tbuckley/cabot-search huggingface dataset:
Simplified procedures to treat periodontal intraosseous defects in esthetic areas
Authors: Leonardo Trombelli, Anna Simonelli, Luigi Minenna, Renata Vecchiatini, Roberto Farina
Journal: Periodontology 2000 (2018)

Abstract Successful treatment of deep intraosseous defects in esthetic areas implies clinical improvement of the lesion consistent with long‐term tooth survival as well as the preservation (or improvement) of esthetics. It is hoped that such treatment end points may be reached through procedures (which we have termed as ‘simplified’) that, on the one hand can be easily and successfully applied by the majority of clinicians, and, on the other hand, are well tolerated by patients in terms of postsurgical pain and discomfort, adverse events and cost. In this review, we describe the technical aspects of the simplified procedures currently available (i.e. nonsurgical therapy and the single flap approach and its variants). Also, we analyze the effect of such procedures on clinical parameters and patient‐centered outcomes. While nonsurgical therapy seems to be appropriate per se in lesions with a probing depth of &lt; 7 mm and a limited intraosseous component, severe intraosseous defects can be successfully treated using simplified surgical procedures. Overall, data support the effectiveness of simplified surgical procedures and indicate that they result in minimal esthetic impairment (i.e. post‐treatment recession) and a more tolerable postoperative course when compared with conventional surgical (double flap) approaches. In particular, the single flap approach was shown to be at least as effective as traditional papilla‐preservation techniques when evaluated either as a stand‐alone protocol or in combination with regenerative devices. Bioactive agents have shown the most appropriate regenerative technology when used in association with simplified surgical procedures.
Treatment strategy and prognostic factors for Krukenberg tumors of gastric origin: Report of a 10-year single-center experience from China.
Authors: Yu Pengfei, Ling Huang, Yian Du
Journal: Journal of Clinical Oncology (2018)

52 Background: Gastric cancer patient with ovarian metastasis, i.e. Krukenberg tumor, is common in clinical practice, but it is still uncertain whether surgical resection of ovarian metastasis could improve the outcome. This study aimed to explore the survival benefit of metastasectomy plus chemotherapy over chemotherapy alone in the treatment of Krukenberg tumors arising from gastric cancer and to identify prognostic factors. Methods: All patients who were diagnosed with gastric cancer and ovarian metastases between January 2005 and December 2014 were included in the current study. Patients were subdivided according to treatment modality: the metastasectomy group (metastasectomy plus chemotherapy) and the non-metastasectomy group (chemotherapy alone). The clinicopathological features and the treatment records were reviewed in detail and their association with survival were analyzed. Results: A total of 152 patients were identified, including 93 patients with synchronous ovarian metastasis and 59 patients with metachronous ovarian metastasis. Overall survival (OS) was significantly better in metastasectomy group relative to the non-metastasectomy group for patients with synchronous ovarian metastasis (19.0 months vs. 11.8 months; P &lt; 0.001) and those with metachronous ovarian metastasis (24.6 months vs. 14.3 months; P = 0.02), respectively. Metastasectomy (hazard ration [HR] 0.486; 95% confidence interval [CI] 0.323–0.729; P &lt; 0.001), peritoneal carcinomatosis (HR 1.934; 95% CI 1.230–3.049; P = 0.004), and expression status of ER-β (HR 0.404; 95% CI 0.251–0.648; P &lt; 0.001) and PR (HR 0.496; 95% CI 0.301–0.817; P &lt; 0.001) were independent predictors of OS. Conclusions: Metastasectomy plus chemotherapy was associated with survival benefits in patients with Krukenberg tumors from gastric cancer. Metastasectomy, peritoneal carcinomatosis, and expression status of ER-β and PR were independent prognostic factors for survival.
The hepatic BMAL1/AKT/lipogenesis axis protects against alcoholic liver disease in mice via promoting PPARα pathway
Authors: Deqiang Zhang, Xin Tong, Bradley B. Nelson, Ethan Jin, Julian Sit, Nicholas Charney, Meichan Yang, M. Bishr Omary, Lei Yin
Journal: Hepatology (2018)

Alcohol liver disease (ALD) is one of the major chronic liver diseases worldwide, ranging from fatty liver, alcoholic hepatitis, cirrhosis, and potentially, hepatocellular carcinoma. Epidemiological studies suggest a potential link between ALD and impaired circadian rhythms, but the role of hepatic circadian proteins in the pathogenesis of ALD remains unknown. Here we show that the circadian clock protein BMAL1 in hepatocytes is both necessary and sufficient to protect mice from ALD. Ethanol diet‐fed mice with liver‐specific knockout ( Bmal1‐LKO ) or depletion of Bmal1 develop more severe liver steatosis and injury as well as a simultaneous suppression of both de novo lipogenesis and fatty acid oxidation, which can be rescued by the supplementation of synthetic PPARα ligands. Restoring de novo lipogenesis in the liver of Bmal1‐LKO mice by constitutively active AKT not only elevates hepatic fatty acid oxidation but also alleviates ethanol‐induced fatty liver and liver injury. Furthermore, hepatic over‐expression of lipogenic transcription factor ChREBP, but not SREBP‐1c, in the liver of Bmal1‐LKO mice also increases fatty acid oxidation and partially reduces ethanol‐induced fatty liver and liver injury. Conclusion : we identified a protective role of BMAL1 in hepatocytes against ALD. The protective action of BMAL1 during alcohol consumption depends on its ability to couple ChREBP‐induced de novo lipogenesis with PPARα‐mediated fatty oxidation. (H epatology 2018).
Margaret McCartney: Do we want an NHS that depends on outsourcing?
Authors: Margaret McCartney
Journal: BMJ (2018)

Carillion, the outsourcing company that provided the NHS with cleaners, porters, and catering, has hit the buffers. The only people surprised by this are those who haven’t been paying attention.

Outsourcing as a principle has been beloved of governments of red and blue hues over the past couple of decades. Under this model, companies are not directly contracted to do certain work: instead, a large company contracts smaller companies to do it.

As outsourcing has become normal the debate on what “privatisation” of the NHS amounts to, or what it would look like, is magnified. What does it matter who …
UTMD-Promoted Co-Delivery of Gemcitabine and miR-21 Inhibitor by Dendrimer-Entrapped Gold Nanoparticles for Pancreatic Cancer Therapy
Authors: Lizhou Lin, Yu Fan, Feng Gao, Lifang Jin, Dan Li, Wenjie Sun, Fan Li, Peng Qin, Qiusheng Shi, Xiangyang Shi, Lianfang Du
Journal: Theranostics (2018)

Conventional chemotherapy of pancreatic cancer (PaCa) suffers the problems of low drug permeability and inherent or acquired drug resistance. Development of new strategies for enhanced therapy still remains a great challenge. Herein, we report a new ultrasound-targeted microbubble destruction (UTMD)-promoted delivery system based on dendrimer-entrapped gold nanoparticles (Au DENPs) for co-delivery of gemcitabine (Gem) and miR-21 inhibitor (miR-21i).
Trainee surgeons warn of dangers of emergency cross cover rotas
Authors: Helen Jaques
Journal: BMJ (2013)

Trainee surgeons have warned that care of patients is being compromised by specialty trainees being made to provide emergency cross cover in specialties different from their own.

Cross cover occurs when doctors who are training in one specialty provide emergency care, usually out of hours or when on call, for another specialty. Some pairs of surgical specialties where cross cover is common are general surgery and urology; ear, nose, and throat (ENT) and maxillofacial surgery; and orthopaedics and plastic surgery. …
CLINICAL AND ECHOCARDIOGRAPHIC PARAMETERS IN PATIENTS WITH ATRIAL FIBRILLATION AND LEFT ATRIAL APPENDAGE THROMBUS
Authors: David H. Hsi, Ashley Zinda, Nicholas Rossi, Steven Sprankle, Allen Mogtader, Renee Bullock-Palmer, Denise Zingrone, Leilei Chung, Xiujie Han
Journal: Journal of the American College of Cardiology (2018)
IMPACT OF SUCCESSFUL PERCUTANEOUS CORONARY INTERVENTION ON CHRONIC TOTAL OCCLUSION OUTCOMES IN MULTI-VESSEL DISEASE PATIENTS
Authors: Seung-Woon Rha, Se Yeon Choi, Byoung Geol Choi, Jae Kyeong Byun, Ahmed Mashaly, Yoonjee Park, Won Young Jang, WooHyeun Kim, Eun Jin Park, Ja Yeon Choi, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2018)
RESISTANCE EXERCISE AND LEFT VENTRICULAR STRUCTURE AS ASSESSED USING CARDIAC COMPUTED TOMOGRAPHY ANGIOGRAPHY: A CONTEMPORARY REASSESSMENT OF THE MORGANROTH HYPOTHESIS
Authors: Dahlia Banerji, Daniel Bittner, Borek Foldyna, Bálint Szilveszter, Nandini Meyersohn, Raza Alvi, James I. Hudson, Udo Hoffmann, Harrison Pope, Aaron Baggish, Michael T. Lu
Journal: Journal of the American College of Cardiology (2018)
The pathway regulating RhoA activity to predict the survival of gastric cancers.
Authors: Jing Gao, Wenwen Huang, Shuo Mu, Songhui Zhao, Shuirong Zhang, Peng Zhang, Sai Ge, Zhongwu Li, Cheng Zhang, Ming Yao, Zhenzhen Liu, Kai Wang, Weiwei Shi, Lin Shen
Journal: Journal of Clinical Oncology (2018)

49 Background: RhoA mutation has been intensively studied for its association with progression in gastric cancer (GC). Recently, mutations in a pathway regulating RhoA activity have been identified as a predictive biomarker in breast cancer. Herein, our aim is to investigate the role of such pathway in the progression of patients with GC receiving chemotherapies. Methods: Two non-overlapped TCGA cohorts (TCGA1, downloaded from GDC, N = 123 and TCGA2, from Cbioportal, N = 312) and a third ACRG cohort (Nature Medicine 2015, N = 295) were assessed for their mutation status of RhoA pathway; meanwhile, a cohort from Chinese GC (CGC, N = 57) was examined with whole exome sequencing (WES). A subset of “Regulation of RhoA activity” pathway (NCI Pathway Interaction), denoted as RhoA_S, was derived from analyzing the expression of RhoA and mutations in TCGA1 without referring to its survival data. Subsequently, RhoA_S was evaluated for its prediction of overall survival (OS) in the above four GC cohorts receiving chemotherapies. Results: GCs with wild-type of RhoA_S as well as gain-of-function of RhoA mutation where the function of RhoA remained active were compared against those with mutated RhoA_S. The frequencies for the mutant RhoA_S were 46.3%, 24.0%, 16.3% and 50.9% for TCGA1, TCGA2, ACRG and CGC, respectively; while the “active” RhoA_S were found more unlikely to respond to chemotherapies and significantly associated with poor clinical outcomes in all four cohorts. The hazard ratios and p-values were 0.513, 0.009 for TCGA1; 0.509, 0.02 for TCGA2; 0.6, 0.04 for ACRG and 0.229, 0.014 for CGC, respectively. Conclusions: Four independent GC cohorts (totally 787 patients) validated RhoA_S as a predictive biomarker for their survival. Not only have our results confirmed gain-of-function in RhoA mutant facilitates the progression of GC patients, but also indicated the regulators of RhoA activity are implicated in their overall survival. This study has provided us an option to extend potentially druggable targets in highly malignant cancers with poor prognosis like GC.
Detection of myositis-specific antibodies: additional notes
Authors: Maria Infantino, Mariangela Manfredi, Valentina Grossi, Maurizio Benucci
Journal: Annals of the Rheumatic Diseases (2018)

With great interest, we read the letters that have commented on the recent European League Against Rheumatism/American College of Rheumatology classification criteria for idiopathic inflammatory myopathies1 (IIMs) and ensuing discussions.2 3 This highlights how harmonising myositis-specific antibodies (MSA) testing methodologies is currently a hot topic of debate among laboratory specialists, clinicians and manufacturers.

I would particularly like to share our own immunology laboratory experience by expanding on the letter entitled ‘Detection of myositis-specific antibodies: additional notes’ by M Mahler and M Fritzler4 with which we wholly agree.

Newer technologies, such as line immunoassays (LIA) and dot blots (DB), which provide greater sensitivity and rapid serological diagnoses, have standardisation and specificity drawbacks, but the tight connection between autoantibodies and clinical phenotypes underline a great need …
Germline variant in <i>HSD3B1</i> (1245 A&gt;C) and response to abiraterone acetate plus prednisone (AA) in men with new onset metastatic castration-resistant prostate cancer (mCRPC).
Authors: Andrew W Hahn, David Michael Gill, Roberto Nussensveig, Austin Poole, James M. Farnham, Lisa A Cannon-Albright, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2018)

173 Background: The HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen. Recently, multiple reports validated the role of HSD3B1 (1245 A&gt;C) variant in predicting response to androgen deprivation therapy (ADT) in castration sensitive prostate cancer. The objective of this study was to correlate HSD3B1 variantwith response AA in first-line therapy for men with mCRPC. Methods: Clinical data and samples were from a prospectively maintained prostate cancer registry at the University of Utah. Genotyping was performed as described by Hearn at al (Lancet Oncology, 2016). Primary endpoint was progression-free survival in first-line AA in men with mCRPC. We performed pre-specified multivariate analyses to assess the independent predictive value of HSD3B1 genotype on PFS on AA (Table). Results: 76 men with mCRPC treated with first-line AA were included. In multivariate analysis, HSD3B1 (1245 A&gt;C) did not predict response to first-line AA (Table). Conclusions: This hypothesis-generating data shows that inherited variant alleles in HSD3B1 do not predict response to first-line AA in mCRPC. This finding could be due to the ability of AA metabolites to act as both agonist (3-keto-5α-abiraterone) and antagonist (Δ 4 -abiraterone) on androgen signaling or our small sample size. [Table: see text]
Developing a Clinical Approach to Air Pollution and Cardiovascular Health
Authors: Michael B. Hadley, Jill Baumgartner, Rajesh Vedanthan
Journal: Circulation (2018)

Nearly 3 billion people are exposed to household air pollution emitted from inefficient cooking and heating stoves, and almost the entire global population is exposed to detectable levels of outdoor air pollution from traffic, industry, and other sources. Over 3 million people die annually of ischemic heart disease or stroke attributed to air pollution, more than from traditional cardiac risk factors such as obesity, diabetes mellitus, or smoking. Clinicians have a role to play in reducing the burden of pollution-attributable cardiovascular disease. However, there currently exists no clear clinical approach to this problem. Here, we provide a blueprint for an evidence-based clinical approach to assessing and mitigating cardiovascular risk from exposure to air pollution. We begin with a discussion of the global burden of pollution-attributable cardiovascular disease, including a review of the mechanisms by which particulate matter air pollution leads to cardiovascular outcomes. Next, we offer a simple patient-screening tool using known risk factors for pollution exposure. We then discuss approaches to quantifying air pollution exposures and cardiovascular risk, including the development of risk maps for clinical catchment areas. We review a collection of interventions for household and outdoor air pollution, which clinicians can tailor to patients and populations at risk. Finally, we identify future research needed to quantify pollution exposures and validate clinical interventions. Overall, we demonstrate that clinicians can be empowered to mitigate the global burden of cardiovascular disease attributable to air pollution.
Genome-Wide Mapping of DNA Accessibility and Binding Sites for CREB and C/EBPβ in Vasopressin-Sensitive Collecting Duct Cells
Authors: Hyun Jun Jung, Viswanathan Raghuram, Jae Wook Lee, Mark A. Knepper
Journal: Journal of the American Society of Nephrology (2018)

Background Renal water excretion is controlled by vasopressin, in part through regulation of the transcription of the aquaporin-2 gene ( Aqp2 ). Methods To identify enhancer regions likely to be involved in the regulation of Aqp2 and other principal cell–specific genes, we used several next generation DNA-sequencing techniques in a well characterized cultured cell model of collecting duct principal cells (mpkCCD). To locate enhancers, we performed the assay for transposase-accessible chromatin using sequencing (ATAC-Seq) to identify accessible regions of DNA and integrated the data with data generated by chromatin immunoprecipitation followed by next generation DNA-sequencing (ChIP-Seq) for CCCTC binding factor (CTCF) binding, histone H3 lysine-27 acetylation, and RNA polymerase II. Results We identified two high-probability enhancers centered 81 kb upstream and 5.8 kb downstream from the Aqp2 transcriptional start site. Motif analysis of these regions and the Aqp2 promoter identified several potential transcription factor binding sites, including sites for two b-ZIP transcription factors: CCAAT/enhancer binding protein- β (C/EBP β ) and cAMP-responsive element binding protein (CREB). To identify genomic binding sites for both, we conducted ChIP-Seq using well characterized antibodies. In the presence of vasopressin, C/EBP β , a pioneer transcription factor critical to cell-specific gene expression, bound strongly at the identified enhancer downstream from Aqp2 . However, over multiple replicates, we found no detectable CREB binding sites within 390 kb of Aqp2 . Thus, any role for CREB in the regulation of Aqp2 gene transcription is likely to be indirect. Conclusions The analysis identified two enhancer regions pertinent to transcriptional regulation of the Aqp2 gene and showed C/EBP β (but not CREB) binding.
Precision Oncology Decision Support: Current Approaches and Strategies for the Future
Authors: Katherine C. Kurnit, Ecaterina E. Ileana Dumbrava, Beate Litzenburger, Yekaterina B. Khotskaya, Amber M. Johnson, Timothy A. Yap, Jordi Rodon, Jia Zeng, Md Abu Shufean, Ann M. Bailey, Nora S. Sánchez, Vijaykumar Holla, John Mendelsohn, Kenna Mills Shaw, Elmer V. Bernstam, Gordon B. Mills, Funda Meric-Bernstam
Journal: Clinical Cancer Research (2018)

With the increasing availability of genomics, routine analysis of advanced cancers is now feasible. Treatment selection is frequently guided by the molecular characteristics of a patient's tumor, and an increasing number of trials are genomically selected. Furthermore, multiple studies have demonstrated the benefit of therapies that are chosen based upon the molecular profile of a tumor. However, the rapid evolution of genomic testing platforms and emergence of new technologies make interpreting molecular testing reports more challenging. More sophisticated precision oncology decision support services are essential. This review outlines existing tools available for health care providers and precision oncology teams and highlights strategies for optimizing decision support. Specific attention is given to the assays currently available for molecular testing, as well as considerations for interpreting alteration information. This article also discusses strategies for identifying and matching patients to clinical trials, current challenges, and proposals for future development of precision oncology decision support.
Government must prioritise efforts to tackle workforce crisis, GPs say
Authors: Abi Rimmer
Journal: BMJ (2014)

The government must prioritise efforts to tackle the “crisis” in the general practice workforce that is “threatening primary care and the safety of patients,” GPs have said.

Delegates at the BMA’s local medical committee (LMC) conference in York unanimously voted in favour of a motion calling on the government to prioritise the “crisis.” Hugh Brown, from Aryshire and Aran LMC, said that, for the first time in his working life, 20% of his local general practices had a vacancy. “This, I propose, is the biggest …
SYK inhibition blocks proliferation and migration of glioma cells and modifies the tumor microenvironment
Authors: Gerald Moncayo, Michal Grzmil, Tatiana Smirnova, Pawel Zmarz, Roland M Huber, Debby Hynx, Hubertus Kohler, Yuhua Wang, Hans-Rudolf Hotz, Nancy E Hynes, Georg Keller, Stephan Frank, Adrian Merlo, Brian A Hemmings
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is one of the most aggressive human brain tumors, with a median survival of 15-18 months. There is a desperate need to find novel therapeutic targets. Various receptor protein kinases have been identified as potential targets; however, response rates in clinical studies have been somewhat disappointing. Targeting the spleen tyrosine kinase (SYK), which acts downstream of a range of oncogenic receptors, may therefore show more promising results.Kinase expression of brain tumor samples including GBM and low-grade tumors were compared with normal brain and normal human astrocytes by microarray analysis. Furthermore, SYK, LYN, SLP76, and PLCG2 protein expressions were analyzed by immunohistochemistry, western blot, and immunofluorescence of additional GBM patient samples, murine glioma samples, and cell lines. SYK was then blocked chemically and genetically in vitro and in vivo in 2 different mouse models. Multiphoton intravital imaging and multicolor flow cytometry were performed in a syngeneic immunocompetent C57BL/6J mouse GL261 glioma model to study the effect of these inhibitors on the tumor microenvironment.SYK, LYN, SLP76, and PLCG2 were found expressed in human and murine glioma samples and cell lines. SYK inhibition blocked proliferation, migration, and colony formation. Flow cytometric and multiphoton imaging imply that targeting SYK in vivo attenuated GBM tumor growth and invasiveness and reduced B and CD11b+ cell mobility and infiltration.Our data suggest that gliomas express a SYK signaling network important in glioma progression, inhibition of which results in reduced invasion with slower tumor progression.
USE AND EFFECTIVENESS OF MANUAL ASPIRATION THROMBECTOMY DURING PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR THE TREATMENT OF ST-ELEVATION MYOCARDIAL INFARCTION IN THE UNITED STATES: AN ANALYSIS FROM THE NCDR CATHPCI REGISTRY
Authors: Eric Alexander Secemsky, Sunil V. Rao, Ajay J. Kirtane, Hector Tamez Aguilar, David Cohen, Robert Yeh
Journal: Journal of the American College of Cardiology (2018)
BMA and NHS Employers to enter talks on renegotiating consultants contract
Authors: Matthew Limb
Journal: BMJ (2013)

The BMA’s consultants committee has agreed to enter talks with NHS Employers on new contract terms for hospital consultants in England and Northern Ireland.

The decision, announced on 18 September after a meeting of the Central Consultants and Specialists Committee, was hailed by NHS Employers as a “once-in-a-generation opportunity” to reshape the way the NHS delivers care. It followed earlier informal discussions between the two organisations that led to publication in July of a draft “heads of terms” document setting out the scope for possible negotiations.1

The chairman of the consultants committee, Paul Flynn, said that the decision was taken after the BMA …