tbuckley/cabot-search huggingface dataset:
Deep learning to detect acute respiratory distress syndrome on chest radiographs: a retrospective study with external validation
Authors: Michael W Sjoding, Daniel Taylor, Jonathan Motyka, Elizabeth Lee, Ivan Co, Dru Claar, Jakob I McSparron, Sardar Ansari, Meeta Prasad Kerlin, John P Reilly, Michael G S Shashaty, Brian J Anderson, Tiffanie K Jones, Harrison M Drebin, Caroline A G Ittner, Nuala J Meyer, Theodore J Iwashyna, Kevin R Ward, Christopher E Gillies
Journal: The Lancet Digital Health (2021)

Acute respiratory distress syndrome (ARDS) is a common, but under-recognised, critical illness syndrome associated with high mortality. An important factor in its under-recognition is the variability in chest radiograph interpretation for ARDS. We sought to train a deep convolutional neural network (CNN) to detect ARDS findings on chest radiographs.CNNs were pretrained on 595 506 radiographs from two centres to identify common chest findings (eg, opacity and effusion), and then trained on 8072 radiographs annotated for ARDS by multiple physicians using various transfer learning approaches. The best performing CNN was tested on chest radiographs in an internal and external cohort, including a subset reviewed by six physicians, including a chest radiologist and physicians trained in intensive care medicine. Chest radiograph data were acquired from four US hospitals.In an internal test set of 1560 chest radiographs from 455 patients with acute hypoxaemic respiratory failure, a CNN could detect ARDS with an area under the receiver operator characteristics curve (AUROC) of 0·92 (95% CI 0·89-0·94). In the subgroup of 413 images reviewed by at least six physicians, its AUROC was 0·93 (95% CI 0·88-0·96), sensitivity 83·0% (95% CI 74·0-91·1), and specificity 88·3% (95% CI 83·1-92·8). Among images with zero of six ARDS annotations (n=155), the median CNN probability was 11%, with six (4%) assigned a probability above 50%. Among images with six of six ARDS annotations (n=27), the median CNN probability was 91%, with two (7%) assigned a probability below 50%. In an external cohort of 958 chest radiographs from 431 patients with sepsis, the AUROC was 0·88 (95% CI 0·85-0·91). When radiographs annotated as equivocal were excluded, the AUROC was 0·93 (0·92-0·95).A CNN can be trained to achieve expert physician-level performance in ARDS detection on chest radiographs. Further research is needed to evaluate the use of these algorithms to support real-time identification of ARDS patients to ensure fidelity with evidence-based care or to support ongoing ARDS research.National Institutes of Health, Department of Defense, and Department of Veterans Affairs.
Outcomes of patients with decreased arterial oxyhaemoglobin saturation on pulmonary arterial hypertension drugs
Authors: Simon Valentin, Arnaud Maurac, Olivier Sitbon, Antoine Beurnier, Emmanuel Gomez, Anne Guillaumot, Laura Textoris, Renaud Fay, Laurent Savale, Xavier Jaïs, David Montani, François Picard, Jean-François Mornex, Grégoire Prevot, François Chabot, Marc Humbert, Ari Chaouat
Journal: European Respiratory Journal (2021)

Background Drugs approved for the treatment of pulmonary arterial hypertension (PAH) improve long-term outcomes. These drugs have pulmonary vasodilator properties which may potentially cause a decrease in arterial oxyhaemoglobin saturation ( S aO 2 ) in some patients. The present retrospective study of the French Pulmonary Hypertension Registry aimed to describe the clinical characteristics and outcomes of patients showing a ≥3% decrease in S aO 2 while treated with PAH drugs. Methods We reviewed 719 PAH patients. The exclusion criteria were PAH associated with congenital heart disease and PAH with overt features of venous/capillaries involvement. Results 173 (24%) patients had a ≥3% decrease in S aO 2 . At diagnosis, they were older with a lower diffusing capacity of the lung for carbon monoxide and a shorter 6-min walk distance compared with those who did not display a ≥3% decrease in S aO 2 . The percentage of patients meeting the European Society of Cardiology/European Respiratory Society (ESC/ERS) low-risk criteria at re-evaluation was significantly lower in those with a ≥3% decrease in S aO 2 and more patients started long-term oxygen therapy in this group (16% versus 5%; p&lt;0.001). A ≥3% decrease in S aO 2 was associated with a poorer survival (hazard ratio 1.81, 95% CI 1.43–2.34; p&lt;0.0001). In a multivariate Cox analysis, a ≥3% decrease in S aO 2 was a prognostic factor independent of age at diagnosis and ESC/ERS risk stratification at follow-up. Conclusions When treated with PAH drugs, a large subset of patients experience a ≥3% decrease in S aO 2 , which is associated with worse long-term outcomes and reduced survival.
Trends in targeted delivery of nanomaterials in colon cancer diagnosis and treatment
Authors: Firdos A. Khan, Reem Albalawi, Faheem H. Pottoo
Journal: Medicinal Research Reviews (2021)

Abstract Colon cancer is an adenocarcinoma, which subsequently develops into malignant tumors, if not treated properly. The current colon cancer therapy mainly revolves around chemotherapy, radiotherapy and surgery, but the search continues for more effective interventions. With the advancement of nanoparticles (NPs), it is now possible to diagnose and treat colon cancers with different types, shapes, and sizes of NPs. Nanoformulations such as quantum dots, iron oxide, polymeric NPs, dendrimers, polypeptides, gold NPs, silver NPs, platinum NPs, and cerium oxide have been either extensively used alone or in combination with other nanomaterials or drugs in colon cancer diagnosis, and treatments. These nanoformulations possess high biocompatibility and bioavailability, which makes them the most suitable candidates for cancer treatment. The size and shape of NPs are critical to achieving an effective drug delivery in cancer treatment and diagnosis. Most NPs currently are under different testing phases (in vitro, preclinical, and clinical), whereas some of them have been approved for therapeutic applications. We have comprehensively reviewed the recent advances in the applications of NPs‐based formulations in colon cancer diagnosis and treatment.
Association of Blood Pressure Classification Using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline With Risk of Heart Failure and Atrial Fibrillation
Authors: Hidehiro Kaneko, Yuichiro Yano, Hidetaka Itoh, Kojiro Morita, Hiroyuki Kiriyama, Tatsuya Kamon, Katsuhito Fujiu, Nobuaki Michihata, Taisuke Jo, Norifumi Takeda, Hiroyuki Morita, Koichi Node, Robert M. Carey, Joao A.C. Lima, Suzanne Oparil, Hideo Yasunaga, Issei Komuro
Journal: Circulation (2021)

Heart failure (HF) and atrial fibrillation (AF) are growing in prevalence worldwide. Few studies have assessed to what extent stage 1 hypertension in the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines is associated with incident HF and AF.Analyses were conducted with a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018 (n=2 196 437; mean age, 44.0±10.9 years; 58.4% men). No participants were taking antihypertensive medication or had a known history of cardiovascular disease. Each participant was categorized as having normal BP (systolic BP <120 mm Hg and diastolic BP <80 mm Hg; n=1 155 885), elevated BP (systolic BP 120-129 mm Hg and diastolic BP <80 mm Hg; n=337 390), stage 1 hypertension (systolic BP 130-139 mm Hg or diastolic BP 80-89 mm Hg; n=459 820), or stage 2 hypertension (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg; n=243 342). Using Cox proportional hazards models, we identified associations between BP groups and HF/AF events. We also calculated the population attributable fractions to estimate the proportion of HF and AF events that would be preventable if participants with stage 1 and stage 2 hypertension were to have normal BP.Over a mean follow-up of 1112±854 days, 28 056 incident HF and 7774 incident AF events occurred. After multivariable adjustment, hazard ratios for HF and AF events were 1.10 (95% CI, 1.05-1.15) and 1.07 (95% CI, 0.99-1.17), respectively, for elevated BP; 1.30 (95% CI, 1.26-1.35) and 1.21 (95% CI, 1.13-1.29), respectively, for stage 1 hypertension; and 2.05 (95% CI, 1.97-2.13) and 1.52 (95% CI, 1.41-1.64), respectively, for stage 2 hypertension versus normal BP. Population attributable fractions for HF associated with stage 1 and stage 2 hypertension were 23.2% (95% CI, 20.3%-26.0%) and 51.2% (95% CI, 49.2%-53.1%), respectively. The population attributable fractions for AF associated with stage 1 and stage 2 hypertension were 17.4% (95% CI, 11.5%-22.9%) and 34.3% (95% CI, 29.1%-39.2%), respectively.Both stage 1 hypertension and stage 2 hypertension were associated with a greater incidence of HF and AF in the general population. The American College of Cardiology/American Heart Association BP classification system may help identify adults at higher risk for HF and AF events.
Potential solutions for discrimination in STEM
Authors: Luisa Maria Diele-Viegas, Tábata Elise Ferreira Cordeiro, Tatiana Emmerich, Juliana Hipólito, Caren Queiroz-Souza, Erilda Sousa, Alianna Cardoso Vançan, Luciana Leite
Journal: Nature Human Behaviour (2021)
Vulnerable Older Adults With Ovarian Cancer—Time to Stop Undertreating
Authors: Stephanie L. Wethington, Deborah K. Armstrong, Stéphanie L. Gaillard
Journal: JAMA Oncology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Disease-specific eQTL screening reveals an anti-fibrotic effect of AGXT2 in non-alcoholic fatty liver disease
Authors: Taekyeong Yoo, Sae Kyung Joo, Hyo Jung Kim, Hyun Young Kim, Hyungtai Sim, Jieun Lee, Hee-Hoon Kim, Sunhee Jung, Youngha Lee, Oveis Jamialahmadi, Stefano Romeo, Won-Il Jeong, Geum-Sook Hwang, Keon Wook Kang, Jae Woo Kim, Won Kim, Murim Choi
Journal: Journal of Hepatology (2021)
Enhanced triacylglycerol catabolism by carboxylesterase 1 promotes aggressive colorectal carcinoma
Authors: Daria Capece, Daniel D’Andrea, Federica Begalli, Laura Goracci, Laura Tornatore, James L. Alexander, Alessandra Di Veroli, Shi-Chi Leow, Thamil S. Vaiyapuri, James K. Ellis, Daniela Verzella, Jason Bennett, Luca Savino, Yue Ma, James S. McKenzie, Maria Luisa Doria, Sam E. Mason, Kern Rei Chng, Hector C. Keun, Gary Frost, Vinay Tergaonkar, Katarzyna Broniowska, Walter Stunkel, Zoltan Takats, James M. Kinross, Gabriele Cruciani, Guido Franzoso
Journal: Journal of Clinical Investigation (2021)

The ability to adapt to low-nutrient microenvironments is essential for tumor cell survival and progression in solid cancers, such as colorectal carcinoma (CRC). Signaling by the NF-κB transcription factor pathway associates with advanced disease stages and shorter survival in patients with CRC. NF-κB has been shown to drive tumor-promoting inflammation, cancer cell survival, and intestinal epithelial cell (IEC) dedifferentiation in mouse models of CRC. However, whether NF-κB affects the metabolic adaptations that fuel aggressive disease in patients with CRC is unknown. Here, we identified carboxylesterase 1 (CES1) as an essential NF-κB-regulated lipase linking obesity-associated inflammation with fat metabolism and adaptation to energy stress in aggressive CRC. CES1 promoted CRC cell survival via cell-autonomous mechanisms that fuel fatty acid oxidation (FAO) and prevent the toxic build-up of triacylglycerols. We found that elevated CES1 expression correlated with worse outcomes in overweight patients with CRC. Accordingly, NF-κB drove CES1 expression in CRC consensus molecular subtype 4 (CMS4), which is associated with obesity, stemness, and inflammation. CES1 was also upregulated by gene amplifications of its transcriptional regulator HNF4A in CMS2 tumors, reinforcing its clinical relevance as a driver of CRC. This subtype-based distribution and unfavorable prognostic correlation distinguished CES1 from other intracellular triacylglycerol lipases and suggest CES1 could provide a route to treat aggressive CRC.
Abstract 14439: Sex Differences in Adiposity and Future Heart Failure With Preserved Ejection Fraction Risk
Authors: Satyam Sarma, Erin Howden, William K Cornwell, Justin S Lawley, Sheryl A Livingston, Mitchel Samels, Braden Everding, Dean Palmer, Benjamin D Levine
Journal: Circulation (2019)

Introduction: Obesity and female sex are important risk factors for HFpEF. It is unknown if the effects of adiposity on cardiovascular morphology differ by sex. Hypothesis: Women with higher body a...
Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study
Authors: Dan Frampton, Tommy Rampling, Aidan Cross, Heather Bailey, Judith Heaney, Matthew Byott, Rebecca Scott, Rebecca Sconza, Joseph Price, Marios Margaritis, Malin Bergstrom, Moira J Spyer, Patricia B Miralhes, Paul Grant, Stuart Kirk, Chris Valerio, Zaheer Mangera, Thaventhran Prabhahar, Jeronimo Moreno-Cuesta, Nish Arulkumaran, Mervyn Singer, Gee Yen Shin, Emilie Sanchez, Stavroula M Paraskevopoulou, Deenan Pillay, Rachel A McKendry, Mariyam Mirfenderesky, Catherine F Houlihan, Eleni Nastouli
Journal: The Lancet Infectious Diseases (2021)

SummaryBackgroundEmergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneous patients with and without the variant.MethodsIn this cohort study, samples positive for SARS-CoV-2 on PCR that were collected from Nov 9, 2020, for patients acutely admitted to one of two hospitals on or before Dec 20, 2020, in London, UK, were sequenced and analysed for the presence of VOC-defining mutations. We fitted Poisson regression models to investigate the association between B.1.1.7 infection and severe disease (defined as point 6 or higher on the WHO ordinal scale within 14 days of symptoms or positive test) and death within 28 days of a positive test and did supplementary genomic analyses in a cohort of chronically shedding patients and in a cohort of remdesivir-treated patients. Viral load was compared by proxy, using PCR cycle threshold values and sequencing read depths.FindingsOf 496 patients with samples positive for SARS-CoV-2 on PCR and who met inclusion criteria, 341 had samples that could be sequenced. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. We found no evidence of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72–1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76–1·38]). We detected no B.1.1.7 VOC-defining mutations in 123 chronically shedding immunocompromised patients or in 32 remdesivir-treated patients. Viral load by proxy was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold value (mean 28·8 [SD 4·7] vs 32·0 [4·8]; p=0·0085) and genomic read depth (1280 [1004] vs 831 [682]; p=0·0011).InterpretationEmerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort.FundingUniversity College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council.
Assessment of arrhythmia mechanism and burden of the infarcted ventricles following remuscularization with pluripotent stem cell-derived cardiomyocyte patches using patient-derived models
Authors: Joseph K Yu, Jialiu A Liang, William H Franceschi, Qinwen Huang, Farhad Pashakhanloo, Eric Sung, Patrick M Boyle, Natalia A Trayanova
Journal: Cardiovascular Research (2021)

Direct remuscularization with pluripotent stem cell-derived cardiomyocytes (PSC-CMs) seeks to address the onset of heart failure post-myocardial infarction (MI) by treating the persistent muscle deficiency that underlies it. However, direct remuscularization with PSC-CMs could potentially be arrhythmogenic. We investigated two possible mechanisms of arrhythmogenesis-focal vs. re-entrant-arising from direct remuscularization with PSC-CM patches in two personalized, human ventricular computer models of post-MI. Moreover, we developed a principled approach for evaluating arrhythmogenicity of direct remuscularization that factors in the VT propensity of the patient-specific post-MI fibrotic substrate and use it to investigate different conditions of patch remuscularization.
Lysine Demethylase 5A Is Required for MYC-Driven Transcription in Multiple Myeloma
Authors: Hiroto Ohguchi, Paul M.C. Park, Tingjian Wang, Berkley E. Gryder, Daisuke Ogiya, Keiji Kurata, Xiaofeng Zhang, Deyao Li, Chengkui Pei, Takeshi Masuda, Catrine Johansson, Virangika K. Wimalasena, Yong Kim, Shinjiro Hino, Shingo Usuki, Yawara Kawano, Mehmet K. Samur, Yu-Tzu Tai, Nikhil C. Munshi, Masao Matsuoka, Sumio Ohtsuki, Mitsuyoshi Nakao, Takashi Minami, Shannon Lauberth, Javed Khan, Udo Oppermann, Adam D. Durbin, Kenneth C. Anderson, Teru Hideshima, Jun Qi
Journal: Blood Cancer Discovery (2021)

Abstract Lysine demethylase 5A (KDM5A) is a negative regulator of histone H3 lysine 4 trimethy­lation (H3K4me3), a histone mark associated with activate gene transcription. We identify that KDM5A interacts with the P-TEFb complex and cooperates with MYC to control MYC-targeted genes in multiple myeloma cells. We develop a cell-permeable and selective KDM5 inhibitor, JQKD82, that increases H3K4me3 but paradoxically inhibits downstream MYC-driven transcriptional output in vitro and in vivo. Using genetic ablation together with our inhibitor, we establish that KDM5A supports MYC target gene transcription independent of MYC itself by supporting TFIIH (CDK7)- and P-TEFb (CDK9)–mediated phosphorylation of RNAPII. These data identify KDM5A as a unique vulnerability in multiple myeloma functioning through regulation of MYC target gene transcription and establish JQKD82 as a tool compound to block KDM5A function as a potential therapeutic strategy for multiple myeloma. Significance: We delineate the function of KDM5A in activating the MYC-driven transcriptional landscape. We develop a cell-permeable KDM5 inhibitor to define the activating role of KDM5A on MYC target gene expression and implicate the therapeutic potential of this compound in mouse models and multiple myeloma patient samples. See related video from the AACR Annual Meeting 2021: https://vimeo.com/554896826
Efficacy of a 300IR house dust mite tablet is consistent when evaluated by the proportion of symptom-controlled days: Results of a large randomised, double-blind placebo-controlled, multicentre trial
Authors: P. Demoly, P. Creticos, Philippe Gevaert, F. De Blay, K. Kowal, M. Le Gall, N. Nenasheva, G. Passalacqua, O. Pfaar, M. Tortajada-Girbes, C. Vidal, T. Casale, J. Corren
Journal: Allergy (2019)
Drug delivery to the pediatric upper airway
Authors: Soheila Ali Akbari Ghavimi, Paul M. Gehret, Matthew R. Aronson, Rossana Schipani, Kyra W.Y. Smith, Ryan C. Borek, John A. Germiller, Ian N. Jacobs, Karen B. Zur, Riccardo Gottardi
Journal: Advanced Drug Delivery Reviews (2021)
Effect of Recombinant Human Perlecan Domain V Tethering Method on Protein Orientation and Blood Contacting Activity on Polyvinyl Chloride
Authors: Keerthana Chandrasekar, Brooke L. Farrugia, Lacey Johnson, Denese Marks, David Irving, Zehra Elgundi, Kieran Lau, Ha Na Kim, Jelena Rnjak‐Kovacina, Marcela M. Bilek, John M. Whitelock, Megan S. Lord
Journal: Advanced Healthcare Materials (2021)

Surface modification of biomaterials is a promising approach to control biofunctionality while retaining the bulk biomaterial properties. Perlecan is the major proteoglycan in the vascular basement membrane that supports low levels of platelet adhesion but not activation. Thus, perlecan is a promising bioactive for blood-contacting applications. This study furthers the mechanistic understanding of platelet interactions with perlecan by establishing that platelets utilize domains III and V of the core protein for adhesion. Polyvinyl chloride (PVC) is functionalized with recombinant human perlecan domain V (rDV) to explore the effect of the tethering method on proteoglycan orientation and bioactivity. Tethering of rDV to PVC is achieved via either physisorption or covalent attachment via plasma immersion ion implantation (PIII) treatment. Both methods of rDV tethering reduce platelet adhesion and activation compared to the pristine PVC, however, the mechanisms are unique for each tethering method. Physisorption of rDV on PVC orientates the molecule to hinder access to the integrin-binding region, which inhibits platelet adhesion. In contrast, PIII treatment orientates rDV to allow access to the integrin-binding region, which is rendered antiadhesive to platelets via the glycosaminoglycan (GAG) chain. These effects demonstrate the potential of rDV biofunctionalization to modulate platelet interactions for blood contacting applications.
Case 11-2021: A 39-Year-Old Woman with Fever, Flank Pain, and Inguinal Lymphadenopathy
Authors: Richelle C. Charles, Madeleine Sertic, Anne M. Neilan, Aliyah R. Sohani
Journal: New England Journal of Medicine (2021)

A 39-year-old woman presented with tender inguinal lymphadenopathy, flank pain, and abdominal pain associated with fever, night sweats, anorexia, and weight loss after visiting Brazil. CT of the abdomen and pelvis revealed bilateral inguinal lymphadenopathy, a right pelvic sidewall lymph node, and a gastrohepatic lymph node. A diagnostic test was performed.