tbuckley/cabot-search huggingface dataset:
Clinical, Genetic, and Radiological Features of Extrapyramidal Movement Disorders in Mitochondrial Disease
Authors: Mika H. Martikainen, Yi Shiau Ng, Gráinne S. Gorman, Charlotte L. Alston, Emma L. Blakely, Andrew M. Schaefer, Patrick F. Chinnery, David J. Burn, Robert W. Taylor, Robert McFarland, Doug M. Turnbull
Journal: JAMA Neurology (2016)

Extrapyramidal movement disorders associated with mitochondrial disease are difficult to treat and can lead to considerable disability. Moreover, potential new treatment trials on the horizon highlight the importance of genotype-phenotype associations and deep phenotyping of the movement disorders related to mitochondrial disease.To describe the phenotype, genetic etiology, and investigation of extrapyramidal movement disorders in a large and well-defined mitochondrial disease cohort.An observational cohort study at a single national referral center. Among 678 patients (87% adults) followed up at the Newcastle mitochondrial disease specialized referral center between January 1, 2000, and January 31, 2015, 42 patients (12 pediatric, 30 adult) with genetic or biochemical evidence of mitochondrial disease and with 1 or more predefined extrapyramidal movement disorders (parkinsonism, dystonia, tremor, chorea, and restless legs syndrome) were included.We investigated the prevalence and genetic causes of dystonia and parkinsonism as well as radiological findings in the context of movement disorders in mitochondrial disease. All patients were interviewed and examined. All available medical notes and clinical, radiological, and genetic investigations were reviewed.Forty-two patients (mean [SD] age, 37 [25] years; 38% female) with mitochondrial disease (12 pediatric [age range, 4-14 years], 30 adult [age range, 20-81 years]) with extrapyramidal movement disorders were identified. Dystonia manifested in 11 pediatric patients (92%), often in the context of Leigh syndrome; parkinsonism predominated in 13 adult patients (43%), among whom 5 (38%) harbored either dominant (n = 1) or recessive (n = 4) mutations in POLG. Eleven adult patients (37%) manifested with either generalized or multifocal dystonia related to mutations in mitochondrial DNA, among which the most common were the m.11778G>A mutation and mutations in MT-ATP6 (3 of 11 patients [27%] each). Bilateral basal ganglia lesions were the most common finding in brain magnetic resonance imaging, usually associated with generalized dystonia or Leigh syndrome.Dystonia, often associated with Leigh syndrome, was the most common extrapyramidal movement disorder among pediatric patients with mitochondrial disease. Parkinsonism was the most prevalent extrapyramidal movement disorder in adults and was commonly associated with POLG mutations; dystonia was predominantly associated with mitochondrial DNA mutations. These findings may help direct genetic screening in a busy neurology outpatient setting.
Weekend admission to psychiatric hospital is not linked to increased risk of death
Authors: Jacqui Wise
Journal: BMJ (2016)

Being admitted to a psychiatric hospital at the weekend is not associated with a higher risk of death than admission during the week, research published in the British Journal of Psychiatry has found.1 However, patients admitted at the weekend had shorter admissions and were more likely to be readmitted, suggesting that weekend patients have ongoing, unresolved treatment needs.

The finding is topical because of the government’s pledge to implement full seven day working in the NHS and impose a new contract on junior doctors. England’s health secretary, Jeremy Hunt, has repeatedly said that excess deaths at weekends are a result of …
Cadmium-Induced Interstitial Cell Tumors in Rats and Mice and Their Prevention by Zinc&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Samuel A. Gunn, Thelma Clark Gould, W. A. D. Anderson
Journal: JNCI Journal of the National Cancer Institute (1963)

A single subcutaneous injection of cadmium chloride to rats and mice selectively damaged the vascular supply of the testis and resulted in complete necrosis of the seminiferous tubules and interstitial tissue. After a few weeks interstitial tissue regenerated, and approximately 1 year later 70 to 80 percent of the animals showed evidence of interstitial cell tumor (ICT) formation. The induction of ICT by cadmium was prevented by the simultaneous administration of a physicochemically similar element, zinc. Studies on the hormonal status of rats treated with cadmium 3 months previously indicated that the content of interstitial cell-stimulating hormone (ICSH) of pituitary glands was higher than control levels. Normal-appearing, regenerating Leydig's cells were not functioning normally, however, as indicated by lowered accessorygland size and function. This was further emphasized by hormonal studies that showed the cadmium-treated rats were completely unresponsive to administered ICSH.
The<i>CDKN2A</i>Tumor-Suppressor Locus — A Tale of Two Proteins
Authors: Bruce E. Clurman, Mark Groudine
Journal: New England Journal of Medicine (1998)

In this issue of the Journal, Monzon et al. report the occurrence of germ-line mutations of the CDKN2A gene in patients with multiple primary melanomas.1 CDKN2A, a tumor-suppressor gene, has a central role in regulating cell division.The loss of function of tumor-suppressor genes is a key event in the multistep process that transforms a normal cell into a cancer cell. In normal cells, the proteins that arise from these genes participate in diverse biologic processes. Some proteins, such as the p53 protein, protect the cell from genetic damage, and their loss leads to the characteristic genomic instability and . . .
Racial Differences in Quantitative Measures of Area and Volumetric Breast Density
Authors: Anne Marie McCarthy, Brad M. Keller, Lauren M. Pantalone, Meng-Kang Hsieh, Marie Synnestvedt, Emily F. Conant, Katrina Armstrong, Despina Kontos
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Increased breast density is a strong risk factor for breast cancer and also decreases the sensitivity of mammographic screening. The purpose of our study was to compare breast density for black and white women using quantitative measures. Methods: Breast density was assessed among 5282 black and 4216 white women screened using digital mammography. Breast Imaging-Reporting and Data System (BI-RADS) density was obtained from radiologists' reports. Quantitative measures for dense area, area percent density (PD), dense volume, and volume percent density were estimated using validated, automated software. Breast density was categorized as dense or nondense based on BI-RADS categories or based on values above and below the median for quantitative measures. Logistic regression was used to estimate the odds of having dense breasts by race, adjusted for age, body mass index (BMI), age at menarche, menopause status, family history of breast or ovarian cancer, parity and age at first birth, and current hormone replacement therapy (HRT) use. All statistical tests were two-sided. Results: There was a statistically significant interaction of race and BMI on breast density. After accounting for age, BMI, and breast cancer risk factors, black women had statistically significantly greater odds of high breast density across all quantitative measures (eg, PD nonobese odds ratio [OR] = 1.18, 95% confidence interval [CI] = 1.02 to 1.37, P = .03, PD obese OR = 1.26, 95% CI = 1.04 to 1.53, P = .02). There was no statistically significant difference in BI-RADS density by race. Conclusions: After accounting for age, BMI, and other risk factors, black women had higher breast density than white women across all quantitative measures previously associated with breast cancer risk. These results may have implications for risk assessment and screening.
Abstract 17250: Serum vs. Imaging Biomarkers of Myocardial Injury in Duchenne Muscular Dystrophy: Findings from the E-SCAR DMD Trial
Authors: Subha V Raman, Kan N Hor, Wojciech Mazur, Nancy Halnon, Tam Tran, Suzanne Smart, Beth McCarthy, John T Kissel, Michael D Taylor, John L Jefferies, Jill Rafael-Fortney, Sharon Roble, Linda H Cripe
Journal: Circulation (2014)

Introduction: Cardiomyopathy has become a leading cause of death in Duchenne muscular dystrophy (DMD). We previously showed that early mineralocorticoid receptor antagonist therapy reduces myocardial damage in a preclinical model of DMD. The Eplerenone for Subclinical Cardiomyopathy in DMD (E-SCAR DMD, NCT01521546) is a multicenter randomized placebo-controlled clinical trial evaluating eplerenone in boys with preserved left ventricular ejection fraction (LVEF) and evident myocardial injury by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Hypothesis: To better define biomarkers of early disease, we hypothesized that LGE has greater sensitivity vs. serum biomarkers for myocardial injury in DMD cardiomyopathy. Methods: Boys with DMD age ≥ 7 years were enrolled across 3 centers. LGE-CMR images were acquired using comparable techniques across 3T scanners, and core laboratory LGE quantification was performed blinded to laboratory findings as a percentage of LV mass using software based on the full-width half-maximum technique. Troponin-I, creatine kinase (CK) and CK isoenzymes were measured from blood samples obtained at the time of CMR examination using standardized clinical assays. Results: 42 boys age 16 ± 7 years had preserved LVEF (57 ± 6%), and LGE-positive regions averaged 5.0 ± 2.6% of LV myocardium. While 100% had evident myocardial injury by LGE, 43% had measurable CK-MB and only 18% had detectable troponin-I in serum (Figure). %LGE was higher (5.4 ± 2.7 vs. 3.3 ± 1.8%, p&lt;0.05) and LVEF was lower (55.4 ± 4.9 vs. 59.0 ± 7.1%, p &lt; 0.01) in boys with detectable vs. those with undetectable troponin-I, whereas detectable CK-MB did not predict higher %LGE or lower LVEF. Conclusion: DMD patients with abnormal myocardium by LGE-CMR may have no detectable abnormalities by serum biomarkers, underscoring the importance of myocardial injury imaging in identifying patients with subclinical cardiomyopathy who may benefit from early treatment.
Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study
Authors: Dae Hyun Yoo, Nenad Prodanovic, Janusz Jaworski, Pedro Miranda, Edgar Ramiterre, Allan Lanzon, Asta Baranauskaite, Piotr Wiland, Carlos Abud-Mendoza, Boycho Oparanov, Svitlana Smiyan, HoUng Kim, Sang Joon Lee, SuYeon Kim, Won Park
Journal: Annals of the Rheumatic Diseases (2016)

Objectives To assess the efficacy and safety of switching from the infliximab reference product (RP; Remicade) to its biosimilar CT-P13 (Remsima, Inflectra) or continuing CT-P13 in patients with rheumatoid arthritis (RA) for an additional six infusions. Methods This open-label extension study recruited patients with RA who had completed the 54-week, randomised, parallel-group study comparing CT-P13 with RP (PLANETRA; NCT01217086 ). CT-P13 (3 mg/kg) was administered intravenously every 8 weeks from weeks 62 to 102. All patients received concomitant methotrexate. Endpoints included American College of Rheumatology 20% (ACR20) response, ACR50, ACR70, immunogenicity and safety. Data were analysed for patients who received CT-P13 for 102 weeks (maintenance group) and for those who received RP for 54 weeks and then switched to CT-P13 (switch group). Results Overall, 302 of 455 patients who completed the PLANETRA study enrolled into the extension. Of these, 158 had received CT-P13 (maintenance group) and 144 RP (switch group). Response rates at week 102 for maintenance versus switch groups, respectively, were 71.7% vs 71.8% for ACR20, 48.0% vs 51.4% for ACR50 and 24.3% vs 26.1% for ACR70. The proportion of patients with antidrug antibodies was comparable between groups (week 102: 40.3% vs 44.8%, respectively). Treatment-emergent adverse events occurred in similar proportions of patients in the two groups during the extension study (53.5% and 53.8%, respectively). Conclusions Comparable efficacy and tolerability were observed in patients who switched from RP to its biosimilar CT-P13 for an additional year and in those who had long-term CT-P13 treatment for 2 years. Trial registration number NCT01571219; Results.
Deep Molecular Responses In Patients With Newly Diagnosed Chronic Myeloid Leukemia Receiving Nilotinib As Assessed Within The EUTOS Laboratory Network In The ENEST1st Study
Authors: Francis J Giles, Michele Baccarani, Tim H. Brümmendorf, Andrzej Hellmann, Francois-Xavier Mahon, Gianantonio Rosti, Giuseppe Saglio, Juan Luis Steegmann, Gert J. Ossenkoppele, Maria Asunción Echeveste, Norbert Gattermann, Laimonas Griskevicius, Philipp D. le Coutre, Bruno Martino, Tamas Masszi, Ljubomir Petrov, Delphine Rea, Johan Richter, Jesper Stentoft, Michel Tulliez, Peter Schuld, Angela Pellegrino, Claudia Walasek, Nicholas C.P. Cross, Andreas Hochhaus
Journal: Blood (2013)
Clinical Diagnosis of Mental Disorders Immediately Before and After Cancer Diagnosis
Authors: Donghao Lu, Therese M. L. Andersson, Katja Fall, Christina M. Hultman, Kamila Czene, Unnur Valdimarsdóttir, Fang Fang
Journal: JAMA Oncology (2016)

Psychiatric comorbidities are common among patients with cancer. However, whether or not there is increased risk of mental disorders during the diagnostic workup leading to a cancer diagnosis was unknown.To examine the relative risks of depression, anxiety, substance abuse, somatoform/conversion disorder, and stress reaction/adjustment disorder during the periods before and after cancer diagnosis compared with individuals without cancer.Nationwide matched cohort study from January 1, 2001, to December 31, 2010, in a Swedish population and health registers.We estimated the time-varying hazard ratios (HRs) of the first clinical diagnosis of the studied mental disorders from 2 years before cancer diagnosis, through the time of diagnosis, and until 10 years after diagnosis, adjusting for age, sex, calendar period, and educational level. To assess milder mental conditions and symptoms, we further assessed the use of related psychiatric medications for patients with cancer diagnosed during 2008-2009.The study included 304 118 patients with cancer and 3 041 174 cancer-free individuals who were randomly selected from the Swedish population and individually matched to the patients with cancer on year of birth and sex. The median age at diagnosis for the patients with cancer was 69 years, and 46.9% of the patients were female. The relative rate for all studied mental disorders started to increase from 10 months before cancer diagnosis (HR, 1.1; 95% CI, 1.1-1.2), peaked during the first week after diagnosis (HR, 6.7; 95% CI, 6.1-7.4), and decreased rapidly thereafter but remained elevated 10 years after diagnosis (HR, 1.1; 95% CI, 1.1-1.2). The rate elevation was clear for all main cancers except nonmelanoma skin cancer and was stronger for cancers of poorer prognosis. Compared with cancer-free individuals, increased use of psychiatric medications was noted from 1 month before cancer diagnosis and peaked around 3 months after diagnosis among patients with cancer.Patients diagnosed as having cancer had increased risks of several common mental disorders from the year before diagnosis. These findings support the existing guidelines of integrating psychological management into cancer care and further call for extended vigilance for multiple mental disorders starting from the time of the cancer diagnostic workup.
Suicide rates rise sharply in the US, figures show
Authors: Michael McCarthy
Journal: BMJ (2016)

After a nearly consistent decline in the last decades of the 20th century, suicide rates in the United States have risen sharply for both men and women in all age groups under 75 years, according to a report from the US National Center for Health Statistics.1

The report found that from 1999 through to 2014 the age adjusted suicide rate increased 24%—from 10.5 to 13 per 100 000 population. …
Cross Talk Pathways Between Coagulation and Inflammation
Authors: Jonathan H. Foley, Edward M. Conway
Journal: Circulation Research (2016)

Anatomic pathology studies performed over 150 years ago revealed that excessive activation of coagulation occurs in the setting of inflammation. However, it has taken over a century since these seminal observations were made to delineate the molecular mechanisms by which these systems interact and the extent to which they participate in the pathogenesis of multiple diseases. There is, in fact, extensive cross talk between coagulation and inflammation, whereby activation of one system may amplify activation of the other, a situation that, if unopposed, may result in tissue damage or even multiorgan failure. Characterizing the common triggers and pathways are key for the strategic design of effective therapeutic interventions. In this review, we highlight some of the key molecular interactions, some of which are already showing promise as therapeutic targets for inflammatory and thrombotic disorders.
Increasing implementation and delivery of pulmonary rehabilitation: key messages from the new ATS/ERS policy statement
Authors: Ioannis Vogiatzis, Carolyn L. Rochester, Martijn A. Spruit, Thierry Troosters, Enrico M. Clini
Journal: European Respiratory Journal (2016)

The goal of the New Policy Statement is to expand provision of pulmonary rehabilitation to suitable patients worldwide http://ow.ly/ZcBJv
Abstract 13: Nkx2-5-notch Signaling Axis Regulates The Proliferation Of The Atrial Myocytes And Conduction System
Authors: Austin Nakano, Yasuhiro Nakashima, Diana A Yanez, Marlin Touma, Haruko Nakano, Artur Jarodzewicz, Maria C Jordan, Matteo Pellegrini, Kenneth P Roos, Kenneth P Roos
Journal: Circulation Research (2014)

Rationale: Tight control of cardiomyocyte proliferation is essential for the formation of four-chambered heart. Although human mutation of NKX2-5 is linked to septal defects and atrioventricular conduction abnormalities, early lethality and hemodynamic alteration in the mutant models have caused controversy as to whether Nkx2-5 regulates cardiomyocyte proliferation. Objective: In this study, we circumvented these limitations by atrial-restricted deletion of Nkx2-5. Method and Results: Atrial-specific Nkx2-5 mutants died shortly after birth with hyperplastic working myocytes and conduction system including two nodes and internodal tracts. Multicolor reporter analysis revealed that Nkx2-5-null cardiomyocytes displayed clonal proliferative activity throughout the atria, indicating the suppressive role of Nkx2-5 in the cardiomyocyte proliferation after chamber ballooning stages. Transcriptome analysis revealed that aberrant activation of Notch signaling underlies hyperproliferation of mutant cardiomyocytes, and forced activation of Notch signaling recapitulates hyperproliferation of working myocytes but not conduction system. Conclusion: Collectively, these data suggest that Nkx2-5 regulates proliferation of atrial working and conduction myocardium in coordination with Notch pathway.
Brief Report: Utilization of the First Biosimilar Infliximab Since Its Approval in South Korea
Authors: Seoyoung C. Kim, Nam‐Kyong Choi, Joongyub Lee, Kyoung‐Eun Kwon, Wesley Eddings, Yoon‐Kyoung Sung, Hong Ji Song, Aaron S. Kesselheim, Daniel H. Solomon
Journal: Arthritis & Rheumatology (2015)

The US Food and Drug Administration is considering an application for a biosimilar version of infliximab, which has been available in South Korea since November 2012. The aim of the present study was to examine the utilization patterns of both branded and biosimilar infliximab and other tumor necrosis factor (TNF) inhibitors in South Korea before and after the introduction of this biosimilar infliximab.Using claims data from April 2009 to March 2014 from the Korean Health Insurance Review and Assessment Service database, which includes the entire South Korean population, the number of claims for biosimilar infliximab was assessed. A segmented linear regression model was used to examine the utilization patterns of infliximab (the branded and biosimilar versions) and other TNF inhibitors (adalimumab and etanercept) before and after the introduction of the biosimilar infliximab.In total, 20,976 TNF inhibitor users were identified from the South Korean claims database, including 983 with a prescription claim for biosimilar infliximab. Among all of the claims for any version of infliximab, the proportion of biosimilar infliximab claims increased to 19% through March 2014. Before November 2012, each month there were 33 (95% confidence interval [95% CI] 32, 35) more infliximab claims, 44 (95% CI 40, 48) more etanercept claims, and 50 (95% CI 47, 53) more adalimumab claims. After November 2012, there were significant changes in the slopes for trend in usage, with additional increases in the use of branded and biosimilar infliximab (9 more claims per month, 95% CI 2, 17) and decreases in the use of etanercept (-52 claims per month, 95% CI -66, -38) and adalimumab (-21 claims per month, 95% CI -35, -6).During the first 15 months since its introduction in South Korea, one-fifth of all infliximab claims were for the biosimilar version. Introduction of biosimilar infliximab may affect the use of other TNF inhibitors, and the magnitude of change in usage will likely differ in other countries.
Defining actionable mutations for oncology therapeutic development
Authors: T. Hedley Carr, Robert McEwen, Brian Dougherty, Justin H. Johnson, Jonathan R. Dry, Zhongwu Lai, Zara Ghazoui, Naomi M. Laing, Darren R. Hodgson, Francisco Cruzalegui, Simon J. Hollingsworth, J. Carl Barrett
Journal: Nature reviews. Cancer (2016)
Modeling the cost-effectiveness of treatment options for patients with clinical stage I non seminomatous germ cell tumors (NGSCT)
Authors: Y. Wong, E. Sherman, G. Hudes, N. Haas, A. Konski, R. Uzzo, R. Greenberg, R. Beck
Journal: Journal of Clinical Oncology (2004)

4525 Background: Survival rates for good risk clinical stage I NGSCT exceed 98%. Although long term outcomes for surveillance (SURV) and primary retroperitoneal lymph node dissection (RPLND) may be equivalent, their relative cost-effectiveness is unknown. Approximately 30% on SURV will relapse and will be treated with chemotherapy (CHEMO) +/- RPLND. We present a pilot study to model the cost effectiveness of SURV vs RPLND. Methods: Patients in 4 health states (>1 year post treatment) were evaluated: a) SURV b) RPLND c) CHEMO or d) RPLND and CHEMO. Utilities were collected using the EuroQol, Time Trade Off (TTO), Standard Gamble (SG) and Visual Analog Scale (VAS). Direct medical costs (DMC) were determined using the 2002 Medicare Fee Schedule. Costas and benefits were discounted 3% annually. Health care resource use was determined using National Comprehensive Cancer Network guidelines. Paients were assumed to have only one relapse and late relapses (more than 3 years) were considered equal in both groups. Quality Adjusted Life Years (QALY) =utility*life years. Cost effective ratio (C/E)=DMC/QALY. Decision analysis was modeled using a Markov process for a 25 year old man and tested using standard and probabilistic sensitivity analysis. Results: Mean utilities are listed in the table below. Total costs for RPLND:$48,372, SURV:$62,598(primarily due to increased diagnostic tests during SURV period). QALY were 23.33 and 24.77 respectively. The incremental C/E for surveillance was $9,870 per QALY, suggesting that SURV is cost effective. Conclusion: Though limited by the small sample size and the disproportionately few patients on SURV alone, this pilot study shows that this is a feasible model for determining cost-effectiveness. This will be used as a model for a future, larger study to further clarify this issue and guide clinicians in making treatment recommendations. No significant financial relationships to disclose.