tbuckley/cabot-search huggingface dataset:
Effect of Long-Acting Injectable Antipsychotics vs Usual Care on Time to First Hospitalization in Early-Phase Schizophrenia
Authors: John M. Kane, Nina R. Schooler, Patricia Marcy, Christoph U. Correll, Eric D. Achtyes, Robert D. Gibbons, Delbert G. Robinson
Journal: JAMA Psychiatry (2020)

Long-acting injectable antipsychotics (LAIs) can potentially reduce hospitalization risk by enhancing medication adherence but are rarely considered for early-phase schizophrenia treatment.To determine whether encouraging use of a LAI compared with usual care delays the time to first hospitalization with patients with early-phase illness.The Prevention of Relapse in Schizophrenia (PRELAPSE) trial was cluster randomized with a follow-up duration of 2 years. The study began in December 2014, was completed in March 2019, and was conducted in 39 mental health centers in 19 US states. Site randomization assigned 19 clinics to encourage treatment with long-acting aripiprazole monohydrate (aripiprazole once monthly [AOM] condition) and 20 to provide treatment as usual (clinician's choice [CC] condition). Participant eligibility criteria included (1) schizophrenia diagnosis confirmed by a structured clinical interview, (2) fewer than 5 years of lifetime antipsychotic use, and (3) age 18 to 35 years. The AOM sites identified 576 potentially eligible participants, of whom 234 (40.6%) enrolled; CC sites identified 685 potentially eligible participants, of whom 255 (37.2%) enrolled.There were no restrictions on treatment at CC sites (including using LAIs) or at AOM sites with the exception that aripiprazole monohydrate had to be prescribed within US Food and Drug Administration-approved guidelines.The primary outcome was time to first psychiatric hospitalization based on participant interviews every 2 months, the service use resource form administered every 4 months, and other sources (eg, health records) as available. Potential events were adjudicated by an independent committee masked to treatment assignment.The 489 participants (368 men [75.3%]) had a mean (SD) age of 25.2 (4.2) years and 225 (46.0%) had 1 year or less lifetime antipsychotic use. Fifty-two AOM (22%) and 91 CC participants (36%) had at least 1 hospitalization. The mean survival time until first hospitalization was 613.7 days (95% CI, 582.3-645.1 days) for AOM participants and 530.6 days (95% CI, 497.3-563.9 days) for CC participants. For time to first hospitalization, the hazard ratio was 0.56 (95% CI, 0.34- 0.92; P = .02), favoring AOM. Survival probabilities were 0.73 (95% CI, 0.65-0.83) for AOM participants and 0.58 (95% CI, 0.50-0.67) for CC participants. The number needed to treat to prevent 1 additional hospitalization was 7 participants treated with AOM compared with CC.Long-acting injectable antipsychotic use by patients with early-phase schizophrenia can significantly delay time to hospitalization, a personally and economically important outcome. Clinicians should more broadly consider LAI treatment for patients with early-phase illness.ClinicalTrials.gov Identifier: NCT02360319.
Improving the Design of Future PCI Trials for Stable Coronary Artery Disease
Authors: Guillaume Marquis-Gravel, David J. Moliterno, Darrel P. Francis, Peter Jüni, Yves D. Rosenberg, Bimmer E. Claessen, Robert J. Mentz, Roxana Mehran, Donald E. Cutlip, Cynthia Chauhan, Susan Quella, Faiez Zannad, Shaun G. Goodman
Journal: Journal of the American College of Cardiology (2020)
Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH
Authors: Theresa J. Hydes, Sujan Ravi, Rohit Loomba, Meagan E. Gray
Journal: Clinical and Molecular Hepatology (2020)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and affects approximately one third of adults in the United States. The disease is becoming a global epidemic as a result of the rising rates of obesity and metabolic disease. Emerging data suggest weight loss of ≥10% overall body weight is beneficial in resolving steatosis and reversing fibrosis. Prospective trials comparing various diets are limited by lack of sufficient power as well as pre- and post-treatment histopathology, and therefore no specific diet is recommended at this time. In this narrative review we examine the pathophysiology behind specific macronutrient components that can either promote or reverse NAFLD to help inform more specific dietary recommendations. Overall, the data supports reducing saturated fat, refined carbohydrates, and red and processed meats in the diet, and increasing the consumption of plant-based foods. Diets that incorporate these recommendations include plant-based diets such as the Dietary Approaches to Stop Hypertension, Mediterranean, vegetarian, and vegan diets.
Correlation Between Dermoscopic and Histologic Features of Uncommon Cutaneous Melanoma Variants—Reply
Authors: Caterina Longo, Michela Lai, Riccardo Pampena
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Extensive Extramedullary Hematopoiesis in Thalassemia
Authors: Sharjeel Usmani, Najeeb Ahmed, Samreen Muzaffar, Fareeda Al Kandari
Journal: Clinical Nuclear Medicine (2020)

We report the case of a 45-year-old man with thalassemia major referred for a bone scan as a workup for generalized bone pain. Tc-MDP SPECT CT showed multiple elongated soft tissue masses along the inner aspects of ribs and along both sides of dorsal spine with calcification and mild tracer uptake. There was also a large lobulated presacral soft tissue mass displacing the bladder and involving the adjacent pelvic bone. Biopsy of mildly avid tracer uptake in pelvic soft tissue mass was extramedullary hematopoiesis confirmed by biopsy.
The Synthetic Small Molecule FL3 Combats Intestinal Tumorigenesis via Axin1-Mediated Inhibition of Wnt/β-Catenin Signaling
Authors: Dakota N. Jackson, Kibrom M. Alula, Yaritza Delgado-Deida, Redouane Tabti, Kevin Turner, Xuan Wang, K. Venuprasad, Rhonda F. Souza, Laurent Désaubry, Arianne L. Theiss
Journal: Cancer Research (2020)

Colorectal cancer exhibits aberrant activation of Wnt/β-catenin signaling. Many inhibitors of the Wnt/β-catenin pathway have been tested for Wnt-dependent cancers including colorectal cancer, but are unsuccessful due to severe adverse reactions. FL3 is a synthetic derivative of natural products called flavaglines, which exhibit anti-inflammatory and cytoprotective properties in intestinal epithelial cells, but has not been previously tested in cell or preclinical models of intestinal tumorigenesis. In vitro studies suggest that flavaglines target prohibitin 1 (PHB1) as a ligand, but this has not been established in the intestine. PHB1 is a highly conserved protein with diverse functions that depend on its posttranslational modifications and subcellular localization. Here, we demonstrate that FL3 combats intestinal tumorigenesis in the azoxymethane-dextran sodium sulfate and ApcMin/+ mouse models and in human colorectal cancer tumor organoids (tumoroids) by inhibiting Wnt/β-catenin signaling via induction of Axin1 expression. FL3 exhibited no change in cell viability in normal intestinal epithelial cells or human matched-normal colonoids. FL3 response was diminished in colorectal cancer cell lines and human colorectal cancer tumoroids harboring a mutation at S45 of β-catenin. PHB1 deficiency in mice or in human colorectal cancer tumoroids abolished FL3-induced expression of Axin1 and drove tumoroid death. In colorectal cancer cells, FL3 treatment blocked phosphorylation of PHB1 at Thr258, resulting in its nuclear translocation and binding to the Axin1 promoter. These results suggest that FL3 inhibits Wnt/β-catenin signaling via PHB1-dependent activation of Axin1. FL3, therefore, represents a novel compound that combats Wnt pathway-dependent cancers, such as colorectal cancer. SIGNIFICANCE: Targeting of PHB1 by FL3 provides a novel mechanism to combat Wnt-driven cancers, with limited intestinal toxicity. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/17/3519/F1.large.jpg.
AB0652 MACHINE LEARNING TO PREDICT EARLY TNF INHIBITOR USERS IN PATIENTS WITH ANKYLOSING SPONDYLITIS
Authors: J. Lee, H. Kim, S. Y. Kang, S. Lee, Y. H. Eun, H. S. Cha, E. M. Koh
Journal: Annals of the Rheumatic Diseases (2020)

Background: Tumor necrosis factor (TNF) inhibitors are important drugs in treating patients with ankylosing spondylitis (AS). However, they are not used as a first-line treatment for AS. There is an insufficient treatment response to the first-line treatment, non-steroidal anti-inflammatory drugs (NSAIDs), in over 40% of patients. If we can predict who will need TNF inhibitors at an earlier phase, adequate treatment can be provided at an appropriate time and potential damages can be avoided. There is no precise predictive model at present. Recently, various machine learning methods show great performances in predictions using clinical data. Objectives: We aim to generate an artificial neural network (ANN) model to predict early TNF inhibitor users in patients with ankylosing spondylitis. Methods: The baseline demographic and laboratory data of patients who visited Samsung Medical Center rheumatology clinic from Dec. 2003 to Sep. 2018 were analyzed. Patients were divided into two groups: early TNF inhibitor users treated by TNF inhibitors within six months of their follow-up (early-TNF users), and the others (non-early-TNF users). Machine learning models were formulated to predict the early-TNF users using the baseline data. Additionally, feature importance analysis was performed to delineate significant baseline characteristics. Results: The numbers of early-TNF and non-early-TNF users were 90 and 509, respectively. The best performing ANN model utilized 3 hidden layers with 50 hidden nodes each; its performance (area under curve (AUC) = 0.75) was superior to logistic regression model, support vector machine, and random forest model (AUC = 0.72, 0.65, and 0.71, respectively) in predicting early-TNF users. Feature importance analysis revealed erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and height as the top significant baseline characteristics for predicting early-TNF users. Among these characteristics, height was revealed by machine learning models but not by conventional statistical techniques. Conclusion: Our model displayed superior performance in predicting early TNF users compared with logistic regression and other machine learning models. Machine learning can be a vital tool in predicting treatment response in various rheumatologic diseases. Disclosure of Interests: None declared
二重微小染色体をもつ急性骨髄性白血病におけるC-myc癌遺伝子の増幅とN-RAS癌遺伝子点突然変異の点突然変異 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Tanaka K, Takechi M, Nishimura S, Oguma N, Kamada N
Journal: Leukemia (1993)
Sodium activates human monocytes via the NADPH oxidase and isolevuglandin formation
Authors: Natalia Ruggeri Barbaro, Justin Van Beusecum, Liang Xiao, Luciana do Carmo, Ashley Pitzer, Roxana Loperena, Jason D Foss, Fernando Elijovich, Cheryl L Laffer, Kim R Montaniel, Cristi L Galindo, Wei Chen, Mingfang Ao, Raymond L Mernaugh, Aseel Alsouqi, Talat A Ikizler, Agnes B Fogo, Heitor Moreno, Shilin Zhao, Sean S Davies, David G Harrison, Annet Kirabo
Journal: Cardiovascular Research (2020)

Prior studies have focused on the role of the kidney and vasculature in salt-induced modulation of blood pressure; however, recent data indicate that sodium accumulates in tissues and can activate immune cells. We sought to examine mechanisms by which salt causes activation of human monocytes both in vivo and in vitro.To study the effect of salt in human monocytes, monocytes were isolated from volunteers to perform several in vitro experiments. Exposure of human monocytes to elevated Na+ex vivo caused a co-ordinated response involving isolevuglandin (IsoLG)-adduct formation, acquisition of a dendritic cell (DC)-like morphology, expression of activation markers CD83 and CD16, and increased production of pro-inflammatory cytokines tumour necrosis factor-α, interleukin (IL)-6, and IL-1β. High salt also caused a marked change in monocyte gene expression as detected by RNA sequencing and enhanced monocyte migration to the chemokine CC motif chemokine ligand 5. NADPH-oxidase inhibition attenuated monocyte activation and IsoLG-adduct formation. The increase in IsoLG-adducts correlated with risk factors including body mass index, pulse pressure. Monocytes exposed to high salt stimulated IL-17A production from autologous CD4+ and CD8+ T cells. In addition, to evaluate the effect of salt in vivo, monocytes and T cells isolated from humans were adoptively transferred to immunodeficient NSG mice. Salt feeding of humanized mice caused monocyte-dependent activation of human T cells reflected by proliferation and accumulation of T cells in the bone marrow. Moreover, we performed a cross-sectional study in 70 prehypertensive subjects. Blood was collected for flow cytometric analysis and 23Na magnetic resonance imaging was performed for tissue sodium measurements. Monocytes from humans with high skin Na+ exhibited increased IsoLG-adduct accumulation and CD83 expression.Human monocytes exhibit co-ordinated increases in parameters of activation, conversion to a DC-like phenotype and ability to activate T cells upon both in vitro and in vivo sodium exposure. The ability of monocytes to be activated by sodium is related to in vivo cardiovascular disease risk factors. We therefore propose that in addition to the kidney and vasculature, immune cells like monocytes convey salt-induced cardiovascular risk in humans.
DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas
Authors: Anat Ben-Shlomo, Nan Deng, Evelyn Ding, Masaaki Yamamoto, Adam Mamelak, Vera Chesnokova, Artak Labadzhyan, Shlomo Melmed
Journal: Journal of Clinical Investigation (2020)

Drivers of sporadic benign pituitary adenoma growth are largely unknown. Whole-exome sequencing of 159 prospectively resected pituitary adenomas showed that somatic copy number alteration (SCNA) rather than mutation is a hallmark of hormone-secreting adenomas and that SCNAs correlate with adenoma phenotype. Using single-gene SCNA pathway analysis, we observed that both cAMP and Fanconi anemia DNA damage repair pathways were affected by SCNAs in growth hormone-secreting (GH-secreting) somatotroph adenomas. As somatotroph differentiation and GH secretion are dependent on cAMP activation and we previously showed DNA damage, aneuploidy, and senescence in somatotroph adenomas, we studied links between cAMP signaling and DNA damage. Stimulation of cAMP in C57BL/6 mouse primary pituitary cultures using forskolin or a long-acting GH-releasing hormone (GHRH) analog increased GH production and DNA damage measured by H2AX phosphorylation and a comet assay. Octreotide, a somatostatin receptor ligand that targets somatotroph adenoma GH secretion in patients with acromegaly, inhibited cAMP and GH and reversed DNA damage induction. In vivo long-acting GHRH treatment also induced pituitary DNA damage in mice. We conclude that cAMP, which induces somatotroph proliferation and GH secretion, may concomitantly induce DNA damage, potentially linking hormone hypersecretion to SCNA and genome instability. These results elucidating somatotroph adenoma pathophysiology identify pathways for targeted treatment.
Response to Comment on Mäkimattila et al. Every Fifth Individual With Type 1 Diabetes Suffers From an Additional Autoimmune Disease: A Finnish Nationwide Study. Diabetes Care 2020;43:1041–1047
Authors: Sari Mäkimattila, Valma Harjutsalo, Carol Forsblom, Per-Henrik Groop
Journal: Diabetes Care (2020)

We thank Bellastella et al. (1) for their interest in our study (2) on autoimmune diseases (ADs) in individuals with type 1 diabetes (T1D). We also thank them for bringing our attention to their observation of similar prevalence rates of additional ADs in an Italian cohort of individuals with T1D.

Bellastella et al. found that 18% of their young cohort had at least one additional AD compared with 22.8% in our older cohort. They also reported a considerably higher prevalence of two additional ADs, 13% vs. 3%, and concluded that the younger age and shorter diabetes duration in their cohort might explain the differences.

We agree that age might explain the diverging results. However, as we stated in our article, older age enables detection of accumulating ADs, but an age difference also inevitably results …
Abstract #4719: Nrf2 and drug resistance in breast cancer cells
Authors: Jun Shen, Emmanual Unni, Angela Brodie, Anil Jaiswal
Journal: Cancer Research (2009)

Breast Cancer is the leading cause of cancer deaths in women. Excellent chemotherapeutic drugs including aromatase inhibitors are available to reduce or eliminate breast cancer. However, breast tumor cells often become resistant to drugs resulting in the loss of their effectiveness against breast cancer. NF-E2 Related Factor 2 (Nrf2) is a nuclear transcription factor that activates a battery of defensive genes. INrf2 constitutively suppresses Nrf2 activity in the absence of stress by functioning as an adapter protein for Cul3/Rbx1 mediated ubiquitination and degradation of Nrf2. When a cell encounters any form of stress Nrf2 dissociates from the INrf2/Cul3-RBX1 complex and translocates into the nucleus. This leads to coordinated induction of a battery of genes encoding drug detoxifying enzymes, antioxidants, multi-drug resistance proteins, ubiquitin enzymes, and proteasomes that protects cells and promote cell survival. We hypothesized that breast cancer cells especially during persistent treatment with drugs generate high amounts of ROS and electrophiles that signals Nrf2 activation leading to drug resistance. Indeed, letrozole resistant breast cancer LTLT cells derived from MCF-7 aromatase expressing cells (MCF-7ca) demonstrated greater than ten-fold higher levels of Nrf2, as compared to drug sensitive MCF7ca cells. Further studies revealed that removal of letrozole treatment led to time dependent decline in Nrf2 levels in drug-resistant LTLT cells. It took approximately 96 hours of removal of letrozole to bring down the Nrf2 to the level in drug-sensitive MCF-7ca cells. The treatment of drug-sensitive MCF-7ca cells with letrozole led to stabilization and nuclear accumulation of Nrf2. Interestingly, antioxidant-mediated activation of Nrf2 in MCF-7 cells led to significantly reduced apoptosis in response to exposure to anti-tumor drug etoposide. The results combined suggest that persistent exposure of drugs leads to Nrf2 activation and drug resistance in breast cancer cells. The drug-resistance is presumably due to Nrf2 activation of proteins that detoxify drugs and neutralize free radicals that cause cell damage and death.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4719.
Ketoacidosis in Children and Adolescents With Newly Diagnosed Type 1 Diabetes During the COVID-19 Pandemic in Germany
Authors: Clemens Kamrath, Kirsten Mönkemöller, Torben Biester, Tilman R. Rohrer, Katharina Warncke, Johanna Hammersen, Reinhard W. Holl
Journal: JAMA (2020)

This study uses diabetes registry data to compare the frequency of diabetic ketoacidosis (DKA) in children and adolescents at time of type 1 diabetes diagnosis in Germany during the first 2 months of the coronavirus disease 2019 (COVID-19) pandemic vs the same time period in 2018 and 2019.
Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study
Authors: Mallika Imwong, Mehul Dhorda, Kyaw Myo Tun, Aung Myint Thu, Aung Pyae Phyo, Stephane Proux, Kanokon Suwannasin, Chanon Kunasol, Suttipat Srisutham, Jureeporn Duanguppama, Ranitha Vongpromek, Cholrawee Promnarate, Aungkana Saejeng, Nardlada Khantikul, Rungniran Sugaram, Supinya Thanapongpichat, Nongyao Sawangjaroen, Kreepol Sutawong, Kay Thwe Han, Ye Htut, Khin Linn, Aye Aye Win, Tin M Hlaing, Rob W van der Pluijm, Mayfong Mayxay, Tiengkham Pongvongsa, Koukeo Phommasone, Rupam Tripura, Thomas J Peto, Lorenz von Seidlein, Chea Nguon, Dysoley Lek, Xin Hui S Chan, Huy Rekol, Rithea Leang, Cheah Huch, Dominic P Kwiatkowski, Olivo Miotto, Elizabeth A Ashley, Myat Phone Kyaw, Sasithon Pukrittayakamee, Nicholas P J Day, Arjen M Dondorp, Frank M Smithuis, Francois H Nosten, Nicholas J White
Journal: The Lancet Infectious Diseases (2020)

The Greater Mekong subregion is a recurrent source of antimalarial drug resistance in Plasmodium falciparum malaria. This study aimed to characterise the extent and spread of resistance across this entire region between 2007 and 2018.