tbuckley/cabot-search huggingface dataset:
Abstract 65: Therapeutically increasing MHC-I expression potentiates immune checkpoint blockade
Authors: Shengqing Gu, Wubing Zhang, Xiaoqing Wang, Peng Jiang, Nicole Traugh, Ziyi Li, Clifford Meyer, Blair Stewig, Yingtian Xie, Xia Bu, Michael Manos, Alba Font-Tello, Evisa Gjini, Ana Lako, Klothilda Lim, Jake Conway, Alok Tewari, Zexian Zeng, Avinash Das Sahu, Collin Tokheim, Jason L. Weirather, Jingxin Fu, Yi Zhang, Benjamin Kroger, Jin Hua Liang, Paloma Cejas, Gordon J. Freeman, Scott J. Rodig, Henry Long, Benjamin E. Gewurz, F. Stephen Hodi, Myles Brown, X. Shirley Liu
Journal: Cancer Research (2021)

We have previously shown that non-cytotoxic concentrations (600-1200 U/ml) of recombinant mouse tumour necrosis factor-alpha (TNF-alpha) can induce differentiation of a subclone (JCS) of the WEHI-3B myelomonocytic leukaemia cell line into mature cells with the characteristics of macrophages. In the present study, the effects of recombinant mouse interleukin-4 (IL-4), either alone or in combination with mouse TNF-alpha, on the growth and differentiation of JCS cells were examined. IL-4 alone (20-5000 U/ml) inhibited the growth of JCS cells in a dose-dependent manner but did not induce cell differentiation. However, combinations of IL-4 and TNF-alpha acted in synergy to inhibit cell proliferation and induce monocytic differentiation of JCS cells, as shown by increased expression of the macrophage differentiation antigens (F4/80, Mac-1), stimulation of phagocytic activity, induction of non-specific esterase and NBT-reducing activities, increased plastic adherence and morphological criteria. Similar synergistic interactions were also shown by human TNF-alpha and mouse IL-4, indicating that TNF-alpha might exert its effects through the low-affinity (p55) TNF receptors. Moreover, the clonogenicity of JCS cells in vitro and their tumorigenicity in vivo were significantly reduced by combined TNF-alpha and IL-4 treatment. Our results indicate that TNF-alpha can act as a differential signal for JCS cells and that its effects are modulated by IL-4. Therefore, the combination of TNF-alpha and IL-4 may be useful in the treatment of some forms of myelomonocytic leukaemia.
Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies
Authors: Bjorn Bakker, Aaron Taudt, Mirjam E. Belderbos, David Porubsky, Diana C. J. Spierings, Tristan V. de Jong, Nancy Halsema, Hinke G. Kazemier, Karina Hoekstra-Wakker, Allan Bradley, Eveline S. J. M. de Bont, Anke van den Berg, Victor Guryev, Peter M. Lansdorp, Maria Colomé-Tatché, Floris Foijer
Journal: Genome biology (2016)

Chromosome instability leads to aneuploidy, a state in which cells have abnormal numbers of chromosomes, and is found in two out of three cancers. In a chromosomal instable p53 deficient mouse model with accelerated lymphomagenesis, we previously observed whole chromosome copy number changes affecting all lymphoma cells. This suggests that chromosome instability is somehow suppressed in the aneuploid lymphomas or that selection for frequently lost/gained chromosomes out-competes the CIN-imposed mis-segregation. To distinguish between these explanations and to examine karyotype dynamics in chromosome instable lymphoma, we use a newly developed single-cell whole genome sequencing (scWGS) platform that provides a complete and unbiased overview of copy number variations (CNV) in individual cells. To analyse these scWGS data, we develop AneuFinder, which allows annotation of copy number changes in a fully automated fashion and quantification of CNV heterogeneity between cells. Single-cell sequencing and AneuFinder analysis reveals high levels of copy number heterogeneity in chromosome instability-driven murine T-cell lymphoma samples, indicating ongoing chromosome instability. Application of this technology to human B cell leukaemias reveals different levels of karyotype heterogeneity in these cancers. Our data show that even though aneuploid tumours select for particular and recurring chromosome combinations, single-cell analysis using AneuFinder reveals copy number heterogeneity. This suggests ongoing chromosome instability that other platforms fail to detect. As chromosome instability might drive tumour evolution, karyotype analysis using single-cell sequencing technology could become an essential tool for cancer treatment stratification.
Case 26-1976
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Robert R. Young, Edward P. Richardson, Stanley J. Robboy
Journal: New England Journal of Medicine (1976)

Presentation of CaseA 64-year-old woman was admitted to the hospital because of inability to walk.She was well until three weeks previously, when she experienced a "pulling" sensation in the right groin that persisted and was accompanied by urinary frequency and dysuria for several days. One week before admission pain developed in the right calf and increased in severity. During the week before entry she had no bowel movements. Four days before entry she began to have "tightness" around the entire chest, and two days later the right leg felt "heavy." On the following day weakness of both legs . . .
Changes in Deoxyribonucleic Acid Content of Rat Liver Cells During Ethionine Intoxication&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: J. Heinrich Holzner, Tibor Barka, Hans Popper
Journal: JNCI Journal of the National Cancer Institute (1959)

Changes in the deoxyribonucleic acid content of individual liver-cell nuclei were followed, during chronic ethionine intoxication, by Feulgen microspectrophotometry and the two-wavelength method. During ethionine intoxication, while substantially all liver cells are either diploid or tetraploid, the ratio of their numbers changes from 0.2 diploid cells per tetraploid cell in the normal animal to 2.6 diploid cells per tetraploid cell after 9 weeks' intoxication. The extensively proliferating interstitial (ductular) cells belong almost completely to the diploid category. The possible explanations of these changes are discussed.
Cardiovascular screening to reduce the burden from cardiovascular disease: microsimulation study to quantify policy options
Authors: Chris Kypridemos, Kirk Allen, Graeme L Hickey, Maria Guzman-Castillo, Piotr Bandosz, Iain Buchan, Simon Capewell, Martin O’Flaherty
Journal: BMJ (2016)

To estimate the potential impact of universal screening for primary prevention of cardiovascular disease (National Health Service Health Checks) on disease burden and socioeconomic inequalities in health in England, and to compare universal screening with alternative feasible strategies. Microsimulation study of a close-to-reality synthetic population. Five scenarios were considered: baseline scenario, assuming that current trends in risk factors will continue in the future; universal screening; screening concentrated only in the most deprived areas; structural population-wide intervention; and combination of population-wide intervention and concentrated screening. Synthetic population with similar characteristics to the community dwelling population of England. Synthetic people with traits informed by the health survey for England. Cardiovascular disease cases and deaths prevented or postponed by 2030, stratified by fifths of socioeconomic status using the index of multiple deprivation. Compared with the baseline scenario, universal screening may prevent or postpone approximately 19 000 cases (interquartile range 11 000-28 000) and 3000 deaths (-1000-6000); concentrated screening 17 000 cases (9000-26 000) and 2000 deaths (-1000-5000); population-wide intervention 67 000 cases (57 000-77 000) and 8000 deaths (4000-11 000); and the combination of the population-wide intervention and concentrated screening 82 000 cases (73 000-93 000) and 9000 deaths (6000-13 000). The most equitable strategy would be the combination of the population-wide intervention and concentrated screening, followed by concentrated screening alone and the population-wide intervention. Universal screening had the least apparent impact on socioeconomic inequalities in health. When primary prevention strategies for reducing cardiovascular disease burden and inequalities are compared, universal screening seems less effective than alternative strategies, which incorporate population-wide approaches. Further research is needed to identify the best mix of population-wide and risk targeted CVD strategies to maximise cost effectiveness and minimise inequalities.
Neuroloeptic effect on desipramine steady-state plasma concentratins
Authors: J C Nelson, P I Jatlow
Journal: American Journal of Psychiatry (1980)

The authors examined the effect of neuroleptic drugs on desipramine steady-state plasma concentration in 30 patients who received similar milligram per kilogram doses of desipramine. Fifteen of these patients also received a neuroloeptic drug and had desipramine plasma levels twice that of the 15 patients who received dispiramine alone. The authros discuss the implications of the magnitude of this difference for therapeutic response and incidence of side effects.
Circulating Metabolites and Survival Among Patients With Pancreatic Cancer
Authors: Chen Yuan, Clary B Clish, Chen Wu, Jared R Mayers, Peter Kraft, Mary K Townsend, Mingfeng Zhang, Shelley S Tworoger, Ying Bao, Zhi Rong Qian, Douglas A Rubinson, Kimmie Ng, Edward L Giovannucci, Shuji Ogino, Meir J Stampfer, John Michael Gaziano, Jing Ma, Howard D Sesso, Garnet L Anderson, Barbara B Cochrane, JoAnn E Manson, Margaret E Torrence, Alec C Kimmelman, Laufey T Amundadottir, Matthew G Vander Heiden, Charles S Fuchs, Brian M Wolpin
Journal: JNCI Journal of the National Cancer Institute (2016)

Background:Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown.
PWE-270 Are urgent suspected colorectal cancer referrals appropriate? an analysis of 772 two week wait referrals
Authors: A Lord, P Thomas, J Winter, N Beck
Journal: Gut (2015)

<h3>Introduction</h3> Following the introduction of a fast track cancer pathway for patients with suspected colorectal cancer (i.e. two week wait clinics) there has been a high demand for this service. Anecdotal experience is that many patients are inappropriately directed to this clinic without meeting NICE criteria. This study aimed to assess appropriateness of GP referrals to a nurse led two week wait colorectal clinic. <h3>Method</h3> A database of all consecutive patients referred to our fast track nurse led clinic was prospectively maintained. Records of all patients referred between September 2012 and January 2014 were obtained and examined retrospectively. Referral forms and letters were inspected to assess whether appropriate information was included and whether the referral criteria were met and diagnoses and outcomes were reviewed. <h3>Results</h3> A total of 772 patients were included in the study. 46.4% of patients were male. The average age was 67, with a range of 22–91. 66.6% of referrals were deemed to be appropriate. Inappropriate referrals were broken down into clinically inappropriate (22.5% of all referrals) or incomplete referrals (10.9%). Incomplete referrals usually involved completely blank referral forms being sent or a failure to provide any clinical details. The most common reasons referrals were judged to be clinically inappropriate were because symptom duration was under 6 weeks (8.4% of all referrals), the patient was under the age specified by NICE guidelines (7.5%) or the change in bowel habit was constipation rather than looser or more frequent stools (3.2%). During the study period, 57 cancers were identified (7.4% of referrals). 46 of these were colorectal cancers and 11 were tumours at other sites detected on cross sectional imaging. 168 patients had polyps, 73 had inflammatory bowel disease, 112 had other benign pathology (e.g. haemorrhoids, diverticulosis) and 307 had normal investigations. There was a 3.9% cancer detection rate in inappropriate referrals compared to 9.1% in appropriate referrals. All of the non-colorectal cancers were detected in the ‘appropriate’ group. <h3>Conclusion</h3> Whilst the majority of referrals to the fast track clinic were appropriate, almost a quarter did not meet NICE criteria and a significant number were sent without appropriate clinical information. This is consistent with other published data. This study demonstrates a higher cancer detection rate in patients that do meet NICE criteria. This has significant consequences for service provision and resources. Given the clarity of NICE criteria on referral forms, it may be that a perception of long waits for ‘routine’ clinics or pressure from patients to be seen quickly plays a role. Engagement with GPs to discuss their experience of clinic access and referral pathways may improve compliance. <h3>Disclosure of interest</h3> None Declared.
Insanity acquittals in New York State, 1965--1978
Authors: H J Steadman
Journal: American Journal of Psychiatry (1980)

The author presents data on the use of the insanity defense to provide a basis for current debates on its revision. Generally, the experience in New York State in 1976--1978 reflects an increasing number of insanity acquittals over 1965--1976, but the characteristics and length of hospitalization of the defendants remained fairly similar. In addition, in some counties the defense was used often, but in others it was not used at all. The author suggests that similar, more sophisticated analyses of the actual operation of the insanity defense be carried out to establish an adequate basis for designing rational social policy.
AB0916 A Survey of Gout Treatment by Brazilian Rheumatologists Evaluated According to the 2012 ACR Guidelines: Table 1.
Authors: A.B. Vargas-Santos, G.D.R. Castelar-Pinheiro, E.S.F. Coutinho, R.B.C. Amorim, N. Schlesinger
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The first ACR guidelines for gout treatment published in 2012<sup>1,2</sup>. <h3>Objectives</h3> To record and analyze gout treatment by rheumatologists in Brazil, according to the 2012 guidelines. <h3>Methods</h3> Our study population were practicing rheumatologists (n=1436) registered in the Brazilian Society of Rheumatology (BSR). The sample size was calculated using PEPI as 304, aiming at a sample error of 5% and an expected proportion of 50% of concordance. Foreseeing a possible failure to contact 30% of the sample, 395 members were randomly selected using "True Random Number Generator" and e-mailed questionnaires. Proportions and their 95% confidence intervals (95% CI) were estimated for nominal variables. Means and standard deviations were calculated for continuous variables. Stata software v12.0 was used for statistical analysis. <h3>Results</h3> 309 rheumatologists replied (78.2%), 58% females; mean age 46 years old (±12); 87% board certified by the BSR. Mean years of practice: 17 years; 53% were solely in private practice; 45% in combined private practice and academia. The first set of questions was regarding treatment of acute gout based on 8 different scenarios thought to impact care including: mono <i>vs.</i> polyarticular involvement, duration of attack (&lt;36h <i>vs.</i> &gt;36h) and creatinine clearance (CrCl) ≥60 <i>vs.</i> &lt;60 ml/min. A combination of an NSAID plus colchicine was the preferred treatment in an otherwise healthy patient, while the combination of a corticosteroid with colchicine was the preferred treatment in patients with CKD. In contrary to ACR guidelines, use of high dose colchicine and initiating colchicine &gt;36h after the onset of the attack were selected, &gt; once, by 10% (95% CI, 6.7 – 13.4) and 20.1% (95% CI, 15.6 – 24.6) of rheumatologists respectively. The main results of the second set of questions are shown in table 1. <h3>Conclusions</h3> In this large survey study of Brazilian rheumatologists, we found great compliance with the 2012 ACR gout guidelines; however, there are knowledge gaps to be filled in some areas including: acute gout treatment, duration of prophylaxis, allopurinol treatment and target SUA level achievement. Based on these data, we are developing a physician practice improvement program aimed at advancing gout education and thus the quality of care in gout patients in Brazil. <h3>References</h3> Khanna D et al. Arthritis Care Res 2012; 64:1431-46. Khanna D et al. Arthritis Care Res 2012; 64:1447-61. <h3>Disclosure of Interest</h3> None declared
Prolonged dual antiplatelet therapy in stable coronary disease: comparative observational study of benefits and harms in unselected versus trial populations
Authors: A Timmis, E Rapsomaniki, S C Chung, M Pujades-Rodriguez, A Moayyeri, D Stogiannis, A D Shah, L Pasea, S Denaxas, C Emmas, H Hemingway
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To estimate the potential magnitude in unselected patients of the benefits and harms of prolonged dual antiplatelet therapy after acute myocardial infarction seen in selected patients with high risk characteristics in trials. <b>Design</b>&nbsp;Observational population based cohort study. <b>Setting</b>&nbsp;PEGASUS-TIMI-54 trial population and CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records). <b>Participants</b>&nbsp;7238 patients who survived a year or more after acute myocardial infarction. <b>Interventions</b>&nbsp;Prolonged dual antiplatelet therapy after acute myocardial infarction. <b>Main outcome measures</b>&nbsp;Recurrent acute myocardial infarction, stroke, or fatal cardiovascular disease. Fatal, severe, or intracranial bleeding. <b>Results</b>&nbsp;1676/7238 (23.1%) patients met trial inclusion and exclusion criteria ("target" population). Compared with the placebo arm in the trial population, in the target population the median age was 12 years higher, there were more women (48.6% <i>v</i> 24.3%), and there was a substantially higher cumulative three year risk of both the primary (benefit) trial endpoint of recurrent acute myocardial infarction, stroke, or fatal cardiovascular disease (18.8% (95% confidence interval 16.3% to 21.8%) <i>v</i> 9.04%) and the primary (harm) endpoint of fatal, severe, or intracranial bleeding (3.0% (2.0% to 4.4%) <i>v</i> 1.26% (TIMI major bleeding)). Application of intention to treat relative risks from the trial (ticagrelor 60 mg daily arm) to CALIBER's target population showed an estimated 101 (95% confidence interval 87 to 117) ischaemic events prevented per 10 000 treated per year and an estimated 75 (50 to 110) excess fatal, severe, or intracranial bleeds caused per 10 000 patients treated per year. Generalisation from CALIBER's target subgroup to all 7238 real world patients who were stable at least one year after acute myocardial infarction showed similar three year risks of ischaemic events (17.2%, 16.0% to 18.5%), with an estimated 92 (86 to 99) events prevented per 10 000 patients treated per year, and similar three year risks of bleeding events (2.3%, 1.8% to 2.9%), with an estimated 58 (45 to 73) events caused per 10 000 patients treated per year. <b>Conclusions</b>&nbsp;This novel use of primary-secondary care linked electronic health records allows characterisation of "healthy trial participant" effects and confirms the potential absolute benefits and harms of dual antiplatelet therapy in representative patients a year or more after acute myocardial infarction.
Case 21-1962
Authors: Hans Popper
Journal: New England Journal of Medicine (1962)

Presentation of CaseA thirty-three-year-old housewife entered the hospital because of pruritus.One year previously she began to experience generalized itching that was unassociated with skin lesions or with any known environmental or emotional factors. The pruritus was generalized from the onset and initially was intermittent, with complete remissions for as long as three weeks. Subsequently, it became constant, was more severe at night, often interfering with sleep, and was aggravated by warmth or by contact with clothing. Thickening and pigmentation of the skin appeared and was attributed by the patient to incessant scratching. Several red patches appeared in the . . .
Epilepsy in pregnancy
Authors: Michael Owen Kinney, James Morrow
Journal: BMJ (2016)

#### What you need to know

In every 1000 pregnancies, between two and five infants are born to women with epilepsy.1 2 3 For such women, pregnancy can be a time of anxiety over maternal and fetal wellbeing.4 5

Most women with epilepsy will not experience an increase in seizure frequency, and in 96% of pregnancies they will deliver a healthy child.6 However, some women (between 14 and 32 per 100) will experience an increase in seizure frequency,7 which can be harmful for the mother or fetus. There are no randomised controlled trials (RCTs) in women with epilepsy regarding antiepileptic drugs. Evidence comes from observational study and registry data and suggests some antiepileptic drugs are associated with an increased risk of congenital and neurodevelopmental abnormalities.8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Some antiepileptic drugs considered safe to the fetus may be associated with increased risk of seizures and maternal mortality.24 25 This review summarises the current evidence regarding women with epilepsy who are pregnant or planning pregnancy.

#### Sources and selection criteria

We performed an electronic search of PubMed for relevant English language publications over the past 10 years. The search terms “pregnancy” and “preconceptual” were individually combined with “epilepsy” as search terms. All abstracts were reviewed …
Refractory Hypotension and “Ventricular Fibrillation” With Large U Waves After Overdose
Authors: Jon B. Cole, Samuel J. Stellpflug, Stephen W. Smith
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Azoxymethane-Induced Liver Hemangiosarcomas in Inbred Strain-2 Guinea Pigs 2
Authors: Tomio Narisawa, Ching-Quo Wong, John H. Weisburger
Journal: JNCI Journal of the National Cancer Institute (1976)

Intrarectal administration of 0.5 ml of a 0.2% solution of azoxymethane twice weekly for 33 weeks to female inbred strain-2 guinea pigs specifically induced multiple liver hemangiosarcomas in 15 of 16 animals 32-54 weeks after the first treatment. No neoplasms and preneoplastic changes were found in the large intestine.
Diagnostic value of computed tomography colonography (CTC) after incomplete optical colonoscopy
Authors: N. Maggialetti, R. Capasso, D. Pinto, M. Carbone, A. Laporta, S. Schipani, C.L. Piccolo, M. Zappia, A. Reginelli, M. D'Innocenzo, L. Brunese
Journal: International Journal of Surgery (2016)