tbuckley/cabot-search huggingface dataset:
Efficacy of a therapeutic treatment using gas‐filled microbubble‐associated phospholipase A2 in a mouse model of honeybee venom allergy
Authors: B. Corthésy, A. Lassus, J. Terrettaz, F. Tranquart, G. Bioley
Journal: Allergy (2016)

Venom immunotherapy is efficient to desensitize people suffering from insect sting allergies. However, the numerous injections required over several years and important risks of severe side reactions complicate the widespread use of immunotherapy. In the search for novel approaches to blunt the overwhelming pro-allergic Th2 response, we evaluated the therapeutic efficacy of a treatment based on a denatured form of the major allergen, phospholipase A2, associated with microbubbles (PLA2denat -MB) in a mouse model of honeybee venom allergy.Antibodies measured by ELISA, T-cell responses assessed by CFSE-based proliferation assays and ELISA, and basophil degranulation were examined after PLA2denat -MB-based therapeutic treatment of sensitized mice. Mice were challenged with a lethal dose of PLA2 to evaluate protection against anaphylaxis.Therapeutic subcutaneous administration of two different PLA2denat -MB formulations, in contrast to PLA2denat alone, reduced allergic symptoms and protected all mice from anaphylaxis-mediated death after allergen challenge. At the functional level, the use of PLA2denat decreased IgE-mediated basophil degranulation as compared to the native form of the allergen. In comparison with PLA2denat alone, both PLA2denat -MB formulations decreased allergen-specific Th2 CD4 T-cell reactivity. At the mechanistic level, PLA2denat -MB containing 20% palmitic acid and PEG induced PLA2-specific IgA and increased Foxp3(+) Treg frequencies and TGF-β production, whereas the formulation bearing 80% palmitic acid triggered the production of IFN-γ, IgG2a, and IgG3.In contrast to conventional PLA2 subcutaneous immunotherapy, the therapeutic administration of PLA2-MB treatment to mice that already had established allergy to PLA2 protects all subsequently challenged animals.
A recent insertion of an alu element on the Y chromosome is a useful marker for human population studies.
Authors: M F Hammer
Journal: Molecular Biology and Evolution (1994)

A member of the Alu family of repeated DNA elements has been identified on the long arm of the human Y chromosome, Yq11. This element, referred to as the Y Alu polymorphic (YAP) element, is present at a specific site on the Y chromosome in some humans and is absent in others. Phylogenetic comparisons with other Alu sequences reveal that the YAP element is a member of the polymorphic subfamily-3 (PSF-3), a previously undefined subfamily of Alu elements. The evolutionary relationships of PSF-3 to other Alu subfamilies support the hypothesis that recently inserted elements result from multiple source genes. The frequency of the YAP element is described in 340 individuals from 14 populations, and the data are combined with those from other populations. There is both significant heterogeneity among populations and a clear pattern in the frequencies of the insertion: sub-Saharan Africans have the highest frequencies, followed by northern Africans, Europeans, Oceanians, and Asians. An interesting exception is the relatively high frequency of the YAP element in Japanese. The greatest genetic distance is observed between the African and non-African populations. The YAP is especially useful for studying human population history from the perspective of male lineages.
포스터 발표 : 소아 간이식 수여자에서 B형 간염 예방접종을 통한 B형 간염 예방
Authors: 서경석, 장성환, 이남준, 최석호, 이건욱
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 공여 장기의 부족으로 간이식에서 불가피하게 anti-HBc (＋) 공여자의 이식편을 이용하며, 수여자는 25-95%까지 B형 간염 감염의 위험성이 있기 때문에 HBIG 혹은 lamivudine으로 B형 간염을 예방한다. 이러한 B형 간염 예방법은 비용이 많이 들고, B형 간염 바이러스의 돌연변이 출현을 유도할 수 있다. 따라서 B형 간염 예방 접종이 효과적이라면 이러한 문제를 해결할 수 있다. 대상과 방법: 1999년 7월부터 2001년 10월까지 생체 간이식을 수여한 19명의 소아를 대상으로 하였다. 9명의 환자는 공여자가 anti-HBc (＋), 10명은 anti-HBc (－) 이었다. 면역억제제로 FK506과 steroid를 사용하였고, steroid는 평균 11.4±4.4개월 동안에 감량하여 중단하였다. B형 간염 예방 접종은 steroid 중단 후 HEPAVAX-GENE 혹은 EUVAX B를 이용하여 피하 주사하였다. B형 간염 항체 양성 반응은 HbsAb titer≥20 IU/L, 양성 반응군 중 저반응군은 최고 HBsAb titez＜1000 IU/L, 고반응군은 최고 HBsAb titer ≥ 1000 IU/L로 정하였다. 항체 추적 기간은 10.0±5.2 (3∼18) 개월이었다. 결과: B형 간염 예방 접종을 받은 19명 중 17명 (89.5%) 에서 B형 간염 항체 검사상 양성 반응을 보였다. anti-HBc (＋) 공여자를 가진 군(n＝9)은 7예 (77.8%)에서 양성이었고, 2예는 B형 간염 예방 접종에 반응하지 않았다. 양성 반응을 보인 7예 중, 저반응군이 4예, 고반응군이 3예이었다. 예방 접종에 반응하지 않았던 2예 중 1예에서 B형 간염이 발생하였다. anti-HBc (－) 공여자를 가진 군(n＝10)은 10예 모두에서 양성 반응을 보였고, 이 중 5예는 저반응군, 5예는 고반응군이었다. 결론: 간이식 소아 수여자, 특히 anti-HBc (＋) 공여자의 이식편을 이용하는 경우, B형 간염에 대한 예방 접종은 효과적인 B형 간염 예방법이라고 생각한다.
Incidence of Multiple Primary Cancers. IV. Cancers of the Female Breast and Genital Organs
Authors: D Schottenfeld, J Berg
Journal: JNCI Journal of the National Cancer Institute (1971)

The incidence of multiple primary cancers of other organs or tissues was studied in patients with carcinomas of the breast (9,792), ovary (921), endometrium (843), and cervix uteri, vagina, or vulva (2,529). The index patients were treated during 1949–62 at the Memorial Sloan-Kettering Cancer Center, and their observed frequency of new primary cancers was compared with the age- and site-specific incidence rates reported by the population-based central registry maintained for New York State (excluding New York City). The incidence of metachronous primary carcinomas in the opposite breast was 6.1/year/1,000 patients, or 4.5 times expectation; in the patients with carcinoma of the breast, the incidence of multiple primary carcinomas of the ovary was 0.6/year/1,000 patients, or twice the normal risk, but one-tenth the risk for incurring a primary carcinoma in the opposite breast. The risk for incurring a metachronous primary carcinoma of the breast by a patient with a previous ovarian carcinoma was 3–4 times the normal risk. In patients with endometrial carcinoma, the risk of a subsequent breast carcinoma was 1.25–2.0 times the normal risk. The demonstration of a positive association of multiple primary carcinomas of the breast, ovary, and endometrium suggests demographic characteristics and etiologic factors common to these diseases. At least 3 of the 5 observed multiple, primary, soft-tissue sarcomas developed as sequelae of previous breast cancers—1 arising in irradiated tissue and 2 in a lymphedematous upper extremity. We could not conclude whether the mutual increases in the incidence of carcinomas of the breast and thyroid were biologically related or were indicative of common etiologic factors.
Intravenous 6-thioguanine or cisplatin, fluorouracil and leucovorin for advanced non-small cell lung cancer: A randomized phase II study of the cancer and leukemia group B
Authors: E.F. Vokes, A.P. Lyss, J.E. Herndon, B. Cooper, M.C. Perry, V. Vinciguerra, K. Mason-Coughlin, M.R. Green
Journal: Annals of Oncology (1992)
Transport, Phosphorylation, and Toxicity of a Tricyclic Nucleoside in Cultured Novikoff Rat Hepatoma Cells and Other Cell Lines and Release of Its Monophosphate by the Cells 2
Authors: Peter G. W. Plagemann
Journal: JNCI Journal of the National Cancer Institute (1976)

1,4,5,6,8-Pentaazaacenaphthylene-3-amino-1 ,5-dihydro-5-methyl-(5-14C)-1-β-D-ribofuranosyl (NSC-154020), a tricyclic 7-deazapurine nucleoside (TCN), was rapidly incorporated into the acid-soluble pool by cultured Novikoff rat hepatoma cells, mouse L-cells, HeLa cells, and HEp-2 cells, but little incorporation into nucleic acids occurred. More than 90% of the intracellular radioactivity was associated with the monophosphate (MP) of the TCN. Initial rates of incorporation of the analogue as a function of substrate concentration followed normal Michaelis-Menten kinetics. Comparison of the kinetic constants for the uptake of adenosine and the TCN and of the inhibition of their uptake by each other suggests that both were transported by the same system (Michaelis constant≈6–10 µM) and with about the same efficiency. The TCN was also phosphorylated in a cellfree extract containing adenosine kinase activity at about the same rate as was adenosine, but no further phosphorylation of the analogue MP occurred. No significant deamination or degradation of the adenosine analogue to its base and ribose-1-phosphate was observed. TCN inhibited the replication of all four types of cells propagated in suspension culture; however, Novikoff cells were several times more sensitive than were the other three cell types, despite the finding that the TCN-MP, probably the main toxic principle, accumulated to about the same concentration in cells of all four lines. Complete inhibition of replication of Novikoff cells and cell death occurred at concentrations as low as 15 µM TCN. At these concentrations, TCN, within 2 hours of its addition, completely inhibited the incorporation of [14C]formate into nucleotides and nucleic acids of Novikoff cells. An inhibition of the de novo synthesis of purine and pyrimidines, however, was not the only toxic effect of the TCN since high concentrations of uridine, adenine, guanine, and hypoxanthine, either alone or combined, failed to prevent the inhibition of cell replication by TCN. Also, between 1 and 3 hours of treatment, 70–80% of the Novikoff cells fragmented into four to eight vesicles per cell. These fragments were impermeable to trypan blue, still exhibited some metabolic activity such as the phosphorylation of AMP and TCN, but failed to replicate when the drug was removed. No similar fragmentation was observed with the other cell lines. Novikoff and L-cells rapidly released TCN-MP into the culture fluid. After 4 hours of incubation, 70–100% of the total radioactivity in the medium was associated with the MP. Only a little TCN-MP was released from HeLa and HEp-2 cells. A TCN-resistant mutant of Novikoff cells failed to phosphorylate the analogue and was deficient in adenosine kinase.
Combination chemotherapy of metastatic melanoma.
Authors: D Berd, M J Mastrangelo
Journal: Journal of Clinical Oncology (1995)

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.1995.13.3.796 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7884439 Combination chemotherapy of metastatic melanoma. D BerdxD BerdSearch for articles by this author , M J MastrangeloxM J MastrangeloSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.3.796 PDF "Combination chemotherapy of metastatic melanoma.." Journal of Clinical Oncology, 13(3), pp. 796–797© 1995 by American Society of Clinical Oncology
Evaluating a Pay-for-Performance Program for Medicaid Children in an Accountable Care Organization
Authors: Sean Gleeson, Kelly Kelleher, William Gardner
Journal: JAMA Pediatrics (2016)

Pay for performance (P4P) is a mechanism by which purchasers of health care offer greater financial rewards to physicians for improving processes or outcomes of care. To our knowledge, P4P has not been studied within the context of a pediatric accountable care organization (ACO).To determine whether P4P promotes pediatric performance improvement in primary care physicians.This retrospective cohort study was conducted from January 1, 2010, to December 31, 2013. A differences-in-differences design was used to test whether P4P improved physician performance in an ACO serving Medicaid children. Data were obtained from 2966 physicians and 323,812 patients. Three groups of physicians were identified: (1) community physicians who received the P4P incentives, (2) nonincentivized community physicians, and (3) nonincentivized physicians employed at a hospital.Pay for performance.Healthcare Effectiveness Data Information Set measure rates for preventive care, chronic care, and acute care primary care services. We examined 21 quality measures, 14 of which were subject to P4P incentives.There were 203 incentivized physicians, 2590 nonincentivized physicians, and 173 nonincentivized hospital physicians. Among them, the incentivized community physicians had greater improvements in performance than the nonincentivized community physicians on 2 of 2 well visits (largest difference was for adolescent well care: odds ratio, 1.05; 99.88% CI, 1.02-1.08), 3 of 10 immunization-incentivized measures (largest difference was for inactivated polio vaccine: odds ratio, 1.14; 99.88% CI, 1.07-1.21), and 2 nonincentivized measures (largest difference was for rotavirus: odds ratio, 1.11; 99.88% CI, 1.04-1.18). The employed physician group at the hospital had greater improvements in performance than the incentivized community physicians on 8 of 14 incentivized measures and 1 of 7 nonincentivized measures (largest difference was for hepatitis A vaccine: odds ratio, 0.34; 99.88% CI, 0.31-0.37).Pay for performance resulted in modest changes in physician performance in a pediatric ACO, but other interventions at the disposal of the ACO may have been even more effective. Further research is required to find methods to enhance quality improvements across large distributed pediatric health systems.
Specificity and sensitivity of forced oscillation measurement during methacholine challenge testing used for diagnosis of asthma
Authors: Zhang Jun, Pan Na, Huang Kewu, Tjeu Souren
Journal: European Respiratory Journal (2011)

This study was designed to investigate specificity and sensitivity of respiratory resistance (Rrs) during methacholine challenge testing (MCh) compared to FEV1 change.

214 subjects (82 male, 132 female; 14 - 77 y) were recruited for MCh. All had a FEV1 ≥70% pred. Asthma treatment mediction was withdrawn.

Baseline forced spirometry (ATS/ERS 2005) data were collected (MasterScreen PFT, CareFusion, Hoechberg, Germany) prior to MCh. Airway hyper responsiveness (AHR) was measured with Astograph J-21 (Chest, Tokyo, Japan). Respiratory resistance (Rrs) is measured continuously through forced oscillation technique (FOT, 3 Hz) during stepwise 1 min. inhalations of doubling MCh (0.049 - 25 mg/mL), until Rrs doubled.

AHR is calculated as cumulative dose of MCh inducing doubling Rrs (Dmin). Dmin = 1 min inhalation MCh at 1.0 mg/mL. Subjects without doubling Rrs are counted as negative Astograph responders.

FEV1 measured after MCh is compared to baseline (FEV1ch). FEV1ch ≥20% and <20% is correlated with Dmin:

![Figure][1] 



1. Dmin ≤3 shows a specificity of 82.2%, with a sensitivity of 60.8%.

2. Dmin ≤10 and Dmin >0.049 ranges showed both good sensitivity but poor specificity.

3. Dmin in relation to FEV1ch had a weak negative correlation: r=0.071.

Cut off point for Dmin ≤3 U for Astograph MCh is a good standard for the clinical diagnosis of asthma with acceptable specificity and sensitivity to detect AHR.

 [1]: pending:yes
Prognostic risk group classification for patients (pts.) with platinum-refractory metastatic urothelial cancer (UC) treated with second-line chemotherapy
Authors: D. J. Vaughn, W. Hwang, S. Munier, C. George
Journal: Journal of Clinical Oncology (2009)

5078 Background: Second-line chemotherapy in pts. with platinum-refractory metastatic UC is associated with low objective response rates and short progression-free and overall survival. Prognostic risk groups in this setting have not been reported. Methods: We studied 151 pts. with platinum-refractory metastatic UC treated with second-line vinflunine (VFL) (Vaughn, GU Cancer Symposium. 2008). Using progression at 6 months as the primary endpoint, baseline patient characteristics were examined in univariate and multivariate analyses. Multivariate logistic regression was used to identify independent predictors of progression at 6 months, and the variable selection result was validated by nonparametric bootstrap. Risk scores were generated from summing the relative importance of the factors identified on multivariate analysis. Patients were classified into risk groups and compared. Results: Of the 151 pts., 80% were male, 54% were aged &gt; 65 years, and 68% had Karnofsky performance status (KPS) &gt; 90%. 115 pts. (76%) progressed or died by 6 months after initiating VFL. The factors associated with an increased odds ratio (OR) for disease progression at 6 months were presence of visceral metastases (OR 8.08; p &lt; 0.001; 2 points), KPS &lt; 90% (OR 6.63; p = 0.002; 2 points), and age &lt; 65 years (OR 3.53; p = 0.008; 1 point). Only 41% of the low-risk group (score 0–1) progressed by 6 months compared to 74% of the intermediate-risk group (score 2) and 91% of the high-risk group (score 3–5). Compared to the low-risk group, the intermediate-risk group had OR for disease progression at 6 months of 4.01 (p = 0.006) and the high-risk group had OR of 15.5 (p &lt; 0.001). Conclusions: We identified risk factors and developed a scoring system that classifies pts. with platinum-refractory UC treated with second-line chemotherapy into risk groups based upon probability of disease progression at 6 months. Similar to the first-line setting, the presence of visceral metastases and decreased KPS predict a worse prognosis. This system should be validated in other independent populations. [Table: see text]
RAG-mediated DNA double-strand breaks activate a cell type–specific checkpoint to inhibit pre–B cell receptor signals
Authors: Jeffrey J. Bednarski, Ruchi Pandey, Emily Schulte, Lynn S. White, Bo-Ruei Chen, Gabriel J. Sandoval, Masako Kohyama, Malay Haldar, Andrew Nickless, Amanda Trott, Genhong Cheng, Kenneth M. Murphy, Craig H. Bassing, Jacqueline E. Payton, Barry P. Sleckman
Journal: The Journal of Experimental Medicine (2016)

DNA double-strand breaks (DSBs) activate a canonical DNA damage response, including highly conserved cell cycle checkpoint pathways that prevent cells with DSBs from progressing through the cell cycle. In developing B cells, pre–B cell receptor (pre–BCR) signals initiate immunoglobulin light (Igl) chain gene assembly, leading to RAG-mediated DNA DSBs. The pre–BCR also promotes cell cycle entry, which could cause aberrant DSB repair and genome instability in pre–B cells. Here, we show that RAG DSBs inhibit pre–BCR signals through the ATM- and NF-κB2–dependent induction of SPIC, a hematopoietic-specific transcriptional repressor. SPIC inhibits expression of the SYK tyrosine kinase and BLNK adaptor, resulting in suppression of pre–BCR signaling. This regulatory circuit prevents the pre–BCR from inducing additional Igl chain gene rearrangements and driving pre–B cells with RAG DSBs into cycle. We propose that pre–B cells toggle between pre–BCR signals and a RAG DSB-dependent checkpoint to maintain genome stability while iteratively assembling Igl chain genes.
Electron Microscopic Analysis of Lymph Node Cellular Activity in Hodgkin's Disease&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J H Frenster, M M Papalian, M A Masek, J A Frenster
Journal: JNCI Journal of the National Cancer Institute (1979)

Five hundred and two cells, selected at random within the pretreatment-involved lymph nodes of patients with the nodular sclerosis type of Hodgkin's disease, were analyzed by electron microscopy for in vivo subcellular activity and intercellular interaction. Subpopulations of neoplastic cells and of lymphocytes were recognized by ultrastructural criteria. Neoplastic cells displayed definite sequences of cell maturation, whereas lymphocytes displayed definite sequences of cell activation. Active lymphocytes were most often found apposed to the more active of the neoplastic cells, and the nuclei of such apposed lymphocytes displayed a progressive preferential asymmetry of distribution of active DNA templates into that half of the lymphocyte nucleus closest to the neoplastic cell. Such close apposition of active polysomal lymphocytes to neoplastic cells may correlate with increased patient survival in Hodgkin's disease.
David Oliver: Jeremy Hunt was wrong to blame the “irresponsible BMA” for his own mistakes
Authors: David Oliver
Journal: BMJ (2016)

On Sunday, Jeremy Hunt gave an unconvincing appearance on the BBC’s Andrew Marr Show . With a further strike by junior doctors planned for Wednesday 10 February, the host doggedly questioned the health secretary.

Marr challenged Hunt’s repeated claims that excess deaths associated with weekend admission were preventable and that medical understaffing was the clear cause. Even when confronted with a critique of his simplistic stance by NHS England’s medical director, Bruce Keogh, or by The BMJ ’s editor, Fiona Godlee, Hunt wouldn’t budge, saying, “She’s wrong.” …
Ligands of EGFR and the insulin-like growth factor family as serum biomarkers for response to EGFR-inhibitors in patients with advanced NSCLC
Authors: M. A. Vollebergh, I. Kappers, M. M. van den Heuvel, J. C. Buning-Kager, C. M. Korse, J. M. Bonfrer, M. Hauptmann, K. E. de Visser, H. M. Klomp, S. C. Linn
Journal: Journal of Clinical Oncology (2009)

8100 Background: To determine whether concentrations of transforming growth factor α (TGFa), amphiregulin (ARG), both ligands of the epidermal growth factor receptor (EGFR), insulin-like growth factor 1(IGF1) or IGF-binding protein 3 (IGFBP3) measured in serum of advanced non-small cell lung cancer (NSCLC) patients are predictive of EGFR-inhibitors (EGFRi) response. Methods: We assessed serum levels of marker candidates using ELISA (TGA and ARG) and chemiluminescent (IGF1 and IGFBP3) assays. Sixty-one advanced NSCLC patients treated with EGFRi (gefitinib or erlotinib, &gt;14 days) were matched for gender, age and histology to a control group of 63 EGFRi-untreated advanced NSCLC patients. We dichotomized marker levels at the 20th, 50th or 80th percentile and evaluated whether the effect of EGFRi treatment on overall survival (OS) differed by marker level based on multivariate proportional hazards regression with an interaction term. We adjusted for gender, smoking, stage, histology and prior chemotherapy. Results: While 6-months OS did not appreciably differ between 50 EGFRi treated and 50 control patients whose TGFa levels were below the 80th percentile (39% vs. 54%, multivariate HR 0.78, 95% CI 0.45–1.34, p=0.359), it was substantially worse for 11 EGFRi treated patients compared with 13 control patients whose TGFa levels were high (9% vs. 42%, multivariate HR 2.38, 95% CI 0.87–6.52, p=0.092). The difference of EGFRi effects by TGFa level was statistically significant (interaction p=0.033). There was no evidence that EGFRi treatment effects differed by levels of ARG, IGF1 and IGFBP3. Patients with high concentrations of IGFBP3 (above the median) had significantly longer OS than patients with low IGFBP3 concentrations, independent of treatment (HR 0.46, 95% CI 0.29–0.73, p=0.001). Conclusions: This is the first study in NSCLC patients of Caucasian origin in which serum concentrations of TGFa are predictive for EGFR-inhibitor response, suggesting this is a potential predictive marker for EGFRi treatment. Furthermore, we coincidentally found that levels of IGFBP3 are predictive for overall survival, indicating this might be a prognostic factor in advanced NSCLC patients. [Table: see text]