tbuckley/cabot-search huggingface dataset:
Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody
Authors: Lianpan Dai, Jian Song, Xishan Lu, Yong-Qiang Deng, Abednego Moki Musyoki, Huijun Cheng, Yanfang Zhang, Yuan Yuan, Hao Song, Joel Haywood, Haixia Xiao, Jinghua Yan, Yi Shi, Cheng-Feng Qin, Jianxun Qi, George F. Gao
Journal: Cell Host & Microbe (2016)
Mutagenic Activation of N-2-Fluorenylacetamide and N-Hydroxy-N-2-fluorenylacetamide in Subcellular Fractions From X/Gf Mice2
Authors: T. V. Reddy, E. K. Weisburger, S. S. Thorgeirsson
Journal: JNCI Journal of the National Cancer Institute (1980)

The Salmonella mutagenesis test system was used to evaluate the in vitro mutagenic potency of N-2-fluorenylacetamide (2-FAA) and N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) mediated by liver and kidney subcellular fractions from X/Gf mice, a strain resistant to 2-FAA carcinogenesis. Pretreatment of the mice with the microsomal inducers 3-methylcholanthrene (MCA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased the number of revertants from both liver and kidney fractions. Mutagenicity of N-OH-2-FAA mediated by liver or kidney microsomes was partially inhibited at 0.001--0.1 microM Paraxon (diethyl-p-nitrophenyl phosphate), an inhibitor of deacetylase enzyme, and the inhibition was complete (98%) in microsomes from control mice (100 microM Paraoxon). Conversely, the liver and kidney microsomal fractions from MCA- and TCDD-treated X/Gf mice were less sensitive to Paraoxon. The inhibition of kidney or liver cytosol-mediated N-OH-2-FAA mutagenicity by Paraoxon was less than that observed with the microsomal fraction (50% inhibition at 1 x 10(-7) and 1 x 10(-5) M Paraoxon, respectively). The mutagenicity of 2-FAA and N-OH-2-FAA mediated by liver or kidney subcellular fractions from X/Gf mice and its response to inducers and inhibitors of mutagenic activation processes appear similar to those observed in species both resistant (cotton rat) and sensitive (Sprague-Dawley rat, NIH Swiss mice) to 2-FAA carcinogenesis.
Carboxyamidotriazole orotate (CTO) in combination with bevacizumab (BEV) for adult patients with recurrent malignant glioma post-BEV failure: Phase 1.
Authors: Annick Desjardins, Katherine B. Peters, Gordana Vlahovic, Dina Randazzo, Susan Boulton, Woody C Massey, Eric S Lipp, James Emmett Herndon, Patrick Healy, Elizabeth Miller, Rashida A. Karmali, Henry S. Friedman
Journal: Journal of Clinical Oncology (2015)

2067 Background: BEV is approved for the treatment of recurrent glioblastoma pts, but there is a lack of effective therapies once a tumor recurs on BEV. CTO, an oral inhibitor of non-voltage-dependent calcium signaling, modulates several pathways (EGFR, MEK, RAS, HDAC, HSP90, WNT/B-catenin, Akt, ERK, VEGF, Bcr-Abl). We postulated that combining CTO with BEV may result in greater VEGF inhibition and might allow salvage post-BEV failure. We are reporting on phase 1 of the study. Methods: Study objectives are to assess the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and activity of CTO when combined with BEV among pts with recurrent WHO grade III or IV MG post-BEV failure. CTO dose escalation has followed a classical 3+3 design at a dose ranging from 225-642mg/m2/day. BEV has been administered intravenously at 10mg/kg every 2 weeks. Pharmacokinetic (PK) sampling is performed during cycle 1 at each dose level. MRI of the brain is evaluated at baseline and every 8 weeks using RANO criteria. Results: To date, 15 pts have been enrolled on study. All pts have WHO grade IV MG. Median age at enrollment is 54 (32-66) years in eight females and seven males. Of the five pts treated at dose level 1 of CTO (225mg/m2/day), three remained stable for 4 cycles and demonstrated CAI (the active moiety of CTO in plasma) levels of 2317 and 361 ng/ml. Of the six pts treated at dose level 2 (293mg/m2/day), one pt remained stable for 7 cycles and one pt experienced a DLT, grade 3 hypertension and fatigue. Four pts were treated on dose level 3 (380 mg/m2/day), but two pts were not eligible for MTD determination, as they discontinued CTO before the end of cycle 1 without experiencing a DLT. Grade 3 study-related adverse events included: fatigue (n = 1), soft tissue infection (n = 1), proteinuria (n = 2) and hypertension (n = 2). No grade 4 or 5 study-related adverse events have been observed. Conclusions: CTO, at a dose of 380mg/m2/day, given in combination with BEV is safe thus far and tolerable. Non-evaluable pts for MTD are being replaced. Some pts having previously failed BEV have remained stable for a period of time on the combination. Further dose escalation is continuing to determine the Phase II dose. Clinical trial information: NCT01954030.
ECT and special problems of informed consent
Authors: C M Culver, R B Ferrell, R M Green
Journal: American Journal of Psychiatry (1980)

The authors examine the question of whether severely depressed patients can validly consent to ECT, indeed whether anyone should be asked to consent to a treatment that some have held is disabling and beyond the range of rational choice. They suggest some clarification in the use of the terms "competent" and "rational." The authors present examples of cases where ECT may appropriately be used with and without a patient's consent. They conclude that except in cases in which patients may die without ECT, physicians will not err morally by respecting patients' informed decisions about treatment.
Branched Retinal Artery Occlusions and Susac Syndrome
Authors: Nikisha Kothari, Ajay E. Kuriyan
Journal: JAMA Neurology (2016)

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 Neurology 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 Neurology journal
Controlled Epstein-Barr Virus Reactivation After Allogenic Transplantation Improves Survival and Is Associated To An Expansion Of Natural Killer Cells (NK)
Authors: Sophie Auger, Mattea Orsini, Patrice Ceballos, Nathalie Fegueux, Bernard Klein, Martin Villalba, Jean-Francois Rossi
Journal: Blood (2013)
Temporally degradable collagen–mimetic hydrogels tuned to chondrogenesis of human mesenchymal stem cells
Authors: Paresh A. Parmar, Stacey C. Skaalure, Lesley W. Chow, Jean-Philippe St-Pierre, Violet Stoichevska, Yong Y. Peng, Jerome A. Werkmeister, John A.M. Ramshaw, Molly M. Stevens
Journal: Biomaterials (2016)

Tissue engineering strategies for repairing and regenerating articular cartilage face critical challenges to recapitulate the dynamic and complex biochemical microenvironment of native tissues. One approach to mimic the biochemical complexity of articular cartilage is through the use of recombinant bacterial collagens as they provide a well-defined biological 'blank template' that can be modified to incorporate bioactive and biodegradable peptide sequences within a precisely defined three-dimensional system. We customized the backbone of a Streptococcal collagen-like 2 (Scl2) protein with heparin-binding, integrin-binding, and hyaluronic acid-binding peptide sequences previously shown to modulate chondrogenesis and then cross-linked the recombinant Scl2 protein with a combination of matrix metalloproteinase 7 (MMP7)- and aggrecanase (ADAMTS4)-cleavable peptides at varying ratios to form biodegradable hydrogels with degradation characteristics matching the temporal expression pattern of these enzymes in human mesenchymal stem cells (hMSCs) during chondrogenesis. hMSCs encapsulated within the hydrogels cross-linked with both degradable peptides exhibited enhanced chondrogenic characteristics as demonstrated by gene expression and extracellular matrix deposition compared to the hydrogels cross-linked with a single peptide. Additionally, these combined peptide hydrogels displayed increased MMP7 and ADAMTS4 activities and yet increased compression moduli after 6 weeks, suggesting a positive correlation between the degradation of the hydrogels and the accumulation of matrix by hMSCs undergoing chondrogenesis. Our results suggest that including dual degradation motifs designed to respond to enzymatic activity of hMSCs going through chondrogenic differentiation led to improvements in chondrogenesis. Our hydrogel system demonstrates a bimodal enzymatically degradable biological platform that can mimic native cellular processes in a temporal manner. As such, this novel collagen-mimetic protein, cross-linked via multiple enzymatically degradable peptides, provides a highly adaptable and well defined platform to recapitulate a high degree of biological complexity, which could be applicable to numerous tissue engineering and regenerative medicine applications.
Inducible Expression of Claudin-1 in Glomerular Podocytes Generates Aberrant Tight Junctions and Proteinuria through Slit Diaphragm Destabilization
Authors: Yongfeng Gong, Abby Sunq, Robyn A. Roth, Jianghui Hou
Journal: Journal of the American Society of Nephrology (2016)

The tight junction (TJ) has a key role in regulating paracellular permeability to water and solutes in the kidney. However, the functional role of the TJ in the glomerular podocyte is unclear. In diabetic nephropathy, the gene expression of claudins, in particular claudin-1, is markedly upregulated in the podocyte, accompanied by a tighter filtration slit and the appearance of TJ-like structures between the foot processes. However, there is no definitive evidence to show slit diaphragm (SD) to TJ transition in vivo . Here, we report the generation of a claudin-1 transgenic mouse model with doxycycline-inducible transgene expression specifically in the glomerular podocyte. We found that induction of claudin-1 gene expression in mature podocytes caused profound proteinuria, and with deep-etching freeze-fracture electron microscopy, we resolved the ultrastructural change in the claudin-1–induced SD-TJ transition. Notably, immunolabeling of kidney proteins revealed that claudin-1 induction destabilized the SD protein complex in podocytes, with significantly reduced expression and altered localization of nephrin and podocin proteins. Mechanistically, claudin-1 interacted with both nephrin and podocin through cis - and trans -associations in cultured cells. Furthermore, the rat puromycin aminonucleoside nephrosis model, previously suspected of undergoing SD-TJ transition, exhibited upregulated expression levels of claudin-1 mRNA and protein in podocytes. Together, our data attest to the novel concept that claudins and the TJ have essential roles in podocyte pathophysiology and that claudin interactions with SD components may facilitate SD-TJ transition that appears to be common to many nephrotic conditions.
PWE-359 Modifiable risk factors for serrated colorectal polyps: a systematic review and meta-analysis
Authors: L Bailie, MB Loughrey, HG Coleman
Journal: Gut (2015)

<h3>Introduction</h3> Certain categories within the classification of serrated polyps (SP) of the colorectum are now understood to carry malignant potential. The serrated pathway accounts for at least 15% of all colorectal cancers. The aim of this systematic review was to investigate the association between modifiable lifestyle factors and risk of SP. <h3>Method</h3> A search was conducted systematically within three databases, Medline, Embase and Web of Science, for relevant literature published by October 2014. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were combined using random effects meta-analyses to assess the risk of SP, where possible. <h3>Results</h3> Thirty-six papers were identified for inclusion in the review, analysing SP risk and seven different lifestyle factors: smoking, alcohol, body fatness, diet, physical activity, non-steroidal anti-inflammatory drug (NSAID) use and/or infectious agents. When comparing the highest and lowest categories of exposure, significant elevated risks of SP were identified for tobacco smoking (OR 2.78, 95% CI 2.30–3.34); alcohol intake (OR 1.36, 95% CI 1.19–1.56), and body mass index (OR 1.46, 95% CI 1.19–1.79). Contrastingly, significant decreased SP risks were observed for NSAID (OR 0.77, 95% CI 0.63–0.94) and aspirin users (OR 0.77, 95% CI 0.65–0.92), compared with non-users. No significant associations were detected for SP risk and physical activity, while associations with dietary factors were mixed. Most studies had not separately identified sessile serrated adenomas/polyps from hyperplastic polyps in their analyses, as publication predated widespread recognition of this novel serrated polyp category. <h3>Conclusion</h3> This systematic review has identified novel associations for several lifestyle factors and risk of SP, subgroups of which have recently been implicated in carcinogenesis. These findings enhance our understanding of potential mechanisms involved, and suggest that SP (and ultimately colorectal cancer) risk could be reduced via changes in lifestyle. Further studies are needed to report on specific SP categories. <h3>Disclosure of interest</h3> None Declared.
Patent ductus arteriosus illuminating an old eponym
Authors: Tom Ford, David Rees
Journal: BMJ (2016)

A 60 year old woman was sent from primary care for assessment of acute left sided pleuritic chest pain and dyspnoea without sputum production. She had been experiencing malaise, intermittent fever, and rigors for four weeks. A patent ductus arteriosus (PDA) had been identified in late adulthood 10 years earlier, after a murmur was detected on routine medical examination. This was confirmed by transthoracic echocardiography; there were no other signs of haemodynamic importance.

At presentation she had a fever (39.0°C) with left sided pleural rub. Precordial examination identified a continuous “machinery” murmur. Electrocardiographic findings were within normal limits and laboratory investigations confirmed normocytic anaemia, leucocytosis, and preserved renal function. Group B streptococcus was isolated from all three separate blood cultures. Her pleural rub corresponded to an abnormality on chest radiography (fig 1⇓).



Fig 1 

1.  What abnormality on chest radiography corresponds to the pleural rub?

2.  Given the clinical presentation and history of PDA, what is the likely cause of this abnormality?

3.  What investigation would confirm the cause of this abnormality?

4.  What is the initial cardiac imaging technique of choice?

### 1. What abnormality on chest radiography corresponds to the pleural rub?

#### Short answer

The wedge shaped peripherally based opacity in the left mid zone.

#### Discussion

The triangular (wedge) shaped opacity in the left mid zone (fig 2⇓) corresponds to the clinical history of left sided pleuritic pain and examination finding of a pleural rub. Such a wedge shaped opacity is eponymously termed “Hampton’s hump”—an old but important plain radiological sign of pulmonary embolism. It was first described in 1940 by the radiologist Aubrey Otis Hampton.1 On close inspection of the enlarged radiograph, smaller scattered opacities …
Hereditary spherocytosis due to a novel frameshift mutation in AE1 cytoplasmic COOH terminal tail: band 3 Vesuvio.
Authors: Silverio Perrotta, Raffaella Polito, Maria Luisa Conte, Bruno Nobili, Stefano Cutillo, Emanuele Miraglia del Giudice, Vincenzo Nigro, Achille Iolascon, Giovanni Amendola
Journal: Blood (1999)
PTU-316 Has a change in bowel prep regime for diabetics improved their outcomes within the bowel cancer screening programme (bcsp)
Authors: N Taggart, M Mbuyongha, L Leedham, G Lowe, H Gibson, W Hymer, D Davies, S Mumtaz-Wong, S Sarkar
Journal: Gut (2015)

<h3>Introduction</h3> Diabetic patients (DM) often have numerous co-morbidities and can suffer from autonomic dysfunction and poor GI motility. Within the Bowel Cancer Screening Programme (BCSP) we have previously shown that using our standard regime of moviprep, that the prep was as described as inadequate in 14% patients all of which needed repeat procedures, but CIR was 92%. This was important as the adenoma detection rate (ADR) in these patients was high at 62%.<sup>1</sup>The bowel prep regime for diabetics was changed to Kleen Prep and this re-audit was performed to close the loop in order to determine whether this intervention was effective. <h3>Method</h3> A re-audit was performed in over 10 months in 2014 on all diabetic patients that had Kleen prep as their primary bowel prep within the Liverpool and Wirral BCSP. The outcomes audited was the amount of inadequate prep, repeat colonoscopy procedures, ADR and Caecal intubation rate (CIR). <h3>Results</h3> 56 patients (64% male) were audited with mean age was X. Median ASA was II. Bowel prep rating was good in 14%, adequate in 77% and inadequate in 9%. All inadequately prep patients needed a repeat procedure. This compared to just 3.65% of inadequate preps over this period. The CIR was far lower in this diabetic group was 89.3%, (One patient had a failed procedure due to looping) which compared to an overall CIR on the programme of 97.3% over this period. The ADR in the diabetic group was 55%, which compared to an ADR of 60.6%. No patients had any adverse events, readmissions or 30-day mortality. <h3>Conclusion</h3> Following our change in regime: Bowel preparation with Kleen prep now just meets below QA &amp;GRS standards resulting in less repeats (9% with Kleen prep verse 14% with moviprep). However, their poor bowel preparation remains a challenge as both CIR and ADR seems to be adversely affected as a consequence. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Do diabetic patients have any worse outcomes than non-diabetic patients at colonoscopy within the bowel cancer screening programme? A Case Controlled Study- BSG, 2012
Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Ian E Krop, Ingrid A Mayer, Vinod Ganju, Maura Dickler, Stephen Johnston, Serafin Morales, Denise A Yardley, Bohuslav Melichar, Andres Forero-Torres, Soo Chin Lee, Richard de Boer, Katarina Petrakova, Susanne Vallentin, Edith A Perez, Martine Piccart, Matthew Ellis, Eric Winer, Steven Gendreau, Mika Derynck, Mark Lackner, Gallia Levy, Jiaheng Qiu, Jing He, Peter Schmid
Journal: The Lancet Oncology (2016)
Is weight phobia always necessary for a diagnosis of anorexia nervosa?
Authors: L K Hsu, S Lee
Journal: American Journal of Psychiatry (1993)

Several reviews of the history of anorexia nervosa have concluded that weight phobia, a basic diagnostic criterion for the disorder, did not emerge as a predominant motive for food refusal until around 1930. In addition, investigators have reported cases of self-starvation without apparent weight phobia in non-Western cultures. Three explanations have been proposed for these findings: 1) patients who do not demonstrate a definite weight phobia are in fact suffering from an eating disorder not otherwise specified, 2) weight phobia has been overlooked or concealed, and 3) there has been a transformation in the content of anorexia nervosa in the West and an analogous situation may be occurring in the developing countries. The authors conclude that a change in the core features of anorexia nervosa in Western cultures since 1930 can be demonstrated. They explore the question of whether anorexia nervosa would be the same illness if the criterion of weight phobia were not required and conclude that anorexia nervosa may be conceptualized in several different ways without including the phenomenon of weight phobia or body image disturbance. Finally, they recommend that because the desire for thinness appears to be culture-bound, anorexia nervosa is the best disorder to use in examining the influence of culture on psychopathology. Therefore, cases of self-starvation in non-Western cultures should be studied carefully because they may clarify the core features of anorexia nervosa.
Thrombomodulin Alfa Treatment For Disseminated Intravascular Coagulation In Acute Promyelocytic Leukemia: A Retrospective Analysis Of The Open-Label, Multicenter Study Cohort
Authors: Tadashi Matsushita, Jyunichi Watanabe, Goichi Honda, Jun Mimuro, Hoyu Takahashi, Hajime Tsuji, Yutaka Eguchi, Isao Kitajima, Yoichi Sakata
Journal: Blood (2013)
Expanded Genetic Codes Create New Mutational Routes to Rifampicin Resistance in<i>Escherichia coli</i>
Authors: Michael J. Hammerling, Jimmy Gollihar, Catherine Mortensen, Razan N. Alnahhas, Andrew D. Ellington, Jeffrey E. Barrick
Journal: Molecular Biology and Evolution (2016)

Until recently, evolutionary questions surrounding the nature of the genetic code have been mostly limited to the realm of conjecture, modeling, and simulation due to the difficulty of altering this fundamental property of living organisms. Concerted genome and protein engineering efforts now make it possible to experimentally study the impact of alternative genetic codes on the evolution of biological systems. We explored how Escherichia coli strains that incorporate a 21st nonstandard amino acid (nsAA) at the recoded amber (TAG) stop codon evolve resistance to the antibiotic rifampicin. Resistance to rifampicin arises from chromosomal mutations in the β subunit of RNA polymerase (RpoB). We found that a variety of mutations that lead to substitutions of nsAAs in the essential RpoB protein confer robust rifampicin resistance. We interpret these results in a framework in which an expanded code can increase evolvability in two distinct ways: by adding a new letter with unique chemical properties to the protein alphabet and by altering the mutational connectivity of amber-adjacent codons by converting a lethal nonsense mutation into a missense mutation. Finally, we consider the implications of these results for the evolution of alternative genetic codes. In our experiments, reliance on a mutation to a reassigned codon for a vital trait is not required for the long-term maintenance of an expanded genetic code and may even destabilize incorporation of an nsAA, a result that is consistent with the codon capture model of genetic code evolution.
Bollywood could play role in tackling antimicrobial resistance, says review lead
Authors: David Payne
Journal: BMJ (2016)

The economist leading an independent UK review into antimicrobial resistance has signalled that its final recommendations could include enlisting Bollywood as part of a global awareness campaign to tackle the problem.

Jim O’Neill said that his team’s review, due to be published later this month, will also propose lump sum payments to drug companies as incentives to develop new drug pipelines.

The UK prime minister, David Cameron, asked O’Neill and his six member team to propose concrete actions when in July 2014 he asked him to lead the review to look at the economic aspects of antimicrobial …