tbuckley/cabot-search huggingface dataset:
Retrospective Analysis of 23 Cases with Human Herpesvirus-6 Associated Encephalitis after Allogeneic Hematopoietic Cell Transplantation.
Authors: Takahiro Fukuda, Katsumichi Fujimaki, Shuichi Taniguchi, Masatsugu Tanaka, Hisashi Gondo, Hideki Akiyama, Takero Shindo, Takahiro Karasuno, Satoshi Yoshihara, Jun Ishikawa, Takashi Ashida, Mahito Misawa, Masao Ogata, Ilseung Choi, Atsuo Maruta, Tomoko Kawano, Tomohiro Myojo, Kazuhiro Masuoka, Tsuyoshi Muta, Koji Kato, Hideho Henzan, Takehiko Mori, Masayuki Ikeda, Tetsushi Yoshikawa, Mine Harada
Journal: Blood (2004)
Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study
Authors: Thalia Velho Barreto de Araújo, Laura Cunha Rodrigues, Ricardo Arraes de Alencar Ximenes, Demócrito de Barros Miranda-Filho, Ulisses Ramos Montarroyos, Ana Paula Lopes de Melo, Sandra Valongueiro, Maria de Fátima Pessoa Militão de Albuquerque, Wayner Vieira Souza, Cynthia Braga, Sinval Pinto Brandão Filho, Marli Tenório Cordeiro, Enrique Vazquez, Danielle Di Cavalcanti Souza Cruz, Cláudio Maierovitch Pessanha Henriques, Luciana Caroline Albuquerque Bezerra, Priscila Mayrelle da Silva Castanha, Rafael Dhalia, Ernesto Torres Azevedo Marques-Júnior, Celina Maria Turchi Martelli
Journal: The Lancet Infectious Diseases (2016)
A2-05: Prognostic value of positron emission tomography in resected stage I non-small cell lung cancer
Authors: Boone W. Goodgame, Farrokh Dehdashti, Zhiyun Yang, Jabi Shriki, Feng Gao, Alexander Patterson, Jennifer Zoole, Bryan Meyers, Barry Siegel, Ramaswamy Govindan
Journal: Journal of Thoracic Oncology (2007)
2016 US lymphoid malignancy statistics by World Health Organization subtypes
Authors: Lauren R. Teras, Carol E. DeSantis, James R. Cerhan, Lindsay M. Morton, Ahmedin Jemal, Christopher R. Flowers
Journal: CA A Cancer Journal for Clinicians (2016)

Collectively, lymphoid neoplasms are the fourth most common cancer and the sixth leading cause of cancer death in the United States. The authors provide contemporary lymphoid neoplasm statistics by subtype based on the 2008 World Health Organization classifications, including the most current US incidence and survival data. Presented for the first time are estimates of the total numbers of US lymphoid neoplasm cases by subtype as well as a detailed evaluation of incidence and survival statistics. In 2016, 136,960 new lymphoid neoplasms are expected. Overall lymphoma incidence rates have declined in recent years, but trends vary by subtype. Precursor lymphoid neoplasm incidence rates increased from 2001 to 2012, particularly for B-cell neoplasms. Among the mature lymphoid neoplasms, the fastest increase was for plasma cell neoplasms. Rates also increased for mantle cell lymphoma (males), marginal zone lymphoma, hairy cell leukemia, and mycosis fungoides. Like incidence, survival for both mature T-cell lymphomas and mature B-cell lymphomas varied by subtype and by race. Patients with peripheral T-cell lymphomas had among the worst 5-year relative survival (36%-56%, depending on race/sex), while those with mycosis fungoides had among the best survival (79%-92%). For B-cell lymphomas, 5-year survival ranged from 83% to 91% for patients with marginal zone lymphoma and from 78% to 92% for those with hairy cell leukemia; but the rates were as low as 47% to 63% for patients with Burkitt lymphoma and 44% to 48% for those with plasma cell neoplasms. In general, black men had the lowest survival across lymphoid malignancy subtypes. These contemporary incidence and survival statistics are useful for developing management strategies for these cancers and can offer clues regarding their etiology. CA Cancer J Clin 2016;66:443-459. © 2016 American Cancer Society.
Comparison of physicochemical characteristics and stability of three novel formulations of paclitaxel: Abraxane, Nanoxel, and Genexol PM
Authors: Niles Ron, Jon Cordia, Andrew Yang, Sherry Ci, Phithi Nguyen, Melissa Hughs, Neil Desai
Journal: Cancer Research (2008)

5622  Background: Abraxane (Abraxis BioScience, Inc., Los Angeles, CA, approved in USA and Canada), Nanoxel (Dabur Pharma, H.P., India, approved in India), and Genexol PM (Samyang Pharmaceuticals, Seoul, Korea, approved in Korea) are 3 commercially approved, novel formulations of paclitaxel. Abraxane consists of albumin-bound injectable nanoparticles of paclitaxel, while Genexol and Nanoxel (utilizing cosolvents) are polymeric-micelle formulations. Abraxane and Genexol are lyophilized products approved for 25°C ± 2°C storage, while Nanoxel is a liquid formulation approved for 2-8°C storage. This study investigated the physicochemical characteristics and short-term stability of the 3 products under recommended clinical use conditions and under accelerated conditions.  Methods: The drugs were reconstituted and prepared per the instructions provided in the respective package inserts. Abraxane and Genexol were reconstituted using the recommended saline diluent, while Nanoxel was mixed and diluted in 10% dextrose. Each drug was reconstituted to 0.7 mg/mL and 5 mg/mL. Physical stability was monitored both visually and microscopically; particle size was measured and monitored over time at room temperature (RT, measured to be 23°C) and 40°C using photon correlation spectroscopy (PCS) (Zetasizer 3000, Malvern, UK). Chemical purity was measured by reduced reversed-phase HPLC (Shimadzu Scientific Instruments, MD).  Results: Following reconstitution, Abraxane was determined to be stable both physically and chemically at RT and 40°C over 24 hrs, with no evidence of nanoparticle size growth at either 0.7 mg/mL or 5 mg/mL. While reconstituted Genexol was stable at RT over 24 hrs, micelle instability resulting in precipitation of paclitaxel in the form of large needle-like crystals for both 0.7 mg/mL and 5 mg/mL formulations was seen between 2 to 4 hrs at 40°C. These observations were confirmed using orthogonal techniques, visual assessment from photomicrographs, and PCS particle size measurement. For Nanoxel at 0.7 mg/mL, a minor, but consistent, increase in particle size was observed at RT over 24 hrs. However, significant aggregation, particle-size growth, and crystallization were seen within 4 hrs at 40°C. HPLC data comparing pre- and post-filtration confirmed that the crystal formation for both Nanoxel and Genexol resulted from paclitaxel precipitation and aggregation. In addition, analytical results showed that Nanoxel had slightly lower paclitaxel purity as compared to either Abraxane or Genexol.  Conclusions: Nanoparticle albumin-bound paclitaxel, Abraxane, showed excellent physicochemical stability as compared to the micellar formulations, Nanoxel and Genexol. Particle size growth and crystal formation were readily apparent in Nanoxel and Genexol, especially in the short term under accelerated conditions.
Validation of a prognostic model integrating Breast Cancer Index (BCI) with tumor size and grade for prediction of distant recurrence in hormone receptor-positive (HR+) breast cancer with 1-3 positive nodes.
Authors: Yi Zhang, Piiha-Lotta Jerevall, Brock Schroeder, Hannah Nolan, Amy Ly, Catherine A Schnabel*, Dennis Sgroi*
Journal: Journal of Clinical Oncology (2016)

541 Background: BCI has been shown to significantly predict risk of overall (10y), early (0-5y), and late ( ≥ 5y) distant recurrence (DR) in HR+, node negative (LN-) breast cancer. A distinct BCI model integrating tumor size and grade (BCIN+) was developed for prediction of DR in HR+ women with 1-3 positive nodes (N1) (Sestak et al., SABCS 2015, P2-08-12). The objective of this blinded study was to independently validate this new model in a large clinical series of HR+ patients with N1 disease. Methods: HR+ N1 patients diagnosed between 1993 to 2007 with ≥ 5y follow-up and available tumor blocks were included (N = 402). BCIN+ risk scores and categories (low vs high, using a pre-defined cutpoint) were determined blinded to clinical outcome. Kaplan-Meier estimates of overall (0-15y) and late ( ≥ 5y) DR, hazard ratios and 95% CIs were estimated. Multivariate analysis adjusting for standard prognostic factors (age, tumor type, surgery type, PR and HER2 status) was performed using Cox proportional hazards model. Results: Mean age was 53y. 99% were ER+, 91% PR+, and 13% HER2+. The majority of tumors were T1 (62%) or T2 (35%), and 17%, 56%, and 26% were grade 1, 2, and 3, respectively. Most patients received 5-year adjuvant endocrine therapy (99%) and chemotherapy (81%). BCIN+ was significantly associated with risk of overall (HR 13.1; 95% CI 3.6-43.9; p < 0.0001) and late DR (HR 5.0; 95% CI 1.5-16.5; p = 0.009) in multivariate analysis. BCIN+ classified 20% and 80% of patients as low and high risk with 15y rates of DR (95% CI) of 1.3% (0.0-3.7%) vs 29.0% (23.3-34.4%),respectively. For patients disease-free at year 5, rates of late DR (5-15y) were 1.3% (0.0-3.7%) vs 16.2% (10.6-21.3%), respectively. Conclusions: In this independent validation, BCIN+ identified a significant proportion of N1 patients that were associated with a considerably low 15y risk of DR after adjuvant chemo- and endocrine therapy. BCIN+ may provide additional prognostic information to facilitate selection of N+ patients for extended endocrine treatment wherein patients identified as BCIN+ low may be considered adequately treated with adjuvant therapy alone.
Hypoxia‐driven Hif2a coordinates mouse liver regeneration by coupling parenchymal growth to vascular expansion
Authors: Philipp Kron, Michael Linecker, Perparim Limani, Andrea Schlegel, Patryk Kambakamba, Jean‐Marie Lehn, Claude Nicolau, Rolf Graf, Bostjan Humar, Pierre‐Alain Clavien
Journal: Hepatology (2016)

Interaction between sinusoidal endothelial cells and hepatocytes is a prerequisite for liver function. Upon tissue loss, both liver cell populations need to be regenerated. Repopulation occurs in a coordinated pattern, first through the regeneration of parenchyme (hepatocytes), which then produces vascular endothelial growth factor (VEGF) to enable the subsequent angiogenic phase. The signals that instruct hepatocytes to induce timely VEGF remain unidentified. Given that liver is highly vascularized, we reasoned that fluctuations in oxygenation after tissue loss may contribute to the coordination between hepatocyte and sinusoidal endothelial cell proliferation. To prevent drops in oxygen after hepatectomy, mice were pretreated with inositol trispyrophosphate (ITPP), an allosteric effector of hemoglobin causing increased O2 release from heme under hypoxic conditions. ITPP treatment delayed liver weight gain after hepatectomy. Comparison with controls revealed the presence of a hypoxic period around the peak of hepatocyte mitosis. Inhibition of hypoxia led to deficient hepatocyte mitosis, suppressed the regenerative Vegf wave, and abrogated the subsequent reconstruction of the sinusoidal network. These ITPP effects were ongoing with the reduction in hepatocellular hypoxia inducible factor 2a (Hif2a). In contrast, Hif1a was unaffected by ITPP. Hif2a knockdown phenocopied all effects of ITPP, including the mitotic deficiencies, Vegf suppression, and angiogenic failure.Oxygen is a key regulator of liver regeneration. Hypoxia-inherent to the expansion of parenchyme-activates Hif2a to couple hepatocyte mitosis with the angiogenic phase. Hif2a acts as a safeguard to initiate sinusoidal reconstruction only upon successful hepatocyte mitosis, thereby enforcing a timely order onto cell type-specific regeneration patterns. These findings portray the hypoxia-driven Hif2a-Vegf axis as a prime node in coordinating sinusoidal endothelial cell-hepatocyte crosstalk during liver regeneration. (Hepatology 2016;64:2198-2209).
Short Progression Free Survival Predicts for Poor Overall Survival In Older Patients with Multiple Myeloma Treated Upfront with Novel Agent-Based Therapy
Authors: Efstathios Kastritis, Maria Roussou, Maria Gavriatopoulou, Magdalini Migkou, Maria Gkotzamanidou, Marina Iakovaki, Eleni Efstathiou, Evangelos Terpos, Meletios A. Dimopoulos
Journal: Blood (2010)
Abstract 2441: Engineering and mapping difficult proteins using comprehensive mutagenesis
Authors: Cheryl Paes, Jason Goodman, Melanie Wescott, Yana Thaker, Anu Thomas, Joseph Couto, Joseph Rucker, Benjamin J. Doranz
Journal: Cancer Research (2015)

Abstract Alanine (Ala) scanning is a widely used mutagenesis approach for systematic evaluation of protein function, which for large targets can be laborious and time-consuming. We have developed a platform technology, Shotgun Mutagenesis, for rapid and comprehensive alanine scanning mutagenesis for protein mapping and engineering applications. Using this technology, every residue in a target protein is individually mutated, expressed in human cells, and assayed for desired functions. Critical mutations are rapidly identified using high-throughput 384-well assays including flow cytometry. Here we used Shotgun Mutagenesis to create comprehensive mutation libraries for different classes of targets including the GPCR CXCR4, bitter taste receptor TAS2R16 and the therapeutic antibody Palivizumab (Synagis). For the cancer target CXCR4, we identified critical residues for antibody binding (epitope mapping) and ligand-dependent activation (functional domain mapping). We also discovered TAS2R16 residues that can be altered for increased expression (protein optimization) and Palivizumab residues which tolerate germline substitutions permitting engineering of a maximally humanized antibody variant (antibody humanization). This platform allows comprehensive protein mapping and engineering of challenging targets previously considered prohibitively time-consuming or expensive, enabling discovery pathways for many untapped therapeutic targets. Citation Format: Cheryl Paes, Jason Goodman, Melanie Wescott, Yana Thaker, Anu Thomas, Joseph Couto, Joseph Rucker, Benjamin J. Doranz. Engineering and mapping difficult proteins using comprehensive mutagenesis. [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 2441. doi:10.1158/1538-7445.AM2015-2441
P2-232: Phase II study of weekly paclitaxel plus carboplatin combination chemotherapy in patients with advanced non-small cell lung cancer
Authors: Sung Hwa Bae, Sun Ah Lee, Kyung Chan Kim, Hun-Mo Ryoo, Dae-Sung Hyun, Sang-Chae Lee, Min Kyoung Kim, Kyung Hee Lee, Myung Soo Hyun
Journal: Journal of Thoracic Oncology (2007)
Defining the Landscape of Resistance Mutations in the Context of Modern Treatment Protocols for Acute Promyelocytic Leukemia (APL).
Authors: Jelena V Jovanovic, Fabien Guidez, Farhad Ravandi, Estelle Duprez, Mukunder Patel, Ken Mills, Steven Kornblau, Maadh Aldouri, Martin Auger, Alan K Burnett, Ellen Solomon, David Grimwade
Journal: Blood (2008)
Refining the use of an electronic medical record (EMR) to define and implement psychosocial distress screening and treatment.
Authors: Joel Marcus
Journal: Journal of Clinical Oncology (2016)

144 Background: All cancer patients experience some level of distress associated with cancer and its treatment at all stages of the disease. Psychological and social problems created or exacerbated by cancer cause additional suffering, weaken adherence to prescribed treatments and threaten patients' return to health." Health care providers often tend to under estimate psychological distress. Screening and early identification of distress promote improved management of symptoms, which facilitates medical care. Psychosocial care must be integrated into the routine treatment of cancer patients, per the Institute of Medicine's 2008 report "Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs." Methods: Developing operational standards for Distress Screening our cancer center both NCCN guideline, Commission on Cancer Standards. These operational standards integrated our Electronic Medical Record to create "best practice advisories" to alert the physician to the possible need for further evaluation of distress and the possible need for referral to Social Work staff or the on-site Psychologist. Results: Referrals to our on-site staff Psychologist at our main campus were monitored. 306 unique patients were referred to our staff psychologist for evaluation and treatment during the 2014 calendar year. In the first three quarters of the 2015 a total of 445 were made. Surgical oncology clinics (Head &amp; Neck, Breast &amp; Upper Gastro-Intestinal) made the majority of referrals. Conclusions: In accordance with published guidelines and accrediting standards our cancer center utilized our electronic medical record to increase our ability to identify psychosocial distress in our population.
P2-072: Angiogenesis gene expression profiling as prognostic marker in non-small cell lung cancer
Authors: Vivian E. van den Boogaart, Victor L. Thijssen, Dirk De Ruysscher, Emiel F. Wouters, Robert Jan van Suylen, Arjan W. Griffioen, Anne-Marie C. Dingemans
Journal: Journal of Thoracic Oncology (2007)
Mechanistic target of rapamycin complex 1 is an essential mediator of metabolic and mitogenic effects of fibroblast growth factor 19 in hepatoma cells
Authors: Zhi Yi Wan, Johann Shane Tian, Hayden Weng Siong Tan, Ai Lee Chow, Arthur Yi Loong Sim, Kenneth Hon Kim Ban, Yun Chau Long
Journal: Hepatology (2016)

Fibroblast growth factor 19 (FGF19) is an important postprandial enterokine which regulates liver metabolism and hepatocyte proliferation. However, the precise mechanism by which FGF19 regulates these cellular effects is poorly understood. Given that mechanistic target of rapamycin complex 1 (mTORC1) regulates numerous postprandial adaptations, we investigated the potential role of mTORC1 in FGF19 action. We found that FGF19 activated mTORC1 in HepG2 and HuH7 human hepatoma cells, differentiated 3T3-L1 adipocytes and mouse liver. FGF19 activates the mTORC1-p70S6K and extracellular signal-regulated kinase (Erk)-p90RSK pathways independently to regulate S6 in an additive manner in hepatoma cells, but it uses mTORC1 as the primary pathway to regulate S6 in 3T3-L1 adipocytes. Thus, mTORC1 is a novel mediator of FGF19 signaling, which can act in parallel with Erk or function as the primary pathway to regulate S6. The FGF19-induced mTORC1 pathway requires amino acids for efficient signaling; thus, involvement of mTORC1 confers amino acid sensitivity to FGF19 signaling. Although Akt and Erk are known to activate mTORC1, we found that FGF19 signals to mTORC1 through a third recently identified mTORC1 regulator, Ras-like (Ral) protein. Pharmacological or genetic inhibition of RalA or RalB abolished FGF19-induced mTORC1 activation, demonstrating that Ral proteins are required for FGF19 to activate mTORC1. FGF19 induced metabolic gene expression, fatty acid oxidation, cell growth, and proliferation in HepG2 cells; and these effects were abolished by mTORC1 inhibition, demonstrating an essential role of mTORC1 in FGF19 action.mTORC1 is a novel and essential mediator of FGF19 action on metabolic and mitogenic programs; thus, the involvement of mTORC1 in FGF19 signaling is an important factor to consider when targeting the pathway for cancer or diabetes therapy. (Hepatology 2016;64:1289-1301).
Patient threatens legal action over lack of compensation for hepatitis C contaminated blood
Authors: Clare Dyer
Journal: BMJ (2016)

A man infected with hepatitis C through NHS treatment with contaminated blood is threatening legal action against the government over a new discretionary compensation scheme, which he claims is unlawful.

Lawyers for Alex Smith, 61, have written to Jeremy Hunt, health secretary for England, threatening to go to the High Court unless he makes changes to the scheme to put those with hepatitis C on an equal footing with those infected with HIV through blood.

The dispute has its roots in what was described by the medical peer Robert Winston as “the worst treatment disaster in the history of …
Gene Tree Discordance Can Generate Patterns of Diminishing Convergence over Time
Authors: Fábio K. Mendes, Yoonsoo Hahn, Matthew W. Hahn
Journal: Molecular Biology and Evolution (2016)

Phenotypic convergence is an exciting outcome of adaptive evolution, occurring when different species find similar solutions to the same problem.Unraveling the molecular basis of convergence provides a way to link genotype to adaptive phenotypes, but can also shed light on the extent to which molecular evolution is repeatable and predictable.Many recent genome-wide studies have uncovered a striking pattern of diminishing convergence over time, ascribing this pattern to the presence of intramolecular epistatic interactions.Here, we consider gene tree discordance as an alternative cause of changes in convergence levels over time in a primate dataset.We demonstrate that gene tree discordance can produce patterns of diminishing convergence by itself, and that controlling for discordance as a cause of apparent convergence makes the pattern disappear.We also show that synonymous substitutions, where neither selection nor epistasis should be prevalent, have the same diminishing pattern of molecular convergence in primates.Finally, we demonstrate that even in situations where biological discordance is not possible, discordance due to errors in species tree inference can drive similar patterns.Though intramolecular epistasis could in principle create a pattern of declining convergence over time, our results suggest a possible alternative explanation for this widespread pattern.These results contribute to a growing appreciation not just of the presence of gene tree discordance, but of the unpredictable effects this discordance can have on analyses of molecular evolution.
Clusterin immuno-expression and its clinical significance in patients with non-small cell lung cancer.
Authors: H. Li, X. Zhu, S. Liu, J. Xiang, H. Chen
Journal: Journal of Clinical Oncology (2010)

e17520 Background: Clusterin is an enigmatic glycoprotein with a nearly ubiquitous tissue distribution. It plays important roles in various pathophysiological processes, including tissue remodeling, reproduction, lipid transport, complement regulation and apoptosis. Clusterin appears to have two main isoforms which are the result of alternative splicing. The secreted form and nuclear form of clusterin were reported to have different roles in human malignancies. The purpose of this study was to examine Clusterin immuno-expression and its clinical significance in a subgroup of Chinese patients with non-small cell lung cancer. Methods: Tissue samples from the primary tumors were obtained from 121 patients with completely resected non-small cell lung cancer. The expression of clusterin protein was analyzed by immunohistochemical staining with an antibody recognizing all isoforms of clusterin. Staining patterns were observed and graded based on intensity and density and correlated with clinical and pathological data. Results: Cytoplasmic and nuclear immnunostaining of clusterin were both observed in this subgroup of patients. Tumors from 70 patients (57.9%) exhibited only positive cytoplasmic staining. Tumors with positive nuclear staining only were observed in 27 patients (22.3%). 16 cases (13.2%) were with both nuclear and plasmic staining. Significant association was observed between positive cytoplasmic expression and histologic type as indicated adenocarcinoma was more likely with only positive cytoplasmic staining. The clusterin immuno-staining was not associated with patients DFS or OS by univariate or multivariate analysis. For patients with chemotherapy, those with positive cytoplasmic staining only had worse survival than other patients. Conclusions: Both plasmic and nuclear immunostaining were observed in tumors of patients with NSCLC. Adenocarcinoma was more likely with positive cytoplasmic staining only. The immuno-expression of clusterin was not associated with the prognosis of this subgroup of patients and patients with only positive cytoplasmic immmunostaining of clusterin seemed to be more sensitive to chemotherapy. No significant financial relationships to disclose.