tbuckley/cabot-search huggingface dataset:
Folic Acid Antagonists during Pregnancy and the Risk of Birth Defects
Authors: Sonia Hernández-Díaz, Martha M. Werler, Alexander M. Walker, Allen A. Mitchell
Journal: New England Journal of Medicine (2000)

Multivitamin supplementation in pregnant women may reduce the risks of cardiovascular defects, oral clefts, and urinary tract defects in their infants. We evaluated whether the folic acid component of multivitamins is responsible for the reduction in risk by examining the associations between maternal use of folic acid antagonists and these congenital malformations.
FRI0531 Immediate and Long Term Outcome of Patients with Kawasaki Disease Treated with Only Intravenous Pulse Methylprednisolone as Primary Therapy
Authors: C.B. Bernal, C. Cuaso, J. Ngo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Kawasaki disease (KD) is an acute multisystem vasculitis predominantly affecting the coronary arteries of still unknown etiology. IV gammaglobulin (IVIG) is the standard treatment to reduce the occurrence of coronary artery abnormalities. Methylprednisolone (MP) added to the standard therapy has been shown to provide no additional benefit in the primary therapy of KD but has a role for IVIG-resistant KD. For developing countries, the financial burden of IVIG poses a significant barrier to treatment. The striking immune perturbances in KD is quite similar to other primary systemic vasculitis which are treated with corticosteroids, hence MP may provide some benefit as a primary therapy for KD. In our institution, parents who cannot afford IVIG consented to intravenous MP as an alternative treatment option. <h3>Objectives</h3> To review the immediate and long term outcome of KD patients treated with IV MP as primary therapy. <h3>Methods</h3> Retrospective chart review of patients who fulfilled the criteria for the diagnosis of KD and treated with IV pulse MP [30mg/kg/dose (maximum of 1 gm/dose) daily for 3 consecutive days] plus high dose aspirin from January 2006 to December 2010 was done. <h3>Results</h3> A total of 22 patients were included in the study. There was clinical improvement in all patients with immediate lysis of fever after the first dose of IV MP and significant decrease in CRP levels. Repeat echocardiography done at 8 weeks, 6 months, 1 year and 2 years from the time of diagnosis by a single pediatric cardiologist revealed no coronary artery abnormalities in all patients. No adverse events reported during and after the infusion. <h3>Conclusions</h3> Methylprednisolone is effective in controlling the systemic manifestations and in preventing coronary aneurysm and safe for patients with KD. It can be an alternative first line treatment for patients who cannot afford IVIG. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3973
None of expected benefits of Labour's IT programme have been achieved, report says
Authors: M. Cross
Journal: BMJ (2013)

The spectre of the last government’s £10bn effort to computerise the NHS in England arose this week over the Department of Health’s ambition to create a “paperless” service.

In a memorandum to parliament the National Audit Office (NAO) reported that virtually none of the expected benefits of the National Programme for IT, set up in 2002 and dismantled into component parts in 2011, had been achieved.1

As …
The Gulf Oil Spill
Authors: Bernard D. Goldstein, Howard J. Osofsky, Maureen Y. Lichtveld
Journal: New England Journal of Medicine (2011)

The 2010 Gulf Oil spill was an occupational, environmental, and community health disaster. This review summarizes the contaminants of concern, toxicologic consequences for humans and the ecosystem, lessons for worker safety, and mental health consequences in the community.
SAT0075 Prevalence of Sexual Dysfunction Among Moroccan Women with Rheumatoid Arthritis: Case-Control Study
Authors: R. Lahlou, S. Rostom, A. Hari, N. bensaoud, L. traki, R. Bahiri, N. hajjaj-hassouni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To assess the prevalence of sexual dysfunction in married women with rheumatoid arthritis (RA) and comparing with a control group. <h3>Methods</h3> We conducted a cross-sectional study including 31 case-control patients with rheumatoid arthritis according to the ACR criteria 1987. Patients with any disease or who are taking medication that may impair sexual function were excluded. The controls were healthy volunteers matched for age and sex. Clinical and sociodemographic characteristics were collected. Sexual function was assessed by self-reported questionnaire the FSFI (index of female sexual function). This score assesses sexual function during the past 4 weeks; it is composed of six domains respectively assessing desire, arousal, lubrication, orgasm, satisfaction and pain. The FSFI total score varies between 1.2 and 36. The threshold score of FSFI ≤ 26 defines a sexual dysfunction. <h3>Results</h3> The mean age was 45 ± 9.1 with a median disease duration of 60 months (24-144). The mean DAS28 was 4.59 ± 1.81 with a median HAQ of 0.75 (0.25 to 1.22). The mean age of controls was 44.7 ± 10 years. The prevalence of sexual dysfunction in RA was 74.1%. There was a significant difference in the total FSFI score between patients 17.17 ± 10 and controls 23.05 ± 8 (p = 0.04). Areas of desire (p patients: 2.07 ± 1 versus control t: 2.9 ± 10), excitement (p: 2.4 ± 1.5 vs t: 3.6 ± 1.6) lubrication (p: 2.7 ± 2 vs t: 3.7 ± 1.8), orgasm (p: t 2 vs 2.8 ± 3.8 ± 1.6) and satisfaction (p: 3.44 ± 1.8 vs. t = 4.7), respectively, were lower in RA patients compared to controls (for all p &lt;0.05), except for the pain domain (p = 3.6 ± 2.60 vs t: 4.10 ± 1.75). The presence of sexual dysfunction did not appear to be associated with age (p = 0.90), menopause (p = 0.79) and psychological status (p = 0.56), whereas the educational level (p &lt; 0, 001). <h3>Conclusions</h3> This study suggests that sexual dysfunction is more common among married patients with RA compared to controls. These dysfunctions were related to desire, arousal, lubrication, orgasm and satisfaction. Further studies are needed to confirm these results. <h3>Disclosure of Interest</h3> None Declared
Abstract 1779: BRCA2 interacts with an essential replication factor, MCM10.
Authors: Allen L. Alcivar, Jianglin Ma, Bing Xia
Journal: Cancer Research (2013)

Abstract The BRCA2 (Breast Cancer 2, early onset) gene is implicated in a variety of familial cancers. Loss of BRCA2 function results in severe defects in DNA double-strand break repair, DNA damage-induced checkpoint response and the stability of stalled DNA replication forks, all of which are important for genomic stability. About 50% of BRCA2 is associated with PALB2 (partner and localizer of BRCA2), which anchors BRCA2 onto chromatin and directs its recruitment to DNA damage sites. By tandem affinity purification of PALB2 we identified MCM10, an essential DNA replication factor, as a component of the PALB2/BRCA2 complex. MCM10 promotes initiation of DNA replication through binding to MCM2-7 helicase complex and recruiting the initial DNA polymerase, pol α, to replication origins. Interestingly, we found that MCM10 binds to BRCA2 instead of PALB2 in the complex. Cells depleted of BRCA2 or MCM10 showed similar instability of stalled replication forks, indicating possible cooperation between the two proteins in fork stabilization following replication stress. Moreover, DNA damage-induced CHK1 activation is markedly reduced in both BRCA2- and MCM10-depleted cells even though RPA (replication protein A) is hyperphosphorylated. Our findings suggest that BRCA2 checkpoint function may be mediated through MCM10 and their interaction may be important for stalled replication fork stability. Domain mapping experiments showed that an evolutionarily conserved coiled-coil motif in the N-terminus of MCM10 which is required for BRCA2 binding and that BRCA2 has at least two MCM10-binding sites, both in its central region. BRCA2 and MCM10 mutants lacking these interaction domains will be used to further test the functional relevance of their interaction. Citation Format: Allen L. Alcivar, Jianglin Ma, Bing Xia. BRCA2 interacts with an essential replication factor, MCM10. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1779. doi:10.1158/1538-7445.AM2013-1779
Prolonged Nightly Fasting and Breast Cancer Prognosis
Authors: Catherine R. Marinac, Sandahl H. Nelson, Caitlin I. Breen, Sheri J. Hartman, Loki Natarajan, John P. Pierce, Shirley W. Flatt, Dorothy D. Sears, Ruth E. Patterson
Journal: JAMA Oncology (2016)

Rodent studies demonstrate that prolonged fasting during the sleep phase positively influences carcinogenesis and metabolic processes that are putatively associated with risk and prognosis of breast cancer. To our knowledge, no studies in humans have examined nightly fasting duration and cancer outcomes.To investigate whether duration of nightly fasting predicted recurrence and mortality among women with early-stage breast cancer and, if so, whether it was associated with risk factors for poor outcomes, including glucoregulation (hemoglobin A1c), chronic inflammation (C-reactive protein), obesity, and sleep.Data were collected from 2413 women with breast cancer but without diabetes mellitus who were aged 27 to 70 years at diagnosis and participated in the prospective Women's Healthy Eating and Living study between March 1, 1995, and May 3, 2007. Data analysis was conducted from May 18 to October 5, 2015.Nightly fasting duration was estimated from 24-hour dietary recalls collected at baseline, year 1, and year 4.Clinical outcomes were invasive breast cancer recurrence and new primary breast tumors during a mean of 7.3 years of study follow-up as well as death from breast cancer or any cause during a mean of 11.4 years of surveillance. Baseline sleep duration was self-reported, and archived blood samples were used to assess concentrations of hemoglobin A1c and C-reactive protein.The cohort of 2413 women (mean [SD] age, 52.4 [8.9] years) reported a mean (SD) fasting duration of 12.5 (1.7) hours per night. In repeated-measures Cox proportional hazards regression models, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76). Nightly fasting less than 13 hours was not associated with a statistically significant higher risk of breast cancer mortality (hazard ratio, 1.21; 95% CI, 0.91-1.60) or a statistically significant higher risk of all-cause mortality (hazard ratio, 1.22; 95% CI, 0.95-1.56). In multivariable linear regression models, each 2-hour increase in the nightly fasting duration was associated with significantly lower hemoglobin A1c levels (β = -0.37; 95% CI, -0.72 to -0.01) and a longer duration of nighttime sleep (β = 0.20; 95% CI, 0.14-0.26).Prolonging the length of the nightly fasting interval may be a simple, nonpharmacologic strategy for reducing the risk of breast cancer recurrence. Improvements in glucoregulation and sleep may be mechanisms linking nightly fasting with breast cancer prognosis.
P4-01-22: Cyclin D1 and Its Prognostic Value in Planning of Endocrine Therapy for Women of Postmenopausal Age with Breast Cancer.
Authors: V Skvortsov, A Manikhas, G Manikhas, A Oganesyan, G Raskin
Journal: Cancer Research (2011)

Abstract Background: Nowadays tamoxifen still remains the primary drug in breast cancer endocrine therapy. However, its application is limited due to the resistance of tumor cells. The search of adequate biomarkers is one of the most actual problems in prognosis of effectiveness of tamoxifen adjuvant therapy. The most perspective biomarker is cell cycle regulator cyclin D. Besides its central role in cell cycle regulation cyclin D1 modulates the estrogen receptors activity and can influence on the effectiveness of treatment with antiestrogenes and aromatase inhibitors. The objective of our work was to evaluate the effectiveness of tamoxifen in adjuvant therapy of hormone-receptor-positive breast cancer in women of postmenopausal age with cyclin D1 expression. Material and Methods: To evaluate the effectiveness of tamoxifen adjuvant application in women with cyclin D1-positive T1-4N0-3M0 breast cancer we have researched 2 retrospective groups of 70 patients that have been on regular medical check-up for a period of 5 years or that had previously undergone treatment. On the basis of the archive histological material we have revealed cyclin D1 in tumor cells. Results: The expression of cyclin was classified in 4 levels: negative, low, moderate and high. Patients with lack of cyclin D1 expression or with low quantitative value (according to our data less than 30%) have no neoplastic process progression throughout the 5 years of tamoxifen adjuvant therapy. These women were both with axillary lymph nodes affection and without it (+N; -N). On the contrary, women with moderate and high cyclin D1 expression (more than 30%) had a relapse of tumor and distant metastasis is prognosed in 5 years of observation (p=0,005). Moderate level of cyclin D1 expression was observed in 45 (64%) patients and 28 (62%) of them had progression with metastasis in bones, 9 (20%) metastasis in soft tissues, 2 (4%) metastasis in lungs and 6 (14%) relapse in postoperative scar. High expression was revealed in 25 (35%) women and 17 (68 %) of them had bone affection, 7 (28%) soft tissue metastasis and 2 (4%) tumor relapse in postoperative scar. Lung metastasis were not observed. The average period of tumor relapse and progression of neoplastic process in patients with cyclin D1-positive breast cancer is 20 months. Discussion: The results of our work suggest that women with hormone-receptor-positive cyclin D1-negative breast cancer on early stages have more prolonged non-relapse period during the tamoxifen adjuvant therapy. Patients with cyclin D1-positive breast cancer are less sensitive to tamoxifen treatment and in adjuvant regime should receive therapy with other effective equivalent drugs (aromatase inhibitors). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-01-22.
Erda Pamela Moffitt
Authors: G. Moffitt
Journal: BMJ (2012)

The daughter of Caymanian parents and the eldest of nine children, Erda Pamela Moffitt (nee Bodden and known as “Pam”) was a conspicuously bright child who was admitted to secondary school at the age of 7, when her primary teachers asked her mother “to remove this precocious pupil” whom they had nothing left to teach. She continued a brilliant school career and ultimately gained a place to study medicine at the Royal Free Hospital.

She arrived in London in 1947 and was shocked at the poverty and destruction that greeted her. She recalled snow coming in through her host family’s bathroom ceiling as a result of bomb damage, and there being no materials available for its repair. In contrast, she greatly appreciated the relative luxury of accommodation in college hall where she recalled that her room had two doors, one being the entrance, and, to her delight, the other access to a walk-in wardrobe. Unintentionally, in that age of austerity, her appearance caused great offence. Always passionate about clothes, she made no attempt to conceal the beautiful and “extravagant” dresses that her mother had sewed for her.

While in London she enjoyed the museums, exhibitions, and theatres. She was able to witness the procession of the royal wedding in 1947, when a wealthy friend from the medical school invited her to watch the pageant from the third floor window of her father’s Pall Mall office. Ultimately however, an absence of any former scientific education …
Doctors Concerned About Age Bias in Cancer Treatment
Authors: John Burklow
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Doctors Concerned About Age Bias in Cancer Treatment Get access John Burklow John Burklow Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 6, 18 March 1992, Page 391, https://doi.org/10.1093/jnci/84.6.391 Published: 18 March 1992
Efficiency of Gamma Probe and Dual-Phase Tc-99m Sestamibi Scintigraphy in Surgery for Patients with Primary Hyperparathyroidism
Authors: Cengiz H Demirkurek, Isik Adalet, Tarik Terzioglu, Selcuk Ozarmagan, Alp Bozbora, Nese Ozbey, Yersu Kapran, Sema Cantez
Journal: Clinical Nuclear Medicine (2003)

The purpose of this study was to determine the value of the intraoperative gamma probe and the efficacy of dual-phase Tc-99m sestamibi imaging in patients with primary hyperparathyroidism.Twenty-one patients with primary hyperparathyroidism were examined prospectively. Results of same-day dual-phase Tc-99m sestamibi scintigraphy and intraoperative gamma probe evaluations were compared with the intraoperative findings and histopathologic diagnoses. A 15-mm handheld gamma probe was used to measure gamma activity in the neck and upper mediastinum. Nuclear mapping by gamma probe showed a single quadrant of neck that emitted gamma radiation significantly greater than the other three quadrants, which correlated with the sestamibi scan.Dual-phase Tc-99m sestamibi scintigraphy determined and localized parathyroid lesions in 20 patients (sensitivity, 94%). Of the 20 parathyroid lesions removed, 15 were located in normal positions, whereas five were explored in ectopic sites (one within the thyroid, one in the anterior mediastinum, one in a retrotracheal position, one in the carotid sheath, and one in the retroesophageal region). Although the index of thyroid nodules varied from 15.8% to 22.9%, the index for parathyroid lesions was 77.3% to 112.8%.These results confirm that parathyroid lesions, especially at ectopic sites, can be treated successfully in shorter operative times with minimal complications with the help of the intraoperative gamma probe.
Abstract C16: miR-148a regulates the expression of PTEN in hepatitis B associated hepatocellular carcinoma
Authors: Ke Yuan, Zhaorui Lian, Bill Sun, Marcia M. Clayton, Irene O. L. Ng, Mark A. Feitelson
Journal: Cancer Research (2011)

Abstract Previous work has shown that hepatitis B virus encoded X antigen (HBx) is a trans-regulatory protein that alters the activity of selected transcription factors and cytoplasmic signal transduction pathways. The resulting changes in host gene expression are thought to contribute importantly to the development and progression of hepatocellular carcinoma (HCC). In this context, HBx up-regulates the expression of a unique gene, URG11, which in turn up-regulates β-catenin, thereby contributing importantly to hepatocarcinogenesis. Changes in the expression levels of microRNAs (miRNAs) are also characteristic of many tumors, including HCC. To determine whether altered miRNA expression contributes to the mechanism whereby HBx and URG11 contribute to HCC, recombinant retroviruses encoding HBx, URG11, or the bacterial chloramphenicol acetyltransferase (CAT) gene (the latter used as a negative control) were used to infect separate cultures of HepG2 and Hep3B cells. When these cells were compared by miRNA array analysis, both HBx and URG11 were shown to promote the expression of miR-148a. This was confirmed by quantitative (q)RT/PCR analysis. Elevated levels of miR-148a strongly correlated with HBx positive staining in liver samples from infected patients by qRT/PCR (P&amp;lt; 0.001). To study the function of miR-148a, anti-miR-148a was introduced into HepG2 and Hep3B cells stably expressing HBx or stably over-expressing URG11. Anti-miR-148a suppressed cell proliferation (P &amp;lt; 0.01), cell cycle progression (P &amp;lt; 0.01), cell migration (P &amp;lt; 0.01), anchorage independent growth in soft agar (P &amp;lt; 0.01) and subcutaneous tumor formation in SCID mice (P &amp;lt; 0.05). Introduction of anti-miR-148a also increased PTEN mRNA and protein expression, suggesting that PTEN was targeted by miR-148a. This was verified in experiments where anti-miR-148a failed to suppress PTEN expression when co-transfected with reporter gene mutants of the 3′UTR of PTEN mRNA. When HBx positive HepG2 and Hep3B cells were transiently transfected with URG11 specific siRNA, both URG11 and miR-148a levels were suppressed, suggesting that up-regulated expression of miR-148a in HBx positive cells was URG11 dependent. Finally, anti-miR-148a blocked the stimulation of Akt signaling by HBx and URG11, resulting in decreased expression of β-catenin (P &amp;lt; 0.05). Thus, miR-148a appears to contribute a central role to HBx/URG11 mediated HCC, and may be an early diagnostic marker and/or therapeutic target associated with this tumor type. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C16.
Abstract 4340: Increased cytokine and chemokine expression in U87MG glioblastoma cells after large clinically relevant single doses of ionizing radiation
Authors: J. Tyson Mcdonald, Jawon Lee, Edward Rietman, Clare Lamont, Heiko Enderling, Michael Peluso, Lynn Hlatky
Journal: Cancer Research (2012)

Abstract BACKGROUND: Stereotactic radiosurgery is an established treatment option that uses high, single fraction doses of radiation to target tumors. Despite the best clinical strategies to eliminate brain tumors using this technique or others (surgery, chemotherapy and/or other radiotherapy techniques), post-therapy recurrence of brain tumors remains a major challenge in patients. To better understand the radiation response, we investigated how such high doses modulate the molecular signaling within glioblastoma cell populations from several days to months after irradiation. METHODS: The glioblastoma cell line, U87MG, was treated with single doses of ionizing radiation between 0 to 16Gy in vitro followed by: examination of cell proliferation; clonogenic survival; extraction of RNA; and subcutaneous injection into nude mice to monitor tumor growth 24 hours after cell irradiation. Genome-wide expression profiling was run on the Illumina HT-12 bead array platform and analysis for significant expressed genes was performed along with network analysis using Ingenuity Pathway Analysis and GenePattern platforms. RESULTS: As expected, high doses of radiation stunted growth of the U87MG cells from 0 to 14 days. Long term, single cell clonogenic survival of the irradiated cells was approximately 3% and 0.01% following 8Gy or 16Gy, respectively. Genome-wide gene expression at 1, 4 and 6 days after irradiation of 8 or 16Gy has revealed a dose-dependent increase in inflammatory cytokines and chemokines. Increased cytokine expression for IL-6 and IL-8 was validated in vitro using qRT-PCR. In vivo, 100% of the untreated U87MG cells formed tumors, whereas less than half of all irradiated treatment groups failed to form tumors. In those samples that did grow despite irradiation, the average time to tumor formation (volume = 300mm3) was 13, 32, 58 and 88 days for 0, 8, 12, and 16Gy respectively while the exponential fits to tumor growth rate was shown to be accelerated after 8Gy but diminished after 12 and 16Gy. IL-6 gene expression was found to be elevated in tumors formed from irradiated cells versus control. CONCLUSION: The data presented here provides novel insight into the cellular and molecular modulation of glioblastoma cell populations by large, clinically relevant, single doses of ionizing radiation. A salient finding is the expression of inflammatory cytokines as a major player in the radiation response at periods long after the irradiation insult. This study was supported by NIH ICBP 1U54CA149233 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4340. doi:1538-7445.AM2012-4340