tbuckley/cabot-search huggingface dataset:
Impact of Hydrogel Elasticity and Adherence on Osteosarcoma Cells and Osteoblasts
Authors: Tongmeng Jiang, Guojie Xu, Xiaoming Chen, Xianyuan Huang, Jinmin Zhao, Li Zheng
Journal: Advanced Healthcare Materials (2019)

Abstract Biochemical and physical properties of extracellular matrix (ECM) control cell behaviors, but how they affect osteosarcoma cells that do not require attachment and their normal counterparts (osteoblasts) that are anchorage‐dependent has not been reported yet. In this study, the effects of matrix elasticity and adherence on osteosarcoma MG63 cells are investigated using four types of scaffolds (collagen type I, matrigel, alginate, and agarose) with varied adhesion ligands and rigidity, as compared with osteoblast hFOB1.19 cells. MG63 cells on 2D films are sensitive to ECM adherence, similar to the situation of hFOB1.19 cultured in both 2D and 3D. However, osteosarcoma cells in 3D hydrogels are sensitive to ECM elasticity rather than adherence, with tumor proliferation and malignancy varied with matrix rigidity. The results indicate that osteosarcomas cells might adopt unnatural characteristics on flat surfaces. But in 3D culture, they recover their normal state independent of adherence, as regulated mainly by ECM elasticity via the integrin‐mediated focal adhesion pathway, which is further confirmed by in vivo studies. In contrast, osteoblasts and 2D cultured osteosarcoma cells are predominantly influenced by ECM bioactivity regulated by integrin‐mediated adherens junction pathway. This study might provide new insights into rational design of scaffolds for tumor/tissue engineering.
A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery
Authors: David Lissauer, Amie Wilson, Catherine A. Hewitt, Lee Middleton, Jonathan R.B. Bishop, Jane Daniels, Abi Merriel, Andrew Weeks, Chisale Mhango, Ronald Mataya, Frank Taulo, Theresa Ngalawesa, Agatha Chirwa, Colleta Mphasa, Tayamika Tambala, Grace Chiudzu, Caroline Mwalwanda, Agnes Mboma, Rahat Qureshi, Iffat Ahmed, Humera Ismail, Olufemi T. Oladapo, Godfrey Mbaruku, Jerome Chibwana, Grace Watts, Beatus Simon, James Ditai, Charles Otim Tom, JaneFrances Acam, John Ekunait, Hellen Unzia, Margaret Iyaku, Joshua J. Makiika, Javier Zamora, Tracy Roberts, Ilias Goranitis, Sarah Bar-Zeev, Nicola Desmond, Sabaratnam Arulkumaran, Zulfiqar A. Bhutta, Ahmet M. Gulmezoglu, Arri Coomarasamy
Journal: New England Journal of Medicine (2019)

Surgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries.
Time to PSA nadir and the risk of death from prostate cancer following radiation and androgen deprivation therapy.
Authors: Luke Roy George Pike, Jing Wu, Ming-Hui Chen, Marian Loffredo, Andrew A. Renshaw, John Pfail, Philip W. Kantoff, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2019)

4 Background: Whether the time to PSA nadir (TTN) has differential prognostic value in men who reach an undetectable versus detectable PSA nadir remains unknown. Methods: Two-hundred and four men from a prospective randomized controlled trial (RCT) involving radiation therapy with or without 6 months of androgen deprivation therapy (ADT) in unfavorable risk CaP at academic or community based centers in Massachusetts, enrolled between 1995 and 2001. Adjusted hazard ratios (AHR) of the risk of CaP-specific mortality (PCSM) calculated using Fine and Gray competing risk regression. Results: After a median follow-up of 18.17 years, 160 men died; 30 (18.75%) of CaP. Amongst men with a PSA nadir ≥ 0.2 ng/ml, a TTN &lt; median (12 months) was significantly associated with an increased PCSM-risk versus the median or more (AHR 5.07, 95% CI 2.10-12.23, p&lt;0.001); whereas this association was not observed among men with a PSA nadir of &lt;0.2 ng/ml, (AHR 9.9, 95% CI 0.23-433.8, p=0.23). Conclusions: Men with both a short TTN and detectable PSA nadir could be considered for entry on RCTs at a novel entry point prior to PSA failure at the time of PSA nadir to complete planned conventional ADT versus that plus agent(s) shown to improve outcomes in men with or at high risk of having castrate-resistant CaP.
Benefits of Early Dental Care Now Hard to Refute
Authors: Paul S. Casamassimo, Arthur J. Nowak
Journal: JAMA Network Open (2019)

Lisa M. Jamieson, PhD; Lisa G. Smithers, BAppSc, GradDipHumNutr, MPH, PhD; Joanne Hedges, MPH; Jacqueline Aldis; Helen Mills; Kostas Kapellas, PhD; Herenia P. Lawrence, PhD; John R. Broughton, PhD; Xiangqun Ju, PhD
SAS doctors to be asked about their workplace experiences for the first time
Authors: Zosia Kmietowicz
Journal: BMJ (2019)

The General Medical Council is to ask the fifth of UK doctors who work as specialty and associate specialists (SAS) and locally employed doctors (LEDs) about their workplace experiences for the first time.

The regulator said it wants to learn more about these doctors’ working practices, opportunities for career development, and the support they receive in the workplace.

Charlie Massey, chief executive of the GMC, …
NHS is to test scrapping the four hour A&amp;E target
Authors: Gareth Iacobucci
Journal: BMJ (2019)

NHS England is to test plans to scrap the current four hour target for seeing and treating patients in hospital accident and emergency departments, as part of a radical shake up of waiting time standards. The proposals come out of a clinical review of all current NHS access standards by NHS England’s medical director, Stephen Powis, which assessed how targets might be altered to reflect advances in clinical practice and service delivery since they were first introduced in the 2000s.1 The interim review, published on 11 March, set out a raft of changes to current standards across urgent and emergency care, elective care, cancer care, and mental health, which it says should be tested during 2019-20. The review proposed replacing the current emergency care targets with five new standards (box 1). Box 1 ### Proposed new emergency care targetsRETURN TO TEXT
A community based assessment of asthma prevalence, management strategies, compliance and treatment perspectives amongst young adults in Melbourne, Australia
Authors: D. Reid, J. Raven, M. Abramson, E. H. Walters
Journal: Thorax (1997)

Morbidity and mortality from asthma has increased world-wide over past decades despite advances in management. Australia leads the world in asthma prevalence with associated high mortality statistics (approximately 800 deaths annually). As part of the 1992-93 European Community Respiratory Health Survey (ECRHS) we assessed asthma prevalence, drug therapy, compliance and treatment perceptions amongst 4500 young adults in Melbourne, Australia. From the first phase of the ECRHS, a random subsample of 1642 subjects (aged 20-45 years) and a further subsample of 433 symptomatic subjects were invited to complete a detailed respiratory questionnaire. Of these 2075 young adults, 757 (n=553 - random, n=204 - symptomatic) completed the questionnaire in the laboratory and a further 119 by telephone interview (42% response rate). Prevalence: Current asthma was reported by 9.7% of respondents in the ECRHS first phase. Of the 'enriched' second phase cohort, a history of physician confirmed asthma was reported by 227 (26%); 143 (63%) of these had current asthma as defined by an attack within the past year (Group I) and 84 (37%) had not (Gp II). Treatment: Of the asthmatics in phase II, 215 (95%) had been prescribed treatment for their asthma. Inhaled corticosteroid (ICS) use in the past 1 year was reported by 85 (37%) subjects. Current asthmatics (Group I) were more likely to have used ICS (n=65, 45%) in the last year than those with no history of recent attacks (Group II; n=20, 24%). B-agonists had been used by 161 (71%), antihistamines by 67 (29.5%), oral methylxanthines by 17 (7%) and oral steroids by 5 (2%) subjects within the past year. 41 (18%) subjects had received immunotherapy for allergies. Compliance: 93 (43%) subjects reported taking treatment as prescribed all of the time, 50 (23%) most of the time, 70 (33%) some of the time and 2 (1%) none of the time. Compliance was not significantly different between Gp. I and Gp. II subjects. Perception: 148 (62%) believed it was bad to take regular preventative treatment and 92 (62%) of these had suffered an attack within the past year. Of the 153 (67%) subjects who only took treatment when necessary for attacks of breathlessness, 80 (52%) took treatment at the onset of the attack but 73 (48%) waited until symptoms became severe. Conclusion: Asthma patient perception and treatment compliance continues to be poor despite national education campaigns. Anti-inflammatory agents remain neglected even in those with current symptoms.
In patients with cancer who were starting chemotherapy, apixaban reduced VTE and increased major bleeding at 180 d
Authors: Edmond Chouinard
Journal: Annals of Internal Medicine (2019)

ACP Journal Club19 March 2019In patients with cancer who were starting chemotherapy, apixaban reduced VTE and increased major bleeding at 180 dEdmond Chouinard, MDEdmond Chouinard, MDCambridge Memorial Hospital, Cambridge, Ontario, Canada (E.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ201903190-029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationCarrier M, Abou-Nassar K, Mallick R, et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019;380:711-9. https://pubmed.ncbi.nlm.nih.gov/30511879Clinical Impact RatingsOncology: References1 Lee AY, Levine MN, Baker RI, et al; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146-53. [PMID: 12853587] Google Scholar2 Young AM, Marshall A, Thirlwall J, et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018;36:2017-23. [PMID: 29746227] Google Scholar3 Lyman GH, Bohlke K, Khorana AA, et al; American Society of Clinical Oncology. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014. J Clin Oncol. 2015;33:654-6. [PMID: 25605844] Google Scholar Author, Article, and Disclosure InformationAffiliations: Cambridge Memorial Hospital, Cambridge, Ontario, Canada (E.C.)This article was published at Annals.org on 5 March 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 March 2019Volume 170, Issue 6Page: JC29KeywordsCancer chemotherapyCancer preventionCancer treatmentChemotherapyHemorrhageProphylaxisSafetyVenous thromboembolism ePublished: 19 March 2019 Issue Published: 19 March 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Annals Graphic Medicine - Watching Time, Body, and Soul
Authors: Nancy M. Oconnor
Journal: Annals of Internal Medicine (2019)

Web Exclusives19 March 2019Annals Graphic Medicine - Watching Time, Body, and SoulFREEView of a Family Member on HospiceNancy M. OconnorNancy M. OconnorAmerican College of Physicians, Philadelphia, Pennsylvania (N.M.O.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G18-0024 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: American College of Physicians, Philadelphia, Pennsylvania (N.M.O.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0024.Corresponding Author: Nancy M. Oconnor; e-mail, [email protected]org.This article was published at Annals.org on 12 March 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 March 2019Volume 170, Issue 6Page: W84-W85KeywordsConflicts of interestDisclosureHealth care ePublished: 12 March 2019 Issue Published: 19 March 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Induction of apoptosis by knockdown of splicing factor SRp20 in pancreatic cancer cell lines.
Authors: Wei Wang
Journal: Journal of Clinical Oncology (2015)

e15221 Background: Pancreatic cancer is one of the malignant tumors which exhibit resistance to chemotherapy, partly due to enhanced anti-apoptotic mechanism. Therefore, exploring new signal in the anti-apoptotic mechanism should improve the efficacy of chemotherapy against pancreatic cancer. SRp20 (SFSR3), the smallest member of the SR protein family, is involved in numerous biological processes. We found that SRp20 is highly expressed in a number of human pancreatic cancer cell lines. To address the role of SRp20, we used specific siRNA targeted for SRp20 to knockdown SRp20 expression. Here we investigated the growth-inhibitory and apoptotic effect of SRP20 knockdown, and the apoptotic pathway induced by SRP20 knockdown in AsPC-1 and MiaPaCa-2 cells. Methods: Cell proliferation was measured by sulforhodamine B (SRB), the expression of apoptotic pathway intermediates was measured by assay of caspase activity, western blot and flow cytometry. SRp20 expression was knocked down by siRNA and measured by western blot. In vivo, AsPC-1 xenografts were treated by SRP20 siRNA or Gemcitabine, and the tumor growth delay was compared; tumor samples were tested by ELISA and western blot. Results: SRP20 knockdown induced cell death of pancreatic cancer through activating the caspase cascade at dose and time-dependent manner; furthermore SRp20 knockdown activates the intrinsicapoptotic pathway. In vivo SRp20 siRNA significantly induced apoptosis and caused tumor growth delay. Conclusions: SRP20 knockdown may have a potential to be an effective agent against pancreatic cancer and the role of SRp20 involved in resistance to apoptosis pathway make it be a potential therapeutic target in pancreatic cancer.
Abstract P367: Application of Hierarchical Cluster Analysis on Five Risk Factors Scores (RFS) to Estimate Individual Patient Risk in Case Where There is No Official Country Specific RFS: Example From Bosnia and Herzegovina
Authors: Enisa Ademovic, Anshul Saxena, Semra Cavaljuga, Emir Veledar
Journal: Circulation (2019)

Objective: The accuracy and applicability of various cardiovascular disease (CVD) risk calculators may not be same in different populations. Wecompared 5 RFS for CVD risk on patients from Bosnia and Herzegovina to explore relations between different RFS and estimate use of theircombination. Methods: We utilized demographic, medical history, and lipid profile data gathered from patients seen in primary care clinic in 2013. FiveRFS namely, 10 year Framingham CHD score, QRISK 2, AHA/ACC ASCVD risk score, Framingham ATP III score, and EU SCORE were calculatedusing demographic, history of diabetes and hypertension, taking any hypertension medication, and lipid profile variables. Additionally, we entered these scores as dimensions in hierarchical cluster analysis to group people based on their risk of developing CVD. Results: There were 1277 patients in thisstudy and majority (65%) were women. The mean (SD) age of the sample was 56.2 (11.4) years. Correlation between these scores are presented inTable 1. We obtained 4 clusters with significant different cluster centers. Clusters were ordered from lowest to highest risk; cluster 1 containing patients with lowest and cluster 4 with highest mean RFS. Cluster centers, which represents mean values for all the RFS are given in Table 2. Conclusion: All risk scores performed well in this population. Only EU SCORE correlated less with other RFS. Obtained clusters are more homogenous and were ableto classify patients better. This novel method of using calculated RFCs as dimensions in clustering produced very good estimates of patient’s risk ofdeveloping CVD by combining several RFS, even in a case where originally RFS were created for and from different population.
Azacitidine in combination with ATRA, valproic acid in elderly AML patients.
Authors: Muhit Ozcan, Sinem Civriz Bozdag, Berna Atesagaoglu, Erden Atilla, Pinar Ataca, Selami Kocak Toprak, Meltem Kurt Yuksel, Pervin Topcuoglu, Onder Arslan, Osman Ilhan, Hamdi Akan, Nahide Konuk, Gunhan Gurman
Journal: Journal of Clinical Oncology (2015)

e18059 Azacitidine in Combination with ATRA, Valproic Acid in Elderly AML Patients Background: Azacitidine (AZA) prolongs overall survival compared with conventional care in elderly patients. Valproic acid (VPA) is a well-known histone deacetylase inhibitor (HDAC) anticonvulsant which induces myeloid differentiation. All-trans retinoic asit (ATRA) increases killing of clonogenic cells by downregulation of BCL-2 when used in combination with cytarabine and idarubicin. ATRA, VPA and AZA combination has shown to be safe and had significant clinical activity in previous studies. Methods: We retrospectively evaluated 15 elderly patients with AML diagnosed between 2009 and 2014 at Ankara University Hematology Department. Patients received AZA 75mg/m^2/day (between days 1-7, intravenous), VPA 35-50mg/kg/day (between days 1-7, peroral), ATRA 45 mg/m^2/day (between days 8-28, peroral). Results: Patient characteristics were shown in Table 1. The combination therapy responses were summarized in Table 2. Grade 4 neutropenia detected in 5/15 (33%), grade 4 thrombocytopenia in 6/15 (40%) patients. Other complications during treatment cycles were as follows: Febrile neutropenia 5/15 (33%), cardiovascular disease 1/15 (0.7%), gastrointestinal bleeding 1/15 (0.7%), hematuria 1/15 (0.7%). Conclusions: We found similar outcomes in combination treatment when compared to previous studies on AZA treatment alone in elderly patients. Myelosupression was more prominent with AZA-ATRA-VPA. Although we haven't detected any central nervous system toxicity with VPA, blood levels should be monitored for neurotoxicity. AML patient characteristics. No of patients(n) 15 Median age 74(61-83) F/M 6/9 ECOG PS (1/2/3) 7/7/1 Cytogenetics (fav/stand/unfav/NA) 0/5/2/8 MDS secondary(n) 9 Extramedullary disease(n) 0 WBC count (n) <10/mm3 ³10/mm3 12 3 Blast percentage 20-29 % ³30% 4 11 Previous CT line 0/1/2 9/5/1 ATRA-AZA-VA combination therapy responses. Median number of treatment cycles 4(1-6) Overall response(n)(%) CR/PR 6(40%) 5(33%)/1(7%) Time to CR 3(2-4) Median follow up (months) 3.5(1-14) Progres to ASCT(n) 3 1 year overall survival(%) 47%±15%
Clinical Impact of Pre-Transplant Intramuscular Adipose Tissue Content on Outcome of Cord Blood Transplantation
Authors: Shuhei Kurosawa, Yuichi Takeuchi, Marina Matsui, Masao Tsukada, Kanichi Iwama, Kazunari Yamada, Kouichi Kaziwara, Hideki Kodo, Yasuzi Kouzai
Journal: Blood (2018)
Genomic drivers of poor prognosis and enzalutamide resistance in metastatic castration-resistant prostate cancer.
Authors: William S. Chen, Rahul Raj Aggarwal, Li Zhang, Shuang Zhao, Tomasz M. Beer, David A Quigley, Adam Foye, Denise Playdle, Paul Lloyd, Matthew Rettig, Martin Gleave, Christopher P. Evans, Primo Lara, Vishal Kothari, Kim N. Chi, Robert Evan Reiter, Christopher Maher, Felix Y Feng, Eric Jay Small, Joshi J. Alumkal
Journal: Journal of Clinical Oncology (2019)

146 Background: Metastatic castration-resistant prostate cancer (mCRPC) is the lethal form of the disease. Several recent efforts have identified genomic alterations in mCRPC, but the clinical implications of these alterations have not been fully elucidated. We conducted a prospective cohort study (n = 101) using whole genome sequencing (WGS) to analyze the association between key driver gene alterations and overall survival. We also performed whole-transcriptome RNA sequencing (RNA-seq) analyses to identify potential mechanisms of enzalutamide resistance in mCRPC. Methods: Metastasis biopsies were obtained in 101 mCRPC patients as part of the multi-institutional West Coast Prostate Cancer Dream Team project. Samples underwent WGS and RNA-seq. The resulting mutation, copy number, and structural variant calls were integrated to determine functional copy number status of candidate genes for downstream clinical analyses. We performed univariate and multivariable analyses to assess the prognostic significance of candidate genomic events with respect to overall survival. To nominate and investigate genomic pathways associated with enzalutamide resistance, we performed expression-based gene set enrichment analysis followed by cross-sectional enrichment and survival analyses related to the top nominated pathway. Results: RB1 loss was associated with poor overall survival (median 14.1 vs. 42.0 months, p &lt; 0.001). When we compared enzalutamide resistant versus naïve samples using gene set enrichment analysis, we identified the Wnt/beta-catenin pathway as the top differentially expressed pathway in enzalutamide-resistant patients. Furthermore, CTNNB1 (beta-catenin) activating mutations were exclusive to enzalutamide-resistant patients (p = 0.013) and predictive of poor overall survival (median 13.6 vs. 41.7 months, p &lt; 0.001). Conclusions: Impaired survival in mCRPC patients is associated with RB1 loss, identified by integrated genomic analysis of CRPC metastasis biopsies. Among men with mCRPC that was enzalutamide-resistant, the Wnt/beta-catenin pathway is nominated as an important predictive (and potentially therapeutic) pathway.
Reply to Law and Walkey: Long-Term Outcomes after Prolonged Mechanical Ventilation: What of Those Cast Away?
Authors: Amal Jubran, Brydon J. B. Grant, Martin J. Tobin
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

from Diogenes the Cynic.In reference to a painting of shipwreck survivors, Diogenes was asked, "Look, you who think the gods have no care of human things, what do you say to so many persons preserved from death by [the gods'] especial favour?"He replied, "Why, I say that their pictures are not here who were cast away, who are by much the greater number" (3).