tbuckley/cabot-search huggingface dataset:
Bone Marrow-derived Cells Contribute to Pathogenesis of Pulmonary Arterial Hypertension.
Authors: Yan L, Chen X, Talati M, Nunley Bw, Gladson S, Blackwell T, Cogan J, Austin E, Wheeler F, Loyd J, West J, Hamid R
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Abstract Pulmonary arterial hypertension (PAH) is a progressive lung disease of the pulmonary microvasculature. Recent studies suggest that bone marrow (BM)-derived circulating cells may play an important role in its pathogenesis. We used a genetic model of PAH, the Bmpr2 mutant mouse, to study the role of bone marrow-derived circulating cells in its pathogenesis. Recipient mice, either Bmpr2R899X mutant or controls, were lethally irradiated and transplanted with either control or Bmpr2R899X BM cells. Donor cells were traced in female recipient mice by Y chromosome painting. Molecular and function insights were provided by expression and cytokine arrays combined with flow cytometry, colony forming and competitive transplant assays. We found that mutant BM cells caused pulmonary arterial hypertension with remodeling and inflammation when transplanted into control mice, while control BM cells had a protective effect against the development of disease, when transplanted into mutant mice. Donor BM derived cells were present in the lungs of recipient mice. Functional and molecular analysis identified mutant BM cells dysfunction suggestive of a PAH phenotype soon after activation of the transgene and long before the development of lung pathology. Our data show that BM cells played key role in PAH pathogenesis and given that the transplanted BM cells were able to drive the lung phenotype. Furthermore the specific cell types involved were derived from HSCs and exhibit dysfunction long before the development of lung pathology.
The Diagnostic Sensitivity of Electrophysiologic Testing in Patients with Syncope Caused by Transient Bradycardia
Authors: Osamu Fujimura, Raymond Yee, George J. Klein, Arjun D. Sharma, K. Atta Boahene
Journal: New England Journal of Medicine (1989)

Although electrophysiologic testing accurately delineates abnormalities in patients with fixed cardiac-conduction defects, its sensitivity in identifying transient rhythm disturbances is unknown. We prospectively studied 21 patients who had electrocardiographically documented intermittent atrioventricular block (n = 13) or sinus pauses (n = 8) causing syncope, but whose cardiac rhythm had reverted to normal by the time of referral. There were 14 men and 7 women, with a mean age (±SD) of 63±13 years. Fourteen patients had organic heart disease, and 8 were taking cardioactive medications. Electrophysiologic testing was performed before the implantation of a permanent pacemaker. Only three of the eight patients with documented sinus pauses had abnormalities during their tests that suggested the correct diagnosis (sensitivity, 37.5 percent), including a prolonged sinus-node recovery time in one and carotid-sinus hypersensitivity in two. Three of the eight patients had abnormalities detected that were unrelated to syncope, including atrial flutter, dual atrioventricular nodal pathways, and sustained monomorphic ventricular tachycardia. Of the 13 patients with documented atrioventricular block, only 2 had abnormalities suggesting the correct diagnosis (sensitivity, 15.4 percent). Additional observations unrelated to syncope among these 13 patients included abnormal sinus-node function, atrial flutter, and atrial fibrillation causing hypotension. These preliminary observations suggest that a negative electrophysiologic test in a patient with a normal cardiac rhythm who has experienced syncope does not exclude a transient bradyarrhythmia as a cause of the syncope. Furthermore, electrophysiologic testing may sometimes reveal unrelated rhythm disturbances that may mistakenly be designated as the cause of the syncope. (N Engl J Med 1989; 321:1703–7.)
Abstract 14649: Association of P Wave Indices with Atrial Fibrillation and Mortality Risk in the Community: the Framingham Heart Study
Authors: Jared W Magnani, Victor M Johnson, Lisa M Sullivan, Eiran Z Gorodeski, Stephen A Lubitz, Patrick T Ellinor, Emelia J Benjamin
Journal: Circulation (2010)

Background: Long-term risk prediction is a priority for prevention of atrial fibrillation (AF). P wave indices (PWI) are non-invasive, electrocardiographic measurements reflecting atrial conduction...
P126 Efficacy of aclidinium bromide compared with tiotropium and placebo in symptomatic patients with moderate to severe chronic obstructive pulmonary disease (COPD): post-hoc analysis of a Phase IIIb study: Abstract P126 Table 1
Authors: J Beier, R Mroz, F Chuecos, E Garcia Gil
Journal: Thorax (2015)

<h3>Introduction and objective</h3> Maintaining bronchodilation and symptom control throughout the day and night is an important COPD therapeutic aim. Here, we compare 24-hour lung function and symptom control in symptomatic patients with moderate to severe COPD treated with aclidinium or tiotropium, two long-acting, muscarinic antagonists. <h3>Methods</h3> This was a post-hoc analysis of a 6-week, double-blind, Phase IIIb study comparing aclidinium 400 µg BID with tiotropium bromide 18 µg QD or placebo in patients with moderate to severe COPD (NCT01462929). Symptomatic patients were defined as having an EXAcerbations of Chronic pulmonary disease Tool-Respiratory Symptoms (E-RS) baseline score ≥ 10 units. Primary endpoint: change from baseline in normalised FEV<sub>1</sub> AUC over 24-hours post-morning dose (AUC<sub>–24/24h</sub>) at Week 6. Other endpoints: change from baseline in morning pre-dose (trough) FEV<sub>1 </sub>and change from baseline in FEV<sub>1 </sub>AUC<sub>0-–2/12h</sub>;<sub> 12-–4/12h</sub>, E-RS, early-morning and night-time symptoms, and limitation of early-morning activities. <h3>Results</h3> A total of 277/414 symptomatic patients were included; mean age was 62.1 years, 54.5% were current smokers, baseline FEV<sub>1</sub> 1.41 ± 0.48 L. At Week 6, aclidinium 400 µg BID improved FEV<sub>1</sub> over 24 h from baseline vs placebo (Table 1). During the night-time period, aclidinium 400 µg BID improved FEV<sub>1 </sub>from baseline vs tiotropium 18 µg QD. At Week 6, improvements in trough FEV<sub>1</sub> from baseline were observed with aclidinium vs tiotropium and placebo. Aclidinium improved E-RS total score from baseline vs tiotropium and placebo. Moreover, aclidinium improved early-morning and night-time symptom severity from baseline vs tiotropium and placebo over the treatment period (see Table 1 for all results described above). Limitation of early-morning activities caused by COPD symptoms was also improved with aclidinium vs tiotropium and placebo (p &lt; 0.05). Tolerability has been previously reported (Beier COPD 2013) where adverse events (AEs) were similar in each arm, few anticholinergic AEs or serious AEs occurred in any group, and aclidinium was well tolerated. <h3>Conclusions</h3> Aclidinium 400 µg BID improved bronchodilation, particularly during the night-time period, as well as early morning, daily and night-time symptoms, and early-morning limitation of activity in symptomatic patients compared with either tiotropium 18 µg QD or placebo.
The teleconference
Authors: David Isaacs, Stephen Isaacs, Dominic Fitzgerald
Journal: BMJ (2006)

The main purpose of a teleconference is to provide protected time to answer emails. It is this, and not cicadas, which accounts for the continual clicking noise in the background of all teleconferences. The most recent email that you will find in your in tray is the agenda for the teleconference, plus multiple attachments, sent 30 seconds before the conference starts. 

There are some important subsidiary functions of teleconferences. The first is professional interaction. You should arrange teleconferences as often as possible, involving colleagues from at least 20 countries spaced at least 1000 km apart. Start the teleconference at a time of your own maximum convenience. In this way you can ensure that your international academic rivals and their immediate family are sleep deprived for much of the year. 

You can also ensure that your academic rivals believe that their faculties are waning, by placing the microphones at a distance from the participants, which ensures that any conversation is audible only to someone with the hearing of a bat. Meanwhile, by taking teleconference calls at home with the door open, allowing them to hear loud squeals of merriment from your children, you provide evidence of your fecundity and your ability to work efficiently from home. 

The etiquette for a teleconference is a hybrid of the English class and the Indian caste systems. Roles are carefully delineated. The chairperson's role is to conduct the teleconference with all the subtlety of Senator McCarthy investigating Communist subversion. The most seasoned clinician is invited for political reasons. He (it is always a he) wanders in and out of the room, pontificating on previously resolved agenda items and laughing at his own jokes in a fatherly way because no one else finds them funny. Workload is inversely related to age: the youngest member organises the time of the teleconference, sets the agenda, and writes the minutes. 

The role of the telecommunication company is to forget to ring all the most important people on time, and then to interrupt the meeting periodically with ear splitting bleeps and say, “Excuse the interruption, but Dr Livingstone has just presumed to join the teleconference.” 

Communication is not one of the purposes of a teleconference. The most refined form of teleconference is a videoconference. The main purpose of a videoconference is to make sure you do not answer your emails.
Brief Communication: Frog Kidney Tumors Induced by Herpesvirus Cultured in Pronephric Cells2
Authors: Kenyon S. Tweedell, Wai Van Wong
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Brief Communication: Frog Kidney Tumors Induced by Herpesvirus Cultured in Pronephric Cells Get access Kenyon S. Tweedell, Kenyon S. Tweedell Search for other works by this author on: Oxford Academic PubMed Google Scholar Wai Van Wong Wai Van Wong Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 2, February 1974, Pages 621–624, https://doi.org/10.1093/jnci/52.2.621 Published: 01 February 1974 Article history Received: 24 July 1973 Accepted: 05 November 1973 Published: 01 February 1974
Prognostic Value of Exercise Testing Soon after Myocardial Infarction
Authors: Pierre Théroux, David D. Waters, Christine Halphen, Jean-Claude Debaisieux, Henry F. Mizgala
Journal: New England Journal of Medicine (1979)

The prognostic value of a limited treadmill exercise test performed one day before hospital discharge after acute myocardial infarction was studied in 210 consecutive patients who had no overt heart failure and had been free of chest pain for at least four days. No complications occurred. During a one-year follow-up period 28 of 43 patients (65 per cent) who had chest pain during the test reported angina, as compared with 60 of 167 (36 per cent) who had no chest pain during the test (P<0.001). The one-year mortality rates were 2.1 per cent (three of 146) in patients without changes in the S — T segment during exercise and 27 per cent (17 of 64) in those with depression of the S — T segment (P<0.001). Sudden death occurred in one of 146 (0.7 per cent) patients who showed no change in the S — T segment and in 10 of 64 (16 per cent) with depression of the segment (P<0.001). Thus, a limited treadmill exercise test performed before hospital discharge after acute myocardial infarction is safe and can predict mortality in the subsequent year. (N Engl J Med 301:341–345, 1979)
Reduced Calcium Absorption after Nephrectomy in Uremic Patients
Authors: Carl W. Oettinger, Richard Merrill, Troy Blanton, William Briggs
Journal: New England Journal of Medicine (1974)

THE kidney has been implicated in calcium homeostasis by converting 25-hydroxyvitamin D3 (25-OH-D3) to 1,25-dihydroxyvitamin D3 (l,25-[OH]2 D3), the most active vitamin D metabolite in promoting calcium absorption from the gastrointestinal tract.1 Bilateral nephrectomy would prevent this biotransformation of 25-OH-D3 to l,25-(OH)2 D3, thereby possibly interfering with calcium absorption. In this study, calcium absorption decreased after nephrectomy, providing indirect support for the currently accepted role of the kidney in vitamin D metabolism.MethodsSeven patients with end-stage renal failure were studied before and after bilateral nephrectomy while awaiting renal . . .
Neoplasms Observed in Untreated and Corn Oil Gavage Control Groups of F344/N Rats and (C57BL/6N × C3H/HeN)F1 (B6C3F1) Mice
Authors: J. K. Haseman, J. E. Huff, G. N. Rao, J. E. Arnold, G. A. Boorman, E. E. McConnell
Journal: JNCI Journal of the National Cancer Institute (1985)

Control data on F344/N rats and (C57BL/6N X C3H/HeN)F1 (B6C3F1) mammary tumor virus-free mice from the National Toxicology Program (NTP) were examined to determine if animals receiving corn oil by gavage showed tumor incidences that differed from those of untreated control animals. Analyses of these data were adjusted for interlaboratory variability, time-related trends, and supplier effects. Two biologically significant effects were found: Male F344/N control rats receiving corn oil by gavage showed a higher (P less than .05) incidence of pancreatic acinar cell adenoma and a lower (P less than .001) incidence of leukemia (primarily mononuclear cell leukemia) than did the corresponding untreated controls. The increased incidences of pancreatic acinar cell adenoma seen in male rats administered corn oil by gavage were associated with elevated body weights observed in these animals relative to untreated controls. Female F344 rats and male and female B6C3F1 mice showed little or no evidence of a difference in tumor incidence between corn oil gavage-treated and untreated controls. A review of nearly 300 carcinogenesis studies done by the National Cancer Institute (NCI) and the NTP revealed that there were no corn oil gavage studies in which increased incidences of pancreatic acinar cell tumors or leukemia in male F344/N rats were the sole evidence of the carcinogenicity of a test chemical. Thus use of corn oil appears to have little impact on the interpretation of NCI-NTP carcinogenicity studies.
Trisomy 12 in B Cells of Patients with B-Cell Chronic Lymphocytic Leukemia
Authors: Sakari Knuutila, Erkki Elonen, Lasse Teerenhovi, Leena Rossi, Ritva Leskinen, Clara D. Bloomfield, Albert de la Chapelle
Journal: New England Journal of Medicine (1986)

Trisomy 12 is the most frequently reported chromosome abnormality in patients with B-cell chronic lymphocytic leukemia, but only normal karyotypes are found in one third of patients with that disorder. Moreover, samples from patients with trisomy 12 also have many normal metaphases. To identify immunologically the cells in which both the trisomy 12 and the normal karyotypes occur, we studied two patients with B-cell chronic lymphocytic leukemia — one whose neoplastic cells demonstrated lambda light-chain clonality and one whose cells had kappa light-chain clonality. We used a recently developed cytogenetic method that allows simultaneous analysis of cell morphology, immunologic phenotype, and karyotype in the same mitotic cell. In cultures of blood cells stimulated with pokeweed mitogen and tetradecanoylphorbol acetate, all the mitotic cells with either the lambda or the kappa immunoglobulin had trisomy 12, whereas all the cells that lacked these light chains or that had T-cell markers (OKT8 or OKT4) had normal karyotypes. These results show that trisomy 12 in B-cell chronic lymphocytic leukemia occurs in the neoplastic B cells, but not in the T cells, and they thus provide an explanation for the common finding of mitoses with normal karyotypes in patients with B-cell chronic lymphocytic leukemia. (N Engl J Med 1986; 314:865–9.)
193TiP: CheckMate 171: A multicenter phase 2 trial of nivolumab (nivo) in patients (pts) with stage IIIB/IV squamous cell (SQ) NSCLC who have received ≥1 prior systemic treatment
Authors: E. Felip, J. Van Meerbeeck, J. Wolf, A. Ardizzoni, A. Li, S. Srinivasan, S. Popat
Journal: Journal of Thoracic Oncology (2016)
Reverse Mutation in Myotonic Dystrophy
Authors: Han G. Brunner, Gert Jansen, Willy Nillesen, Marcel R. Nelen, Christine de Die, Chris J. Howeler, Bernard A. van Oost, Be Wieringa, Hans-Hilger Ropers, Hubert Smeets
Journal: New England Journal of Medicine (1993)

Myotonic dystrophy is a multisystem disorder that is transmitted in an autosomal dominant fashion and is characterized by muscular weakness and atrophy, clinical and electromyographic evidence of myotonia, ocular cataract, and various other abnormalities, such as cardiac conduction disturbances, testicular atrophy in males, premature balding, increased risk from anesthesia, and mental retardation in cases with early onset1. It is the most common inherited muscular dystrophy of adulthood, with an incidence of approximately 1 per 7500 people. The clinical expression of myotonic dystrophy is variable, ranging from neonatal mortality to a complete absence of symptoms. Recently, the disorder has been . . .
Abstract P1-11-03: Patient reporting pain intensity immediately after surgery can be associated with underlying depression in women with breast cancer
Authors: YS Kim, JW Lee, J Kim, SB Lee, J Yu, BS Ko, HJ Kim, BH Son, SH Ahn
Journal: Cancer Research (2016)

Abstract Objective The aims of this study were to determine the prevalence of severe, definite depression symptoms, as measured using the Center for Epidemiological Studies Depression Scale (CES-D), and the association between high CES-D scores (i.e., ≥25) and sociodemographic and perioperative factors during perioperative period. Methods Among 1690 consecutive breast cancer patients who were admitted for definitive breast surgery during the study period, 1499 patients were included in this study. Patients with a past medical history of psychiatric medication or support, a plan for elective surgery due to locoregional recurrence or any metastatic disease were excluded. The CES-D score was checked 1 day before definitive surgeries. The sociodemographic data and perioperative data were analyzed. Results The mean CES-D score was 18.5, with 24.1% (362/1499) and 56.7% (850/1499) having high CES-D scores of ≥25 and ≥16, respectively. Multivariate analysis revealed that the number of family members with any malignancy (≥2 vs 0), sedative medication (yes vs no) and postoperative numeric rating scale (NRS) scores (persistent, severe pain vs stably mild pain) were significant associated factors for severe, definite depression symptoms [CES-D score of ≥25: adjusted odds ratio (OR)=1.56, 95% confidence interval (CI)=1.10–2.21, P=0.013; adjusted OR=1.65, 95% CI=1.00–2.71, P=0.048; and adjusted OR=2.14, 95% CI=1.15–3.95, P=0.016, respectively]. Conclusion Depression may increase the intensity of postoperative acute pain. Self-reporting of persistent postoperative pain intensity is potentially useful in detecting hidden depression symptoms in breast cancer patients during the perioperative period. Citation Format: Kim YS, Lee JW, Kim J, Lee SB, Yu J, Ko BS, Kim HJ, Son BH, Ahn SH. Patient reporting pain intensity immediately after surgery can be associated with underlying depression in women with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-11-03.
Metformin Use and Survival of Patients With Pancreatic Cancer: A Cautionary Lesson
Authors: Roongruedee Chaiteerakij, Gloria M. Petersen, William R. Bamlet, Kari G. Chaffee, David B. Zhen, Patrick A. Burch, Emma R. Leof, Lewis R. Roberts, Ann L. Oberg
Journal: Journal of Clinical Oncology (2016)

The inclusion of metformin in the treatment arms of cancer clinical trials is based on improved survival that has been demonstrated in retrospective epidemiologic studies; however, unintended biases may exist when analysis is performed by using a conventional Cox proportional hazards regression model with dichotomous ever/never categorization. We examined the impact of metformin exposure definitions, analytical methods, and patient selection on the estimated effect size of metformin exposure on survival in a large cohort of patients with pancreatic ductal adenocarcinoma (PDAC).Of newly diagnosed patients with PDAC with diabetes, 980 were retrospectively included, and exposure to metformin documented. Median survival was assessed by using Kaplan-Meier and log-rank methods. Hazard ratios (HR) and 95% CIs were computed to compare time-varying covariate analysis with conventional Cox proportional hazards regression analysis.Median survival of metformin users versus nonusers was 9.9 versus 8.9 months, respectively. By the time-varying covariate analysis, metformin use was not statistically significantly associated with improved survival (HR, 0.93; 95% CI, 0.81 to1.07; P = .28). There was no evidence of benefit in the subset of patients who were naïve to metformin at the time of PDAC diagnosis (most representative of patients enrolled in clinical trials; HR, 1.01; 95% CI, 0.80 to 1.30; P = .89); however, when the analysis was performed by using the conventional Cox model, an artificial survival benefit of metformin was detected (HR, 0.88; 95% CI, 0.77 to 1.01; P = .08), which suggested biased results from the conventional Cox analysis.Our findings did not suggest the benefit of metformin use after patients are diagnosed with PDAC. We highlight the importance of patient selection and appropriate statistical analytical methods when studying medication exposure and cancer survival.
Urinary Excretion of Iron-Binding Protein in the Nephrotic Syndrome
Authors: David Rifkind, Howard M. Kravetz, Vernon Knight, Arthur L. Schade
Journal: New England Journal of Medicine (1961)

ALTHOUGH siderophilin (transferrin) is present in the urine of nephrotic patients1 and is often in low concentration in the serum of these patients,1 , 2 the quantitative aspects of siderophilinuria in renal disease have not been extensively investigated. Urinary siderophilin loss is reported here in 2 patients with the nephrotic syndrome, and in 1 of these cases the influence of a steroid-induced remission upon this loss is described. In this case, the urinary excretion of siderophilin in a twenty-four-hour period was found to exceed the total circulating quantity of this specific iron-binding serum globulin.MethodsSamples of serum for iron and siderophilin . . .
Weil's Disease
Authors: E. Craig Heringman, Jack H. Phillips
Journal: New England Journal of Medicine (1947)

ALTHOUGH Weil's disease is frequently mentioned in various classifications of the causes of jaundice, it has attracted little attention as a condition that can simulate an acute surgical condition of the abdomen. This is not at all surprising because the disease is generally considered to be quite rare in this country. In fact, state and city health departments have only recently become equipped to undertake the proper diagnostic laboratory procedures.We became interested in this problem during a review of cases of jaundice at Charity Hospital of Louisiana in New Orleans, in which it was found that operations had been . . .