tbuckley/cabot-search huggingface dataset:
Abstract PO-061: Deciphering radiation resistance in head and neck cancer using patient derived organoids
Authors: Vui King Vincent-Chong, Christian Gluck, Pamela A. Hershberger, Satrajit Sinha, Mukund Seshadri
Journal: Clinical Cancer Research (2021)

Abstract Radiation therapy (RT) is an integral component of the standard of care for patients with head and neck squamous cell carcinoma (HNSCC). While advances in radiation delivery methods have led to improved outcomes, radioresistance poses a significant therapeutic challenge and a major cause of poor prognosis in this patient population. To date, a majority of studies investigating mechanisms of radioresistance have employed in vitro monolayer cell culture models that lack the heterogeneity and cell-extracellular matrix interactions. To overcome this limitation, we established and credentialed a panel of 3D patient-derived organoid (PDO) models of HNSCC to identify molecular signatures and signaling pathways that contribute to radiation resistance. A total of 7 PDOs were established from surgical HNSCC specimens and credentialed using a combination of histologic/immunohistochemical evaluation (H&amp;E, cytokeratin, p16), genotyping (HPV), whole exome sequencing (WES) and RNA sequencing analysis. Radiation response of the PDO panel was also examined and assessed for concordance with patient response and PDOs were ranked based on their radiosensitivity and bioinformatic analysis was performed on radiosensitive and radioresistance PDOs to identify molecular pathways associated with resistance. All PDOs retained the histology, p16/HPV status and mutational landscape (p53, HLA-A) of donor patient tissues. Radiation response of PDOs showed excellent (100%) concordance with patient responses (n=5 with history of radiation treatment). RNA-seq revealed identified pathways associated with epithelial mesenchymal transition (IGFBP2, TIMP1, TIMP2, LAMA3, LOXL1), NOTCH signaling (NOTCH1, HES1, FZD1, FZD5, DTX1, NOTCH3, FZD7), E2F targets and G2M checkpoint signaling (MCM2, MCM7, MCM4, PCNA) and the p53 pathway (SFN, NDRG1, ALOX15B). Collectively, our findings illustrate the translational utility of PDOs as a robust platform in identifying potential therapeutic targets that could overcome radiation resistance in HNSCC. Ongoing studies are evaluating the potential of PDOs to serve as a screening platform to identify radiosensitizers through repurposing of FDA-approved drugs to facilitate rapid clinical translation. Citation Format: Vui King Vincent-Chong, Christian Gluck, Pamela A. Hershberger, Satrajit Sinha, Mukund Seshadri. Deciphering radiation resistance in head and neck cancer using patient derived organoids [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-061.
Utility of 18F-FDG PET/CT Imaging in Diagnosing Pulmonary Prosthetic Valve Endocarditis in a Pediatric Patient
Authors: Dariya Hardisky, Rosamaria Tricarico, John M. Kelly, Adam J. Bobbey, Mitchel R. Stacy
Journal: Clinical Nuclear Medicine (2021)

Abstract A 15-year-old girl with a history of complex congenital heart disease and prior pulmonary valve replacement presented with suspected endocarditis. PET/CT imaging with 18 F-FDG was performed to evaluate the potential presence of intracardiac vegetations after previously inconclusive findings from CT angiography, transthoracic echocardiography, and transesophageal echocardiography. PET/CT detected heterogeneous, asymmetric, increased 18 F-FDG uptake in the region of the pulmonary valve prosthesis, typical for infection, and confirmed diagnosis of bacterial infective endocarditis. This report highlights the utility of 18 F-FDG PET/CT imaging to complement the Duke criteria for determining the diagnosis and therapeutic management of pediatric patients with infective endocarditis.
Coronavirus from cities to forests: mapping vulnerable interfaces and hotspots for SARS-CoV-2 spillover from humans to biodiversity
Authors: André Luís Acosta, Fernando Xavier, António Saraiva, José Sabino, Nuno Faria, Ester Sabino, Maria Anice Mureb Salum
Journal: The Lancet Planetary Health (2021)

BackgroundWith the continuous spreading of SARS-CoV-2 globally, the probability for interactions between humans who are infected and wildlife tends to grow intensely, as well as the likelihood of viral spillover from humans to biodiversity. This aspect is of great concern for wildlife conservation and human health, because the list of highly susceptible animal groups that have contracted SARS-CoV-2 (bats, mustelids, and primates) is large and, once infected, these groups can act as vectors and reservoirs, becoming a substrate for viral mutations and recombinations and boosting the risk of new strains emerging, which can return to humans as new diseases. Little is known about the inducing factors facilitating coronavirus spillover from one species to another, but it can be argued that interface zones between wild fauna and humans, which are narrow edges between anthropic (cities, roads, parks, ecotourism sites, and agricultural frontiers) and sylvatic habitat, are zones of increased interaction between humans and wild animals, and thus have a higher probability of viral spillover events than other areas. In a similar context, the habitat compression by forest fragmentation also brings species and infected beings closer, reducing their home ranges and intensifying the risk of spillover among wild populations. Therefore, on the basis of the premise for zoonosis—the greater human–animal interaction, the greater risk of viral spillover—we aimed to identify the most and least susceptible areas to viral spillover in Brazil.MethodsWe developed an approach combining ecological modelling (Biomod2: modelling habitat suitability for 158 bat and 49 primate species) and geographical information systems (by using demographic indicators, roads, and related variables) to map the most and least susceptible areas to spillover in Brazil. This map indicates priority areas for serological surveillance of fauna for monitoring the spillover and circulation of SARS-CoV-2 strains and variants in Brazilian biodiversity.FindingsAmong our most relevant preliminary results, we found that forested areas surrounding the São Paulo Metropolitan Area are among the most susceptible areas for spillover. This resulted from the combination of high contaminated human density and high density of non-human primates interacting with humans in these transitional areas.InterpretationBecause of the high resolution of the results, the map can be useful for action planning and decision making in conservation and health, since susceptible areas denote not only a greater risk of virus jumping from humans to animals, but also of coronaviruses returning from fauna to humans in new viral strains.FundingFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; 2019/12988-7 and 2018/14389-0).
Abstract 182: Transesophageal Echocardiography for Assessment of Fluid Responsiveness After Resuscitation From Cardiac Arrest
Authors: Matthias Gruenewald, Patrick Meybohm, Sebastian Koerner, Jochen Renner, Jens Scholz, Berthold Bein
Journal: Circulation (2010)

Background: Fluid therapy for hemodynamic stabilization after cardiac arrest is challenging as hypovolemia and fluid overload may cause circulatory failure. Therefore, predicting fluid responsivene...
<scp>EBV</scp>‐positive diffuse large B‐cell lymphoma, not otherwise specified: 2022 update on diagnosis, risk‐stratification, and management
Authors: Luis Malpica, Mario L. Marques‐Piubelli, Brady E. Beltran, Julio C. Chavez, Roberto N. Miranda, Jorge J. Castillo
Journal: American Journal of Hematology (2022)

Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an entity included in the WHO classification of lymphoid neoplasms since 2016. EBV+ DLBCL, NOS, is an aggressive B-cell lymphoma associated with EBV infection, and a poor prognosis with standard chemotherapeutic approaches.The diagnosis is made through a careful pathological evaluation. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for percentage of positive cells has not been defined. The differential diagnosis includes plasmablastic lymphoma (PBL), DLBCL associated with chronic inflammation, primary effusion lymphoma (PEL), among others.The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers.Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. Therefore, the inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.
The general fault in our fault lines
Authors: Kai Ruggeri, Bojana Većkalov, Lana Bojanić, Thomas L. Andersen, Sarah Ashcroft-Jones, Nélida Ayacaxli, Paula Barea-Arroyo, Mari Louise Berge, Ludvig D. Bjørndal, Aslı Bursalıoğlu, Vanessa Bühler, Martin Čadek, Melis Çetinçelik, Georgia Clay, Anna Cortijos-Bernabeu, Kaja Damnjanović, Tatianna M. Dugue, Maya Esberg, Celia Esteban-Serna, Ezra N. Felder, Maja Friedemann, Darianna I. Frontera-Villanueva, Patricia Gale, Eduardo Garcia-Garzon, Sandra J. Geiger, Leya George, Allegra Girardello, Aleksandra Gracheva, Anastasia Gracheva, Marquis Guillory, Marlene Hecht, Katharina Herte, Barbora Hubená, William Ingalls, Lea Jakob, Margo Janssens, Hannes Jarke, Ondřej Kácha, Kalina Nikolova Kalinova, Ralitsa Karakasheva, Peggah R. Khorrami, Žan Lep, Samuel Lins, Ingvild S. Lofthus, Salomé Mamede, Silvana Mareva, Mafalda F. Mascarenhas, Lucy McGill, Sara Morales-Izquierdo, Bettina Moltrecht, Tasja S. Mueller, Marzia Musetti, Joakim Nelsson, Thiago Otto, Alessandro F. Paul, Irena Pavlović, Marija B. Petrović, Dora Popović, Gerhard M. Prinz, Josip Razum, Ivaylo Sakelariev, Vivian Samuels, Inés Sanguino, Nicolas Say, Jakob Schuck, Irem Soysal, Anna Louise Todsen, Markus R. Tünte, Milica Vdovic, Jáchym Vintr, Maja Vovko, Marek A. Vranka, Lisa Wagner, Lauren Wilkins, Manou Willems, Elizabeth Wisdom, Aleksandra Yosifova, Sandy Zeng, Mahmoud A. Ahmed, Twinkle Dwarkanath, Mina Cikara, Jeffrey Lees, Tomas Folke
Journal: Nature Human Behaviour (2021)

Pervading global narratives suggest that political polarization is increasing, yet the accuracy of such group meta-perceptions has been drawn into question. A recent US study suggests that these beliefs are inaccurate and drive polarized beliefs about out-groups. However, it also found that informing people of inaccuracies reduces those negative beliefs. In this work, we explore whether these results generalize to other countries. To achieve this, we replicate two of the original experiments with 10,207 participants across 26 countries. We focus on local group divisions, which we refer to as fault lines. We find broad generalizability for both inaccurate meta-perceptions and reduced negative motive attribution through a simple disclosure intervention. We conclude that inaccurate and negative group meta-perceptions are exhibited in myriad contexts and that informing individuals of their misperceptions can yield positive benefits for intergroup relations. Such generalizability highlights a robust phenomenon with implications for political discourse worldwide. Ruggeri et al. tested perceptions of opposing political party members in 10,207 participants from 26 countries. Results show that beliefs about others are overly negative but could be more realistic with transparency about actual group beliefs.
Long-term recurrence rates of actinic keratosis: A systematic review and pooled analysis of randomized controlled trials
Authors: Theresa Steeb, Anja Wessely, Anne Petzold, Titus J. Brinker, Lutz Schmitz, Oliver Schöffski, Carola Berking, Markus V. Heppt
Journal: Journal of the American Academy of Dermatology (2021)
Functional and Economic Impact of INOCA and Influence of Coronary Microvascular Dysfunction
Authors: Christopher L. Schumann, Roshin C. Mathew, John-Henry L. Dean, Yang Yang, Pelbreton C. Balfour, Peter W. Shaw, Austin A. Robinson, Michael Salerno, Christopher M. Kramer, Jamieson M. Bourque
Journal: JACC. Cardiovascular imaging (2021)
A Randomized, Open-Label Comparison of Once-Weekly Insulin Icodec Titration Strategies Versus Once-Daily Insulin Glargine U100
Authors: Ildiko Lingvay, John B. Buse, Edward Franek, Melissa V. Hansen, Mette M. Koefoed, Chantal Mathieu, Jeremy Pettus, Karolina Stachlewska, Julio Rosenstock
Journal: Diabetes Care (2021)

OBJECTIVE Insulin icodec is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms. RESEARCH DESIGN AND METHODS This was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naive adults (n = 205) with type 2 diabetes and HbA1c 7–10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (prebreakfast self-measured blood glucose target 80–130 mg/dL; adjustment ±21 units/week; n = 51), B (80–130 mg/dL; ±28 units/week; n = 51), or C (70–108 mg/dL; ±28 units/week; n = 52), or once-daily insulin glargine 100 units/mL (IGlar U100) (80–130 mg/dL; ±4 units/day; n = 51), all titrated weekly. Percentage of time in range (TIR) (70–180 mg/dL) during weeks 15 and 16 was measured using continuous glucose monitoring. RESULTS TIR improved from baseline (means: A, 57.0%; B, 55.2%; C, 51.0%; IGlar U100, 55.3%) to weeks 15 and 16 (estimated mean: A, 76.6%; B, 83.0%; C, 80.9%; IGlar U100, 75.9%). TIR was greater for titration B than for IGlar U100 (estimated treatment difference 7.08%-points; 95% CI 2.12 to 12.04; P = 0.005). No unexpected safety signals were observed. Level 2 hypoglycemia (&amp;lt;54 mg/dL) was low in all groups (0.05, 0.15, 0.38, 0.00 events per patient-year of exposure for icodec titrations A, B, and C and IGlar U100, respectively), with no episodes of severe hypoglycemia. CONCLUSIONS Once-weekly icodec was efficacious and well tolerated across all three titration algorithms investigated. The results for icodec titration A (80–130 mg/dL; ±21 units/week) displayed the best balance between glycemic control and risk of hypoglycemia.
Saad Shakir Al-Dujaily
Authors: Bilal Saad Al’Dujaily
Journal: BMJ (2021)

My father, Saad Shakir Al-Dujaily, came to the UK from Saddam Hussein’s Iraq, after being blacklisted by the regime. Having trained as a doctor in Baghdad’s famous medical city in 1973 he practised in Iraq until 1981, when he had very little option but to leave. Saad chose the UK, where he served the NHS for 40 …
DEEP VENOUS THROMBOSIS DETECTED ON SYSTEMATIC SCREENING WITH ULTRASOUND IN SEVERE COVID-19 IS ASSOCIATED WITH HIGHER ODDS OF MECHANICAL VENTILATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Mouhand F.H. Mohamed, Mahmood Mubasher, Mhd Baraa Habib, Ibrahim Y. Abubeker
Journal: Journal of the American College of Cardiology (2021)
Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1
Authors: Paul Bastard, Elizaveta Orlova, Leila Sozaeva, Romain Lévy, Alyssa James, Monica M. Schmitt, Sebastian Ochoa, Maria Kareva, Yulia Rodina, Adrian Gervais, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Anna-Lena Neehus, Elana Shaw, Mélanie Migaud, Lucy Bizien, Olov Ekwall, Stefan Berg, Guglielmo Beccuti, Lucia Ghizzoni, Gérard Thiriez, Arthur Pavot, Cécile Goujard, Marie-Louise Frémond, Edwin Carter, Anya Rothenbuhler, Agnès Linglart, Brigite Mignot, Aurélie Comte, Nathalie Cheikh, Olivier Hermine, Lars Breivik, Eystein S. Husebye, Sébastien Humbert, Pierre Rohrlich, Alain Coaquette, Fanny Vuoto, Karine Faure, Nizar Mahlaoui, Primož Kotnik, Tadej Battelino, Katarina Trebušak Podkrajšek, Kai Kisand, Elise M.N. Ferré, Thomas DiMaggio, Lindsey B. Rosen, Peter D. Burbelo, Martin McIntyre, Nelli Y. Kann, Anna Shcherbina, Maria Pavlova, Anna Kolodkina, Steven M. Holland, Shen-Ying Zhang, Yanick J. Crow, Luigi D. Notarangelo, Helen C. Su, Laurent Abel, Mark S. Anderson, Emmanuelle Jouanguy, Bénédicte Neven, Anne Puel, Jean-Laurent Casanova, Michail S. Lionakis
Journal: The Journal of Experimental Medicine (2021)

Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
Seronegative Lyme Disease
Authors: Raymond J. Dattwyler, David J. Volkman, Benjamin J. Luft, John J. Halperin, Josephine Thomas, Marc G. Golightly
Journal: New England Journal of Medicine (1988)

The diagnosis of Lyme disease often depends on the measurement of serum antibodies to Borrelia burgdorferi, the spirochete that causes this disorder. Although prompt treatment with antibiotics may abrogate the antibody response to the infection, symptoms persist in some patients. We studied 17 patients who had presented with acute Lyme disease and received prompt treatment with oral antibiotics, but in whom chronic Lyme disease subsequently developed. Although these patients had clinically active disease, none had diagnostic levels of antibodies to B. burgdorferi on either a standard enzyme-linked immunosorbent assay or immunofluorescence assay. On Western blot analysis, the level of immunoglobulin reactivity against B. burgdorferi in serum from these patients was no greater than that in serum from normal controls. The patients had a vigorous T-cell proliferative response to whole B. burgdorferi, with a mean (±SEM) stimulation index of 17.8±3.3, similar to that (15.8±3.2) in 18 patients with chronic Lyme disease who had detectable antibodies. The T-cell response of both groups was greater than that of a control group of healthy subjects (3.1+0.5; P<0.001). We conclude that the presence of chronic Lyme disease cannot be excluded by the absence of antibodies against B. burgdorferi and that a specific T-cell blastogenic response to B. burgdorferi is evidence of infection in sero-negative patients with clinical indications of chronic Lyme disease. (N Engl J Med 1988; 319:1441–6.)
Time at Home as a Patient-Centered End Point for Surgical Cancer Treatment—Reply
Authors: Tyler R. Chesney, Julie Hallet
Journal: JAMA Surgery (2021)

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PRO-THROMBOTIC SIGNATURE FROM NEUTROPHIL ACTIVATION AND DECREASED ADAMTS13 TO VWF RATIO IS A KEY DRIVER OF CARDIAC INJURY IN HOSPITALIZED PATIENTS WITH COVID-19
Authors: Stephen Yishu Wang, Alexander B. Pine, Michael Mankbadi, C. Hong Chang, Daria Madeeva, Hanming Zhang, Abdel R.B. Dajani, Ian Crandall, Lissa Sugeng, Alfred I. Lee, Hyung Chun
Journal: Journal of the American College of Cardiology (2021)
Metabolic needs of the kidney graft undergoing normothermic machine perfusion
Authors: Asel S. Arykbaeva, Dorottya K. de Vries, Jason B. Doppenberg, Marten A. Engelse, Thomas Hankemeier, Amy C. Harms, Leonie G. Wijermars, Alexander F. Schaapherder, Jaap A. Bakker, Rutger J. Ploeg, Ian P.J. Alwayn, Jan H.N. Lindeman
Journal: Kidney International (2021)

Normothermic machine perfusion (NMP) is emerging as a novel preservation strategy. During NMP, the organ is maintained in a metabolically active state that may not only provide superior organ preservation, but that also facilitates viability testing before transplantation, and ex situ resuscitation of marginal kidney grafts. Although the prevailing perfusion protocols for renal NMP are refined from initial pioneering studies concerning short periods of NMP, it could be argued that these protocols are not optimally tailored to address the putatively compromised metabolic plasticity of marginal donor grafts (i.e., in the context of viability testing and/or preservation), or to meet the metabolic prerequisites associated with prolonged perfusions and the required anabolic state in the context of organ regeneration. Herein, we provide a theoretical framework for the metabolic requirements for renal NMP. Aspects are discussed along the lines of carbohydrates, fatty acids, amino acids, and micronutrients required for optimal NMP of an isolated kidney. In addition, considerations for monitoring aspects of metabolic status during NMP are discussed.