tbuckley/cabot-search huggingface dataset:
Current versus historical population sizes in vertebrate species with high gene flow: a comparison based on mitochondrial DNA lineages and inbreeding theory for neutral mutations.
Authors: J C Avise, R M Ball, J Arnold
Journal: Molecular Biology and Evolution (1988)

Using inbreeding theory as applied to neutral alleles inherited maternally, we generate expected probability distributions of times to identity by descent for random pairs of mitochondrial genotypes within a population or within an entire species characterized by high gene flow. For comparisons with these expectations, empirical distributions of times to most recent common ancestry were calculated (by conventional mtDNA clock calibrations) from mtDNA haplotype distances observed within each of three vertebrate species--American eels, hardhead catfish, and redwinged blackbirds. These species were chosen for analysis because census population size in each is currently large and because both genetic and life-history data are consistent with the postulate that historical gene flow within these species has been high. The observed molecular distances among mtDNA lineages were two to three orders of magnitude lower than predicted from census sizes of breeding females, suggesting that rate of mtDNA evolution is decelerated in these species and/or that long-term effective population size is vastly smaller than present-day population size. Several considerations point to the latter possibility as most likely. The genetic structure of any species is greatly influenced by historical demography; even for species that are currently abundant, mtDNA gene lineages appear to have been channeled through fairly small numbers of ancestors.
Treatment of cancer-associated hemolytic uremic syndrome with staphylococcal protein A immunoperfusion.
Authors: S Korec, P S Schein, F P Smith, J R Neefe, P V Woolley, R M Goldberg, T M Phillips
Journal: Journal of Clinical Oncology (1986)

Plasma perfusion over filters containing staphylococcal protein A (SPA) was used to treat 11 patients with adenocarcinoma who developed a hemolytic uremic syndrome. Immunoperfusion resulted in complete clearance of pretreatment elevated levels of circulating immune complexes in eight of the 11 patients with normalization of complement values depressed at the start of the therapy in seven. A significant rise in platelets and erythrocyte counts was achieved in nine patients, and stabilization of progressive renal impairment was achieved in six. The response was incomplete and short lived in three patients with clinically evident tumor recurrence, whereas long-term control of the syndrome was demonstrated in seven patients in complete tumor remission (no recurrence with median follow-up of 9 months). SPA immunoperfusion appears to be an effective form of therapy for this otherwise fatal syndrome.
Phase 1/2 Study of Oral Rucaparib: Updated Phase 1 and Preliminary Phase 2 Results
Authors: R. Kristeleit, R. Shapira-Frommer, H. Burris, M.R. Patel, P.M. Lorusso, A.M. Oza, J. Balmaña, S.M. Domchek, L. Chen, A. Montes, R. Plummer, H. Arkenau, L. Maloney, E. Dominy, G. Shapiro
Journal: Annals of Oncology (2014)
Standard whole brain radiation therapy (WBRT) with supplemental oxygen (O<sub>2</sub>), with or without RSR13 (efaproxiral)in patients with brain metastases: Results of the randomized REACH (RT-009) study
Authors: J. Suh, B. Stea, A. Nabid, J. Kresl, A. Fortin, J. P. Mercier, N. Senzer, E. Chang, J. B. Holz, E. Shaw
Journal: Journal of Clinical Oncology (2004)

1534 Background: Brain metastases represent a common cause of morbidity and mortality among cancer pts. The effectiveness of WBRT as primary therapy for brain metastases is limited by tissue hypoxia, which has been shown to cause radioresistance in solid tumors. RSR13 (efaproxiral) is a novel radiation sensitizer that acts as an allosteric modifier of hemoglobin, facilitates O2 release and decreases tissue hypoxia. Methods: A randomized, open-label Phase 3 study was conducted comparing RSR13 and WBRT to WBRT alone in pts. with newly diagnosed brain metastases from various solid tumors. In the RSR13 arm (n=271), pts. received RSR13 (75–100 mg/kg/d, IV) plus O2 followed by WBRT (30 Gy, 3 Gy/d x 10 days). In the Control arm (n=267), pts. received WBRT plus O2. The primary endpoint was survival. Secondary endpoints were RR in the brain, TTP, cause of death and QoL. Results: A total of 538 pts. were enrolled over 29 months at 82 sites in 12 countries. In the overall study population (n=538), the RSR13 arm demonstrated a 17.6% improvement in median survival time (MST) over the Control arm (5.26 mo vs. 4.47 mo; p=0.17). The survival benefit for RSR13 was statistically significant in a Cox multiple regression model (Hazard Ratio 0.78 [95% CI 0.64, 0.94], p=0.010). Pts. with breast cancer or NSCLC (n=414) receiving RSR13 had a 32.4% increase in MST vs. Control (5.91 vs. 4.47 mo; p=0.12). In pts. with breast cancer (n=115) the MST almost doubled in those who received RSR13 vs. Control (8.67 vs. 4.57 mo; p=0.006). The percentage of breast cancer pts. with stable/improved KPS at 3 months was significantly higher in the RSR13 arm (35% vs 18%, p=0.001). Related SAEs that are part of the RSR13 safety profile occurred in 7% of pts. The most common RSR13-related SAE was hypoxemia (3.4 %), which is dose-dependent and effectively managed with increased supplemental O2. Conclusions: The addition of RSR13 to WBRT was well tolerated and led to a 22% reduction in the risk of death for all pts. A near doubling in MST and significant improvement in QoL were observed in pts. with brain metastases from breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Allos Therapeutics, Inc. Allos Therapeutics Allos Therapeutics, Inc. Allos Therapeutics
Prisoners at Guantanamo Bay
Authors: P. Connor
Journal: BMJ (2002)

Editor—How patronising of Marshall to imagine that he knows what is happening in Guantanamo Bay.1 His letter is merely an excuse for espousing his view that American officials are torturing their prisoners.

The American authorities have allowed the International Committee of the Red Cross and other bodies, as well as the British government, to have access to the prisoners. Indeed, it is my understanding (through the media here in the United States) that the Red Cross has already made recommendations to the American government, which are being acted on while its full report is awaited. I do not think that the government is trying to hide the prisoners' treatment in any way.

Forrest attempts to manipulate the situation by suggesting that the now infamous photograph of the prisoners after their arrival from Afghanistan shows how they are managed on a daily basis.2 How blind. Politics dictate. I also believe that the prisoners at Guantanamo Bay should be treated humanely and afforded the protection of the Geneva Convention. Like many others, however, I do not have any sympathy for them. I suggest that the reports and comments from those bodies that have had access to Guantanamo Bay may be more accurate and tenable than the concerns of Marshall.

We are doctors and are bound by international convention as well as our own moral and ethical boundaries. In our treatment of any patient we must follow our conscience.
S124 The BODE Index is an independent determinant of arterial stiffness in Chronic Obstructive Pulmonary Disease (COPD): Abstract S124 Table 1
Authors: M Fisk, NS Gale, D Mohan, CM McEniery, JR Forman, CE Bolton, W MacNee, JR Cockcroft, J Fuld, PMA Calverley, J Cheriyan, R Tal-Singer, MI Polkey, IB Wilkinson
Journal: Thorax (2015)

<h3>Introduction</h3> COPD is associated with increased cardiovascular events, independent of established risk factors. Arterial stiffness and carotid intima-media thickness (CIMT) are surrogates of cardiovascular risk and we sought to determine their relationship with COPD severity and prognosis in the ERICA (Evaluation of role of inflammation in airways disease) multi-site UK study: the largest cohort study focusing on cardiovascular manifestations in COPD. <h3>Methods</h3> Spirometry, haemodynamic measures (aortic pulse wave velocity (aPWV), augmentation index (AIx), peripheral and central blood pressure (BP)) and CIMT (ultrasound measure of carotid artery intima-media layer thickness) were performed in 729 COPD subjects aged ≥40 years. COPD severity was classified by BODE Index [BMI, Obstruction (FEV1), Dyspnoea (mMRC score), Exercise tolerance (6-minute walk distance)], a validated score based on clinical variables and predictor of mortality in COPD. <h3>Results</h3> Mean aPWV was 10.3 (SD 2.6) m/s, AIx 27 (10)%, brachial BP 144/82 (18/11) mmHg, central BP 131/82 (18/11) mmHg, CIMT 0.86 (0.4) mm. BODE correlated with aPWV (p &lt; 0.0001) and this was maintained when adjusted for study site, age, supine heart rate (HR) mean arterial pressure (MAP), years smoked and cardiovascular comorbidities (MI, stroke, diabetes, peripheral vascular disease), p &lt; 0.0001. BODE was also associated with AIx when adjusted for site, age, seated HR and MAP, years smoked and cardiovascular comorbidities, p &lt; 0.01. The constituent variables of BODE did not have the same significant association with both aPWV and AIx, Table 1. An inverse correlation of BODE with central systolic BP (p = 0.003) was observed and this was maintained after adjustment for study site, age and HR p = 0.03. There was no significant relationship between BODE and CIMT. <h3>Conclusions</h3> BODE is associated with arterial stiffness in COPD, independent of traditional risk factors. Its negative relationship with systolic pressure suggests increasing arterial stiffness with COPD severity, is independent of blood pressure. The BODE Index composite variables are not on the causal pathway for vascular stiffness, so its positive association likely reflects patient susceptibility to injury from smoke or other irritants in the lungs and vasculature. BODE may also enhance cardiovascular risk stratification in COPD, since its relationship with stiffness was independent of self-reported cardiovascular comorbidities.
Stage IV non-small-cell lung cancer: the guides are perplexed.
Authors: R B Livingston
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.11.1591 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2553878 Stage IV non-small-cell lung cancer: the guides are perplexed. R B LivingstonxR B LivingstonSearch for articles by this author Show More University of Washington, Seattle. https://doi.org/10.1200/JCO.1989.7.11.1591 First Page PDF © 1989 by American Society of Clinical Oncology
한국인에서 Chemokine 수용체 (CCR5) promoter 유전자 다형성과 B형간염 바이러스 감염 후 임상 경과와의 상관성
Authors: 장혜영 ( Hye Young Chang ), 안상훈 ( Sang Hoon Ahn ), 김도영 ( Do Young Kim ), 신전수 ( Jeon Soo Shin ), 김용수 ( Yong Soo Kim ), 홍선표 ( Sun Pyo Hong ), 정현재 ( Hyun Jae Chung ), 김수옥 ( Soo Ok Kim ), 유왕돈 ( Wang Don Yoo ), 한광협 ( Kwang Hyub Han )
Journal: Clinical and Molecular Hepatology (2005)

목적: 숙주의 면역 유전적 요인은 바이러스 감염과 관련하여 중요한 역할을 한다. CCR5 promoter의 유전적 다형성은 HIV 감염 후 질환의 진행성과 연관이 있다. 그러나 아직까지 HBV 감염과의 연관성은 보고된 바 없다. 따라서 본 연구에서는 CCR5 promoter의 유전자 다형성과 HBV 감염과의 관계를 조사하였다. 대상과 방법: 총 377명의 환자를 대상으로 하였으며 이들을 자연 치유군[HBsAg (-), anti-HBc (+), anti-
Mifepristone (RU-486) in androgen independent prostate cancer
Authors: J. H. Hayes, W. K. Oh, P. W. Kantoff, J. B. Manola, M. R. Smith, E. P. Gelmann, G. Bubley, S. P. Balk, M. Taplin
Journal: Journal of Clinical Oncology (2006)

14508 Background: The androgen receptor (AR) plays a critical role in the development and progression of prostate cancer, and available antiandrogens do not turn off AR transcription completely. Mifepristone (RU-486) is a potent inhibitor of AR and acts by both competing with dihydrotestosterone (DHT) and binding with the AR co-repressor nuclear receptor co-repressor (NCoR), converting AR from a transcriptional activator to a transcriptional repressor. Methods: 22 patients with AIPC, PSA ≥5 ng/mL, and documented bone metastases were treated with mifepristone 200 mg PO QD until disease progression. Correlative studies include measurement of testosterone, cortisol, androstenedione, DHT, DHEA (dehydroepiandrosterone), and DHEA sulfate levels at baseline and during therapy. Results: Patients were treated a median of 84 days (range 10–182 d). Median PSA at time of enrollment was 41.9 ng/mL (range 5.2–1930.9 ng/mL). No patients demonstrated a PSA response. 13 patients have discontinued treatment, 12 for progressive disease (11 PSA progression and 1 bony progression) and 1 for grade 3 toxicity (GI bleed after 10 d on treatment). 6 patients are still on therapy with stable disease after a median 98 d. In 11 patients, baseline testosterone levels were mean 28.4 ng/dL (range &lt;20–49 ng/dL). After one month of therapy, testosterone increased to mean 66.6 ng/dL (range 16–104 ng/dL) (p = 0.001). Compared to baseline, one month androstenedione and DHEAS levels were elevated in the majority of patients. Conclusions: Mifepristone demonstrated limited activity in AIPC patients. Potential efficacy was most likely limited by a rapid elevation in testosterone levels. We hypothesize that inhibition of glucocorticoid receptor led to an increase in ACTH with subsequent elevation of adrenal androgens and conversion to DHT. These preliminary data suggest that even moderate increases in systemic testosterone levels may stimulate tumor growth. These data also emphasize the continued importance of adrenal androgens and AR transcription in prostate cancer biology. No significant financial relationships to disclose.
Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis
Authors: Erik Schoenmakers, Bradley Carlson, Maura Agostini, Carla Moran, Odelia Rajanayagam, Elena Bochukova, Ryuta Tobe, Rachel Peat, Evelien Gevers, Francesco Muntoni, Pascale Guicheney, Nadia Schoenmakers, Sadaf Farooqi, Greta Lyons, Dolph Hatfield, Krishna Chatterjee
Journal: Journal of Clinical Investigation (2016)

Selenium is a trace element that is essential for human health and is incorporated into more than 25 human selenocysteine-containing (Sec-containing) proteins via unique Sec-insertion machinery that includes a specific, nuclear genome-encoded, transfer RNA (tRNA[Ser]Sec). Here, we have identified a human tRNA[Ser]Sec mutation in a proband who presented with a variety of symptoms, including abdominal pain, fatigue, muscle weakness, and low plasma levels of selenium. This mutation resulted in a marked reduction in expression of stress-related, but not housekeeping, selenoproteins. Evaluation of primary cells from the homozygous proband and a heterozygous parent indicated that the observed deficit in stress-related selenoprotein production is likely mediated by reduced expression and diminished 2'-O-methylribosylation at uridine 34 in mutant tRNA[Ser]Sec. Moreover, this methylribosylation defect was restored by cellular complementation with normal tRNA[Ser]Sec. This study identifies a tRNA mutation that selectively impairs synthesis of stress-related selenoproteins and demonstrates the importance of tRNA modification for normal selenoprotein synthesis.
The Curious Case of the Baffling Biological
Authors: Bruce D. Cheson
Journal: Journal of Clinical Oncology (2000)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.10.2007 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10811663 The Curious Case of the Baffling Biological Bruce D. Cheson, MDxBruce D. ChesonSearch for articles by this author Show More National Cancer Institute, Bethesda, MD https://doi.org/10.1200/JCO.2000.18.10.2007 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Gefitinib (G) treatment outcome after progression on erlotinib (E) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: F. Grossi, A. Brianti, C. Defferrari, M. Loprevite, G. Catania, P. Pronzato
Journal: Journal of Clinical Oncology (2007)

18138 Background: Two case reports describe a response to E after failure of G (Garfield DH, J Clin Oncol 2005) or to G after failure of E (Choong NW et al, Nat Clin Pract Oncol 2006) in patients (pts) with advanced NSCLC. Otherwise, a limited experience in 5 pts suggests that E is not effective in pts progressing on G (Viswanathan A et al, Lung Cancer 2005). Aim of this study was the evaluation of response and time to progression (TTP) in advanced NSCLC pts treated with G after failure of E. Methods: Pts received G 250 mg/day after disease progression (PD) with E 150 mg/day. Pts accrual was stopped on August 2006 after the approval of E for use in Italy and the consequent closure of the G compassionate-use program. Results: From May 2005 to August 2006, 15 pts were enrolled. Median age 65 years (50–85); males= 14 pts (93%); never/former smokers= 4/10 pts (26/67%); adenocarcinoma= 10 pts (67%); PS 0/1= 5/10 pts (33/67%); in 2 pts (13%) E was administered as first-line therapy, 8 pts (53%) received 2 prior lines of chemotherapy (CT) and 3 pts (20%) received CT between E and G. One patient (7%) had a partial response (PR) and 5 pts (33%) had disease stabilization (SD) with E; with G no PR and 6 SD (40%) were obtained. Five out of 6 RP/SD pts with E, had SD with G; 8 out of 9 PD pts with E, had PD with G; 1 SD patient with E, progressed with G and 1 vice versa. TTP in RP/SD pts was 7.2 and 3.4 months for E and G respectively; in PD pts TTP was 1.7 and 1.6 for E and G respectively. Conclusions: Our data suggest that there is a benefit with G in pts who had RP/SD with E and that is associated with a good TTP. Conversely G is not recommended in pts that immediately progressed after E. Moreover these results support the rationale of treating PD pts with an EGFR TKI with another one; it may be worthwhile to collect more data on E. No significant financial relationships to disclose.
Spontaneous fracture of the catheter of a totally implantable venous access port: case report of a rare complication.
Authors: J Noyen, J Hoorntje, Z de Langen, J W Leemslag, D Sleijfer
Journal: Journal of Clinical Oncology (1987)

A case of spontaneous fracture of the outlet catheter of a totally implantable venous access port (IVAP) is presented. Thirty-seven weeks after implantation, the outlet catheter was broken at the entrance into the left subclavian vein. The distal part was embolized in the left pulmonary artery. The embolized remnant was retrieved in an outpatient setting, using a grasping forcipal catheter through a 7 French longsheath. Experimental study of the catheter revealed that it had been broken due to a local cause, probably the long-standing compression at the narrow space between clavicle and first rib. It is emphasized to ascertain the position and intactness of an IVAP before using it to infuse cytostatic agents.
Response and toxicity to a dose-intensive multi-agent chemotherapy induction regimen for high risk neuroblastoma (HR-NB): A Children's Oncology Group (COG A3973) study
Authors: S. G. Kreissman, J. G. Villablanca, L. Diller, W. B. London, J. M. Maris, J. R. Park, C. P. Reynolds, D. von Allmen, S. L. Cohn, K. K. Matthay
Journal: Journal of Clinical Oncology (2007)

9505 Background: Myeloablative consolidation improves outcome for HR-NB pts, especially for pts in CR prior to consolidation. We assessed the toxicity and CR+VGPR rate of a dose-intensive multi-agent chemotherapy induction based upon the N7 regimen (JCO 22:4888, 2004) prior to myeloablative consolidation and peripheral blood autologous stem cell transplant (ASCT). Methods: Between 2/2001 and 3/2006, 489 eligible newly diagnosed HR- NB pts received the following induction consisting of 6 cycles of chemotherapy q 21 days. Cycles 1, 2, 4 &amp; 6: cyclophosphamide 4.2 g/m 2 , doxorubicin 75 mg/m 2 , and vincristine 2 mg/m 2 and Cycles 3 &amp;5: cisplatin 200 mg/m 2 and etoposide 600 mg/m 2 . Surgical resection of primary occurred after cycle 5. Following induction pts received purged or unpurged ASCT (as randomized), radiation, and then 13-cis-retinoic acid (13-cis-RA). Response was assessed after cycles 2 &amp; 6 using the International Neuroblastoma Response Criteria and analyzed as intent-to-treat. Results: Median age was 3.1 yrs, 44% of 392 tumors tested had MYCN amplification. Fourteen pts (3%) died during induction (5 infection, 4 bleed into tumor, 4 compromised organ function from tumor, 1 unrelated to tumor/therapy). Patients experienced the following grade 3 &amp; 4 toxicities at least once during induction: neutropenia 70%, thrombocytopenia 71%, hearing loss 6%, cardiac function 2% and renal function 3%. Documented infection occurred in 24% of cycles (90% bacterial, 3% viral, 7% fungal). Responses among the 489 pts at end of induction were CR 24%, VGPR 28%, PR 26%, SD 7%, and PD15%, with morphologically detectable bone marrow (BM) disease cleared in 87% and no disease remaining by MIBG scan in 55% of pts MIBG positive at baseline. Conclusions: Despite increased dose intensity of this regimen, toxicity was not excessive compared to prior HR-NB regimens. In a multi-center setting, the A3973 induction chemotherapy achieved morphologic BM clearance in 87% of pts prior to consolidation. The CR/VGPR rate of 52% is similar to that of prior less intensive regimens. The impact of this induction response on survival within the context of ASCT and 13-cis-RA on COG A3973 will be determined with longer follow-up. No significant financial relationships to disclose.
Effect of US Drug Enforcement Administration’s Rescheduling of Hydrocodone Combination Analgesic Products on Opioid Analgesic Prescribing
Authors: Christopher M. Jones, Peter G. Lurie, Douglas C. Throckmorton
Journal: JAMA Internal Medicine (2016)

This study examines national patterns to identify effects on opioid analgesic prescribing before and after the US Drug Enforcement Administration's rescheduling of hydrocodone combination analgesic products.
Myocardial Collagen Cross-Linking Is Associated With Heart Failure Hospitalization in Patients With Hypertensive Heart Failure
Authors: Begoña López, Susana Ravassa, Arantxa González, Elena Zubillaga, Claudia Bonavila, Magda Bergés, Kattalin Echegaray, Javier Beaumont, María U. Moreno, Gorka San José, Mariano Larman, Ramón Querejeta, Javier Díez
Journal: Journal of the American College of Cardiology (2016)