tbuckley/cabot-search huggingface dataset:
<i>Notes from the Field</i>: Carbapenem-resistant Enterobacteriaceae Producing OXA-48-like Carbapenemases — United States, 2010–2015
Authors: Meghan Lyman, Maroya Walters, David Lonsway, Kamile Rasheed, Brandi Limbago, Alexander Kallen
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Carbapenem-resistant Enterobacteriaceae (CRE) are bacteria that are often resistant to most classes of antibiotics and cause health care-associated infections with high mortality rates. Among CRE, strains that carry plasmid-encoded carbapenemase enzymes that inactivate carbapenem antibiotics are of greatest public health concern because of their potential for rapid global dissemination, as evidenced by the increasing distribution of CRE that produce the Klebsiella pneumoniae carbapenemase and the New Delhi metallo-β-lactamase. Newly described resistance in Enterobacteriaceae, such as plasmid-mediated resistance to the last-line antimicrobial colistin, recently detected in China, and resistance to the newly approved antimicrobial, ceftazidime-avibactam, identified from a U.S. K. pneumoniae carbapenemase-producing isolate, highlight the continued urgency to delay spread of CRE. Monitoring the emergence of carbapenemases is crucial to limiting their spread; identification of patients carrying carbapenemase-producing CRE should result in the institution of transmission-based precautions and enhanced environmental cleaning to prevent transmission.* The OXA-48 carbapenemase was first identified in Enterobacteriaceae in Turkey in 2001, and OXA-48-like variants have subsequently been reported around the world. The first U.S. reports of OXA-48-like carbapenemases were published in 2013 and included retrospectively identified isolates from 2009 and two isolates collected in 2012 from patients in Virginia who had recently been hospitalized outside the United States. Although there are limited additional published reports from the United States, CDC continues to receive reprots of these organisms. This report describes patients identified as carrying CRE producing OXA-48-like carbapenemases in the United States during June 2010-August 2015.
Abstract 2364: Overexpression of SATB1 (Special AT-Rich Sequence-Binding Protein 1) in prostate cancer potentiates metastatic phenotype
Authors: Sanjeev Shukla, Gregory T. MacLennan, Pingfu Fu, Sanjay Gupta
Journal: Cancer Research (2010)

Abstract One of the reasons for the most prostate cancer-related deaths is the growth of secondary tumors due to metastases and not the primary organ-confined carcinoma. Metastasis in cancer cells results in acquiring abilities of increased motility and invasiveness, to home in other parts of the body. The key regulator involved in the control of metastasis genes in prostate cancer is presently unknown. Special AT-rich sequence-binding protein 1 (SATB1) is a transcription factor and functions as genome organizer. SATB1 being a transcription factor tend to bind with AT rich base unpaired sequences of the target gene. SATB1 acquires a “3 D chickenwire” network by forming anchor loops around chromatin, recruits chromatin remodeling complexes on the anchorage sites, and regulates histone modifications by rendering DNA sequences accessible or inaccessible for transcription. Earlier studies suggested the role of SATB1 in breast cancer progression. We aimed to observe the role of SATB1 in prostate cancer progression. We used different grades of human prostate cancer specimens, non tumorigenic and aggressive prostate cancer cells. Immunohistochemical evaluation of SATB1 in prostate cancer specimens of various Gleason grades exhibited significantly increased expression with increase in Gleason grade. A progressive increase in nuclear SATB1 expression was observed as tumor grade increased along with its presence in the cytoplasm. Further, SATB1 protein levels were higher in human prostate cancer cell lines viz. HPV-CA-10, DU145, DUPro, PC-3, PC-3M compared to non-tumorigenic prostate epithelial cells PZ-HPV-7. Nuclear expression of SATB1 was higher in biologically aggressive subclones of prostate cancer cells. Introduction of SATB1 through transient infections into non-tumorigenic PZ-HPV-7 cells increased its invasiveness and migration capabilities, whereas these properties were inhibited by silencing SATB1 through shRNA techniques. Furthermore, knock down of SATB1 caused increased E-cadherin expression and simultaneous reduction in matrix metalloproteinase-9 expression, providing further evidence that SATB1 significantly influences the metastasis process. Taken together, our results suggest that SATB1 is a master regulator of the metastasis process in prostate cancer and, therefore, could be considered as an independent prognostic factor and a potential therapeutic target for prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2364.
Acute phencyclidine (PCP) intoxication: quantitative urine levels and clinical management
Authors: S Walker, J A Yesavage, J R Tinklenberg
Journal: American Journal of Psychiatry (1981)

In this article we present retrospective data on the management of 100 patients with phencyclidine (PCP) intoxication (DSM-III category 305.9) and discuss the relationships between PCP intoxication and the patients’ quantitative urine levels of PCP. We address the questions of whether PCP urine levels are correlated with the patients’ violent outbursts or with their duration of hospitalization. Urine levels were exammed in relation to the pharmacologic treatment received. Clinical management of PCP intoxication is a panticularly confusing area because the present literature on PCP intoxication is nonquantitative and contradictory. Some clinical investigators have suggested that diazepam (1) or neuroleptics (2) may be efficacious, while others have argued that diazepam impairs recovery by slowing excretion of PCP (2) and that phenothiazines may induce dangerous orthostatic hypotensive crises
Reversible Metronidazole-Induced Lesions of the Cerebellar Dentate Nuclei
Authors: Bryan K. Woodruff, Eelco F.M. Wijdicks, William F. Marshall
Journal: New England Journal of Medicine (2002)

To the Editor: The toxic effects of metronidazole include ataxia, peripheral neuropathy, and seizures.1 There have been two reported cases in which abnormalities of the dentate nucleus on magnetic resonance imaging (MRI) were associated with metronidazole treatment.2,3 We describe two additional cases of new-onset ataxia and dysarthria associated with the use of metronidazole. We also document the reversibility of both the clinical symptoms and the MRI abnormalities after discontinuation of the drug. Ataxia and dysarthria developed approximately one month after the initiation of antibiotic therapy in a 62-year-old man with multiple epidural abscesses. He had been treated with metronidazole . . .
Muramyl dipeptide
Authors: VK Viswanathan
Journal: Gut Microbes (2014)

The robust expression of microbial pattern recognition receptors such as TLR4 and Nod2 in intestinal stem cells reflects an active communication dynamic between the host and the gut microbiota. A new study reveals that muramyl dipeptide, the bacterial cell wall peptidoglycan motif, activates Nod2 within crypt base columnar Lgr5-positive stem cells and promotes their survival. Apart from the immediate relevance to the growth of organoids for in vitro experiments, the study raises new questions about the molecular mechanisms whereby gut microbes influence intestinal physiology.
SAT0300 Microcirculation and Macrovascular Disease in Systemic Sclerosis – A Nailfold Capillary Study
Authors: A. Nordin, L. Björnådal, E. Roubi, K. Jensen-Urstad, E. Svenungsson
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Emerging evidence demonstrate that patients with systemic sclerosis (SSc) suffer from both micro- and macrovascular disease. Structural changes in nailfold capillaries, a marker of microvascular involvement, has been associated with clinical symptoms such as digital ulcers and pulmonary arterial hypertension. <h3>Objectives</h3> In this study we investigated the association between nailfold capillary changes and macrovascular ischemic arterial events (IAE), wich includes ischemic heart disease (IHD), ischemic peripheral vascular disease (IPVD) and ischemic cerebrovascular disease (ICVD). <h3>Methods</h3> 163 consecutive patients fulfilling the new 2013 EULAR/ACR classification criteria for SSc participated. Widefield nailfold capillaroscopy was performed on all. Presence of enlarged capillary loops, avascular regions, and nailfold capillary density was recorded. Disease characteristics, autoantibodies, previous digital ulcers, previous IAE, the duration and severity of Raynaud9s phenomenon (RP) and the echocardiographic/Doppler estimated pulmonary arterial pressure (ePAP) were tabulated. <h3>Results</h3> Mean age was 61±13 years and 83% were female. Enlarged capillary loops or avascular regions were found in 52% and 55% respectively. Mean nailfold capillary density was 13.5±4.5 loops/3mm. 13% had a history of IAE, 17% had an ePAP&gt;35 mmHg and 39% had a history of digital ulcers. Enlarged capillary loops were associated with a shorter disease duration and presence of anticentromere antibodies (ACA), p=0.01. Occurrence of avascular regions was associated with a longer disease- and RP duration (p&lt;0.01), ACA (p&lt;0.0001), digital ulcers (p&lt;0.001) and limited cutaneous SSc (p&lt;0.01). A low capillary density was more common among patients with a higher ePAP (p=0.03), ACA (p=0.03), digital ulcers (p&lt;0.01) and IAE (p=0.04), especially IPVD (p=0.05). <h3>Conclusions</h3> A low nailfold capillary density, a measure of microvascular involvement, was associated with macrovascular disease. Moreover, our results confirm that a low capillary nailfold density was associated with ACA and clinical signs of vascular involvement such as digital ulcers and a higher ePAP. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5495
A CLINICAL SCORE TO PREDICT INCIDENT STATIN INDUCED MYALGIA: A RETROSPECTIVE COHORT STUDY
Authors: Ghanshyam Palamaner Subash Shantha, Anita A. Kumar, Kongkiat Chaikriangkrai, Aref Bin Abdulhak, Rami Kafa, Rudhir Tandon, Hakeem Ayinde, Michael Giudici, Lawrence Cheskin
Journal: Journal of the American College of Cardiology (2016)
DR-08 * MSK1/ -CATENIN SIGNALING MEDIATES RESISTANCE TO PI3K/mTOR INHIBITORS IN GLIOBLASTOMA
Authors: S. Wu, S. Zheng, R. Verhaak, D. Koul, W. K. A. Yung
Journal: Neuro-Oncology (2014)

Glioblastoma, with aberrant activation of growth factor signaling pathways, represents a compelling disease for kinase inhibitor therapy. Despite the evidence defining the PI3K network as a high quality target, regulatory feedback loops as well as cross-talk with other networks make understanding and targeting the PI3K network a challenging task. As a result of selective pressure by PI3 kinase inhibitors, glioblastoma: 1) up-regulates compensatory survival pathways and 2) utilizes complimentary pathways as a predominant mechanism of escape from anti-PI3K drugs, which can be eliminated by concomitant use of complimentary inhibitors. Here, we tested these hypotheses, using a large panel of glioma cells and glioma initiating stem cell (GIC) lines treated with PI3K inhibitors. A differential response to PI3K pathway inhibitors divided GICs into responder and non-responder groups, identifying molecular profiles that distinguish the two groups. Gene expression profiling before and after PI3K inhibitor treatment was analyzed by Affymetrix microarrays to identify molecular targets/signatures contributing resistance to PI3K inhibitors. We identified mitogen- and stress-activated protein kinase 1 (MSK1) was markedly induced after PI3K/mTOR inhibitor treatment. MSK1 depletion attenuated GIC resistance to PI3K/mTOR inhibitors, and overexpression of MSK1 potentiated the resistance to PI3K/mTOR inhibitors. Further investigation identified β-catenin as a direct interacting protein of MSK1. Interestingly, MSK1 phosphorylated β-catenin at ser552 and regulated β-catenin nuclear translocation and transcriptional activity. More interestingly, we showed that overexpression of S552D-β-catenin reversed MSK1-shRNA-attenuated resistance to PI3K/mTOR inhibition. Disruption of MSK1 synergized with PI3K/mTOR inhibitors to extend survival in an intracranial animal model, accompanied by decreased phosphorylation of β-catenin at Ser552. Taken together, our results suggested that PI3K/mTOR inhibitors activated MSK1/β-catenin signaling, which may serve as an escape survival signaling mechanism upon PI3K/mTOR inhibition in glioblastoma. Therefore targeting PI3K/mTOR pathway together with MSK-1 might show increased therapeutic benefit when used as combination regimen.
Abstract 2215: Association between acquired uniparental disomy and homozygous mutations and HER2/neu, ER, and PR status in breast cancer: Meta-analysis
Authors: Musaffe Tuna, John A. Foekens, Christopher I. Amos
Journal: Cancer Research (2010)

Abstract Mutations in genes that encode components of cellular signaling networks are a hallmark of cancer. However, sequencing the whole genome for each tumor sample is challenging. A novel form of abnormality called acquired uniparental disomy (aUPD) was recently found, which can pinpoint a region containing mutated genes predisposing to various cancers, therefore identifying a candidate region for subsequent next-generation. We conducted a large meta-analysis of genomic data from the Gene Expression Omnibus database to retrieve genome-wide regions of aUPD in breast tumor samples using approaches that can reliably detect aUPD. aUPD was identified in 40.57% of the samples. The most recurrent aUPD regions were located at chromosomes 17q, 3p, 13q, and 11q. These data suggest that multiple genes may be targeted for homozygous mutations. Then we found association between aUPD and homozygous point alterations by integrating our data with previously published mutation data on reference gene sequences in breast tumors. We also evaluated the data for any correlation between the most recurrent aUPD region at chromosome 17q and HER2/neu, ER, and PR status, and we found a statistically significant correlation between aUPD at chromosome 17q and HER2/neu-, ER- and PR-negative breast cancers. We conclude that aUPD is a common and nonrandom new molecular mechanism in breast tumorigenesis. Identifying UPD regions would be a more effective approach to take than randomly sequencing the genome for discovering novel candidate genes for mutation. An integrative view of aUPD and homozygous sequence alterations on a genome-wide scale should provide further valuable insights into breast tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2215.
Abstract 156: MicroRNA expression profiling of human esophageal metaplastic changes
Authors: Matteo Fassan, Stefano Volinia, Jeff Palatini, Marco Pizzi, Cecilia Fernandez-Cymering, Giorgio Battaglia, Mariangela Balistreri, Carlo M. Croce, Giovanni Zaninotto, Ermanno Ancona, Massimo Rugge
Journal: Cancer Research (2011)

Abstract For nearly the last two decades, the diagnosis of Barrett's mucosa (BM) strictly required histologically documented intestinal metaplasia (IM). More recently, a precancerous potential has been also associated to non-goblet columnar metaplasia (i.e. gastric metaplasia, [GM]). Molecular profiling can be applied to characterize the precancerous meaning of non-intestinal versus intestinal metaplastic transformation of the native squamous esophageal mucosa. MicroRNAs (miRNAs) are a class of small non-coding RNAs controlling gene expression and they are reportedly dysregulated in Barrett's carcinogenesis. To investigate the role of miRNAs in the natural history of esophageal metaplasia, miRNA microarray analysis (OSU-CCC version 4.0; Ohio State University) was performed in a series of 30 matched biopsy samples (10 native squamous epithelium [N], 10 GM and 10 IM) from 10 long-segment BE-patients. Microarray findings were validated by qRT-PCR using another series of 20 consecutive BE-patients. miRNA profiling consistently disclosed different metaplasia-specific miRNA signatures for N versus GM, and N versus IM. Comparing the two signatures disclosed that they had 11 significantly dysregulated miRNAs in common, 8 of which were proportionally dysregulated in the sequence N-GM-IM (2 overexpressed [hsa-miR-192 and hsa-miR-215] and 6 underexpressed [hsa-miR-18a*; hsa-miR-20a, hsa-miR-106a, hsa-miR-203, hsa-miR-205 and hsa-miR-769-5p]). Specific miRNAs are involved in the natural history of BE. Molecular profiling of phenotypical lesions included in Barrett's carcinogenesis supports the hypothesis that squamous epithelium is converted initially into non-goblet columnar epithelium, before goblet cell metaplasia sets in. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 156. doi:10.1158/1538-7445.AM2011-156
Abstract 3803: 3,3-Diindolylmethane enhances Taxotere-induced apoptosis in breast cancer cells through FoXM1 downregulation
Authors: KM Rahman, Aamir Ahmad, Shadan Ali, Zhiwei Wang, Seema Sethi, Wael Sakr
Journal: Cancer Research (2010)

Abstract Emerging evidence suggests that the transcription factor Forkhead Box M1 (FoxM1) is associated with the aggressive human carcinomas, including breast cancer. Since elevated expression of FoxM1 is observed in human breast cancers, FoxM1 has attracted growing attention as a potential target for the prevention or therapeutic intervention in breast cancer. However, no information is currently available regarding how down-regulation of FoxM1 could be achieved by any agents without toxicity, and whether this down-regulation could result in any benefit for patients diagnosed with breast cancer. 3,3′-diindolylmethane is a chemopreventive agent that has shown anti-tumor effects in various tumors. Currently there are no reports documenting the role of DIM in the inhibition of FoXM1, which will sensitize breast cancer cells to conventional therapeutic agents. Using a variety of breast cancer cells, we investigated the effect of DIM alone and in combination with Taxotere. Using multiple approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, gene transfection, flow cytometry, real-time reverse transcription-PCR, Western blotting, migration, invasion, and angiogenesis assays, we found that DIM enhanced Taxotere-induced apoptotic cell death in breast cancer cells. These enhancing effect were related to the down-regulation of FoxM1, as well as the inhibition of cell growth, decrease in cell migration, and invasion of breast cancer cells. We also found that knockdown of FoXM1 expression by small interfering RNA transfection increased DIM-induced cell growth inhibition and apoptosis, whereas overexpression of FoxM1 by cDNA transfection minimized DIM-induced cell growth inhibition and apoptosis in breast cancer cells. Furthermore, combination treatment significantly inhibited tumor growth, and the results were correlated with the down-regulation of FoXM1. From these results, we conclude that inactivation of FoxM1 and its target genes by DIM enhanced the therapeutic efficacy of Taxotere in breast cancer, which could be useful for the treatment and/or prevention of aggressive breast cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3803.
Hyperfractionated Irradiation with or without Concurrent Chemotherapy for Locally Advanced Head and Neck Cancer
Authors: David M. Brizel, Mary E. Albers, Samuel R. Fisher, Richard L. Scher, William J. Richtsmeier, Vera Hars, Stephen L. George, Andrew T. Huang, Leonard R. Prosnitz
Journal: New England Journal of Medicine (1998)

Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone.
Glucose Intolerance in Cystic Fibrosis
Authors: Stuart Handwerger, Jesse Roth, Phillip Gorden, Paul di Sant'Agnese, Deborah F. Carpenter, Georges Peter
Journal: New England Journal of Medicine (1969)

Abstract Moderate to severe oral glucose intolerance was observed in 42 per cent of 31 patients with cystic fibrosis of the pancreas. Serum insulin concentrations after glucose were low in all patients regardless of glucose tolerance. When glucagon or tolbutamide was infused at the height of the reduced insulin response to oral glucose, serum insulin levels promptly increased 100 per cent or more in all cases. Since family histories, characteristic complications and post-mortem signs of diabetes mellitus were absent and the decrease in the number of beta cells was only modest, the glucose intolerance in cystic fibrosis is probably not due to coexistent diabetes mellitus or to beta-cell loss but, rather, to the anatomic disorganization of the islands of Langerhans produced by fibrosis of the pancreas.