tbuckley/cabot-search huggingface dataset:
Clinic Blood Pressure Underestimates Ambulatory Blood Pressure in an Untreated Employer-Based US Population
Authors: Joseph E. Schwartz, Matthew M. Burg, Daichi Shimbo, Joan E. Broderick, Arthur A. Stone, Joji Ishikawa, Richard Sloan, Tyla Yurgel, Steven Grossman, Thomas G. Pickering
Journal: Circulation (2016)

Background: Ambulatory blood pressure (ABP) is consistently superior to clinic blood pressure (CBP) as a predictor of cardiovascular morbidity and mortality risk. A common perception is that ABP is usually lower than CBP. The relationship of the CBP minus ABP difference to age has not been examined in the United States. Methods: Between 2005 and 2012, 888 healthy, employed, middle-aged (mean±SD age, 45±10.4 years) individuals (59% female, 7.4% black, 12% Hispanic) with screening BP &lt;160/105 mm Hg and not taking antihypertensive medication completed 3 separate clinic BP assessments and a 24-hour ABP recording for the Masked Hypertension Study. The distributions of CBP, mean awake ABP (aABP), and the CBP−aABP difference in the full sample and by demographic characteristics were compared. Locally weighted scatterplot smoothing was used to model the relationship of the BP measures to age and body mass index. The prevalence of discrepancies in ABP- versus CBP-defined hypertension status—white-coat hypertension and masked hypertension—were also examined. Results: Average systolic/diastolic aABP (123.0/77.4±10.3/7.4 mm Hg) was significantly higher than the average of 9 CBP readings over 3 visits (116.0/75.4±11.6/7.7 mm Hg). aABP exceeded CBP by &gt;10 mm Hg much more frequently than CBP exceeded aABP. The difference (aABP&gt;CBP) was most pronounced in young adults and those with normal body mass index. The systolic difference progressively diminished, but did not disappear, at older ages and higher body mass indexes. The diastolic difference vanished around age 65 and reversed (CBP&gt;aABP) for body mass index &gt;32.5 kg/m 2 . Whereas 5.3% of participants were hypertensive by CBP, 19.2% were hypertensive by aABP; 15.7% of those with nonelevated CBP had masked hypertension. Conclusions: Contrary to a widely held belief, based primarily on cohort studies of patients with elevated CBP, ABP is not usually lower than CBP, at least not among healthy, employed individuals. Furthermore, a substantial proportion of otherwise healthy individuals with nonelevated CBP have masked hypertension. Demonstrated CBP−aABP gradients, if confirmed in representative samples (eg, NHANES [National Health and Nutrition Examination Survey]), could provide guidance for primary care physicians as to when, for a given CBP, 24-hour ABP would be useful to identify or rule out masked hypertension.
Wheeze In Infancy Decreases Airway Distensibility Assessed At 3 Years Of Age
Authors: A. Kumar, D. Czovek, C. Shackleton, M. Sarna, D. Whiley, A. Alsaleh, T. Sloots, Z. Gingl, Z. Hantos, K. Grimwood, S. Lambert, P. D. Sly
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Characterization of Oncogene Dysregulation in Multiple Myeloma by Combined FISH and DNA Microarray Analyses.
Authors: Antonino Neri, Sonia Fabris, Luca Agnelli, Michela Mattioli, Luca Baldini, Domenica Ronchetti, Fortunato Morabito, Donata Verdelli, Lucia Nobili, Daniela Intini, Vincenzo Callea, Caterina Stelitano, Luigia Lombardi
Journal: Blood (2004)
Indirubin-3'-Monoxime Induces Apoptosis and Autophagy In Acute Lymphoblastic Leukemia Cells and Chronic Myelogenous Leukemia Cells, Exhibits Limited Cytotoxicity In CD34+ Hematopoietic Stem Cells, Lymphocytes and Granulocytes
Authors: Ming-Yang Lee, Yi-Wen Liu, Ming-Ho Chen, Jing-Jing Chuang
Journal: Blood (2010)
Abstract 2103: SOX2 suppresses PTEN expression via miR-19a in esophageal squamous cell carcinoma
Authors: Yasuyuki Gen, Kohichiroh Yasui, Tomoko Kitaichi, Osamu Dohi, Yoshito Ito
Journal: Cancer Research (2015)

Abstract We previously showed that SOX2, a master regulator during embryogenesis, is an amplification target of 3q26.33 in esophageal squamous cell carcinoma (ESCC), and that SOX2 promotes ESCC proliferation in vitro and in vivo via activation of the AKT/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. However, the mechanisms by which SOX2 promotes AKT/mTORC1 signaling remain to be elucidated. We determined that SOX2 decreased PTEN, a negative regulator of AKT signaling, via microRNA (miRNA) in ESCC cells. SOX2 knockdown increased PTEN and decreased phosphorylated AKT (p-AKT), and PTEN knockdown restored p-AKT decreased by SOX2 knockdown in SOX2 amplified ESCC cells (KYSE70, KYSE140 and TE10 cells), indicating that SOX2 elevates p-AKT via PTEN suppression in these cells. DICER knockdown increased PTEN expression without SOX2 expression change in these cells, suggesting that PTEN expression is regulated by miRNA. Therefore we hypothesized that SOX2 may suppress PTEN expression through miRNA regulation. To examine whether SOX2 modulate the expression of miRNAs, we investigated the expression of cancer-related 84 miRNAs using miRNA PCR arrays, and found that SOX2 elevated miR-17∼92 cluster (miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92) in KYSE70 cells. Quantitative RT-PCR confirmed that the expression of mir-17∼92 cluster is elevated by SOX2 in KYSE70, KYSE140, and TE10 cells. Of these miRNA, transfection of miR-19a mimic suppressed PTEN and conversely miR-19a inhibition elevated PTEN in these cells. Collectively, SOX2 may suppress PTEN expression via miR-19a in ESCC cells. Citation Format: Yasuyuki Gen, Kohichiroh Yasui, Tomoko Kitaichi, Osamu Dohi, Yoshito Ito. SOX2 suppresses PTEN expression via miR-19a in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2103. doi:10.1158/1538-7445.AM2015-2103
Abstract 3616: Development of a Sox2 targeting therapy for the treatment of lung squamous cell carcinoma
Authors: Naomasa Ishida, Takuya Fukazawa, Munenori Takaoka, Tomoki Yamatsuji, Ichiro Morita, Minoru Haisa, Nagio Takaoka, Yoshio Naomoto
Journal: Cancer Research (2015)

Abstract Despite the recent development of several effective molecular targeted agents, lung cancer is the most common cause of cancer related deaths worldwide. Recently, molecular targeted therapies for pulmonary adenocarcinoma with mutant EGFR or ALK fusions have reduced non-tumor toxicity and have extended patient survival time compared to conventional chemotherapies. However, the development of molecular targeting drugs for NSCLC has made apparent the fact that histology is an important factor and molecularly targeted therapies have been more effective in pulmonary adenocarcinoma than in lung squamous cell carcinoma. Therefore, specific therapies that target lung squamous cell carcinoma are desperately needed. Sox2 is a master pluripotency controller that was recently identified as a novel major oncogene, recurrently amplified and activated in lung squamous cell carcinoma. Immunohistochemistry shows that Sox2 expression is seen in approximately 55% of human pulmonary adenocarcinoma sections. On the other hand Sox2 expression is detected in more than 90% of lung squamous cell carcinoma sections. Inhibition of Sox2 by siRNA suppresses cell viability and colony formation of Sox2 expressing EBC2 and LK2 lung squamous cell carcinoma cells. Moreover, Sox2 siRNA inhibits lung squamous cell carcinoma growth in vivo in a xenograft mouse model derived from EBC2 cells. Flowcytometric analysis demonstrated that Annexin V positive and PI negative cell populations were not changed 48 hours after Sox2 silencing in EBC2 lung squamous cell carcinoma cells. Microarray analysis demonstrated that the expression of several cell cycle related genes were changed after Sox2 silencing in Sox2 expressing lung squamous cell carcinoma cells. Cell cycle analysis showed that Sox2 silencing significantly increased the G1 population in the cells. These results indicate that Sox2 silencing might produce an antitumor effect via G1 cell cycle arrest. Citation Format: Naomasa Ishida, Takuya Fukazawa, Munenori Takaoka, Tomoki Yamatsuji, Ichiro Morita, Minoru Haisa, Nagio Takaoka, Yoshio Naomoto. Development of a Sox2 targeting therapy for the treatment of lung squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3616. doi:10.1158/1538-7445.AM2015-3616
Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis
Authors: Peter A. Merkel, Gang Xie, Paul A. Monach, Xuemei Ji, Dominic J. Ciavatta, Jinyoung Byun, Benjamin D. Pinder, Ai Zhao, Jinyi Zhang, Yohannes Tadesse, David Qian, Matthew Weirauch, Rajan Nair, Alex Tsoi, Christian Pagnoux, Simon Carette, Sharon Chung, David Cuthbertson, John C. Davis, Paul F. Dellaripa, Lindsy Forbess, Ora Gewurz‐Singer, Gary S. Hoffman, Nader Khalidi, Curry Koening, Carol A. Langford, Alfred D. Mahr, Carol McAlear, Larry Moreland, E. Philip Seo, Ulrich Specks, Robert F. Spiera, Antoine Sreih, E. William St.Clair, John H. Stone, Steven R. Ytterberg, James T. Elder, Jia Qu, Toshiki Ochi, Naoto Hirano, Jeffrey C. Edberg, Ronald J. Falk, Christopher I. Amos, Katherine A. Siminovitch
Journal: Arthritis & Rheumatology (2016)

Objective To identify risk alleles relevant to the causal and biologic mechanisms of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). Methods A genome‐wide association study and subsequent replication study were conducted in a total cohort of 1,986 cases of AAV (patients with granulomatosis with polyangiitis [Wegener's] [GPA] or microscopic polyangiitis [MPA]) and 4,723 healthy controls. Meta‐analysis of these data sets and functional annotation of identified risk loci were performed, and candidate disease variants with unknown functional effects were investigated for their impact on gene expression and/or protein function. Results Among the genome‐wide significant associations identified, the largest effect on risk of AAV came from the single‐nucleotide polymorphism variants rs141530233 and rs1042169 at the HLA–DPB1 locus (odds ratio [OR] 2.99 and OR 2.82, respectively) which, together with a third variant, rs386699872, constitute a triallelic risk haplotype associated with reduced expression of the HLA–DPB1 gene and HLA–DP protein in B cells and monocytes and with increased frequency of complementary proteinase 3 (PR3)–reactive T cells relative to that in carriers of the protective haplotype. Significant associations were also observed at the SERPINA1 and PTPN22 loci, the peak signals arising from functionally relevant missense variants, and at PRTN3 , in which the top‐scoring variant correlated with increased PRTN3 expression in neutrophils. Effects of individual loci on AAV risk differed between patients with GPA and those with MPA or between patients with PR3‐ANCAs and those with myeloperoxidase‐ANCAs, but the collective population attributable fraction for these variants was substantive, at 77%. Conclusion This study reveals the association of susceptibility to GPA and MPA with functional gene variants that explain much of the genetic etiology of AAV, could influence and possibly be predictors of the clinical presentation, and appear to alter immune cell proteins and responses likely to be key factors in the pathogenesis of AAV.
590. Anti-EGFR Aptamer-Conjugated Lipoplexses, a Novel Gene Delivery Strategy for Triple Negative Breast Cancer Therapy
Authors: Min Woo Kim, Hwa Yeon Jeong, Seong Jae Kang, In Ho Jeong, Moon Jung Choi, Young Myoung You, Chan Su Im, Yong Serk Park
Journal: Molecular Therapy (2016)

Basal-like breast cancer, one of the subtypes of breast cancer, have been focused because of their pathologic features like absence of three common markers such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu). The basal subtype is also called triple negative breast cancer (TNBC) and has shown a higher rate of metastasis, poor prognosis, unresponsive to therapy. Especially, their lack of HER2 expression and aggressive progression make it difficult to utilize HER2-targeted therapeutics and diagnostics to the metastatic TNBC. In this study, theranostic cationic liposomes consisting of quantum dots (QDs) and O,O'-dimyristyl-N-lysyl glutamate (DMKE) were prepared. The quantum dot-incorporating cationic liposomes (QCLs) were then complexed with Bcl-2 and PKC- λ/ι small interfering RNA (siRNA) for silencing of genes inhibiting apoptosis, and promoting cell proliferation, and cell migrations. The cationic characteristics of the QCLs provided an effective siRNA transfection in vitro, but it had limitations in in vivo applications. To enhance cancer-directed delivery, epidermal growth factor receptor (EGFR) aptamer-polyethylene glycol conjugates were inserted into the prepared QCLs. The advantages of the two-step strategy of QCL preparation include effective QD formulation, in vivo long circulation, and TNBC specific gene silencing. This study suggests that EGFR aptamer-conjugated QCL can be utilized as a useful theranostic agent for TNBC subtype breast cancers.
A Randomized Comparison of Total-Marrow Irradiation, Busulfan and Cyclophosphamide with Tandem High-Dose Melphalan in Patients with Multiple Myeloma.
Authors: Stefan Knop, Katja Bauer, Holger Hebart, Hannes Wandt, Lorenz Trumper, Peter Liebisch, Georg Maschmeyer, Dietrich Peest, Hans H. Wolf, Nikolaus Kroger, Christian Straka, Michael Pfreundschuh, Paolo Coser, Christoph Meisner, Lothar Kanz, Hermann Einsele
Journal: Blood (2007)
Outcomes of Patients with Newly-Diagnosed Acute Myeloid Leukemia Over the Last 5 Decades At M.D. Anderson Cancer Center
Authors: Alfonso Quintás-Cardama, Hagop Kantarjian, Farhad Ravandi, Guillermo Garcia-Manero, Stefan Faderl, Pierce Sherry, Mark Brandt, Gautam Borthakur, Michael Keating, Emil Freireich, Jorge E Cortes
Journal: Blood (2011)
712. Improved Reduction in GM2 Ganglioside Accumulation in Tay-Sachs Mice Using a New Hexosaminidase Variant
Authors: Subha Karumuthil-Melethil, Patrick Thompson, Jagdeep S. Walia, Brian Mark, Don Mahuran, Steven J. Gray
Journal: Molecular Therapy (2015)

GM2 gangliosidosis is a family of three genetic neurodegenerative disorders caused by the accumulation of GM2 gangliosides (GM2). Two of these are due to the deficiency of one of 2 similar but non-identical subunits that comprise heterodimeric β-hexosaminidase A (HexA) which hydrolyzes GM2. Mutations in the α-subunit (encoded by HEXA) of the enzyme HexA lead to Tay-Sachs disease (TSD), wherein mutations in the β-subunit (encoded by HEXB) lead to Sandhoff disease (SD). In their acute infantile forms, both rapidly progress with fatal neurological deterioration during childhood. The most significant pathological feature of TSD and SD is GM2 accumulation in neurons. Since functional HexA is a heterodimer of the α- and β-subunits, the efficacy of overexpressing only the deficient subunit in a gene therapy approach is limited by the levels of the endogenous subunit. An effective approach to treat either TSD or SD would be to express the α- and β-subunits at equimolar ratios from the same vector, which for AAV has been limited by size restrictions. The present study used a new variant of the Hex α-subunit, containing critical sequences from the β-subunit that can form a stable homodimer (HexM) capable of hydrolyzing GM2. A self-complementary (sc) AAV genome was designed with a synthetic promoter to allow packaging of HEXM. To test the efficacy of HEXM compared to that of the unmodified HEXA, these were packaged into scAAV9 vectors and injected stereotaxically into 4 or 15 month old TSD mice along with an identical titer of scAAV9/GFP vector to track vector spread. The mice were euthanized after 4 weeks and brain sections were subjected to IHC analysis against GFP and GM2. The HexA-like activity was assessed by clearance of GM2 within the injected region, compared to the contralateral brain hemisphere. Qualitatively, a marked reduction of GM2 was apparent in the areas of highest GFP expression. The various Hex vectors showed a clear difference in their ability to degrade GM2. As predicted, human HEXM was more capable of clearing GM2 aggregates than human HEXA at either 4 or 15 months of age. Interestingly, mouse HEXA was more effective than human HEXA, indicating a species-incompatibility, presumably in the formation of a human α- and murine β-subunit heterodimer. This incompatibility further reinforces the utility of HexM to form a functional homodimer independent of the endogenous α- and β-subunit, which should be effective in treating both TSD and SD. In conclusion, modified HEXM can form a functional homodimer capable of clearing GM2 aggregates. It can be packaged in a scAAV9 vector, which is amenable for strategies directed at widespread CNS gene transfer. These technological advances overcome previous barriers and provide pivotal reagents to develop a translatable gene therapy for TSD and SD.
Donor-to-Recipient Weight Ratio Is Independently Associated with CD34+ Yield in Healthy Donors Undergoing Peripheral Blood Stem Cell Collection for Allogeneic Transplantation
Authors: Mark A Fiala, Soo Park, Camille N. Abboud, Amanda F. Cashen, Meagan Jacoby, Iskra Pusic, Rizwan Romee, Mark A. Schroeder, Geoffrey L. Uy, Ravi Vij, Peter Westervelt, Tanya M Wildes, John F. DiPersio, Keith E. Stockerl-Goldstein
Journal: Blood (2014)
245. MicroRNA Expression in Bone Marrow-Derived Human MSCs
Authors: Ian H. Bellayr, Jennifer G. Catalano, Raj K. Puri
Journal: Molecular Therapy (2016)

Multipotent stromal cells (MSCs) are being studied in the field of regenerative medicine for their capacity for multi-differentiation. These cells can be isolated from multiple tissue types. The current literature indicates that MSCs have an immunoregulatory capacity, which can suppress the immune system. MicroRNAs (miRNAs) are short non-coding RNAs that are responsible for regulating gene expression. Through targeting binding to gene transcripts, miRNAs have been observed to impact MSC function such as proliferation, differentiation, migration and apoptosis. Studies have shown that various miRNAs are expressed in MSCs; however, the impact of cellular expansion and donor variability on the miRNA expression is not well understood. Six commercially available MSC lines were expanded from passage 3 to 7 and their miRNA expression was evaluated using microarray technology. Statistical analyses of our data revealed that 71 miRNAs out of 939 examined were expressed by this set of MSC lines at all passages and the expression of 13 miRNAs were significantly different between passage 3 and 7. The expression of six miRNAs with the largest fold changes was further evaluated using RT-qPCR for both the original MSC lines and a second set of seven MSC lines expanded from passage 4 to 8. By RT-qPCR only 2 miRNAs, miR-638 and miR-572 were upregulated at passage 7 compared to passage 3 for the original MSC lines by 1.71 and 1.54 fold, respectively; and upregulated at passage 8 compared to passage 4 for the second set of MSC lines, 1.34 and 1.59 fold, respectively. These 2 miRNAs distinguish aging MSCs expanded in culture. These novel results may be useful in establishing critical quality attributes for limiting clinical applications of MSCs beyond specific cellular expansion protocols.
378. Isocitrate Dehydrogenase 2 Overexpression Ameliorates Ischemia Reperfusion Injury to the Kidney
Authors: Devin Bready, Peter Corridon, Shijun Zhang, David Basile, Robert Bacallao, Simon Atkinson
Journal: Molecular Therapy (2015)

Acute Kidney Injury (AKI) is a significant contributor to morbidity and mortality, affecting 35% of critical care patients and 7% of hospital admissions nationwide. Furthermore, the 60 day mortality rate for AKI patients requiring renal replacement therapy was as high as 53.6%. Understanding the molecular underpinnings responsible for the variation in response to injury is an important step to addressing AKI. Previous work on AKI resistant Brown Norway s rats indicated that several proteins active in metabolism were overexpressed post-injury. Among these was Isocitrate Dehydrogenase 2 (IDH2), a mitochondria-enzyme that has a crucial role in metabolism.. In order to assess the contribution of heightened expression of IDH2 to AKI resistance, the protein was overexpressed in a highly oxygen-dependent cell line derived from mouse proximal tubule (S3 cells). Overexpression was confirmed via western blotting. The membrane potential of the mitochondria was assessed by use of the cationic dye JC-1. Mitochondrial polarization, as measured by the red-shift of JC-1 dye, was increased by 11% (p<0.02, n=16) in cells overexpressing IDH2 versus those that were sham transfected. Initial assessment of cell death performed by propidium iodide staining and Hoechst counterstaining followed by flow cytometry analysis indicated a reduction in the fraction of cells that had undergone cell death. Subsequent imaging studies were performed utilizing both propidium iodide and Hoechst to assess apoptotic versus necrotic cell death as determined by cellular morphology. Once the protective effect of IDH2 overexpression was confirmed in cell culture, the in vivo efficacy was tested using hydrodynamic delivery to kidneys of Sprague Dawley rats. Delivery of naked IDH2 plasmid DNA (600 μg in 500 μl) to the left kidney was achieved by rapid injection into the renal vein while blood flow into, and out of the kidney was occluded. Uptake and overexpression of IDH2 was confirmed by western blot analysis using the right kidney as a control. After one week of recovery, a 40 minute ischemia/reperfusion injury was induced by bilateral renal pedicle cross clamping. In comparison to the sham gene delivery group, IDH2 overexpressing animals exhibited an 82% reduction in peak post-injury serum creatinine levels (p<0.01). TMRM staining coupled with intravital microscopy confirmed increased mitochondrial potential seen in the earlier JC-1 experiments and histology indicated that proximal tubule architecture was preserved. Our work indicates that modulating levels of IDH2 helps decrease susceptibility to and severity of AKI. This finding coupled with the new gene delivery technique of hydrodynamic delivery offers an avenue towards devising rational gene therapies to protect susceptible populations and the possibility that, with other candidate genes, regeneration of the kidney can be induced.
Hepatitis B Virus Reactivation and Alemtuzumab Therapy.
Authors: Emilio Iannitto, Viviana Minardi, Giuseppina Calvaruso, Antonino Mulè, Donatella Ferraro, Emanuele Ammatuna, Antonio Craxì, Vincenzo Abbadessa, Rosellina Di Stefano
Journal: Blood (2004)
A Pilot Study of Tapered Oral Dexamethasone for the Acute Chest Syndrome of Sickle Cell Disease.
Authors: Charles T. Quinn, Marie J. Stuart, Karen Kesler, Kenneth I. Ataga, Winfred C. Wang, Lori Styles, Kim Smith-Whitley, Ted Wun, Suba Krishnan, Frans A. Kuypers, Yamaja Setty, Nigel S. Key, Seungshin Rhee, George R. Buchanan
Journal: Blood (2009)
Phase II Study of Arsenic Trioxide Plus Ascorbic Acid for Relapsed and Refractory Lymphoid Malignancies: A Wisconsin Oncology Network Study.
Authors: Brad S. Kahl, Harish G. Ahuja, Federico A. Sanchez, Gilberto A. Rodrigues, Peter M. Voorhees, Emily A. Stevens, Jamie Smith, Nancy Turman, KyungMann Kim, Howard H. Bailey
Journal: Blood (2004)
GNB1 Activating Mutations Promote Myeloid and Lymphoid Neoplasms Targetable By Combined PI3K/mTOR Inhibition
Authors: Akinori Yoda, Guillaume Adelmant, Jerome Tamburini, Bjoern Chapuy, Nobuaki Shindoh, Yuka Yoda, Oliver Weigert, Nadja Kopp, Shuo-Chieh Wu, Sunhee S. Kim, Huiyun Liu, Trevor Tivey, Amanda L Christie, Kutlu G Elpek, Joseph Card, Kira Gritsman, Jason Gotlib, Michael W. Deininger, Hideki Makishima, Shannon Turley, Nathalie Javidi-Sharifi, Jaroslaw P. Maciejewski, Scott J Rodig, Jeffrey W. Tyner, Jarrod A Marto, David M. Weinstock, Andrew A. Lane
Journal: Blood (2014)