tbuckley/cabot-search huggingface dataset:
Abstract 047: Impact of Acculturation on Framingham Cardiovascular Risk Factors Among Elderly Mexican Americans
Authors: Lenny Lopez, Carmen A Peralta, Mary N Haan, Anne Lee, Allison Aiello
Journal: Circulation (2012)

Background: Acculturation is the process by which immigrant groups adopt the cultural practices and values of the host country. Higher levels of acculturation among Latinos have been shown to be associated with a higher prevalence of traditional CVD Framingham risk factors (FRFs) in some studies. The association of acculturation and prevalence of traditional CVD risk factors in elderly Latinos is less well established. Hypothesis: Higher acculturation is associated with higher CVD FRFs prevalence. Methods: We evaluated the association of acculturation with prevalence of FRF among 1,789 elderly men and women from the Sacramento Area Latino Study on Aging (SALSA) using multivariate linear and logistic regression. SALSA is a well-characterized, NIH funded cohort study of Mexican Americans aged &gt; 60 followed since 1998–1999. Acculturation was measured using the validated bidimensional Acculturation Rating Scale for Mexican Americans-II and modeled as a continuous variable per interquantile range increase (IQR). We adjusted for age, gender, nativity status, income, insurance and the use of antihyperglycemic and antihypertensive medications. To evaluate whether differences in behavior may mediate the association of acculturation and FRFs we further adjusted for social and behavioral factors (marital status, physical activity, smoking, alcohol). We tested for the interaction of acculturation with FRF by nativity status. Results: Median age was 69.8 ± 7.1 and the overall IQR was 24 points. The mean acculturation score for US born Mexican Americans was 30.7 ±9.9 compared to 13.5 ± 9.4 for foreign born (p&lt;0.001). Higher acculturation was associated with lower SBP (beta −1.79, 95%CI [−3.55, −0.02] per IQR increase in acculturation score) and lower LDL (beta −3.59, 95% CI [−6.79, −0.39] per IQR increase in acculturation score) after age and sex adjustment. Acculturation was not associated with total cholesterol, HDL, DM, BMI or smoking (all p values &gt;0.05). The association of acculturation and SBP was attenuated after adjustment (beta −0.90, 95% CI [−2.99, 1.19] per IQR increase in acculturation score. Higher acculturation remained associated with lower LDL levels (β=−4.82, 95% CI [−8.7, −0.9] per IQR increase in acculturation score) after full adjustment. Stratification by nativity status did not affect these results. Conclusions: Contrary to other reports in middle-aged persons, higher levels of acculturation were associated with lower LDL and not higher prevalence of CVD FRFs in a large cohort of elderly Mexican Americans. The effect of acculturation in CVD risk factors may differ across the life course.
Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance
Authors: Frederik H. Verbrugge, Pieter Martens, Koen Ameloot, Veerle Haemels, Joris Penders, Matthias Dupont, Wai Hong Wilson Tang, Walter Droogné, Wilfried Mullens
Journal: European Journal of Heart Failure (2019)
Engineered targeting tLyp-1 exosomes as gene therapy vectors for efficient delivery of siRNA into lung cancer cells
Authors: Jing Bai, Jialun Duan, Rui Liu, Yafei Du, Qian Luo, Yinuo Cui, Zhanbo Su, Jiarui Xu, Ying Xie, Wanliang Lu
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Natural exosomes can express specific proteins and carbohydrate molecules on the surface and hence have demonstrated the great potentials for gene therapy of cancer. However, the use of natural exosomes is restricted by their low transfection efficiency. Here, we report a novel targeting tLyp-1 exosome by gene recombinant engineering for delivery of siRNA to cancer and cancer stem cells. To reach such a purpose, the engineered tLyp-1-lamp2b plasmids were constructed and amplified in Escherichia coli. The tLyp-1-lamp2b plasmids were further used to transfect HEK293T tool cells and the targeting tLyp-1 exosomes were isolated from secretion of the transfected HEK293T cells. Afterwards, the artificially synthesized siRNA was encapsulated into targeting tLyp-1 exosomes by electroporation technology. Finally, the targeting siRNA tLyp-1 exosomes were used to transfect cancer or cancer stem cells. Results showed that the engineered targeting tLyp-1 exosomes had a nanosized structure (approximately 100 nm) and high transfection efficiency into lung cancer and cancer stem cells. The function verifications demonstrated that the targeting siRNA tLyp-1 exosomes were able to knock-down the target gene of cancer cells and to reduce the stemness of cancer stem cells. In conclusion, the targeting tLyp-1 exosomes are successfully engineered, and can be used for gene therapy with a high transfection efficiency. Therefore, the engineered targeting tLyp-1 exosomes offer a promising gene delivery platform for future cancer therapy.
M2 macrophages correlated with symptom severity and promote type 2 inflammation in allergic rhinitis
Authors: Hongfei Lou, Yanran Huang, Hui Chen, Yang Wang, Luo Zhang, Chengshuo Wang
Journal: Allergy (2019)

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Abstract P5-05-16: Role of estrogen receptor alpha acetylation in estrogen-dependent gene regulation in breast cancers
Authors: YM Vasquez, R Setlem, S Murakami, WL Kraus
Journal: Cancer Research (2019)

Abstract Estrogens, such as 17β-estradiol (E2), act through estrogen receptor alpha (ERα), a ligand-regulated transcription factor that binds across the genome to promote enhancer formation and regulate gene expression. ERα is expressed in approximately 70% of breast cancers, where it regulates the transcription of genes involved in mitogenic and inflammatory pathways. We are exploring the the acetylation of ERα on lysines 266 and 268, a modification that enhances the DNA binding and transcriptional activities of ERα. ERα acetylation is catalyzed by the lysine acetyltransferases p300 and CBP in an E2- and steroid receptor coregulator (SRC)-dependent manner. Acetylation-dependent activation of ERα has potential implications in breast cancers associated with enhanced coregulator interactions, such as SRC-3/Amplified in Breast (AIB1) gene amplifications and gain-of-function ERα mutations in endocrine resistant metastatic tumors, such as Y537S and D538G. Increased association of ERα with SRCs and p300/CBP leading to enhanced ERα acetylation may promote gain-of-function ERα activity. Our hypothesis is that acetylation of ERα alters its function by increasing E2-responsive gene transcription and signaling in breast cancers. Our current efforts are focused on investigating the role of ERα acetylation on chromatin binding and accessibility, enhancer activity, and target gene transcription. We are using the ER-positive MCF-7 breast cancer cell line with a knockdown/re-expression strategy with biochemical mimics of acetylated (K266/268Q) or unacetylated (K266/268R) ERα. Genomic ERα binding profiles using chromatin immunoprecipitation-sequencing (ChIP-seq) has defined overlapping, but unique, sets of transcriptional targets and recruitment kinetics for the ERα mutants. Current efforts are focused on defining global transcriptional responses associated with the unique binding activities using precision run-on sequencing (PRO-seq). Ultimately, our goal is to define how acetylation affects the binding of ERα to chromatin and its effect on the transcriptional activity of E2-target genes in breast cancers in the context of gain-of-function ERα mutations and coregulator amplifications. Supported in part by a postdoctoral fellowship from the Lalor Foundation to YMV, and grants from the NIDDK, NICHD, and CPRIT to WLK, as well as support from the Cecil H. and Ida Green Center for Reproductive Biology Sciences Endowment. Citation Format: Vasquez YM, Setlem R, Murakami S, Kraus WL. Role of estrogen receptor alpha acetylation in estrogen-dependent gene regulation in breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-05-16.
Abstract P5-16-07: Short-term outcomes and QoL following autologous fat transfer in oncoplastic and reconstructive breast surgery
Authors: V Bjelic-Radisic, K Oberfichtner, P Wurzer, E Trapp, T Rappl, J Reisniger, L-P Kamolz, K Tamussino
Journal: Cancer Research (2019)

Abstract Background: Breast cancer (BC) is with 30% among all cancers the most common cancer among women in Austria. Regarding therapy and management of BC, surgical treatments with resection and reconstruction play a crucial role. Breast-conserving therapy (BCT) represents a common procedure. However, mastectomy is still needed in about 30% of the patients with the diagnosis BC and as prophylactic surgery in indicated cases. Recently, autologous fat transfer (AFT, lipofilling) has been used to improve cosmesis in oncoplastic and reconstructive breast surgery. There is a gap of evidence for the oncological safety as well as the benefit for quality of life (QoL) in patients who had an AFT after the BC or prophylactic surgery. Material and methods: We assessed peri-and postoperative results, oncological outcomes and QoL in 55 patients undergoing AFT after BCT or mastectomy at our department between 2013 and 2018. QoL was assessed with the EORTC QLQ C30 and QLQ-BRECON23 questionnaires. Results: Overall, 55 patients (73 breasts) underwent AFT after BCT or mastectomy. 39 patients had a diagnosis of invasive BC (four bilateral) and six patients a diagnosis of DCIS. 24 mastectomies were done as prophylactic surgery. AFT was done in 22 cases with nipple sparing mastectomy (NSM), in 30 cases with skin sparing mastectomy (SSM), in 9 cases with simple mastectomy ± reconstruction and in 12 cases with BCT. The number of AFT sessions was 1-8 (mean 1.8). The injected fat volume per session was 30-390 ml. There were 10 (14%) complications: 3 hematomas (none needed reintervention), local inflammation requiring antibiotic therapy (n=3), formation of an oil cyst (n=1), and fat necrosis (n=3). In two cases of fat necrosis biopsy was performed to confirm the diagnosis. After a median follow-up of 34 months there was one recurrence (Paget´s disease after BC). QoL data will be presented at the meeting. Conclusion: Lipofilling after mastectomy for cancer appears to be oncologically safe. Our complication rate is relatively high, although additional surgical intervention (biopsy) was only necessary in two cases. Patients considering AFT should be informed about additional risk for biopsy, as well as other common complications. Citation Format: Bjelic-Radisic V, Oberfichtner K, Wurzer P, Trapp E, Rappl T, Reisniger J, Kamolz L-P, Tamussino K. Short-term outcomes and QoL following autologous fat transfer in oncoplastic and reconstructive breast surgery [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-16-07.
Abstract 2097: Gemini vitamin D analogs inhibit estrogen receptor positive and estrogen receptor negative mammary tumorigenesis without hypercalcemic toxicity
Authors: Hong Jin Lee, Shiby Paul, Yan Ji, Nadi Atalla, Paul E Thomas, Hubert Maehr, Milan Uskokovic, Nanjoo Suh
Journal: Cancer Research (2008)

Abstract Numerous preclinical, epidemiological and clinical studies with vitamin D and analogs have suggested the benefits of vitamin D and analogs for prevention and treatment of cancer. However, the hypercalcemic effects have limited the use of 1α,25(OH)2D3, the hormonally active form of vitamin D, and many of its classical synthetic analogs as potent agents for cancer prevention and treatment. To identify vitamin D analogs with better efficacy and low toxicity, we have tested more than 60 novel Gemini vitamin D analogs, which have a unique structure of two six-carbon chains with a C-20-normal and a C-20-epi side chain. Our initial studies found that some Gemini analogs are many-fold more active than 1α,25(OH)2D3 in growth inhibition assay. We further examined the inhibitory effect of selected Gemini vitamin D analogs against mammary carcinogenesis in vivo by using N-methyl-N-nitrosourea (NMU)-induced mammary tumor model which is ER-positive. Among Gemini vitamin D analogs we tested, Gemini 0072 and Gemini 0097 treated groups showed approximately 60% suppressive activity in NMU-induced mammary tumor growth compared to the control group. In a dose dependent experiment, Gemini 0097 significantly reduced the average tumor burden per rat without affecting the body weight. At all doses tested, Gemini 0097 did not exert any calcemic toxicity. In addition, we determined the inhibitory effect of Gemini 0097 in MCF10DCIS xenograft model of ER-negative mammary tumors. Gemini 0097 significantly inhibited MCF10DCIS xenograft tumor growth without calcemic toxicity. We analyzed the tumor samples and found that the inhibitory effect of Gemini 0097 in vivo was through (a) increasing cyclin dependent kinase inhibitor, p21 and (b) inducing insulin-like growth factor binding protein 3 (IGFBP3) in both ER-positive and ER-negative mammary tumors. Our results suggest that Gemini vitamin D analogs may be potent agents for the prevention and treatment of both ER positive and ER negative breast cancer without calcemic toxicity.
Image-Guided Intravenous Alteplase for Stroke — Shattering a Time Window
Authors: Randolph S. Marshall
Journal: New England Journal of Medicine (2019)

The era of time-based treatment with intravenous alteplase in patients with acute stroke may finally be drawing to a close. As the only approved pharmacologic treatment for acute stroke, and one that has been used since 1995, alteplase is still limited to patients whose stroke began within 4.5 hours before the infusion.1 Several attempts have been made to show the safety and efficacy of unrestricted thrombolysis beyond 4.5 hours, but they failed. The time window was based on sound preclinical evidence. An influential experiment in rodents showed that a 15-minute occlusion of the middle cerebral artery produced selective neuronal necrosis . . .
Translating Protective Hypothermia During Cardiac Arrest Into Clinical Practice
Authors: Karen G. Hirsch, Clifton W. Callaway
Journal: JAMA (2019)

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Abstract SY15-02: Constructing and deconstructing cancer using mouse models and RNAi
Authors: Scott W. Lowe
Journal: Cancer Research (2010)

Abstract Cancer arises through an evolutionary process whereby normal cells acquire mutations that erode growth controls, leading to the inappropriate expansion of aberrantly proliferating cells. Such mutations can involve activation of oncogenes or inactivation of tumor-suppressor genes, each contributing one or more new capabilities to the developing cancer cell. However, cancer is not an inevitable consequence of oncogenic mutations; instead, cells acquiring such mutations can be eliminated or kept in check by innate tumor-suppressor programs that can be activated in these damaged cells. Our laboratory studies tumor-suppressor networks controlling apoptosis and senescence and how their disruption influences malignant behavior. We previously showed that apoptosis and cellular senescence are potent barriers to oncogene-driven tumorigenesis and that each contributes to the antitumor action of many chemotherapeutic drugs. Thus, not only do mutations that disrupt apoptosis and senescence promote tumor progression but, depending on the particular lesion, they can also reduce the efficacy of cancer therapy. To facilitate our research, we have recently developed new mouse cancer models based on the genetic manipulation of stem and progenitor cells ex vivo followed by transplantation of the altered cells into the appropriate organ of syngeneic recipient mice. This approach allows us to rapidly study the impact of many genes and gene combinations on tumorigenesis in a “mosaic” setting where tumor-initiating cells are embedded in normal tissues. Furthermore, we have developed powerful methods for using RNAi to suppress gene function in vivo in either a stable and reversible manner. Current efforts in the laboratory strive to integrate mosaic mouse models, RNA interference, and cancer genomics to identify new components of tumor suppressor gene networks and characterize their impact on tumorigenesis and treatment response. In addition, we are developing new RNAi interference methods to explore the role of tumor suppressor genes in tumor maintenance, and the cell death mechanisms involved in tumor regression. Citation Format: Scott W. Lowe. Constructing and deconstructing cancer using mouse models and RNAi [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY15-02
Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis
Authors: Anne Berghöfer
Journal: BMJ (2013)

The paper

Abstract

Objective —To assess whether lithium has a specific preventive effect for suicide and self harm in people with unipolar and bipolar mood disorders.

Design —Systematic review and meta-analysis.

Data sources —Medline, Embase, CINAHL, PsycINFO, CENTRAL, web based clinical trial registries, major textbooks, authors of important papers and other experts in the discipline, and websites of pharmaceutical companies that manufacture lithium or the comparator drugs (up to January 2013).

Inclusion criteria —Randomised controlled trials comparing lithium with placebo or active drugs in long term treatment for mood disorders.

Review methods —Two reviewers assessed studies for inclusion and risk of bias and extracted data. The main outcomes were the number of people who completed suicide, engaged in deliberate self harm, and died from any cause.

Results —48 randomised controlled trials (6674 participants, 15 comparisons) were included. Lithium was more effective than placebo in reducing the number of suicides (odds ratio 0.13, 95% confidence interval 0.03 to 0.66) and deaths from any cause (0.38, 0.15 to 0.95). No clear benefits were observed for lithium compared with placebo in preventing deliberate self harm (0.60, 0.27 to 1.32). In unipolar depression, lithium was associated with a reduced risk of suicide (0.36, 0.13 to 0.98) and also the number of total deaths (0.13, 0.02 to 0.76) compared with placebo. When lithium was compared with each active individual treatment a statistically significant difference was found only with carbamazepine for deliberate self harm. Lithium tended to be generally better than the other active comparators, with small statistical variation between the results.

Conclusions —Lithium is an effective treatment for reducing the risk of suicide in people with mood disorders. Lithium may exert its …
Abstract P1-02-06: Breast cancer screening in the Republic of Belarus: Advantages and learning perspective
Authors: O Trusova, V Osharin, V Smelov, L Wilkinson, R Given-Wilson
Journal: Cancer Research (2019)

Abstract Background: Breast cancer (BC) is the most common cancer among women in the Republic of Belarus. To reduce BC-related mortality, the implementation of organized pilot BC screening programmes using digital mammography has been supported by the European Union as part of the BELMED project. During recent years Belarus has developed its own digital mammographs and software that allows storing and processing images in the DICOM format. To assure digital mammographic performance in the local context, the first external clinical image quality assessment (QA) of Belarus mammograms was performed by a leading UK radiologist. Methods: The reviewed mammograms from 88 (out of 2,267) Belarus women (mean age: 59.5 years; SD:5.7) attending the a breast screening pilot in Minsk were examined as 81 with positive and 7 with negative findings, according to Belarus readers. This included all 10 histologically confirmed BCs. Within the framework of BELMED project, a total of 400 mammographic images were selected for evaluation by a leading expert radiologist from the UK Public Health England Breast Screening Programme. Evaluated mammographic images were classified according to the Belarus (non-BIRADS) and BIRADS (the UK radiologist) categories, associtated with a follow-up plan. Gradings were compared across categories (the Cohen's Kappa) and according to the proportion of cases referred for further tests (the Wilcoxon signed rank test). Results: The reviewer concluded that approximately 50% of the positive mammograms didn't require futher assessment in screening according to the UK radiologist. All histologically confirmed BCs were not among those downgraded. Substantial agreement was found in the gradings for BC (Kappa: 0.66, p&amp;lt;0.001). The study has resulted in adopting the BIRADS classification in the country and launching additional training of radiologists (e.d. in biopsy) and radiographers (in positioning). Conclusions: To minimize additional tests on women, comprehensive QA (audit and regular check of mammographic technique, the opinion of physicists, etc.) is essential. Applying the implementation research may result in further improvement of the national BC programme. Improved practice can be promoted by continous image review and training for individual staff (i.e., through BELMED, in collaboration with UK training centres) to further improve the skills of Belarus specialists and increase the quality of BC screening programme in Belarus. Citation Format: Trusova O, Osharin V, Smelov V, Wilkinson L, Given-Wilson R. Breast cancer screening in the Republic of Belarus: Advantages and learning perspective [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-02-06.
Getting on the carousel
Authors: Neil Chanchlani
Journal: BMJ (2012)

Since 2007, almost all UK medical students will have taken the United Kingdom Clinical Aptitude Test (UKCAT), a standardised test that universities use as part of admissions criteria. Similar tests exist in the US (Medical College Admissions Test) and are soon to be rolled out in India (National Eligibility cum Entrance Test). One of the aims of these tests is to widen access to medicine to under-represented groups. Such groups include those from low socio-economic backgrounds and ethnic minorities. But …