tbuckley/cabot-search huggingface dataset:
Margaret McCartney: Disrespecting confidentiality isn't the answer to FGM
Authors: M. McCartney
Journal: BMJ (2015)

On 31 October new provisions of the Serious Crime Act came into force in England and Wales. This new law compels healthcare professionals, social workers, and teachers to report to the police any cases of female genital mutilation (FGM) in girls or women who appear to have had the procedure before age 18.1

The law is one of several interventions that the government has offered to try to reduce such abuse. These include guidance on commissioning new services for women, money for international development, and the ability for courts to charge guardians for failing to protect girls from FGM. And doctors must now take part in the Department of Health’s “enhanced data collection” on FGM. This means that we must submit information that identifies patients, …
Childhood Leukemia and Maternal Infectious Diseases During Pregnancy2
Authors: Mary G. McCrea Curnen, Andre A. O. Varma, Barbara W. Christine, Livia R. Turgeon
Journal: JNCI Journal of the National Cancer Institute (1974)

A retrospective correlation study was conducted to test the hypothesis that children born of women exposed to influenza, German measles, measles, mumps, whooping cough, chickenpox, or poliomyelitis during pregnancy have a higher risk of developing leukemia. The Connecticut Tumor Registry has records of 431 children born in Connecticut who developed leukemia during their first 10 years of life. The 10-year leukemia rates of the 27 annual birth cohorts, from 1935 through 1961, demonstrated a nonsignificant upward trend. Likewise, there was no significant seasonal variation by month of birth. The monthly incidence in Connecticut for the seven infectious diseases was used to define epidemic and nonepidemic months. Ten-year rates for lymphocytic, myelocytic, and other types of leukemia were computed for each monthly birth cohort. Birth cohortswho lived through highprevalence periods of infectious diseasesduring their first, second, or third trimester of gestation were compared to the remaining control cohorts who were less likely to have been exposed to these infections. The 2 risk groups had no significant differences in leukemia rates.
Differential expression of human telomerase reverse transcriptase β-site remaining alternative splicing variants (hTERT β+ ASV) in gastric carcinogenesis
Authors: X. Geng
Journal: Journal of Clinical Oncology (2009)

e15641 Background: To investigate the changes of hTERT alternative splicing variants pattern in gastric cancer, precancerous lesions and normal gastric mucosa tissue. Methods: Three alternative splicing sites (α, β, γ) were selected and designed PCR primer. The expression of 8 hTERT alternative splicing variants (ASVs) in gastric cancer, precancerous lesions and normal gastric mucosa were detected by Semi-nested RT-PCR. The expression of β-site remaining ASV (β + ASV) in specimens of gastric cancer and specimens of precancerous lesions was detected by SYBER Green real-time PCR. Telomerase enzyme activity was evaluated associated with the different hTERT ASVs. Results: The positive rate of active full-length (α + β + γ + ) ASV was significantly higher in gastric cancer than in precancerous lesions and normal mucosa (94.7% vs. 40.0% and 0, P&lt;0.05). The positive rates of other ASVs were not different among the 3 groups(P&gt;0.05). The positive rates of β + ASVs (including α + β + γ + ASV, α-deletion ASV, γ-deletion ASV, αγ-deletion ASV) were 11.1% in normal mucosa,40.0% in precancerous lesions and 94.7% in gastric cancer (P&lt;0.05). SYBR Green real-time RT-PCR showed that the expression level of β + ASV was 6.99 times higher in gastric cancer than in precancerous lesions. Further, increased telomerase enzyme activity was only associated with expression of the full-length hTERT isoform. Conclusions: hTERT alternative splicing pattern is different during gastric carcinogenesis. β + ASV was widely expressed in gastric carcinogenesis and may provide some information for diagnosis of gastric cancer or precancerous lesions. The gene expression patterns of hTERT alternative splicing variants may provide some useful information for diagnosis of gastric cancer and precancerous lesions. No significant financial relationships to disclose.
Mechanisms of the Inhibitory Action of p -Hydroxyacetanilide on Carcinogenesis by N -2-Fluorenylacetamide or N -Hydroxy- N -2-fluorenylacetamide 2
Authors: Letitia C. Mohan, Preston H. Grantham, Elizabeth K. Weisburger, John H. Weisburger, Jane B. Idoine
Journal: JNCI Journal of the National Cancer Institute (1976)

The metabolism of N-2-fluorenylacetamide (FAA) and N-hydroxy-2-fluorenylacetamide (N-OH-FAA) was studied in groups of rats that had been prefed the protective agent p-hydroxyacetanilide (p-OH-AA) alone or in combination with each of the carcinogens for 4 weeks. Compared with controls, pretreatment increased the percentage of metabolites in the urine, chiefly as glucuronic acid conjugates, whereas the fecal excretion of FAA metabolites was lowered. The levels of total and tissue-bound material in the liver and blood plasma were also lower after prefeeding. Liver aryl hydrocarbon hydroxylase and liver deacetylase were not affected by p-OH-AA pretreatment. However, liver glucuronyl transferase was increased by either prefeeding with p-OH-AA and/or the carcinogen. The protective effect of p-OH-AA against liver tumor induction with FAA or N-OH-FAA may in part result from a combination of the decreased binding of carcinogen to hepatic cellular macromolecules and the increased excretion as the glucuronide conjugates.
Small cell bronchogenic carcinoma: factors associated with pneumonia during chemotherapy.
Authors: C L Dixon, M Valdivieso, T Umsawasdi, G Dubois, D Patton, T Chen, M K Ali, G P Bodey
Journal: Journal of Clinical Oncology (1984)

Sixty-five patients with small cell bronchogenic carcinoma were treated with intensive induction chemotherapy and supportive treatment. The clinical course of 43 patients who had pretreatment spirometry and arterial blood gases was studied. Thirteen patients developed pneumonia. Moderate hypoxemia, advanced age, and a low forced expiratory flow 25%-75% were associated with the development of pneumonia. Endobronchial obstruction and neutropenia, other factors associated with infection in cancer patients, appeared to be less important in this patient population.
Correlation between quadriceps strength and five exercise tests in subjects with chronic obstructive pulmonary disease (COPD)
Authors: Theresa C. Harvey-Dunstan, J. Radhakrishnan, L. Houchen-Wolloff, R.M. Tal-Singer, M.I. Polkey, M.D. Morgan, M.C. Steiner, S.J. Singh
Journal: European Respiratory Journal (2014)

Introduction 

There is interest to understand the correlation between quadriceps strength and exercise performance in subjects with COPD when considering the contribution of peripheral muscle weakness to exercise limitation.

Aims and Objectives 

We wished to compare the relationship between quadriceps strength and different exercise test protocols.

Methods 

Subjects with symptomatic COPD (MRC>3, GOLD Stage >2) were recruited ([ISRCTN 64759523][1]). Subjects performed two symptom-limited tests for the Incremental Shuttle Walk Test (ISWT), Endurance Shuttle Walk Test (ESWT), incremental and constant work rate cardiopulmonary cycle tests (ICE & CWR), Six-Minute Walk Test (6MWT) and Quadriceps Maximal Voluntary Contraction (QMVC). Baseline data were analysed using bivariate correlation.

Results 

20 subjects (85% male, mean[SD] age 64[6.7]years, FEV1 %predicted 48[16], FEV1/FVC 44[12.2], Body Mass Index 29.3[7.1], median MRC of 3, were studied. There was a significant correlation to QMVC with both the ESWT ( p =0.004, r =0.65; Figure1)

![Figure][2] 



and CWR loaded duration ( p =0.03, r =0.51). There were no significant correlations between ICE loaded duration or peak oxygen uptake ( p =0.88 and p =0.05 respectively), 6MWT ( p =0.053) or ISWT ( p =0.228).

Conclusions 

There is a significant positive correlation in quadriceps strength to the endurance tests that is not observed in the incremental or 6MWT protocols.

 [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN64759523
 [2]: pending:yes
Climate change, conflict and health
Authors: Devin C Bowles, Colin D Butler, Neil Morisetti
Journal: Journal of the Royal Society of Medicine (2015)

Summary Future climate change is predicted to diminish essential natural resource availability in many regions and perhaps globally. The resulting scarcity of water, food and livelihoods could lead to increasingly desperate populations that challenge governments, enhancing the risk of intra- and interstate conflict. Defence establishments and some political scientists view climate change as a potential threat to peace. While the medical literature increasingly recognises climate change as a fundamental health risk, the dimension of climate change-associated conflict has so far received little attention, despite its profound health implications. Many analysts link climate change with a heightened risk of conflict via causal pathways which involve diminishing or changing resource availability. Plausible consequences include: increased frequency of civil conflict in developing countries; terrorism, asymmetric warfare, state failure; and major regional conflicts. The medical understanding of these threats is inadequate, given the scale of health implications. The medical and public health communities have often been reluctant to interpret conflict as a health issue. However, at times, medical workers have proven powerful and effective peace advocates, most notably with regard to nuclear disarmament. The public is more motivated to mitigate climate change when it is framed as a health issue. Improved medical understanding of the association between climate change and conflict could strengthen mitigation efforts and increase cooperation to cope with the climate change that is now inevitable.
High Levels of Dietary Fat: Alteration of Hepatic Promutagen Activation in the Rat&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A J Alldrick, I R Rowland, B G Lake, J Flynn
Journal: JNCI Journal of the National Cancer Institute (1987)

Male Ola:Sprague-Dawley rats were fed diets containing either low or high levels of fats. After being fed these diets for 4 weeks, the rats were killed and individual hepatic postmito-chondrial (S9) fractions were prepared. The ability of these fractions to convert the heterocyclic aromatic amines (HAAs)—2-amino-3-methylimidazo[4,5-f]quinoline;2-amino-3,4-dimethylimidazo[4,5-f] quinoline; and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (compounds produced during the cooking of proteinaceous food) —to bacterial mutagens was studied, with the use of Salmonella typhimurium TA98 as indicator. Fractions from rats fed high-fat diets exhibited a greater ability to activate the HAAs than did those from rats fed the low-fat diet. The magnitude of the increase was dependent on the type of fat used.
Understanding Spatial Genome Organization: Methods and Insights
Authors: Vijay Ramani, Jay Shendure, Zhijun Duan
Journal: Genomics Proteomics & Bioinformatics (2016)

Abstract The manner by which eukaryotic genomes are packaged into nuclei while maintaining crucial nuclear functions remains one of the fundamental mysteries in biology. Over the last ten years, we have witnessed rapid advances in both microscopic and nucleic acid-based approaches to map genome architecture, and the application of these approaches to the dissection of higher-order chromosomal structures has yielded much new information. It is becoming increasingly clear, for example, that interphase chromosomes form stable, multilevel hierarchical structures. Among them, self-associating domains like so-called topologically associating domains (TADs) appear to be building blocks for large-scale genomic organization. This review describes features of these broadly-defined hierarchical structures, insights into the mechanisms underlying their formation, our current understanding of how interactions in the nuclear space are linked to gene regulation, and important future directions for the field.
Adherence of neutrophils to human peritoneal mesothelial cells
Authors: T Liberek, N Topley, W Luttmann, J D Williams
Journal: Journal of the American Society of Nephrology (1996)

Peritonitis is accompanied by a massive influx of polymorphonuclear leukocytes (PMN) into the peritoneal cavity, little is known, however, about the process of neutrophil transmigration across the peritoneal membrane. The study presented here, therefore, investigates the adherence of human PMN to human peritoneal mesothelial cell monolayers and examines the importance of intercellular adhesion molecule-1 (ICAM-1) in the process. Human peritoneal mesothelial cells (HPMC) constitutively expressed ICAM-1 protein and mRNA. Stimulation with IL-1 beta or TNF alpha resulted in time- and dose-dependent upregulation of ICAM-1 mRNA transcript and increased cell-surface immunoreactive protein expression. Peak surface expression of ICAM-1 occurred between 12 and 24 h after cytokine stimulation when the level of expression was increased by on average threefold above control. The adherence of PMN to HPMC after stimulation with either IL-1 beta or TNF alpha was both dose- and time-dependent. Peaks of PMN binding to HPMC occurred at 2 and 12 h after stimulation. After 12 h, the number of PMN binding to HPMC increased from 71.3 +/- 12.5 in control cells to 180 +/- 36.5 and 125 +/- 23.6 (x 10(3) PMN), after IL-1 beta (100 pg/mL) and TNF alpha (1000 pg/mL), respectively (z = 2.52 and 2.38, N = 6, P < 0.02 versus control for both). The roles of HPMC ICAM-1 and the PMN counter receptor LFA-1 (CD11a/CD18) in the adherence of PMN to HPMC were confirmed by using anti-CAM Fab2' fragments, and anti-integrin antibodies, all of which significantly reduced the adherence of PMN to both control and cytokine-treated HPMC. These data suggest that ICAM-1 expression by HPMC may be one mechanism by which neutrophils adhere to the mesothelium during their transmigration into the inflamed peritoneal cavity.
Ectopic expression and oncogenesis of Mer tyrosine kinase in E2A-PBX1 expressing B-cell acute lymphoblastic leukemia
Authors: K. K. Sawczyn, C. C. Porter, J. DeGregori, D. K. Graham
Journal: Journal of Clinical Oncology (2007)

9561 Background: Mer is a receptor tyrosine kinase that belongs to a tyrosine kinase subfamily including Axl and Tyro-3. Mer is expressed in monocytes/macrophages, dendritic cells and platelets, but not in lymphocytes or thymocytes. However, prior DNA array studies have suggested an aberrant expression of Mer in B-cell ALL (B-ALL) expressing the E2A-PBX1 fusion protein associated with t(1;19). We investigated the potential oncogenic role of Mer in E2A-PBX1 expressing B-ALL. Methods: Mer expression was evaluated in diagnostic bone marrow samples in pediatric patients with E2A-PBX1 B-ALL (EP+) and non-E2A-PBX1 B-ALL (EP-) by quantitative RT-PCR, Western blot, and flow cytometry. Using the REH B-ALL cell line with a zinc-inducible E2A-PBX1, induction of Mer expression was evaluated by Western blot. A mouse model was developed by retroviral infection of E2A-PBX1 fusion protein into Mer wild-type (WT), transgenic (TG), and knock-out (KO) mouse bone marrow cells followed by transplantation of these cells into sublethally irradiated WT recipients. Evaluation was done for E2A-PBX1 expression in peripheral blood and bone marrow cells were analyzed by flow cytometry for the development of leukemia. Results: Thirteen EP+ and 14 EP- patient samples were processed. All 13 EP+ samples had Mer protein expression by flow cytometry and/or Western blot. Conversely, 1/14 EP- samples was weakly positive for Mer protein expression by flow cytometry and Western blot. Quantitative RT-PCR was performed on 4 EP+ samples and 6 EP- samples. There was a 7–324 fold increase in Mer expression in EP+ samples when compared to the mean Mer expression of EP- samples. In our mouse transplant model, the median time to develop leukemia from Mer TG/E2A-PBX1 and Mer KO/E2A-PBX1 mice was 92 days and 117 days, respectively, with one KO mouse still surviving disease free at 140 days post-transplant. Conclusions: Mer is ectopically expressed in E2A-PBX1 expressing B-ALL. Mer TG/E2A-PBX1 mice develop leukemia sooner than Mer KO/E2A-PBX1 mice, suggesting cooperativity between the oncogenes. Mer may be an attractive therapeutic target for patients with E2A-PBX1 expressing ALL. No significant financial relationships to disclose.
Late-breaking abstract: A relative plasma elafin deficiency in children with cystic fibrosis (CF) is associated with pulmonary disease
Authors: Alex Yacob, Jacquelyn Zirbes, Colleen Dunn, Roham Zamanian, Richard Bland, Marlene Rabinovitch, Mark Nicolls, Carlos Milla
Journal: European Respiratory Journal (2014)

Elafin is an inducible potent and selective serine elastase inhibitor with additional anti-inflammatory and anti-microbial properties. We hypothesized that a relative deficiency in circulating Elafin levels in relation to elastase, reflecting an imbalance in anti-elastolytic capacity, will be associated with the severity of lung disease in children with CF. Plasma samples were obtained from 35 children with CF free from exacerbation and compared to a group of 82 healthy individuals. Samples were assayed in duplicate by ELISA for Elafin and elastase concentrations, and the ratio of circulating elastase to Elafin (e:E) was calculated for each subject. Lung disease severity was assessed by forced expiratory volume in 1 second (FEV1). CF patients (17F, 18M) had a mean (SD) age of 12.8 (4) years, a FEV1 Z-score of -1.64 (1.7) and a Body Mass Index (BMI) z-score of 0.12 (0.9); 22% were infected with Pseudomonas, 75% with S. aureus and 8% were co-infected. Elafin levels were significantly lower in the CF patients compared to controls (17.2 vs. 75.4 ng/mL, p<0.001), whereas elastase levels were comparable (80.4 vs. 94.5 ng/mL, p=0.3). Mean e:E ratio in the CF children was 5.9 (3.1), which was significantly higher than the control group at 2.3 (1.8), (p<0.001). FEV1 Z-scores were not correlated with Elafin levels (p=0.4) but inversely correlated with elastase and e:E ratio (p <0.05 for both). Infection status, age or gender did not modify these associations. We conclude that in children with CF a relative deficiency in Elafin as reflected in a high e:E ratio is associated with the severity of lung disease. Elafin replenishment therapy could be a potential effective intervention.
Single-agent maintenance therapy for advanced-stage non-small cell lung cancer: A meta-analysis.
Authors: M. Behera, T. K. Owonikoko, Z. Chen, S. A. Kono, F. R. Khuri, C. P. Belani, S. S. Ramalingam
Journal: Journal of Clinical Oncology (2011)

7553 Background: Maintenance therapy is a new treatment paradigm following first-line combination chemotherapy for patients with advanced non-small cell lung cancer (NSCLC). We conducted a meta-analysis of randomized studies that evaluated single agent maintenance therapy. Methods: We conducted an electronic literature search of public databases (MEDLINE, EMBASE, Cochrane library) and manual search of conference proceedings of ASCO and World Conference on Lung Cancer using relevant terms. Eligible studies were identified and reviewed independently by two co-authors. Randomized trials that reported the effect of single agent maintenance therapy on survival in NSCLC patients were included. A formal meta-analysis was conducted using Comprehensive Meta Analysis software (Version 2.0). The outcome data were pooled and reported as hazard ratio (HR). The primary outcome of interest was overall survival (OS) and secondary outcome was progression free survival (PFS). Results: We reviewed 210 published reports. Ten were eligible for inclusion (3 meeting abstracts, 7 journal publications) with a total of 3451 patients (maintenance arm/control arm- 1942/1509, median age 62.5 years, male -72 %). The OS (HR 0.87, 95% CI 0.82 to 0.94, P=0.0003) and PFS (HR 0.84, 95% CI 0.80 to 0.88, P< 0.0001) were superior with maintenance therapy. ‘Switch’ maintenance therapy was associated with significant OS and PFS improvement (HR 0.86 CI 0.80 to 0.93, P= 0.00046; PFS HR 0.71 CI 0.66 to 0.77, P<0.0001). Despite a modest improvement in PFS (HR 0.92, CI 0.87 to 0.98, P= 0.007), “continuation” maintenance therapy was not associated with survival benefit (HR 0.92, CI 0.77 to 1.08, P=0.33). Improvements in OS and PFS were observed with EGFR-targeted agents (HR 0.86, CI 0.78 to 0.95, P= 0.006; HR 0.76 CI 0.70 to 0.83, P<0.0001) and cytotoxic agents (HR 0.88, CI 0.80 to 0.97, P=0.018; HR 0.87, CI 0.82 to 0.91, P<0.0001). Conclusions: Single agent maintenance therapy improves overall survival, though statistical significance was only noted with ‘switch’ maintenance. Survival benefit was observed for chemotherapy and EGFR-targeted therapy. Supported by NIH P01 CA116676. TKO, FRK and SSR are Distinguished Cancer Scholars of the Georgia Cancer Coalition.
Repeated anti-CEA-radioimmunotherapy (RAIT) with <sup>131</sup>iodine-labetuzumab after resection of colorectal liver metastases (CLM): Long-term results of a prospective phase II study.
Authors: Kia Homayounfar, Carsten O. Sahlmann, Martin Niessner, Johannes Meller, Lena-Christin Conradi, Jerzy Dyczkowski, B. Michael Ghadimi, Heinz Becker, David M. Goldenberg, Torsten Liersch
Journal: Journal of Clinical Oncology (2015)

719 Background: Previously, single anti-CEA-radioimmunotherapy (RAIT) with 131 iodine(I)-labetuzumab after complete (R0) resection of CEA-positive CLM was well tolerated and improved overall survival (OS) compared to a control group without RAIT. In this phase II study, we examined safety, feasibility, and long-term efficacy of repeated RAIT in the same setting. Methods: After R0-resection of CEA-positive CLM, 63 pts (42 m, 21 f; median age, 64.5 yrs) with synchronous (n=33) or metachronous (n=30) CLM received RAIT with 40-50 mCi/m 2 per dose. 45 pts were intermediate/high risk for early metastatic relapse according to the Fong score. Restaging with CT/MRI and FDG-PET was performed prior to each RAIT. Pts with persistent elevated serum CEA-levels or inconclusive lesions during post-operative restaging received RAIT, but were classified as “non-adjuvant.” Toxicity was classified according to NCI-CTC v2.0. Time to progression (TTP), OS and cancer-specific survival (CSS) were calculated. The median follow-up was 54 (range 6-127) mos. Results: After the first cycle of RAIT 14 of 63 pts experienced grade 4 hematological toxicity. Nineteen pts did not receive the second cycle of RAIT due to prolonged toxicity, impaired performance status (n=6), or metastatic relapse (n=13). The latter were further treated by resection (n=3) or systemic chemotherapy (n=10). Forty-four pts received the planned second cycle of RAIT. Of these, 4 pts newly experienced grade 4 hematological toxicity. For all 63 pts, the median TTP, OS and CSS were 13, 57 and 92 months, respectively. The truly “adjuvant” pts (n=39) had a an improved median TTP (26 vs. 6.6 mos, p&lt;0.0001), OS (76 vs. 42 mos, p=0.03) and CSS (not reached vs. 42 mos, p=0.003) in comparison to “non-adjuvant” pts (n=24). Conclusions: Repeated anti-CEA-RAIT with 131 I-labetuzumab is safe, feasible, and well-tolerated (100% compliance), with expected hematological toxicity. The long-term survival after RAIT is very encouraging, in particular for pts deemed truly “adjuvant” post-salvage resection of CLM at restaging prior to RAIT.