tbuckley/cabot-search huggingface dataset:
Prevalence of patients with self‐reported hidradenitis suppurativa in a cohort of Danish blood donors: a cross‐sectional study
Authors: P. Theut Riis, O.B. Pedersen, V. Sigsgaard, C. Erikstrup, H.M. Paarup, K.R. Nielsen, K.S. Burgdorf, H. Hjalgrim, K. Rostgaard, K. Banasik, H. Ullum, G.B. Jemec
Journal: British Journal of Dermatology (2018)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent inflamed nodules. No pathognomonic test is available for HS; hence the diagnosis is based on three clinical criteria.To estimate the cross-sectional prevalence and characterize patients with HS in the Danish Blood Donor Study cohort.A questionnaire previously developed containing HS screening questions, the Major Depression Inventory, the Short Form-12, as well as questions about height, weight and drinking habits was answered by 27 765 blood donors.The prevalence of HS was 1·8% [95% confidence interval (CI) 1·6-2·0%] in the cohort of Danish blood donors. Donors with HS were on average 4·7 years younger (P < 0·001), had 1·3 kg m-2 higher mean body mass index (BMI) (P < 0·001) and were significantly more likely to smoke [odds ratio (OR) 1·44, 17·9% vs. 13·1%, P = 0·002] compared with donors without HS. Furthermore, significantly more donors with HS were classified as having moderate depression (3·2% vs. 0·7%, P < 0·001). Also, significantly more patients with HS were apprenticeship educated, received educational support and sickness or cash benefits.The prevalence of HS in the cohort of blood donors was estimated to 1·8% (95% CI 1·6-2·0%). Donors with HS reported characteristics similar to those reported for hospital-based patients with HS such as higher BMI, smoking rates and lower socioeconomic status than donors without HS.
Functions and Mechanisms of Tumor Necrosis Factor-α and Noncoding RNAs in Bone-Invasive Pituitary Adenomas
Authors: Haibo Zhu, Jing Guo, Yutao Shen, Wei Dong, Hua Gao, Yazhou Miao, Chuzhong Li, Yazhuo Zhang
Journal: Clinical Cancer Research (2018)

Purpose: To explore the molecular mechanism and prognosis of bone-invasive pituitary adenomas (BIPA).Experimental design: A total of 274 patients with pituitary adenomas were followed up. Transcriptomic microarrays analysis was performed on 10 pituitary adenomas, including five BIPAs and five non-bone-invasive pituitary adenomas (NBIPA). The targeted molecular markers were validated by qRT-PCR, IHC, ELISA, and osteoclast differentiation.Results: Clinical variable analyses revealed a significant correlation between bone invasion and female sex, large tumor volume, non-gross total resection (NGTR), and tumor regrowth. BIPAs had worse progression-free survival (PFS) than did NBIPAs in the NGTR and nonfunctional pituitary adenoma (NFPA) groups. Gene ontology functional and KEGG pathway analyses showed that the biological processes and pathways were primarily immune and inflammatory pathways. Pathway act work showed that osteoclast differentiation pathway was significantly implicated in the pathway network. BIPAs had higher expression of TNFα than that of NBIPAs on IHC. In vitro, TNFα could induce RAW264.7 cells to differentiate into mature osteoclasts, leading to bone destruction. NR_033258, lncRNA SNHG24, miR-181c-5p, and miR-454-3p can regulate TNFα expression.Conclusions: BIPAs had worse PFS than did NBIPAs in the NGTR and NFPA groups. Inflammatory and immune factors play an important role in BIPAs. TNFα can directly induce osteoclast differentiation in BIPAs. NR_033258, lncRNA SNHG24, miR-181c-5p, and miR-454-3p can regulate TNFα expression. TNFα and its related lncRNAs and miRNAs represent potential therapeutic targets for bone-invasive pituitary adenomas in the future. Clin Cancer Res; 24(22); 5757-66. ©2018 AACR.
Hydrogel-forming microneedles enhance transdermal delivery of metformin hydrochloride
Authors: Eman M. Migdadi, Aaron J. Courtenay, Ismaiel A. Tekko, Maelíosa T.C. McCrudden, Mary-Carmel Kearney, Emma McAlister, Helen O. McCarthy, Ryan F. Donnelly
Journal: Journal of Controlled Release (2018)

We investigated, for the first time, the potential for a hydrogel-forming microneedle (MN) patch to deliver the high-dose drug metformin HCl transdermally in a sustained manner. This may minimize some gastrointestinal side effects and small intestine absorption variations associated with oral delivery. Patches (two layers) were assembled from a lyophilised drug reservoir layer, with the MN layer made from aqueous blend of 20% w/w poly (methylvinylether-co-maleic acid) crosslinked by esterification with 7.5% w/w poly (ethylene glycol) 10,000 Da. >90% of metformin was recovered from homogeneous drug reservoirs. Drug reservoir dissolution time in PBS (pH 7.4) was <10 min. MN penetrated a validated skin model Parafilm® M consistently. Permeation of metformin HCl across dermatomed neonatal porcine skin in vitro was enhanced by using MN. The combined MN and metformin HCl reservoir patch (containing 75 mg or 50 mg metformin HCl, respectively) delivered 9.71 ± 2.22 mg and 10.04 ± 1.92 mg at 6 h, respectively, and 28.15 ± 2.37 mg and 23.25 ± 3.58 mg at 24 h, respectively.In comparison, 0.34 ± 0.39 mg and 0.85 ± 0.68 mg was delivered at 6 h, respectively, and 0.39 ± 0.39 mg and 1.01 ± 0.84 mg was delivered at 24 h, respectively, from a control set-up employing only the drug reservoirs. In vivo, metformin HCl was detected in rat plasma at 1 h post MN application at a concentration of 0.62 ± 0.51 μg/mL, increasing to 3.76 ± 2.58 μg/ml at 3 h. A maximal concentration of 3.77 ± 2.09 μg/ml was achieved at 24 h. Css was 3.2 μg/mL. Metformin transdermal bioavailability using MNs was estimated as 30%.Hydrogel-forming MN are a promising technology that has demonstrated successful transdermal delivery of metformin HCl. Potential clearly exists for administration of other high-dose drugs using this system.
Survey reveals poor public awareness of miscarriage
Authors: S. Mayor
Journal: BMJ (2015)

Many people mistakenly think that miscarriage is rare and that lifestyle factors during pregnancy are a common cause, show the results of a survey of US adults reported in Obstetrics & Gynecology .1

“Miscarriage is a traditionally taboo subject that is rarely discussed publicly,” explained the study’s lead author, Zev Williams, director of the Program for Early and Recurrent Pregnancy Loss at the Albert Einstein College of Medicine, New York. “We initiated this …
Wales to scrap health authorities
Authors: Roger Dobson
Journal: BMJ (2001)

All five health authorities in Wales are to be scrapped as part of a radical reorganisation of the NHS in the principality by the Welsh Assembly.

Under the plans, the assembly itself will take direct control of its health responsibilities through a newly created Health and Well-Being Partnership Council. Local health groups will also be expanded and strengthened and community health councils retained.

The plan also sets targets for training 1385 medical students and 3800 nurses by 2004 and for reducing turnover and vacancy levels. …
Quartz Crystal Microbalance (QCM) Piezo-Immunosensors: A Novel Technique to Study CD20 Antigen Interaction with Rituximab and Its Clinical Implications
Authors: Mohammad Muhsin Chisti, Liang Tan, Justin F. Klamerus, Peiling Lin, Ishmael Jaiyesimi, Abdul Rehman, Xiang Zeng
Journal: Blood (2014)
Imported Melioidosis—South Florida, 2005
Authors: A. Kite-Powell, J. R. Livengood, J. Suarez, R. Hopkins, T. A. Clark, D. Chertow
Journal: JAMA (2006)

Therefore, CDC determined that this particular group of persons vaccinated by the SC route was sufficiently protected and that revaccination was not necessary.CDC cautions health-care providers to be aware that the licensed route of vaccine administration can vary among similar vaccines and recommends that providers carefully review and follow the route of administration indicated on the vaccine label and package insert before administering vaccines.This is especially important after introduction of a new vaccine product.
PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells
Authors: Athena Georgilis, Sabrina Klotz, Christopher J. Hanley, Nicolas Herranz, Benedikt Weirich, Beatriz Morancho, Ana Carolina Leote, Luana D'Artista, Suchira Gallage, Marco Seehawer, Thomas Carroll, Gopuraja Dharmalingam, Keng Boon Wee, Marco Mellone, Joaquim Pombo, Danijela Heide, Ernesto Guccione, Joaquín Arribas, Nuno L. Barbosa-Morais, Mathias Heikenwalder, Gareth J. Thomas, Lars Zender, Jesús Gil
Journal: Cancer Cell (2018)

Oncogene-induced senescence is a potent tumor-suppressive response. Paradoxically, senescence also induces an inflammatory secretome that promotes carcinogenesis and age-related pathologies. Consequently, the senescence-associated secretory phenotype (SASP) is a potential therapeutic target. Here, we describe an RNAi screen for SASP regulators. We identified 50 druggable targets whose knockdown suppresses the inflammatory secretome and differentially affects other SASP components. Among the screen candidates was PTBP1. PTBP1 regulates the alternative splicing of genes involved in intracellular trafficking, such as EXOC7, to control the SASP. Inhibition of PTBP1 prevents the pro-tumorigenic effects of the SASP and impairs immune surveillance without increasing the risk of tumorigenesis. In conclusion, our study identifies SASP inhibition as a powerful and safe therapy against inflammation-driven cancer.
Tetraspanin CD82 affects migration, attachment and invasion of rheumatoid arthritis synovial fibroblasts
Authors: Elena Neumann, Maria C Schwarz, Rebecca Hasseli, Marie-Lisa Hülser, Simon Classen, Michael Sauerbier, Stefan Rehart, Ulf Mueller-Ladner
Journal: Annals of the Rheumatic Diseases (2018)

Tetraspanins function as membrane adaptors altering cell-cell fusion, antigen presentation, receptor-mediated signal transduction and cell motility via interaction with membrane proteins including other tetraspanins and adhesion molecules such as integrins. CD82 is expressed in several malignant cells and well described as tumour metastasis suppressor. Rheumatoid arthritis (RA) is based on persistent synovial inflammation and joint destruction driven to a large extent by transformed-appearing activated synovial fibroblasts (SF) with an increased migratory potential. <h3>Objective</h3> CD82 is upregulated in RA synovial fibroblasts (RASF) compared with osteoarthritis (OA) SF as well as within RA compared with OA synovial lining layer (LL) and the role of CD82 in RASF was evaluated. <h3>Methods</h3> CD82 and integrin immunofluorescence was performed. Lentiviral CD82 overexpression and siRNA-mediated knockdown was confirmed (realtime-PCR, Western blot, immunocytochemistry). RASF migration (Boyden chamber, scrape assay), attachment towards plastic/Matrigel, RASF-binding to endothelial cells (EC) and CD82 expression during long-term invasion in the SCID-mouse-model were evaluated. <h3>Results</h3> CD82 was induced by proinflammatory stimuli in SF. In RA-synovium, CD82 was expressed in RASF close to blood vessels, LL, sites of cartilage invasion and colocalised with distinct integrins involved in tumour metastasis suppression but also in RA-synovium by RASF. CD82 overexpression led to reduced RASF migration, cell-matrix and RASF-EC adhesion. Reduced CD82 expression (observed in the sublining) increased RASF migration and matrix adhesion whereas RASF-EC-interaction was reduced. In SCID mice, the presence of CD82 on cartilage-invading RASF was confirmed. <h3>Conclusion</h3> CD82 could contribute to RASF migration to sites of inflammation and tissue damage, where CD82 keeps aggressive RASF on site.
Physiologically Based Pharmacokinetic (PBPK) Modeling of the Bisphenols BPA, BPS, BPF, and BPAF with New Experimental Metabolic Parameters: Comparing the Pharmacokinetic Behavior of BPA with Its Substitutes
Authors: Cecile Karrer, Thomas Roiss, Natalie von Goetz, Darja Gramec Skledar, Lucija Peterlin Mašič, Konrad Hungerbühler
Journal: Environmental Health Perspectives (2018)

Background: The endocrine disrupting chemical bisphenol A (BPA) has been facing stricter regulations in recent years. BPA analogs, such as the bisphenols S, F, and AF (BPS, BPF, and BPAF) are increasingly used as replacement chemicals, although they were found to exert estrogenic effects similar to those of BPA. Research has shown that only the parent compounds have affinity to the estrogen receptors, suggesting that the pharmacokinetic behavior of bisphenols (BPs) can influence their potency. Objectives: Our goal was to compare the pharmacokinetic behaviors of BPA, BPS, BPF, and BPAF for different age groups after environmentally relevant external exposures by taking into account substance-specific metabolism kinetics and partitioning behavior. This comparison allowed us to investigate the consequences of replacing BPA with other BPs. Methods: We readjusted a physiologically based pharmacokinetic (PBPK) model for peroral exposure to BPA and extended it to include dermal exposure. We experimentally assessed hepatic and intestinal glucuronidation kinetics of BPS, BPF, and BPAF to parametrize the model for these BPs and calibrated the BPS model with a biomonitoring study. We used the PBPK models to compare resulting internal exposures and focused on females of childbearing age in a two-dimensional Monte Carlo uncertainty analysis. Results: Within environmentally relevant concentration ranges, BPAF and BPS were glucuronized at highest and lowest rates, respectively, in the intestine and the liver. The predominant routes of BPS and BPAF exposure were peroral and dermal exposure, respectively. The calibration of the BPS model with measured concentrations showed that enterohepatic recirculation may be important. Assuming equal external exposures, BPS exposure led to the highest internal concentrations of unconjugated BPs. Conclusions: Our data suggest that the replacement of BPA with structural analogs may not lower the risk for endocrine disruption. Exposure to both BPS and BPAF might be more critical than BPA exposure, if their respective estrogenic potencies are taken into account. https://doi.org/10.1289/EHP2739
BIOPSIES ARE NOT RELIABLE IN THE WORK-UP OF COLORECTAL POLYPS
Authors: CF Frimand Rönnow, I Stenfors, E Toth, H Thorlacius
Journal: Endoscopy (2018)

Biopsies are routinely taken in the work-up of colorectal polyps. However, biopsies can cause submucosal fibrosis and make subsequent endoscopic removal more difficult. Moreover, it is not clear how representative biopsies are of the colorectal lesions from which they were taken. The aim of this study was to examine how biopsy results in terms of dysplastic grade correlate with final diagnosis after complete removal of colorectal polyps.
Microbial Detection: Gold Nanoplate‐Enhanced Chemiluminescence and Macromolecular Shielding for Rapid Microbial Diagnostics (Adv. Healthcare Mater. 13/2018)
Authors: Minh‐Phuong Ngoc Bui, John Brockgreitens, Abdennour Abbas
Journal: Advanced Healthcare Materials (2018)

In article 1701506, Abdennour Abbas and co-workers introduce a new rapid microbial detection method using nanoplate-enhanced chemiluminescence. The method combines specific macromolecular shielding of the target bacteria with oxidative etching of triangular gold nanoplates to generate enhanced and stable chemiluminescence signals. The detection can be performed within one hour using a hand-held luminometer.
Targeted breast screening could reduce overdiagnosis and be more cost effective, study finds
Authors: Jacqui Thornton
Journal: BMJ (2018)

A risk stratified approach could improve the cost effectiveness of the UK’s breast screening programme and reduce the “cost” of overdiagnosis to women, a study has found.

Not offering breast cancer screening to women at lower risk would still maintain a reduction in breast cancer deaths, said the authors of a modelling study published in JAMA Oncology .1 However, the charity Breast Cancer Now, while supporting a risk based approach, found it “extremely concerning” that this particular model would see more women die overall.

The screening programme in the UK invites all women aged 50 to 69 for digital mammography every three years. The risk of developing breast cancer varies, and the current “one size …
Impact of socioeconomic status on extent of disease at diagnosis and cancer and ocular outcomes in retinoblastoma: A population-based analysis.
Authors: Bao Truong, Adam L. Green, Paola Friedrich-Medina, Junne Kamihara, A. Lindsay Frazier, Karina Braga Ribeiro, Carlos Rodriguez-Galindo
Journal: Journal of Clinical Oncology (2013)

10011 Background: The strong correlation between early diagnosis and improved outcomes has been consistently reported for retinoblastoma; extent of disease and eye preservation are associated with delayed diagnosis. In this study, we aimed to analyze the impact of socioeconomic status (SES) and ethnicity on extent on disease and cancer and ocular outcomes. Methods: All retinoblastoma cases (0-9 years) recorded in 18 SEER registries between 2000-2009 were included. The county-based disparity variables analyzed included poverty level, education attainment, language isolation, crowding, and percentage of immigrants. The cut-off values were defined as the median values for the cohort of patients. We also analyzed the impact of gender, race, and ethnicity. We tested for the association between SES and ethnicity with the percentage of extraocular disease and enucleation. Relative survival was calculated using Ederer II method; estimates were compared using Z-score. Results: We identified 753 cases. Percentage of extraocular cases was consistently higher in US counties with low SES indicators: higher vs. lower poverty status (29.3% vs. 22.1%, p=0.028); lower vs. higher education attainment (30.6% vs. 22.7%, p=0.003); higher vs. lower crowding (33.2% vs. 18.1%, p&lt;0.001); higher vs. lower language isolation (32.2% vs. 19.3%, p&lt;0.001); higher vs. lower percentage of immigrants (30.1% vs. 21.4%, p=0.008). Hispanic patients had significantly higher percentage of extraocular disease (35.2% vs. 20.9%, p&lt;0.001). Poor ocular outcomes, reflected by high percentage of enucleation, were associated with counties with low education attainment (p=0.025), and with Hispanic origin (p=0.019). Decreased survival was associated with language isolation (p=0.016), but not with Hispanic origin or other SES indicators. Conclusions: Our study highlights significant disparities in the care and outcome of children with retinoblastoma. A low SES negatively impacts extent of disease, presumably by limiting access to primary care and delaying diagnosis. Hispanic patients have more advanced disease and higher enucleation rates, although survival is not significantly different.
A RARE CASE OF OESOPHAGUS DIVERTICULUM
Authors: P Golovics, K Rabai, E Molnar, F Zsigmond, L Herszenyi
Journal: Endoscopy (2018)

A 81-year-old male patient was admitted to the tercier center gastroenterology department. His complains were dysphagia, epigastrial pain, vomiting and food regurgitation. During the 2-month-long complains there was no bleeding or weight loss. The patient was medically treated due to reflux in the past 20 years by the GP. In his medical history, he had an operation and received hormonal injection therapy due to prostate cancer.
HVAD: The ENDURANCE Supplemental Trial
Authors: Carmelo A. Milano, Joseph G. Rogers, Antone J. Tatooles, Geetha Bhat, Mark S. Slaughter, Emma J. Birks, Nahush A. Mokadam, Claudius Mahr, Jeffrey S. Miller, David W. Markham, Valluvan Jeevanandam, Nir Uriel, Keith D. Aaronson, Thomas A. Vassiliades, Francis D. Pagani
Journal: JACC Heart Failure (2018)

The aim of this study was to prospectively evaluate the impact of blood pressure management on stroke rates in patients receiving the HeartWare HVAD System. The ENDURANCE trial demonstrated noninferiority of the HeartWare HVAD System versus control (HeartMate II) in patients with advanced heart failure ineligible for heart transplantation. However, stroke was more common in HVAD subjects. Post hoc analyses demonstrated increased mean arterial blood pressure as a significant independent risk factor for stroke. The ENDURANCE Supplemental Trial was a prospective, multicenter evaluation of 465 patients with advanced heart failure ineligible for transplantation, randomized 2:1 to HVAD (n = 308) or control (n = 157). The primary endpoint was the 12-month incidence of transient ischemic attack or stroke with residual deficit 24 weeks post-event. Secondary endpoints included the composite of freedom from death, disabling stroke, and need for device replacement or urgent transplantation, as well as comparisons of stroke or transient ischemic attack rates in HVAD cohorts in ENDURANCE Supplemental and ENDURANCE. The enhanced blood pressure protocol significantly reduced mean arterial blood pressure. The primary endpoint was not achieved (14.7% with HVAD vs. 12.1% with control, noninferiority [margin 6%] p = 0.14). However, the secondary composite endpoint demonstrated superiority of HVAD (76.1%) versus control (66.9%) (p = 0.04). The incidence of stroke in HVAD subjects was reduced 24.2% in ENDURANCE Supplemental compared with ENDURANCE (p = 0.10), and hemorrhagic cerebrovascular accident was reduced by 50.5% (p = 0.02). The ENDURANCE Supplemental Trial failed to demonstrate noninferiority of HVAD versus control regarding the pre-specified primary endpoint. However, the trial confirmed that BP management is associated with reduced stroke rates in HVAD subjects. HVAD subjects, relative to control subjects, more commonly achieved the composite endpoint (freedom from death, disabling stroke, and device replacement or urgent transplantation). (A Clinical Trial to Evaluate the HeartWare™ Ventricular Assist System [ENDURANCE SUPPLEMENTAL TRIAL] [DT2]; NCT01966458)