tbuckley/cabot-search huggingface dataset:
Xrcc3 and Nbs1 Are Required for the Production of Extrachromosomal Telomeric Circles in Human Alternative Lengthening of Telomere Cells
Authors: Sarah A. Compton, Jun-Hyuk Choi, Anthony J. Cesare, Sezgin Özgür, Jack D. Griffith
Journal: Cancer Research (2007)

The maintenance of telomere length is essential for the indefinite proliferation of cancer cells. This is most often achieved by the activation of telomerase; however, a substantial number of cancers lack detectable telomerase activity and are classified as using an alternative lengthening of telomeres (ALT) pathway. We showed recently that ALT cells have a high level of extrachromosomal telomeric circles (t circles) that may be a specific marker of the ALT phenotype. The mechanism underlying t circle production and the requirement of t circles in ALT remain unclear. Understanding the specific requirements of ALT is key to developing diagnostic tools and therapies that target this pathway and is critical for the treatment of cancers in which ALT is prevalent, including cancers of neuroepithelial and mesenchymal origin. In this study, we used short hairpin RNAs directed at either Xrcc3 or Nbs1, two proteins involved in the homologous recombination pathway, to determine the role of these proteins in t circle production and the requirement of t circles in maintaining the ALT pathway. We show that Xrcc3 and Nbs1 are indeed required for the production of t circles in human ALT. However, these cells continue to proliferate in the absence of t circles, suggesting that they are not required for the survival of ALT cells.
Locums make up a fifth of doctors in emergency units at weekends
Authors: A. O'Dowd
Journal: BMJ (2013)

A locum company has warned that the NHS will not be able to continue with what it says is a “chronic” shortage of doctors working in hospital emergency departments.

HCL Workforce Solutions, a commercial provider of healthcare professionals to the NHS, said that acute care hospital trusts in England were facing a dangerous combination of factors that were undermining their ability to maintain sufficient emergency services and called for a long term radical review of emergency medical staffing.

In a report the company said that each month its medical locum division, HCL Doctors, received an average of 3200 requests for a locum doctor from NHS emergency departments–the highest number of requests from any specialty and accounting for more than 40% of all requests.1

The report used data from the HCL Doctors division, …
Effect of Cryptococcus neoformans on the immune system of immunocompetent patients
Authors: Jinlin Wang, Yongfeng Luo, Xiaoqun Wei, Yanping Zai, Shiyue Li
Journal: European Respiratory Journal (2012)

On one hand the host immune system regulates the susceptibility and resistance to cryptococcal infection, on the other Cn can also affect T-cell activation and polarization during infection. Cn may potentially interfere with the differentiation of Th1 cells, which may be an escape mechanism of evade host defence and contribute to the cryptococcal infection in immunocompetent paients. However, most of these effects on T-cell biology were only found in cell and animal studies so far. Objectives: to determine the effect of Cn on the immune system of immunocompetent patients. Methods Twenty immunocompetent patients with pulmonary cryptococcal infection were enrolled. Blood plasma concentrations of IFN-γ, IL-4 and IL-12 were measured using Elisa. PBMC were then isolated and incubated with or without IL-12 for 48 hours, followed by the assay of IFN-γ and IL-4 concentration in the supernatant. Results plasma IFN-γ was greatly decreased in the patients when compared to the healthy controls. No significant differences in plasma IL-4 and IL-12 were observed. Although IL-12 treatment can both increase IFN-γ level in PBMC culture supernatant from the two groups, the increment for cryptococcal infection patients was much lower(3.1-fold) compared with that from healthy control(7.4-fold). IL-12 treatment had no observed effect on the IL-4 production of PBMC. Conclusions cryptococcal infection can damage the host immune system, leading to a deficient response to the IL-12 stimulation and an impaired Th1 polarization. This may explain the persistence of Cn in the immunocompetent patients.
Impairment of Natural Killer Cytotoxic Activity and Interferon γ Production in Ccaat/Enhancer Binding Protein γ–Deficient Mice
Authors: Tsuneyasu Kaisho, Hiroko Tsutsui, Takashi Tanaka, Tohru Tsujimura, Kiyoshi Takeda, Taro Kawai, Nobuaki Yoshida, Kenji Nakanishi, Shizuo Akira
Journal: The Journal of Experimental Medicine (1999)

We have investigated in vivo roles of CCAAT/enhancer binding protein γ (C/EBPγ) by gene targeting. C/EBPγ-deficient (C/EBPγ2/−) mice showed a high mortality rate within 48 h after birth. To analyze the roles of C/EBPγ in lymphoid lineage cells, bone marrow chimeras were established. C/EBPγ2/− chimeras showed normal T and B cell development. However, cytolytic functions of their splenic natural killer (NK) cells after stimulation with cytokines such as interleukin (IL)-12, IL-18, and IL-2 were significantly reduced as compared with those of control chimera NK cells. In addition, the ability of C/EBPγ−/− chimera splenocytes to produce interferon (IFN)-γ in response to IL-12 and/or IL-18 was markedly impaired. NK cells could be generated in vitro with normal surface marker expression in the presence of IL-15 from C/EBPγ2/− newborn spleen cells. However, they also showed lower cytotoxic activity and IFN-γ production when stimulated with IL-12 plus IL-18 than control NK cells, as observed in C/EBPγ2/− chimera splenocytes. In conclusion, our study reveals that C/EBPγ is a critical transcription factor involved in the functional maturation of NK cells.
Surgeons Leading Health Care Reform
Authors: James F. Burdick
Journal: JAMA Surgery (2013)

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 Surgery 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 Surgery journal
Neoral conversion from Sandimmune in maintenance renal transplant patients
Authors: J J Curtis, M Lynn, P A Jones
Journal: Journal of the American Society of Nephrology (1998)

When converting maintenance renal allograft recipients from Sandimmune (cyclosporin A [CsA]) to Neoral (CsA-microemulsion [CsA-ME]), a dose conversion ratio of 1:1 may not be optimal, in part because of the variability in absorption of the CsA formulation of cyclosporine. After conversion using a 1:1 dose ratio, an individualized approach to the management of dosing was applied. In this article, close monitoring, which began at the time of conversion, and rapid response to potentially meaningful changes in cyclosporine trough levels early in the postconversion course were used to maintain patients' cyclosporine troughs at preconversion levels. The results of cyclosporine dose changes after converting stable, maintenance renal transplant patients from CsA (once daily and twice daily) to CsA-ME (twice daily) during 52 wk of follow-up are reported. Most patients (87.2%) required CsA-ME dose reduction to maintain preconversion trough levels, and 64% of the patients attained their CsA-ME maintenance dose by study week 4. Logistic regression analysis identified one significant predictor concerning the week 52 CsA-ME dose: patients converted from CsA doses > or = 4.0 mg/kg per d were more likely to require dose reduction (P < 0.0001). Although firm guidelines for dose modification after conversion from CsA to CsA-ME cannot be provided because of the individual nature of cyclosporine absorption, an individualized approach to patient management is recommended. Patients with higher CsA doses before conversion are particularly likely to require dose reduction early in the postconversion course. With CsA-ME, good absorbers of cyclosporine remain good absorbers, or become better absorbers, whereas poor absorbers become good absorbers.
Prolonged clinical remission in patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type treated with cladribine: 6 year follow-up of a phase II trial
Authors: G. Jäger, P. Neumeister, F. Quehenberger, S. Wöhrer, W. Linkesch, M. Raderer
Journal: Annals of Oncology (2006)
Diagnostic tests of hyperventilation syndrome
Authors: J Vansteenkiste, F Rochette, M Demedts
Journal: European Respiratory Journal (1991)

In 90 patients referred to the pulmonary function laboratory for evaluation of hyperventilation syndrome (HVS) and in whom somatic causes of the complaints had been excluded, we investigated the degree of concordance between three widely applied diagnostic methods: 1) the standardized Nijmegen questionnaire on major daily complaints; 2) the reproduction of the same symptoms during the hyperventilation provocation test (HVPT); and 3) the responses of end-tidal CO2 fraction (FETCO2) during the HVPT. In 86% of the patients a concordance was found between Nijmegen questionnaire (i.e. score of 24/64 or more) and symptom reproduction during HVPT (i.e. recognition of at least 2 major daily complaints). Based on these combined data we made a definite diagnosis of HVS in 37 patients, of non-HVS in 40 patients, and we retained only a possible HVS in 13 patients. Each of the 16 complaints in the questionnaire contributed significantly to the distinction between HVS and non-HVS patients, and a striking similarity in rank order of daily complaints and reproduced symptoms was found. The responses in FETCO, during HVPT had little additional diagnostic value. A spontaneous fall of at least 0.25% FETCO2 during the 5 min adaptation period before the HVPT, was most reliably correlated with the aforementioned diagnostic criteria of HVS: specificity 83%, sensitivity 57%, and accuracy 70%. Neither the 3 min FETCO2 ratio nor the 5 min FETCO2 ratio during recovery after the HVPT showed a good correlation with the other diagnostic criteria. The response of FETCO2 during HVPT did especially not provide additional useful diagnostic information in the 13 patients with only possible HVS.
CAM and EBM: arguments for convergence
Authors: N. Koutouvidis
Journal: Journal of the Royal Society of Medicine (2003)

The expansion of complementary and alternative medicine (CAM) during the past two decades has generated many articles in medical journals; and, whether the authors are for or against CAM, the emphasis has been on its distinction from evidence-based medicine (EBM). In this paper I look instead at points of convergence that might open the way to future coordination, collaboration and integration. For our purposes, the most suitable definition of integration is ‘the combination of previously racially segregated social facilities into a nonsegregated system’ (Collin’s English Dictionary). In the past, scholars and investigators polarized the debate by disparaging references to the other side. For instance, CAM was portrayed as userfriendly, holistic, mild, simple and liberal,1 EBM as technological, aggressive, and paternalistic;2 or, in the other direction CAM was dismissed as a form of magic3 while EBM reigned supreme through its foundation in experiment and reason.4 Voices towards mutual understanding have not been absent, but the conventional physician usually wishes the complementary practitioner to perform his art in the manner of a conventional physician, and vice versa. There are philosophical differences. EBM is mainly based on modernist assumptions, while CAM is chiefly akin to postmodern reasoning.5 EBM gets its scientific rigour from positivism, empiricism and experiment. CAM gains its appeal by addressing the patient’s spirituality and social sensitivity, the mind–body relationship and the role of nature in healing, and by an absence of authoritarianism.6,7 Even when subscribing to the biopsychosocial paradigm, medicine has undeniably lost some of its Hippocratic holism; but CAM advocates face an equally cogent complaint—how are people to be protected against quackery?8 The dialogue can be focused on two major areas—the relation between modernism and postmodernism; and the notion of spirituality and the mind–body relationship. Modernism and postmodernism
Exploring the conceptual and semantic structure of human kinship: An experimental investigation of Chinese kin terms
Authors: Chao Liu, Yue Ge, Xiaoqin Mai, Yue-Jia Luo
Journal: Behavioral and Brain Sciences (2010)

Abstract We designed an experiment to test the application of optimality theory (OT) in kinship terminology studies. Specifically, we examined the OT constraints within a set of behavioral data using Chinese kin terms. The results from this behavioral approach support and extend Jones' linguistic approach by identifying underlying cognitive mechanisms that can explain and predict behavioral responses in kinship identification.
A prospective study of renal disease in patients with early rheumatoid arthritis
Authors: Y Koseki
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVES</h3> This prospective study was designed to clarify the frequency, causes, and clinical course of renal disease in patients with early rheumatoid arthritis (RA). <h3>METHODS</h3> 235 patients (185 women, mean age 49.4 years) with early RA of less than one year9s duration were enrolled and assessed monthly. Proteinuria was defined as a positive dipstick result and microscopic haematuria was defined as the presence of ⩾5 red blood cells per high power field. Urinary abnormalities lasting three months or longer were defined as persistent abnormalities. <h3>RESULTS</h3> At entry, 40 patients exhibited haematuria, two had a raised serum creatinine concentration, and none had proteinuria. During the observation period (average 42 months), persistent haematuria was found in 43, persistent proteinuria in 17, and a raised serum creatinine concentration in 14 patients. Persistent proteinuria was caused by drugs in 14 of 17 patients and disappeared in most cases. Risk factors for drug induced proteinuria included a raised C reactive protein and erythrocyte sedimentation rate and age over 50 at entry. Drugs resulted in a raised serum creatinine concentration in eight of 14 patients. The incidence of haematuria at entry did not differ among patients who had been treated with non-steroidal anti-inflammatory drugs, disease modifying antirheumatic drugs, or no drugs. In some patients with isolated haematuria, the haematuria appeared when the activity of RA was high and resolved when it was low. <h3>CONCLUSIONS</h3> This study suggests that a raised serum creatinine concentration or persistent proteinuria in patients with early RA is predominantly drug related whereas, in contrast, isolated haematuria is more directly associated with the activity of the disease process.
Short-term change in self-reported COPD symptoms after smoking cessation in an internet sample
Authors: J-F. Etter
Journal: European Respiratory Journal (2009)

Smoking is the first risk factor for chronic obstructive pulmonary disease (COPD). Some recent reports suggest that, unexpectedly, some respiratory symptoms may increase transiently after smoking cessation, but there is a dearth of short-term data to test this hypothesis. The aim of the present study was to assess the validity of an online screening tool and to describe short-term associations between smoking behaviour and self-reported respiratory symptoms, in cross-sectional and longitudinal data. An internet survey was conducted in 2003–2009, on a smoking cessation website, with a follow-up survey after 30 days. There were 15,916 participants at baseline and 1,831 at follow-up. In the 252 baseline smokers who had quit smoking at 30-day follow-up, there was a substantial decrease in the proportion of participants who declared that they often coughed even without a cold (from 51.6% at baseline to 15.5% at follow-up), expectorated when they coughed in the morning (from 47.6% to 19.4%), were out of breath after climbing stairs or after a quick walk (from 75.0% to 48.4%), and who had a wheezing respiration (from 33.7% to 10.3%) (p&lt;0.001 for all before/after comparisons). In participants who did not change their smoking behaviour between assessments, the test–retest reliability was r = 0.87 for a score summing these four symptoms. Smoking cessation was followed by a rapid and substantial improvement in self-reported respiratory symptoms. COPD is largely underdiagnosed and undertreated. Internet screening is reliable and may allow for the early detection of COPD symptoms at a large scale, in patients who may otherwise have no access to COPD case-finding efforts.
Significant Association of Oncogene YAP1 with Poor Prognosis and Cetuximab Resistance in Colorectal Cancer Patients
Authors: Keun-Wook Lee, Sung Sook Lee, Sang-Bae Kim, Bo Hwa Sohn, Hyun-Sung Lee, Hee-Jin Jang, Yun-Yong Park, Scott Kopetz, Sung Soo Kim, Sang Cheul Oh, Ju-Seog Lee
Journal: Clinical Cancer Research (2014)

Activation of YAP1, a novel oncogene in the Hippo pathway, has been observed in many cancers, including colorectal cancer. We investigated whether activation of YAP1 is significantly associated with prognosis or treatment outcomes in colorectal cancer.A gene expression signature reflecting YAP1 activation was identified in colorectal cancer cells, and patients with colorectal cancer were stratified into two groups according to this signature: activated YAP1 colorectal cancer (AYCC) or inactivated YAP1 colorectal cancer (IYCC). Stratified patients in five test cohorts were evaluated to determine the effect of the signature on colorectal cancer prognosis and response to cetuximab treatment.The activated YAP1 signature was associated with poor prognosis for colorectal cancer in four independent patient cohorts with stage I-III disease (total n = 1,028). In a multivariate analysis, the impact of the YAP1 signature on disease-free survival was independent of other clinical variables [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.25-2.13; P < 0.001]. In patients with stage IV colorectal cancer and wild-type KRAS, IYCC patients had a better disease control rate and progression-free survival (PFS) after cetuximab monotherapy than did AYCC patients; however, in patients with KRAS mutations, PFS duration after cetuximab monotherapy was not different between IYCC and AYCC patients. In multivariate analysis, the effect of YAP1 activation on PFS was independent of KRAS mutation status and other clinical variables (HR, 1.82; 95% CI, 1.05-3.16; P = 0.03).Activation of YAP1 is highly associated with poor prognosis for colorectal cancer and may be useful in identifying patients with metastatic colorectal cancer resistant to cetuximab.
Patient Information and Decision Aids in Oncology: Need for Communication Between Patients and Physicians
Authors: Dirk Vordermark
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: In their recent contribution to Journal of Clinical Oncology, Brace et al report on the knowledge and opinions of physicians caring for patients with cancer in the province of Ontario, Canada, about patient decision aids. Decision aids have been defined as “interventions designed to help people make specific and deliberative choices among options by providing information about the options and outcomes that is relevant to a person s health status.” Such tools play a role in assisting patients in making informed decisions about specific treatment options (eg, surgery v radiotherapy v watchful waiting in early-stage prostate cancer) and also in opting for or against cancer screening procedures. In their questionnaire survey, Brace et al found that, of 477 responders, 69% were aware of patient decision aids and 24% (40% of responding medical oncologists) actually used decision aids in their practices. Brace et al must be congratulated for collecting this comprehensive data set on the oncologists’ perspective on this important topic. However, it is possible that the rates of decision aid use by patients may actually be higher than suggested by the percentages for physicians responding to the questionnaire. Access to diseasespecific patient decision aids is provided freely on the Internet, and patients may make use of these tools without discussing them with their treating oncologists. We have been interested in patterns of patient information (eg, the importance of specific media or the rate of Internet use to obtain such information) in radiation oncology. In two independent crosssectional surveys of patients undergoing radiotherapy at university radiation oncology departments in Germany in the years 2000 and 2008, we found rates of 21% and 41%, respectively, of patients with cancer who had obtained information about the disease or its treatment via the Internet. Importantly, of those who received information via the Internet, only 24% (2000 study) and 39% (2008 study) stated that they had discussed the information with their treating physicians. Applying these findings to the physician data on decision aids, which may be limited by different settings and cultural backgrounds, one could speculate that the actual use of decision aids by patients with cancer may be much higher than reflected by the data of Brace et al. A previous meta-analysis of randomized controlled trials of the effects of cancer-related decision aids suggested that the knowledge of patients with cancer is increased, whereas their anxiety is not—an effect that was most clearly shown for screening decisions. Improving communication between patients and oncologists about information, including decisions aids, obtained via the Internet should serve two purposes: to provide patients with access to objective additional information that is helpful in the decision-making process and to integrate this knowledge into the patient-physician interaction.