tbuckley/cabot-search huggingface dataset:
The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons
Authors: Ingo Braasch, Andrew R Gehrke, Jeramiah J Smith, Kazuhiko Kawasaki, Tereza Manousaki, Jeremy Pasquier, Angel Amores, Thomas Desvignes, Peter Batzel, Julian Catchen, Aaron M Berlin, Michael S Campbell, Daniel Barrell, Kyle J Martin, John F Mulley, Vydianathan Ravi, Alison P Lee, Tetsuya Nakamura, Domitille Chalopin, Shaohua Fan, Dustin Wcisel, Cristian Cañestro, Jason Sydes, Felix E G Beaudry, Yi Sun, Jana Hertel, Michael J Beam, Mario Fasold, Mikio Ishiyama, Jeremy Johnson, Steffi Kehr, Marcia Lara, John H Letaw, Gary W Litman, Ronda T Litman, Masato Mikami, Tatsuya Ota, Nil Ratan Saha, Louise Williams, Peter F Stadler, Han Wang, John S Taylor, Quenton Fontenot, Allyse Ferrara, Stephen M J Searle, Bronwen Aken, Mark Yandell, Igor Schneider, Jeffrey A Yoder, Jean-Nicolas Volff, Axel Meyer, Chris T Amemiya, Byrappa Venkatesh, Peter W H Holland, Yann Guiguen, Julien Bobe, Neil H Shubin, Federica Di Palma, Jessica Alföldi, Kerstin Lindblad-Toh, John H Postlethwait
Journal: Nature Genetics (2016)

Ingo Braasch, John Postlethwait and colleagues report the genome of the spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before genome duplication. Their data provide insights into the evolution of genes involved in immunity, mineralization and development and facilitate the comparison of cis-regulatory elements between teleosts and humans. To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.
Abstract B35: BMP regulation of cancer stem cell quiescence is responsible for chemotherapeutic resistance in glioblastoma
Authors: Megan YiJun Wu, Angela Celebre, Jeffrey Chan, Jennifer Guan, Karan Dhand, James Loukides, Jason Karamchandani, Sunit Das
Journal: Cancer Research (2015)

Abstract Introduction: Cancer stem cells (CSCs) represent a distinct cellular population that has been implicated in tumor recurrence following chemotherapy. Accumulating evidence indicates that BMP signaling plays an important role in the regulation of CSCs, and may be involved in the resistance of CSCs to cytotoxic drugs. The role of BMP pathway regulation of the CSC phenotype responsible for treatment resistance in glioblastoma (GBM) has not been explored. Methods: Paraffin-embedded (FFPE) samples from GBM patients were used to evaluate the expression of markers for BMP signaling (pSMAD1/5/8), proliferation (PCNA), and stemness (SOX2) by immunostaining. We tested the self-renewal capacity of primary patient-derived glioma stem cell (GSC) lines using a sphere formation assay. Expression of stemness markers SOX2 and Bmi-1 in BMP4 treated and untreated GSCs, was analyzed by Western blotting. We also performed xenograft transplantation, whereby GSCs were injected intracranially into immunedeficient mice. When tumor formation was confirmed post-injection, mice were administrated EdU and sacrificed at successive time points thereafter. The frequency of all EdU positive cells as well as ID-1positive/ EdU positive cells was quantified from the primary tumor sections throughout the labeling and chase. To study chemoresistance in glioblastoma, GSC lines were treated with graded concentrations of temozolomide (TMZ). Results: We found that pSMAD1/5/8 positive cells in primary patient tumors were largely PCNA-negative. BMP4 treatment inhibited GSC proliferation and self-renewal (sphere-formation), but did not abolish expression of markers of stemness, such as Sox2 and Bmi-1, or tumorigenicity. In our in vivo model, we found ID-1 positive cells retain EdU following a long-term chase. Taken together, these results demonstrate that BMP4-enriched cells possess the characteristics of a quiescent stem cell population. BMP4 treatment protects GSCs against TMZ-induced growth inhibition. Furthermore, pSMAD1/5/8-expressing cells do not possess the DNA damage marker gamma-H2AX following TMZ treatment, suggesting that activation of the BMP pathway protects GSCs against TMZ-induced DNA damage. Conclusion: This study establishes that the BMP signaling pathway is involved in the maintenance of GSC quiescence and may play a role in glioblastoma chemoresistance. Citation Format: Megan YiJun Wu, Angela Celebre, Jeffrey Chan, Jennifer Guan, Karan Dhand, James Loukides, Jason Karamchandani, Sunit Das. BMP regulation of cancer stem cell quiescence is responsible for chemotherapeutic resistance in glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr B35.
Betahistine for Meniere’s disease
Authors: Jonny Harcourt, Stefano Cosentino
Journal: BMJ (2016)

Betahistine is ineffective, patients urgently need better alternatives

The publication of a very well constructed randomised controlled trial1 of betahistine (Serc) for Meniere’s disease underlines the lack of evidence for the efficacy of this drug at both low and high doses. What does this mean for current and future users?

Meniere’s disease is one of the most puzzling inner ear syndromes. It is typically described with a collection of symptoms, which might not occur all at once in the same person. These include tinnitus, vertigo, sensorineural hearing loss, and aural fullness. Currently, we don’t have a precise idea of aetiology, despite many efforts to indentify underlying causes. Common sensory or pathophysiological elements have been observed—such as endolymphatic hydrops (a distension of the membranous labyrinth2)—and some aetiological theories have been proposed, none of which has been able to inform a one-for-all treatment.

The general approach to treatment is influenced by the severity of the symptoms, by the professional and personal views of the treating specialist, and by …
Sentinel lymphadenectomy for the staging of clinical axillary node-negative breast cancer before neoadjuvant chemotherapy
Authors: M. Jean Pierre, J. Extra, J. Jacquemier, M. Buttarelli, E. Lambaudie, M. Bannier, I. Brenot Rossi, G. Houvenaeghel
Journal: Journal of Clinical Oncology (2009)

e11575 Background: Several authors reported sentinel lymph node biopsy after neoadjuvant chemotherapy. Nevertheless, the ideal time of sentinel lymph node biopsy is still a matter of debate. Methods: We evaluated the feasibility and the accuracy of sentinel lymph node biopsy before neoadjuvant chemotherapy using a combined procedure (blue dye and radio-labelled detection) in a homogeneous cohort study with clinically axillary node-negative breast cancer. Study candidates were patients referred to the Institut Paoli-Calmettes Cancer Center (Marseille, France) for the treatment of invasive breast cancer. Patients were included in the study if they had tumor more than 3 cm in diameter without palpable axillary lymph node for which a neoadjuvant chemotherapy was indicated in order to enhance the likelihood of breast conservation. An axillary lymph node dissection was performed after completion of neoadjuvant chemotherapy. Results: From September 2005 to September 2007, thirty-one women with T2 or T3 invasive breast cancer without palpable axillary lymph node underwent sentinel lymph node biopsy before neoadjuvant chemotherapy and an axillary lymph node dissection after neoadjuvant chemotherapy. Among the 20 women who had metastatic sentinel lymph node biopsy (65%), 4 (20%) had additional metastatic node on axillary lymph node dissection. By contrast, all the 11 women who had no metastatic sentinel lymph node biopsy had no involved nodes in the axillary lymph node dissection. The sentinel lymph node biopsy identification rate before neoadjuvant chemotherapy was 100% with any false negative. Conclusions: Sentinel lymph node biopsy before neoadjuvant chemotherapy is a feasible and an accurate diagnostic tool to predict the pre-therapeutic axilla status. These findings suggest that axillary lymph node dissection may be avoided in patients with a negative sentinel lymph node biopsy performed before neoadjuvant chemotherapy. No significant financial relationships to disclose.
Modeling the Effect of Shared Care to Optimize Acne Referrals From Primary Care Clinicians to Dermatologists
Authors: Kristina J. Liu, Rebecca I. Hartman, Cara Joyce, Arash Mostaghimi
Journal: JAMA Dermatology (2016)

Access to dermatologists remains a nationwide challenge. Optimizing referrals to a dermatologist may reduce patient wait times.To model the effect of algorithm-based acne treatment by primary care clinicians on referral patterns and costs.Overall, 253 referrals from primary care clinicians to dermatologists for acne from January 2014 through March 2015 were reviewed at Brigham and Women's Hospital. No-show rate, diagnostic concordance between primary care clinicians and dermatologists, treatment at the time of referral, and treatment by a dermatologist were ascertained, and we modeled 2 treatment algorithms-initiation of topical treatments by primary care clinicians (algorithm A) and initiation of topical treatments and oral antibiotics by primary care clinicians (algorithm B)-to identify the most effective referral patterns and costs.The primary outcome was the elimination of unnecessary appointments with a dermatologist. Secondary outcomes included reduction in delay to treatment, health care cost savings, and decrease in no-show rate.Overall, 150 of 253 referred patients were seen and treated by a dermatologist; 127 patients (50.2%) were not on prescription acne treatment at the time of dermatology referral. Model A reduced initial referrals in 72 of 150 cases (48.0%), eliminated referrals in 60 of 150 cases (40%), and reduced average delay-to-treatment by 28.6 days. This resulted in cost savings of $20.28 per patient, reduction of wait time by 5 days per patient, and decreased the no-show rate by 13%. Model B reduced initial referrals in 130 of 150 cases (86.7%), eliminated referrals in 108 of 150 cases (72%), and reduced average delay-to-treatment by 27.9 days. This resulted in cost savings of $35.68 per patient, shortened wait-time by 9 days per patient, and decreased the no-show rate by 24%.Algorithm-based treatment of acne by primary care clinicians may eliminate unnecessary appointments, reduce wait time for treatment, lower costs, and reduce patient no-shows.
Distinct Features Identified in Adult Atopic Dermatitis Subjects Based on Age of Onset
Authors: Peck Y. Ong, Denise C. Babineau, Alice Lail, Keli Artis, Gloria L. David, Lynda C. Schneider, Mark Boguniewicz, Anna De Benedetto, Jon M. Hanifin, Eric L. Simpson, Amy S. Paller, Emma Guttman-Yassky, Kathleen C. Barnes, Donald Y. Leung, Lisa A. Beck
Journal: Journal of Allergy and Clinical Immunology (2016)
Invasive Breast Cancer Version 1.2016, NCCN Clinical Practice Guidelines in Oncology
Authors: William J. Gradishar, Benjamin O. Anderson, Ron Balassanian, Sarah L. Blair, Harold J. Burstein, Amy Cyr, Anthony D. Elias, William B. Farrar, Andres Forero, Sharon Hermes Giordano, Matthew Goetz, Lori J. Goldstein, Clifford A. Hudis, Steven J. Isakoff, P. Kelly Marcom, Ingrid A. Mayer, Beryl McCormick, Meena Moran, Sameer A. Patel, Lori J. Pierce, Elizabeth C. Reed, Kilian E. Salerno, Lee S. Schwartzberg, Karen Lisa Smith, Mary Lou Smith, Hatem Soliman, George Somlo, Melinda Telli, John H. Ward, Dorothy A. Shead, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2016)

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This article outlines the NCCN Guidelines specific to breast cancer that is locoregional (restricted to one region of the body), and discusses the management of clinical stage I, II, and IIIA (T3N1M0) tumors. For NCCN Guidelines on systemic adjuvant therapy after locoregional management of clinical stage I, II and IIIA (T3N1M0) and for management for other clinical stages of breast cancer, see the complete version of these guidelines at NCCN.org.
Abstract 12478: Fibroblast Growth Factor 23 in Acute Myocardial Infarction Complicated by Cardiogenic Shock - A Biomarker Substudy of the IABP-SHOCK II-trial
Authors: Georg Fuernau, Janine Poess, Daniel Denks, Steffen Desch, Gunner H Heine, Ingo Eitel, Sarah Seiler, Suzanne de Waha, Andreas Link, Gerhard C Schuler, Volker Adams, Michael Bohm, Holger Thiele
Journal: Circulation (2013)
Thromboxane Governs the Differentiation of Adipose-Derived Stromal Cells Toward Endothelial Cells In Vitro and In Vivo
Authors: Yujun Shen, Shengkai Zuo, Yuanyang Wang, Hongfei Shi, Shuai Yan, Di Chen, Bing Xiao, Jian Zhang, Yanjun Gong, Maohua Shi, Juan Tang, Deping Kong, Luheng Lu, Yu Yu, Bin Zhou, Sheng-Zhong Duan, Claudio Schneider, Colin D. Funk, Ying Yu
Journal: Circulation Research (2016)

Autologous adipose-derived stromal cells (ASCs) offer great promise as angiogenic cell therapy for ischemic diseases. Because of their limited self-renewal capacity and pluripotentiality, the therapeutic efficacy of ASCs is still relatively low. Thromboxane has been shown to play an important role in the maintenance of vascular homeostasis. However, little is known about the effects of thromboxane on ASC-mediated angiogenesis.To explore the role of the thromboxane-prostanoid receptor (TP) in mediating the angiogenic capacity of ASCs in vivo.ASCs were prepared from mouse epididymal fat pads and induced to differentiate into endothelial cells (ECs) by vascular endothelial growth factor. Cyclooxygenase-2 expression, thromboxane production, and TP expression were upregulated in ASCs on vascular endothelial growth factor treatment. Genetic deletion or pharmacological inhibition of TP in mouse or human ASCs accelerated EC differentiation and increased tube formation in vitro, enhanced angiogenesis in in vivo Matrigel plugs and ischemic mouse hindlimbs. TP deficiency resulted in a significant cellular accumulation of β-catenin by suppression of calpain-mediated degradation in ASCs. Knockdown of β-catenin completely abrogated the enhanced EC differentiation of TP-deficient ASCs, whereas inhibition of calpain reversed the suppressed angiogenic capacity of TP re-expressed ASCs. Moreover, TP was coupled with Gαq to induce calpain-mediated suppression of β-catenin signaling through calcium influx in ASCs.Thromboxane restrained EC differentiation of ASCs through TP-mediated repression of the calpain-dependent β-catenin signaling pathway. These results indicate that TP inhibition could be a promising strategy for therapy utilizing ASCs in the treatment of ischemic diseases.
Activity of 8F4, a T-cell receptor-like anti-PR1/HLA-A2 antibody, against primary human AML in vivo
Authors: A Sergeeva, H He, K Ruisaard, L St John, G Alatrash, K Clise-Dwyer, D Li, R Patenia, R Hong, P Sukhumalchandra, M J You, M Gagea, Q Ma, J J Molldrem
Journal: Leukemia (2016)
Is dangerousness an issue for physicians in emergency commitment?
Authors: M A Peszke
Journal: American Journal of Psychiatry (1975)

The laws of many of the states require a physician to determine that a mentally ill individual presents a danger to others before the disturbed person can be civilly committed for involuntary treatment. The author contends that the prediction of dangerousness is not and should not be within the competence of medicine, but that physicians are competent to judge whether or not the severity of mental illness impairs a patient's competence to make an informed decision regarding treatment. The basic issue in emergency commitment is the patient's welfare, not his potential dangerousness. Dr. Alan A. Stone comments on Dr. Peszke's presentation.
Prostate-specific Antigen Decline After 4 Weeks of Treatment with Abiraterone Acetate and Overall Survival in Patients with Metastatic Castration-resistant Prostate Cancer
Authors: Pasquale Rescigno, David Lorente, Diletta Bianchini, Roberta Ferraldeschi, Michael P. Kolinsky, Spyridon Sideris, Zafeiris Zafeiriou, Semini Sumanasuriya, Alan D. Smith, Niven Mehra, Anuradha Jayaram, Raquel Perez-Lopez, Joaquin Mateo, Chris Parker, David P. Dearnaley, Nina Tunariu, Alison Reid, Gerhardt Attard, Johann S. de Bono
Journal: European Urology (2016)

The availability of multiple new treatments for metastatic castration-resistant prostate cancer (mCRPC) mandates earlier treatment switches in the absence of a response. A decline in prostate-specific antigen (PSA) is widely used to monitor treatment response, but is not validated as an intermediate endpoint for overall survival (OS).To evaluate the association between early PSA decline and OS following abiraterone acetate (AA) treatment.We identified mCRPC patients treated with AA before or after docetaxel at the Royal Marsden NHS Foundation Trust between 2006 and 2014. Early PSA decline was defined as a 30% decrease in PSA at 4 wk relative to baseline, and early PSA rise as a 25% increase.Association with OS was analyzed using multivariate Cox regression and log-rank analyses. Spearman's rho correlation coefficient (r) was calculated to evaluate the association between PSA changes at 4 wk and 12 wk.There were 274 patients eligible for this analysis. A 30% PSA decline at 4 wk was associated with longer OS (25.8 vs 15.1 mo; hazard ratio [HR] 0.47, p<0.001), and a 25% PSA rise at 4 wk with shorter OS (15.1 vs 23.8 mo; HR 1.7, p=0.001) in both univariate and multivariable models. The percentage PSA decline at 4 wk was significantly correlated with the percentage PSA change at 12 wk (r=0.82; p<0.001). Patients achieving a 30% PSA decline at 4 wk were 11.7 times more likely to achieve a 50% PSA decrease at 12 wk (sensitivity 90.9%, specificity 79.4%). Limitations include the retrospective design of this analysis.Patients not achieving 30% PSA decline after 4 wk of AA have a lower likelihood of achieving PSA response at 12 wk and significantly inferior OS. Prospective multicentre validation studies are needed to confirm these findings.Prostate-specific antigen (PSA) is commonly used to evaluate response to treatment in metastatic castration-resistant prostate cancer. Expert recommendations discourage reliance on PSA changes earlier than 12 wk after treatment initiation. Our data suggest that early PSA changes are associated with survival in patients receiving abiraterone acetate.
Treatment of acute hepatitis C with interferon alpha 2b prevents chronicity.
Authors: Jean Delwaide, N. Bourgeois, Christiane Gerard, F. Mokkadem, E. Wain, B. Bastens, J. Fevery, M. Gehenot, O. Lemoine, J. P. Martinet, G. Robaeys, B. Servais, A. Van Gossum, H. Van Vlierberghe
Journal: Gut (2000)
Loss of a chromosomal region with synteny to human 13q14 occurs in mouse chronic lymphocytic leukemia that originates from early-generated B-1 B cells
Authors: K Hayakawa, A M Formica, M J Colombo, S A Shinton, J Brill-Dashoff, H C Morse III, Y-S Li, R R Hardy
Journal: Leukemia (2016)
Comparison of 6-Mercaptopurine and Busulfan in Chronic Granulocytic Leukemia
Authors: CHARLES M. HUGULEY, JAMES GRIZZLE, R. WAYNE RUNDLES, WARREN N. BELL, CHARLES C. CORLEY, W. B. FROMMEYER, B. G. GREENBERG, WILLIAM HAMMACK, JOHN C. HERION, G. WATSON JAMES, WILLIAM E. LARSEN, VIRGIL LOEB, LOUIS A. LEONE, JEFFRESS G. PALMER, SLOAN J. WILSON
Journal: Blood (1963)
Host Responses Within Solid Tumors. I. Monocytic Effector Cells Within Rat Sarcomas&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: J S Haskill, J W Proctor, Y Yamamura
Journal: JNCI Journal of the National Cancer Institute (1975)

Morphologic studies of two unrelated progressively growing sarcomas in rats revealed the presence of a large proportion of host cells distinct from tumor cells. Enzymatically or mechanically dispersed tumor suspensions were fractionated by the velocity sedimentation method, which resulted in a separation of host and tumor cells. The host cells had the typical morphology of macrophages and also were adherent to a plastic surface after a short incubation period. The proportion of host cells was greater in a young (10 or 12 days) than in an older tumor (35 days). These macrophage-like host cells isolated from sarcomas 12 and 35 days after implantation inhibited the colony formation of tumor cells in vitro in the nonspecific manner ascribed to activated macrophages. In addition to these effector cells, the host fraction contained macrophage precursors able to proliferate in vitro but apparently inhibited by the presence of tumor cells. The results indicated that these macrophage-like effector cells may be the predominant host reaction within some rat sarcomas, and also that thymus- and bone marrow-derived lymphocytes act only indirectly if they are involved.
Self-mutilation in personality disorders: psychological and biological correlates
Authors: D Simeon, B Stanley, A Frances, J J Mann, R Winchel, M Stanley
Journal: American Journal of Psychiatry (1992)

The goal of this study was to determine whether self-mutilators with personality disorders differ from nonmutilators with personality disorders in impulsivity, aggression, and other psychopathology and whether serotonergic dysfunction contributes to self-mutilation.Twenty-six self-mutilators with personality disorders were matched to 26 control subjects with personality disorders for gender, age, education, axis I diagnosis of affective disorder, and axis II diagnosis of personality disorder. Numerous indexes of psychopathology as well as CSF 5-hydroxyindoleacetic acid (5-HIAA) levels and platelet imipramine binding sites (Bmax) and affinity (Kd) were determined.Self-mutilators had significantly more severe character pathology, had greater lifetime aggression, and were more antisocial than the control subjects. The self-mutilators scored higher on the Hamilton Rating Scale for Depression but not on the Beck Depression Inventory or the Beck Hopelessness Scale. The two groups did not differ on the Buss-Durkee Hostility and Guilt Inventory or on the Sensation Seeking Scale. The degree of self-mutilation was significantly correlated with impulsivity, chronic anger, and somatic anxiety. Both self-mutilation and impulsivity showed significant negative correlations with Bmax, although the two groups did not differ in CSF 5-HIAA levels or in platelet imipramine binding.The results demonstrate the contribution of severe character pathology, aggression, impulsivity, anxiety, and anger to self-mutilation and provide preliminary support for the hypothesis of underlying serotonergic dysfunction facilitating self-mutilation.