tbuckley/cabot-search huggingface dataset:
Abstract 211: Automated and Non-invasive Estimation of QT Interval from Microscopy Images of Stem Cell-Derived Cardiomyocytes
Authors: Mahnaz Maddah, Kevin Loewke
Journal: Circulation Research (2014)

A promising application of induced pluripotent stem cells (iPSCs) is the generation of patient-specific cardiomyocytes (CMs), which can be used for drug development and safety testing related to cardiovascular health. iPSC-derived CMs can be used for preclinical testing of new drugs that may cause drug-induced arrhythmia or long QT syndrome, as well as post-market safety testing of existing drugs. The measurement of QT interval for iPSC-derived CMs is commonly analyzed using electrophysiological potentials captured by a micro-electrode array (MEA). While such systems are the current standard for characterization, they can be expensive and low-throughput, require high cell plating density, and due to the direct contact between cells and electrodes, may cause undesirable cellular response. Here, we present a new method to non-invasively measure the QT-interval in iPSC-derived CMs using video microscopy and computer vision analysis. Our algorithms can reliably and automatically extract beating signal characteristics such as frequency, irregularity, and duration through image analysis of cardiomyocyte motion. Through a correlative study with MEA, we demonstrate that a non-invasive measurement of QT interval can be derived from the duration of visible cellular motion that occurs during contraction and relaxation. We also show that our system can accurately characterize the cellular response from the addition of compounds known to modulate beating frequency and irregularity. Our measurement technique is robust, automated, and requires no physical or chemical contact with the cells, making it ideal for cardiovascular drug development and cardiotoxicity testing.
Timed sequential chemotherapy for previously treated patients with acute myeloid leukemia: long-term follow-up of the etoposide, mitoxantrone, and cytarabine-86 trial.
Authors: E Archimbaud, X Thomas, V Leblond, M Michallet, P Fenaux, C Cordonnier, F Dreyfus, X Troussard, J Jaubert, P Travade
Journal: Journal of Clinical Oncology (1995)

PURPOSE To confirm and extend encouraging preliminary results of timed sequential chemotherapy (TSC) in patients with previously treated acute myelogenous leukemia (AML). PATIENTS AND METHODS We report the results of the regimen of mitoxantrone on days 1 to 3, etoposide on days 8 to 10, and cytarabine on days 1 to 3 and 8 to 10 (EMA) in 133 patients, with a median follow-up of 40 months. RESULTS Sixty percent of patients, with a 95% confidence interval (CI) ranging from 51% to 68%, achieved complete remission (CR), including 44% (CI, 32% to 57%) of refractory patients and 76% (CI, 64% to 86%) of late first-relapse patients (P = .0002). Twenty-nine percent of patients did not respond to therapy, and 11% died from toxicity. Median duration of neutropenia and thrombocytopenia was 31 days and 29 days, respectively. Severe nonhematologic toxicity included sepsis in 54% of patients and mucositis in 23%. Postinduction therapy included a second course of EMA in 27 patients, maintenance in 10, autologous bone marrow transplantation (BMT) in 12, and allogeneic BMT in 13. Median survival of patients who did not have transplantation performed is 7 months, with 11% (CI, 4% to 18%) survival at 5 years. Median disease-free survival (DFS) is 8 months with 20% (CI, 8% to 32%) DFS at 5 years. Twenty-eight percent (CI, 15% to 44%) of nontransplanted patients who achieved CR had an inversion of CR duration. Previous refractoriness was the main factor associated with poor prognosis for CR achievement, DFS, and survival. CONCLUSION These results confirm initial reports on TSC and show that approximately 20% of patients with first relapse after therapy can enjoy prolonged DFS using chemotherapy only.
Multidrug resistant TB is less transmissible than drug susceptible strains, study shows
Authors: S. Mayor
Journal: BMJ (2015)

Multidrug resistant tuberculosis (TB) is only about half as transmissible as drug susceptible TB among household contacts, a study has found, suggesting that the fitness of the resistant TB strain is less than those that respond to drug treatment1 and providing encouraging new information on the chances of containing its spread.

The fitness of Mycobacterium tuberculosis —defined as its ability to reproduce, be transmitted, and cause disease in another person—is …
Experimental Production of Testicular Teratomas in Mice of Strains 129, A/He, and Their F&lt;sub&gt;1&lt;/sub&gt; Hybrids&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Leroy C. Stevens
Journal: JNCI Journal of the National Cancer Institute (1970)

Testicular teratomas were experimentally produced from primordial germ cells in mice of strains 129, A/He, and their F1 hybrids by grafting 12- and 13-day fetal genital ridges into histocompatible adult testes. Male grafts developed into testes and most of them had several teratomatous foci. The incidence of teratomas (97%) was higher in hybrid grafts than in grafts from either parent strain, and the hybrid grafts were very susceptible to teratocarcinogenesis during days 12 and 13 of gestation, whereas grafts from the parent strains were very susceptible during only 1 of these days. The incidence of teratomas in hybrids was higher when the mother was of strain 129, indicating a maternal influence on teratocarcinogenesis. Strain 129 grafts were most susceptible during day 12, and strain A/He during day 13 of gestation. All experimentally produced teratomas developed similarly to the spontaneous teratomas of strain 129 mice. They originated from primordial germ cells within the seminiferous tubules. The primordial germ cells developed into clusters of undifferentiated embryonic cells. The embryonic cells gave rise to the three primary germ layers and to more embryonic cells. The germ layers differentiated into many kinds of normal appearing but disorganized adult tissues. Spontaneous teratomas occur in about 10% of strain 129 males, but are extremely rare in strain A/He and unknown in 129 × A/He hybrids/These hybrids and strain A/He mice will be especially useful for study of teratocarcinogenesis because of their high incidence of experimentally produced teratomas and their extremely low incidence of spontaneous teratomas.
Enuresis in obstructive sleep apnea syndrome patients
Authors: Dimosthenis Lykouras, Maria Sargianou, Kiriakos Karkoulias, Fotios Sampsonas, Kleanthis Theodoropoulos, Angeliki Skoura, Apostolos Voulgaridis, Kostas Spiropoulos
Journal: European Respiratory Journal (2012)

Introduction : Although in children with obstructive sleep apnea syndrome (OSAS) secondary involuntary nocturnal voiding (enuresis) is a common and well recognized symptom, it is encountered less frequently in adults suffering from OSAS.   Aims and Objectives : The aim of our study was to reveal the extent of the symptom of enuresis among adult OSAS patients in the Greek population.   Methods : The patients recruited in this study underwent overnight polysomnography and existing co-morbidities were recorded according to a relative questionnaire. The cohort consisted of 165 patients, 121 of which were males and 44 were females.   Results : Statistical analysis was performed using the ANOVA test. Our results revealed that patients presenting enuresis had a greater apnea/hypopnea index (AHI). Mean age of our patients was 55 years and the average BMI turned out 21.41 kg/m 2 . A percentage of 65% of the cohort population were current smokers, 75% were consuming at least one coffee daily and only 2% were consuming alcohol on a daily basis. We also used multivariate analysis to examine the role of several factors such as age, deliveries in women, coffee consumption, diuretics, Diabetes Mellitus (DM), the number of arousals, the lowest SaO2 during sleep, smoking habits, sleep efficiency and AHI in enuresis in OSAS patients.   Conclusions : Our study showed that patients without enuresis had a lower AHI than those complaining for involuntary nocturnal voiding (p=0.03). A better understanding of the pathogenesis of enuresis needs follow-up of the CPAP treatment and urodynamics of the bladder.
<scp>eQTL</scp> of bronchial epithelial cells and bronchial alveolar lavage deciphers <scp>GWAS</scp>‐identified asthma genes
Authors: X. Li, A. T. Hastie, G. A. Hawkins, W. C. Moore, E. J. Ampleford, J. Milosevic, H. Li, W. W. Busse, S. C. Erzurum, N. Kaminski, S. E. Wenzel, D. A. Meyers, E. R. Bleecker
Journal: Allergy (2015)

Abstract Background Genome‐wide association studies ( GWAS s) have identified various genes associated with asthma, yet, causal genes or single nucleotide polymorphisms ( SNP s) remain elusive. We sought to dissect functional genes/ SNP s for asthma by combining expression quantitative trait loci ( eQTL s) and GWAS s. Methods Cis ‐ eQTL analyses of 34 asthma genes were performed in cells from human bronchial epithelial biopsy ( BEC , n = 107) and from bronchial alveolar lavage ( BAL , n = 94). Results For TSLP ‐ WDR 36 region, rs3806932 (G allele protective against eosinophilic esophagitis) and rs2416257 (A allele associated with lower eosinophil counts and protective against asthma) were correlated with decreased expression of TSLP in BAL ( P = 7.9 × 10 −11 and 5.4 × 10 −4 , respectively) and BEC , but not WDR 36 . Surprisingly, rs1837253 (consistently associated with asthma) showed no correlation with TSLP expression levels. For ORMDL 3‐ GSDMB region, rs8067378 (G allele protective against asthma) was correlated with decreased expression of GSDMB in BEC and BAL ( P = 1.3 × 10 −4 and 0.04) but not ORMDL 3 . rs992969 in the promoter region of IL 33 (A allele associated with higher eosinophil counts and risk for asthma) was correlated with increased expression of IL 33 in BEC ( P = 1.3 × 10 −6 ) but not in BAL . Conclusions Our study illustrates cell‐type‐specific regulation of the expression of asthma‐related genes documenting SNP s in TSLP , GSDMB , IL 33 , HLA ‐ DQB 1 , C11orf30 , DEXI , CDHR 3 , and ZBTB 10 affect asthma risk through cis ‐regulation of its gene expression. Whenever possible, disease‐relevant tissues should be used for transcription analysis. SNP s in TSLP may affect asthma risk through up‐regulating TSLP mRNA expression or protein secretion. Further functional studies are warranted.
A prospective randomized trial evaluating prophylactic antibiotics to prevent triple-lumen catheter-related sepsis in patients treated with immunotherapy.
Authors: S N Bock, R E Lee, B Fisher, J T Rubin, D J Schwartzentruber, J P Wei, D P Callender, J C Yang, M T Lotze, P A Pizzo
Journal: Journal of Clinical Oncology (1990)

During a 15-month period, 92 patients undergoing 129 treatment episodes of immunotherapy with interleukin-2 (IL-2) alone or with immune cells underwent insertion of central venous catheters (CVCs) in the Surgery Branch, National Cancer Institute. Before each catheter insertion patients were prospectively randomized into one of three treatment groups; therapy with intravenous (IV) placebo using D5W, IV oxacillin, or change of the catheter to a new site every 72 hours. The mean duration of catheterization was 3.8 +/- 1.1 days. No patient in the oxacillin arm developed catheter-related sepsis, while eight patients in the control arms (five, line change, three, placebo) developed catheter-related sepsis (P2 = .050). Seven episodes of catheter-related sepsis were due to Staphylococcus aureus and one was due to Staphylococcus epidermidis. Catheter colonization was reduced significantly in the oxacillin arm versus control arms (P = .0001). Staphylococcus aureus, Staphylococcus epidermidis, and other coagulase-negative Staphylococci were sensitive to oxacillin in 89%, 60%, and 50% of cultures, respectively. No evidence of bacterial overgrowth, candida colonization, or candidemia was observed in these patients. Thus this trial demonstrates that treatment with prophylactic oxacillin can decrease the incidence of catheter-related sepsis in patients undergoing immunotherapy with interleukin-2 (IL-2). To our knowledge this is the first prospective randomized trial to evaluate the prophylactic use of systemic antibiotics in the prophylaxis of CVC sepsis.
Influence of age in the clinical differentiation of atypical pneumonia in adults
Authors: Naoyuki Miyashita, Yasuhiro Kawai, Mika Kubo, Kazunobu Ouchi, Niro Okimoto
Journal: European Respiratory Journal (2012)

Background and objective:   The Japanese Respiratory Society (JRS) scoring system is a useful tool in the early and simple presumptive diagnosis of atypical pneumonia,  Mycoplasma pneumoniae  and  Chlamydia pneumoniae  pneumonia. However, it has been suggested that it seems to be difficult to diagnose atypical pneumonia in the elderly using this system. In the present study, we evaluated the accuracy and usefulness of the JRS scoring system in the different age groups.    Methods:   We analyzed 262 cases of  M. pneumoniae , 98 cases of  C. pneumoniae  and 364 cases of common bacterial pneumonia.    Results:   The frequency of co-morbid illnesses and higher risk classes in the elderly (age  ≥ 60 years) group was significantly higher than those of non-elderly patients (age     Conclusions:   Our results indicate that it is difficult to distinguish between atypical pneumonia and bacterial pneumonia in the elderly using the JRS scoring system. When treating patients aged  ≥ 60 years, physicians should choose fluoroquinolones or β-lactams + macrolides as empirical first-choice drugs, so as to always include potential antibiotic cover for atypical pathogens.
CQC plans to test quality of NHS across whole local areas
Authors: Adrian O’Dowd
Journal: BMJ (2015)

The way the NHS is regulated could change to include reviews of services across whole healthcare areas rather than regular separate inspections of each part of the NHS, under plans by the main NHS regulator, the Care Quality Commission (CQC). A “lighter touch” approach to regulating general practice may also be a feature of the new system being considered.

The CQC has announced that it will run “Quality of Care in a Place” pilots (www.cqc.org.uk/content/quality-care-place), consisting of place based inspections in two areas—Greater Manchester and North Lincolnshire—to test how well coordinated health and care services are in local areas. …
Vitamin A for treating shigellosis
Authors: M. A. Salam, W. A. Khan, U. Dhar, A. Ronan, N. C Rollins, M. L Bennish, S. Hossain, R. Biswas, I. Kabir, S. Sarker, G. Fuchs, D. Mahalanabis, M. Dibley
Journal: BMJ (1999)

Editor—Hossain et al conclude that vitamin A along with standard antibiotic reduces the severity of acute shigellosis and that vitamin A supplementation should be added to the standard treatment for acute shigellosis.1 We disagree with those conclusions.

The benefit of vitamin A as adjuvant treatment for shigellosis can be judged only in a study in which patients receive adequate antimicrobial treatment.2 In Hossain et al’s study 64% of patients were infected with strains of shigella resistant to nalidixic acid, which was used to treat study patients. It is unclear how many patients were given an alternative effective antibiotic or when treatment was changed.

The inadequacy of antimicrobial treatment in this study is reflected in clinical cure rates of less than 50% in patients who did and did not receive vitamin A supplements. That is not acceptable as adequate antimicrobial treatment routinely achieves a cure rate of 65% or more. 3 4 Indeed, Hossain and colleagues calculated their sample size based on a 98% cure rate in the vitamin A group.1

Their definition of cure included the absence of mucus or blood in stools. These measures are not good indicators of overall clinical status and are subject to variation between observers. It is important to know which component of the definition of clinical cure (three or fewer formed stools, no visible stool blood or mucus, afebrile) used in the study accounted for the difference in cure rates between groups and if there were any differences in more objective outcome measures, such as total number of stools during the study or duration of fever. 3 5

The authors contend that the differences in reported outcome between groups may have been because vitamin A supplementation stimulated phagocytosis and cell mediated killing of pathogens. The similar rate of clearance of shigella observed in the two groups seems to contradict this contention. The rapid divergence (by 24 hours) between groups in the proportion of patients with clinical cure suggests a more rapid response than could reasonably be expected to be achieved by vitamin A “enhanced repair of the micro-ulcers in the gut epithelium.”

Vitamin A has an important role in public health in developing countries. The rationale for its use, however, must come from well conducted studies in which children receive effective primary treatment for their illness (in this case effective antibiotics), and for which there are clear, reproducible, and clinically relevant definitions of treatment outcome.
Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial.
Authors: W Eberhardt, H Wilke, G Stamatis, M Stuschke, A Harstrick, H Menker, B Krause, M R Müeller, M Stahl, M Flasshove, V Budach, D Greschuchna, N Konietzko, H Sack, S Seeber
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the feasibility and efficacy of an intensive multimodality approach with combination chemotherapy, hyperfractionated accelerated chemoradiotherapy, and definitive surgery in prognostically unfavorable subgroups of locally advanced non-small-cell lung cancer stages IIIA and IIIB (LAD-NSCLC). PATIENTS AND METHODS Following staging, including mediastinoscopy, 94 patients with inoperable LAD-NSCLC were treated preoperatively with chemotherapy (three courses of split-dose cisplatin and etoposide [PE]) followed by concurrent chemoradiotherapy (one course of PE combined with 45 Gy hyperfractionated accelerated radiotherapy). After repeat mediastinoscopy, patients underwent surgery 4 weeks postradiation. RESULTS Of 94 consecutive patients (52 stage IIIA [&gt; or = two lymph node levels involved] and 42 stage IIIB [no pleural effusion, no supraclavicular nodes]), 62 (66%) completed induction and underwent surgery. Complete resection (R0) was achieved in 50 (53% of all patients) and pathologic complete response (PCR) in 24 (26%). After a median follow-up of 43 months, the median survival time was 20 months for IIIA, 18 months for IIIB, and 42 months for R0 patients. Calculated survival rates at 4 years were 31%, 26%, and 46%. Two patients died of sepsis preoperatively and four died postoperatively of pleural empyema (n = 1), stump insufficiency (n = 2), and cardiac failure (n = 1). Other toxicities were acceptable-mainly hematologic during chemotherapy or chemoradiotherapy and esophagitis during chemoradiotherapy. CONCLUSION This intensive multimodality treatment is feasible and demonstrates high efficacy in prognostically unfavorable LAD-NSCLC subgroups with high R0 rates and improved long-term survival compared with historical controls
The Electrocardiogram in General Practice: Its Use and Its Interpretation
Authors: D C Macallan, J A Bell, M Braddick, K Endersby, J Rizzo-Naudi
Journal: Journal of the Royal Society of Medicine (1990)

General practitioners in one health district were surveyed by postal questionnaire (including 15 sample electrocardiogram tracings) to assess their usage and competence in interpretation of the electrocardiogram. A response rate of 60% was achieved, of whom 40% said they used the electrocardiogram at least monthly and 43% used it ‘always’ or ‘usually’ in patients with suspected myocardial infarction at home. Overall competence in recognizing a variety of abnormalities was felt to be good. Recent qualification, the possession of a higher qualification (MRCP/MRCGP) and frequency of usage were associated with better performance. Even so, unequivocal acute myocardial infarction was misdiagnosed by 20% of respondents. These findings have implications for the provision of electrocardiographic services in primary care and the management of patients in the home with suspected myocardial infarction, particularly with the advent of thrombolytic therapy.
Serum viral duplex-linear DNA proportion increases with the progression of liver disease in patients infected with HBV
Authors: Xing-Liang Zhao, Jian-Rong Yang, Sheng-Zhang Lin, Hui Ma, Fang Guo, Rui-Feng Yang, Heng-Hui Zhang, Jin-Chao Han, Lai Wei, Xiao-Ben Pan
Journal: Gut (2015)

<h3>Objective</h3> HBV has two forms of genomic DNA, relaxed-circular DNA (rcDNA) and duplex-linear DNA (dlDNA). Compared to rcDNA, dlDNA has been demonstrated to integrate more frequently into host cellular chromosomes, which may have oncogenic consequences. However, the dlDNA proportion relative to total HBV DNA and its clinical significance in patients remain to be investigated. <h3>Design</h3> Based on the structural difference between rcDNA and dlDNA, we developed a peptide nucleic acid (PNA)-mediated quantitative real-time PCR (qPCR) clamping assay to measure the proportions of dlDNA in total HBV DNA in sera obtained from patients with chronic hepatitis B (CHB), liver cirrhosis (LC) or LC-developed hepatocellular carcinoma (HCC). The factors that influence the proportion of dlDNA were also investigated. <h3>Results</h3> The average dlDNA proportion was approximately 7% in the sera of chronic HBV-infected patients and was elevated in CHB patients with abnormal levels of alanine aminotransferase. The sera dlDNA proportions increased to approximately 14% and 20% in the patients with LC and HCC, respectively. Interferon-α treatment slightly increased the dlDNA proportion in the responders; and nucleotide analogue therapy spuriously elevated the proportion. Moreover, treatment of human hepatoma cells supporting HBV replication with inflammatory cytokines significantly altered the dlDNA proportion in vitro. <h3>Conclusions</h3> Using a novel PNA-mediated qPCR clamping assay, we first showed that serum dlDNA proportions progressively increased during the development of HBV-related liver diseases. The dlDNA proportion can be regulated by inflammatory cytokines, suggesting an association among inflammation, increased production of HBV dlDNA and development of HCC.
Breast Neoplasms in Women Treated With X-Rays for Acute Postpartum Mastitis 2
Authors: Roy E. Shore, Louis H. Hempelmann, Eugene Kowaluk, Paula S. Mansur, Bernard S. Pasternack, Roy E. Albert, Glenn E. Haughie
Journal: JNCI Journal of the National Cancer Institute (1977)

Breast cancer has been studied by mail survey up to 34 years in 571 of 606 women treated with X-rays for acute postpartum mastitis. The incidence of neoplasms was compared with that of three nonirradiated control groups—nonirradiated sisters of the treated women, women with acute postpartum mastitis not treated with X-rays, and their nonirradiated sisters. For the irradiated group, with a mean dose of 247 rads to both breasts, the overall relative risk of breast cancer was 2.2 for years 10–34 post irradiation and 3.6 for years 20–34. The dose response for malignant and benign breast neoplasms was compatible with a linear fit. For comparable total doses, fractionation of exposure did not reduce carcinogenic action. Women over age 30 years at radiation treatment had as great an excess risk of breast cancer as did younger women. The overall excess risk of developing breast cancer was about 8–10 cases per million women per rad per year, an increase of about 0.5% per rad.