tbuckley/cabot-search huggingface dataset:
A novel bioluminescent mouse model and effective therapy for humoral hypercalcemia of malignancy in adult T-cell leukemia/lymphoma
Authors: Sherry Shu, M.V.P. Nadella, Wessel Dirksen, Soledad Fernandez, Nanda Thudi, Jillian Werbeck, Thomas Rosol
Journal: Cancer Research (2007)

4883  Adult T-cell lymphoma/leukemia (ATLL) is an often fatal T-lymphocyte malignancy caused by infection with human T-cell lymphotropic virus type 1 (HTLV-1). ATLL patients develop severe complications including humoral hypercalcemia of malignancy (HHM) resulting from increased osteoclastic bone resorption. Cytokines, such as tumor necrosis factor-β (TNF-β), and parathyroid hormone-related protein (PTHrP) induce osteoclastic bone resorption and the expression of these genes can be activated by NF-κB. A proteasome inhibitor, PS-341, disrupts the NF-κB pathway. In addition, bisphosphonates, such as zoledronic acid (zol), have been used for treatment of HHM; however, little is known about the effects of these two drugs on tumor burden and HHM in ATLL patients. Our goal was to establish an in vivo model to evaluate the effects of NF-κB disruption and osteoclastic inhibition on the development of ATLL and HHM. To examine the in vitro effects on proliferation, cell viability and apoptosis, the MTT, trypan blue exclusion and TUNEL assays were performed, respectively. PS-341 significantly inhibited proliferation (IC50 = 10 nM), decreased viability (50% reduction at 25 nM), and induced apoptosis (43% at 20 nM). PS-341 also inhibited PTHrP expression in ATLL cells using real-time RT-PCR. To monitor tumor burden in vivo by noninvasive bioluminescent imaging (BLI), ATLL cells were transduced with a luciferase reporter gene. Forty million cells were injected into NOD/SCID mice and mice were treated with vehicle alone, PS-341 alone, zol alone, or a combination of PS-341 and zol. The BLI signals, plasma calcium concentrations and the cell numbers obtained from abdominal lavage in treatment groups were significantly lower than the vehicle control group (all p values were
Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size
Authors: Wenzel M Hackeng, Lodewijk A A Brosens, Joo Young Kim, Roderick O'Sullivan, You-Na Sung, Ta-Chiang Liu, Dengfeng Cao, Michelle Heayn, Jacqueline Brosnan-Cashman, Soyeon An, Folkert H M Morsink, Charlotte M Heidsma, Gerlof D Valk, Menno R Vriens, Els Nieveen van Dijkum, G Johan A Offerhaus, Koen M A Dreijerink, Herbert Zeh, Amer H Zureikat, Melissa Hogg, Kenneth Lee, David Geller, J Wallis Marsh, Alessandro Paniccia, Melanie Ongchin, James F Pingpank, Nathan Bahary, Muaz Aijazi, Randall Brand, Jennifer Chennat, Rohit Das, Kenneth E Fasanella, Asif Khalid, Kevin McGrath, Savreet Sarkaria, Harkirat Singh, Adam Slivka, Michael Nalesnik, Xiaoli Han, Marina N Nikiforova, Rita Teresa Lawlor, Andrea Mafficini, Boris Rusev, Vincenzo Corbo, Claudio Luchini, Samantha Bersani, Antonio Pea, Sara Cingarlini, Luca Landoni, Roberto Salvia, Massimo Milione, Michele Milella, Aldo Scarpa, Seung-Mo Hong, Christopher M Heaphy, Aatur D Singhi
Journal: Gut (2021)

Objective Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. Design An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). Results ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p&lt;0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p&lt;0.001 and p&lt;0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p&lt;0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). Conclusions ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.
SAT0562 BURDEN OF RHEUMATIC DISEASE AMONG KOREAN WOMEN IN CHILDBEARING YEARS BASED ON THE NATIONAL HEALTH INSURANCE SERVICE
Authors: Min Kyung Chung, Jin Su Park, Hyun Sun Lim, Chan Hee Lee, Jisoo Lee
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Many rheumatic diseases (RDs) predominantly affect women in their reproductive years, and have a significant impact on childbearing, but its burden remains incompletely understood. <h3>Objectives:</h3> The study aimed to identify the prevalence and incidence of RDs among Korean women in childbearing years, and the effect of the diseases on prevalence of comorbidities, medication use, and pregnancy rate. <h3>Methods:</h3> From National Health Insurance Service data during 2009-2016, we identified 9,217,139 women aged between 20-44 years. Among these women, we estimated the prevalence and incidence of RDs including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS). Prevalence of chronic diseases such as cancer (Ca), hypertension (HT), hyperlipidemia (HLD), and diabetes mellitus (DM) was compared in women with or without RDs. The prescription prevalence of medications including NSAIDs and corticosteroids were compared according to the presence of RDs. We also investigated pregnancy rate in women with rheumatic or chronic diseases, and control subjects without rheumatic or chronic diseases. <h3>Results:</h3> Overall prevalence of RDs was 56.3 per 100,000 20-44 aged females, and overall incidence was 7.68 cases per 100,000 person-years. Women with RDs had increased risk for overall chronic diseases (OR 3.0), and for Ca (OR 1.3), HT (OR 1.4), HLD (OR 2.9), and DM (OR 2.8), respectively (p&lt;0.0001). The prescription of NSAIDs and steroids was significantly more frequent in women with RDs than those without (81.62% vs 21.79% in NSAIDs, 77.83% vs 4.28% in steroids, p&lt;0.0001). Pregnancy rate was significantly lower in women with RDs compared with the controls (15.92% vs 19.30%, p&lt;0.001). Among women with RDs, women with RA were less likely to become pregnant (OR 0.80, p&lt;0.0001), whereas women with SLE and AS showed no significant difference in pregnancy rate compared with the normal controls. <h3>Conclusion:</h3> RDs are a significant burden for women in childbearing years causing increased co-morbidities and medication use and causing reduced pregnancy rate. <h3>References</h3> [1] Sung YK, Cho SK, Choi CB, Bae SC. Prevalence and incidence of rheumatoid arthritis in South Korea. Rheumatol Int2013;33:1525-32. [2] Sammaritano LR. Pregnancy in rheumatic disease patients. J Clin Rheumatol 2013;19:259-66. [3] Castaneda S, Nurmohamed MT, Gonzalez-Gay MA. Cardiovascular disease in inflammatory rheumatic diseases. Best Pract Res Clin Rheumatol 2016;30:851-69. <h3>Disclosure of Interests:</h3> None declared
Climate change, hunger, and rural health through the lens of farming styles: an agent-based model to assess the potential role of peasant farming
Authors: Simon J Lloyd, Zaid Chalabi
Journal: The Lancet Planetary Health (2021)

BackgroundUndernutrition is a major contributor to the global burden of disease, and global-level health impact models suggest that climate change-mediated reductions in food quantity and quality will negatively impact undernutrition. These models, however, capture just some of the processes that will shape future nutrition. We aimed to assess how different farm development trajectories might impact on hunger and health-supporting conditions in rural areas under climate change.MethodsWe developed an agent-based model in which producer-consumer smallholders practise different styles of farming in the global food system. The model represents a hypothetical rural community in which subsistence farmers can develop their farm by adopting an entrepreneurial style (highly market dependent) or by maintaining a peasant style (agroecology). The model was parameterised using globally representative average estimates (eg, the rate of climate change, crop yields, and weather-related losses) from the existing literature. We used the model to explore how patterns of farming styles, under various style preference, climate, policy, and price transmission scenarios, impact on hunger and health-supporting conditions (ie, incomes, work, inequality, and real land productivity) in rural areas.FindingsSimulations without climate change or agricultural policy found that style preference patterns influence production, food price, and incomes, and that there were trade-offs between them. For instance, entrepreneurial-oriented futures had the highest production and lowest prices but were simultaneously those in which farming livelihoods tended to be inviable. Simulations with climate change and agricultural policy found that peasant-orientated agroecology futures had the highest production and prices equal to or lower than those under entrepreneurial-oriented futures, and better supported health in rural areas. There were, however, contradictory effects on nutrition, with benefits and harms for different groups.InterpretationCollectively, the findings suggest that when attempting to understand how climate change might affect future nutrition and health, patterns of farming styles—along with the fates of the households that practise them—are of importance. These issues, including the potential role of peasant farming, have been neglected in previous global-level climate-nutrition modelling, but go to the heart of current debates on the future of farming, and thus should be given more prominence in future work.FundingNone.
Time-Limited Trials and Potentially Nonbeneficial Treatment in the ICU—Willing to Wait for It
Authors: Richard E. Leiter, James A. Tulsky
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Abstract 274: Identifying the Optimal Cerebral Perfusion Pressure Following Hypoxic-Ischemic Brain Injury
Authors: Izad-Yar D Rasheed, Benjamin S Abella, W. Andrew Kofke, Ramani Balu
Journal: Circulation (2019)

Introduction: The optimal cerebral perfusion pressure (CPP) following hypoxic-ischemic brain injury (HIBI) is currently unknown. We retrospectively analyzed intracranial monitoring data from a cohort of patients with HIBI to identify a threshold level for CPP that optimizes cerebrovascular pressure reactivity (a surrogate for CA) while limiting the risk of intracranial hypertension and brain tissue hypoxia. Hypothesis: We hypothesized that higher CPP values would be associated with improved cerebrovascular pressure reactivity. Methods: ICP, brain tissue oxygen (P bt O 2 ), MAP, and CPP (defined as MAP - ICP) were recorded continuously and time synchronized for all patients using a bedside monitor (CNS Monitor, Moberg Research). Pressure Reactivity Index (PRx) was calculated as the time varying correlation between MAP and ICP over 5 min intervals updated every minute. The degree of CA impairment (defined as % time PRx &gt; 0.2) was plotted against MAP and CPP, respectively. The relationships between ICP and P bt O 2 versus CPP, as well as ICP and P bt O 2 versus % time PRx &gt; 0.2, were similarly calculated. Results: We analyzed 37 patients (33 cardiac arrest, 4 prolonged hypoxia) with HIBI who underwent intracranial neuromonitoring over a 3 year period. Lower CPP values were associated with higher degrees of CA impairment. The cumulative burden of elevated PRx was significantly lower for CPP values above a cutoff of 85 mmHg compared to lower CPP values (p &lt; 0.001, Wilcoxon rank sum test). A similar cutoff for MAP could not be identified, although lower MAP values were also associated with greater CA impairment. Intracranial hypertension (ICP &gt; 20 mmHg) and brain hypoxia (P bt O2 &lt; 20 mmHg) were both associated with CA impairment (p &lt; 0.001 and p &lt; 0.001, respectively, Wilcoxon rank sum test). Conclusions: Higher CPP and MAP values appear to be associated with improved CA after HIBI. Given that CA impairment is associated with both intracranial hypertension and brain hypoxia, our work reaffirms the notion that higher blood pressure targets may improve outcome after HIBI. The identification of a distinct CPP cutoff for CA optimization suggests that targeting CPP instead of MAP may be advantageous, although further work is required to clarify this issue.
Covid-19: Spike in cases in Chile is blamed on people mixing after first vaccine shot
Authors: Luke Taylor
Journal: BMJ (2021)

Covid-19: Spike in cases in Chile is blamed on people mixing after first vaccine shot Luke TaylorCases of the novel coronavirus are surging in Chile despite the country having one of the most successful vaccine rollouts in the world.Chile reported 7370 infections on 18 April, down slightly on the record high of 9151 cases reported on 9 April.Some 96% of the intensive care beds in the country are occupied as hospitals come under growing strain from the most severe coronavirus outbreak yet.
Abstract 16085: Digoxin is Associated With Increased Mortality in Patients With Atrial Fibrillation Without Concomitant Heart Failure
Authors: Maciej Tysarowski, Nigri Rafael, Hyoeun Kim, Emad Aziz
Journal: Circulation (2020)

Introduction: There is conflicting data on the effect of digoxin on all-cause mortality in patients with atrial fibrillation (AF), especially in patients with heart failure (HF). Hypothesis: We hypothesized that in patients with AF, mortality rates associated with digoxin treatment are different among patients with HF and without HF. Methods: We conducted a cohort study of hospitalized patients with AF assessing the effects of digoxin on all-cause mortality. We divided patients into two groups: with and without HF. We performed Cox regression analysis to assess hazard ratios (HR) for all-cause mortality depending on digoxin treatment and used propensity score matching to adjust for differences in background characteristics between treatment groups. Results: Among 2179 consecutive patients, the median age was 73 ± 14 (table), 53% patient were male, 49% had HF, 19% were discharged on digoxin. Median left ventricular ejection fraction in the cohort was 60 (IQR 40-65). Among patients with HF, 35% had preserved, 18% had mid-range and 48% had reduced left ventricular ejection fraction. The mean follow-up time was 3 ± 2.1 years. After adjustment, in patients with HF, there was no statistically significant difference in mortality between the digoxin subgroups ( A , HR=1.01 [95% CI 0.76 to 1.35], p=0.92). In contrast, after adjustment, in patients without HF there was a statistically significant increased mortality in the digoxin subgroup ( B , HR=2.23, [95% CI 1.42 to 3.51], p&lt;0.001). Conclusions: Digoxin use was associated with increased mortality in patients with AF and without concomitant HF. This suggests that clinicians should be careful in prescribing digoxin for rate control in AF, especially in patients without concomitant HF.
PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress
Authors: James S. Chavez, Jennifer L. Rabe, Dirk Loeffler, Kelly C. Higa, Giovanny Hernandez, Taylor S. Mills, Nouraiz Ahmed, Rachel L. Gessner, Zhonghe Ke, Beau M. Idler, Katia E. Niño, Hyunmin Kim, Jason R. Myers, Brett M. Stevens, Pavel Davizon-Castillo, Craig T. Jordan, Hideaki Nakajima, John Ashton, Robert S. Welner, Timm Schroeder, James DeGregori, Eric M. Pietras
Journal: The Journal of Experimental Medicine (2021)

Hematopoietic stem cells (HSCs) are capable of entering the cell cycle to replenish the blood system in response to inflammatory cues; however, excessive proliferation in response to chronic inflammation can lead to either HSC attrition or expansion. The mechanism(s) that limit HSC proliferation and expansion triggered by inflammatory signals are poorly defined. Here, we show that long-term HSCs (HSCLT) rapidly repress protein synthesis and cell cycle genes following treatment with the proinflammatory cytokine interleukin (IL)-1. This gene program is associated with activation of the transcription factor PU.1 and direct PU.1 binding at repressed target genes. Notably, PU.1 is required to repress cell cycle and protein synthesis genes, and IL-1 exposure triggers aberrant protein synthesis and cell cycle activity in PU.1-deficient HSCs. These features are associated with expansion of phenotypic PU.1-deficient HSCs. Thus, we identify a PU.1-dependent mechanism triggered by innate immune stimulation that limits HSC proliferation and pool size. These findings provide insight into how HSCs maintain homeostasis during inflammatory stress.
Sponge particulates for biomedical applications: Biofunctionalization, multi-drug shielding, and theranostic applications
Authors: Huaqing Zhang, Yi Jin, Cheng Chi, Guochen Han, Wenxin Jiang, Zhen Wang, Hao Cheng, Chenshuang Zhang, Gang Wang, Chenhua Sun, Yun Chen, Yilong Xi, Mengting Liu, Xie Gao, Xiujun Lin, Lingyu Lv, Jianping Zhou, Yang Ding
Journal: Biomaterials (2021)
MORTALITY IN LATINOS WITH COVID-19, UNIVERSITY OF MIAMI EXPERIENCE
Authors: Raul A. Montanez-Valverde, Victor Becerra-Gonzales, Leonardo Knijnik, Gerardo Zablah, Daniel Lopez, Paul Elias, Sunita Mahabir, Sayari Patel, Rosario Colombo, Carlos Alfonso
Journal: Journal of the American College of Cardiology (2021)
Using digital surveillance tools for near real-time mapping of the risk of infectious disease spread
Authors: Sangeeta Bhatia, Britta Lassmann, Emily Cohn, Angel N. Desai, Malwina Carrion, Moritz U. G. Kraemer, Mark Herringer, John Brownstein, Larry Madoff, Anne Cori, Pierre Nouvellet
Journal: npj Digital Medicine (2021)

Abstract Data from digital disease surveillance tools such as ProMED and HealthMap can complement the field surveillance during ongoing outbreaks. Our aim was to investigate the use of data collected through ProMED and HealthMap in real-time outbreak analysis. We developed a flexible statistical model to quantify spatial heterogeneity in the risk of spread of an outbreak and to forecast short term incidence trends. The model was applied retrospectively to data collected by ProMED and HealthMap during the 2013–2016 West African Ebola epidemic and for comparison, to WHO data. Using ProMED and HealthMap data, the model was able to robustly quantify the risk of disease spread 1–4 weeks in advance and for countries at risk of case importations, quantify where this risk comes from. Our study highlights that ProMED and HealthMap data could be used in real-time to quantify the spatial heterogeneity in risk of spread of an outbreak.
Efficacy and Safety of the 64Cu(II)Cl2 PET/CT for Urological Malignancies
Authors: Manlio Mascia, Carlo Villano, Valerio De Francesco, Luigi Schips, Michele Marchioni, Luca Cindolo
Journal: Clinical Nuclear Medicine (2021)

Purpose of the Report The aim of this study was to evaluate safety and efficacy of copper-64(II)dichloride ( 64 Cu(II)Cl 2 ) as a new PET tracer for urological malignancies (UMs). Methods Patients with UM were enrolled in a prospective study. All patients were staged with preoperative CT and 64 Cu(II)Cl 2 PET/CT. Patient characteristics, anatomical and functional imaging, and final histopathology were recorded. Surgical specimens for histopathological examination were collected. To determine time-activity curves for 64 Cu(II)Cl 2 uptake in UM and normal tissues, SUVs were calculated. The safety of 64 Cu(II)Cl 2 was assessed. Results Twenty-three patients were included. An administered activity of 174.7 MBq (4.72 mCi) for 64 Cu(II)Cl 2 was equal to 9.80 mSv of the effective dose. The median SUVmax values were 5.7, 0.9, 1.8, and 9.8 for the prostate, bladder, penis, and kidney, respectively. Median SUVmax values were higher in organs with a malignancy in comparison with healthy tissue (prostate [11.5 vs 5.3, P &lt; 0.001], bladder [6.2 vs 0.9, P = 0.007], and penis [3.9 vs 1.3, P = 0.027]), but not in the kidneys (5.0 vs 10.4, P = 0.998). The highest area under the curve (AUC) was reported for prostate cancer (AUC, 0.978), and the lowest for penile cancer (AUC, 0.775). The detection rates based on the best suggested cutoff according to the SUVmax were 85.7% (6/7) for prostate and bladder and 83.3% (5/6) for penile cancer. Neither drug-related effects nor physiologic responses occurred, nor adverse reactions. Conclusions 64 Cu(II)Cl 2 is an effective and well-tolerated tracer in patients with UM. Our results show higher SUVmax in cancer patients than in healthy subjects. Our findings suggest that 64 Cu(II)Cl 2 PET/CT is useful in patients affected by prostate, bladder, and penis cancer.
Abstract 11768: Adipose Tissue Area and Progression of Coronary Plaque Among HIV-Infected- and Uninfected Men: Multicenter Aids Cohort Study (MACS)
Authors: Kazuhiro Osawa, Wendy S Post, Sabina Haberlen, Rine Nakanishi, Frank J Palella, Todd T Brown, Mallory Witt, Lawrence Kingsley, Rahmani Sina, Negin Nezarat, Nasim Sheidaee, Eranthi Jayawardena, Nicolas Kim, Michael Kim, Nicolai Hathiramani, Matthew J Budoff
Journal: Circulation (2018)

Introduction: Subcutaneous lipoatrophy and central lipohypertrophy are common among HIV-infected (HIV+) persons and may contribute to co-morbid conditions, such as cardiovascular disease (CVD). Hyp...