tbuckley/cabot-search huggingface dataset:
Comprehensive diagnostics of acute myeloid leukemia by whole transcriptome RNA sequencing
Authors: Wibowo Arindrarto, Daniel M. Borràs, Ruben A. L. de Groen, Redmar R. van den Berg, Irene J. Locher, Saskia A. M. E. van Diessen, Rosalie van der Holst, Edith D. van der Meijden, M. Willy Honders, Rick H. de Leeuw, Wina Verlaat, Inge Jedema, Wilma G. M. Kroes, Jeroen Knijnenburg, Tom van Wezel, Joost S. P. Vermaat, Peter J. M. Valk, Bart Janssen, Peter de Knijff, Cornelis A. M. van Bergen, Erik B. van den Akker, Peter A. C. ’t Hoen, Szymon M. Kiełbasa, Jeroen F. J. Laros, Marieke Griffioen, Hendrik Veelken
Journal: Leukemia (2020)

Acute myeloid leukemia (AML) is caused by genetic aberrations that also govern the prognosis of patients and guide risk-adapted and targeted therapy. Genetic aberrations in AML are structurally diverse and currently detected by different diagnostic assays. This study sought to establish whole transcriptome RNA sequencing as single, comprehensive, and flexible platform for AML diagnostics. We developed HAMLET (Human AML Expedited Transcriptomics) as bioinformatics pipeline for simultaneous detection of fusion genes, small variants, tandem duplications, and gene expression with all information assembled in an annotated, user-friendly output file. Whole transcriptome RNA sequencing was performed on 100 AML cases and HAMLET results were validated by reference assays and targeted resequencing. The data showed that HAMLET accurately detected all fusion genes and overexpression of EVI1 irrespective of 3q26 aberrations. In addition, small variants in 13 genes that are often mutated in AML were called with 99.2% sensitivity and 100% specificity, and tandem duplications in FLT3 and KMT2A were detected by a novel algorithm based on soft-clipped reads with 100% sensitivity and 97.1% specificity. In conclusion, HAMLET has the potential to provide accurate comprehensive diagnostic information relevant for AML classification, risk assessment and targeted therapy on a single technology platform.
Abstract P181: Atherogenic Lipoproteins and Incident Atherosclerotic Cardiovascular Disease in the Framingham Offspring Study
Authors: Hiroaki Ikezaki, Elise Lim, Ching-Ti Liu, L Adrienne Cupples, Bela F Asztalos, Ernst J Schaefer
Journal: Circulation (2020)

Introduction: Elevated plasma low-density lipoprotein cholesterol (LDL-C), small-dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), triglycerides (TG), remnant-lipoprotein cholesterol (RLP-C), triglyceride-rich lipoprotein-C (TRL-C), very low-density lipoprotein cholesterol (VLDL-C), and lipoprotein(a) [Lp(a)] levels have been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, these parameters have not been included in risk factors for ASCVD in the pooled cohort equation (PCE). Hypothesis: We assessed the hypothesis that these atherogenic lipoprotein parameters add significant information for ASCVD risk prediction in the Framingham Offspring Study. Methods: We evaluated 3,147 subjects without ASCVD at baseline (mean age 58 years) from participants of Framingham Offspring Study cycle 6, 677 (21.5%) of whom developed inclusive ASCVD over 16 years. Biomarkers of risk were assessed in frozen plasma samples. Total cholesterol, TG, HDL-C, direct LDL-C, sdLDL-C, LDL-TG, Lp(a), RLP-C, and TRL-C were measured by standardized automated analysis. Calculated LDL-C, large buoyant low-density lipoprotein cholesterol (lbLDL-C), VLDL-C, and non-HDL-C values were calculated. Data were analyzed using Cox proportional regression analysis and net reclassification improvement (NRI) analysis to identify parameters significantly associated with the incidence of ASCVD after controlling for standard ASCVD risk factor and applying the PCE model. Results: All specialized lipoprotein parameters were significant ASCVD risk factors on univariate analysis, but only direct LDL-C, sdLDL-C, and Lp(a) were significant on multivariate analysis with standard risk factors in the model. Together these parameters significantly improved the model c statistic (0.716 vs 0.732, P &lt; 0.05) and net risk reclassification (mean NRI 0.104, P &lt; 0.01) for ASCVD risk. Using the ASCVD risk pooled cohort equation, sdLDL-C, TG, LDL-TG, LDL-C, RLP-C, and TRL-C individually added significant information, but no other parameter added significant information with sdLDL-C (hazard ratio 1.30 for 75th vs 25th percentile, P &lt; 0.0001) in the model. Conclusions: In multivariate analysis, sdLDL-C, direct LDL-C, and Lp(a) contributed significantly to ASCVD risk, but only sdLDL-C added significant risk information to the PCE model, indicating that sdLDL-C may be the most atherogenic lipoprotein particle.
Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial
Authors: Elaine W. Yu, Liu Gao, Petr Stastka, Michael C. Cheney, Jasmin Mahabamunuge, Mariam Torres Soto, Christopher B. Ford, Jessica A. Bryant, Matthew R. Henn, Elizabeth L. Hohmann
Journal: PLoS Medicine (2020)

Background There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity. Methods and findings FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild–moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m2 and 41.3 ± 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus −3% ± 32% in placebo group, mean difference 9%, 95% CI −5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI −0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference −0.1 kg, 95% CI −1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI −0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention. Conclusions Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study. Trial registration ClinicalTrials.gov NCT02530385.
A Solitary Scaly Plaque on the Lower Extremity of a Young Girl
Authors: Ashlee M. Margheim, Emily C. McKenzie
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
Autologous cell–based therapy for male and female pattern hair loss using dermal sheath cup cells: A randomized placebo-controlled double-blinded dose-finding clinical study
Authors: Ryoji Tsuboi, Shiro Niiyama, Ryokichi Irisawa, Kazutoshi Harada, Yosuke Nakazawa, Jiro Kishimoto
Journal: Journal of the American Academy of Dermatology (2020)
Direct genome editing of patient-derived xenografts using CRISPR-Cas9 enables rapid in vivo functional genomics
Authors: Christopher H. Hulton, Emily A. Costa, Nisargbhai S. Shah, Alvaro Quintanal-Villalonga, Glenn Heller, Elisa de Stanchina, Charles M. Rudin, John T. Poirier
Journal: Nature Cancer (2020)
An open-label phase II clinical trial of PTK787 in patients with progressive neuroendocrine cancer
Authors: L. B. Anthony, J. McCall, J. Nunez, T. O’Dorisio, S. O’Dorisio
Journal: Journal of Clinical Oncology (2007)

14127 Background: PTK787 is an orally active angiogenesis inhibitor blocking all known vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptor (PDGFR)-tyrosine kinases . The majority of metastatic neuroendocrine malignancies express VEGF and PDGF receptors. Since both growth factors have been implicated in tumor-induced angiogenesis, PTK787 offers a novel approach for inhibiting tumor growth. Methods: In a phase II trial, we investigated the safety and antitumor activity of PTK787 in patients who had biopsy-proven metastatic neuroendocrine cancer, such as carcinoid, and had shown evidence of progression on somatostatin analog therapy. Eligible patients had measurable lesions other than bone, a Karnofsky performance status &gt; 60% and normal hematologic, renal and hepatic functions. Patients on octreotide therapy were required to be on a stable dose not exceeding 30 mg monthly of the LAR formulation. Initial dosing of PTK787 was 1,250 mg daily. Results: Eight patients (5 males) were enrolled between 5/20/05 to 9/09/06. Median age was 61 years (range, 48 to 65). There was 1 withdrawal of consent. The median time on study was 6.2 ± 2.1 mos with 1 patient continuing on treatment as of January 2007. Three patients required a 10–28 day discontinuation for rising SGOT/SGPT, alkaline phosphatase and Grade2 proteinuria. Resumption of PTK787 at 1,000 mg daily was well tolerated in 1 patient. One patient developed carcinoid crises with fever, flushing, rising 5-HIAA accompanied by Grade 2 proteinuria. A partial (&gt;50% decrease in 5-HIAA) biochemical response was observed in 25% of the patients. The observed radiographic (CT scans) and scintigraphic (OctreoScan) responses in 6 patients has been stable disease at 3 and 6 mos. Recruitment to this trial continues. Conclusions: PTK787 results in a 25% biochemical partial response rate in neuroendocrine tumor patients with progressive disease following somatostatin analog therapy. Alternative dosing schedules are planned to improve tolerability. [Table: see text]
Dual target gene therapy to EML4-ALK NSCLC by a gold nanoshell-based system: Erratum
Authors: Siwen Li, Yuxi Liu, Yalan Rui, Liping Tang, Samuel Achilefu, Yueqing Gu
Journal: Theranostics (2020)

[This corrects the article DOI: 10.7150/thno.24469.].
Abstract P375: Prospective Associations of Accelerometer-measured Physical Activity and Sedentary Time With Cardiometabolic Multimorbidity in the CARDIA Study
Authors: Kelsie M Full, Kelley Gabriel, Kara M Whitaker, Cora E Lewis, Barbara Sternfeld, Bethany Barone Gibbs, Stephen Sidney, Jared P Reis, David R Jacobs, Pamela SCHREINER
Journal: Circulation (2020)

Background: Cardiometabolic multimorbidity is rising rapidly in the US. This condition is associated with greater health care burden and risk for adverse outcomes, including mortality. We investigated the relations of sedentary time (ST), light intensity physical activity (LPA), and moderate to vigorous intensity physical activity (MVPA) with future cardiometabolic multimorbidity in mid-life. Methods: Participants were 1,863 adults (mean ± SD age=45±4 years, 58% female, 39% Black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study who wore an ActiGraph 7164 accelerometer in 2005-2006 (baseline). Cardiometabolic multimorbidity was defined as ≥2 measured cardiometabolic conditions (untreated/uncontrolled hypertension and hyperlipidemia, diabetes mellitus, chronic kidney disease, and clinical cardiovascular outcomes). Separate logistic regression models provided estimates of prospective associations of accelerometer-measured ST, LPA, and MVPA with cardiometabolic multimorbidity 10 years later in participants with &lt;2 cardiometabolic conditions at baseline. Interactions by age, sex, and race were explored. Results: The highest (&gt;47.3 min/d) vs. lowest (&lt;17.5 min/d) quartile of MVPA was associated with lower odds of cardiometabolic multimorbidity (OR: 0.61; CI: 0.37, 0.99) 10-years later. This association did not differ by age, race, or sex. Overall, there was no association between ST and cardiometabolic multimorbidity. However, a significant interaction was observed by age (p value=0.03). In age-stratified analyses, among participants ≥46 years at baseline, the highest (&gt;9.3 hr/d) vs. lowest (&lt;7.1 hr/d) quartile of ST was associated with higher odds of cardiometabolic multimorbidity (OR: 2.86; CI: 1.36, 6.17). No associations were observed between LPA and cardiometabolic multimorbidity. Conclusions: In mid-life adults with &lt;2 conditions at baseline, greater daily MVPA was associated with lower odds of future cardiometabolic multimorbidity burden 10 years later.
Abstract 173: The Neuroprotective Effect Of JZL184 is Comparable With Therapeutic Hypothermia in a Rat Model of Cardiac Arrest
Authors: Jing Xu, Guanghui Zheng, Juntao Hu, Weiwei Ge, Jennifer Bradley, Mary Ann A Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2019)

Introduction: JZL184 is a synthetic monoacylglycerol lipase inhibitor that reduces brain edema, infarct size and alleviates inflammation following cerebral ischemia in experimental studies. In this study, we compared its cerebral protective effects with therapeutic hypothermia following cardiopulmonary resuscitation (CPR) in a rat model. Hypothesis: JZL184 will have similar neuroprotective effects to therapeutic hypothermia after cardiac arrest (CA) by reducing brain and blood brain barrier (BBB) injury and preserving cerebral microcirculation following CPR. Methods: Thirty six male Sprague-Dawley rats weighing between 450-550 g were randomized: 1) control 2) hypothermia 3) JZL184. Ventricular fibrillation was induced and untreated for 6 min for all rats. Resuscitation was attempted with a 4 Joule defibrillation after 8 min of CPR. Immediately following resuscitation, either hypothermia (33+0.5 o C) or JZL184 (16 mg/k, IP) was administered. Cerebral microcirculation, S-100β, NSE and Evan’s Blue (EB) concentrations were analyzed at 6hrs after resuscitation. Results: NSE and S-100β levels were higher in control compared to hypothermia and JZL18 at 6hr post ROSC (p &lt; 0.001) (Fig. 1). Compared with control, there was a significant decrease in brain permeability to EB in Hypothermia and JZL184 after 6hr post ROSC (p&lt;0.001) (Fig. 2). Microvascular flow index (MFI) was reduced in control compared with hypothermia and JZL184 6hr post ROSC (p &lt;0.01). Conclusions: JZL184 administered following resuscitation reduced brain and BBB injury and preserved cerebral microcirculation at 6 hr post arrest to the same extent as hypothermia in a rat model of cardiac arrest.
Abstract P523: Effect Of Alcohol And Tobacco Among Those With Thyroid Problems
Authors: Francisco E Ramirez, Elijah Hartman, Neil Nedley
Journal: Circulation (2020)

Background: This study documents the effect that alcohol and tobacco have on those with thyroid problems who participated in an 8 week lifestyle education program. Methods: Participants from the a depression and anxiety educational program were studied. Those who chose to participate met once a week for 8 weeks for a 2 hour program. It consisted of a 45 minute DVD presentation followed by a small group discussion. No doctor patient relationship was established. The program was offered by certified facilitators and focused on educating participants on healthy behaviors such as exercise, plant-based diets, sleep hygiene and others. Each participant answered the Depression and Anxiety Assessment Test (registration TX 7-398-022) both pre and post program. It assessed depression level based on DSM-5 [The Diagnostic and Statistical Manual of Mental Disorders Volume 5] criteria, use of tobacco and alcohol as well as clinical history including thyroid function. The degree of morbid thoughts was ranked from 0-3 ([0] having none or rare; [1] having them 1/4 of the days; [2] being 1/2 of the days; [3] being almost every day in a period of 2 weeks). Results: From n=6118 participants that finished the 8 week program, n=561 participants had thyroid problem those participants were used in the study. The group mean age was 53, SD 15.0, and 82.7% were female. From this group, n=42 (7.5%) were using alcohol and n=44 (7.8%) were tobacco users. Among the those using alcohol, baseline mean depression was 14.67 (SD 6.6), suicidal ideation score was 1.2 at the end of the program mean depression was 9.62 (SD 6.6, p &lt; .001), and suicide thoughts were 0.33. Among the tobacco users, baseline mean depression was 16.23 (SD 6.8) suicidal thought were 1.50 at the end of the program mean depression was 8.84 (SD 5.8, p &lt; .001), 0.34 for suicide thoughts. Among the non-tobacco users, baseline mean depression was 12.44 (SD 7.3), suicidal thoughts was 0.86 at the end of the program depression was 7.95 (SD 6.6, p &lt; .001), and suicidal thoughts were 0.25. Among the non-alcohol users, baseline mean depression was 12.58 (SD 7.4), suicidal thoughts was 0.88 at the end of the program mean depression was 7.89 (SD 6.5, p &lt; .001), suicidal thoughts were 0.25. Conclusion: The findings suggest this program is effective at reducing depression, suicidal thoughts, among individuals with thyroid dysfunction who use alcohol or tobacco; however greater benefit may be achieved by abstaining from both substances.
Updated Hepatitis C Virus Screening Recommendation—A Step Forward
Authors: Jennifer C. Price, Danielle Brandman
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
Descemet Membrane Endothelial Keratoplasty versus Ultrathin Descemet Stripping Automated Endothelial Keratoplasty
Authors: Suryan L. Dunker, Mor M. Dickman, Robert P.L. Wisse, Siamak Nobacht, Robert H.J. Wijdh, Marjolijn C. Bartels, Mei L. Tang, Frank J.H.M. van den Biggelaar, Pieter J. Kruit, Rudy M.M.A. Nuijts
Journal: Ophthalmology (2020)
Phase II: Combination of cladribine, cyclophosphamide, mitoxantrone, rituximab (R-CCM) in patients with relapsed and refractory follicular and mantle cell lymphoma, results of a prospective study at Kitasato University
Authors: Y. Suzuki, M. Danbara, M. Hayama, T. Togano, M. Ohsaka, K. Miyazaki, R. Horie, M. Higashihara
Journal: Journal of Clinical Oncology (2007)

18542 Background: Indolent non-Hodgkin’s lymphoma (I-NHL) account for 20% of all of NHL in Japan, and they are increasing in number. More than 80% of the patients who achieve a complete remission with the initial treatment, will require salvage therapy. Recently, cladribine (2-CdA), a purine analogue is receiving much attention, because, even as a single agent, it has shown a high efficacy for I-NHL. The aim of our study was to determine the effectiveness and toxicity of combined chemotherapy consisting of 2-CdA, cyclophosphamide (CYP), mitoxantrone (MIT), rituximab (R-CCM) in the treatment of refractory or relapsed I-NHL. Methods: Patient eligibility criteria were: Previously treated patients with I-NHL, refractory or relapsed disease, no chemotherapy or irradiation within 4 weeks prior to the study, life expectancy of at least 3 months, age: 20–75, perfomance status of 0–3, adequate function ( bone marrow, liver, kidney, lung, heart) and written informed consent. The treatment regimen was: 2-CdA given at a dose of 0.09 mg/kg/day in a 2-h intravenous infusion from day 2–4, CYP 200 mg/m2/day from day 2–4, MIT 8 mg/m2/day on day 2 and rituximab 375 mg/m2/day on day .Primary end point was overall response rate. Results: 9 patients were enrolled, 7 (2 with mantle cell lymphoma, MCL; and 5 with follicular lymphoma, FL) were eligible. Mean Age was 63(51–72). The mean observation time was 121 days(47–314). Overall response rate (complete and partial) just after this therapy was 85.7%, one was progressive disease. One of PR one relapsed and died ten months after this regimen. The major toxicity was myelosuppression. Grade-III and -IV neutropenia was seen in 7 patients, grade-III thrombocytopenia in one and grade-III hemorrhagic cystitis in one, but all of them recovered from these toxicity. After the treatment, Grade-IV pneumonia and grade-III left-ventricular diastolic dysfunction was seen in the PD patient and passed away. Conclusions: the R-CCM is effective and safe in a combined regimen for relapsed and refractory I-NHL patients. We have just begun this new regimen, therefore, further investigations with larger population are warranted. No significant financial relationships to disclose.
Abstract 15020: Women Have a Higher Acute Mortality Rate After Intra-Aortic Balloon Pump (IABP) Use During Cardiogenic Shock
Authors: Po-Yuan Chang, Jung-Chi Hsu, Chuhuang Chen
Journal: Circulation (2019)

Introduction: Intra-aortic balloon pump (IABP) has been the most widely used device of mechanical circulatory support in cardiogenic shock and high-risk coronary interventions for decades. Our aim ...