tbuckley/cabot-search huggingface dataset:
Abstract 956: Anticancer effects of silibinin-induced small nucleolar RNA 11B on bladder cancer cells
Authors: Soichiro Yamamura, Yozo Mitsui, Shahana Majid, Hannah Nip, Nathan Bucay, Sharanjot Saini, Guoren Deng, Varahram Shahryary, Rajvir Dahiya, Yuichiro Tanaka
Journal: Cancer Research (2016)

Abstract Silibinin is the major active constituent of silymarin, an extract of milk thistle seeds. Silibinin has been shown to have significant anti-cancer effects in a variety of malignancies. However, the molecular mechanisms of silibinin action in bladder cancer have not been reported. In the present study, we found that silibinin (10 μM) significantly suppressed proliferation and invasion of T24 and UM-UC-3 bladder cancer cells. We analyzed various pathways as possible mechanisms of silibinin action using RNA-Seq technology in bladder cancer cell lines. Analysis of RNA-seq data identified silibinin targets that down-regulate the actin cytoskeleton pathway. Analysis of RNA-seq data also identified the mitogen-activated protein (MAP) kinase signaling pathway as a silibinin-down-regulated pathway. These pathways were also found to crosstalk through Ras and phosphatidylinositide 3-kinase (PI3K). These data show that silibinin anti-cancer effects are through down-regulation of actin cytoskeleton and MAP kinase pathways in bladder cancer. We also found that silibinin induced small nucleolar RNA 11B (SNORD11B) and that SNORD11B suppressed proliferation and invasion of bladder cancer cells. We will discuss the pathway of the anti-cancer effects of SNORD11B. Citation Format: Soichiro Yamamura, Yozo Mitsui, Shahana Majid, Hannah Nip, Nathan Bucay, Sharanjot Saini, Guoren Deng, Varahram Shahryary, Rajvir Dahiya, Yuichiro Tanaka. Anticancer effects of silibinin-induced small nucleolar RNA 11B on bladder cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 956.
A placebo-controlled, randomized phase II study of conatumumab (C) or AMG 479 (A) or placebo (P) plus gemcitabine (G) in patients (pts) with metastatic pancreatic cancer (mPC).
Authors: H. L. Kindler, D. A. Richards, J. Stephenson, L. E. Garbo, C. S. Rocha Lima, H. Safran, J. S. Wiezorek, E. G. Feigal, S. Bray, C. Fuchs
Journal: Journal of Clinical Oncology (2010)

4035 Background: C, a death receptor 5 agonist, and A, an insulin-like growth factor receptor 1 antagonist, are investigational, fully human monoclonal antibodies with preclinical activity in PC models. We conducted a 3-arm, placebo-controlled, randomized phase II study evaluating both agents in mPC pts. Methods: Eligible pts had no prior therapy for mPC; PS 0-1; no poorly controlled diabetes. Primary endpoint: 6-month (mo) overall survival (OS). The study was designed to estimate the efficacy of adding C or A to G; 120 pts provides 80% power to detect a difference between a 6-mo OS of 45% for P and 69% for C or A. Stratification: PS (0 vs. 1). Pts were randomly allocated 1:1:1 to Arm 1: C + G (double-blinded); Arm 2: A + G (open-label due to anticipated thrombocytopenia and hyperglycemia); Arm 3: P + G (double-blinded). Pts received C 10 mg/kg, or A 12 mg/kg, or P intravenously (IV) days (D) 1 and 15 and G 1000 mg/m2 IV over 30 minutes D 1, 8, 15 Q28 D. CT scans: Q 2 cycles. Results: 125 pts (Arms 1/2/3: 41/42/42 pts) at 37 centers enrolled 3/08-4/09; 41/40/40 received ≥ 1 dose of study drug. Median age 61/66/61 years; male 59/60/62%; PS 1 59/55/62%; liver metastases 66/71/79%. Deaths to date 68/48/57%. Efficacy is shown in the table. Grade 3/4 adverse events (% pts, Arms 1/2/3): neutropenia 22/18/13%; thrombocytopenia 15/15/8%; fatigue 12/10/5%; hyperglycemia 2/15/3%. No post-dose anti-C nor anti-A antibodies were detected. Conclusions: The addition of C or A to G is well-tolerated and results in trends toward longer PFS, improved 6-mo OS, and higher rates of stable disease, when compared with G + P. Follow-up is ongoing, and updated efficacy and safety data will be available for presentation. Arm 1 Arm 2 Arm 3 Arm 1 vs. 3 Arm 2 vs. 3 6-mo OS 59.7% 56.6% 50.1% 9.6% 5.7% (95% CI) (42.9, 73.1) (40.8, 69.7) (33.4, 64.7) (−12.5, 31.8) (−16.0, 27.4) Median PFS 3.9 5.1 2.1 HR = 0.65 HR = 0.60 (95% CI), mo (3.4, 5.4) (3.2, 6.0) (1.9, 3.3) (0.39, 1.07); p = 0.095 (0.36, 1.01); p = 0.055 Median OS 7.5 7.3 6.2 HR = 0.90 HR = 0.69 (95% CI), mo (5.8, 10) (5.3, NE) (4.1, 12.9) (0.5, 1.59); p = 0.71 (0.38, 1.25); p = 0.22 Partial response 0/38 (0%) 1/38 (3%) 2/40 (5%) Stable disease 24/38 (63%) 19/38 (50%) 13/40 (33%) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bristol-Myers Squibb, Genentech, ImClone Systems, Merck, Pozen, Roche Amgen Amgen, Lilly
Development of inhalable hyaluronan/mannitol composite dry powders for flucytosine repositioning in local therapy of lung infections
Authors: G. Costabile, I. d'Angelo, R. d'Emmanuele di Villa Bianca, E. Mitidieri, B. Pompili, P. Del Porto, L. Leoni, P. Visca, A. Miro, F. Quaglia, F. Imperi, R. Sorrentino, F. Ungaro
Journal: Journal of Controlled Release (2016)
Abstract 2782: The effect of LINE-1 methylation level on survival in pancreatic cancer
Authors: Kensuke Yamamura, Yoshifumi Baba, Lei Zhou, Xiaobo Zhang, Keisuke Kosumi, Katunobu Taki, Kazuto Harada, Takatsugu Ishimoto, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Tan Xiaodong, Hideo Baba
Journal: Cancer Research (2016)

Abstract Background: Genome-wide DNA hypomethylation plays an important role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1 (LINE-1) is a good indicator of the global DNA methylation level. In previous studies, we demonstrated that LINE-1 hypomethylation was strongly associated with a poor prognosis in some types of cancers including esophageal cancer, gastric cancer, and hepatocellular carcinoma, supporting its potential role as a prognostic marker. However, the relationship between LINE-1 hypomethylation and clinical outcome in pancreatic cancer remains unclear. Methods: LINE-1 methylation level in 126 samples resected pancreatic cancers was measured by pyrosequencing assay, and the prognostic value of LINE-1 methylation level in pancreatic cancer was examined. Results: Pancreatic cancers showed significantly lower LINE-1 methylation levels compared to matched non tumorous parenchyma (P = 0.039; N = 36). Tumoral LINE-1 methylation range was 41.3-92.8 (N = 126; mean: 77.7; median: 78.5; standard deviation: 5.7). However, LINE-1 hypomethylation was not significantly associated with overall survival, cancer specific survival, disease-free survival [log-rank p = 0.30, p = 0.18 and p = 0.50, respectively]. Conclusion: The present result suggested that LINE-1 hypomethylation in pancreatic cancer is not associated with poor prognosis. In this study, our cohort was small, therefore further accumulation of data may be needed in order to confirm the effect of LINE-1 methylation level on survival in pancreatic cancer. Citation Format: Kensuke Yamamura, Yoshifumi Baba, Lei Zhou, Xiaobo Zhang, Keisuke Kosumi, Katunobu Taki, Kazuto Harada, Takatsugu Ishimoto, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Tan Xiaodong, Hideo Baba. The effect of LINE-1 methylation level on survival in pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2782.
The Transfer Of Dabigatran and Rivaroxaban Across a Dually Perfused Isolated Human Placental Cotyledon – Implications For Therapy In Pregnancy
Authors: Priya Bapat, Reuven Kedar, Nir Melamed, Jeremy Matlow, Angelika Lubetsky, Katarina Aleksa, Howard Berger, Gideon Koren
Journal: Blood (2013)
Case 2-1964
Authors: Guillermo C. Sanchez, Robert E. Scully
Journal: New England Journal of Medicine (1964)

Presentation of CaseA seventy-six-year-old man entered the hospital because of pain in the chest.The patient had been well until one year previously, when he began to experience exertional dyspnea and a dull pain in the anterior portion of the chest, which was provoked by exercise and relieved promptly by rest. Two days before admission the chest pain became persistent, accompanied by mild sweating but without nausea. On the day of entry the pain radiated down the right arm for a short time. There was no history of edema, hypertension, diabetes or weight loss.Physical examination revealed a ruddy-faced . . .
Geoffrey James Roberts
Authors: Rebecca Roberts
Journal: BMJ (2016)

Geoffrey James Roberts (“Geoff”) was born in Stockport in 1949, the youngest child of Stella and Roland Roberts. He graduated from Manchester University Medical School in 1972, the first member of his family to go to university, having funded his studies by breeding turkeys to sell for Christmas and working as the medic in the local sausage factory.

Keen on outdoor sports and with the Queen’s Scouts medal under his belt, he spent his summers at university rock climbing and sailing, crewing for one of the consultant surgeons on a trip around the coastline of the British Isles.

After medical school he contemplated a surgical career, working as a junior surgeon at Manchester Royal Infirmary, before embarking on a career in general practice. Geoff felt early on as a GP that he wanted a different sort of challenge and made the transition away from clinical medicine into what would become a passionate crusade to improve systems for the better of patients and their families and advocating on their behalf.

Leaving the world of direct clinical practice, Geoff went to work for the Medical Defence Union. He initially started as assistant secretary in …
T315I-Mutated BCR-ABL Induces a Distinct and Specific Molecular Signature With High Expression Of Zinc Finger (ZNF) Transcription Factors
Authors: Christophe Desterke, Djamel Aggoune, Marie Laure Bonnet, Nais Prade, Jean-Claude Chomel, Eric Delabesse, Ali G Turhan
Journal: Blood (2013)
Abstract 637: Establishment of a realistic patient-derived xenograft (PDX) model for prostate cancer bone metastasis
Authors: Yvonne Konkol, Maija Valta, Jenni Bernoulli, Pekka Taimen, Peter Boström, Pirkko Härkönen, Jussi Halleen, Johanna M. Tuomela
Journal: Cancer Research (2016)

Abstract Bone metastases are frequent and fatal outcome of advanced prostate cancer. Many of the currently used preclinical models lack typical characteristics of the heterogenic human disease. We improved existing methodology by using fresh patient-derived material in a xenograft model of bone metastasis. Clinical prostate tumor specimens were collected from robotic-assisted laparoscopic radical prostatectomy operations in Turku University Hospital (Turku, Finland). Patient-derived tumor tissue of Gleason grade 8-10 tumors (n = 5) were cut into small pieces, digested overnight, and then cell suspension was intratibially inoculated into the bone marrow cavity of nude mice (n = 8-10/patient). X-ray pictures were taken and blood samples were collected once a month. Mice were sacrificed 6 months after tumor cell inoculation, and hind limbs and lungs were collected for histological and immunohistochemical analysis. PSA was measured from serum using commercial kit. X-rays demonstrated osteosclerotic bone lesions. Immunohistochemical analysis showed that 80% of tumors in bone expressed similar characteristics compared with original tumor (androgen receptor AR, prostate specific antigen PSA, proliferation marker Ki67). However, no changes were seen in serum PSA. Lung metastases were detected in 50% of tumor-bearing mice. Interestingly, the most of lung metastases were negative for AR and PSA, which indicates that the cell population that forms metastases may be undifferentiated clone of heterogenic tumor and therefore the most aggressive. Our platform provides new tools for prostate cancer research. Citation Format: Yvonne Konkol, Maija Valta, Jenni Bernoulli, Pekka Taimen, Peter Boström, Pirkko Härkönen, Jussi Halleen, Johanna M. Tuomela. Establishment of a realistic patient-derived xenograft (PDX) model for prostate cancer bone metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 637.
P179 The Effectiveness of Chemical Pleurodesis Agents in Spontaneous Pneumothorax: A Systematic Review: Abstract P179 Table 1
Authors: RJ Hallifax, A Yousuf, JP Corcoran, I Psallidas, NM Rahman
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Spontaneous Pneumothorax (SP) is a common pathology. Recurrence rates (RR) for Primary SP (PSP) are often quoted as approximately 30% (individual studies reporting anywhere between 17 and 49%), with less data available on Secondary SP (SSP) recurrence rates. Recurrence prevention at first episode remains controversial. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second episode. There are numerous candidate agents for chemical pleurodesis. This study aimed to comprehensively review the existing literature regarding chemical pleurodesis as a treatment modality. <h3>Methods</h3> The systematic review methodology was based on the PRISMA approach and principles. Literature searches of multiple databases (PubMed, Embase, Medline, Web of Science, Cochrane Library) used combinations of terms including “spontaneous”, “pneumothor*”, “chemical”, “talc”, “tetracycline”, “minocycline”, “iodopovidine”, and “blood”. Abstracts were reviewed for relevance by two authors, who subsequently assessed and extracted data from the full articles. <h3>Results</h3> Of 522 abstracts reviewed; 427 were excluded (e.g. case reports, letters, reviews, animal models or basic science articles); an additional 4 papers included via back-referencing. 99 full text papers were reviewed; 58 were excluded for the following reasons: foreign language only, not available, or inadequate data/follow-up information. The remaining 41 papers’ data were extracted, showing variation in size, quality and type of studies. Eight randomised trials across differing patient groups (both medical and surgical) report markedly varying recurrence rates (Table 1). Six prospective series (n = 398) found thoracoscopic talc insufflation (RR: 3 to 7%) and tetracycline (9% via chest drain or poudrage) to be effective; with iodopovidone less so (13%). Of 27 retrospective case series (n = 4,990), seven were reasonable quality, finding good efficacy of adding talc or silver nitrate post-bullectomy (RR: 1 to 2%); better than minocycline or acromycin post-bullectomy (3 and 4%) or talc post-electrocoagulation (5%). The remaining 20 were poorer quality with high risk of bias, assessing 7 different agents. <h3>Conclusions</h3> Numerous agents have been used for chemical pleurodesis for spontaneous pneumothorax. Chemical pleurodesis post-surgical treatment or via thoracoscopy appears most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised and comparative trials.
IL-2/B7.1 Fusagene Transduction of AML Blasts by a Self-Inactivating Lentiviral Vector Stimulates T Cell Responses in Vitro: A Strategy To Generate Whole Cell Vaccines for AML.
Authors: Lucas Chan, Nicola Hardwick, Dave Darling, Joanna Galea-Lauri, Joop Gäken, Stephen Devereux, Mike Kemeny, Ghulam Mufti, Farzin Farzaneh
Journal: Blood (2004)
Complex Karyotype in Mantle Cell Lymphoma (MCL) Is Associated with Inferior Progression-Free Survival in Patients (pts) Receiving R-Hypercvad Followed By Autologous Stem Cell Transplant
Authors: Michael Jinpyo Lee, Jeffrey Switchenko, Janeen S Thomas, Jean L. Koff, Loretta Nastoupil, Mary Jo Lechowicz, Amelia A Langston, Christopher Flowers, Jonathon B. Cohen
Journal: Blood (2015)
Authors’ reply: Influenza vaccination coverage in the United Kingdom
Authors: P R Blank, M Schwenkglenks, T D Szucs
Journal: Eurosurveillance (2008)

At a closer look, our coverage results for this age group and those reported by the HPA are quite similar for 2003-4 (70% vs. 71%, respectively) and 2005-6 (78% vs. 75%, respectively) while our coverage results for 2004-5 and 2006-7 are indeed substantially lower. Given confidence interval widths, as shown in Figure 2 of our report, chance alone does not appear to be a likely explanation for this discrepancy.
Abstract 10: Silibinin exhibits anti-cachectic and anti-cancerous property by modulating metabolic properties of pancreatic cancer cells
Authors: Surendra K. Shukla, Aneesha Dasgupta, Kamiya Mehla, Venugopal Gunda, Enza Vernucci, Joshua Soucheck, Gennifer Goode, Ryan King, Anusha Mishra, Ibha Rai, Sangeetha Natrajan, Nina Chaika, Fang Yu, Pankaj K. Singh
Journal: Cancer Research (2016)

Abstract Cancer cachexia is a systemic syndrome characterized by progressive weight loss of the patient due to muscle wasting and fat depletion with or without anorexia. About 80% of pancreatic ductal adenocarcinoma (PDAC) patients exhibits cachectic phenotype and it significantly contributes in mortality and morbidity of the disease. In present study we have evaluated the effect of bioactive molecule silibinin on pancreatic cancer progression and cachectic properties by utilizing in vitro as well as in vivo models of PDAC. We observed that silibinin inhibits growth and induces apoptosis in multiple pancreatic cancer cell lines in a dose-dependent manner. We also observed silibinin-mediated reduction in the expression of key glycolytic genes and inhibition of glucose uptake and lactate secretion. By performing LC-MS/MS based metabolomics, we observed that silibinin treatment leads to global metabolic alterations in pancreatic cancer cells. Pancreatic cancer cells treated with silibinin exhibited reduced expression of c-MYC level, a key metabolic regulator. Furthermore, we observed that silibinin-mediated STAT3 inhibition leads to reduced c-MYC expression. Ectopic expression of constitutively active STAT3 significantly attenuated the effect of silibinin on c-MYC expression and metabolic phenotype of pancreatic cancer cells. Silibinin treatment also inhibited tumor growth and progression of cachexia. Silibinin treatment to tumor-bearing mice also lead to increased food intake, increased grip strength and body coordination. Overall, our results demonstrate that silibinin exhibits anti-cachectic and anti-cancerous properties by inducing metabolic reprogramming in pancreatic cancer cells. Citation Format: Surendra K. Shukla, Aneesha Dasgupta, Kamiya Mehla, Venugopal Gunda, Enza Vernucci, Joshua Soucheck, Gennifer Goode, Ryan King, Anusha Mishra, Ibha Rai, Sangeetha Natrajan, Nina Chaika, Fang Yu, Pankaj K. Singh. Silibinin exhibits anti-cachectic and anti-cancerous property by modulating metabolic properties of pancreatic cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 10.
Epigenetic activation of the drug transporter OCT2 sensitizes renal cell carcinoma to oxaliplatin
Authors: Yanqing Liu, Xiaoli Zheng, Qinqin Yu, Hua Wang, Fuqing Tan, Qianying Zhu, Lingmin Yuan, Huidi Jiang, Lushan Yu, Su Zeng
Journal: Science Translational Medicine (2016)

Renal cell carcinoma (RCC) is known for its multidrug resistance. Using data obtained from the cancer transcriptome database Oncomine and the proteome database The Human Protein Atlas, we identified the repression of organic cation transporter OCT2 as a potential factor contributing to oxaliplatin resistance in RCC. By analyzing OCT2 expression in collected patient tissues and commercial tissue microarray specimens, we demonstrated OCT2 repression in RCC at both transcription and protein levels. Epigenetic analysis revealed that the repressed OCT2 promoter in RCC is characterized by hypermethylated CpG islands and the absence of H3K4 methylation. Further mechanistic studies showed that DNA hypermethylation blocked MYC activation of OCT2 by disrupting its interaction with the E-Box motif, which prevented MYC from recruiting MLL1 to catalyze H3K4me3 at the OCT2 promoter and resulted in repressed OCT2 transcription. Targeting this mechanism, we designed a sequential combination therapy and demonstrated that epigenetic activation of OCT2 by decitabine sensitizes RCC cells to oxaliplatin both in vitro and in xenografts. Our study highlights the potential of translating "omics" data into the development of targeted therapies.
Monocyte Induction of E-Selectin–Mediated Endothelial Activation Releases VE-Cadherin Junctions to Promote Tumor Cell Extravasation in the Metastasis Cascade
Authors: Irina Häuselmann, Marko Roblek, Darya Protsyuk, Volker Huck, Lucia Knopfova, Sandra Grässle, Alexander T. Bauer, Stefan W. Schneider, Lubor Borsig
Journal: Cancer Research (2016)

Tumor cells interact with blood constituents and these interactions promote metastasis. Selectins are vascular receptors facilitating interactions of tumor cells with platelets, leukocytes, and endothelium, but the role of endothelial E-selectin remains unclear. Here we show that E-selectin is a major receptor for monocyte recruitment to tumor cell-activated endothelium. Experimental and spontaneous lung metastasis using murine tumor cells, without E-selectin ligands, were attenuated in E-selectin-deficient mice. Tumor cell-derived CCL2 promoted endothelial activation, resulting in enhanced endothelial E-selectin expression. The recruitment of inflammatory monocytes to metastasizing tumor cells was dependent on the local endothelial activation and the presence of E-selectin. Monocytes promoted transendothelial migration of tumor cells through the induction of E-selectin-dependent endothelial retractions and a subsequent modulation of tight junctions through dephosphorylation of VE-cadherin. Thus, endothelial E-selectin shapes the tumor microenvironment through the recruitment, adhesion, and activation of monocytes that facilitate tumor cell extravasation and thereby metastasis. These findings provide evidence that endothelial E-selectin is a novel factor contributing to endothelial retraction required for efficient lung metastasis. Cancer Res; 76(18); 5302-12. ©2016 AACR.
Variable bleeding phenotype in an Amish pedigree with von Willebrand disease
Authors: Sweta Gupta, Meadow Heiman, Natalie Duncan, Jesse Hinckley, Jorge Di Paola, Amy D Shapiro
Journal: American Journal of Hematology (2016)

Through a cross-sectional study design, the bleeding phenotype in the Amish in Indiana (IN) and Wisconsin (WI) was described using two different bleeding scores. von Willebrand factor (VWF) testing was performed and bleeding questionnaires from Centers for Disease Control and Prevention (CDC) and European MCMDM-1 (Tosetto bleeding score (BS)) were administered to the IN and WI cohort respectively. Seven hundred and seventy nine subjects were recruited, 17% were diagnosed with VWD based on Ristocetin cofactor, VWF:RCo < 30 IU/dl. Majority of the affected (AF), 67%, were tested and had a common mutation c.4120 C > T. The WI AF were much younger at a mean age 15 years vs 26 years in IN AF cohort. The AF subjects had a median VWF:RCo of 13IU/dl with a statistically significant higher median BS 1 versus 0 in the WI AF vs WI Unaffected (UA), 2 vs 1 in the IN AF vs IN UA, P < 0.01. Adults had a higher median BS compared to children in the WI and IN cohort, 2 vs 1 and 3 vs 1 respectively (P < 0.05) but there was no statistically significant difference in the BS between males and females in either cohort. The common symptoms reported were epistaxis and gingival oozing. BS ≥ 3 and BS ≥ 4 were observed in 46% of AF IN and 16.6% of AF WI, respectively. There was significant variability in the bleeding phenotype, with an overall low BS in the affected Amish with VWD, despite a unifying mutation. Am. J. Hematol. 91:E431-E435, 2016. © 2016 Wiley Periodicals, Inc.