tbuckley/cabot-search huggingface dataset:
Getting to Zero Transmission of ERCP Infections
Authors: Jeffrey Tokar, John I. Allen, Michael L. Kochman
Journal: JAMA Surgery (2015)

To the Editor We read with interest the Viewpoint by Keswani and Soper1 and wish to comment on it. In March, the American Gastroenterological Association held a meeting, “Getting to Zero,” which covered many of the endoscopic retrograde cholangiopancreatography (ERCP) infection issues discussed.2-4
The Epitope Study on the SARS-CoV Nucleocapsid Protein
Authors: Shuting Li, Liang Lin, Hao Wang, Jianning Yin, Yan Ren, Zhe Zhao, Jie Wen, Cuiqi Zhou, Xumin Zhang, Xiaolei Li, Jingqiang Wang, Zhengfeng Zhou, Jinxiu Liu, Jianmin Shao, Tingting Lei, Jianqiu Fang, Ningzhi Xu, Siqi Liu
Journal: Genomics Proteomics & Bioinformatics (2003)

Abstract The nucleocapsid protein (N protein) has been found to be an antigenic protein in a number of coronaviruses. Whether the N protein in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is antigenic remains to be elucidated. Using Western blot and Enzyme-linked Immunosorbent Assay (ELISA), the recombinant N proteins and the synthesized peptides derived from the N protein were screened in sera from SARS patients. All patient sera in this study displayed strong positive immunoreactivities against the recombinant N proteins, whereas normal sera gave negative immunoresponses to these proteins, indicating that the N protein of SARS-CoV is an antigenic protein. Furthermore, the epitope sites in the N protein were determined by competition experiments, in which the recombinant proteins or the synthesized peptides competed against the SARS-CoV proteins to bind to the antibodies raised in SARS sera. One epitope site located at the C-terminus was confirmed as the most antigenic region in this protein. A detailed screening of peptide with ELISA demonstrated that the amino sequence from Codons 371 to 407 was the epitope site at the C-terminus of the N protein. Understanding of the epitope sites could be very significant for developing an effective diagnostic approach to SARS.
Chronic underfunding in palliative care is key cause of poor care of dying people
Authors: Adrian O’Dowd
Journal: BMJ (2015)

Longstanding underfunding of palliative care training and services is a major cause in the NHS in England of failure to provide good care, MPs have been told.

Experts in palliative care appearing before the parliamentary select committee on public administration and constitutional affairs on 15 September said that doctors received only a tiny amount of formal training in this aspect of care.

The committee was holding a one-off evidence session on the findings of the Office of the Parliamentary and Health Service Ombudsman’s May 2015 report Dying Without Dignity .1 That report said that terminally ill people were enduring painful and upsetting deaths because of failures by the NHS in England to properly …
P223 Validity and interpretation of spirometry for patients in primary care
Authors: KJ Rothnie, H Mullerova, H Goss, J Chandan, JK Quint
Journal: Thorax (2015)

<h3>Background</h3> Previous studies have questioned the validity and interpretation of spirometry undertaken in primary care. Knowing that data are accurate is important as many respiratory diseases are diagnosed and managed in primary care. Additionally researchers use data entered into electronic health records both as single measurements and to track changes in lung function over time. We aimed to determine whether spirometry undertaken in primary care for patients suspected to have COPD was of sufficient quality, and was correctly interpreted. <h3>Methods</h3> As part of previous studies to validate the recording of COPD diagnosis and exacerbations of COPD in the clinical practice research datalink (CPRD) we obtained additional information from GPs which included spirometry traces. In this subset, a respiratory physician assessed spirometry traces for: 1) quality and 2) diagnostic interpretation. We used logistic regression to assess predictors of GPs interpretation of spirometric traces with the outcome of COPD diagnosis confirmed by respiratory physician adjudication of spirometry traces as correct and age, sex and previous record for asthma as covariates. <h3>Results</h3> We obtained spirometry traces for 306 patients, of which 221 (72.2%) were conducted in primary care. 96.5% of traces were of adequate quality such that a valid interpretation could be made. Of those traces which were of adequate quality and conducted in primary care, and in whom a GP diagnosis of COPD had been made (N = 218), 73.4% showed obstruction, suggestive of COPD (Table 1). There was some evidence that correct interpretation of spirometry (either as obstructive, restrictive or normal) was influenced by a previous asthma diagnosis (OR 0.49, 95% CI 0.26–0.93). There was no evidence that correct interpretation was modified by age (OR 0.98, 0.96–1.01) or sex (OR 1.28, 0.69–2.38). <h3>Conclusions</h3> Spirometry is performed in primary care to a high standard. Interpretation in patients with suspected COPD in primary care is moderate. Efforts should be made to improve spirometry interpretation for high quality patient care, and for research. As quality of spirometry measurements were high, researchers could use actual recorded values of FEV<sub>1</sub> and FVC, however should exercise caution with using interpretation of spirometry values documented in primary care records.
P21 upregulation by grape seed extract involves generation of reactive oxygen species and sustained activation of ERK1/2 in HT29 cells
Authors: Manjinder Kaur, Rajesh Agarwal, Chapla Agarwal
Journal: Cancer Research (2008)

3058   Cell cycle progression is a tightly regulated process inside normal cells, which is achieved by concerted action of various cyclins, cyclin-dependent kinases and their inhibitors. Any abnormality in this regulation provides unlimited replicative potential to the cells, which is a basic underlying defect in cancer. Accordingly, the strategies which could put a check on this uncontrolled proliferation, such as targeting expression and function of cell cycle regulatory molecules that favors growth inhibition, are highly desirable. In our completed studies, we found that grape seed extract (GSE) inhibits the growth and induces apoptosis in human colon carcinoma HT29 cells under both  in vitro  and  in vivo  conditions. At molecular level, we found that GSE upregulates the levels of p21/WAF1 in both HT29 cells in culture as well as xenograft in athymic nude mice. Based on these recent findings, here we conducted detailed studies to elucidate the mechanism of p21 upregulation by GSE in HT29 cells. Treatment of cells with GSE (0-100 µg/ml) resulted in a strong dose- and time-dependent phosphorylation of ERK1/2, consistent with p21 induction. For example, time course study revealed that an increase in ERK1/2 phosphorylation following GSE treatment occurs as early as 30min and was sustained till 6h of treatment time. Similarly, the upregulation of p21 levels following GSE treatment of cells was seen as early as 30mins which increased further in a time dependent manner till 6h. Together, these observations suggested a possible link between upregulation of p21 by GSE and a sustained activation of ERK1/2 phosphorylation, which was confirmed by pharmacological inhibitor studies where two different MEK inhibitors, PD98059 and U0126, abrogated GSE-induced p21 upregulation. In other studies assessing the upstream effector of ERK1/2 phosphorylation by GSE, we observed that pretreatment of cells with N-acetylcysteine inhibits ERK1/2 phosphorylation as well as p21 upregulation, suggesting that generation of reactive oxygen species is an upstream event in this signaling cascade. Additional studies, where cells were treated with actinomycin D or cycloheximide along with GSE, showed almost complete decrease in GSE-caused upregulation of p21 protein levels; however, cycloheximide chase experiment revealed that GSE does not alter p21 protein stability. Together, these observations suggest that GSE possibly upregulates p21 at transcriptional and/or translational levels via reactive oxygen species-generated sustained activation of ERK1/2, supporting the fact that this could be an important molecular target based approach for colon cancer prevention and intervention by dietary phytochemicals including grape seed extract.
Transmission among healthcare worker contacts with a Middle East respiratory syndrome patient in a single Korean centre
Authors: T. Kim, J. Jung, S.-M. Kim, D.-W. Seo, Y.S. Lee, W.Y. Kim, K.S. Lim, H. Sung, M.-N. Kim, Y.P. Chong, S.-O. Lee, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-H. Kim
Journal: Clinical Microbiology and Infection (2015)
Streptococcus thermophilus CRISPR-Cas9 Systems Enable Specific Editing of the Human Genome
Authors: Maximilian Müller, Ciaran M Lee, Giedrius Gasiunas, Timothy H Davis, Thomas J Cradick, Virginijus Siksnys, Gang Bao, Toni Cathomen, Claudio Mussolino
Journal: Molecular Therapy (2015)

RNA-guided nucleases (RGNs) based on the type II CRISPR-Cas9 system of Streptococcus pyogenes (Sp) have been widely used for genome editing in experimental models. However, the nontrivial level of off-target activity reported in several human cells may hamper clinical translation. RGN specificity depends on both the guide RNA (gRNA) and the protospacer adjacent motif (PAM) recognized by the Cas9 protein. We hypothesized that more stringent PAM requirements reduce the occurrence of off-target mutagenesis. To test this postulation, we generated RGNs based on two Streptococcus thermophilus (St) Cas9 proteins, which recognize longer PAMs, and performed a side-by-side comparison of the three RGN systems targeted to matching sites in two endogenous human loci, PRKDC and CARD11. Our results demonstrate that in samples with comparable on-target cleavage activities, significantly lower off-target mutagenesis was detected using St-based RGNs as compared to the standard Sp-RGNs. Moreover, similarly to SpCas9, the StCas9 proteins accepted truncated gRNAs, suggesting that the specificities of St-based RGNs can be further improved. In conclusion, our results show that Cas9 proteins with longer or more restrictive PAM requirements provide a safe alternative to SpCas9-based RGNs and hence a valuable option for future human gene therapy applications. RNA-guided nucleases (RGNs) based on the type II CRISPR-Cas9 system of Streptococcus pyogenes (Sp) have been widely used for genome editing in experimental models. However, the nontrivial level of off-target activity reported in several human cells may hamper clinical translation. RGN specificity depends on both the guide RNA (gRNA) and the protospacer adjacent motif (PAM) recognized by the Cas9 protein. We hypothesized that more stringent PAM requirements reduce the occurrence of off-target mutagenesis. To test this postulation, we generated RGNs based on two Streptococcus thermophilus (St) Cas9 proteins, which recognize longer PAMs, and performed a side-by-side comparison of the three RGN systems targeted to matching sites in two endogenous human loci, PRKDC and CARD11. Our results demonstrate that in samples with comparable on-target cleavage activities, significantly lower off-target mutagenesis was detected using St-based RGNs as compared to the standard Sp-RGNs. Moreover, similarly to SpCas9, the StCas9 proteins accepted truncated gRNAs, suggesting that the specificities of St-based RGNs can be further improved. In conclusion, our results show that Cas9 proteins with longer or more restrictive PAM requirements provide a safe alternative to SpCas9-based RGNs and hence a valuable option for future human gene therapy applications.
Heart Rate Variability and Posttraumatic Stress Disorder
Authors: Arpi Minassian, Dewleen G. Baker, Victoria B. Risbrough
Journal: JAMA Psychiatry (2015)

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 Psychiatry 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 Psychiatry journal
Phosphorylation Of The Cytoplasmic Tyrosine Residues Of c-Mpl Is Not Required To Preserve Intact Receptor Dependent Hematopoietic Stem Cell Survival Signaling
Authors: Jacqueline Roy, Angela Epp, Junli Feng, Sandra Ziegler, Radek C. Skoda, Neil C. Josephson
Journal: Blood (2013)
Equipment designed to reduce risk of severe traumatic injuries in alpine ski racing: constructive collaboration between the International Ski Federation, industry and science
Authors: Erich Müller, Jörg Spörri, Josef Kröll, Hubert Hörterer
Journal: British Journal of Sports Medicine (2015)

Developing and implementing effective prevention measures is vital to protect the health of athletes. In 2006, the International Ski Federation (FIS) established the FIS Injury Surveillance System. Following the sequence of injury prevention research suggested by van Mechelen et al ,1 various studies characterised the epidemiology, risk factors and mechanisms of injuries in alpine ski racing.2–5 From 2006 to 2012, the absolute rate that World Cup athletes sustained injuries was 36.2 injuries/100 athletes/season.2 Across all competition disciplines, most injuries are known to occur while turning, either resulting from specific mechanisms while the skier is still skiing or during crashes.3 According to the perception of 61 expert stakeholders of the World Cup ski racing community, one key injury risk factor is the ‘system ski, binding, plate and boot’.4 Experts stated that the ski equipment used at this time was ‘too aggressive at the ski-snow-interaction’, ‘too direct in force transmission’ and ‘hard to get off the edge once the ski is carving’.4 Moreover, ‘speed in general’ was another major …
A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma
Authors: Beata Holkova, Adriana Zingone, Maciej Kmieciak, Prithviraj Bose, Ashraf Z. Badros, Peter M. Voorhees, Rachid Baz, Neha Korde, Hui-Yi Lin, Jin-Qiu Chen, Michelle Herrmann, Liqiang Xi, Mark Raffeld, Xiuhua Zhao, Wen Wan, Mary Beth Tombes, Ellen Shrader, Caryn Weir-Wiggins, Heidi Sankala, Kevin T. Hogan, Austin Doyle, Christina M. Annunziata, Martha Wellons, John D. Roberts, Daniel Sullivan, Ola Landgren, Steven Grant
Journal: Clinical Cancer Research (2015)

AZD6244 is a MEK1/2 inhibitor with significant preclinical activity in multiple myeloma cells. This phase II study used a two-stage Simon design to determine the AZD6244 response rate in patients with relapsed or refractory multiple myeloma.AZD6244 (75 mg) was administered orally, twice a day, continuously for 28-day cycles. Response was evaluated after three cycles.Thirty-six patients received therapy. The median age was 65 years (range: 43-81) and the median number of prior therapies was 5 (range: 2-11). The most common grade 3 and 4 toxicities included anemia, neutropenia, thrombocytopenia, diarrhea, and fatigue. Three deaths occurred possibly related to AZD6244 (2 due to sepsis, 1 due to acute kidney injury). After AZD6244 discontinuation, three additional deaths occurred due to disease progression. The response rate (CR + PR) was 5.6% with a mean duration of response of 4.95 months and median progression-free survival time of 3.52 months. One patient had a very good partial response (VGPR), 1 patient had a partial response, 17 patients had stable disease, 13 patients had progressive disease, and 4 patients could not be assessed for response. Pharmacodynamic studies revealed variable effects on bone marrow CD138(+) cell MEK1/2 and ERK1/2 phosphorylation. The best clinical response, a prolonged VGPR, occurred in a patient with an MMSET translocation.Single-agent AZD6244 was tolerable and had minimal activity in this heavily pretreated population.
Age Threshold for Increased Stroke Risk Among Patients With Atrial Fibrillation
Authors: Tze-Fan Chao, Kang-Ling Wang, Chia-Jen Liu, Yenn-Jiang Lin, Shih-Lin Chang, Li-Wei Lo, Yu-Feng Hu, Ta-Chuan Tuan, Fa-Po Chung, Jo-Nan Liao, Tzeng-Ji Chen, Chern-En Chiang, Gregory Y.H. Lip, Shih-Ann Chen
Journal: Journal of the American College of Cardiology (2015)
Successful treatment of pure endodermal sinus tumors in adult men.
Authors: C D Chong, C J Logothetis, A C von Eschenbach, A G Ayala, M L Samuels
Journal: Journal of Clinical Oncology (1988)

Seven adult men with pure endodermal sinus tumors (EST) were treated with cyclical combination chemotherapy Cytoxan (cyclophosphamide; Bristol-Myers Company, Evansville, IL), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin/vinblastine and bleomycin (CISCAII/VBIV) and surgery at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1978 through 1985. Six tumors were of extragonadal origin (four anterior mediastinum, one pelvic, one prostate), and one was of gonadal origin with retroperitoneal metastasis. All patients presented with advanced local disease and a relative absence of distant metastasis. Alpha-fetoprotein (AFP) levels were elevated in six patients (median, 4,400 ng/mL; range, 2,580 to 31,200 ng/mL). Six patients achieved a complete remission (CR): one with chemotherapy alone, one with initial surgery followed by chemotherapy, and four with chemotherapy followed by consolidative surgery. The remaining patient died of progressive disease. Of the six patients who achieved a CR, five are alive with no evidence of disease (+17, +23, +34, +43, +59 months); one patient developed recurrent disease at 6 months after completion of therapy and is currently undergoing salvage chemotherapy. Of the four patients who underwent postchemotherapy surgery, three were operated on for a marker-negative stable mass; in these patients, no viable tumor was found at pathologic review. The remaining patient underwent surgery for a stable mass with a persistent elevation in AFP levels. He was found to have 95% necrosis with 5% viable tumor and remains disease free without further therapy. The observed changes in AFP levels correlated with regression and progression of tumor; a normal AFP was consistent with a CR, and elevation was consistent with residual tumor. These seven patients demonstrate that when adult men with EST are treated aggressively with combination chemotherapy and surgery, high cure rates can be achieved.
In vitro generation of allo-reactive human NK cells from umblillical cord blood CD34+ progenitor cells
Authors: Yong-Oon Ahn, Ha-Ram Park, Seong-Ho Kang, Jahyang Choi, Tae Min Kim, Dae Seog Heo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Compare to autologous NK cells, allogeneic NK cells have more anti-tumor cytotoxicity without GVHD. Adoptive transfer of allo-reactive NK cell can be ideally used combined with other immunotherapy. However, in vivo persistency of transferred NK cells in the recipients are still an
Histidine‐rich glycoprotein promotes macrophage activation and inflammation in chronic liver disease
Authors: Matthias Bartneck, Viktor Fech, Josef Ehling, Olivier Govaere, Klaudia Theresa Warzecha, Kanishka Hittatiya, Mihael Vucur, Jérémie Gautheron, Tom Luedde, Christian Trautwein, Twan Lammers, Tania Roskams, Willi Jahnen‐Dechent, Frank Tacke
Journal: Hepatology (2015)

Pathogen‐ and injury‐related danger signals as well as cytokines released by immune cells influence the functional differentiation of macrophages in chronic inflammation. Recently, the liver‐derived plasma protein, histidine‐rich glycoprotein (HRG), was demonstrated, in mouse tumor models, to mediate the transition of alternatively activated (M2) to proinflammatory (M1) macrophages, which limit tumor growth and metastasis. We hypothesized that liver‐derived HRG is a critical endogenous modulator of hepatic macrophage functionality and investigated its implications for liver inflammation and fibrosis by comparing C57BL/6N wild‐type (WT) and Hrg−/− mice. In homeostatic conditions, hepatic macrophages were overall reduced and preferentially polarized toward the anti‐inflammatory M2 subtype in Hrg−/− mice. Upon chronic liver damage induced by CCl 4 or methionine‐choline‐deficient (MCD) diet, liver injury and fibrosis were attenuated in Hrg−/− , compared to WT, mice. Macrophage populations were reduced and skewed toward M2 polarization in injured livers of Hrg−/− mice. Moreover, HRG‐deficient mice showed significantly enhanced hepatic vascularization by micro‐computed tomography and histology, corroborating proangiogenic activities of M2‐polarized liver macrophages. Purified HRG protein induced, but HRG‐deficient serum prevented, M1 macrophage differentiation in vitro . Accordingly, Hrg−/− mice transplanted with Hrg+/+ bone marrow, but not Hrg−/− ‐transplanted Hrg+/+ mice, remained protected from experimental steatohepatitis. Consistent with these findings, patients with chronic hepatitis C and nonalcoholic steatohepatitis significantly up‐regulated hepatocytic HRG expression, which was associated with M1 polarization of adjacent macrophages. Conclusions: Liver‐derived HRG, similar to alarmins, appears to be an endogenous molecular factor promoting polarization of hepatic macrophages toward the M1 phenotype, thereby promoting chronic liver injury and fibrosis progression, but limiting angiogenesis. Therefore, controlling tissue levels of HRG or PGF might be a promising strategy in chronic inflammatory liver diseases. (H epatology 2016;63:1310‐1324)
Treatment for Chlamydia Infection — Doxycycline versus Azithromycin
Authors: Thomas C. Quinn, Charlotte A. Gaydos
Journal: New England Journal of Medicine (2015)

Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection in the United States. In 2013, a total of 1.4 million cases were reported, and 3 million persons were estimated to be infected. Worldwide, 131 million persons are estimated to be infected with C. trachomatis. Untreated infections in women can result in pelvic inflammatory disease, infertility, ectopic pregnancy, and chronic pelvic pain. In men, the infection can be associated with urethritis, epididymitis, and, in men who have sex with men, proctitis. The Centers for Disease Control and Prevention (CDC) recommends that all sexually active women younger than 25 . . .