tbuckley/cabot-search huggingface dataset:
Public health consultants to be asked how NHS reforms have affected their work
Authors: Abi Rimmer
Journal: BMJ (2013)

Public health consultants are being surveyed on how the government’s changes to the NHS have affected their work.

The Centre for Workforce Intelligence is asking all consultants and specialists in public health in England about their roles and any issues arising since local authorities took responsibility for public health in April (www.smartsurvey.co.uk/s.asp?i=93785XGUPM).

The survey aims to offer insight into the public health workforce since the formation of Public Health England (PHE) and …
Soft‐tissue dehiscence coverage at peri‐implant sites
Authors: Claudio Mazzotti, Martina Stefanini, Pietro Felice, Valentina Bentivogli, Ilham Mounssif, Giovanni Zucchelli
Journal: Periodontology 2000 (2018)

Soft-tissue dehiscence at the facial aspect of an osteointegrated implant is a common complication which impacts on the final esthetic result. The etiology and ways of diagnosing this condition are still controversial. Many factors seem to influence the position of the peri-implant soft-tissue margin, and some of these have been studied more carefully than others. Various surgical and combination surgical-prosthetic approaches have been described to treat soft-tissue dehiscence, with the latter appearing to be more predictable. This paper focuses on the factors affecting peri-implant soft-tissue margins and describes the different treatment approaches, reported in the literature, to treat buccal soft-tissue dehiscence, with more focus on the prosthetic-surgical-prosthetic approach.
Protein S Protects against Podocyte Injury in Diabetic Nephropathy
Authors: Fang Zhong, Haibing Chen, Yifan Xie, Evren U. Azeloglu, Chengguo Wei, Weijia Zhang, Zhengzhe Li, Peter Y. Chuang, Belinda Jim, Hong Li, Firas Elmastour, Jalish M. Riyad, Thomas Weber, Hongyu Chen, Yongjun Wang, Aihua Zhang, Weiping Jia, Kyung Lee, John C. He
Journal: Journal of the American Society of Nephrology (2018)

Background Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear.Methods To assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors. Because increased activation of Axl by the PS homolog Gas6 has been implicated in DN progression, we further examined the role of PS in DN.Results In human kidneys, glomerular PS expression was elevated in early DN but suppressed in advanced DN. However, plasma PS concentrations did not differ between patients with DN and healthy controls. A prominent increase of PS expression also colocalized with the expression of podocyte markers in early diabetic kidneys. In cultured podocytes, high-glucose treatment elevated PS expression, and PS knockdown further enhanced the high-glucose-induced apoptosis. Conversely, PS overexpression in cultured podocytes dampened the high-glucose- and TNF-α-induced expression of proinflammatory mediators. Tyro3 receptor was upregulated in response to high glucose and mediated the anti-inflammatory response of PS. Podocyte-specific PS loss resulted in accelerated DN in streptozotocin-induced diabetic mice, whereas the transient induction of PS expression in glomerular cells in vivo attenuated albuminuria and podocyte loss in diabetic OVE26 mice.Conclusions Our results support a protective role of PS against glomerular injury in DN progression.
Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort
Authors: Thibault Fiolet, Bernard Srour, Laury Sellem, Emmanuelle Kesse-Guyot, Benjamin Allès, Caroline Méjean, Mélanie Deschasaux, Philippine Fassier, Paule Latino-Martel, Marie Beslay, Serge Hercberg, Céline Lavalette, Carlos A Monteiro, Chantal Julia, Mathilde Touvier
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To assess the prospective associations between consumption of ultra-processed food and risk of cancer. <h3>Design</h3> Population based cohort study. <h3>Setting and participants</h3> 104 980 participants aged at least 18 years (median age 42.8 years) from the French NutriNet-Santé cohort (2009-17). Dietary intakes were collected using repeated 24 hour dietary records, designed to register participants’ usual consumption for 3300 different food items. These were categorised according to their degree of processing by the NOVA classification. <h3>Main outcome measures</h3> Associations between ultra-processed food intake and risk of overall, breast, prostate, and colorectal cancer assessed by multivariable Cox proportional hazard models adjusted for known risk factors. <h3>Results</h3> Ultra-processed food intake was associated with higher overall cancer risk (n=2228 cases; hazard ratio for a 10% increment in the proportion of ultra-processed food in the diet 1.12 (95% confidence interval 1.06 to 1.18); P for trend&lt;0.001) and breast cancer risk (n=739 cases; hazard ratio 1.11 (1.02 to 1.22); P for trend=0.02). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet (lipid, sodium, and carbohydrate intakes and/or a Western pattern derived by principal component analysis). <h3>Conclusions</h3> In this large prospective study, a 10% increase in the proportion of ultra-processed foods in the diet was associated with a significant increase of greater than 10% in risks of overall and breast cancer. Further studies are needed to better understand the relative effect of the various dimensions of processing (nutritional composition, food additives, contact materials, and neoformed contaminants) in these associations. <h3>Study registration</h3> Clinicaltrials.gov NCT03335644.
P003 IGF1R signalling is essential for neurological symptoms in RA
Authors: KM Andersson, L Juzokaite, C Wasen, A Stokowska, L Leifsdottir, MC Erlandsson, M Pekna, M Pekny, K Olmarker, M Kalm, MI Bokarewa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> In addition to inflammation of the joints, rheumatoid arthritis (RA) has a neurological part consisting of pain, fatigue, depression and cognitive deterioration. These symptoms are critical for the patients' ability to cope with daily life, but are not alleviated completely with modern antirheumatic drugs. Sufficient IGF1R signalling is important for neurogenesis in the hippocampus. Its misbalance correlates with depression and anxiety. <h3>Objectives</h3> The aim of this study was to evaluate the pathological changes in the brain during experimental RA and investigate their connexion to IGF1R. <h3>Methods</h3> Characteristics of pain, depression and anxiety were collected among 214 RA patients and analysed in relation to IGF1R expression in WBC. Experimental RA was induced by immunisation with collagen II. Inhibition of IGF1R was achieved by injection of shRNA-producing lentiviral construct. The behavioural pattern of each mouse was recorded by filming. The hippocampus was analysed morphometrically, and gene and protein expression were analysed by qPCR and immunohistochemistry, respectively. <h3>Results</h3> The RA patients' perception of depression and anxiety was associated with high IGF1R expression in WBC. This group of patients was also less physically active. In experimental RA, an enrichment of IBA1 +microglia and high expression of CD68 and IL-1b was found in the hippocampus. This was followed by an increased density of IGF1R+cells in cornu ammoni, and a decreased neurogenesis by limited expression DCX in the subgranular layer of the dentate gyrus. This results in a significant reduction of the hippocampus area. These changes in the brain were associated with immobility in RA mice. Treatment with shRNA targeting IGF1R improved arthritis, but led to increased immobility. <h3>Conclusions</h3> RA induces remote inflammation in the hippocampus reducing neurogenesis and physical activity. The neurological symptoms in patients and in experimental RA are connected to IGF1R expression and signalling, and further expands our knowledge of neurological processes in RA. <h3>Disclosure of interest</h3> None declared
Risk of depression among patients with acne in the U.K.: a population-based cohort study
Authors: I.A. Vallerand, R.T. Lewinson, L.M. Parsons, M.W. Lowerison, A.D. Frolkis, G.G. Kaplan, C. Barnabe, A.G.M. Bulloch, S.B. Patten
Journal: British Journal of Dermatology (2018)
The impact of bad press
Authors: Tom Moberly
Journal: BMJ (2014)

Over the past two decades the media’s portrayal of doctors has gradually shifted from appreciation and respect towards antipathy and resentment, but in recent months this growing hostility seems to have stepped up a gear or two.

In May the Times ran a column about the medical workforce under the heading “These overpaid doctors must stop whingeing.” At the BMA’s annual representative …
CORONARY BIFURCATION BENCH FOR SEQUENTIAL PROXIMAL OPTIMIZING TECHNIQUE USING MULTIMODALITY IMAGING
Authors: Teruyoshi Kume, Ryotaro Yamada, Terumasa Koyama, Tomoko Tamada, Koichiro Imai, Kenzo Fukuhara, Ai Kawamura, Hiroshi Okamoto, Yoji Neishi, Shiro Uemura
Journal: Journal of the American College of Cardiology (2018)
Whole-exome sequencing reveals acquisition of mutations leading to the onset of donor cell leukemia after hematopoietic transplantation: a model of leukemogenesis
Authors: Julia Suárez-González, Carolina Martínez-Laperche, Nerea Martínez, Gabriela Rodríguez-Macías, Mi Kwon, Pascual Balsalobre, Diego Carbonell, María Chicano, David Serrano, Juan Carlos Triviño, Miguel Ángel Piris, Jorge Gayoso, José Luis Díez-Martín, Ismael Buño
Journal: Leukemia (2018)
Abstract 351: The Family Study: Assessment of the Risk for Sudden Cardiac Arrest in Family Members of Cardiac Arrest Patients
Authors: Katherine S Allan, Theresa Aves, Laurie J Morrison, Jack Tu, Matthew Guttman, Paul Dorian
Journal: Circulation (2013)

Background: Sudden cardiac arrest (SCA) is devastating for the patient’s family, friends, and community. There is limited information on its identifiable familial predisposition. Objectives: To evaluate the familial risk pattern for SCA in family members of cases compared to age-and-sex matched control groups. Incidence of prior symptoms and SCA triggers were also compared. Methods: We used a prospectively collected, population-based registry of all out-of-hospital cardiac arrests (OHCAs) in the Greater Toronto Area, to identify cases from 2010-2012. Cases were defined as SCA patients aged 18-65 who arrested from a cardiac cause and were treated by Emergency Medical Services. Two relatives per patient were interviewed regarding symptoms prior to the arrest, cardiac history and family history of SCA. Control patients with known coronary heart disease (CHD) and healthy participants were recruited from PCI procedures and the Family Practice Units at St. Michael’s Hospital. Results: Complete family and medical history was obtained for 66 SCA cases, 56 heart disease patients and 27 healthy controls. Underlying diseases were CHD in 77%, non-CHD structural heart disease in 9%, primary arrhythmic in 3% and presumed cardiac of unknown etiology in 11%. A higher proportion of SCA individuals had a family history of SCA in 1st degree relatives (19/66; 28.8%) than 1st degree relatives of healthy controls (2/27; 7%; p=0.006) and 1st degree relatives of patients with heart disease (14/56; 25%) (Table 1). Among families with SCA, 3/66 (4.5%) had a history of &gt;1 relative with SCA, vs. none in either control group. Most SCA patients experienced one or more warning symptoms in the hour preceding an arrest (40/66; 61%); 24/66 (36%) experienced a cardiac arrest during or following exercise. Conclusion: Family members of SCA patients have a higher SCA prevalence than family members of healthy controls. A high proportion of SCA patients experienced symptoms in the hour preceding their arrest.
The Physiological, Pathological and Molecular Basis of Nonalcoholic Steatohepatitis Associated Cardiomyopathy
Authors: A Oseini, S Toldo, M Seneshaw, D P Kumar, P K Santhekadur, Min H-K., E Mezzaroma, P Bedossa, A G Mauro, F Quaini, C Frati, A Falco, S Koduru, B A Banini, F Mirshahi, A Abbate, O Rider, M Siddiqui, A J Sanyal
Journal: Hepatology (2017)
Cost-effectiveness of front-line trials in metastatic colorectal cancer: Integrating the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) with the costs of drugs.
Authors: Andrea Bonetti, Jcopo Giuliani
Journal: Journal of Clinical Oncology (2017)

6622 Background: In Western Countries, colorectal cancer (CRC) is the second most common cause of death from cancer. In light of the relevant expenses of drugs it might be interesting to make a balance between the cost of the drugs and clinical parameters of interest such as progression free survival (PFS). Methods: Phase III randomized clinical trials (RCTs) that compared at least two front-line chemotherapy regimens for mCRC patients were evaluated. Differences in PFS between the different arms were calculated and compared with the pharmacological costs (at the Pharmacy of our Hospital) needed to get one month of PFS. Subsequently we applied the ESMO-MCBS (a 1 to 5 scale) to the above phase III RCTs. Results: Overall 28 phase III RCTs, including 19 958 patients, were analyzed. The FOLFOX resulted the least expensive (56 € per month of PFS gained) while the addition of irinotecan to FOLFOX (FOLFOXIRI) increased only marginally the costs (90 € per month of PFS gained). Treatments including the monoclonal antibodies showed a cost per month of PFS gained of 2823 € (FOLFIRI with cetuximab in KRAS wild-type patients and liver-only metastases), of € 15 822 (FOLFOX with panitumumab in KRAS wild type) and of 13 383 € (FOLFOX with bevacizumab). According to the ESMO-MCBS the treatments including an EGFR-inhibitor (cetuximab or panitunumab) were associated with a score of 4 while the inclusion of bevacizumab reached a score of 3. The remaining phase III RCTs obtained a low (grade 1-2) score.Dividing the costs per month of PFS gained with the grade of ESMO-MCBS, for each RCTs, we obtained the costs of each point of ESMO-MCBS per month of PFS gained. FOLFOX was confirmed as being the least expensive (18.7 €) while among treatments including a targeted biological agent panitunumab in combination with FOLFOX in K-RAS wild type patients was less expensive (3955 €) than the combinations FOLFOX-bevacizumab (13 383 €) and FOLFIRI-cetuximab in K-RAS wild type patients (21 854.6 €). Conclusions: Our data demonstrate a huge difference in cost per month of PFS gained and per each point of the ESMO-MCBS in modern front line treatments in mCRC.
Use of Oxyhemoglobin Saturation or Oxygen Tension—An Unsolved Question
Authors: Itamar Nitzan, Francis B. Mimouni, Cathy Hammerman
Journal: JAMA Pediatrics (2018)

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Social determinants of mental disorders and the Sustainable Development Goals: a systematic review of reviews
Authors: Crick Lund, Carrie Brooke-Sumner, Florence Baingana, Emily Claire Baron, Erica Breuer, Prabha Chandra, Johannes Haushofer, Helen Herrman, Mark Jordans, Christian Kieling, Maria Elena Medina-Mora, Ellen Morgan, Olayinka Omigbodun, Wietse Tol, Vikram Patel, Shekhar Saxena
Journal: The Lancet Psychiatry (2018)
A phase 1b investigation of safety/efficacy of nivolumab and ABI-009 (<i>nab</i>-rapamycin) in advanced undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), chondrosarcoma (CS), osteosarcoma (OS) and Ewing sarcoma.
Authors: Erlinda Maria Gordon, Victoria S. Chua-Alcala, Katherine Kim, Doris M Quon, Sant P Chawla
Journal: Journal of Clinical Oncology (2018)

TPS45 Background: Immune checkpoint inhibitors that promote sustained T cell activation may have synergistic activity with an mTOR inhibitor. Objectives: (1) To investigate the maximum tolerated dose of ABI-009, an mTOR inhibitor, when given sequentially with nivolumab, a PD-1 inhibitor, in advanced UPS, LPS, CS, OS and Ewing sarcoma; (2) To investigate the disease control rate (DCR), progression free survival (PFS), recurrence-free survival (RFS) and overall survival using nivolumab/ABI-009 combination therapy in advanced UPS, LPS, CS, OS and Ewing sarcoma; (3) To correlate disease control rate (DCR) based on Immune-related Response Criteria (irRECIST) with that based on RECIST v1.1, and to correlate PFS with PD-L1 and other biomarker expression in patients’ tumors. Methods: Forty to fifty previously treated patients with UPS, LPS, CS, OS or Ewing sarcoma will be enrolled. This is a phase 1b study using a defined dose of nivolumab 240 mg and escalating doses of ABI-009 56,75,100 mg/m 2 given i.v. I. Dose Escalation Phase 1 Part of Study: The study will employ the standard “cohort of three” design. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. II. Expansion Phase 1b Part of Study: An additional 22-28 patients will receive ABI-009 at the MTD and defined doses of nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients in the expansion phase of the study may continue treatment until significant disease progression or unacceptable toxicity occurs. Statistical Considerations: Categorical variables will be summarized by the n and percent in each category. Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. Clinical trial information: NCT03190174.
RESPIRE: breathing new life into bronchiectasis
Authors: Sanjay H. Chotirmall, James D. Chalmers
Journal: European Respiratory Journal (2018)

RESPIRE, definable as "the recovery of hope, courage and strength after a time of difficulty", is apt in the context of bronchiectasis therapy. Despite its recent renaissance, including the publication of the first international guidelines for the management of bronchiectasis, only a single treatment recommendation in the 2017 European Respiratory Society guidelines was supported by high-quality evidence [1]. This is a timely reminder of the real and challenging battle ahead, to deliver evidence-based appropriate and effective therapies to patients. In this issue of the European Respiratory Journal , a major "blow" in this battle has been struck and appears to have landed its intended target [2, 3]. The RESPIRE 1 and 2 trials evaluated 32.5 mg ciprofloxacin dry powder inhalation (DPI) administered twice daily versus placebo in two separate 2×2 arm trials. Taken together, these two trials represent the largest clinical trial programme ever conducted in bronchiectasis. Each trial studied a 14- and 28-day on/off drug regime over a 48-week period. The two trials differed by: 1) their enrolling countries; and 2) statistical handling of the data. RESPIRE 1 largely enrolled across Europe, North and South America, Australia and included Japan, while RESPIRE 2 focused on Asia and Eastern Europe. The inclusion criteria were the same for each set of trials, requiring patients with bronchiectasis infected with one of a list of the most commonly identified pathogens, and a history of ≥2 exacerbations in the previous year. The RESPIRE trials provide promise for bronchiectasis <http://ow.ly/Vxqq30hSgjx>
BMA tells pay review body that doctors are working longer hours without recognition
Authors: Abi Rimmer
Journal: BMJ (2014)

The BMA has told the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) that doctors were being asked to work increasingly long hours without any recognition.

As part of written evidence to the DDRB, the government answered questions posed by the BMA in its evidence to the review body.1 The review body is taking evidence from both parties to make …
HSF1 Is Essential for Myeloma Cell Survival and A Promising Therapeutic Target
Authors: Jacqueline H.L. Fok, Somaieh Hedayat, Lei Zhang, Lauren I. Aronson, Fabio Mirabella, Charlotte Pawlyn, Michael D. Bright, Christopher P. Wardell, Jonathan J. Keats, Emmanuel De Billy, Carl S. Rye, Nicola E.A. Chessum, Keith Jones, Gareth J. Morgan, Suzanne A. Eccles, Paul Workman, Faith E. Davies
Journal: Clinical Cancer Research (2018)

Myeloma is a plasma cell malignancy characterized by the overproduction of immunoglobulin, and is therefore susceptible to therapies targeting protein homeostasis. We hypothesized that heat shock factor 1 (HSF1) was an attractive therapeutic target for myeloma due to its direct regulation of transcriptional programs implicated in both protein homeostasis and the oncogenic phenotype. Here, we interrogate HSF1 as a therapeutic target in myeloma using bioinformatic, genetic, and pharmacologic means.
EXOSOMES PRODUCED BY HUMAN AMNIOTIC MESENCHYMAL STEM CELL-DERIVED INDUCED PLURIPOTENT STEM CELLS MODULATE IMMUNE RESPONSE IN MURINE MYOCARDIAL INJURY MODEL
Authors: Albert Jang, Hye Sun Seo, Daniel Bornstaedt, Ji Hye Jung, Evgeniya Vaskova, Phillip Yang
Journal: Journal of the American College of Cardiology (2018)
Abstract ES10-2: A novel human derived organoid platform for breast cancer research
Authors: O Kopper
Journal: Cancer Research (2018)

Abstract Breast cancer (BC) is a heterogeneous disease consisting of multiple tumor subtypes. We have recently established a novel human derived 3D in-vitro platform, which enables long-term expansion of BC organoids. Thus, we were able to derive ∼100 BC organoid lines from both primary and metastatic tumors. These lines represent the diversity of the disease and faithfully recapitulate the histology, hormone receptor and HER2 status of the tumors from which they were derived. Whole genome sequencing analysis of tumor-organoid pairs, demonstrated that copy number alterations and single nucleotide variations, were broadly maintained, even after extended passaging. BC organoids allowed performing in-vitro drug screens that were consistent with in-vivo xenografts and patient response. Thus, we suggest that this platform can be utilized as a valuable tool for BC research, facilitate drug development and present us with new opportunities for personalized medicine. Citation Format: Kopper O. A novel human derived organoid platform for breast cancer research [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES10-2.