tbuckley/cabot-search huggingface dataset:
Preliminary results of a phase I clinical trial of CYT-6091: A pegylated colloidal gold-TNF nanomedicine
Authors: S. K. Libutti, G. F. Paciotti, L. Myer, R. Haynes, W. E. Gannon, M. Eugeni, G. Seidel, Y. Shutack, N. Yuldasheva, L. Tamarkin
Journal: Journal of Clinical Oncology (2007)

3603 Background: CYT-6091, a nanotherapeutic manufactured by covalently linking tumor necrosis factor-a (TNF) onto the surface of 30 nm particles of pegylated colloidal gold, avoids uptake by the reticuloendothelial system (RES) and distributes primarily to solid tumors. In tumor bearing mice, CYT-6091 shows little to no uptake by the RES and increases intra-tumor TNF levels 10-fold. Electron micrographs show the accumulation of gold nanoparticles in tumors, with few particles in healthy tissue. In dogs with naturally occurring cancers and healthy rabbits, CYT-6091 caused fever but no hypotension, the known DLT for TNF. Methods: CYT-6091 is being tested in a phase I open label trial in solid tumor, advanced stage disease patients. Patients (n=3/dose), admitted to the NIH Clinical Center ICU, receive two IV injections of CYT-6091 on day 0 and 14. Doses start at 50 μg/m 2 of TNF and increase by 50 μg/m 2 increments to 300 μg/m 2 . Vital signs are monitored and blood samples are drawn over 48 hours. The primary endpoint of the study is to determine the MTD for CYT-6091. Secondary endpoints include PK, disease response (staged 45 days post treatment), and the detection of gold nanoparticles in tumors and in adjacent healthy tissue. Results: Seven patients have been treated to date. The three treated with the lowest dose (50 μg/m 2 ) exhibited a febrile response, which was mitigated by acetaminophen and indomethacin pretreatment. None of the seven patients treated with 50, 100 or 150 μg/m 2 showed a DLT hypotensive response, and blood chemistries and urinalysis were not significantly different following treatment. PK estimates for the TNF T1/2, administered as CYT-6091, are 117, 145 and 127 minutes for 50, 100 and 150 μg/m 2 , respectively. Electron micrographs of tumor biopsies and adjacent healthy tissue show as much as a 10-fold increase in the number of gold nanoparticles in tumors from 5 of 6 patients compared to adjacent healthy tissue. Conclusion: These observations are the first definitive demonstration in man of the tumor targeting of a systemically administered, colloidal gold-based nanomedicine. No significant financial relationships to disclose.
Atypical PKC controls β-secretase expression and thereby regulates production of Alzheimer plaque precursor Aβ in brain and insulin receptor degradation in liver.
Authors: Mini P. Sajan, Ursula Braun, Michael Leitges, Colin Park, David M. Diamond, Jin Wu, Barbara C. Hansen, Mildred Acevedo Duncan, Christopher A. Apostolatos, Andre H. Apostolatos, Mark Kindy, Robert V. Farese
Journal: Metabolism (2020)
Extending Personalized Medicine From Mothers to Newborns
Authors: Stefania Triunfo
Journal: JAMA Pediatrics (2020)

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 Pediatrics 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 Pediatrics journal
Abstract MP56: Progression of Hyperglycemia in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Mary R Rooney, Andreea Rawlings, James S Pankow, Justin Echouffo Tcheugui, Josef Coresh, A Richey Sharrett, Elizabeth Selvin
Journal: Circulation (2020)

Introduction: Despite the high prevalence of prediabetes and diabetes in old age, the progression of hyperglycemia in older adults is not well-characterized. Objective: To characterize prevalence and predictors of hyperglycemia progression during 5 years of follow-up among 2894 older adults without diabetes (mean age 76, 60% female, 18% black). Methods: Using data from the ARIC Study, we report according to hyperglycemia (normal or prediabetes) status at baseline (visit 5, 2011-13) the incidence of visit 6 (2016-17) outcomes (normoglycemia, prediabetes, diabetes, or mortality). Multinomial logistic regression was used to identify predictors of these outcomes stratified by baseline hyperglycemia status. In a sensitivity analysis, we applied inverse probability of attrition weights (IPAW) to account for informative missingness. Results: Most participants (64%) with normal HbA1c at baseline had normal HbA1c at the follow-up visit, 19% progressed to prediabetes, 16% died, and 1% developed diabetes (HbA1c ≥6.5% or diabetes medication use or self-report diagnosis). Among participants with prediabetes at baseline, most remained prediabetic 5 years later (61%), 18% died, 14% reverted to normoglycemia, and 7% developed diabetes. Black participants, men, and those with hypercholesterolemia had a higher risk of hyperglycemia progression ( Table ). Physical activity was inversely associated with risk of progression. Body mass index (BMI) in older age was not associated with hyperglycemia progression and BMI was inversely associated with mortality. Results were similar when we used IPAW. Conclusions: In this community-based population of older adults, progression from prediabetes to diabetes was relatively uncommon over the 5 year period. Risk factors for hyperglycemia progression and mortality, such as BMI, may differ when measured in older adulthood. We also identified subgroups with higher risk of hyperglycemia progression in older age and who may benefit from targeted diabetes prevention efforts.
Male and Female Physician Suicidality
Authors: Dante Duarte, Mirret M. El-Hagrassy, Tiago Castro e Couto, Wagner Gurgel, Felipe Fregni, Humberto Correa
Journal: JAMA Psychiatry (2020)

Population-based findings on physician suicide are of great relevance because this is an important and understudied topic.To evaluate male and female physician suicide risks compared with the general population from 1980 to date and test whether there is a reduction of SMR in cohorts after 1980 compared with before 1980 via a meta-analysis, modeling studies, and a systematic review emphasizing physician suicide risk factors.This study uses studies retrieved from PubMed, Scielo, PsycINFO, and Lilacs for human studies published by October 3, 2019, using the search term "(((suicide) OR (self-harm) OR (suicidality)) AND ((physicians) OR (doctors)))." Databases were also searched from countries listed in articles selected for review. Data were also extracted from an existing article by other authors to facilitate comparisons of the pre-1980 suicide rate with the post-1980 changes.Original articles assessing male and/or female physician suicide were included; for the meta-analysis, only cohorts from 1980 to the present were included.The preregistered systematic review and meta-analysis followed Cochrane, PRISMA, and MOOSE guidelines. Data were extracted into standardized tables per a prespecified structured checklist, and quality scores were added. Heterogeneity was tested via Q test, I2, and τ2. For pooled effect estimates, we used random-effects models. The Begg and Egger tests, sensitivity analyses, and meta-regression were performed. Proportional mortality ratios were presented when SMR data could not be extracted.Suicide SMRs for male and female physicians from 1980 to the present and changes over time (before and after 1980).Of 7877 search results, 32 articles were included in the systematic review and 9 articles and data sets in the meta-analysis. Meta-analysis showed a significantly higher suicide SMR in female physicians compared with women in general (1.46 [95% CI, 1.02-1.91]) and a significantly lower suicide SMR in male physicians compared with men in general (0.67 [95% CI, 0.55-0.79]). Male and female physician SMRs significantly decreased after 1980 vs before 1980 (male physicians: SMR, -0.84 [95% CI, -1.26 to -0.42]; P < .001; female physicians: SMR, -1.96 [95% CI, -3.09 to -0.84]; P = .002). No evidence of publication bias was found.In this study, suicide SMR was found to be high in female physicians and low in male physicians since 1980 but also to have decreased over time in both groups. Physician suicides are multifactorial, and further research into these factors is critical.
Soundings: Walking the walk
Authors: James Owen Drife
Journal: BMJ (2003)

Since January each consultant obstetrician in our hospital has been spending a week at a time in the delivery suite. The days of the senior registrar are long gone and now there aren't enough registrars. After years of preaching the need for a consultant based service, I could hardly refuse to join the rota.

I had not done routine labour ward sessions since my lecturer days. For 20 years it had been emergencies only, often at the end of a phone. Of course I had written and lectured about intrapartum care and pontificated as an expert witness. I could talk the talk. Now I had to walk the walk.

Cancelling other commitments proved surprisingly easy. The rota is published a year in advance. There is quiet pleasure in sending apologies to committees on the grounds of clinical indispensability.

In the delivery suite office, reality reigns. The midwives huddle over shift rotas in their free moments, ingeniously working out how to keep the place staffed. On the board is a list of the region's neonatal nurseries, each permanently marked “closed.” What matters is which ones are “very closed.”

The bells, the bells. At the locked front door are streams of relatives. On the phones are endless queries that can rarely be answered by either the hard pressed ward clerk or the professor.

Some things have changed. A computer gives instant access to evidence. Applying it remains an art, however, and the final arbiter is still the midwife's gut feeling. The biggest transformation is in anaesthesia. In this epidural era, shrieks are rare. At caesarean section a radio plays while the woman chats to her partner.

Some things stay the same. Just before an instrumental delivery there is still that moment when you feel alone with the baby, knowing a mistake is not an option.

Hands-on work is immensely satisfying. You end the week with a frontline soldier's contempt for the generals. Then you remember that you are one, or a brigadier at least. Next week you will talk about the midwives' dedication and it will sound like platitudes. You will complain about national understaffing and people will shrug. Talking the talk could make a difference if only you could get it right. You suspect that you are not as good at it as you thought.
Co-opted transposons help perpetuate conserved higher-order chromosomal structures
Authors: Mayank NK Choudhary, Ryan Z. Friedman, Julia T. Wang, Hyo Sik Jang, Xiaoyu Zhuo, Ting Wang
Journal: Genome biology (2020)

Abstract Background Transposable elements (TEs) make up half of mammalian genomes and shape genome regulation by harboring binding sites for regulatory factors. These include binding sites for architectural proteins, such as CTCF, RAD21, and SMC3, that are involved in tethering chromatin loops and marking domain boundaries. The 3D organization of the mammalian genome is intimately linked to its function and is remarkably conserved. However, the mechanisms by which these structural intricacies emerge and evolve have not been thoroughly probed. Results Here, we show that TEs contribute extensively to both the formation of species-specific loops in humans and mice through deposition of novel anchoring motifs, as well as to the maintenance of conserved loops across both species through CTCF binding site turnover. The latter function demonstrates the ability of TEs to contribute to genome plasticity and reinforce conserved genome architecture as redundant loop anchors. Deleting such candidate TEs in human cells leads to the collapse of conserved loop and domain structures. These TEs are also marked by reduced DNA methylation and bear mutational signatures of hypomethylation through evolutionary time. Conclusions TEs have long been considered a source of genetic innovation. By examining their contribution to genome topology, we show that TEs can contribute to regulatory plasticity by inducing redundancy and potentiating genetic drift locally while conserving genome architecture globally, revealing a paradigm for defining regulatory conservation in the noncoding genome beyond classic sequence-level conservation.
Nonculprit Lesion Myocardial Infarction Following Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome
Authors: Benjamin M. Scirica, Brian A. Bergmark, David A. Morrow, Elliott M. Antman, Marc P. Bonaca, Sabina A. Murphy, Marc S. Sabatine, Eugene Braunwald, Stephen D. Wiviott
Journal: Journal of the American College of Cardiology (2020)
A common variant in PNPLA3 is associated with age at diagnosis of NAFLD in patients from a multi-ethnic biobank
Authors: Ryan W. Walker, Gillian M. Belbin, Elena P. Sorokin, Tielman Van Vleck, Genevieve L. Wojcik, Arden Moscati, Christopher R. Gignoux, Judy Cho, Noura S. Abul-Husn, Girish Nadkarni, Eimear E. Kenny, Ruth J.F. Loos
Journal: Journal of Hepatology (2020)
Abstract P464: Progression of Obesity and Physical Inactivity in Chilean Medical and Dentistry Schools Students. A Call for Action
Authors: Daniela Sandoval, Franco Bello, Miguel Bravo, Tomas E Romero
Journal: Circulation (2020)

Background: In Chile obesity has increased (25.1% to 34%), and sedentary lifestyle has remained at 86.7% since 2010 to 2017 despite National programs and campaigns for improvements. It is unknown the prevalence of these and other lifestyle factors in students of medical careers, the expected future promotors of healthy lifestyles throughout their work. Objectives: To determine prevalence of obesity, physical inactivity, emotional stress, smoking and use of alcohol in first year students at University of Chile Faculties of Medicine and Dentistry at admission and throughout their first academic year. Methods: In a longitudinal randomized sample of 253 students (186 females) who completed the study, weight, height, waist circumference, waist circumference-weight ratio, BMI, food consumption, smoking (Glover-Nilsson Test) alcohol use (AUDIT), perceived stress level (PSS), and physical activity (GPAQ) at the first week, 3 and 6 months after their admission were measured. Cochran Test for dichotomic variables and Friedman test for non-parametric variables were used. Results: Average age was 19.1 ± 0.95 years, and blood pressure (first week) 117.2 ± 14.9 / 68.8 ± 8.7 mm/Hg. All the other results are listed in Table 1. Significant increasing prevalence of obesity (general and abdominal, 6.3% to 10.3%) and physical inactivity (&lt; 600 MET/min/week, 16.6% to 22.9%), and poor eating habits with similar sex trends were found. High level PSS persisted throughout the study. Smoking in 17.8 % the first week without significant changes and harmful alcohol consumption declined significantly since admission (10.7 to 5.1%). Conclusions: Progressive obesity and physical inactivity, persistent highly perceived stress, poor eating habits, prevalence of smoking and harmful consumption of alcohol in first year medical students are of concern. Inclusion of lifestyle counseling in the curriculum and revision of its priorities and structure should be considered. A longer follow-up in a larger student cohort is being planned.
Implications of the 5-lipoxygenase allelic variants c.760G&gt;A and -1279 G&gt;T in the nutritional and inflammatory status in Mexican Young Population
Authors: Yesica Sughey Gonzalez-Torres, Napoleon Gonzalez-Silva, Blanca Zuami Villagran-De la Mora, Luis Felipe Guzman-Rodriguez, Angel Perez-Reyes, Christian Martin Rodriguez-Razon, Ana Gabriela Colima-Fausto, Patricia Noemi Vargas-Becerra, Sergio Sanchez-Enriquez, Maritza Roxana Garcia-Garcia
Journal: Metabolism (2020)
メトトレキサートの効果が不十分な患者におけるトシリズマブ追加またはトシリズマブ単独療法への切り替え: 2年間の関節リウマチを対象とした無作為化対照戦略試験(ACT-RAY)の24週間にわたる徴候的および構造的結果 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Dougados Maxime, Kissel Karsten, Sheeran Tom, Tak Paul P, Conaghan Philip G, Mola Emilio Martin, Schett Georg, Amital Howard, Navarro-Sarabia Federico, Hou Antony, Bernasconi Corrado, Huizinga Twj
Journal: Annals of the Rheumatic Diseases (2013)
Asthma, Chronic Obstructive Pulmonary Disease, and Subsequent Risk for Incident Rheumatoid Arthritis Among Women: A Prospective Cohort Study
Authors: Julia A. Ford, Xinyi Liu, Su H. Chu, Bing Lu, Michael H. Cho, Edwin K. Silverman, Karen H. Costenbader, Carlos A. Camargo, Jeffrey A. Sparks
Journal: Arthritis & Rheumatology (2020)

Objective Inflamed airways are hypothesized to contribute to rheumatoid arthritis ( RA ) pathogenesis due to RA ‐related autoantibody production, and smoking is the strongest environmental RA risk factor. However, the role of chronic airway diseases in RA development is unclear. We undertook this study to investigate whether asthma and chronic obstructive pulmonary disease ( COPD ) were each associated with RA . Methods We performed a prospective cohort study of 205,153 women in the Nurses’ Health Study ( NHS , 1988–2014) and NHSII (1991–2015). Exposures were self‐reported physician‐diagnosed asthma or COPD confirmed by validated supplemental questionnaires. The primary outcome was incident RA confirmed by medical record review by 2 rheumatologists. Covariates (including smoking pack‐years/status) were assessed via biennial questionnaires. Multivariable hazard ratios ( HR s) and 95% confidence intervals ( CI s) for RA were estimated using Cox regression. Results We identified 15,148 women with confirmed asthma, 3,573 women with confirmed COPD , and 1,060 incident RA cases during 4,384,471 person‐years (median 24.0 years/participant) of follow‐up in the NHS and NHSII . Asthma was associated with increased RA risk ( HR 1.53 [95% CI 1.24–1.88]) compared to no asthma/ COPD after adjustment for covariates, including smoking pack‐years/status. Asthma remained associated with increased RA risk when analyzing only never‐smokers ( HR 1.53 [95% CI 1.14–2.05]). COPD was also associated with increased RA risk ( HR 1.89 [95% CI 1.31–2.75]). The association of COPD with RA was most pronounced in the subgroup of ever‐smokers age &gt;55 years ( HR 2.20 [95% CI 1.38–3.51]). Conclusion Asthma and COPD were each associated with increased risk of incident RA , independent of smoking status/intensity and other potential confounders. These results provide support for the hypothesis that chronic airway inflammation may be crucial in RA pathogenesis.
Assessment of an Algorithm for Prescription of Oral Anticoagulation for Patients With Atrial Fibrillation in Emergency Departments
Authors: Clare L. Atzema, Jiming Fang, Jafna L. Cox, Alice S. Chong, Karen Tu, Peter C. Austin
Journal: JAMA Network Open (2020)

This retrospective study uses a Canadian reporting system to validate an algorithm that identifies oral anticoagulation prescriptions given to patients with atrial fibrillation treated in emergency departments.
Abstract P383: Trends in Selected Chronic Conditions and Behavioral Risk Factors Among Women of Reproductive Age: Behavioral Risk Factor Surveillance System, 2011-2017
Authors: Donald K Hayes, Jean Y Ko, Cheryl L Robbins
Journal: Circulation (2020)

Introduction: Chronic disease causes significant morbidity and mortality across the lifespan. Public health approaches that reduce or prevent risk factors along with effective management of chronic diseases can improve health. This study describes trends of chronic conditions and related risk factors among reproductive aged women. Methods: Data from the 2011-2017 Behavioral Risk Factor Surveillance System, a representative state-based telephone survey of health behavior in US adults, were analyzed among 265,544 women of reproductive age, 18-44 years. We estimated adjusted prevalence ratios (APR) using predicted marginals to assess trends over time for 12 chronic conditions and related risk factors accounting for age, race/ethnicity, education, and health care coverage. Results: From 2011-2017, estimates of the following decreased: smoking (20.7%—15.9%; P-value &lt;0.001), gestational diabetes (3.1%—2.7%; 0.003), and high cholesterol (19.0%—16.7%, 2011-2015; &lt;0.001). Whereas the estimates increased for depression (20.4%—24.9%; &lt;0.001), and obesity (24.6%—27.6%; &lt;0.001). There were no differences over time for heavy alcohol consumption, binge drinking, diabetes, pregnancy-related high blood pressure, or high blood pressure. In the adjusted analysis, WRA were more likely to report asthma (APR=1.06; 95%CI=1.01—1.11), physical inactivity (1.08; 1.04—1.12), obesity (1.15; 1.11—1.19), and depression (1.29; 1.25—1.34) in 2017 compared to 2011. They were less likely to report high cholesterol (0.89; 0.85—0.94; 2011-2015), smoking (0.86; 0.82—0.89); and gestational diabetes (0.84; 0.75—0.94). Conclusions: Future research should examine why some chronic conditions and related risk factors improved while others worsened. That research may support the development of targeted interventions to promote improvements and reverse the worsening trends in chronic disease and related risk factors, potentially preventing adverse reproductive and long-term health outcomes among women of reproductive age.