tbuckley/cabot-search huggingface dataset:
Intrahepatic cholangiocarcinoma: Ambitious operations and outcomes.
Authors: Mustafa Raoof, Sinziana Dumitra, Philip Hg Ituarte, Laleh Melstrom, Susanne Warner, Yuman Fong, Gagandeep Singh
Journal: Journal of Clinical Oncology (2016)

345 Background: Data from specialized institutions suggests that resection for large ( &gt; 7cm) and mutifocal intrahepatic cholangiocarcinoma (ICC) is safe and feasible. We aim to study this hypothesis using a population-based dataset. Methods: This is a study of a contemporary cohort from California Cancer Registry database (2004-2011) that was merged with Office of Statewide Health Planning and Development inpatient database. All patients with ICC that underwent resection or ablation were included. Tumors were classified into two groups; intrahepatic, small ( &lt; 7cm) &amp; solitary (ISS) vs. extrahepatic extension, large or multifocal (ELM). Mortality was recorded at 90 days. Overall survival (OS) analysis was performed using the Kaplan-Meier and Cox-proportional hazard model. Results: Of the total 275 patients that met the inclusion criteria, 55% were female, 52% were white and median age was 65 years (IQR 55-72). Majority of patients had &gt; 3 segment resection 59% (Ablation 10%, 1-3 segments 30%). Portal lymphadenectomy was performed in 45% of patients. Vascular Invasion was found in 22% of patients, 14% were bilobar and 20% were node positive. Median follow up was 23 months (IQR 13-40). Number of ISS tumors (139, 50.5%) and ELM tumors (136, 49.5%) was similar. The two groups were comparable in regards to age, sex, race, comorbidities, extent of surgery, portal lymphadenectomy, node positivity. ELM tumors were more likely to have vessel invasion (27% vs. 17%, p = 0.048) and be bilobar (26% vs. 2%, p &lt; 0.001). There was no significant difference in overall complication rate (ISS 34%, ELM 27%, p = 0.19) and mortality rate (both groups &lt; 1%, p = 0.32). A multivariate Cox-proportional hazard model demonstrated that age &gt; 60 years, &gt; 1 comorbidity, high grade tumors, ELM tumors (HR 1.63: 95%CI 1.11-2.40; p = 0.013) and LN positivity (HR 2.30: 95%CI 1.49-3.54; p &lt; 0.001) are independently associated with worse OS. Conclusions: Surgical resection of tumors &gt; 7cm, multifocal lesions involving contiguous extrahepatic organs is safe with acceptable morbidity and mortality. Age &gt; 60 years, grade, comorbidity, ELM tumors and LN positivity are independent predictors of worse OS.
476TiP Phase II study of BI1482694 in patients (pts) with T790M-positive non-small cell lung cancer (NSCLC) after treatment with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)
Authors: P.A. Jånne, J. Son, I. Voccia, M. Uttenreuther-Fischer, K. Park
Journal: Annals of Oncology (2015)
Towards More Comprehensive Projections of Urban Heat-Related Mortality: Estimates for New York City under Multiple Population, Adaptation, and Climate Scenarios
Authors: Elisaveta P. Petkova, Jan K. Vink, Radley M. Horton, Antonio Gasparrini, Daniel A. Bader, Joe D. Francis, Patrick L. Kinney
Journal: Environmental Health Perspectives (2016)

High temperatures have substantial impacts on mortality and, with growing concerns about climate change, numerous studies have developed projections of future heat-related deaths around the world. Projections of temperature-related mortality are often limited by insufficient information to formulate hypotheses about population sensitivity to high temperatures and future demographics.The present study derived projections of temperature-related mortality in New York City by taking into account future patterns of adaptation or demographic change, both of which can have profound influences on future health burdens.We adopted a novel approach to modeling heat adaptation by incorporating an analysis of the observed population response to heat in New York City over the course of eight decades. This approach projected heat-related mortality until the end of the 21st century based on observed trends in adaptation over a substantial portion of the 20th century. In addition, we incorporated a range of new scenarios for population change until the end of the 21st century. We then estimated future heat-related deaths in New York City by combining the changing temperature-mortality relationship and population scenarios with downscaled temperature projections from the 33 global climate models (GCMs) and two Representative Concentration Pathways (RCPs).The median number of projected annual heat-related deaths across the 33 GCMs varied greatly by RCP and adaptation and population change scenario, ranging from 167 to 3,331 in the 2080s compared with 638 heat-related deaths annually between 2000 and 2006.These findings provide a more complete picture of the range of potential future heat-related mortality risks across the 21st century in New York City, and they highlight the importance of both demographic change and adaptation responses in modifying future risks. Citation: Petkova EP, Vink JK, Horton RM, Gasparrini A, Bader DA, Francis JD, Kinney PL. 2017. Towards more comprehensive projections of urban heat-related mortality: estimates for New York City under multiple population, adaptation, and climate scenarios. Environ Health Perspect 125:47-55; http://dx.doi.org/10.1289/EHP166.
The Role of Proliferation in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer: A Gene Expression–Based Meta-Analysis
Authors: Daniel G. Stover, Jonathan L. Coloff, William T. Barry, Joan S. Brugge, Eric P. Winer, Laura M. Selfors
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To provide further insight into the role of proliferation and other cellular processes in chemosensitivity and resistance, we evaluated the association of a diverse set of gene expression signatures with response to neoadjuvant chemotherapy (NAC) in breast cancer. Experimental Design: Expression data from primary breast cancer biopsies for 1,419 patients in 17 studies prior to NAC were identified and aggregated using common normalization procedures. Clinicopathologic characteristics, including response to NAC, were collected. Scores for 125 previously published breast cancer–related gene expression signatures were calculated for each tumor. Results: Within each receptor-based subgroup or PAM50 subtype, breast tumors with high proliferation signature scores were significantly more likely to achieve pathologic complete response to NAC. To distinguish “proliferation-associated” from “proliferation-independent” signatures, we used correlation and linear modeling approaches. Most signatures associated with response to NAC were proliferation associated: 90.5% (38/42) in ER+/HER2− and 63.3% (38/60) in triple-negative breast cancer (TNBC). Proliferation-independent signatures predictive of response to NAC in ER+/HER2− breast cancer were related to immune activity, while those in TNBC comprised a diverse set of signatures, including immune, DNA damage, signaling pathways (PI3K, AKT, Ras, and EGFR), and “stemness” phenotypes. Conclusions: Proliferation differences account for the vast majority of predictive capacity of gene expression signatures in neoadjuvant chemosensitivity for ER+/HER2− breast cancers and, to a lesser extent, TNBCs. Immune activation signatures are proliferation-independent predictors of pathologic complete response in ER+/HER2− breast cancers. In TNBCs, significant proliferation-independent signatures include gene sets that represent a diverse set of cellular processes. Clin Cancer Res; 22(24); 6039–50. ©2016 AACR.
Molecular Pathways: The Balance between Cancer and the Immune System Challenges the Therapeutic Specificity of Targeting Nuclear Factor-κB Signaling for Cancer Treatment
Authors: Kristen P. Zeligs, Monica K. Neuman, Christina M. Annunziata
Journal: Clinical Cancer Research (2016)

The NF-κB signaling pathway is a complex network linking extracellular stimuli to cell survival and proliferation. Cytoplasmic signaling to activate NF-κB can occur as part of the DNA damage response or in response to a large variety of activators, including viruses, inflammation, and cell death. NF-κB transcription factors play a fundamental role in tumorigenesis and are implicated in the origination and propagation of both hematologic and solid tumor types, including melanoma, breast, prostate, ovarian, pancreatic, colon, lung, and thyroid cancers. On the other hand, NF-κB signaling is key to immune function and is likely necessary for antitumor immunity. This presents a dilemma when designing therapeutic approaches to target NF-κB. There is growing interest in identifying novel modulators to inhibit NF-κB activity as impeding different steps of the NF-κB pathway has potential to slow tumor growth, progression, and resistance to chemotherapy. Despite significant advances in our understanding of this pathway, our ability to effectively clinically block key targets for cancer therapy remains limited due to on-target effects in normal tissues. Tumor specificity is critical to developing therapeutic strategies targeting this antiapoptotic signaling pathway to maintain antitumor immune surveillance when applying such therapy to patients. Clin Cancer Res; 22(17); 4302-8. ©2016 AACR.
Invasive procedures carried out on children without anaesthesia
Authors: David Spurgeon
Journal: BMJ (2001)

Many invasive bone marrow procedures are still carried out in conscious children despite the availability of safe and effective modern anaesthetic and deep sedation techniques, a survey has found. A greater proportion of North American centres used less effective pain reducing methods than did comparable centres in Europe.

The study, reported in the journal Archives of Disease in Childhood (2001;85:12-5), consisted of a postal survey of 118 European and North American paediatric oncology centres. Questionnaires were sent to all units in the Pediatric Oncology Group and the United Kingdom Children's Cancer Study …
Fatty acid oxidation is required for the respiration and proliferation of malignant glioma cells
Authors: Hua Lin, Shaan Patel, Valerie S. Affleck, Ian Wilson, Douglass M. Turnbull, Abhijit R. Joshi, Ross Maxwell, Elizabeth A. Stoll
Journal: Neuro-Oncology (2016)

Abstract Background. Glioma is the most common form of primary malignant brain tumor in adults, with approximately 4 cases per 100 000 people each year. Gliomas, like many tumors, are thought to primarily metabolize glucose for energy production; however, the reliance upon glycolysis has recently been called into question. In this study, we aimed to identify the metabolic fuel requirements of human glioma cells. Methods. We used database searches and tissue culture resources to evaluate genotype and protein expression, tracked oxygen consumption rates to study metabolic responses to various substrates, performed histochemical techniques and fluorescence-activated cell sorting-based mitotic profiling to study cellular proliferation rates, and employed an animal model of malignant glioma to evaluate a new therapeutic intervention. Results. We observed the presence of enzymes required for fatty acid oxidation within human glioma tissues. In addition, we demonstrated that this metabolic pathway is a major contributor to aerobic respiration in primary-cultured cells isolated from human glioma and grown under serum-free conditions. Moreover, inhibiting fatty acid oxidation reduces proliferative activity in these primary-cultured cells and prolongs survival in a syngeneic mouse model of malignant glioma. Conclusions. Fatty acid oxidation enzymes are present and active within glioma tissues. Targeting this metabolic pathway reduces energy production and cellular proliferation in glioma cells. The drug etomoxir may provide therapeutic benefit to patients with malignant glioma. In addition, the expression of fatty acid oxidation enzymes may provide prognostic indicators for clinical practice.
Targeting mTOR Signaling Leads To Complete and Durable Responses In Children With Multi-Lineage Autoimmune Cytopenias, Including ALPS, SLE, Evans and CVID
Authors: David T. Teachey, TIffaney Vincent, Kim Smith-Whitley, Michele P Lambert, Alix E. Seif, James T. Casper, Stephan A Grupp
Journal: Blood (2013)
Diversion of the mentally ill into the criminal justice system: the police intervention perspective
Authors: J C Bonovitz, J S Bonovitz
Journal: American Journal of Psychiatry (1981)

The authors used longitudinal data from a suburban police department to assess whether increasing numbers of mentally ill individuals are coming to police attention in a state that has restrictive civil commitment laws. To test the hypothesis that police would arrest disruptive but nondangerous individuals to expedite their removal from the community, the authors studied the outcomes of all incidents involving a mentally ill individual during a 5-month period. Mental-illness-related incidents coming to police attention increased 227.6% from 1975 to 1979. Although a 13% arrest rate was reported for nondangerous incidents, police officers invoked the penal code only as a last resort.
Psychiatric syndromes in Huntington's disease
Authors: E D Caine, I Shoulson
Journal: American Journal of Psychiatry (1983)

Thirty patients with Huntington's disease, a genetically transmitted neuropsychiatric disorder that can be diagnosed reliably, were evaluated systematically for psychopathology, followed for extended periods, and treated with psychopharmacological medications when necessary. DSM-III criteria were used for establishing syndromic diagnoses. Twenty-four individuals demonstrated substantial behavioral abnormalities, including affective and schizophrenic syndromes, changes of personality, and disorders that could not be classified adequately. Pharmacotherapy was modestly beneficial in some cases. Consideration of the array of behavioral disturbances encountered in this pathogenetically unified disorder suggests that a dimensional approach to symptom classification might prove more useful heuristically than present typological methods.
Case 19-1972
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Edward P. Richardson, Umberto De Girolami
Journal: New England Journal of Medicine (1972)

PRESENTATION OF CASEA 58-year-old man was admitted to the hospital because of a progressive neurologic disorder.Twenty-one years previously he was found to have chronic lymphocytic leukemia. He felt well and received no treatment other than intermittent radiation therapy to the spleen until 16 months before admission, when there was the onset of progressive weakness and insomnia. Two months later he entered the hospital, where fever and hepatosplenomegaly were found. The white-cell count was 16,000, with 80 per cent mature lymphocytes. X-ray films of the chest showed scarring in both upper lobes and hilar calcifications; multiple cultures were negative. . . .
Repeat Prostate-Specific Antigen Tests Before Prostate Biopsy Decisions
Authors: Tobias Nordström, Jan Adolfsson, Henrik Grönberg, Martin Eklund
Journal: JNCI Journal of the National Cancer Institute (2016)

Despite limited scientific support, a repeat prostate-specific antigen (PSA) test before prostate biopsy decisions is common. We analyzed biopsy outcomes in 1686 men from the STHLM3 study with PSA 3-10 ng/mL and two PSA tests taken within eight weeks and before prostate biopsy using percentages and multinomial logistic regression. We found that omitting prostate biopsy for men with PSA values decreasing to PSAs of 3 ng/mL or less would save 16.8% of biopsy procedures, while missing 5.4% of the cancers with Gleason scores (GSs) of 7 or higher. The proportion of cancers with GSs of 6 or lower was independent of the first PSA value, as well as of PSA change. Also, the risk of tumors with GSs of 7 or higher decreased with both decreasing and increasing PSA levels: It was 18.6% (95% confidence interval [CI] = 16.3% to 20.9%) for men with PSA changes of less than 20%, 12.1% (95% CI = 8.0% to 16.2%) for men with PSA levels increasing at least 20%, and 6.6% (95% CI = 3.8% to 9.3%) for men with PSA levels decreasing at least 20%.
Autoimmune sclerosing cholangitis: An atypical association with kawasaki disease
Authors: Richard A. Rosencrantz, Tiangui Huang, Pierre‐Yves Sonke, Deepali Tewari, Praveen N. Chander
Journal: Hepatology (2016)

Rosencrantz, Richard A.; Huang, Tiangui; Sonke, Pierre‐Yves; Tewari, Deepali; Chander, Praveen N. Author Information
Results from the International, Randomized Phase 3 Study of Ibrutinib Versus Chlorambucil in Patients 65 Years and Older with Treatment-Naïve CLL/SLL (RESONATE-2TM)
Authors: Alessandra Tedeschi, Paul M. Barr, Tadeusz Robak, Carolyn Owen, Paolo Ghia, Osnat Bairey, Peter Hillmen, Nancy L Bartlett, Jianyong Li, David Simpson, Sebastian Grosicki, Stephen Devereux, Helen McCarthy, Steven Coutre, Hang Quach, Gianluca Gaidano, Zvenyslava Maslyak, Don A. Stevens, Ann Janssens, Fritz Offner, Jiří Mayer, Michael O'Dwyer, Andrzej Hellmann, Anna Schuh, Tanya Siddiqi, Aaron Polliack, Constantine S. Tam, Michael Keating, Deepali Suri, Cathy Zhou, Fong Clow, Lori Styles, Danelle F. James, Thomas J. Kipps, Jan A. Burger
Journal: Blood (2015)
Journal: Nature Medicine
Authors: PJ Openshaw
Journal: BMJ (1999)

Nature America, annual subscription £110 ISSN 10788956 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Whether we like it or not, the impact factor is set to be a dominant force in biomedical publishing. Impact is calculated by the frequency with which articles are cited, and review journals published in the United States therefore do well. The highest impact factor for a primary research journal is currently held by Nature Genetics (38.8 citations per article per year), followed by Cell (37.3). In a subject where success breeds success, what chance does a new journal have? Nature Medicine , launched in January 1995, confounds those who might believe that “None” would be an appropriate answer. It now lies third in the ranking of primary research journals, with an impact factor of 28.1. This stunning achievement in part depends on the good name of … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Myeloma Canada Research Network (MCRN)-001 Trial Utilizing Bortezomib (btz)-Based Induction, Enhanced Conditioning with IV Busulfan + Melphalan (BuMel) and Lenalidomide (len) Maintenance in Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplant (ASCT): A National Canadian Study Evaluating Achievement of Minimal Residual Disease (MRD) Negativity and Involved Serum HevyliteTMÂ chain (HLC) Normalization
Authors: Donna Reece, Giovanni Piza Rodriguez, Mariela Pantoja, Darrell White, Christopher P. Venner, Julie Stakiw, Michael Sebag, Terrance Comeau, Kevin Song, Jean Roy, Leonard Minuk, Jason Tay, Vishal Kukreti, Suzanne Trudel, Prica Anca, Rodger Tiedemann, Christine Chen, Harminder Paul
Journal: Blood (2015)
Can routine genetic testing help to end TB transmission?
Authors: Martin Dedicoat, Graham S Cooke
Journal: Thorax (2016)

TB incidence may be finally falling in England; 6520 cases were notified in 2014 giving an estimated annual incidence of 12/100 000.1 There has been a year-on-year decrease in notified cases since 2011, but TB incidence in England still remains unacceptably high and in excess of most European Union countries.2 A strategy to reduce and eventually eliminate TB as a public health problem was released by Public Health England (PHE) and National Health Service England in 2015.3 It identifies 10 areas where improvements in current practice can improve TB control, which include ensuring comprehensive contact tracing, tackling TB in underserved populations, systematic implementation of new entrant latent TB screening, strengthening surveillance and monitoring and providing universal access to high-quality diagnostics.

The introduction of routine genetic testing of cultured TB isolates in 2010 by PHE has the potential to improve our understanding of each of these challenges. In Thorax , Hamblion et al use data from 2010 to 2012 to provide some insight into TB transmission in London, the unofficial TB capital of Europe and home to approximately 40% of TB cases in England.4

The methodology using 24 loci mycobacterial interspersed repetitive units–variable number of tandem repeats (MIRU–VNTR) typing has been well validated.5 TB cases were classed as clustered if they matched to another case on at least 23 typed loci. Clustered cases were compared …
A Case of Wiskott-Aldrich Syndrome With Dual Mutations in Exon 10 of the WASP Gene: An Additional De Novo One-Base Insertion, Which Restores Frame Shift Due to an Inherent One-Base Deletion, Detected in the Major Population of the Patient's Peripheral Blood Lymphocytes
Authors: Tadashi Ariga, Masafumi Yamada, Yukio Sakiyama, Osamu Tatsuzawa
Journal: Blood (1998)
The study of teaching needs an inclusive functional definition
Authors: Laurel Fogarty
Journal: Behavioral and Brain Sciences (2015)

Abstract Frameworks that facilitate interdisciplinary communication on the topic of teaching are certainly needed. However, these frameworks require a solid and widely accepted definition of teaching on which to build. As Kline states, the functional definition forms a good basis for productive comparative work. I briefly discuss the most contentious aspects of the functional definition, and suggest that these issues must be resolved before more detailed frameworks become useful.
PKCδ-targeted intervention relieves chronic pain in a murine sickle cell disease model
Authors: Ying He, Diana J. Wilkie, Jonathan Nazari, Rui Wang, Robert O. Messing, Joseph DeSimone, Robert E. Molokie, Zaijie Jim Wang
Journal: Journal of Clinical Investigation (2016)

Pain is a life-long symptom in sickle cell disease (SCD) and a predictor of disease progression and mortality, but little is known about its molecular mechanisms. Here, we characterized pain in a targeted knockin mouse model of SCD (TOW mouse) that exclusively expresses human alleles encoding normal α- and sickle β-globin. TOW mice exhibited ongoing spontaneous pain behavior and increased sensitivity to evoked pain compared with littermate control mice expressing normal human hemoglobins. PKCδ activation was elevated in the superficial laminae of the spinal cord dorsal horn in TOW mice, specifically in GABAergic inhibitory neurons. Functional inhibition and neuron-specific silencing of PKCδ attenuated spontaneous pain, mechanical allodynia, and heat hyperalgesia in TOW mice. Furthermore, we took a hematopoietic stem cell transplantation approach to generating a SCD model in PKCδ-deficient mice. Neither spontaneous pain nor evoked pain was detected in the mice lacking PKCδ despite full establishment of SCD phenotypes. These findings support a critical role of spinal PKCδ in the development of chronic pain in SCD, which may become a potential target for pharmacological interventions.