tbuckley/cabot-search huggingface dataset:
Oral Anticoagulants, Proton Pump Inhibitors, and Fracture
Authors: Chika Edward Uzoigwe, Luis Carlos Sanchez Franco, Ignacio Gascon Conde
Journal: JAMA Internal Medicine (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 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
Optimizing synthetic nucleic acid and protein nanocarriers: The chemical evolution approach
Authors: Franziska Freitag, Ernst Wagner
Journal: Advanced Drug Delivery Reviews (2020)

Optimizing synthetic nanocarriers is like searching for a needle in a haystack. How to find the most suitable carrier for intracellular delivery of a specified macromolecular nanoagent for a given disease target location? Here, we review different synthetic 'chemical evolution' strategies that have been pursued. Libraries of nanocarriers have been generated either by unbiased combinatorial chemistry or by variation and novel combination of known functional delivery elements. As in natural evolution, definition of nanocarriers as sequences, as barcode or design principle, may fuel chemical evolution. Screening in appropriate test system may not only provide delivery candidates, but also a refined understanding of cellular delivery including novel, unpredictable mechanisms. Combined with rational design and computational algorithms, candidates can be further optimized in subsequent evolution cycles into nanocarriers with improved safety and efficacy. Optimization of nanocarriers differs for various cargos, as illustrated for plasmid DNA, siRNA, mRNA, proteins, or genome-editing nucleases.
A study of the drug secukinumab in the treatment of palmoplantar psoriasis
Authors: A.B. Gottlieb, A. Kubanov, M. Doorn, J. Sullivan, K.A. Papp, R. You, P. Regnault, J.A. Frueh
Journal: British Journal of Dermatology (2020)

Palmoplantar psoriasis is a chronic (long term) and difficult‐to‐treat form of psoriasis that affects the palms of the hands and the soles of the feet. The disease causes reddish, scaly plaques on the palms and/or soles with or without the presence of such scales elsewhere on the body. Since palms and soles are affected, the patient can have serious issues in carrying out tasks of daily life such as walking, bathing and eating. This can lead to severe disturbance of their quality of life, and such patients may withdraw socially or suffer from depression and lack of confidence. A drug called secukinumab has been shown to offer rapid and long‐lasting effectiveness in treating patients with plaque psoriasis (psoriasis with scales on back, trunk, hands and legs); however, its effect on palmoplantar psoriasis had not been exclusively studied. A randomized control trial is a type of clinical trial in which patients are randomly assigned to a treatment group, and there is also a control group who do not receive any of the treatments being studied. GESTURE, the largest and longest duration randomized controlled study, was conducted to assess the efficacy and safety of secukinumab in people with palmoplantar psoriasis. Both the immediate (16 weeks) and long‐term (2.5 years) results were evaluated. Treatment with secukinumab resulted in quick improvements (starting as early as Week 2) in these patients and the Week 16 results proved the efficacy of secukinumab in palmoplantar psoriasis. The patients were further treated and followed‐up until 2.5 years to understand if the effects are continued or if the disease returns (known as relapse). The 2.5‐year results confirmed that secukinumab treatment resulted in long‐lasting effectiveness in patients with palmoplantar psoriasis. Patients experienced improved hand and feet functioning and therefore improved quality of life. No safety issues were identified. This is a summary of the study: Sustained efficacy of secukinumab in patients with moderate‐to‐severe palmoplantar psoriasis: 2.5‐year results from GESTURE, a randomized, double‐blind, placebo‐controlled trial
A Public Health Approach to Global Child Sex Trafficking
Authors: Jordan Greenbaum
Journal: Annual Review of Public Health (2020)

Human trafficking and child sex trafficking and sexual exploitation in particular are global public health issues with widespread, lasting impacts on children, families, and communities. Traditionally, human trafficking has been treated as a law enforcement problem with an emphasis on the arrest and prosecution of traffickers. However, use of a public health approach focuses efforts on those impacted by exploitation: trafficked persons, their families, and the population at large. It promotes strategies to build a solid scientific evidence base that allows development, implementation, and evaluation of prevention and intervention efforts, informs policy and program development, and guides international efforts at eradication. This article uses the public health approach to address human trafficking, with a focus on child sex trafficking and exploitation. Recommendations are made for public health professionals to contribute to antitrafficking efforts globally.
Treatment and unmet needs in steroid-refractory acute graft-versus-host disease
Authors: Florent Malard, Xiao-Jun Huang, Joycelyn P. Y. Sim
Journal: Leukemia (2020)

Acute graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (alloHCT) and is a major cause of morbidity and mortality. Systemic steroid therapy is the first-line treatment for aGVHD, although about half of patients will become refractory to treatment. As the number of patients undergoing alloHCT increases, developing safe and effective treatments for aGVHD will become increasingly important, especially for those whose disease becomes refractory to systemic steroid therapy. This paper reviews current treatment options for patients with steroid-refractory aGVHD and discusses data from recently published clinical studies to outline emerging therapeutic strategies.
NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020
Authors: Mary B. Daly, Robert Pilarski, Matthew B. Yurgelun, Michael P. Berry, Saundra S. Buys, Patricia Dickson, Susan M. Domchek, Ahmed Elkhanany, Susan Friedman, Judy E. Garber, Michael Goggins, Mollie L. Hutton, Seema Khan, Catherine Klein, Wendy Kohlmann, Allison W. Kurian, Christine Laronga, Jennifer K. Litton, Julie S. Mak, Carolyn S. Menendez, Sofia D. Merajver, Barbara S. Norquist, Kenneth Offit, Tuya Pal, Holly J. Pederson, Gwen Reiser, Kristen Mahoney Shannon, Kala Visvanathan, Jeffrey N. Weitzel, Myra J. Wick, Kari B. Wisinski, Mary A. Dwyer, Susan D. Darlow
Journal: Journal of the National Comprehensive Cancer Network (2020)

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2 , pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry.
Ribonucleic Acid Synthesis in Experimental Cardiac Hypertrophy in Rats
Authors: BARRY L. FANBURG, BARRY I. POSNER
Journal: Circulation Research (1968)

Cardiac hypertrophy was induced in rats by constriction of the aortic arch. Hearts from rats with aortic constriction increased in weight about 50% above those of control rats by 7 days after operation. RNA concentration increased between 24 and 48 hours after constriction and, thereafter, returned toward the control level. DNA concentration of hearts from rats with aortic constriction remained unchanged from that of sham-operated rats. Labeling of heart RNA with 32 P was increased relative to that of sham-operated rats within the first 4 hours after aortic constriction. However, RNA labeling, relative to the labeling of AMP derived from ATP, increased above that of sham-operated rats only after 4 hours of aortic constriction and rose to maximum or near maximum values by 8 hours after operation. Various methods of extraction of RNA showed that the increase in labeling involved all the major species of RNA (28S, 18S, and 4S), and no evidence was found for the selective stimulation of a minority species. The nucleotide base composition of the various species of heart RNA of rats with aortic constriction was not significantly different from that of normal rats during the 4- to 8-hour period after operation. There was no terminal labeling of sRNA in hearts of either normal animals or those with aortic constriction.
Chest Computed Tomography for Detection of Coronavirus Disease 2019 (COVID-19): Don't Rush the Science
Authors: Michael D. Hope, Constantine A. Raptis, Travis S. Henry
Journal: Annals of Internal Medicine (2020)

East respiratory syndrome]" and "CT should not be used to screen for or as a first-line test to diagnose This is a cautionary tale from the radiology community about the consequences of rushing the scientific review process.The best intentions can lead to unforeseen consequences.This may become more relevant as we push forward with potential treatments and vaccines for COVID-19.
Controversies of renin–angiotensin system inhibition during the COVID-19 pandemic
Authors: Andrew M. South, Laurie Tomlinson, Daniel Edmonston, Swapnil Hiremath, Matthew A. Sparks
Journal: Nature Reviews Nephrology (2020)

The current COVID-19 pandemic is associated with unprecedented morbidity and mortality. Early reports suggested an association between disease severity and hypertension but did not account for sources of confounding. However, the responsible virus — SARS-CoV-2 — gains entry to host cells via angiotensin-converting enzyme 2 (ACE2), highlighting the need to understand the relationship between the virus and the renin–angiotensin system (RAS) and how this might be affected by RAS inhibitors.
Association of Preeclampsia in Term Births With Neurodevelopmental Disorders in Offspring
Authors: Bob Z. Sun, Dag Moster, Quaker E. Harmon, Allen J. Wilcox
Journal: JAMA Psychiatry (2020)

Preeclampsia during pregnancy has been linked to an increased risk of cerebral palsy in offspring. Less is known about the role of preeclampsia in other neurodevelopmental disorders.To determine the association between preeclampsia and a range of adverse neurodevelopmental outcomes in offspring after excluding preterm births.This prospective, population-based cohort study included singleton children born at term from January 1, 1991, through December 31, 2009, and followed up through December 31, 2014 (to 5 years of age), using Norway's Medical Birth Registry and linked to other demographic, social, and health information by Statistics Norway. Data were analyzed from May 30, 2018, to November 17, 2019.Maternal preeclampsia.Associations between preeclampsia in term pregnancies and cerebral palsy, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), epilepsy, intellectual disability, and vision or hearing loss using multivariable logistic regression.The cohort consisted of 980 560 children born at term (48.8% female and 51.2% male; mean [SD] gestational age, 39.8 [1.4] weeks) with a mean (SD) follow-up of 14.0 (5.6) years. Among these children, 28 068 (2.9%) were exposed to preeclampsia. Exposed children were at increased risk of ADHD (adjusted odds ratio [OR], 1.18; 95% CI, 1.05-1.33), ASD (adjusted OR, 1.29; 95% CI, 1.08-1.54), epilepsy (adjusted OR, 1.50; 95% CI, 1.16-1.93), and intellectual disability (adjusted OR, 1.50; 95% CI, 1.13-1.97); there was also an apparent association between preeclampsia exposure and cerebral palsy (adjusted OR, 1.30; 95% CI, 0.94-1.80).Preeclampsia is a well-established threat to the mother. Other than the hazards associated with preterm delivery, the risks to offspring from preeclampsia are usually regarded as less important. This study's findings suggest that preeclampsia at term may have lasting effects on neurodevelopment of the child.
Increased extracellular vesicles mediate inflammatory signalling in cystic fibrosis
Authors: Zivile Useckaite, Mark P Ward, Anne Trappe, Rebecca Reilly, Jenny Lennon, Holly Davage, David Matallanas, Hilary Cassidy, Eugene T Dillon, Kiva Brennan, Sarah L Doyle, Suzanne Carter, Seamas Donnelly, Barry Linnane, Edward F McKone, Paul McNally, Judith A Coppinger
Journal: Thorax (2020)

Rationale Mutations in the cystic fibrosis transmembrane regulator ( CFTR ) gene form the basis of cystic fibrosis (CF). There remains an important knowledge gap in CF as to how diminished CFTR activity leads to the dominant inflammatory response within CF airways. Objectives To investigate if extracellular vesicles (EVs) contribute to inflammatory signalling in CF. Methods EVs released from CFBE41o-, CuFi-5, 16HBE14o- and NuLi-1 cells were characterised by nanoparticle tracking analysis (NTA). EVs isolated from bronchoalveolar lavage fluid (BALF) from 30 people with CF (PWCF) were analysed by NTA and mass spectrometry and compared with controls. Neutrophils were isolated from the blood of 8 PWCF to examine neutrophil migration in the presence of CFBE41o- EVs. Results A significantly higher level of EVs were released from CFBE41o- (p&lt;0.0001) and CuFi-5 (p=0.0209) relative to control cell lines. A significantly higher level of EVs were detected in BALF of PWCF, in three different age groups relative to controls (p=0.01, 0.001, 0.002). A significantly lower level of EVs were released from CFBE41o- (p&lt;0.001) and CuFi-5 (p=0.0002) cell lines treated with CFTR modulators. Significant changes in the protein expression of 126 unique proteins was determined in EVs obtained from the BALF of PWCF of different age groups (p&lt;0.001–0.05). A significant increase in chemotaxis of neutrophils derived from PWCF was observed in the presence of CFBE41o EVs (p=0.0024) compared with controls. Conclusion This study demonstrates that EVs are produced in CF airway cells, have differential protein expression at different ages and drive neutrophil recruitment in CF.
2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: Executive Summary
Authors: Win-Kuang Shen, Robert S. Sheldon, David G. Benditt, Mitchell I. Cohen, Daniel E. Forman, Zachary D. Goldberger, Blair P. Grubb, Mohamed H. Hamdan, Andrew D. Krahn, Mark S. Link, Brian Olshansky, Satish R. Raj, Roopinder Kaur Sandhu, Dan Sorajja, Benjamin C. Sun, Clyde W. Yancy
Journal: Journal of the American College of Cardiology (2017)
Lessons from covid-19: visiting patients at home and assessing comorbidities
Authors: Anna M H Stevens
Journal: BMJ (2020)

What might we learn from the covid-19 pandemic?1 Before the pandemic, a patient with complex comorbidities who was unwell at home would have been visited by a general practitioner. This would sometimes be followed by a visit from a district nurse to check blood tests, a visit from a relative who needed to fetch medication from a pharmacy, a referral to the local Health Hub for …
Abstract 15816: Echocardiographic Assessment of Pulmonary Arterial Stiffness in Human Immunodeficiency Virus Infected Patients
Authors: Idris Bugra Cerik, Murat Meric, Metin Coksevim, Hatun Ozturk Cerik, Okan Gulel, Korhan Soylu, Sydin Deveci, Mahmut Sahin
Journal: Circulation (2017)

Introduction: Pulmonary hypertension is among the complications of HIV infection. Despite the emergence of effective therapy, pulmonary arterial hypertension is commonly at an advanced stage when r...
Dual Targeting of CDK4/6 and BCL2 Pathways Augments Tumor Response in Estrogen Receptor–Positive Breast Cancer
Authors: James R. Whittle, François Vaillant, Elliot Surgenor, Antonia N. Policheni, Göknur Giner, Bianca D. Capaldo, Huei-Rong Chen, He K. Liu, Johanna F. Dekkers, Norman Sachs, Hans Clevers, Andrew Fellowes, Thomas Green, Huiling Xu, Stephen B. Fox, Marco J. Herold, Gordon K. Smyth, Daniel H.D. Gray, Jane E. Visvader, Geoffrey J. Lindeman
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Although cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly extend tumor response in patients with metastatic estrogen receptor–positive (ER+) breast cancer, relapse is almost inevitable. This may, in part, reflect the failure of CDK4/6 inhibitors to induce apoptotic cell death. We therefore evaluated combination therapy with ABT-199 (venetoclax), a potent and selective BCL2 inhibitor. Experimental Design: BCL2 family member expression was assessed following treatment with endocrine therapy and the CDK4/6 inhibitor palbociclib. Functional assays were used to determine the impact of adding ABT-199 to fulvestrant and palbociclib in ER+ breast cancer cell lines, patient-derived organoid (PDO), and patient-derived xenograft (PDX) models. A syngeneic ER+ mouse mammary tumor model was used to study the effect of combination therapy on the immune system. Results: Triple therapy was well tolerated and produced a superior and more durable tumor response compared with single or doublet therapy. This was associated with marked apoptosis, including of senescent cells, indicative of senolysis. Unexpectedly, ABT-199 resulted in Rb dephosphorylation and reduced G1–S cyclins, most notably at high doses, thereby intensifying the fulvestrant/palbociclib–induced cell-cycle arrest. Interestingly, a CRISPR/Cas9 screen suggested that ABT-199 could mitigate loss of Rb (and potentially other mechanisms of acquired resistance) to palbociclib. ABT-199 did not abrogate the favorable immunomodulatory effects of palbociclib in a syngeneic ER+ mammary tumor model and extended tumor response when combined with anti-PD1 therapy. Conclusions: This study illustrates the potential for targeting BCL2 in combination with CDK4/6 inhibitors and supports investigation of combination therapy in ER+ breast cancer.
Case 11-2020: A 37-Year-Old Man with Facial Droop, Dysarthria, and Kidney Failure
Authors: Jeffrey S. Berns, Otto Rapalino, Andrew Z. Fenves, Joseph B. El Khoury, Veronica E. Klepeis, Melis N. Anahtar
Journal: New England Journal of Medicine (2020)

A 37-year-old man with a history of injection-drug use presented with a facial droop, dysarthria, and kidney failure. The creatinine level was 16.1 mg per deciliter. Ultrasonography showed enlarged kidneys; CT showed decreased attenuation in the deep frontal white matter and striatal region on the left side. A diagnostic test was performed.
The benefits of iron supplementation following blood donation vary with baseline iron status
Authors: Alan E. Mast, Aniko Szabo, Mars Stone, Ritchard G. Cable, Bryan R. Spencer, Joseph E. Kiss
Journal: American Journal of Hematology (2020)

Whole blood donation rapidly removes approximately 10% of a donor's blood volume and stimulates substantial changes in iron metabolism and erythropoiesis. We sought to identify donors who benefit from iron supplementation, describe the nature of the benefit, and define the time course for recovery from donation. Blood samples were collected over 24 weeks following whole blood donation from 193 participants, with 96 participants randomized to 37.5 mg daily oral iron. Changes in total body, red blood cell (RBC), and storage iron, hepcidin, erythropoietin, and reticulocyte count were modeled using semiparametric curves in a mixed model. and the changes were compared among six groups defined by baseline ferritin (<12; 12-50; ≥50 ng/mL) and iron supplementation. The effect of oral iron on storage and RBC iron recovery was minimal in donors with baseline ferritin ≥50 ng/mL, but sizeable when ferritin was <50 ng/mL. Iron initially absorbed went to RBC and storage iron pools when ferritin was <12 ng/mL but went mostly to RBCs when ferritin was ≥12 ng/mL. Donors with ferritin ≥12 ng/mL had a "ripple" increase in reticulocytes ~100 days after donation indicating physiological responses occur months following donation. Thus, iron supplements markedly enhance recovery from whole blood donation in donors with ferritin <50 ng/mL. However, full recovery from donation requires over 100 days when taking iron. The findings also highlight the value of the study of blood donors for understanding human hemoglobin and iron metabolism and their usefulness for future studies as additional biomarkers are discovered.
Covid-19: testing times
Authors: Nick J Beeching, Tom E Fletcher, Mike B J Beadsworth
Journal: BMJ (2020)

Rapid near patient testing for both current and past infections is urgently required "Test, test, test" is the key to controlling the spread of SARS-CoV-2 and its clinical manifestation, covid-19, according to the World Health Organisation.1However, three months after notification of the novel coronavirus infection in China, there is inadequate access to appropriate diagnostic tests globally and confusion among healthcare professionals and the public about prioritisation of testing and interpretation of results.The virus is spread by the respiratory route, primarily by droplets and contact with contaminated surfaces and fomites, and by aerosol formation during invasive respiratory procedures.Virus is also found in urine, faeces, and saliva.2345Asymptomatic shedding seems to be common, especially in children, and can spread infection.67The incubation period from infection to first symptom is typically 5 to 7 days, with a range of 4-14 days.Diagnosis of current infection relies on tests to detect virus in various body fluids.Antibody tests on blood are used to confirm past infection and presumed immunity to repeat infection, although duration and effectiveness of such protection are not yet known.
The COVID-19 Global Rheumatology Alliance: collecting data in a pandemic
Authors: Philip C. Robinson, Jinoos Yazdany
Journal: Nature Reviews Rheumatology (2020)

The global COVID-19 pandemic has the potential to severely affect those with rheumatic diseases or who are taking immunosuppressive therapies. Information is lacking as to how these groups will fare if they become infected. A global alliance has rapidly formed to try to address this information deficit.