tbuckley/cabot-search huggingface dataset:
Association Between Teaching Status and Mortality in US Hospitals
Authors: Laura G. Burke, Austin B. Frakt, Dhruv Khullar, E. John Orav, Ashish K. Jha
Journal: JAMA (2017)

Few studies have analyzed contemporary data on outcomes at US teaching hospitals vs nonteaching hospitals.To examine risk-adjusted outcomes for patients admitted to teaching vs nonteaching hospitals across a broad range of medical and surgical conditions.Use of national Medicare data to compare mortality rates in US teaching and nonteaching hospitals for all hospitalizations and for common medical and surgical conditions among Medicare beneficiaries 65 years and older.Hospital teaching status: major teaching hospitals (members of the Council of Teaching Hospitals), minor teaching hospitals (other hospitals with medical school affiliation), and nonteaching hospitals (remaining hospitals).Primary outcome was 30-day mortality rate for all hospitalizations and for 15 common medical and 6 surgical conditions. Secondary outcomes included 30-day mortality stratified by hospital size and 7-day mortality and 90-day mortality for all hospitalizations as well as for individual medical and surgical conditions.The sample consisted of 21 451 824 total hospitalizations at 4483 hospitals, of which 250 (5.6%) were major teaching, 894 (19.9%) were minor teaching, and 3339 (74.3%) were nonteaching hospitals. Unadjusted 30-day mortality was 8.1% at major teaching hospitals, 9.2% at minor teaching hospitals, and 9.6% at nonteaching hospitals, with a 1.5% (95% CI, 1.3%-1.7%; P < .001) mortality difference between major teaching hospitals and nonteaching hospitals. After adjusting for patient and hospital characteristics, the same pattern persisted (8.3% mortality at major teaching vs 9.2% at minor teaching and 9.5% at nonteaching), but the difference in mortality between major and nonteaching hospitals was smaller (1.2% [95% CI, 1.0%-1.4%]; P < .001). After stratifying by hospital size, 187 large (≥400 beds) major teaching hospitals had lower adjusted overall 30-day mortality relative to 76 large nonteaching hospitals (8.1% vs 9.4%; 1.2% difference [95% CI, 0.9%-1.5%]; P < .001). This same pattern of lower overall 30-day mortality at teaching hospitals was observed for medium-sized (100-399 beds) hospitals (8.6% vs 9.3% and 9.4%; 0.8% difference between 61 major and 1207 nonteaching hospitals [95% CI, 0.4%-1.3%]; P = .003). Among small (≤99 beds) hospitals, 187 minor teaching hospitals had lower overall 30-day mortality relative to 2056 nonteaching hospitals (9.5% vs 9.9%; 0.4% difference [95% CI, 0.1%-0.7%]; P = .01).Among hospitalizations for US Medicare beneficiaries, major teaching hospital status was associated with lower mortality rates for common conditions compared with nonteaching hospitals. Further study is needed to understand the reasons for these differences.
ATRT-01. OVEREXPRESSION OF TEAD4 IN ATYPICAL TERATOID/RHABDOID TUMOR: NEW INSIGHT TO THE PATHOPHYSIOLOGY OF AN AGGRESSIVE BRAIN TUMOR
Authors: Mario Suzuki, Akihide Kondo, Ikuko Ogino, Hajime Arai, Tadanori Tomita, Simone T. Sredni
Journal: Neuro-Oncology (2017)

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal brain tumor that occurs mainly in early childhood. Although most of the tumors are characterized by inactivating mutations of the tumor suppressor gene, SMARCB1, the biological basis of its tumorigenesis and aggressiveness is still unknown. PROCEDURE: We performed high-throughput copy number variation analysis of primary cell lines generated from primary and relapsed tumors from one of our patients to identify new genes involved in AT/RT biology. The expression of the identified gene was validated in 29 AT/RT samples by gene expression profiling, quantitative real-time polymerase chain reaction, and immunohisto- chemistry (IHC). Furthermore, we investigated the function of this gene by mutating it in rhabdoid tumor cells. RESULTS: TEAD4 amplification was detected in the primary cell lines and its overexpression was confirmed at mRNA and protein levels in an independent cohort of AT/RT samples. TEAD4’s co- activator, YAP1, and the downstream targets, MYC and CCND1, were also found to be upregulated in AT/RT when compared to medulloblastoma. IHC showed TEAD4 and YAP1 overexpression in all samples. Cell proliferation and migration were significantly reduced in TEAD4-mutated cells. CONCLUSIONS: We report the overexpression of TEAD4 in AT/RT, which is a key component of Hippo pathway. Recent reports revealed that dysregulation of the Hippo pathway is implicated in tumori- genesis and poor prognosis of several human cancers. Our results suggest that TEAD4 plays a role in the pathophysiology of AT/RT, which represents a new insight into the biology of this aggressive tumor.
Governments must be open about prices they pay for drugs, says WHO
Authors: Anne Gulland
Journal: BMJ (2017)

Governments must be transparent about how much they pay for drugs in a bid to ensure a fair price, the World Health Organisation has said.

Marie-Paule Kieny, WHO’s assistant director general for health systems and innovation, told a press conference at the end of a meeting on the affordability of drugs that governments had to play a stronger role in setting policies on pharmaceuticals and should discuss how to share information on pricing.

“We need more transparency on pricing from all stakeholders, from …
Intralesional Sodium Thiosulfate Treatment for Calcinosis Cutis in the Setting of Lupus Panniculitis
Authors: Nicole S. Gunasekera, Lia E. Gracey Maniar, Cecilia Lezcano, Alvaro C. Laga, Joseph F. Merola
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Abstract 340: IL-10 And HSCRP Were Predictors For The Attenuation Of Heart Functions In Myocardial Ischemia Swine
Authors: Shuzhen Guo, Wenjing Chuo, Yong Wang, Jianxin Chen, Juan Wang, Xuanchao Feng, Hongjian Lian, Hua Xie, Xue Yu, Liangtao Luo, Wei Wang
Journal: Circulation Research (2013)

Background and Objective: Inflammation was one of the most important pathophysiological processes during myocardial ischemia. However, it is still poorly understood about the possibilities of these pro- or anti-inflammation factors be used as prognostic parameters for subsequent attenuation of heart functions. Methods and Results: Chinese experimental mini swines (25±4 kg) were instrumented with a size-matched Ameroid constrictor on the left anterior descending branch (LAD) under general anesthesia in sterile conditions (N=15). And a sham group (N=6) was included. 4 weeks after thoracotomy, more than 90% occlusion of the LAD was proved by coronary angiography. Early stage of ischemia was found by echocardiography which showed focal ischemia in the anterior wall of left ventricular (from apex to papillary muscle level) and unchanged ejection fraction. Meanwhile, Enzyme-linked immunosorbent assay of serum showed that IL-8 (86.83 ±10.96 vs. 130.3 ±10.94-pg/ml, P =0.0322) and IL-10 (0.9619 ±0.1421 vs. 1.660 ±0.1607-pg/ml, P =0.0111) were dramatically decreased compared to sham group, while no significant changes were found in IL-1 (0.3075 ±0.03558 vs. 0.3045 ±0.057371 -ng/ml, P = 0.9643), IL-6 (307.7 ±27.81 vs. 315.8 ±23.07-pg/ml, P =0.8637), high sensitivity C reactive protein (hsCRP) (12.94 ±1.324 vs. 9.943 ±1.442-ng/ml, P =0.2087) and TNF-a(1.769 ±0.1467 vs. 1.260 ±0.3209-ng/ml, P =0.1121). Furthermore, 8 weeks after thoracotomy, ejection fraction(EF) of myocardial ischemia animals were dramatically attenuated (44.69 ±4.494 vs. 60.60 ±3.420-%, P =0.0428). Subsequent EF (8 weeks postoperation) showed a good linear regression with the IL-10 and hsCRP concentration in the early stage of myocardial ischemia (4 weeks postoperation) (EF= 0.525+ 0.132* IL-10- 0.015* hsCRP, P =0.001) when stepwise regression was performed with all inflammation related factors above as dependent variables. Conclusion: These results demonstrate that lower IL-10 and higher hsCRP in serum may be predictors for the attenuation of heart function caused by myocardial ischemia. Further Clinical trials may help to prove the efficiency of these novel insights of prognosis for ischemia heart diseases.
EPND-07. MOLECULAR HETEROGENEITY AMONG PEDIATRIC POSTERIOR FOSSA EPENDYMOMA
Authors: Kristian Pajtler, Ji Wen, Martin Sill, Tong Lin, Jens Hübner, Vijay Ramaswamy, Chandanamali Punchihewa, David Jones, Hendrik Witt, Lukas Chavez, Ruth Tatevossian, Richard Grundy, Thomas Merchant, Michael Taylor, Stefan Pfister, Andrey Korshunov, Marcel Kool, David Ellison
Journal: Neuro-Oncology (2017)

Previously, we have identified nine distinct molecular groups of ependymoma across all age groups, three in each major anatomical compartment of the CNS: spinal, posterior fossa, and supratentorial. These nine molecular groups are genetically, epigenetically, transcriptionally, demographically, and clinically distinct. Pediatric intracranial ependymomas are either affiliated with the RELA and YAP1 supratentorial groups or with the posterior fossa PFA group. RELA and YAP1 ependymomas harbor recurrent and distinct fusion genes that drive the disease, but PFA ependymomas lack significant recurrent mutations, and the specific oncogenic events underlying these tumors remain undefined. Observing distinct outcomes among children with PFA ependymomas, we tested the hypothesis that further molecular diversity with clinical utility, including possible novel genetic alterations, may exist among these tumors. Genome-wide DNA methylation profiles of 681 pediatric PFA ependymomas were analyzed by unsupervised consensus hierarchical clustering and t-distributed stochastic neighbor embedding (tsne), which identified not only three major distinct molecular subgroups of PFA ependymoma: PFA-1, PFA-2, and PFA-3, but additional small subgroups that segregate within PFA-1 and PFA-2. Subgroups were characterized by distinct clinical and genetic characteristics; most PFA-3 tumors harbored 1q gain and occurred in children significantly older than those with PFA-1 and PFA-2 tumors. Some of the small subgroups demonstrated distinctive copy number alterations or gene mutations, e.g. H3 K27M. Outcome data revealed considerable heterogeneity among the different subgroups, overall survival at 5 years was >90% for one subgroup, but <20% for two others. We conclude that further molecular refinement of pediatric PFA ependymomas has clinical utility and the potential for enhanced risk assessment or therapeutic stratification. In addition, identification of PFA subgroups and further molecular heterogeneity within these subgroups may help to identify the drivers of PFA ependymomas.
An Integrated Chemical Environment to Support 21st-Century Toxicology
Authors: Shannon M. Bell, Jason Phillips, Alexander Sedykh, Arpit Tandon, Catherine Sprankle, Stephen Q. Morefield, Andy Shapiro, David Allen, Ruchir Shah, Elizabeth A. Maull, Warren M. Casey, Nicole C. Kleinstreuer
Journal: Environmental Health Perspectives (2017)

Summary: Access to high-quality reference data is essential for the development, validation, and implementation of in vitro and in silico approaches that reduce and replace the use of animals in toxicity testing. Currently, these data must often be pooled from a variety of disparate sources to efficiently link a set of assay responses and model predictions to an outcome or hazard classification. To provide a central access point for these purposes, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods developed the Integrated Chemical Environment (ICE) web resource. The ICE data integrator allows users to retrieve and combine data sets and to develop hypotheses through data exploration. Open-source computational workflows and models will be available for download and application to local data. ICE currently includes curated in vivo test data, reference chemical information, in vitro assay data (including Tox21TM/ToxCast™ high-throughput screening data), and in silico model predictions. Users can query these data collections focusing on end points of interest such as acute systemic toxicity, endocrine disruption, skin sensitization, and many others. ICE is publicly accessible at https://ice.ntp.niehs.nih.gov. https://doi.org/10.1289/EHP1759
Circulating tumor DNA as a highly specific diagnostic marker for colorectal cancer.
Authors: Andre Marziali, Valentina Vysotskaia, Matthew Wiggin
Journal: Journal of Clinical Oncology (2014)

e22126 Background: Circulating tumor DNA (ctDNA) from cancer patient plasma is a promising biomarker with applications in screening, treatment selection, therapy response monitoring, minimal residual disease detection, and surveillance. We investigate the value of ctDNA as a biomarker in colorectal cancer to augment clinical decision-making. Methods: We present a ctDNA detection assay simultaneously capable of single molecule sensitivity, specificity to 0.01%– 0.001% mutation abundance versus wild-type, and multiplexing over 100 mutations from a single plasma sample. The employs a proprietary target selection process that removes wild-type DNA prior to library construction to greatly reduce the error rate of DNA sequencing. Using this assay, we analysed plasma from three cohorts of individuals including normal controls (n=13), age-matched normal controls (n=17), and colorectal cancer patients (n=17) across all stages of disease whose blood was drawn prior to treatment or surgery, and whose diagnosis confirms the presence of a tumor. Tissue from the primary tumor biopsy was also collected and analysed with the OnTarget assay. Results: We find a high correlation between the tumor mutational profile and the plasma mutation profile even for early stage patients demonstrating high sensitivity (92% plasma-tissue concordance over all patients) and exceptional specificity (100%: no false positives in normal cohorts). Additionally, mutations deemed from clinical evidence to originate from distant metastatic sites are detected in the plasma, highlighting the promise of the liquid biopsy approach for application in clinical care. We present concordance, sensitivity, and specificity results from the colorectal cancer patient cohort and the cohort of healthy individuals. Conclusions: Initial assay results from 30 healthy individuals and 17 CRC patients indicate that OnTarget detection of ctDNA provides an exceptionally specific assay for the presence of colorectal tumors and may have utility as a biomarker to guide colorectal cancer management across early-stage and metastatic disease.
Bio-inspired crosslinking and matrix-drug interactions for advanced wound dressings with long-term antimicrobial activity
Authors: Chetna Dhand, Mayandi Venkatesh, Veluchami Amutha Barathi, Sriram Harini, Samiran Bairagi, Eunice Goh Tze Leng, Nandhakumar Muruganandham, Kenny Zhi Wei Low, Mobashar Hussain Urf Turabe Fazil, Xian Jun Loh, Dinesh Kumar Srinivasan, Shou Ping Liu, Roger W. Beuerman, Navin Kumar Verma, Seeram Ramakrishna, Rajamani Lakshminarayanan
Journal: Biomaterials (2017)

There is a growing demand for durable advanced wound dressings for the management of persistent infections after deep burn injuries. Herein, we demonstrated the preparation of durable antimicrobial nanofiber mats, by taking advantage of strong interfacial interactions between polyhydroxy antibiotics (with varying number of OH groups) and gelatin and their in-situ crosslinking with polydopamine (pDA) using ammonium carbonate diffusion method. Polydopamine crosslinking did not interfere with the antimicrobial efficacy of the loaded antibiotics. Interestingly, incorporation of antibiotics containing more number of alcoholic OH groups (NOH ≥ 5) delayed the release kinetics with complete retention of antimicrobial activity for an extended period of time (20 days). The antimicrobials-loaded mats displayed superior mechanical and thermal properties than gelatin or pDA-crosslinked gelatin mats. Mats containing polyhydroxy antifungals showed enhanced aqueous stability and retained nanofibrous morphology under aqueous environment for more than 4 weeks. This approach can be expanded to produce mats with broad spectrum antimicrobial properties by incorporating the combination of antibacterial and antifungal drugs. Direct electrospinning of vancomycin-loaded electrospun nanofibers onto a bandage gauze and subsequent crosslinking produced non-adherent durable advanced wound dressings that could be easily applied to the injured sites and readily detached after treatment. In a partial thickness burn injury model in piglets, the drug-loaded mats displayed comparable wound closure to commercially available silver-based dressings. This prototype wound dressing designed for easy handling and with long-lasting antimicrobial properties represents an effective option for treating life-threatening microbial infections due to thermal injuries.
EPND-09. THE ONCOGENIC EFFECT OF C11ORF95-RELA FUSION MOSTLY DERIVES FROM FACTOR OTHER THAN NF-ΚB ACTIVATION IN SUPRATENTORIAL EPENDYMOMA
Authors: Tatsuya Ozawa, Sonali Arora, Frank Szulzewsky, Eric Holland
Journal: Neuro-Oncology (2017)

Recent deep molecular analyses of Ependymomas (EPNs) have revealed that supratentorial ependymomas (ST-EPNs) consisted of two different molecular subgroups denoted as ST-EPN-YAP1 and -RELA which associates with YAP1- and RELA-involved fusion gene, respectively. These fusion genes may provide significant and distinct therapeutic insights for each EPN subtypes. ST-EPN-RELA subgroup associates with C11orf95-RELA fusion gene (CR). The presence of RELA as one component of the CR leads to the suggestion that NF-kB activity may be essential for oncogenesis and a viable therapeutic target in these tumors. So far, we have demonstrated that the CR was a potent oncogene which was capable of inducing human EPN-like tumor in mice. However it still remains to be cleared whether NF-kB/RelA activity involved in the CR-induced tumor formation. Therefore, we undertook an extensive analysis of the connection between NF-kB/RelA activity and oncogenesis for the CR. We created various CR mutants with modification(s) in phosphorylation or acetylation site of RelA portion and tested their oncogenic potential in mice. These mutants presented superior or inferior tumor forming potential than the CR. When NF-kB/RelA activity of these mutants was measured with luciferase reporter assay in cultured fibroblasts, prominent NF-kB activity was not observed in any CR mutants and there was no correlation between NF-kB/RelA activity and tumor forming potential. Further when NF-kB activity of these CR mutants was examined using cultured fibroblasts and mouse tumors in RNA-seq, minimal NF-kB activity was observed in these mutants but not correlated with their tumor forming potential as well. These results suggested that NF-kB/RelA activity is unlikely essential for the process of tumor initiation in the CR-induced EPN formation, and the oncogenic effect of CR mostly derives from factor other than NF-kB activation. Therefore we will need further elaborate investigation whether NF-kB/RelA pathway is a right therapeutic target for these tumors.
Junior doctor is struck off over false research claims
Authors: Clare Dyer
Journal: BMJ (2017)

A junior doctor who was suspended for dishonesty in 2011 has been struck off after making false claims in an abstract for a conference presentation.

Harman Mattu, who qualified at the University of London in 2006, told “blatant lies” in an abstract for presentation at an Imperial College clinical education conference, a medical practitioners tribunal heard.

While working at West Middlesex Hospital in London in 2015 he developed a statement of clinical guidelines with four junior colleagues, which was intended to be uploaded to an app. But he did not credit the others in the abstract he submitted to the conference.

In the …
Autologous Stem Cell Transplant: A Cost Effective and Efficacious Treatment for Newly Diagnosed Multiple Myeloma
Authors: Seema Niphadkar, Indumathy Varadarajan, Tiffany Pompa, Kevin Y Hou, Kathleen Degen, Mariola Vazquez-Martinez, Stuthi Perimbeti, Kristine Ward, Maneesh Jain, Michael Styler
Journal: Blood (2016)
Counterterrorism policy is incoherent and ill conceived
Authors: Philip J Mc Garry
Journal: BMJ (2017)

Godlee asks whether doctors should engage with counterterrorism.1 As a doctor who worked through much of the terrorism in Northern Ireland, where paramilitaries killed over 3200 people, I am bemused, disturbed, and increasingly appalled at the over-reaction to the limited terrorist threat in Britain. …
Post-concussion abnormalities in the m60 somatosensory evoked field recorded by magnetoencephalography
Authors: Richard Wennberg, Youssef El-Rahimy, Nat Shampur, Luis Garcia Dominguez
Journal: British Journal of Sports Medicine (2017)

Objective We sought to determine whether magnetoencephalography (MEG) might reliably document the presence of neurophysiologic dysfunction after acute concussion. Based on a previous evoked potential study, 1 we analysed somatosensory evoked fields (SEFs) elicited by stimulation of the median nerve at the wrist. Design Case-control study. Setting Academic tertiary care centre. Participants Five patients with acute concussion (&lt;10 days post-injury); mean age 32±18 yrs, 3 women. 23 age/sex matched controls with no history of concussion. Assessment of risk factor Independent variable, concussion. Outcome measures Dependent variables, bilateral peak latencies of M20, M30, and M60 SEFs. Main results No differences were found between patients (24 recorded values) and controls (46 recorded values) in M20 (21.7±1.6 ms vs. 22.3±1.5 ms) or M30 (35.4±3.8 ms vs. 33.5±3.3 ms) latencies. M60 latencies were significantly delayed in patients compared to controls (90.4±21.5 ms vs. 64.0±8.6 ms; Mann Whitney U-test, U=186.5, p=0.0001). All symptomatic patients had an abnormally delayed M60 value&gt;2 SDs from the control mean on at least one side. Follow-up patient recordings showed gradual decreases in abnormal M60 latencies over months; weekly MEG and ImPACT testing in one patient showed normalisation of verbal memory at week 2, visual memory and symptom scores at week 5 and M60 latencies at week 10. Conclusions The M60 SEF represents the first intracortical stage of neuronal processing of external somatosensory input to the brain. In this preliminary study we found significant differences in M60 latencies between subjects with acute concussion and controls, as well as within subject changes during recovery in the weeks after concussion. Competing interests None.