, vector control) and significant global investment in malaria elimination.There is no generally available P. vivax vaccine, nor is there likely to be one in the near future.• The latest-generation RDTs used for P. vivax diagnosis have sensitivities comparable to microscopy.Ultrasensitive PCR methods which can detect parasite densities as low as 28/ml have revealed a much higher prevalence of asymptomatic P. vivax infection in malaria endemic regions than previously estimated.• Chloroquine remains an effective schizonticide for vivax malaria, except in Indonesia, Sabah and Papua New Guinea where there is high-level chloroquine resistance.Artemisinin combination therapies are effective alternative schizonticides that unify the treatment of all malarias.Relapses contribute significantly to the burden of P. vivax infections.Prevention of relapse requires "radical cure" with an 8-aminoquinoline (primaquine daily for 7 to 14 days, or single-dose tafenoquine).These drugs cause oxidant haemolysis in G6PD deficiency, so safe use requires G6PD testing.Overall, the risks of primaquine haemolysis have been overemphasised and the benefits of relapse prevention underappreciated.• Qualitative screening tests for G6PD deficiency (detecting <30% normal enzyme activity) are adequate for screening before giving primaquine for radical cure, but a quantitative point of care G6PD test to detect <70% normal enzyme activity is needed for tafenoquine.• Radical curative efficacy depends on the total 8-aminoquinoline dose given; higher primaquine doses (7 mg base/kg rather than 3.5 mg base/kg) are required in parts of Southeast Asia and Oceania.The currently recommended dose of tafenoquine (300 mg) is sub-optimal.In low transmission settings, elimination of vivax malaria is possible with current tools.
Neutralizing monoclonal antibodies for treatment of COVID-19
Authors: Peter C. Taylor, Andrew C. Adams, Matthew M. Hufford, Inmaculada de la Torre, Kevin Winthrop, Robert L. Gottlieb
Journal: Nature reviews. Immunology (2021)

Several neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials. With the US Food and Drug Administration recently granting emergency use authorizations for neutralizing mAbs in non-hospitalized patients with mild-to-moderate COVID-19, there is an urgent need to discuss the broader potential of these novel therapies and to develop strategies to deploy them effectively in clinical practice, given limited initial availability. Here, we review the precedent for passive immunization and lessons learned from using antibody therapies for viral infections such as respiratory syncytial virus, Ebola virus and SARS-CoV infections. We then focus on the deployment of convalescent plasma and neutralizing mAbs for treatment of SARS-CoV-2. We review specific clinical questions, including the rationale for stratification of patients, potential biomarkers, known risk factors and temporal considerations for optimal clinical use. To answer these questions, there is a need to understand factors such as the kinetics of viral load and its correlation with clinical outcomes, endogenous antibody responses, pharmacokinetic properties of neutralizing mAbs and the potential benefit of combining antibodies to defend against emerging viral variants.
Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial
Authors: Lone B Enebo, Kasper K Berthelsen, Martin Kankam, Michael T Lund, Domenica M Rubino, Altynai Satylganova, David C W Lau
Journal: The Lancet (2021)
Spatial proteomic characterization of HER2-positive breast tumors through neoadjuvant therapy predicts response
Authors: Katherine L. McNamara, Jennifer L. Caswell-Jin, Rohan Joshi, Zhicheng Ma, Eran Kotler, Gregory R. Bean, Michelle Kriner, Zoey Zhou, Margaret Hoang, Joseph Beechem, Jason Zoeller, Michael F. Press, Dennis J. Slamon, Sara A. Hurvitz, Christina Curtis
Journal: Nature Cancer (2021)
Modified search, coagulation, and clipping with polyglycolic acid sheet and fibrin glue to reduce delayed bleeding risk after endoscopic submucosal dissection near the dentate line
Authors: Satoshi Abiko, Ayumu Yoshikawa, Kazuaki Harada, Naoki Kawagishi, Itsuki Sano, Hisashi Oda, Takuto Miyagishima
Journal: Endoscopy (2021)

A randomized trial of patients with large nonpedunculated colorectal lesions undergoing endoscopic resection showed that clip closure of mucosal defects in patients with a risk of bleeding could reduce delayed bleeding [1]. However, empirically, lesions near the dentate line are considered to display less wall mobility, and endoscopic ligation is difficult. In post-gastric endoscopic submucosal dissection (ESD) ulcers, which are similarly difficult to close by endoscopic ligation, we have used a modified search, coagulation, and clipping (MSCC) method using polyglycolic acid sheets (PGA) and fibrin glue (PMSCC) for patients at high risk of delayed bleeding [2], and reported good results with no delayed bleeding among nine patients [3]. We therefore devised a new strategy using PMSCC for patients at high risk of delayed bleeding after colorectal ESD near the dentate line.
NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021
Authors: Susan M. Swetter, John A. Thompson, Mark R. Albertini, Christopher A. Barker, Joel Baumgartner, Genevieve Boland, Bartosz Chmielowski, Dominick DiMaio, Alison Durham, Ryan C. Fields, Martin D. Fleming, Anjela Galan, Brian Gastman, Kenneth Grossmann, Samantha Guild, Ashley Holder, Douglas Johnson, Richard W. Joseph, Giorgos Karakousis, Kari Kendra, Julie R. Lange, Ryan Lanning, Kim Margolin, Anthony J. Olszanski, Patrick A. Ott, Merrick I. Ross, April K. Salama, Rohit Sharma, Joseph Skitzki, Jeffrey Sosman, Evan Wuthrick, Nicole R. McMillian, Anita M. Engh
Journal: Journal of the National Comprehensive Cancer Network (2021)

Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2.2020), and Brain Metastases Management (added in v3.2020). The v1.2021 update included additional modifications of these sections and notable revisions to Principles of: Pathology, Surgical Margins for Wide Excision of Primary Melanoma, Sentinel Lymph Node Biopsy, Completion/Therapeutic Lymph Node Dissection, and Radiation Therapy. These NCCN Guidelines Insights discuss the important changes to pathology and surgery recommendations, as well as additions to systemic therapy options for patients with advanced disease.
Lupus Anticoagulant Single Positivity During the Acute Phase of COVID‐19 Is Not Associated With Venous Thromboembolism or In‐Hospital Mortality
Authors: Nicolas Gendron, Marie‐Agnès Dragon‐Durey, Richard Chocron, Luc Darnige, Georges Jourdi, Aurélien Philippe, Camille Chenevier‐Gobeaux, Jérôme Hadjadj, Jérôme Duchemin, Lina Khider, Nader Yatim, Guillaume Goudot, Daphné Krzisch, Benjamin Debuc, Laetitia Mauge, Françoise Levavasseur, Frédéric Pene, Jeremy Boussier, Elise Sourdeau, Julie Brichet, Nadège Ochat, Claire Goulvestre, Christophe Peronino, Tali‐Anne Szwebel, Franck Pages, Pascale Gaussem, Charles‐Marc Samama, Cherifa Cheurfa, Benjamin Planquette, Olivier Sanchez, Jean‐Luc Diehl, Tristan Mirault, Michaela Fontenay, Benjamin Terrier, David M. Smadja
Journal: Arthritis & Rheumatology (2021)

Objective The clinical relevance of antiphospholipid antibodies (aPLs) in COVID‐19 is controversial. This study was undertaken to investigate the prevalence and prognostic value of conventional and nonconventional aPLs in patients with COVID‐19. Methods This was a multicenter, prospective observational study in a French cohort of patients hospitalized with suspected COVID‐19. Results Two hundred forty‐nine patients were hospitalized with suspected COVID‐19, in whom COVID‐19 was confirmed in 154 and not confirmed in 95. We found a significant increase in lupus anticoagulant (LAC) positivity among patients with COVID‐19 compared to patients without COVID‐19 (60.9% versus 23.7%; P &lt; 0.001), while prevalence of conventional aPLs (IgG and IgM anti–β 2 ‐glycoprotein I and IgG and IgM anticardiolipin isotypes) and nonconventional aPLs (IgA isotype of anticardiolipin, IgA isotype of anti‐β 2 ‐glycoprotein I, IgG and IgM isotypes of anti–phosphatidylserine/prothrombin, and IgG and IgM isotypes of antiprothrombin) was low in both groups. Patients with COVID‐19 who were positive for LAC, as compared to patients with COVID‐19 who were negative for LAC, had higher levels of fibrinogen (median 6.0 gm/liter [interquartile range 5.0–7.0] versus 5.3 gm/liter [interquartile range 4.3–6.4]; P = 0.028) and C‐reactive protein (CRP) (median 115.5 mg/liter [interquartile range 66.0–204.8] versus 91.8 mg/liter [interquartile range 27.0–155.1]; P = 0.019). Univariate analysis did not show any association between LAC positivity and higher risks of venous thromboembolism (VTE) (odds ratio 1.02 [95% confidence interval 0.44–2.43], P = 0.95) or in‐hospital mortality (odds ratio 1.80 [95% confidence interval 0.70–5.05], P = 0.24). With and without adjustment for CRP level, age, and sex, Kaplan‐Meier survival curves according to LAC positivity confirmed the absence of an association with VTE or in‐hospital mortality (unadjusted P = 0.64 and P = 0.26, respectively; adjusted hazard ratio 1.13 [95% confidence interval 0.48–2.60] and 1.80 [95% confidence interval 0.67–5.01], respectively). Conclusion Patients with COVID‐19 have an increased prevalence of LAC positivity associated with biologic markers of inflammation. However, LAC positivity at the time of hospital admission is not associated with VTE risk and/or in‐hospital mortality.
Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study
Authors: Robert L Coleman, Domenica Lorusso, Christine Gennigens, Antonio González-Martín, Leslie Randall, David Cibula, Bente Lund, Linn Woelber, Sandro Pignata, Frederic Forget, Andrés Redondo, Signe Diness Vindeløv, Menghui Chen, Jeffrey R Harris, Margaret Smith, Leonardo Viana Nicacio, Melinda S L Teng, Annouschka Laenen, Reshma Rangwala, Luis Manso, Mansoor Mirza, Bradley J Monk, Ignace Vergote, Francesco Raspagliesi, Bohuslav Melichar, Lydia Gaba Garcia, Amanda Jackson, Stephanie Henry, Zdenek Kral, Philipp Harter, Ugo De Giorgi, Maria Bjurberg, Michael Gold, David O'Malley, Brigitte Honhon, Christof Vulsteke, Eveline De Cuypere, Hannelore Denys, Jean-Francois Baurain, Claudio Zamagni, Meaghan Tenney, Mary Gordinier, William Bradley, Matthew Schlumbrecht, Nicola Spirtos, Nicole Concin, Sven Mahner, Giovanni Scambia, Charles Leath, Robin Farias-Eisner, Joshua Cohen, Carolyn Muller, Sumeet Bhatia
Journal: The Lancet Oncology (2021)
ELEVATION OF NT-PROBNP LEVEL IS ASSOCIATED WITH HIGHER IN-HOSPITAL MORTALITY FOR COVID-19 IN ETHNIC MINORITY COMMUNITY
Authors: Preeti Jadhav, Bing Yue, Miguel Rodriguez Guerra, Niel Shah, Sun Haozhe, Haiming Tang, Shoaib Ashraf, Nikee Shrestha, Harika Kalangi, Sunita Karki, Sameer Kandhi, Siddharth Chinta, Amandeep Singh, Jonathan N. Bella, Timothy J Vittorio
Journal: Journal of the American College of Cardiology (2021)
Abstract 415: Underlying Liver Disease and Survival Outcomes in Out-Of-Hospital Cardiac Arrest
Authors: Jieun Pak, Ki Hong Kim, Jong Hwan Kim, Sun Young Lee, Ki Jeong Hong, Sang Do Shin
Journal: Circulation (2019)

Introduction: It is unclear whether underlying liver disease can affect survival outcomes of out-of-hospital cardiac arrest (OHCA) patients. This study aims to evaluate the association between underlying liver disease and survival outcomes of OHCA patients. Methods: This study was a cross-sectional study using a nationwide OHCA registry in Korea. Adult OHCA patients with presumed cardiac etiology from 2013 to 2015 were included. The main exposure was underlying liver disease which was identified from medical record review. We categorized patients into 3 groups: chronic liver disease (CLD) with cirrhosis, CLD without cirrhosis and no CLD group. The primary outcome was discharge with good neurological recovery (cerebral performance category 1 or 2) and the secondary outcome was survival to discharge. Multivariable logistic regression was performed to calculate odds ratios (OR) with 95% confidence intervals (CIs) after adjusting for potential confounders. Results: A total of 8,844 patients, 1,323 (15%) patients had CLD with cirrhosis and 361 (4.1%) patients had CLD without cirrhosis. Good neurological recovery rate was 0.6% in CLD with cirrhosis group, 8.9% in CLD without cirrhosis group and 8.7% in no CLD group (P&lt;0.0001). Compared to no CLD group, CLD with cirrhosis group was less likely to have favorable outcomes (adjusted OR [95% CI]: 0.28 [0.13-0.62] for good neurological recovery and 0.35 [0.21-0.59] for survival to discharge). There was no significant difference in favorable outcomes between no CLD group and CLD without cirrhosis group (adjusted OR [95% CI]: 1.64 [0.92-2.92] for good neurological recovery and 1.38 [0.87-2.19] for survival to discharge). Conclusion: Underlying CLD was associated with survival outcomes of OHCA patients. CLD with cirrhosis was associated with poor neurological recovery for OHCA patients.
Carcinoma of the Liver in Children and Adolescents
Authors: Consolato M. Sergi
Journal: Liver Cancer (2021)

Liver cancer, predominantly hepatocellular carcinoma, is the second most common cause of cancer-related death in adults. Although infrequent in children, hepatocellular carcinoma is a terrifying diagnosis. Rising levels of obesity and obesity-associated lipid metabolic reprogramming of hepatocytes are increasing the prevalence of lipid-rich hepatocellular carcinoma in young adults. Most pediatric liver cancers occur in otherwise healthy liver, with some exceptions such as progressive familial intrahepatic cholestasis, hereditary tyrosinemia, alpha-1-antitrypsin deficiency, and genetic hemochromatosis. In the last decade, although aggressive multidisciplinary treatments including surgical resection and chemotherapy have remarkably improved patient outcomes in terms of decreased recurrence rate and increased overall survival rate, in children with unresectable liver cancer, the 5-year survival rate is still less than 20%. This chapter provides an overview of malignant epithelial tumors of the liver in children and adolescents. Hepatocellular carcinoma, lipid-rich hepatocellular carcinoma, fibrolamellar carcinoma, and cholangiocellular carcinoma are discussed.
Maternal and Perinatal Risk Factors for Pediatric Nonalcoholic Fatty Liver Disease: A Systematic Review
Authors: Ilya Querter, Nele S. Pauwels, Ruth De Bruyne, Ellen Dupont, Xavier Verhelst, Lindsey Devisscher, Hans Van Vlierberghe, Anja Geerts, Sander Lefere
Journal: Clinical Gastroenterology and Hepatology (2021)
Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity
Authors: Sanne E. de Jong, Vincent van Unen, Mikhael D. Manurung, Koen A. Stam, Jelle J. Goeman, Simon P. Jochems, Thomas Höllt, Nicola Pezzotti, Yoanne D. Mouwenda, Madeleine Eunice Betouke Ongwe, Freia-Raphaella Lorenz, Yvonne C. M. Kruize, Shohreh Azimi, Marion H. König, Anna Vilanova, Elmar Eisemann, Boudewijn P. F. Lelieveldt, Meta Roestenberg, B. Kim Lee Sim, Marcel J. T. Reinders, Rolf Fendel, Stephen L. Hoffman, Peter G. Kremsner, Frits Koning, Benjamin Mordmüller, Bertrand Lell, Maria Yazdanbakhsh
Journal: Nature Immunology (2021)