tbuckley/cabot-search huggingface dataset:
Abstract MP070: Saturated Fat Intake by Food Source and Risk of Incident Coronary Heart Disease in Men: the Kuopio Ischaemic Heart Disease Risk Factor Study
Authors: Jyrki K Virtanen, Timo T Koskinen, Heli E Virtanen, Jaakko Mursu, Tomi-Pekka Tuomainen, Sari Voutilainen
Journal: Circulation (2017)

Introduction: The epidemiological evidence of the role of dietary saturated fatty acids (SFA) in the etiology of coronary heart disease (CHD) is inconsistent. However, the proportions of different SFAs in different foods vary, and food sources of SFA (such as dairy and meat products) have had distinct associations with risk of CHD and its risk factors. Hypothesis: We assessed the hypothesis that SFA from different food sources have distinct associations with CHD risk in men. Methods: A total of 1981 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study from eastern Finland, aged 42-60 years and free of CHD at baseline, were included. The consumption of foods was assessed with instructed 4-day food recording by household measures. Dietary intakes were adjusted for total energy using the residuals method. Multivariable-adjusted Cox regression analyses included age, examination year, body mass index, diabetes, hypertension, family history of CHD, smoking, education, leisure-time physical activity, and intakes of alcohol, energy, fiber, polyunsaturated fatty acids, and fruits, berries and vegetables. Fatal and nonfatal CHD events were ascertained from national registries, with no loss to follow-up. Results: The mean±SD total SFA intake was 49.1±10.4 g/d (18.1 E%). SFA from dairy (16.1±7.7 g/d, excluding butter), butter (16.0±11.1 g/d), plant sources (6.7±5.0 g/d), processed red meat (4.7±4.2 g/d), and unprocessed red meat (3.6±2.7 g/d) contributed most to the total intake. During the mean follow-up of 19.6 years, 458 CHD events occurred. The extreme-quartile hazard ratios (95% CIs) were 1.08 (0.79-1.47, P-trend=0.57) for the highest vs. the lowest quartile of total SFA, 0.99 (0.75-1.32, P-trend=0.93) for total dairy SFA, 1.17 (0.84-1.63, P-trend=0.45) for butter SFA, 0.96 (95% CI 0.70-1.32, P-trend=0.62) for plant SFA, 1.09 (0.82-1.44, P-trend=0.76) for processed red meat SFA, and 1.15 (0.88-1.49, P-trend=0.29) for SFA from unprocessed red meat. Only SFA from fermented dairy (mean±SD intake 4.6±4.6 g/d) was associated with the risk (hazard ratio in the highest vs. the lowest quartile 0.69, 95% CI 0.52-0.91, P-trend=0.02). The associations were not appreciably different with a shorter, 10-y follow-up (199 cases). Conclusions: Our results suggest an overall non-significant role for SFA intake in the CHD risk and little difference in the associations with SFA from various food sources. Because milk is the raw material in all dairy products, the inverse association with fermented dairy likely reflects other constituents in these products than SFA.
Brainstem blood brain barrier disruption using focused ultrasound: A demonstration of feasibility and enhanced doxorubicin delivery
Authors: Saira Alli, Carlyn A. Figueiredo, Brian Golbourn, Nesrin Sabha, Megan Yijun Wu, Andrew Bondoc, Amanda Luck, Daniel Coluccia, Colin Maslink, Christian Smith, Heiko Wurdak, Kullervo Hynynen, Meaghan O'Reilly, James T. Rutka
Journal: Journal of Controlled Release (2018)
Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis
Authors: Amarnath Marthi, Killian Donovan, Richard Haynes, David C. Wheeler, Colin Baigent, Christopher M. Rooney, Martin J. Landray, Sharon M. Moe, Jun Yang, Lisa Holland, Romina di Giuseppe, Annet Bouma-de Krijger, Borislava Mihaylova, William G. Herrington
Journal: Journal of the American Society of Nephrology (2018)

Background Fibroblast growth factor-23 (FGF-23) has been hypothesized to play a role in the increased risk of cardiovascular disease in patients with CKD.Methods We identified prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. Maximally adjusted risk ratios (RRs) were extracted for each outcome and scaled to a comparison of the top versus bottom third of the baseline FGF-23 concentration, and the results aggregated.Results Depending on the assay used, median FGF-23 concentrations were 43-74 RU/ml and 38-47 pg/ml in 17 general population cohorts; 102-392 RU/ml in nine cohorts of patients with CKD not requiring dialysis; and 79-4212 RU/ml and 2526-5555 pg/ml in eight cohorts of patients on dialysis. Overall, comparing participants in the top and bottom FGF-23 concentration thirds, the summary RRs (95% confidence intervals [95% CIs]) were 1.33 (1.12 to 1.58) for myocardial infarction, 1.26 (1.13 to 1.41) for stroke, 1.48 (1.29 to 1.69) for heart failure, 1.42 (1.27 to 1.60) for cardiovascular mortality, and 1.70 (1.52 to 1.91) for all-cause mortality. The summary RR for noncardiovascular mortality, calculated indirectly, was 1.52 (95% CI, 1.28 to 1.79). When studies were ordered by average differences in FGF-23 concentration between the top and bottom thirds, there was no trend in RRs across the studies.Conclusions The similarly-sized associations between increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes, together with the absence of any exposure-response relationship, suggest that the relationship between FGF-23 and cardiovascular disease risk may be noncausal.
Abstract 11807: Impact of Abdominal Aortic Calcification on Long Term Cardiovascular Outcomes in Patients With Chronic Kidney Disease
Authors: Yosuke Tatami, Susumu Suzuki, Hideki Ishii, Kazuhiro Harada, Kenshi Hirayama, Yohei Shibata, Tomoyuki Ota, Yoshinari Yasuda, Toyoaki Murohara
Journal: Circulation (2015)

Introduction: Abdominal aortic calcification (AAC) was related to cardiovascular (CV) events in hemodialysis patients. However, little is known about predictive value of the AAC for CV events in chronic kidney disease (CKD) patients. Hypothesis: The purpose of this study was to investigate the prevalence and the predictive value of AAC in asymptomatic CKD patients. Methods: We prospectively evaluated 347 asymptomatic CKD patients (mean estimated glomerular filtration rate: 46.6 ± 22.9 mL/min/1.73 m2). A non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI) as a semi-quantitative measure of aortic calcification. Major adverse cardiovascular events (MACE) were defined as the composite endpoint of cardiovascular death, myocardial infarction, stroke, heart failure, and any coronary revascularization. Results: Among the subjects, AAC was present in 296 patients (86.3%), as defined by ACI &gt; 0, and the median ACI was 11.4% (interquartile ranges; 1.38 - 30.7%). During the median follow-up of 41.5 months, a total of 33 MACEs were observed. Event-free survival rate was significantly associated with ACI tertiles, patients with the high tertile of ACI had the highest risk of MACE compared to the other two groups (high, middle and low tertile; 74.3%, 93.0%, and 96.5%, respectively, p&lt; 0.001). The Cox proportional hazard models adjusted for conventional risk factors showed that the ACI was independently associated with MACE (hazard ratio 1.032, 95% confidence interval, 1.009- 1.055, p= 0.006). Conclusions: Evaluation of the AAC may provide useful information for predicting adverse clinical outcomes among asymptomatic CKD patients.
BAPIO calls for single visa route for non-EU doctors to boost NHS workforce and prevent brain drain
Authors: Abi Rimmer
Journal: BMJ (2018)

The British Association of Physicians of Indian Origin (BAPIO) wants to see a new visa category for overseas doctors to help tackle the NHS workforce crisis and avoid brain drain.

Figures recently gathered by the Campaign for Science and Engineering showed that over 1500 visa applications from doctors from outside the European Economic Area (EEA) wanting to work in the UK were refused over a four month period.1

A monthly cap on the number of certificates of sponsorship that employers can apply for has meant that many doctors who have been offered jobs in the NHS have been unable to gain the visa they need.

Speaking to the Health Service Journal earlier this month, the health secretary, Jeremy Hunt, said he would raise the prospect of creating a dedicated immigration visa category for health and social care staff with the …
Hunger strikes in UK detention centres: injustice provokes desperate protests
Authors: Frank Arnold
Journal: BMJ (2018)

History provides helpful context to the editorial by Dexter and Katona about hunger strikes in UK immigration detention centres.1 On the 100th anniversary of the first law allowing some women to vote, the prime minister praised “Marion Wallace Dunlop . . . who staged the first suffragette hunger strike . . . the right to vote was not handed over willingly. Rather it had to be forced, over …
Abstract 16778: Cardiac Hypertrophy in Neonates With Congenital Heart Disease Delays Maturational Changes in Cardiac Energy Metabolism via Decreased Mitochondrial Acetylation
Authors: Arata Fukushima, Liyan Zhang, Alda Huqi, Victoria H Lam, Tariq Altamimi, Cory S Wagg, Sonia Rawat, Khushmol K Dhaliwal, Lisa K Hornberger, Paul F Kantor, Ivan M Rebeyka, Gary D Lopaschuk
Journal: Circulation (2016)

Background:  A rapid increase in fatty acid oxidation occurs in the heart following birth. However, cardiac hypertrophy, that occurs secondary to congenital heart diseases (CHDs), delays this normal maturation of fatty acid oxidation, thereby decreasing energetic capacity and increasing the susceptibility of the heart to ischemic injury during corrective surgery. Recently, increased cardiac acetylation has emerged as an important post-translational modification that increases fatty acid oxidation. We therefore examined what effect cardiac hypertrophy has on the acetylation control of fatty acid oxidation in the human neonates.   Methods and Results:  A total of 145 right ventricular biopsy samples were collected from neonatal patients undergoing corrective surgery for CHDs, and were stratified according to patient age (0-20 days, n=58; 21-100 days, n=41; and 101-200 days, n=46), as well as the absence (n=83) or presence (n=62) of hypertrophy (assessed by echocardiography). An increase in overall myocardial protein acetylation was seen with increasing age in non-hypertrophied hearts. In contrast, no age-dependent increase in acetylation was observed in hypertrophied hearts, in concert with an increase in mitochondrial deacetylase SIRT3, and a blunted increase in mitochondrial acetyltransferase GCN5L1. An age-dependent hyperacetylation of the fatty acid oxidation enzymes long chain acyl CoA dehydrogenase (LCAD) and β-hydroxyacyl CoA dehydrogenase (β-HAD) was observed only in non-hypertrophied hearts, which was positively correlated with their enzyme activities. Similar results were also observed in a volume-overload hypertrophy in newborn rabbits, where decreased acetylation of LCAD and β-HAD and decreased fatty acid oxidation was evident compared to non-hypertrophied rabbit hearts. Furthermore, acetylation of PGC-1α, a transcriptional regulator for mitochondrial biogenesis, decreased with age only in non-hypertrophied hearts, along with decreased expression of the nuclear acetyltransferase GCN5 and nuclear deacetylase SIRT6.   Conclusions:  The presence of cardiac hypertrophy in CHDs patients prevents the normal increase in myocardial acetylation following birth, resulting in a delayed maturation of fatty acid oxidation.
202. Therapeutic and Tumor-Specific Immunity Induced by Combination of Dendritic Cells and Oncolytic Adenovirus Expressing IL-12 and 4–1BBL
Journal: Molecular Therapy (2010)

Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12- and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12- and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12- and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic.
Harnessing Human Decellularized Blood Vessel Matrices and Cellular Construct Implants to Promote Bone Healing in an Ex Vivo Organotypic Bone Defect Model
Authors: Stefanie Inglis, Karl Heinrich Schneider, Janos M. Kanczler, Heinz Redl, Richard O. C. Oreffo
Journal: Advanced Healthcare Materials (2018)

Abstract Decellularized matrices offer a beneficial substitute for biomimetic scaffolds in tissue engineering. The current study examines the potential of decellularized placental vessel sleeves (PVS) as a periosteal protective sleeve to enhance bone regeneration in embryonic day 18 chick femurs contained within the PVS and cultured organotypically over a 10 day period. The femurs are inserted into decellularized biocompatibility‐tested PVS and maintained in an organotypic culture for a period of 10 days. In femurs containing decellularized PVS, a significant increase in bone volume ( p &lt; 0.001) is evident, demonstrated by microcomputed tomography (µCT) compared to femurs without PVS. Histological and immunohistological analyses reveal extensive integration of decellularized PVS with the bone periosteum, and enhanced conservation of bone architecture within the PVS. In addition, the expressions of hypoxia inducible factor‐1 alpha (HIF‐1α), type II collagen (COL‐II), and proteoglycans are observed, indicating a possible repair mechanism via a cartilaginous stage of the bone tissue within the sleeve. The use of decellularized matrices like PVS offers a promising therapeutic strategy in surgical tissue replacement, promoting biocompatibility and architecture of the tissue as well as a factor‐rich niche environment with negligible immunogenicity.
Increased B3GALNT2 in hepatocellular carcinoma promotes macrophage recruitment via reducing acetoacetate secretion and elevating MIF activity
Authors: Tianxiao Yang, Yilin Wang, Wenjuan Dai, Xixi Zheng, Jing Wang, Shushu Song, Lan Fang, Jiangfan Zhou, Weicheng Wu, Jianxin Gu
Journal: Journal of Hematology & Oncology (2018)

Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent cancer and the third leading cause of tumor-related death, so it is urgently needed to discover efficient markers and targets for therapy. β-1,3-N-acetylgalactosaminyltransferase II (B3GALNT2) belongs to the β-1,3-glycosyltransferases (b3GT) family and has been reported to regulate development of both normal and tumor tissues. However, studies on the functions of B3GALNT2 in cancer are quite limited. Here we investigated the potential role of B3GALNT2 in HCC progression. Western blot, qPCR, and immunohistochemistry assays were performed to quantify the relative expression of B3GALNT2 in HCC. The functions of B3GALNT2 in tumor progression were evaluated in HCC cell lines and nude mice. Metabolomics analysis was applied to detect alternatively expressed small molecules. Enzyme activity assays were employed to determine the tautomerase activity of macrophage inhibitory factor (MIF). For expression analysis, higher levels of B3GALNT2 were observed in tumor tissues compared with adjacent normal tissues, and upregulation of B3GALNT2 correlated with increased tumor size and worse overall survival. Changing levels of B3GALNT2 did not influence cell viability in vitro but promoted tumor growth via enhancing macrophage recruitment in vivo. Furthermore, acetoacetate was identified as a key molecule in B3GALNT2-mediated macrophage recruitment. Mechanistically, B3GALNT2 downregulated expression of enzymes involved in acetoacetate-related metabolism, and reduction of acetoacetate revived MIF activity, thus promoting macrophage recruitment. This study evaluated B3GALNT2 as a tumor marker in HCC and revealed functions of B3GALNT2 in metabolic transformation and microenvironmental remodeling in HCC. Mechanistically, B3GALNT2 reduced expression of some metabolic enzymes and thus downregulated levels of secreted acetoacetate. This relieved the activity of MIF and enhanced macrophage recruitment to promote tumor growth.
Government’s response to £239m worth of inquiries has been “opaque,” says NAO
Authors: Adrian O’Dowd
Journal: BMJ (2018)

Around £240m (€274m; $320m) of taxpayers’ money has been spent on government inquiries since 2005, but evidence that recommendations from these high profile investigations have been adopted is lacking, the UK public spending watchdog has concluded.

The report by the National Audit Office into government funded inquiries, including those on NHS matters, describes uncertainty and variation in the relative costs of inquiries, the effects they had, and how they were carried out.1

In all, the watchdog found that the government spent at least £239m on the 26 inquiries that have concluded since 2005 and that they lasted on average 40 months.

It focused on 10 inquiries started and concluded since 2005, when a new legislative framework …
Simple paired heavy- and light-chain antibody repertoire sequencing using endoplasmic reticulum microsomes
Authors: Praneeth Reddy Devulapally, Jörg Bürger, Thorsten Mielke, Zoltán Konthur, Hans Lehrach, Marie-Laure Yaspo, Jörn Glökler, Hans-Jörg Warnatz
Journal: Genome Medicine (2018)

Existing methods for paired antibody heavy- and light-chain repertoire sequencing rely on specialized equipment and are limited by their commercial availability and high costs. Here, we report a novel simple and cost-effective emulsion-based single-cell paired antibody repertoire sequencing method that employs only basic laboratory equipment. We performed a proof-of-concept using mixed mouse hybridoma cells and we also showed that our method can be used for discovery of novel antigen-specific monoclonal antibodies by sequencing human CD19+ B cell IgM and IgG repertoires isolated from peripheral whole blood before and seven days after Td (Tetanus toxoid/Diphtheria toxoid) booster immunization. We anticipate broad applicability of our method for providing insights into adaptive immune responses associated with various diseases, vaccinations, and cancer immunotherapies.
Evaluation of minimal residual disease using next-generation flow cytometry in patients with AL amyloidosis
Authors: Efstathios Kastritis, Ioannis V. Kostopoulos, Evangelos Terpos, Bruno Paiva, Despina Fotiou, Maria Gavriatopoulou, Nikolaos Kanellias, Dimitrios C. Ziogas, Maria Roussou, Magdalini Migkou, Evangelos Eleutherakis-Papaiakovou, Ioannis P. Trougakos, Ourania Tsitsilonis, Meletios A. Dimopoulos
Journal: Blood Cancer Journal (2018)
An unusual rash on the feet
Authors: Claire Wilson, Noha Elshimy
Journal: BMJ (2018)

A 51 year old white homosexual man was admitted with cellulitis of the left leg. His medical history included psoriasis, for which he had received six years of methotrexate. The methotrexate was stopped 11 years before this presentation and he had not experienced any active psoriasis since then. Examination revealed multiple painless, indurated violaceous plaques and verrucous growths on the dorsal and plantar aspects of both feet (fig 1). Further questioning revealed that these lesions had been present for more than 10 months. There was no evidence of psoriasis on examination. What investigation would you request?



Fig 1 
Violaceous plaques and verrucous growths on both feet



These lesions are characteristic of cutaneous Kaposi’s sarcoma. Methotrexate immunosuppression alone is unlikely to cause the condition, so an HIV …
NHS’s botched outsourcing of primary care support services put patients at risk, says watchdog
Authors: Gareth Iacobucci
Journal: BMJ (2018)

NHS England and the private firm Capita failed to recognise the risks in outsourcing primary care support services and potentially put patients at risk of serious harm, a damning report by the National Audit Office (NAO) has concluded.

In August 2015, NHS England entered into a seven year, £330m (€376m; $446m) contract with Capita to deliver support services to 39 000 GPs, dentists, opticians, and pharmacists. NHS England aimed to reduce its costs by 35% from the first year of the contract, and Capita expected to make a loss of £64m in the first two years of the contract and to recoup costs in later years.

But the service has been plagued by problems,12 including delays in transferring medical records …
Anthracycline, gemcitabine, and pazopanib in epithelioid sarcoma: Results of a retrospective multi-institutional case series.
Authors: Anna Maria Frezza, Naofumi Asano, Robin Jones, Ravin Ratan, Pawel Teterycz, Hans Gelderblom, Kjetil Boye, Mehdi Brahmi, Emanuela Palmerini, Nadia Hindi, Antonella Brunello, Ingrid Desar, Giovanni Grignani, Alexander A. Fedenko, Bruno Vincenzi, Zsuzsanna Papai, Akira Kawai, Salvatore Lo Vullo, Paolo Giovanni Casali, Silvia Stacchiotti
Journal: Journal of Clinical Oncology (2017)

11065 Background: To report on a multi-institution retrospective study on the activity of anthracycline-based (Ab) and gemcitabine-based (Gb) regimens as well as pazopanib (P) in patients with advanced epithelioid sarcoma (ES) treated within 16 sarcoma reference centres in Europe, US and Japan. Methods: Patients with a histologically confirmed diagnosis of locally advanced/metastatic ES were selected. Classic and distal subtypes were defined based on morphology (WHO 2014). INI1 expression is under evaluation.Response was evaluated by RECIST.Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. Results: Ninety ES patients were identified (Table 1). They were treated with Ab (72), Gb (30) and P (20); 25 pts received more than one treatment. The median follow-up for Ab, Gb and P groups was 32, 24 and 22 months, respectively. The response rate (RR) for Ab was 25% (95% CI 16%-37%), with a median PFS and OS of 6 and 17 months. The RR for Gb was 23% (95% CI 10% - 42%), with 1 complete response and a median PFS and OS of 5 and 20 months. In the P group, no objective responses were reported, and median PFS and OS were 3 and 9 months. A non-statistically significant trend towards a greater RR in proximal than classic subtype was seen in both Ab (27% vs 22%) and Gb (30% vs 13%) groups. Conclusions: This retrospective series, the largest currently available, confirms the activity of Ab and Gb in ES, with a similar RR and PFS in both groups. In this population, the value of P seems limited. These data may serve as a benchmark for trials of novel agents in ES. [Table: see text]
Glycogen-nucleic acid constructs for gene silencing in multicellular tumor spheroids
Authors: Marcin Wojnilowicz, Quinn A. Besford, Yun-Long Wu, Xian Jun Loh, Julia A. Braunger, Agata Glab, Christina Cortez-Jugo, Frank Caruso, Francesca Cavalieri
Journal: Biomaterials (2018)
Rapid Progression of Adult T-Cell Leukemia–Lymphoma after PD-1 Inhibitor Therapy
Authors: Lee Ratner, Thomas A Waldmann, Murali Janakiram, Jonathan E Brammer
Journal: New England Journal of Medicine (2018)

Progression of T-Cell Leukemia with Nivolumab Three patients with chronic, smoldering, and acute subtypes of adult T-cell leukemia–lymphoma had rapid disease progression and increased viral replica...