tbuckley/cabot-search huggingface dataset:
Histone H5 in the Immature Blood Cells of Chickens With Leukosis Induced by Avian Leukosis Virus Strain E26
Authors: N. Sotirov
Journal: JNCI Journal of the National Cancer Institute (1981)

Whole histone was isolated from the immature cells of the peripheral blood of White Leghorn chickens, line 151, with leukosis experimentally induced by avian leukosis virus, strain E26 (ALV-E26). Histone H5 was demonstrated in all samples of these cells and was characterized by electrophoresis in polyacrylamide gel, extraction with perchloric acid, amino acid analysis, and immunodiffusion in agarose gel. Histone H5 was not detected in the myeloblasts of chickens with myeloblastosis caused by the avian myeloblastosis virus. It was concluded that the immature cells (IBC-E26) obtained from the peripheral blood of chickens responding positively to ALV-E26 belonged to the erythroid blood cell series and that ALV-E26 induced in vivo erythroblastosis but not myeloblastosis in chickens. The relative amount of histone H5 in IBC-E26 was two times higher than that in the erythroblasts obtained from the peripheral blood of chickens with erythroblastosis caused by avian erythroblastosis virus, strain R of Engelbreth-Holm. Thus the erythroblasts in the circulating blood of chickens with leukosis induced by ALV-E26 seemed to be more differentiated.
Accuracy of Wearable Devices for Estimating Total Energy Expenditure
Authors: Haruka Murakami, Ryoko Kawakami, Satoshi Nakae, Yoshio Nakata, Kazuko Ishikawa-Takata, Shigeho Tanaka, Motohiko Miyachi
Journal: JAMA Internal Medicine (2016)

The hope is that the focus on moving to more valuebased payment models will begin to bring in more measures of the effects this has on patient outcomes, which are the most important measure of the effects of changes in the use of health care services.That, along with the focus on comparative effectiveness analysis, which attempts to provide information on the differential clinical effects of using various interventions and treatment agents on different types of patients, should improve the ability to treat patients in a more clinically and cost-effective manner.To say that much remains in the path to accomplishing the objectives associated with value-based payment models is an understatement.However, this analysis suggests that the move to reduce overvalued payments can have differentiated effects, reducing the use of a procedure by physicians and other health care professionals who are not trained to use it while maintaining similar levels of its use by those who are trained in the use of the procedure.The CMS should consider using this strategy for other potentially overvalued services, particularly those that have a high cost, such as the use of proton beam therapy, which is a very expensive intervention with little clinical evidence supporting its use.
Soft drink makers consider legal challenge against sugar tax
Authors: Nigel Hawkes
Journal: BMJ (2016)

The government’s plans to tax soft drinks containing sugar may be challenged in court by manufacturers who say that they are discriminatory because they exclude other drinks, such as fruit juices and milkshakes.

The soft drinks levy, a surprise addition to the 2016 budget, will see soft drinks containing more than 5 g of sugar per 100 mL taxed at a rate of 18p a litre and those containing over 8 g taxed at 24p a litre.1 The chancellor of the exchequer, George Osborne, said that talks would be held with the industry over the introduction of the levy, which would not start until 2017-18.

The industry will not commit itself in advance of such talks, but Gavin Partington, director general of the British Soft Drinks Association, said that all …
Congenital Glutamine Deficiency with Glutamine Synthetase Mutations
Authors: Christopher Rose, Rajiv Jalan
Journal: New England Journal of Medicine (2006)

than 80 percent of the predicted value).Accordingly, the results of the SUPER study cannot be extrapolated for patients with pulmonary hypertension related to lung diseases.Drs. Hoeper and Welte are correct in their suggestion that there is a linear trend in the response among the doses in the hemodynamic measures and in the percentages of patients who improved by at least one WHO functional class.The absence of a dose-response effect on the primary end point (exercise capacity) or on tolerability with the three sildenafil doses (20 mg, 40 mg, and 80 mg three times daily) may be related to complete inhibition of phosphodiesterase type 5 with the lowest dose.However, in the extension study, all patients were treated with 80 mg three times daily (if tolerated), and we do not have prospective information on the long-term efficacy of the approved dose of 20 mg three times daily.Based on these data, 20 mg three times daily appears to be a reasonable initial dose; an increase to 40 mg three times daily, 80 mg three times daily, or both may be considered in order to achieve or maintain favorable effects.We recognize that limited data are currently available regarding the optimal dose of sildenafil for long-term treatment and that the use of higher doses may be hampered by the restricted approval.
Abstract 9991: The Product of Blood Hemoglobin and Regional Brain Oxygen Saturation is a Simple and Excellent Predictor for a Short-term Neurological Outcome in Patients with Post Cardiac Arrest Syndrome
Authors: Kei Hayashida, Masaru Suzuki, Akiko Shiroshita-Takeshita, Noritoshi Ito, Kei Nishiyama, Hideki Arimoto, Takashi Unoki, Tomohiko Orita, Akira Murai, Tomoyuki Endo, Tomorou Watanabe, Hideaki Anan, Tsuyoshi Hatada, Masanori Mizobuchi, Hideto Yasuda, Yutaro Nishi, Shingo Hori
Journal: Circulation (2012)

BACKGROUND: It has been suggested that brain tissue oxygenation (rSO2) and blood hemoglobin (Hb) at hospital arrival are independently crucial for a prognosis in post cardiac arrest syndrome (PCAS). Although it has been reported that rSO2 correlates with Hb in perioperative patients, this correlation has not been demonstrated during CPR. The product of Hb and rSO2 might represent tissue oxy-Hb level, theoretically. Therefore, it was speculated that the product during CPR predicts neurological outcome in PCAS. AIM: To investigate the relationship between the product of Hb and rSO2 on hospital arrival and good neurological outcome at 30 days in PCAS patients. METHODS: The database of the J-POP registry (multicenter observational study) has prospectively enrolled 764 OHCA patients. Of these, 193 PCAS patients admitted to the wards after ROSC were included in this study. Hb and rSO2 were obtained during resuscitation within 3 min after hospital arrival. The neurological outcome was evaluated by CPC at 30 days, and CPC1 and 2 were defined as favorable neurological outcome. RESULTS: Among 193 PCAS patients, 27 presented favorable outcome (14%) and median [IQR] of Hb and rSO2 were 12.0g/dL [10.4-13.8] and 35% [15-55]. The favorable outcome group showed higher Hb (13.8+/-2.5 vs. 11.7+/-2.7, p&lt;0.001) and rSO2 (58.6 +/- 20.5 vs. 30.6+/-21.0, p&lt;0.001) compared to the unfavorable group. The ROC analysis revealed the product of Hb and rSO2 significantly predicted the favorable outcome (AUC, 0.861; optimal cut-off point, 411; sensitivity, 0.917; specificity, 0.709). When divided into 4 groups by quartile of the product of Hb and rSO2 level, the ratio of patients with favorable outcome was 4.2% in the first quartile (Q1, the product&lt;182), 4.2% in Q2 (183-257), 16.6% in Q3 (258-627), and 75.0% in Q4 (&gt;628), respectively (chi-square test: p&lt;0.001). CONCLUSIONS: The product of blood Hb and rSO2 level during resuscitation is a simple and excellent predictor for a 30-day neurological outcome in patients with PCAS.
Ruling in and ruling out with elastography in compensated advanced chronic liver disease
Authors: Salvador Augustin, Mónica Pons, Joan Genesca
Journal: Gut (2016)

The recent letter by Jansen et al 1 presenting an algorithm to rule out clinically significant portal hypertension (CSPH) by combining shear-wave elastography of liver (L-SWE) and spleen (S-SWE) is an important contribution to the increasing knowledge regarding non-invasive assessment of patients with compensated advanced chronic liver disease (cACLD). Baveno VI recommendations focused on transient elastography as a tool to rule in CSPH in patients with the authors cACLD of viral etiology,2 ,3 but there is no doubt that other related elastography techniques should work similarly. Also, recent UK guidelines on variceal bleeding introduced elastography for variceal screening and diagnosis.4

In their study, the authors concluded that combining L-SWE <16 kPa with S-SWE <26.6 kPa showed a very high sensitivity (98.6%), with a remarkable negative predictive value for CSPH (96.3%). However, we have a few comments about the design and interpretation of results that we hope may enhance the transferability of these excellent results to …
Reduced physical activity in lymphangioleiomyomatosis compared with COPD and healthy controls: disease-specific impact and clinical correlates
Authors: Thomas Bahmer, Henrik Watz, Benjamin Waschki, Marco Gramm, Helgo Magnussen, Klaus F Rabe, Hubert Wirtz, Detlef Kirsten, Anne Kirsten
Journal: Thorax (2016)

<h3>Rationale</h3> Sporadic lymphangioleiomyomatosis (LAM) is an orphan lung disease for which daily physical activity has not been studied so far and it is unclear whether a disease-specific impact beyond airflow limitation exists. Clinical correlates indicating reduced physical activity in addition to established parameters like airflow limitation and hypoxaemia are largely undetermined. <h3>Method</h3> We measured physical activity (steps per day, SPD; physical activity level, PAL; minutes of moderate activity, MMA) in 34 women with LAM, 32 FEV<sub>1</sub>-matched female patients with COPD and 15 age-matched healthy women for 1 week using an accelerometer. In addition, we assessed lung function measurements, questionnaires for generic and respiratory health status (12-Item Short Form Survey, SF-12; St. George9s Respiratory Questionnaire, SGRQ), dyspnoea (modified Medical Research Council dyspnoea scale, mMRC) and fatigue (Multidimensional Fatigue Inventory, MFI-20). <h3>Results</h3> Patients with LAM (mean age 52.7 years, mean FEV<sub>1</sub> 62.7% predicted) showed reduced SPD, PAL and MMA (p&lt;0.01) compared with healthy controls and reduced MMA (p=0.032) compared with female patients with COPD (mean age 65.2 years, mean FEV<sub>1</sub> 62.6% predicted). In multivariate regression analyses, adjusting for FEV<sub>1</sub> and long-term oxygen therapy, either generic health status (SF-12 physical health) or fatigue (MFI-20) were the strongest independent predictors for SPD in patients with LAM (p=0.006 and p=0.004, respectively). <h3>Conclusions</h3> Physical activity in daily life is substatially reduced in LAM, when compared with healthy controls and COPD - indicating a disease specific impact. The regular assessment of fatigue and generic health status may improve disease management in LAM by taking daily physical activity of patients with LAM more adequately into account.
US pledges better protection for babies born to addicts
Authors: Owen Dyer
Journal: BMJ (2016)

The US federal government has promised a congressional committee that it will “take a more proactive approach” to enforce a 2003 law requiring states to report and protect drug affected newborns.

The Committee on Education and the Workforce launched a probe into failures to follow up neonates treated for opioid abstinence syndrome, after an investigation by the Reuters news agency last year found that the Keeping Children and Families Safe Act was being widely ignored by hospitals and state child protection agencies.1

The Reuters investigation reported over 110 deaths among children released from hospital after being treated for …
UTX in muscle regeneration — the right dose and the right time
Authors: Ling Liu, Thomas A. Rando
Journal: Journal of Clinical Investigation (2016)

Precise epigenetic modifications in stem cells control developmental programs and cell fate decisions. In particular, the addition or removal of trimethylation of histone 3 lysine 27 (H3K27me3) at lineage-specific genes has been linked to the repression of gene expression, and a precise balance of methyltransferases and demethylases within cells determines H3K27me3 levels. The demethylase UTX is essential for development and tissue homeostasis; however, a role for UTX in stem cell–mediated tissue regeneration is unknown. In this issue of the JCI, Dilworth and colleagues reveal that UTX and its demethylase activity are required in the muscle stem cell lineage for muscle regeneration in response to injury. Specifically, UTX mediates the removal of H3K27me3 in the promoter of the transcription factor myogenin, which regulates myogenic differentiation. The results of this study provide important insight into the contribution of epigenetic regulation in stem cell–mediated regeneration of adult tissues.
GENO-36GLIOMA SPHERE-FORMING CELLS REVEAL INTRINSIC GLOBAL HYPERMETHYLATION ASSOCIATED WITH GBM RADIATION RESISTANCE
Authors: Qianghu Wang, Eskil Eskilsson, Ravesanker Ezhilarasan, Siyuan Zheng, Joy Gumin, Tim Heffernan, Giulio Draetta, Frederick Lang, Roel Verhaak, Erik Sulman
Journal: Neuro-Oncology (2015)

Glioma sphere-forming cells (GSCs) are important models for understanding glioma biology and development of novel therapies.We performed clonogenic assays to explore the relationship between methylation status and radiation response in twelve IDH wild type GSCs irradiated with 2-, 4-, and
ANTIGENIC VARIANTS OF EASTERN EQUINE ENCEPHALITIS VIRUS
Authors: Jordi Casals
Journal: The Journal of Experimental Medicine (1964)

A study by hemagglutination-inhibition test showed that 19 strains of eastern equine encephalitis virus grouped themselves in two main types, which have been designated North American and South American. The former consists of ten strains from the eastern half of the United States, from Massachusetts to Florida; Jamaica, the Dominican Republic, and, subject to confirmation, Thailand. The South American type comprises nine strains from Panama, Trinidad, British Guiana, Brazil, and Argentina. The strains were isolated from different natural hosts over a period of 30 years.
Response of Strain HR/De Mice to Painting With Urethan
Authors: Margaret K. Derwger
Journal: JNCI Journal of the National Cancer Institute (1962)

Groups of strain HR/De mice, consisting of haired and hairless animals of both sexes, were painted continuously on an interscapular area with a 40 percent solution of urethan in ethylene glycol or with ethylene glycol alone. The incidence of epidermoid carcinomas was significantly increased in hairless mice painted with urethan in ethylene glycol, but the incidence of papillomas of the skin was not increased in hairless animals painted with urethan in ethylene glycol or with ethylene glycol alone. Both epidermoid carcinomas and papillomas of the skin arose earlier in hairless mice painted with urethan in ethylene glycol than in hairless mice painted with ethylene glycol alone. Pulmonary tumors occurred in a significantly greater number of haired mice than hairless mice painted with urethan in ethylene glycol. The data indicate that the reduction in susceptibility is due to action of the hairless (hr) gene itself. Hemangioendotheliomas occurred frequently and arose early in haired and hairless mice painted with urethan in ethylene glycol, the most frequent site being the liver which often had multiple tumors. Three of these lesions were successfully transplanted, which indicated that they were neoplasms.
Production of Autochthonous Prostate Cancer in Lobund-Wistar Rats by Treatments With &lt;italic&gt;N&lt;/italic&gt;-Nitroso-&lt;italic&gt;N&lt;/italic&gt;-methylurea and Testosterone&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M Pollard, P H Luckert
Journal: JNCI Journal of the National Cancer Institute (1986)

More than 50% of Lobund-Wistar (L-W) strain rats developed large, palpable prostate adenocarcinomas (PAs) following treatments with N-nitroso-N-methylurea (CAS: 684-93-5) and testosterone propionate [(TP) CAS: 57-85-2], and most of the tumor-bearing rats manifested metastatic lesions. The incubation periods averaged 10.6 months. Within the same timeframe, no L-W rat developed a similar palpable PA when treated only with TP. In L-W rats, TP acted as a tumor enhancement agent, with primary emphasis on the development of prostate cancer.
&lt;italic&gt;Brief Communication:&lt;/italic&gt; Detection of Mouse Mammary Tumor Virus in Cat Kidney Cells Infected With Purified B Particles From Rill Milk&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: E Y Lasfargues, B Kramarsky, J C Lasfargues, D H Moore
Journal: JNCI Journal of the National Cancer Institute (1974)

A feline kidney cell line (CRFK-F2) was experimentally infected with B particles obtained by isopycnic banding of Rill milk on a Ficoll gradient. Free B particles were found in the culture supernatants 3 months post inoculation. Murine mammary tumor virus (MuMTV) antigen was then detected by membrane immunofluorescence; about 20% of the cells showed this specific antigen on their surfaces a year after infection. Electron microscopy revealed formation of virions in microvilli and accumulation of specific antibodies on their surfaces. Idiogram and zymogram studies confirmed that the cultivated cells were not of mouse origin. Active budding of MuMTV has not been detected in renewed attempts to infect these cells with Rill milk virus or an MuMTV from a BALB/cfC3H tumor celiline.
Methodologic standards for treatment outcome research in schizophrenia
Authors: W T Carpenter, D W Heinrichs, T E Hanlon
Journal: American Journal of Psychiatry (1981)

Considerable progress has been made in increasing the formal correctness of outcome research in schizophrenia by employing strict methodologic standards. However, based on a recent review of the literature, the authors note that insufficient attention has been directed toward the meaningfulness of such research. The interest of a particular study derives from its application beyond the specific patients treated; lack of attention to meaningfulness encourages the researcher to posit unjustified or overly generalized conclusions, resulting in the widespread adoption of questionable treatment strategies or the dismissal of potentially useful ones. Increased attention to meaningfulness will make the conclusions of this type of research more valuable, both from pragmatic and theoretical standpoints.
Abstract 15945: Cdc42 is Required for Lymphatic Branching, Maturation and Valve Formation During Development
Authors: Yixin Jin, Yang Liu, Hailin Chen, Rui Wang, Hongjiang Si, Sathish Srinivasan, Shenyuan Zhang, Mariappan Muthuchamy, David Zawieja, Xu Peng
Journal: Circulation (2015)

Cdc42 is a Ras-related GTPase that plays an important role in regulation of actin cytoskeletal architecture. Blocking the ability of Cdc42 to activate its effectors has been shown to inhibit a range of cellular functions including cell polarization, migration, proliferation and differentiation. Consistent with its critical roles in vitro, the inactivation of Cdc42 in mice resulted in embryonic lethality before E6.5. The early embryonic lethal phenotype of Cdc42-null mice has made it not useful for studies on the interesting questions of the roles and mechanisms of Cdc42 in the vascular development. To overcome this problem, we have generated an endothelial cell (EC) specific Cdc42 knockout mouse line by crossing Cdc42/flox mice with vascular endothelial cadherin Cre mice. Our results have demonstrated that the deletion of Cdc42 in ECs resulted in embryonic lethality with severe edema. Whole mount immunofluorescence staining showed mesentery collecting lymphatic vessel maturation and valve formation defects. Interestingly, lymphangiogenesis in the intestine wall was totally disrupted in Cdc42 EC knockout embryos. Moreover, we analyzed the role of Cdc42 in lymphatic vessel formation in the skin. We found that Cdc42 is required for tip cells filopodia formation and the deletion of Cdc42 in endothelial cells impaired lymphatic vessel sprouting, branching and the mutant lymphatic vessels displayed blunt-ended, bulbous lymphatic. We also noted that the size of lymphatic lumen was significantly increased. Taken together, our data suggested that Cdc42 plays an essential role in lymphatic branching, maturation and valve formation during development.
Prevalence of <i>BRCA1</i> and <i>BRCA2</i> mutations in Jewish women with triple negative breast cancer
Authors: E. A. Comen, M. Davids, T. Kirchhoff, L. Balistreri, J. Hansen, K. Kosarin, K. Offit, M. E. Robson
Journal: Journal of Clinical Oncology (2008)

22002 Background: Approximately 10% of Ashkenazi Jewish (AJ) women with breast cancer (BC) carry one of three mutations in BRCA1 or BRCA2 (BRCA1 185delAG or 5382insC, BRCA2 6174delT). There is an association between BRCA1 mutations and 'triple negative' (TripNeg) phenotype (estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 non- overexpressing). TripNeg is not over-represented in BRCA2-BC. We sought to determine the predictive value of the TripNeg phenotype for the presence of any BRCA mutation in a cohort of Jewish women ascertained without respect to family history (FH). Methods: DNA samples were collected between 8/2000 and 6/2004 from 495 Jewish women with BC(median age at diagnosis 57 years) treated at a single institution. Medical records were reviewed and samples annotated with limited clinical information. Patients were considered to be ER or PR negative if fewer than 10% of cells stained by IHC, and HER2 negative if they were 0–1+ by IHC or 2+ with FISH < 2.0. Samples were genotyped for AJ founder mutations. Results: 389 (78.6%) of patients were ER+, 280 (56.6%) were PR+, and 96 (19.4%) were ER-/PR-. Most patients (n=388, 78.4%) were HER2-. TripNeg phenotype was observed in 65 (13.1%). Founder mutations were detected in 52 samples (10.5%, BRCA1 in 5.5% (n=27), BRCA2 in 5.1% (n=25)). Compared to women without mutations (mut neg), BRCA1 mutation carriers (but not BRCA2 carriers) were younger at diagnosis (P <0.001) and more likely to have a family history of breast cancer (P = 0.004). BRCA1 carriers were more likely than mut neg women to be ER-/PR- (74% vs 16%, P < 0.001) and TripNeg (70.4% vs 9.8%, P<0.001). The positive predictive value (PPV) of TripNeg for a BRCA1 mutation was 29% overall, 48% in women diagnosed < 50 yrs, and 14% in women diagnosed ≥50. Although 24% of BRCA2-BC were TripNeg, BRCA2 carriers were not significantly more likely than non-carriers to be ER-/PR- or TripNeg. TripNeg phenotype was significantly associated with detecting a mutation in either BRCA1 or BRCA2, but only 25/52 (48%) mutation-associated cancers were TripNeg. Conclusion: TripNeg phenotype predicts for BRCA1 mutation, but many women with mutations do not have TripNeg disease. Overemphasis on TripNeg to select for genetic testing may lead to under-recognition of hereditary breast cancer. No significant financial relationships to disclose.
Targeted Agents: Management of Dermatologic Toxicities
Authors: Barbara Burtness
Journal: Journal of the National Comprehensive Cancer Network (2014)

Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of many cancers, and the cutaneous toxicity profile associated with these agents has become prominent. In fact, dermatologic side effects have also been reported with other targeted agents, including both BRAF and mTOR inhibitors. During her presentation at the NCCN 19th Annual Conference, Dr. Barbara Burtness reviewed the array of skin complications caused by many targeted therapies, focusing on the more common culprits, the role of prophylactic versus reactive management strategies, the need to be attentive to potential infections, the importance of mastering local measures to improve quality of life and cosmetic issues, the therapeutic mainstays (oral and topical antibiotics and topical steroids), and the preference of improving these cutaneous complications over suspending anticancer treatment.