tbuckley/cabot-search huggingface dataset:
Microangiopathy, Arterial Stiffness, and Risk Stratification in Patients With Type 2 Diabetes
Authors: Alexios S. Antonopoulos, Gerasimos Siasos, Dimitris Tousoulis
Journal: JAMA Cardiology (2017)

To the Editor We read with interest the article by Scirica et al1 on the prognostic implications of biomarker assessment in patients with type 2 diabetes. Although their findings are extremely interesting, other factors involved in cardiovascular outcome have not been completely evaluated.
A novel link between keratoderma and cardiomyopathy: contiguous gene deletion involving the desmoglein gene cluster
Authors: S. Brown, J. Ahmed, S. Zwolinski, P. Brennan, N. Rajan
Journal: British Journal of Dermatology (2017)

DEAR EDITOR, Desmocollin and desmoglein are important proteins in intercellular adhesion in both the skin and the heart. 1 Heterozygous mutations in the desmocollin 2 (DSC2) 2 and desmoglein 2 (DSG2) 3 genes can both result in desmosomal dysfunction in cardiomyocytes, leading to development of fibrofatty tissue, termed arrhythmogenic right ventricular cardiomyopathy (ARVC).Heterozygous truncating mutations in desmoglein 1 (DSG1), an intervening gene, can present as a striate palmoplantar keratoderma, while homozygous DSG1 mutations can cause severe dermatitis, allergies and metabolic wasting. 4Unlike mutations in plakoglobins and desmoplakins, which affect both tissues, the desmogleins, desmocollins and plakophilins typically affect either the skin or the heart. 1 Here
Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers
Authors: Per Hydbring, Yinan Wang, Anne Fassl, Xiaoting Li, Veronica Matia, Tobias Otto, Yoon Jong Choi, Katharine E. Sweeney, Jan M. Suski, Hao Yin, Roman L. Bogorad, Shom Goel, Haluk Yuzugullu, Kevin J. Kauffman, Junghoon Yang, Chong Jin, Yingxiang Li, Davide Floris, Richard Swanson, Kimmie Ng, Ewa Sicinska, Lars Anders, Jean J. Zhao, Kornelia Polyak, Daniel G. Anderson, Cheng Li, Piotr Sicinski
Journal: Cancer Cell (2017)
Intersect-then-combine approach: improving the performance of somatic variant calling in whole exome sequencing data using multiple aligners and callers
Authors: Maurizio Callari, Stephen-John Sammut, Leticia De Mattos-Arruda, Alejandra Bruna, Oscar M. Rueda, Suet-Feung Chin, Carlos Caldas
Journal: Genome Medicine (2017)

Bioinformatic analysis of genomic sequencing data to identify somatic mutations in cancer samples is far from achieving the required robustness and standardisation. In this study we generated a whole exome sequencing benchmark dataset using the platinum genome sample NA12878 and developed an intersect-then-combine (ITC) approach to increase the accuracy in calling single nucleotide variants (SNVs) and indels in tumour-normal pairs. We evaluated the effect of alignment, base quality recalibration, mutation caller and filtering on sensitivity and false positive rate. The ITC approach increased the sensitivity up to 17.1%, without increasing the false positive rate per megabase (FPR/Mb) and its validity was confirmed in a set of clinical samples.
The effect of a supervised exercise program on arm girth measurements in breast cancer survivors.
Authors: Laura M. Leach, Amy Kleski, Kathy Spencer, Michelle LaLonde, Thomas J. Sweeney, Teresa Caulin-Glaser
Journal: Journal of Clinical Oncology (2012)

9115 Background: There is minimal research examining the effect of cardiovascular and resistance exercise after surgery and/or radiation treatment to the breast and axillary area. Currently there are no guidelines for activity restrictions; however, medical providers historically have recommended limiting activity of the affected arm in an attempt to prevent the development of lymphedema. This could potentially affect future quality of life and other medical issues in breast cancer survivors. Methods: Female breast cancer survivors (n=79) completed an 8-week group exercise program meeting two days per week for cardiovascular and resistance training. Participants were also encouraged to exercise independently in addition to their group sessions. Bilateral arm girth measurements were performed on all participants upon program entry and exit. Measurements were taken distal to the ulnar styloid process (wrist) and three inches above (upper arm) and below (elbow) the lateral epicondyle of the elbow. All participants included in this analysis attended ≥ 70% of the group exercise sessions and had complete entry and exit measurements. Results: Participants attended an average of 15.94 ± 3.75 exercise sessions during the 8 week program. Changes in arm girth measurement were compared for the surgical side and non-surgical sides of the body using paired t-tests. Arm girth changes in the surgical side of the body were compared to the non-surgical side of the body using the Wilcoxon Ranked Sum test. The surgical and the non-surgical arm girths did not significantly increase at the wrist (p=0.55 and p=0.76), elbow (p=0.31 and p=0.24) or upper arm (p=0.18 and p=0.42). The changes in arm girth observed on the surgical body side were not significantly different from the changes observed on the non-surgical side (wrist (p=0.67), elbow (p=0.44), and upper arm (p=0.36). Conclusions: A structured, group-based exercise program involving both cardiovascular and resistance training did not significantly increase arm girth measurements in breast cancer survivors.
Treatment of Higher-Risk Myelodysplastic Syndrome (MDS) by American Hematology-Oncology Providers (AHOP's): Changes in 1st-Line Treatment Preferences Over Time in Relation to Cytogenetics &amp; Survival Data From Randomized Studies (2006–2010),
Authors: James M. Foran, Michael G. Heckman, Michael E. Williams, Joanne Willey, Mark R. Green
Journal: Blood (2011)
Efficacy and Safety of Immunosuppressive Therapy with Horse Antithymocyte Globulin (ATGAM) Plus Ciclosporine in 341 Patients with Acquired Aplastic Anemia: Report of the French Patient-Named Program on Behalf of the French Reference Center for Aplastic Anemia
Authors: Regis Peffault De Latour, Reza Tabrizi, Felipe Suarez, Thierry Lamy, Mohamad Mohty, Christian Récher, Charlotte Jubert, Marlène Pasquet, Claire Galambrun, Stéphanie Nguyen, Jean-Yves Cahn, Thorsten Brawn, Eric Deconinck, Jacques-Olivier Bay, Fiorenza Barraco, Gerard Socie
Journal: Blood (2016)
Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer
Authors: Fergus J. Couch, Hermela Shimelis, Chunling Hu, Steven N. Hart, Eric C. Polley, Jie Na, Emily Hallberg, Raymond Moore, Abigail Thomas, Jenna Lilyquist, Bingjian Feng, Rachel McFarland, Tina Pesaran, Robert Huether, Holly LaDuca, Elizabeth C. Chao, David E. Goldgar, Jill S. Dolinsky
Journal: JAMA Oncology (2017)

Germline pathogenic variants in BRCA1 and BRCA2 predispose to an increased lifetime risk of breast cancer. However, the relevance of germline variants in other genes from multigene hereditary cancer testing panels is not well defined.To determine the risks of breast cancer associated with germline variants in cancer predisposition genes.A study population of 65 057 patients with breast cancer receiving germline genetic testing of cancer predisposition genes with hereditary cancer multigene panels. Associations between pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes and breast cancer risk were estimated in a case-control analysis of patients with breast cancer and Exome Aggregation Consortium reference controls. The women underwent testing between March 15, 2012, and June 30, 2016.Breast cancer risk conferred by pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes.The mean (SD) age at diagnosis for the 65 057 women included in the analysis was 48.5 (11.1) years. The frequency of pathogenic variants in 21 panel genes identified in 41 611 consecutively tested white women with breast cancer was estimated at 10.2%. After exclusion of BRCA1, BRCA2, and syndromic breast cancer genes (CDH1, PTEN, and TP53), observed pathogenic variants in 5 of 16 genes were associated with high or moderately increased risks of breast cancer: ATM (OR, 2.78; 95% CI, 2.22-3.62), BARD1 (OR, 2.16; 95% CI, 1.31-3.63), CHEK2 (OR, 1.48; 95% CI, 1.31-1.67), PALB2 (OR, 7.46; 95% CI, 5.12-11.19), and RAD51D (OR, 3.07; 95% CI, 1.21-7.88). Conversely, variants in the BRIP1 and RAD51C ovarian cancer risk genes; the MRE11A, RAD50, and NBN MRN complex genes; the MLH1 and PMS2 mismatch repair genes; and NF1 were not associated with increased risks of breast cancer.This study establishes several panel genes as high- and moderate-risk breast cancer genes and provides estimates of breast cancer risk associated with pathogenic variants in these genes among individuals qualifying for clinical genetic testing.
Neoadjuvant concurrent chemoradiotherapy plus superior rectal arterial infusion chemotherapy in locally advanced rectal cancer (LARC): A pilot study from a single institute.
Authors: Dong Wang, Chunxue Li, Jinlu Shan, Yi Qing, Mengxia Li, Xian Yu, Hualiang Xiao, Yan Feng, Xuemei Li
Journal: Journal of Clinical Oncology (2015)

e14608 Background: Rectal cancer represents 30% of all colorectal cancers, with about 40,000 new cases per year. In the past two decades the management of rectal cancer has made important progress highlighting the important role of a multimodal strategic approach that combines surgery, radiation therapy and chemotherapy. Nowadays, surgery remains the primary treatment and neo-adjuvant chemoradiotherapy, based on fluoropyrimidine continuous infusion, is considered the standard in locally advanced rectal cancer (LARC). Arterial infusion through the superior rectal artery is conventionally used in palliative care of inoperable LARC, while its application in neoadjuvant therapy of LARC remains unreported. Methods: Twenty-four patients with LARC (clinically T3-4, any N) were randomized in two arms: those treated with neoadjuvant concurrent systematic chemoradiotherapy consisting of 46Gy/23/ff concurrent with S1 (40-60 mg bid) and on days 1-28 (NACT-RT) or concurrent superior rectal artery chemotherapy infusion (oxaliplatin 85 mg/sqm) with oral S1 and radiotherapy with the same regime (NATACE-RT). Surgery was performed after 4-6weeks. The primary end point for the current report was the pathological response. Results: Twenty out of 24 patients were evaluated (NACT-RT 10, NATACE-RT 10); 10/14 in the NACT-RT arm and all patients in the NATACE-RT arm received the preoperative treatment as in the protocol and underwent a radical resection. One out of 10 in the NACT-RT group showed a complete pathologic response (pCR), whereas 9/10 in the NATACE-RT group showed a pCR. The overall downstaging rates did not show any significant difference between the two arms. The OS and DFS are under observation. Conclusions: The current pilot study suggests that the application of TACE in patients with LARC significantly increases the pCR when compared with conventional NACT-RT and is associated with better tolerance and an equal downstaging effect.
Erythrocyte sialoglycoproteins engage Siglec-9 on neutrophils to suppress activation
Authors: Anel Lizcano, Ismael Secundino, Simon Döhrmann, Ross Corriden, Cristina Rohena, Sandra Diaz, Pradipta Ghosh, Lingquan Deng, Victor Nizet, Ajit Varki
Journal: Blood (2017)
In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases
Authors: Go Oshima, Nining Guo, Chunbai He, Melinda E. Stack, Christopher Poon, Abhineet Uppal, Sean C. Wightman, Akash Parekh, Kinga B. Skowron, Mitchell C. Posner, Wenbin Lin, Nikolai N. Khodarev, Ralph R. Weichselbaum
Journal: Molecular Therapy (2017)

Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs. Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs.
Isolation of Single Human Cord Blood-Derived CD34-Negative Hematopoietic Stem Cells (HSCs) Residing at the Apex of the Human HSC Hierarchy
Authors: Keisuke Sumide, Yoshikazu Matsuoka, Ryusuke Nakatsuka, Hiroshi Kawamura, Tatsuya Fujioka, Hiroaki Asano, Yoshiaki Sonoda
Journal: Blood (2016)
Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance
Authors: Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Atsuo Ochi, Daniel W Heindel, Ki Buom Lee, Constantinos P Zambirinis, Gautam SD Balasubramania Pandian, Shivraj Savadkar, Alejandro Torres-Hernandez, Shruti Nayak, Ding Wang, Mautin Hundeyin, Brian Diskin, Berk Aykut, Gregor Werba, Rocky M Barilla, Robert Rodriguez, Steven Chang, Lawrence Gardner, Lara K Mahal, Beatrix Ueberheide, George Miller
Journal: Nature Medicine (2017)
Identification of six new genetic loci associated with atrial fibrillation in the Japanese population
Authors: Siew-Kee Low, Atsushi Takahashi, Yusuke Ebana, Kouichi Ozaki, Ingrid E Christophersen, Patrick T Ellinor, Soichi Ogishima, Masayuki Yamamoto, Mamoru Satoh, Makoto Sasaki, Taiki Yamaji, Motoki Iwasaki, Shoichiro Tsugane, Keitaro Tanaka, Mariko Naito, Kenji Wakai, Hideo Tanaka, Tetsushi Furukawa, Michiaki Kubo, Kaoru Ito, Yoichiro Kamatani, Toshihiro Tanaka
Journal: Nature Genetics (2017)
Effect of Resveratrol on Walking Performance in Older People With Peripheral Artery Disease
Authors: Mary M. McDermott, Christiaan Leeuwenburgh, Jack M. Guralnik, Lu Tian, Robert Sufit, Lihui Zhao, Michael H. Criqui, Melina R. Kibbe, James H. Stein, Donald Lloyd-Jones, Stephen D. Anton, Tamar S. Polonsky, Ying Gao, Rafael de Cabo, Luigi Ferrucci
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> Research shows that resveratrol, a sirtuin activator in red wine, improves exercise endurance and skeletal-muscle oxidative metabolism in animals and may enhance vascular function in humans. Resveratrol supplement sales exceed $30 million annually in the United States, but few data are available regarding its efficacy in humans. <h3>Objective</h3> To determine whether resveratrol, 125 mg/d or 500 mg/d, improves the 6-minute walk performance in patients with peripheral artery disease (PAD). <h3>Design, Setting, and Participants</h3> This parallel-design, double-blind, randomized clinical trial, called Resveratrol to Improve Outcomes in Older People With PAD (RESTORE), was conducted at Northwestern University. Sixty-six participants 65 years or older with PAD were randomized to receive a daily capsule of resveratrol, 125 mg or 500 mg, or placebo for 6 months. Participants were randomized using a randomly permuted block method stratified by baseline 6-minute walk test performance. This trial was conducted between January 1, 2015, and August 5, 2016, and data analyses were performed according to the intention-to-treat concept. <h3>Interventions</h3> Administration of resveratrol, 125 or 500 mg/d, or placebo once daily. <h3>Main Outcomes and Measures</h3> The primary outcome measure was the change in 6-minute walk distance at the 6-month follow-up. One of the secondary outcomes was change in maximal treadmill walking time. Because of the preliminary nature of the trial, the a priori power calculation used a 1-sided test with a significance level of<i>P</i> &lt; .10. <h3>Results</h3> The 66 participants were predominantly men (45 [68%]), had a mean (SD) age of 74.4 (6.6) years, and had a mean (SD) ankle brachial index of 0.67 (0.18). Sixty-four (97%) completed follow-up. Six-month mean (SE) changes in 6-minute walk distance were 4.6 (8.1) m for the 125-mg resveratrol group, −12.8 (7.5) m for the 500-mg resveratrol group, and −12.3 (7.9) m for the placebo group (<i>P</i> = .07 for the 125-mg resveratrol group vs placebo;<i>P</i> = .96 for the 500-mg resveratrol group vs placebo). Six-month mean (SE) changes in maximal treadmill walking time were 0.5 (2.3) minutes for the 125-mg resveratrol group, −0.6 (2.1) minutes for the 500-mg resveratrol group, and 0.4 (2.1) minutes for the placebo group (<i>P</i> = .18 for the 125-mg resveratrol group vs placebo;<i>P</i> = .12 for the 500-mg resveratrol group vs placebo). <h3>Conclusions and Relevance</h3> The RESTORE trial found no consistent evidence that resveratrol improves walking performance in patients 65 years or older with PAD. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02246660
Identification of a novel crizotinib-sensitive BCL11A-ALK gene fusion in a nonsmall cell lung cancer patient
Authors: Qing Tian, Wen-Jing Deng, Zong-Wei Li
Journal: European Respiratory Journal (2017)

Until now, more than 10 different ALK fusion partners have been discovered in nonsmall cell lung cancer (NSCLC): EML4, KIF5B, KLC1, TFG, TPR, HIP1, STRN, DCTN1, SQSTM1 and BIRC 6, among others [1, 2]. We report here a novel ALK fusion partner in a NSCLC patient who responded well to the ALK inhibitor crizotinib. We report a novel ALK fusion partner in a NSCLC patient who responded well to the ALK inhibitor crizotinib <http://ow.ly/7O6f309KyFb>
Distinct Regulatory Effects of Myeloid Cell and Endothelial Cell NAPDH Oxidase 2 on Blood Pressure
Authors: Can Martin Sag, Moritz Schnelle, Juqian Zhang, Colin E. Murdoch, Sabine Kossmann, Andrea Protti, Celio X.C. Santos, Greta Sawyer, Xiaohong Zhang, Heloise Mongue-Din, Daniel A. Richards, Alison C. Brewer, Oleksandra Prysyazhna, Lars S. Maier, Philip Wenzel, Philip J. Eaton, Ajay M. Shah
Journal: Circulation (2017)

Background: Hypertension caused by increased renin-angiotensin system activation is associated with elevated reactive oxygen species production. Previous studies implicate NADPH oxidase (Nox) proteins as important reactive oxygen species sources during renin-angiotensin system activation, with different Nox isoforms being potentially involved. Among these, Nox2 is expressed in multiple cell types, including endothelial cells, fibroblasts, immune cells, and microglia. Blood pressure (BP) is regulated at the central nervous system, renal, and vascular levels, but the cell-specific role of Nox2 in BP regulation is unknown. Methods: We generated a novel mouse model with a floxed Nox2 gene and used Tie2-Cre, LysM Cre, or Cdh5-CreERT2 driver lines to develop cell-specific models of Nox2 perturbation to investigate its role in BP regulation. Results: Unexpectedly, Nox2 deletion in myeloid but not endothelial cells resulted in a significant reduction in basal BP. Both Tie2-CreNox2 knockout (KO) mice (in which Nox2 was deficient in both endothelial cells and myeloid cells) and LysM CreNox2KO mice (in which Nox2 was deficient in myeloid cells) had significantly lower BP than littermate controls, whereas basal BP was unaltered in Cdh5-CreERT2 Nox2KO mice (in which Nox2 is deficient only in endothelial cells). The lower BP was attributable to an increased NO bioavailability that dynamically dilated resistance vessels in vivo under basal conditions without a change in renal function. Myeloid-specific Nox2 deletion had no effect on angiotensin II–induced hypertension, which, however, was blunted in Tie2-CreNox2KO mice, along with preservation of endothelium-dependent relaxation during angiotensin II stimulation. Conclusions: We identify a hitherto unrecognized modulation of basal BP by myeloid cell Nox2, whereas endothelial cell Nox2 regulates angiotensin II–induced hypertension. These results identify distinct cell-specific roles for Nox2 in BP regulation.
Benzodiazepines are linked to pneumonia risk in patients with dementia
Authors: Jacqui Wise
Journal: BMJ (2017)

The risk of pneumonia should be added to the list of potential harms associated with benzodiazepines in patients with dementia, researchers have reported in a study published in the Canadian Medical Association Journal .1

The large Finnish study found that benzodiazepines were linked to a 30% increased risk of pneumonia in patients with Alzheimer’s disease, and this risk was highest at the start of treatment.

Benzodiazepines are known to be associated with injuries from falls and deteriorating cognitive function. …
Short‐Term Pulmonary Function Trends Are Predictive of Mortality in Interstitial Lung Disease Associated With Systemic Sclerosis
Authors: Nicole S. Goh, Rachel K. Hoyles, Christopher P. Denton, David M. Hansell, Elisabetta A. Renzoni, Toby M. Maher, Andrew G. Nicholson, Athol U. Wells
Journal: Arthritis & Rheumatology (2017)

Objective To determine the prognostic value of pulmonary function test (PFT) trends at 1 and 2 years in interstitial lung disease (ILD) associated with systemic sclerosis (SSc). Methods The prognostic significance of PFT trends at 1 year (n = 162) and 2 years (n = 140) was examined against 15‐year survival in patients with SSc‐associated ILD. PFT trends, expressed as continuous change and as categorical change in separate analyses, were examined against mortality in univariate and multivariate models. SSc‐associated ILD was defined at presentation as either limited lung fibrosis or extensive lung fibrosis, using the United Kingdom Raynaud's and Scleroderma Association severity staging system. Results One‐year PFT trends were predictive of mortality only in patients with extensive lung fibrosis: categorical change in the forced vital capacity (FVC), alone or in combination with categorical change in the diffusing capacity for carbon monoxide (DL co ), had greater prognostic significance than continuous change in the FVC or trends in other PFT variables. Taking into account both prognostic value and sensitivity to change, the optimal definition of progression for trial purposes was an FVC and DL co composite end point, consisting of either an FVC decline from baseline of ≥10% or an FVC decline of 5–9% in association with a DL co decline of ≥15%. At 2 years, gas transfer trends had the greatest prognostic significance, in the whole cohort and in those with limited lung fibrosis. However, in patients with extensive lung fibrosis, the above‐defined FVC and DL co composite end point was the strongest prognostic determinant. Larger changes in the FVC:DL co ratio than in the carbon monoxide transfer coefficient were required to achieve prognostic significance. Conclusion Based on linkages to long‐term outcomes, these findings provide support for use of routine spirometry and gas transfer monitoring in patients with SSc‐associated ILD, with further evaluation of a composite FVC and DL co end point warranted for trial purposes.