tbuckley/cabot-search huggingface dataset:
Abstract 12047: Quality of Life in Adults With Congenital Heart Disease Worldwide: A Multilevel Study in 15 Countries
Authors: Silke Apers, Adrienne H Kovacs, Koen Luyckx, Philip Moons
Journal: Circulation (2015)

Objectives: Health care should be evaluated not only on the basis of saving lives, but also in terms of improving the quality of life (QOL). However, results regarding QOL in adults with congenital heart disease (CHD) are inconsistent and vary across the world. Methodological differences and limitations hamper the interpretation of these results. Therefore, we aimed (1) to describe QOL in an international sample of adults with CHD using a uniform method; (2) to investigate the association between patient characteristics and variation in QOL; and (3) to explore international variation in QOL and the relationship with country-specific characteristics. Methods: For this cross-sectional multilevel study, patients were recruited from adult CHD centers or national registries from 15 countries. QOL was assessed by a linear analog scale (0-100). Patient characteristics included sex, age, marital status, educational level, employment status, CHD complexity and patient-reported New York Heart Association (NYHA) class. Country-specific characteristics included national happiness score and six cultural dimensions. Multilevel generalized linear mixed models were conducted and Empirical Bayes estimates for QOL were calculated to account for the sample size in each country. Results: In total, 4,028 adults with CHD were enrolled (median age=32 y; 53% women; 26% mild, 49% moderate, 26% complex CHD). Median QOL for the total sample was 80. Age, marital status, employment status and NYHA class were significantly associated with variation in QOL (p&lt;.001). Australia had the highest QOL estimate (82) and Japan the lowest (72). Four countries had a QOL estimate of ≥80 (i.e., Australia, Switzerland, USA, Malta). After adjusting for patient characteristics, happiness and cultural dimensions were not significantly associated with variation in QOL. Conclusions: This is the first international study comprehensively assessing QOL in any subgroup of cardiac patients. We found that QOL in adults with CHD varies across countries and is related to patient characteristics but not to country-specific characteristics. The identification of significant patient characteristics can support the development of interventions targeting the QOL of adults with CHD around the world.
Prospective pan-cancer germline testing using MSK-IMPACT informs clinical translation in 751 patients with pediatric solid tumors
Authors: Elise M. Fiala, Gowtham Jayakumaran, Audrey Mauguen, Jennifer A. Kennedy, Nancy Bouvier, Yelena Kemel, Megan Harlan Fleischut, Anna Maio, Erin E. Salo-Mullen, Margaret Sheehan, Angela G. Arnold, Alicia Latham, Maria I. Carlo, Karen Cadoo, Semanti Murkherjee, Emily K. Slotkin, Tanya Trippett, Julia Glade Bender, Paul A. Meyers, Leonard Wexler, Filemon S. Dela Cruz, Nai-Kong Cheung, Ellen Basu, Alex Kentsis, Michael Ortiz, Jasmine H. Francis, Ira J. Dunkel, Yasmin Khakoo, Stephen Gilheeney, Sameer Farouk Sait, Christopher J. Forlenza, Maria Sulis, Matthias Karajannis, Shakeel Modak, Justin T. Gerstle, Todd E. Heaton, Stephen Roberts, Ciyu Yang, Sowmya Jairam, Joseph Vijai, Sabine Topka, Danielle N. Friedman, Zsofia K. Stadler, Mark Robson, Michael F. Berger, Nikolaus Schultz, Marc Ladanyi, Richard J. O’Reilly, David H. Abramson, Ozge Ceyhan-Birsoy, Liying Zhang, Diana Mandelker, Neerav N. Shukla, Andrew L. Kung, Kenneth Offit, Ahmet Zehir, Michael F. Walsh
Journal: Nature Cancer (2021)
Preclinical evaluation of the Hsp90 inhibitor SNX-5422 in ibrutinib resistant CLL
Authors: Timothy L. Chen, Bonnie Harrington, Jean Truxall, Ronni Wasmuth, Alexander Prouty, Shelby Sloan, Amy M. Lehman, Deepa Sampath, Eric Orlemans, Robert A. Baiocchi, Lapo Alinari, John C. Byrd, Jennifer A. Woyach, Erin Hertlein
Journal: Journal of Hematology & Oncology (2021)

B-cell receptor (BCR) antagonists such as the BTK inhibitor ibrutinib have proven to effectively target chronic lymphocytic leukemia (CLL) tumor cells, leading to impressive response rates in these patients. However patients do still relapse on ibrutinib, and the progressive disease is often quite aggressive requiring immediate treatment. Several strategies are being pursued to treat patients who relapse on ibrutinib therapy. As the most common form of relapse is the development of a mutant form of BTK which limits ibrutinib binding, agents which lead to degradation of the BTK protein are a promising strategy. Our study explores the efficacy of the Hsp90 inhibitor, SNX-5422, in CLL. The SNX Hsp90 inhibitor was effective in primary CLL cells, as well as B-cell lines expressing either BTK wild type or C481 mutant BTK, which has been identified as the primary resistance mechanism to ibrutinib in CLL patients. Furthermore the combination of SNX-5422 and ibrutinib provided a remarkable in vivo survival benefit in the Eμ-TCL1 mouse model of CLL compared to the vehicle or single agent groups (51 day median survival in the vehicle and ibrutinib groups versus 100 day median survival in the combination). We report here preclinical data suggesting that the Hsp90 inhibitor SNX-5422, which has been pursued in clinical trials in both solid tumor and hematological malignancies, is a potential therapy for ibrutinib resistant CLL.
Coupled liquid biopsy and bioinformatics for pancreatic cancer early detection and precision prognostication
Authors: Jun Hou, XueTao Li, Ke-Ping Xie
Journal: Molecular Cancer (2021)

Abstract Early detection and diagnosis are the key to successful clinical management of pancreatic cancer and improve the patient outcome. However, due to the absence of early symptoms and the aggressiveness of pancreatic cancer, its 5-year survival rate remains below 5 %. Compared to tissue samples, liquid biopsies are of particular interest in clinical settings with respect to minimal invasiveness, repeated sampling, complete representation of the entire or multi-site tumor bulks. The potential of liquid biopsies in pancreatic cancer has been demonstrated by many studies which prove that liquid biopsies are able to detect early emergency of pancreatic cancer cells, residual disease, and recurrence. More interestingly, they show potential to delineate the heterogeneity, spatial and temporal, of pancreatic cancer. However, the performance of liquid biopsies for the diagnosis varies largely across different studies depending of the technique employed and also the type and stage of the tumor. One approach to improve the detect performance of liquid biopsies is to intensively inspect circulome and to define integrated biomarkers which simultaneously profile circulating tumor cells and DNA, extracellular vesicles, and circulating DNA, or cell free DNA and proteins. Moreover, the diagnostic validity and accuracy of liquid biopsies still need to be comprehensively demonstrated and validated.
B-type Natriuretic Peptide Levels Do Not Predict the Need for Mechanical Ventilation in Hospitalized Patients With COVID-19
Authors: D. Perry, T. U. Azam, H. Shadid, M. Pan, H. Berlin, C. Meloche, R. Feroze, J. Leya, P. O'Hayer, E. Anderson, R. Kaakati, B. Abbas, K. Padalia, P. Blakley, P. Zhao, L. L. Zhao, S. Hayek
Journal: Circulation (2020)
Long-term dupilumab treatment for chronic refractory generalized prurigo nodularis: A retrospective cohort study
Authors: Jorge R. Georgakopoulos, David Croitoru, Tina Felfeli, Raed Alhusayen, Perla Lansang, Neil H. Shear, Jensen Yeung, Scott Walsh
Journal: Journal of the American Academy of Dermatology (2021)
Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and Hypertension
Authors: Kotaro Haruhara, Takaya Sasaki, Natasha de Zoysa, Yusuke Okabayashi, Go Kanzaki, Izumi Yamamoto, Ian S. Harper, Victor G. Puelles, Akira Shimizu, Luise A. Cullen-McEwen, Nobuo Tsuboi, Takashi Yokoo, John F. Bertram
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Podocyte depletion and low nephron number are associated with glomerulosclerosis and CKD. However, the relationship between podometrics and nephron number has not previously been reported. The authors estimated podometric parameters and nephron number in 30 Japanese kidney donors. Their podocyte density and number per glomerulus were similar to values reported for other racial groups, whereas they had fewer nonsclerotic nephrons compared with other races. Total podocyte number per kidney declined at a rate of 5.63 million podocytes per year, with 80% of podocyte loss resulting from glomerulosclerosis-associated glomerular loss, and the remainder occurring in healthy glomeruli. Hypertension was associated with lower podocyte density and larger podocyte volume, independent of age. These approaches could be of value in evaluating the kidney in health and disease. Background Podocyte depletion, low nephron number, aging, and hypertension are associated with glomerulosclerosis and CKD. However, the relationship between podometrics and nephron number has not previously been examined. Methods To investigate podometrics and nephron number in healthy Japanese individuals, a population characterized by a relatively low nephron number, we immunostained single paraffin sections from 30 Japanese living-kidney donors (median age, 57 years) with podocyte-specific markers and analyzed images obtained with confocal microscopy. We used model-based stereology to estimate podometrics, and a combined enhanced–computed tomography/biopsy-specimen stereology method to estimate nephron number. Results The median number of nonsclerotic nephrons per kidney was 659,000 (interquartile range [IQR], 564,000–825,000). The median podocyte number and podocyte density were 518 (IQR, 428–601) per tuft and 219 (IQR, 180–253) per 10 6 μ m 3 , respectively; these values are similar to those previously reported for other races. Total podocyte number per kidney (obtained by multiplying the individual number of nonsclerotic glomeruli by podocyte number per glomerulus) was 376 million (IQR, 259–449 million) and ranged 7.4-fold between donors. On average, these healthy kidneys lost 5.63 million podocytes per kidney per year, with most of this loss associated with glomerular loss resulting from global glomerulosclerosis, rather than podocyte loss from healthy glomeruli. Hypertension was associated with lower podocyte density and larger podocyte volume, independent of age. Conclusions Estimation of the number of nephrons, podocytes, and other podometric parameters in individual kidneys provides new insights into the relationships between these parameters, age, and hypertension in the kidney. This approach might be of considerable value in evaluating the kidney in health and disease.
Effects of Lactobacillus reuteri supplementation on the gut microbiota in extremely preterm infants in a randomized placebo-controlled trial
Authors: Magalí Martí, Johanne E. Spreckels, Purnika Damindi Ranasinghe, Erik Wejryd, Giovanna Marchini, Eva Sverremark-Ekström, Maria C. Jenmalm, Thomas Abrahamsson
Journal: Cell Reports Medicine (2021)

Extremely low birth weight (ELBW) infants often develop an altered gut microbiota composition, which is related to clinical complications, such as necrotizing enterocolitis and sepsis. Probiotic supplementation may reduce these complications, and modulation of the gut microbiome is a potential mechanism underlying the probiotic effectiveness. In a randomized, double-blind, placebo-controlled trial, we assessed the effect of Lactobacillus reuteri supplementation, from birth to post-menstrual week (PMW)36, on infant gut microbiota. We performed 16S amplicon sequencing in 558 stool samples from 132 ELBW preterm infants at 1 week, 2 weeks, 3 weeks, 4 weeks, PMW36, and 2 years. Probiotic supplementation results in increased bacterial diversity and increased L. reuteri abundance during the 1st month. At 1 week, probiotic supplementation also results in a lower abundance of Enterobacteriaceae and Staphylococcaceae. No effects were found at 2 years. In conclusion, probiotics may exert benefits by modulating the gut microbiota composition during the 1st month in ELBW infants.
Evaluation of the Clinical Benefit of Cancer Drugs Submitted for Reimbursement Recommendation Decisions in Canada
Authors: Daniel E. Meyers, Kristina Jenei, Timothy M. Chisamore, Bishal Gyawali
Journal: JAMA Internal Medicine (2021)

<h3>Importance</h3> Cancer drugs approved by the US Food and Drug Administration have come under scrutiny for marginal clinical benefits; however, the clinical benefits of cancer drugs recommended for reimbursement in Canada have not been adequately studied. <h3>Objective</h3> To assess the differences in the clinical evidence and benefit of cancer drugs that received a positive vs a negative recommendation for provincial reimbursement in Canada. <h3>Design, Setting, and Participants</h3> This cohort study obtained publicly available regulatory documents from the pan-Canadian Oncology Drug Review (pCODR) and corresponding clinical trial documentation. All cancer drugs with a solid tumor indication that were submitted from the inception of the pCODR (July 2011) to February 2020 were evaluated. To be included, submissions had to have a final reimbursement recommendation; submissions that were incomplete, were withdrawn, or had a pending decision were excluded. <h3>Exposures</h3> A completed reimbursement recommendation decision from the pCODR. <h3>Main Outcomes and Measures</h3> Final reimbursement recommendation (positive vs negative); trial characteristics; and relevant clinical outcomes (ie, overall survival [OS] and progression-free survival [PFS]), including the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores available at the time of pCODR assessment. <h3>Results</h3> Between 2011 and 2020, the pCODR issued 104 reimbursement recommendation decisions for cancer drugs with a solid tumor indication. Among these drug submissions, 78 (75.0%) received a positive recommendation, of which 72 (92.3%) were conditional. Drugs that received a positive recommendation compared with those with a negative recommendation were more likely to have phase 3 randomized clinical trial design (92.3% [72 of 78] vs 53.8% [14 of 26];<i>P</i> &lt; .001) and have substantial benefit according to the ESMO-MCBS scores (61.5% [48 of 78] vs 19.2% [5 of 26];<i>P</i> &lt; .001). The most common primary end points associated with the successful submissions were PFS (53.9%) and OS (32.1%). Overall, 39 of 78 submissions (50.0%) that received a positive recommendation had shown OS benefit, with median (interquartile range) OS gains of 3.7 (2.7-6.5) months. <h3>Conclusions and Relevance</h3> This cohort study found that, although the pCODR takes into account the magnitude of clinical benefit, only half of the cancer drugs that received a positive recommendation had evidence of improved OS and the survival gains were usually modest. These results suggest that, although the pCODR helps filter out some cancer drugs with low quality of evidence and low magnitude of benefit, cancer drugs without meaningful patient benefit continue to enter the Canadian market; these findings are important for making reimbursement policy decisions globally.
Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis
Authors: Sorawat Sangkaew, Damien Ming, Adhiratha Boonyasiri, Kate Honeyford, Siripen Kalayanarooj, Sophie Yacoub, Ilaria Dorigatti, Alison Holmes
Journal: The Lancet Infectious Diseases (2021)

The ability to accurately predict early progression of dengue to severe disease is crucial for patient triage and clinical management. Previous systematic reviews and meta-analyses have found significant heterogeneity in predictors of severe disease due to large variation in these factors during the time course of the illness. We aimed to identify factors associated with progression to severe dengue disease that are detectable specifically in the febrile phase.
Tear <i>N</i>‐glycomics in vernal and atopic keratoconjunctivitis
Authors: Angela Messina, Angelo Palmigiano, Claudia Tosto, Donata Agata Romeo, Luisa Sturiale, Domenico Garozzo, Andrea Leonardi
Journal: Allergy (2021)

Tear fluid N-Glycome from patients affected with vernal (VKC) and atopic keratoconjunctivitis (AKC) was investigated to identify specific changes in tears and to recognize possible glyco-biomarkers.The analysis of the N-glycans was performed using matrix-assisted laser desorption ionization mass spectrometry on single tear samples. Tears from control normal subjects (CTRL), VKC and AKC patients were processed and treated with peptide N-glycosidase F (PNGase F) to deglycosylate N-glycoproteins. Released N-glycans were purified, permethylated, and analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and tandem mass spectrometry (MALDI-TOF MS and MALDI-TOF MS/MS).More than 150 complex N-glycans, including highly fucosylated biantennary, triantennary, tetra-antennary, and bisecting species, were observed in our spectra. Three distinct patterns for CTRL, VKC, and AKC patients were identified in terms of relative intensities for some N-glycans structures. Major variations involved bisecting and hyperfucosylated glycoforms. The most intense ions were associated with species at m/z 1907.0 (asialo, agalacto, bisected, biantennary structure-NGA2B) in CTRL MS profiles, at m/z 2605.3 and 2966.5 in VKC, and at m/z 2792.4 in AKC corresponding to a well-known biantennary, disialylated N-glycan. Several peaks were associated with structures bearing one or two Lewis X epitopes. Structures were confirmed by MS/MS analysis. Quantitative differences among the three groups were statistically significant.Tear MS profiles are rich in specific glycoforms, particularly those with a high fucosylation degree, indicating both core and peripheral decoration. Tear N-glycome analysis provided important information for a better comprehension of VKC and AKC alterations at the molecular level.
Outcomes of persons with COVID-19 in hospitals with and without standard treatment with (Hydroxy)chloroquine
Authors: E. J. G. Peters, D. Collard, S. Van Assen, M. Beudel, M. K. Bomers, J. Buijs, L. R. De Haan, W. De Ruijter, R. A. Douma, P. W. G. Elbers, A. Goorhuis, N. C. Gritters van den Oever, G. H. H. Knarren, H. S. Moeniralam, R. L. M. Mostard, M. J. R. Quanjel, A. C. Reidinga, R. Renckens, J. P. W. Van Den Bergh, I. N. Vlasveld, J. J. Sikkens, B. J. H. van den Born, A. H. Zwinderman
Journal: Clinical Microbiology and Infection (2020)
A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment
Authors: Alessia Balestrini, Victory Joseph, Michelle Dourado, Rebecca M. Reese, Shannon D. Shields, Lionel Rougé, Daniel D. Bravo, Tania Chernov-Rogan, Cary D. Austin, Huifen Chen, Lan Wang, Elisia Villemure, Daniel G.M. Shore, Vishal A. Verma, Baihua Hu, Yong Chen, Laurie Leong, Chris Bjornson, Kathy Hötzel, Alvin Gogineni, Wyne P. Lee, Eric Suto, Xiumin Wu, John Liu, Juan Zhang, Vineela Gandham, Jianyong Wang, Jian Payandeh, Claudio Ciferri, Alberto Estevez, Christopher P. Arthur, Jens Kortmann, Ryan L. Wong, Jose E. Heredia, Jonas Doerr, Min Jung, Jason A. Vander Heiden, Merone Roose-Girma, Lucinda Tam, Kai H. Barck, Richard A.D. Carano, Han Ting Ding, Bobby Brillantes, Christine Tam, Xiaoying Yang, Simon S. Gao, Justin Q. Ly, Liling Liu, Liuxi Chen, Bianca M. Liederer, Joseph H. Lin, Steven Magnuson, Jun Chen, David H. Hackos, Justin Elstrott, Alexis Rohou, Brian S. Safina, Matthew Volgraf, Rebecca N. Bauer, Lorena Riol-Blanco
Journal: The Journal of Experimental Medicine (2021)

Despite the development of effective therapies, a substantial proportion of asthmatics continue to have uncontrolled symptoms, airflow limitation, and exacerbations. Transient receptor potential cation channel member A1 (TRPA1) agonists are elevated in human asthmatic airways, and in rodents, TRPA1 is involved in the induction of airway inflammation and hyperreactivity. Here, the discovery and early clinical development of GDC-0334, a highly potent, selective, and orally bioavailable TRPA1 antagonist, is described. GDC-0334 inhibited TRPA1 function on airway smooth muscle and sensory neurons, decreasing edema, dermal blood flow (DBF), cough, and allergic airway inflammation in several preclinical species. In a healthy volunteer Phase 1 study, treatment with GDC-0334 reduced TRPA1 agonist-induced DBF, pain, and itch, demonstrating GDC-0334 target engagement in humans. These data provide therapeutic rationale for evaluating TRPA1 inhibition as a clinical therapy for asthma.
Declining Life Expectancy in the United States
Authors: Atheendar S. Venkataramani, Rourke O’Brien, Alexander C. Tsai
Journal: JAMA (2021)

This Viewpoint reviews the social and economic drivers of declines in longevity in the US, especially among lower socioeconomic status groups, and proposes policy options for the Biden-Harris administration to mitigate the trend, including an increase in the federally mandated minimum wage.
Leveraging individual differences to understand grounded procedures
Authors: Adam K. Fetterman, Michael D. Robinson, Brian P. Meier
Journal: Behavioral and Brain Sciences (2021)

Abstract We applaud the goals and execution of the target article, but note that individual differences do not receive much attention. This is a shortcoming because individual differences can play a vital role in theory testing. In our commentary, we describe programs of research of this type and also apply similar thinking to the mechanisms proposed in the target article.
Inotuzumab Ozogamicin for Relapsed/Refractory Acute Lymphoblastic Leukemia in the INO-VATE Trial: CD22 Pharmacodynamics, Efficacy, and Safety by Baseline CD22
Authors: Hagop M. Kantarjian, Wendy Stock, Ryan D. Cassaday, Daniel J. DeAngelo, Elias Jabbour, Susan M. O'Brien, Matthias Stelljes, Tao Wang, M. Luisa Paccagnella, Kevin Nguyen, Barbara Sleight, Erik Vandendries, Alexander Neuhof, A. Douglas Laird, Anjali S. Advani
Journal: Clinical Cancer Research (2021)

Abstract Purpose: We assessed the relationship between cluster of differentiation-22 (CD22) expression and outcomes of inotuzumab ozogamicin versus standard of care (SC) in INO-VATE (NCT01564784). Patients and Methods: Adults with relapsed/refractory B-cell precursor CD22-positive (by local or central laboratory) acute lymphoblastic leukemia were randomized to inotuzumab ozogamicin (n = 164) or SC (n = 162). Outcomes were analyzed by baseline CD22 positivity (percentage of leukemic blasts CD22 positive, ≥90% vs. &amp;lt;90%) and CD22 receptor density [molecules of equivalent soluble fluorochrome (MESF), quartile analysis]. Results: Most patients had high (≥90%) CD22 positivity per central laboratory. The response rate was significantly higher with inotuzumab ozogamicin versus SC. Minimal/measurable residual disease negativity, duration of remission (DoR), progression-free survival, and overall survival (OS) were significantly better with inotuzumab ozogamicin versus SC in patients with CD22 positivity ≥90%. Fewer patients had CD22 positivity &amp;lt;90%; for whom, response rates were higher with inotuzumab ozogamicin versus SC, but DoR and OS appeared similar. Similar trends were evident in quartile analyses of CD22 MESF and CD22 positivity per local laboratory. Among inotuzumab ozogamicin–responding patients with subsequent relapse, decrease in CD22 positivity and receptor density was evident, but not the emergence of CD22 negativity. Rates of grade ≥3 hematologic adverse events (AEs) were similar and hepatobiliary AEs rate was higher for inotuzumab ozogamicin versus SC. No apparent relationship was observed between the rates of hematologic and hepatic AEs and CD22 expression. Conclusions: Inotuzumab ozogamicin demonstrated a favorable benefit–risk profile versus SC in patients with higher and lower CD22 expression. Patients with high CD22 expression and normal cytogenetics benefited the most from inotuzumab ozogamicin therapy.