tbuckley/cabot-search huggingface dataset:
The predictive value of SS-16 in clinically diagnosed Parkinson’s disease patients: comparison with 99mTc-TRODAT-1 SPECT scans
Authors: Wenyan Kang, Fangyi Dong, Dunhui Li, Thomas J. Quinn, Shengdi Chen, Jun Liu
Journal: Translational Neurodegeneration (2016)

Dopamine transporter based imaging has high diagnostic performance in distinguishing patients with Parkinson's disease (PD) from patients with non-Parkinsonian syndromes. Our previous study indicated that the "Sniffin' Sticks" odor identification test (SS-16) acts as a valid instrument for olfactory assessment in Chinese PD patients. The aim of the study was to compare the efficacy of the two methods in diagnosing PD. Fifty-two PD patients were involved in this study and underwent single photon emission computed tomography (SPECT) imaging using the labeled dopamine transporter radiotracer 99mTc-TRODAT-1 to assess nigrostriatal dopaminergic function. Olfactory function was assessed with the "Sniffin' Sticks" odor identification test (SS-16) in all patients who received DAT-SPECT scanning. Statistical analysis (SPSS version 21) was carried out to determine the diagnostic accuracy of SS-16 as well as its correlation with 99mTc-TRODAT-1 SPECT, its positive predictive value (PPV), and negative predictive value (NPV). We identified a negative correlation between SS-16 and DAT SPECT (Kappa = 0.269, p = 0.004). By using the 99mTc-TRODAT-1 uptake results as the gold standard, the sensitivity and specificity of SS-16 was 56.8 and 37.5 %, respectively. Furthermore, the negative and positive predictive values were calculated as 13.6 and 83.3 %, respectively. SS-16 would not be used as a diagnostic tool for early stage PD patients. Negative results of SS-16 would not exclude the diagnosis of PD. Further tests are needed for validation.
Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease
Authors: Veeral Ajmera, Emily R. Perito, Nathan M. Bass, Norah A. Terrault, Katherine P. Yates, Ryan Gill, Rohit Loomba, Anna Mae Diehl, Bradley E. Aouizerat
Journal: Hepatology (2016)

Despite the high prevalence of nonalcoholic fatty liver disease (NAFLD), therapeutic options and noninvasive markers of disease activity and severity remain limited. We investigated the association between plasma biomarkers and liver histology in order to identify markers of disease activity and severity in patients with biopsy-proven NAFLD. Thirty-two plasma biomarkers chosen a priori as possible discriminators of NAFLD were measured in participants enrolled in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network. Dichotomized histologic outcomes were evaluated using centrally read biopsies. Biomarkers with statistically significant associations with NAFLD histology were evaluated in multivariable models adjusted for clinical factors. Of 648 participants (74.4% white, 61.7% female, mean age 47.7 years), 58.0% had definite NASH, 55.5% had mild/no fibrosis (stage 0-1), and 44.4% had significant fibrosis (stage 2-4). Increased activated plasminogen activator inhibitor 1 had a strong association with definite NASH compared to not NASH or borderline NASH in multivariable analysis (odds ratio = 1.20, 95% confidence interval 1.08-1.34, P < 0.001). Biomarkers associated with significant fibrosis (versus mild/no fibrosis) in multivariable analysis included higher levels of interleukin-8, monocyte chemoattractant protein-1, resistin, soluble interleukin-1 receptor I, soluble interleukin-2 receptor alpha, and tumor necrosis factor alpha and lower levels of insulin-like growth factor 2. Conclusions: Specific plasma biomarkers are significantly associated with disease activity and severity of fibrosis in NAFLD and are potentially valuable tools for noninvasive stratification of patients with NAFLD and identification of targets for therapeutic intervention. (Hepatology 2017;65:65-77).
The postdoctoral apprenticeship
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2016)

Much has been written already about whether the scientific machine is churning out too many PhDs and postdocs when there are a limited number of academic jobs and the competition for funding and space in competitive journals is intense. But gratifyingly, there exists a vast array of other scientific careers. We need to mentor and advise trainees about the diverse and rewarding professional opportunities that are available beyond the postdoctoral apprenticeship period.
Next-generation genotype imputation service and methods
Authors: Sayantan Das, Lukas Forer, Sebastian Schönherr, Carlo Sidore, Adam E Locke, Alan Kwong, Scott I Vrieze, Emily Y Chew, Shawn Levy, Matt McGue, David Schlessinger, Dwight Stambolian, Po-Ru Loh, William G Iacono, Anand Swaroop, Laura J Scott, Francesco Cucca, Florian Kronenberg, Michael Boehnke, Gonçalo R Abecasis, Christian Fuchsberger
Journal: Nature Genetics (2016)
Pre-Surgical Levels Of Circulating Cell-Derived Microparticles Are Most Significant Predictors Of Transfusion Requirement In Coronary Artery Bypass Graft Surgery
Authors: Wenche Jy, Orlando Gomez-Marin, John R Morgan, Max E Johansen, Carlos Bidot, Sherry Shariatmadar, Yeon S Ahn
Journal: Blood (2013)
Impact of sleep disordered breathing on behaviour among elementary school-aged children: a cross-sectional analysis of a large community-based sample
Authors: Dale L. Smith, David Gozal, Scott J. Hunter, Mona F. Philby, Jaeson Kaylegian, Leila Kheirandish-Gozal
Journal: European Respiratory Journal (2016)

Sleep disordered breathing (SDB) in children has been associated with inattention, impulsivity and hyperactivity, but the associations between SDB severity and the type and severity of behavioural disruption are unclear. 1022 children aged 5–7 years old prospectively underwent sleep studies and behavioural assessments through completion of standardised instruments. Participants were subdivided into four categorical groups based on the apnoea–hypopnoea index (AHI; measured per hour of total sleep time (hTST)), i.e. Group 1: nonsnoring and AHI &lt;1 hTST –1 ; Group 2: habitual snoring and AHI &lt;1 hTST –1 ; Group 3: habitual snoring and AHI 1–5 hTST –1 ; and Group 4: habitual snoring and AHI &gt;5 hTST –1 , followed by comparisons of behavioural functioning across the groups. All 10 behavioural variables differed significantly between Group 1 and all other groups. Post hoc comparisons indicated that Group 2 was the most impaired for most behavioural measures. Furthermore, differences between Group 2 and more severe sleep pathology conditions were rarely significant. This large community-based paediatric cohort confirms earlier findings highlighting a significant impact of SDB on behavioural regulation, with the greatest impact being already apparent among habitually snoring children. Thus, a likely low asymptote exists regarding SDB behavioural impact, such that further increases in severity do not measurably increase parent-rated difficulties with behavioural regulation relative to controls. Our findings do support the need for considering early intervention, particularly among those children manifesting a behavioural impact of SDB.
Defining antigen-specific plasmablast and memory B cell subsets in human blood after viral infection or vaccination
Authors: Ali H Ellebedy, Katherine J L Jackson, Haydn T Kissick, Helder I Nakaya, Carl W Davis, Krishna M Roskin, Anita K McElroy, Christine M Oshansky, Rivka Elbein, Shine Thomas, George M Lyon, Christina F Spiropoulou, Aneesh K Mehta, Paul G Thomas, Scott D Boyd, Rafi Ahmed
Journal: Nature Immunology (2016)
Persistence of androgen receptor (AR) expression in patients (pts) with small cell prostate cancer (SCPC): Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).
Authors: Rahul Raj Aggarwal, Jack Youngren, Artem Sokolov, Jiaoti Huang, George Thomas, Adam Foye, Joshi J. Alumkal, Charles J. Ryan, Tomasz M. Beer, Christopher P. Evans, Martin Gleave, Matthew Rettig, Eric Jay Small
Journal: Journal of Clinical Oncology (2016)

288 Background: Historically, SCPC has been regarded as an AR-null subtype observed in ~ 1% of pts. In castration-resistant metastatic biopsies, we have observed a higher frequency of SCPC (~ 15%), associated with shortened survival. We sought to contrast AR signaling between adenocarcinoma and SCPC. Methods: Pts underwent a metastatic tumor biopsy of bone or soft tissue. Formalin fixed, paraffin-embedded tissue underwent pathologic review, fluorescence in situ hybridization (FISH) for assessment of AR amplification, and assessment of AR expression by immunohistochemistry (IHC). A novel AR transcriptional signature was applied to RNA sequencing data from frozen tissue. AR-V7 transcripts in biopsy tissue were quantified and compared to AR-full length (AR-FL) expression. Results: Overall, 70 of 114 biopsies were AR amplified by FISH (61%). AR amplification was seen in similar proportions of adenocarcinoma (53%) and small cell tumors (54%) (p = ns). AR expression by IHC was observed in 27/32 (84%) and 5/6 (83%) of evaluable adenocarcinoma and SCPC biopsies, respectively (p = ns). AR was localized to nucleus in 85% of biopsies and did not differ by histology. AR-V7 splice variants were detected in all evaluable biopsies. Neither the absolute AR-FL expression level nor the ratio of AR-V7/AR-FL differed by histology. AR transcriptional signature scores were lower in SCPC versus adenocarcinoma (p = 0.029); scores were not correlated with AR-V7/AR-FL transcript ratio (r = 0.16). Of the 5 pts with SCPC identified on biopsy subsequently treated with abiraterone or enzalutamide, 3 achieved PSA declines &gt; 50%. Conclusions: Contrary to the classical description of SCPC as an AR-null phenotype, the majority of metastatic SCPC biopsies were positive for AR amplification and expression, reflecting their likely clonal origin from adenocarcinoma. AR transcriptional activity was lower in SCPC, potentially related to epigenetic or post-translational modulation of AR activity upon transdifferentiation from adenocarcinoma to SCPC. As novel therapeutic targets are identified in SCPC, continued co-targeting of the AR may be warranted.
Treatment recommendations from the Eighth International Workshop on Waldenström’s Macroglobulinemia
Authors: Véronique Leblond, Efstathios Kastritis, Ranjana Advani, Stephen M. Ansell, Christian Buske, Jorge J. Castillo, Ramón García-Sanz, Morie Gertz, Eva Kimby, Charalampia Kyriakou, Giampaolo Merlini, Monique C. Minnema, Pierre Morel, Enrica Morra, Mathias Rummel, Ashutosh Wechalekar, Christopher J. Patterson, Steven P. Treon, Meletios A. Dimopoulos
Journal: Blood (2016)
Human CD40 ligand deficiency dysregulates the macrophage transcriptome causing functional defects that are improved by exogenous IFN-γ
Authors: Otavio Cabral-Marques, Rodrigo Nalio Ramos, Lena F. Schimke, Taj Ali Khan, Eduardo Pinheiro Amaral, Caio César Barbosa Bomfim, Osvaldo Reis Junior, Tabata Takahashi França, Christina Arslanian, Joanna Darck Carola Correia Lima, Cristina Worm Weber, Janaíra Fernandes Ferreira, Fabiola Scancetti Tavares, Jing Sun, Maria Regina D'Imperio Lima, Marília Seelaender, Vera Lucia Garcia Calich, José Alexandre Marzagão Barbuto, Beatriz Tavares Costa-Carvalho, Gabriela Riemekasten, Gisela Seminario, Liliana Bezrodnik, Luigi Notarangelo, Troy R. Torgerson, Hans D. Ochs, Antonio Condino-Neto
Journal: Journal of Allergy and Clinical Immunology (2016)
Adverse Drug Events in Hospitalized Patients
Authors: Marina Morgutti
Journal: JAMA (1997)

<h3>To the Editor.</h3> —In the 3 articles on ADEs,<sup>1-3</sup>the estimated annual additional costs associated with preventable ADEs occurring during hospitalization were substantial and justify investing in efforts to reduce these events to the lowest possible incidence. We would like to point out, from a global "systemic" point of view, the impact of hospitalization due to preventable ADEs. In a prospective study we estimated incidence, causes, and severity of all drug-related visits to an emergency department of a 900-bed multidisciplinary public hospital in Milan (northern Italy). Visits for any cause were recorded daily during the first week of each month from October 1994 to September 1995. Age, sex, and diagnosis of patients were collected for each visit. Events related to drug consumption were identified and described through a structured form. Clinical records were retrieved for drug-related hospital admissions. Adverse drug reactions were defined according to the World Health Organization definition.<sup>4</sup>Other
What to Expect When [Your Employer Suspects] You’re Expecting
Authors: Stephanie R. Morain, Leah R. Fowler, Jessica L. Roberts
Journal: JAMA Internal Medicine (2016)

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
Drug approval and research assessment: arguments for reform
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2016)

The effects of the UK’s prospective exit from the European Union are in hot dispute. Arguments for and against continue to be keenly contested except, that is, when the conversation turns to science and medicine. Here, the loudest voices and most prominent arguments suggest that the decision taken by the public will cause harm. One such argument is around the future of the European Medicines Agency, which is based in London but is expected to relocate to mainland Europe. Our editorialists from Italy are mindful of this change but argue for a deeper reform of the work of the agency. Livio Garratini et al. identify a central flaw in the Agency’s operations, whereby approval for drug safety and efficacy rests with the agency but assessment of cost-effectiveness is devolved to individual countries. A better approach, and Brexit is an opportunity to take it, is for the Agency to take on both activities, allowing countries to better negotiate drug prices to make new drugs more affordable for the
Major Morbidity and Mortality Differences Between Hematopoietic Cell Transplantation Survivors and Other Cancer Survivors
Authors: Eric J Chow, Kara Cushing-Haugen, Wendy Leisenring, Michael Boeckh, Guang-Shing Cheng, Stephanie J. Lee, Paul J. Martin, Beth Mueller, Stephen Schwartz, K. Scott Baker
Journal: Blood (2014)
Managed Care: Ethical Issues-Reply
Authors: Howard Brody
Journal: JAMA (1995)

<h3>In Reply.</h3> —We agree with Dr Rosner that today's managed care environment poses a number of challenges to the ethics of the physician-patient relationship. We disagree with his diagnosis that the problem lies with the very concept of managed care, rather than how it is implemented. The letter captures a sense of "traditional" medical ethics with the statement, "The ethics of medical care should be totally divorced from the costs of rendering that care," a goal the author acknowledges as impractical. We argue that the flaw with that seductive but ultimately untenable view of medical ethics is as much theoretical as practical—it assumes ethical medical care is that provided in a world in which all resources are infinite; and that means in turn that each physician has infinite time and infinite energy for each patient. "Traditional" medicine was never like that; physicians always spent more time and energy (if not
Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA
Authors: W. Vaughn McCall, Ruth M. Benca, Peter B. Rosenquist, Mary Anne Riley, Laryssa McCloud, Jill C. Newman, Doug Case, Meredith Rumble, Andrew D. Krystal
Journal: American Journal of Psychiatry (2016)

Objective: Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. Method: This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. Results: Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. Conclusions: The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.
Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats
Authors: Yifeng Zhang, Jiankun Xu, Ye Chun Ruan, Mei Kuen Yu, Micheal O'Laughlin, Helen Wise, Di Chen, Li Tian, Dufang Shi, Jiali Wang, Sihui Chen, Jian Q Feng, Dick Ho Kiu Chow, Xinhui Xie, Lizhen Zheng, Le Huang, Shuo Huang, Kwoksui Leung, Na Lu, Lan Zhao, Huafang Li, Dewei Zhao, Xia Guo, Kaiming Chan, Frank Witte, Hsiao Chang Chan, Yufeng Zheng, Ling Qin
Journal: Nature Medicine (2016)
Clinical relevance of insulin regulatory pathways in non-small cell lung cancer (NSCLC) progression.
Authors: Y. Bellil, A. M. Burke, I. S. Chan, W. Mostertz, A. Potti
Journal: Journal of Clinical Oncology (2010)

7012 Background: Insulin and insulin-like growth factors are key regulators of normal metabolism and growth. Independently, and via interactions with the epidermal growth factor receptor (EGFR), the insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1R) are implicated in the development and progression of NSCLC. Though novel agents targeting the IR/IGF-1R pathway are under investigation, no molecular markers exist to guide therapy. Methods: After confirming IR and IGF-1R pathway activation, RNA from control, insulin and IGF treated cells was submitted for gene expression profiling. Using binary regression, an in vitro gene signature for IR and IGF-1R pathway activation was generated and validated in two independent early stage (I-IIIA) NSCLC data sets (cohort 1, n= 442, cohort 2, n=170) and in 63 NSCLC cell lines. Matrigel invasion, EGFR tyrosine-kinase inhibition (TKI) resistance, and miRNA expression were assayed and correlated to predicted pathway activation. Results: Hierarchical clustering of predicted IR/IGF-1R pathway activation ranging from high to low revealed four prognostic clusters. NSCLC tumors with concomitant high activation of IR and IGF-1R pathway had a significantly worse survival compared to those with low-intermediate activation (cohort 1, p=0.008; cohort 2, p=0.02). Invasiveness was increased in NSCLC cell lines predicted to have high pathway activation (p=0.003), as were miRNAs associated with invasiveness and metastasis (miR-155, miR-373). Conversely, miRNAs associated with tumor suppression (let-7 family) were enriched in the low- intermediate cluster. Moreover, cell lines resistant to EGFR-TKIs were more likely to have high IR/IGF-1R pathway activation (p=0.04). Work is ongoing to evaluate the differential susceptibility to EGFR-TKIs, and identify IR/IGF-1R related miRNA targets mediating EGFR-TKI resistance. Conclusions: A transcriptomic-based strategy delineates patterns of the IR/IGF-1R pathways that are prognostic in NSCLC, and identifies cohorts of patients who may be candidates for adjuvant therapy with IGF-1R inhibitors. Such a directed approach could improve therapeutic efficacy and subvert EGFR resistance mechanisms in NSCLC. No significant financial relationships to disclose.
Characterization of Five Homozygous ADAMTS13 Mutations in Hereditary Thrombotic Thrombocytopenic Purpura – Towards a Phenotype-Genotype Correlation?
Authors: Sara C Meyer, Shengyu Jin, Wenjing Cao, X. Long Zheng, Bernhard Lammle, Johanna A Kremer Hovinga
Journal: Blood (2008)
Medical Care Costs Associated With Long-term Weight Maintenance Versus Weight Gain Among Patients With Type 2 Diabetes
Authors: Gregory A. Nichols, Kelly Bell, Teresa M. Kimes, Maureen O’Keeffe-Rosetti
Journal: Diabetes Care (2016)

Weight loss is recommended for overweight patients with diabetes but avoidance of weight gain may be a more realistic goal. We calculated the 4-year economic impact of maintaining body weight versus gaining weight.Among 8,154 patients with type 2 diabetes, we calculated weight change as the difference between the first body weight measure in 2010 and the last measure in 2013 and calculated mean glycated hemoglobin (A1C) from all measurements from 2010 to 2013. We created four analysis groups: weight change <5% and A1C <7%; weight gain ≥5% and A1C <7%; weight change <5% and A1C ≥7%; and weight gain ≥5% and A1C ≥7%. We compared change in medical costs between 2010 and 2013, adjusted for demographic and clinical characteristics.Patients who maintained weight within 5% of baseline experienced a reduction in costs of about $400 regardless of A1C. In contrast, patients who gained ≥5% of baseline weight and had mean A1C ≥7% had an increase in costs of $1,473 (P < 0.001). Those who gained >5% of their baseline weight with mean A1C <7% had a modest increase in costs ($387, NS).Patients who gained at least 5% of their baseline body weight and did not maintain A1C <7% over 4 years experienced a 14% increase in medical costs, whereas those who maintained good glycemic control had a mean cost increase of 3.3%. However, patients who maintained weight within 5% of baseline had costs that were ∼5% lower than baseline. Avoidance of weight gain may reduce costs in the long-term.