tbuckley/cabot-search huggingface dataset:
Noninterventional statistical comparison of BTS and CHEST guidelines for size and severity in primary pneumothorax
Authors: Marko Z. Nikolić, Laurence S.C. Lok, Katharina Mattishent, Sarah Barth, Bernard Yung, Natalie M. Cummings, Donna Wade, Yusuf Vali, Katie Chong, Alexander Wilkinson, Theresia Mikolasch, Seema Brij, H.S. Jenkins, Ajay V. Kamath, Mark Pasteur, Thomas G. Hopkins, James Wason, Stefan J. Marciniak
Journal: European Respiratory Journal (2015)

Primary spontaneous pneumothorax (PSP) occurs in apparently healthy young people with an incidence of 12.5 cases per 100 000 per year [1]. Attempts to develop standardised care guidelines for this condition have been severely hampered by a lack of high-quality clinical research into this condition. The American College of Chest Physicians (CHEST) concluded in 2001 that "insufficient data exist…to develop an evidence-based document" and so produced a consensus statement based on expert opinion [2]. Similarly, the British Thoracic Society (BTS) 2010 guidelines are based predominantly on nonanalytical studies and expert opinion [3]. In both documents, the size of the presenting PSP is used to determine initial treatment. A "small" PSP without respiratory compromise is thought not to require intervention, while a "large" PSP has typically been treated either by aspiration or intrapleural drainage. Implicit in these definitions is the belief that large pneumothoraces will not respond well to conservative management. Remarkably, no consensus regarding the definition of PSP severity exists, with CHEST and the BTS each using different arbitrary measurements of the presentation chest radiograph. When these measurements were compared directly to one another, they showed poor correlation [4]. This lack of a clinically useful radiological biomarker for pneumothoraces requiring intervention hinders the development of evidence-based care of this condition. We wished to determine whether the BTS definition of large pneumothorax (>2 cm at the hilum) or CHEST definition (>3 cm from apex to cupola) better predicts the requirement for intercostal chest drain (ICD) insertion. Hilar rather than apical interpleural distance more accurately predicts need for intercostal chest drain insertion <http://ow.ly/JvKFY>
EXPERIMENTS ON THE EPIDEMIOLOGY OF PSEUDORABIES
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1935)

Pseudorabies is a very fatal but non-contagious disease in cattle and the common laboratory animals. It is a relatively mild yet highly contagious disease in swine. It has been shown that in swine the nose serves both for the entrance and the exit of the virus. Furthermore, it has been observed that fatal pseudorabies infections in rabbits can be induced merely by bringing their abraded skin into contact with the noses of infected swine. The blood sera of swine on two farms where pseudorabies had occurred among the cattle were found to be capable of neutralizing pseudorabies virus. It is believed that in these instances the swine had a mild and unrecognized pseudorabies infection and transmitted their disease to the cattle with which they were associated, by transfer of the virus on their noses to the abraded skin of the cattle.
In Vivo Antitumor Activity of Various Forms of Delayed-Type Hypersensitivity in Mice&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: P H Lagrange, P M Thickstun
Journal: JNCI Journal of the National Cancer Institute (1979)

Relationships among various forms of delayed-type hypersensitivity (DTH) and nonspecific resistance to Lewis lung tumor were studied in syngeneic and semisyngeneic mice. Only the tuberculin type of DTH obviated a virulent inoculum of 10(6) tumor cells. The Jones-Mote type of DTH, even modified by cyclophosphamide pretreatment, produced a significant local inflammatory reaction which was unable to destroy tumor cells. The antitumor effect of the tuberculin type was observed in BCG-or in Corynbacterium parvum-immune mice and also in sheep red blood cell-immunized mice, but only after the modulating effect of BCG. The antitumor activity of the DTH reaction was anatomically restricted and time related, and it required local persistence of specific antigen. A minimal number of bacteria, 1 times 10(6) living or heat-killed BCG organisms, were equally able to eradicate 10(5) tumor cells in BCG-immune mice. Biphasic effects on tumor growth were observed when systemic specific inflammatory reactions were elicited in BCG-immune mice. However, tumor-specific immunity was never observed, inasmuch as BCG-immune mice surviving injection of a mixture of BCG and tumor cells did not resist a second tumor cell challenge.
Better reporting for better research: a checklist for reproducibility
Authors: Amye Kenall, Scott Edmunds, Laurie Goodman, Liz Bal, Louisa Flintoft, Daniel R Shanahan, Tim Shipley
Journal: Genome biology (2015)

How easy is it to reproduce or replicate the findings of a published paper?In 2013 one researcher, Phil Bourne, asked just this.How easy would it be to reproduce the results of a computational biology paper?[1].The answer: 280 hours.Such a number is surprising, given the theoretical reproducibility of computational research and given Bourne was attempting to reproduce work done in his own lab.Now at the National Institutes of Health (NIH) as Associate Director of Data Sciences, Bourne is concerned with the reproducibility of all NIH funded work, not just his own-and the problem is large.In addition to work in computational biology (which theoretically should be more easily reproducible than "wet lab" work), hallmark papers in cancer through to psychology have been flagged as largely unreproducible [2,3].Closer to home, GigaScience has carried out similar work to quantify reproducibility in their content.Despite being scrutinized and tested by seven referees, it still took about half a man-month worth of resources to reproduce the results reported in just one of the tables [4]."Reproducibility" is now increasingly on the radar of funders and is making its rounds in the wider media as well, with concerns of reproducibility making headlines at The Economist [5] and New York Times [6], amongst other outlets.
Selective development of T helper (Th)2 cells induced by continuous administration of low dose soluble proteins to normal and beta(2)-microglobulin-deficient BALB/c mice.
Authors: J C Guery, F Galbiati, S Smiroldo, L Adorini
Journal: The Journal of Experimental Medicine (1996)

Continuous administration of soluble proteins, delivered over a 10-d period by a mini-osmotic pump implanted subcutaneously, induces a long-lasting inhibition of antigen-specific T cell proliferation in lymph node cells from BALB/c mice subsequently primed with antigen in adjuvant. The decreased T cell proliferative response is associated with a down-regulation of the T helper cell (Th)1 cytokines interleukin (IL)-2 and interferon (IFN)-gamma and with a strong increase in the secretion of the Th2 cytokines IL-4 and IL-5 by antigen specific CD4+ T cells. This is accompanied by predominant inhibition of antigen-specific antibody production of IgG2a and IgG2b, rather than IgG1 isotype. Interestingly, inhibition of Th1 and priming of Th2 cells is also induced in beta(2) microglobulin-deficient BALB/c mice, indicating that neither CD8+ nor CD4+ NK1.1+ T cells, respectively, are required. The polarization in Th2 cells is stably maintained by T cell lines, all composed of CD4+/CD8- cells expressing T cell receptor for antigen (TCR) alpha/beta chains, derived from BALB/c mice treated with continuous antigen administration, indicating that they originate from Th2 cells fully differentiated in vivo. This polarization is induced in BALB/c mice by continuous administration of any protein antigen tested, including soluble extracts from pathogenic microorganisms. Priming of Th2 cells is dose dependent and it is optimal for low rather than high doses of protein. Blocking endogenous IL-4 in vivo inhibits expansion of antigen-specific Th2 cells, but does not restore IFN-gamma production by T cells from mice treated with soluble antigen-specific Th2 cells, but does not restore IFN-gamma production by T cells from mice treated with soluble antigen, indicating the involvement of two independent mechanisms. Consistent with this, Th2 cell development, but not inhibition of Th1 cells, depends on non-major histocompatibility complex genetic predisposition, since the Th2 response is amplified in BALB/c as compared to DBA/2, C3H, or C57BL/6 mice whereas tested. These findings support the hypothesis that continuous release of low amounts of protein antigens from pathogenic microorganisms may polarize the immune response toward a Th2 phenotype in susceptible mouse strains.
Lurasidone in the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo- and Olanzapine-Controlled Study
Authors: Herbert Y. Meltzer, Josephine Cucchiaro, Robert Silva, Masaaki Ogasa, Debra Phillips, Jane Xu, Amir H. Kalali, Edward Schweizer, Andrei Pikalov, Antony Loebel
Journal: American Journal of Psychiatry (2011)

Lurasidone is a recently approved antipsychotic drug for schizophrenia, with daily doses up to 80 mg. Doses above that level were associated with increased levels of akathisia in this 6-week study. At recommended doses, lurasidone is efficacious for both positive and negative symptoms with no effect on metabolic parameters. Olanzapine was associated with greater significant improvement on some measures but also had increased metabolic effects.
CELLULAR MEDIATORS OF ANTI-<i>LISTERIA</i> IMMUNITY AS AN ENLARGED POPULATION OF SHORT-LIVED, REPLICATING T CELLS
Authors: Robert J. North
Journal: The Journal of Experimental Medicine (1973)

An intravenous immunizing infection with the facultative, intracellular parasite, Listeria monocytogenes results in the production in the spleen of a population of immunologically-committed lymphocytes which can adoptively immunize normal recipients against a lethal challenge infection. These cellular mediators of immunity are first produced in the spleen between days 2 and 4 of infection and reach peak production on day 6. Their production then progressively decreases until about day 20 when their presence can no longer be detected. Increased production of cellular mediators is coincident with major increases in cell division, cellularity, and spleen weight. Decreased production of cellular mediators, on the other hand, is associated with decreases in cell division, cellularity, and spleen weight. Again, the level of delayed sensitivity to Listeria antigens expressed by the host at any one time is proportional to the number of cellular mediators in the spleen. Increased production of cellular mediators is also associated with major increases in the total numbers of replicating T cells and B cells in the spleen. That the cellular mediators of immunity are part of the replicating T cell population, rather than the B cell population, is evidenced by their susceptibility to anti-theta serum and by their resistance to anti-Ig serum. Furthermore, they can be completely eliminated from the spleen by a brief pulse of the antimitotic drug, vinblastine. This study allows the conclusion that the cellular mediators of anti-Listeria immunity belong to an expanded population of rapidly dividing, short-lived T cells. It is suggested that they have the same properties as the T cell effectors of allograft immunity.
Chemoresistant KM12C Colon Cancer Cells Are Addicted to Low Cyclic AMP Levels in a Phosphodiesterase 4–Regulated Compartment via Effects on Phosphoinositide 3-Kinase
Authors: David G. McEwan, Valerie G. Brunton, George S. Baillie, Nicholas R. Leslie, Miles D. Houslay, Margaret C. Frame
Journal: Cancer Research (2007)

Abstract One of the major problems in treating colon cancer is chemoresistance to cytotoxic chemotherapeutic agents. There is therefore a need to devise new strategies to inhibit colon cancer cell growth and survival. Here, we show that a combination of low doses of the adenylyl cyclase activator forskolin together with the specific cyclic AMP (cAMP) phosphodiesterase-4 (PDE4) inhibitor rolipram, but not the cAMP phosphodiesterase-3 (PDE3) inhibitor cilostamide, causes profound growth arrest of chemoresistant KM12C colon cancer cells. Low-dose forskolin causes KM12C cells to exit the cell cycle in G1 by inducing p27Kip1 and primes cells for apoptosis on addition of rolipram. The effect of the low-dose forskolin/rolipram combination is mediated by displacement of the phosphatidylinositol 3,4,5-trisphosphate/phosphoinositide 3-kinase signaling module from the plasma membrane and suppression of the Akt/protein kinase-B oncogene pathway, to which KM12C cells are addicted for growth. The cAMP and phosphoinositide 3-kinase pathways form a critical intersection in this response, and reexpression of the tumor suppressor lipid phosphatase, phosphatase and tensin homologue, which is commonly lost or mutated in colon cancer, sensitizes KM12C cells to growth inhibition by challenge with low-dose forskolin. Certain chemoresistant colon cancer cells are therefore exquisitely sensitive to subtle elevation of cAMP by a synergistic low-dose adenylyl cyclase activator/PDE4 inhibitor combination. Indeed, these cells are addicted to maintenance of low cAMP concentrations in a compartment that is regulated by PDE4. Well-tolerated doses of PDE4 inhibitors that are already in clinical development for other therapeutic indications may provide an exciting new strategy for the treatment of colon cancer. [Cancer Res 2007;67(11):5248–57]
MB-32 * FEASIBILITY OF VORINOSTAT COMBINED WITH ISOTRETINOIN AND CHEMOTHERAPY FOR YOUNG CHILDREN WITH NEWLY DIAGNOSED EMBRYONAL BRAIN TUMORS: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY
Authors: S. Leary, L. Kilburn, J. R. Geyer, J. M. Olson, T. MacDonald, D. Ellison, M. Kocak, A. Onar, R. Ermoian, T. Y. Poussaint, J. M. Boyett, L. Kun, M. Fouladi
Journal: Neuro-Oncology (2015)

BACKGROUND: Pre-clinical evaluation of vorinostat and isotretinoin demonstrated cytotoxicity in medulloblastoma (MB) and synergistic activity when combined with cisplatin. This study sought to evaluate the feasibility of combining vorinostat and isotretinoin with cytotoxic chemotherapy in young children with newly diagnosed brain tumors. METHODS: Eligible patients were less than 4 years of age with newly diagnosed medulloblastoma (MB) or supratentorial primitive neuroectodermal tumor (CNS-PNET). Localized desmoplastic MB was excluded. Treatment consisted of 3 induction cycles given every 21 days with vorinostat and isotretinoin(days 1-4), cisplatin(day 4), vincristine(days 4,11,18), cyclophosphamide(days 5-6), and etoposide(days 4-6); 3 consolidation cycles with carboplatin and thiotepa(days 1-2) with stem cell rescue(day 4); and 12 cycles of monthly maintenance therapy with vorinostat and isotretinoin. Patients with M0 MB received focal radiation therapy following consolidation therapy; others received radiation at the discretion of the treating physician. Craniospinal radiation was not allowed on protocol. RESULTS: 31 patients received treatment on study; 19 (61.3%) were male; 7 (22.6%) had spinal cord or cerebrospinal fluid metastasis at diagnosis. Diagnosis was MB for 20, other CNS-PNET for 11. 24/31 patients completed 3 cycles of induction therapy within the pre-specified feasibility endpoint of 98 days. Eight experienced disease progression on therapy. Twelve completed therapy, five continue on therapy, five discontinued study treatment without progression, and one died of pulmonary toxicity following second cycle of consolidation. Two-year Progression Free Survival and Overall Survival for the entire cohort were 64.4% (SE ±11.1%) and 75.6% (SE ±10.0%), respectively; 68.2% (SE ±12.8%) and 77.0% (SE ±11.1%) for MB. Frozen tumor was collected from 30/31 tumors. CONCLUSION: It is feasible to administer vorinostat with isotretinoin and chemotherapy to young children with newly diagnosed MB or CNS-PNET. This multimodality therapy regimen resulted in encouraging progression-free survival without craniospinal radiation in a high-risk group of young children. Genomic studies are planned.
New progestagens for contraceptive use
Authors: Regine Sitruk-Ware
Journal: Human Reproduction Update (2005)

The progestins have different pharmacologic properties depending upon the parent molecule, usually testosterone or progesterone (P), from which they are derived. Very small structural changes in the parent molecule may induce considerable differences in the activity of the derivative. In hormonal contraceptives, progestins represent the major agent designed for suppressing ovulation and are used in combination with estrogen (E) usually ethinyl-estradiol (EE). The development of new generations of progestins with improved selectivity profiles has been a great challenge. Steroidal and nonsteroidal progesterone receptor (PR) agonists have been synthesized as well, although the latter are still in a very early stage of development. Several new progestins, have been synthesized in the last two decades. These include dienogest (DNG), drospirenone (DRSP), Nestorone (NES), nomegestrol acetate (NOMAc) and trimegestone (TMG). These new progestins have been designed to have no androgenic or estrogenic actions and to be closer in activity to the physiological hormone P. DRSP differs from the classic progestins as it is derived from spirolactone. It is essentially an antimineralocorticoid steroid with no androgenic effect but a partial antiandrogenic effect. The antiovulatory potency of the different progestins varies. TMG and NES are the most potent progestins synthesized to date, followed by two of the older progestins, keto-desogestrel (keto-DSG) and levonorgestrel (LNG). The new molecules TMG, DRSP and DNG also have antiandrogenic activity. Striking differences exist regarding the side effects among the progestins and the combination with EE leads to other reactions related to the E itself and whether the associated progestin counterbalances, more or less, the estrogenic action. The 19-norprogesterone molecules and the new molecules DRSP and DNG are not androgenic and, therefore, have no negative effect on the lipid profile. Given their pharmacological properties, it is likely that the new progestins may have neutral effects on metabolic or vascular risks. However, this hypothesis must be confirmed in large clinical trials.
Alveolar hemorrhage. Diagnostic criteria and results in 194 immunocompromised hosts.
Authors: A De Lassence, J Fleury-Feith, E Escudier, J Beaune, J F Bernaudin, C Cordonnier
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

To establish the diagnosis of alveolar hemorrhage (AH) in cells recovered by bronchoalveolar lavage (BAL), Golde and colleagues created a score based on the hemosiderin content of alveolar macrophages stained with Prussian blue. We used an easier method, calculating the percentage of siderophages among the total alveolar macrophages recovered by BAL. We have retrospectively studied this method in 240 BALs performed in 194 immunocompromised patients. Prussian blue staining was performed on each BAL sample, and the Golde score was calculated for 47 samples chosen at random. The methods were compared for diagnosing AH. The percentage of siderophages correlated well with the Golde score. AH was defined by at least 20% siderophages. This definition was validated by comparison with the method of Kahn and coworkers. AH was present in 87 (36%) of the samples and was significantly associated with four parameters: thrombocytopenia (< 50,000/mm3), other abnormal coagulation parameters, renal failure (creatinine > or = 2.5 mg/dl), and a history of heavy smoking. The diagnosis of AH did not correlate with either the cause or the outcome of pneumonia. AH was seen more frequently in cardiac transplant patients (75%). In our experience, (1) a percentage of siderophages > or = 20% is sufficient and is an easier determinant of the diagnosis of AH than the Golde score; and (2) AH is rarely the sole cause of lung injury and is usually associated with other causes of pneumonia. AH may be considered more as a sign than as a distinct disease in this population.
Low Serum Adiponectin Predicts Future Risk for Asthma in Women
Authors: Akshay Sood, Clifford Qualls, Mark Schuyler, Bharat Thyagarajan, Michael W. Steffes, Lewis J. Smith, David R. Jacobs
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Our previous cross-sectional study showed that serum adiponectin is inversely associated with asthma among women. However, it is not known if serum adiponectin predicts future development of asthma or if asthma affects subsequent serum adiponectin concentrations among women.To determine longitudinal association between serum adiponectin and incident asthma among women.We used data from examinations at Years 10, 15, and 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. In our primary analysis, the association of CARDIA Year 15 serum adiponectin concentration with Year 20 incident asthma was evaluated. In our secondary analysis, the converse direction, that is, the association of CARDIA Year 10 prevalent asthma with Year 15 serum adiponectin, was evaluated, using logistic regression techniques.Our primary analysis included 1,450 women, mostly premenopausal. Multivariable analyses demonstrated that the lowest tertile of Year 15 serum adiponectin concentration (<7 mg/L) predicted significantly higher risk for incident asthma at Year 20 among women (odds ratio, 2.07; 95% confidence interval, 1.05, 4.10), and particularly among current smokers (interaction P = 0.051). Further, low serum adiponectin was more important than body mass index in predicting the risk for incident asthma among women. We also showed that the converse relationship was not true; that is, Year 10 prevalent asthma did not predict Year 15 serum adiponectin concentrations in women.Serum adiponectin affects future risk for asthma in women and not vice versa. Measures that raise systemic adiponectin concentrations may lead to newer ways to prevent asthma among women, particularly among those who smoke.
Alimentary-Tract Ganglioneuromatosis
Authors: J. Aidan Carney, Vay L. W. Go, Glen W. Sizemore, Alvin B. Hayles
Journal: New England Journal of Medicine (1976)

Although the syndrome of multiple endocrine neoplasia, type 2b, is known to comprise mucosal ganglioneuromatosis, medullary thyroid carcinoma, pheochromocytoma and skeletal anomalies, we wish to document the importance of the alimentary-tract components. In nine patients with this syndrome, we found diffuse ganglioneuromatosis extending from the lips to the rectum. Alimentary symptoms, constipation or diarrhea or both were present in six of these patients. Similar symptoms were present in six of seven other affected patients from whom alimentary-tract tissue was not obtained. Five of the 16 patients had megacolon, which led to operation in four, and a sixth patient had colectomy for diverticulitis complicating diffuse diverticulosis. The alimentary manifestations warrant greater emphasis, not only because they were prominent in the patients whom we studied but also because in 14, these manifestations were present before the endocrine neoplasms were detected. (N Engl J Med 295:1287–1291, 1976)