tbuckley/cabot-search huggingface dataset:
Epidemiology and survival of idiopathic pulmonary fibrosis from national data in Canada
Authors: Robert B. Hopkins, Natasha Burke, Charlene Fell, Genevieve Dion, Martin Kolb
Journal: European Respiratory Journal (2016)

Idiopathic pulmonary fibrosis (IPF) is a rare disease, with estimates of prevalence varying considerably across countries due to paucity in data collection. The aim of this study was to investigate the prevalence and incidence of IPF in Canada using administrative data requiring minimal extrapolation. We used mandatory national administrative data from 2007–2011 to identify IPF cases of all ages with an International Classification of Diseases (Version 10, Canadian) diagnosis code of J84.1. We used a broad definition that excluded cases with subsequent diagnosis of other interstitial lung diseases, and a narrow definition that required further diagnostic testing prior to IPF diagnosis. We explored survival and quality of life. For all ages, the broad prevalence of IPF was 41.8 per 100 000 (14 259 cases) and was higher for men. The incidence rate was 18.7 per 100 000 (6390 cases) and was higher for men. The narrow prevalence was 20.0 per 100 000 (6822 cases) and incidence was 9.0 per 100 000 (3057 cases). The 4-year risk of death was 41.0% and the quality of life with IPF after 2 years was lower than for Global Initiative for Chronic Obstructive Lung Disease stage IV chronic obstructive pulmonary disease. Using comprehensive national data, the prevalence of IPF in Canada was higher than other national estimates, suggesting that either IPF may be more common in Canada or that data capture may have been previously limited.
Uniform requirements for manuscripts submitted to biomedical journals. International Committee of Medical Journal Editors
Authors: L H Clever, L A Colaianni, F Davidoff, R Glass, R Horton, G Lundberg, M Nylenna, R G Robinson, R Smith, B P Squires, R Utiger, M VanDer Weyden, P Woolf
Journal: JAMA (1997)

In the 13 years since it was first published the "Uniform requirements for manuscripts submitted to biomedical journals" (the Vancouver style), developed by the International Committee of Medical Journal Editors, has been widely accepted by both authors and editors; over 400 journals have stated that they will consider manuscripts that conform to its requirements. This is the fourth edition of the "Uniform requirements."
DUSP8 Regulates Cardiac Ventricular Remodeling by Altering ERK1/2 Signaling
Authors: Ruijie Liu, Jop H. van Berlo, Allen J. York, Ronald J. Vagnozzi, Marjorie Maillet, Jeffery D. Molkentin
Journal: Circulation Research (2016)

Mitogen-activated protein kinase (MAPK) signaling regulates the growth response of the adult myocardium in response to increased cardiac workload or pathological insults. The dual-specificity phosphatases (DUSPs) are critical effectors, which dephosphorylate the MAPKs to control the basal tone, amplitude, and duration of MAPK signaling.To examine DUSP8 as a regulator of MAPK signaling in the heart and its impact on ventricular and cardiac myocyte growth dynamics.Dusp8 gene-deleted mice and transgenic mice with inducible expression of DUSP8 in the heart were used here to investigate how this MAPK-phosphatase might regulate intracellular signaling and cardiac growth dynamics in vivo. Dusp8 gene-deleted mice were mildly hypercontractile at baseline with a cardiac phenotype of concentric ventricular remodeling, which protected them from progressing towards heart failure in 2 surgery-induced disease models. Cardiac-specific overexpression of DUSP8 produced spontaneous eccentric remodeling and ventricular dilation with heart failure. At the cellular level, adult cardiac myocytes from Dusp8 gene-deleted mice were thicker and shorter, whereas DUSP8 overexpression promoted cardiac myocyte lengthening with a loss of thickness. Mechanistically, activation of extracellular signal-regulated kinases 1/2 were selectively increased in Dusp8 gene-deleted hearts at baseline and following acute pathological stress stimulation, whereas p38 MAPK and c-Jun N-terminal kinases were mostly unaffected.These results indicate that DUSP8 controls basal and acute stress-induced extracellular signal-regulated kinases 1/2 signaling in adult cardiac myocytes that then alters the length-width growth dynamics of individual cardiac myocytes, which further alters contractility, ventricular remodeling, and disease susceptibility.
Genetic Diagnosis through Whole-Exome Sequencing
Authors: Paul A van der Zwaag, Jan D H Jongbloed, J Peter van Tintelen
Journal: New England Journal of Medicine (2014)

To the Editor: Yang et al. (Oct. 17 issue)(1) report the application of whole-exome sequencing in 250 patients with a potentially genetic disease, which resulted in a molecular diagnosis in 25% of them. A total of 30 patients had medically actionable incidental findings in a total of 16 genes; 18 of these patients had genotypes that the American College of Medical Genetics and Genomics has recommended be reported to the ordering physician.(2) As noted in the editorial by Jacob,(3) reporting these incidental findings is a gray area. We advocate a role for a team of specialized professionals to interpret such ...
Improving neoadjuvant chemoradiotherapy for rectal cancer with CRLX101, a nanoparticle-drug conjugate, with a camptothecin payload.
Authors: Andrew Wang, Xi Tian, Minh Nguyen, Autumn Jackson McRee, Hanna Kelly Sanoff, Bert H. O'Neil, Meliessa G. Hennessy, Scott Eliasof, Edward Graeme Garmey, Joel E. Tepper
Journal: Journal of Clinical Oncology (2015)

645 Background: There has been great interest in developing novel agents and strategies to improve chemoradiotherapy (CRT) for locally advanced rectal cancer. Irinotecan, a camptothecin (CPT) analogue, held high potential, but the combination was clinically infeasible due to severe gastrointestinal toxicities. CRLX101, a dynamically tumor targeted nanoparticle-drug conjugate differentially delivers CPT into cancer cells and appears to durably suppress HIF-1α as well as topoisomerase 1, but with less gastrointestinal toxicities than irinotecan. We therefore hypothesized that the addition of CRLX101 to CRT may further improve the therapeutic index in this setting. Methods: CRLX101 was evaluated using murine flank xenograft models (SW480 and HT29) of colorectal cancer alone or in combination with radiotherapy (XRT) and/or 5-FU and compared to CPT plus CRT. Skin toxicity and hematologic toxicity were also studied. In addition, a Phase Ib/II clinical trial (LCCC1315) evaluating the addition of CRLX101 to CRT in the neo-adjuvant treatment of rectal cancer is currently underway. A standard 3 + 3 design was used for the phase Ib with a CRLX101 starting dose of 12 mg/m 2 in the first cohort escalating to the CRLX101 monotherapy MTD of 15 mg/m 2 in the second. The primary phase 2 end-point is the pathological complete response (pCR) rate from treatment. Results: In the HT29 xenografts model, CRLX101+5FU+XRT delayed tumor growth significantly more than the other treatment regimens evaluated. In the SW480 xenografts model, both CRLX101+5FU+XRT and CRLX101+XRT delayed tumor growth more than other regimens, but there was no statistical advantage to the addition of 5-FU to CRLX101+XRT in this model. The addition of CRLX101 to 5FU+XRT did not increase hematologic or skin toxicities. In the ongoing clinical trial, none of the first 3 patients enrolled (the first dosing cohort) have experienced dose limiting toxicities and 1 out of 3 patients had a pCR. Conclusions: CRLX101 has been shown in preclinical experiments to improve the therapeutic index of CRT for rectal cancer. Preliminary clinical data suggest that CRLX101+5FU+XRT treatment is well tolerated. Clinical trial information: NCT02010567.
Response to opioids in three patients with restless legs syndrome
Authors: P T Trzepacz, E J Violette, M J Sateia
Journal: American Journal of Psychiatry (1984)

Three patients with restless legs syndrome, two of whom also had nocturnal myoclonus, responded well to treatment with low doses of opioids. The pathophysiology of the syndrome and the mechanism of opioids' therapeutic action are discussed.
Glucocorticoid resistance in depression: the dexamethasone suppression test and lymphocyte sensitivity to dexamethasone
Authors: M T Lowy, A T Reder, J P Antel, H Y Meltzer
Journal: American Journal of Psychiatry (1984)

Approximately 50% of depressed patients are resistant to the cortisol-suppressing effect of dexamethasone. To determine if glucocorticoid resistance could be a more generalized phenomenon in depressed patients, mitogen stimulation tests were performed on lymphocytes from 12 depressed patients and 12 control subjects before and after dexamethasone administration. Suppression of serum cortisol following administration of 1 mg of dexamethasone in four depressed patients and 11 control subjects was associated with a decreased lymphoproliferative response, but no such change occurred in the eight depressed patients and the single control subject who did not suppress cortisol. The dexamethasone-induced changes in the mitogen responses were positively correlated with the highest postdexamethasone serum cortisol values.
Bone Marrow Cell Based Enzyme Replacement Prolongs Survival and Improves Disease Phenotypes In a Mouse Model Of Lethal Hypophosphatasia
Authors: Osamu Iijima, Koichi Miyake, Aki Nakamura, Tsutomu Igarashi, Chizu Kanokoda, Atsushi Watanabe, Takashi Shimada
Journal: Blood (2013)
Duration of psychosis and outcome in first-episode schizophrenia
Authors: A D Loebel, J A Lieberman, J M Alvir, D I Mayerhoff, S H Geisler, S R Szymanski
Journal: American Journal of Psychiatry (1992)

This study was undertaken to assess the potential effect of duration of untreated illness on outcome in a group of first-episode schizophrenic patients.Seventy patients with schizophrenia diagnosed according to the Research Diagnostic Criteria entered the study and were followed for up to 3 years. All patients received standardized treatment and uniform assessments both during the acute phase of their illness and throughout the follow-up period. Outcome was measured in terms of time to remission of acute psychotic symptoms as well as degree of symptom remission.The mean duration of psychotic symptoms before initial treatment was 52 weeks, preceded by a substantial prepsychotic period. According to survival analysis, duration of illness before treatment was found to be significantly associated with time to remission as well as with level of remission. The effect of duration of illness on outcome remained significant when diagnosis and gender variables, themselves associated with outcome, were controlled in a regression analysis. Duration of illness was not correlated with age at onset, mode of onset, premorbid adjustment, or severity of illness at entry into the study.Duration of psychosis before treatment may be an important predictor of outcome in first-episode schizophrenia. Acute psychotic symptoms could reflect an active morbid process which, if not ameliorated by neuroleptic drug treatment, may result in lasting morbidity. Further implications of these findings are discussed.
Effect of chloride or glucose on the incidence of lactate-induced panic attacks
Authors: D T George, T Lindquist, D J Nutt, P W Ragan, T Alim, V McFarlane, J Leviss, M J Eckardt, M Linnoila
Journal: American Journal of Psychiatry (1995)

This study was designed to test the hypothesis that the addition of chloride to a lactate infusion would reduce the frequency of panic attacks.The subjects included 14 healthy volunteers and 20 patients meeting the DSM-IV criteria for panic disorder. All subjects received an infusion of lactate dissolved in 0.9% sodium chloride and an infusion of lactate dissolved in 5% dextrose in water on separate days in a random-order, double-blind procedure. Blood pressure, heart rate, and panic symptoms were measured at 3-minute intervals during the infusions. The occurrence of panic attacks was ascertained through the subjects' reports of losing control, panicking, or "going crazy" and the presence of at least four Research Diagnostic Criteria symptoms of a panic attack.Fifteen (75%) of the patients with panic disorder reported a panic attack during one of the infusions or both; no healthy volunteers had a panic attack. The patients with panic disorder were significantly more likely to have a panic attack during the lactate/sodium chloride infusion than during the infusion of lactate/5% dextrose in water. The number of panic attack symptoms reported at 3-minute intervals did not differ between the two types of infusion.The coadministration of glucose resulted in a reduced sensitivity to the panicogenic effects of lactate. The hypothesis that adding chloride to the infusion would reduce the frequency of lactate-induced panic attacks was not supported.
On Boro-Glyceride in Operative Surgery
Authors: R. Barwel
Journal: BMJ (1882)

CASE VI.Central Necrosis of Astragalus.-FrancesS., aged -12, a delicate looking girl, was admitted on December x8th, i88i.Twelve months before admission, swelling appeared on the outer side of the ankle.Pain, most severe -at night, preceded the swelling 'by some months.Gradually the whole ankle-joint became soft.and swollen, like an ordinary white swelling of the ankle.Tenderness on pressure was most marked over the lower end of the fibula.A plaster-of-Paris splint was worn till March 2ISt, I882, when she returned to the hospital, feeling no better.In less than a month after removing the plaster-of- Paris, and whilst the limb was still kept fixed, the ankle-joint showed undoubted signs of suppuration; the temperature rose, and rigors set in.On April 17th, an incision was therefore made in front of the inner, and another behind and below the' outer, malleolus.On intro- ducing the finger into the outer wound, I felt a small movable frag- ment of rough bone close to the' articular facet for the outer malleolus.This was lodged in a cavity in the astragalus which was large enough, after the removal of the fragment, to receive the tip of the finger, and was limited' by perfectly smooth and uniformly hard walls.The joint was washed out with a solution of tincture of iodine, the wounds covered with terebene and oil on lint, and the limb immovably fixed on a splint.Subsequently, the terebene was changed for iodoform, which was dusted over the weak exuberant granulations-which had fotmed.The limb was still kept immovably fixed.No pain has been suffered since the operation; the joint has resumed almost its natural shape, and the wounds are all but cicatrised.I look forward to the patient recover- ing with a slightly movable joint.REMARKS.-The operation which was performed in these cases was not, strictly speaking, trephining.In two of them, after dividing the periosteum by a linear incision, and peeling it off for a certain dis- tance, pus was seen to ooze up through a small opening in the bone; and the abscess-cavity was opened up by applying the gouge to this spot.In three other cases, after dividing and peeling off the periosteum in the same way, a drill was first introduced, and then the drill-hole was enlarged with the gouge.It is not always sufficient to use a drill under the impression that, if a cavity be reached, pus will escape from it along the side of the drill, or through the hole made by it, after its removal; for, as Case I shows, a little pus with a fragment of necrosed bone may occupy a cavity, but not declare itself by welling up; or the pus may be only semifluid', and too thick to flow, as in Case v.Under
Memorial to Dr. Fairlie Clarke
Authors: V. Pearson
Journal: BMJ (1885)

If my memory serves me, Mr. Braine, in a paper read before the Medical Society of London, advocated the employment of Ormsby's inhaler.This instrument is open to the objection that it allows a saturated atmosphere of ether to impinge suddenly upon the delicate and sensitive mucous membrane of the larynx and respiratory tract in general, often giving rise to most alarming dyspnoea from spasm of the glottis.This, then, is one of the many dangers
Body surface area as a prognostic marker in chronic heart failure patients: results from the Heart Failure Registry of the Heart Failure Association of the European Society of Cardiology
Authors: Barak Zafrir, Nabeeh Salman, Maria G. Crespo‐Leiro, Stefan D. Anker, Andrew J. Coats, Roberto Ferrari, Gerasimos Filippatos, Aldo P. Maggioni, Alexandre Mebazaa, Massimo Francesco Piepoli, Frank Ruschitzka, Maria J. Paniagua‐Martin, Javier Segovia, Cecile Laroche, Offer Amir
Journal: European Journal of Heart Failure (2016)
Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma
Authors: Meletios A. Dimopoulos, Antonio Palumbo, Paolo Corradini, Michele Cavo, Michel Delforge, Francesco Di Raimondo, Katja C. Weisel, Albert Oriol, Markus Hansson, Angelo Vacca, María Jesús Blanchard, Hartmut Goldschmidt, Chantal Doyen, Martin Kaiser, Mario Petrini, Pekka Anttila, Anna Maria Cafro, Reinier Raymakers, Jesus San-Miguel, Felipe de Arriba, Stefan Knop, Christoph Röllig, Enrique M. Ocio, Gareth Morgan, Neil Miller, Mathew Simcock, Teresa Peluso, Jennifer Herring, Lars Sternas, Mohamed H. Zaki, Philippe Moreau
Journal: Blood (2016)
A Note on the Occurrence of Virus-like Particles in the Spontaneous Hepatomas of C3H Mice&lt;xref ref-type="fn" rid="fn1"&gt;1&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: D W FAWCETT, J W WILSON
Journal: JNCI Journal of the National Cancer Institute (1955)

Journal Article A Note on the Occurrence of Virus-like Particles in the Spontaneous Hepatomas of C3H Mice, Get access Don W. Fawcett, Don W. Fawcett Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Walter Wilson J. Walter Wilson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue Supplement_5, April 1955, Pages 1505–1511, https://doi.org/10.1093/jnci/15.Supplement_5.1505 Published: 01 April 1955
Abstract P6-02-04: Screen detected and interval cancers; genomic analysis points to different molecular etiology?
Authors: KL Gorringe, SM Hunter, D Byrne, L Devereux, SM Rowley, K Elder, R Huynh, V Pridmore, J Hopper, A Kavanagh, G Mitchell, BG Mann, SB Fox, IG Campbell
Journal: Cancer Research (2016)

Abstract Breast cancers diagnosed after a negative mammogram but prior to the next screening episode are termed "interval cancers" and comprise as many as 25% of all cancers detected in women attending population-based screening programs. The high interval cancer rate is a major problem affecting the effectiveness of mammographic screening. It is unclear whether interval cancers represent a distinct biological entity compared to screen-detected cancers or whether their designation is simply an arbitrary outcome of screening timing. Using an Australian prospective population-based cohort of over 53,000 women (lifepool), 537 cases of breast carcinoma (in situ and invasive breast cancer) were identified, of which 293 had known screening status at time of diagnosis. Pathology reports, mammographic density data, germline DNA and tumor tissue were available for analysis. Screen and interval cases showed no significant differences in mammographic density or PR status but there were trends towards higher proportions of ER negative and HER2 positive cases in interval cancers (p&amp;lt;0.1). Interval cancers also had a younger age at diagnosis (p&amp;lt;0.01), increased tumor size (p&amp;lt;0.01) and higher grade (p&amp;lt;0.01). Copy number analysis was performed on a subset of invasive breast cancer cases using OncoScan MIP arrays. No difference in the overall number of copy number aberrations or fraction of the genome altered were observed, however specific differences were noted between interval and screen detected cases. These included copy number changes on chromosomes 8 and 11. Analysis of germline DNA was performed using a panel sequencing approach of known breast cancer genes as well as lower-penetrance SNPs. Pathogenic mutations in BRCA1, BRCA2, TP53 and PALB2 were identified in 1/13 interval cases (in BRCA2), 1/66 screen-detected cases and 8/74 cases with currently unknown screen/interval status. Screen detected cancers may thus have a reduced contribution from high-penetrance predisposing variants. Citation Format: Gorringe KL, Hunter SM, Byrne D, Devereux L, Rowley SM, Elder K, Huynh R, Pridmore V, Hopper J, Kavanagh A, Mitchell G, Mann BG, Fox SB, Campbell IG. Screen detected and interval cancers; genomic analysis points to different molecular etiology?. [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 P6-02-04.
Predisposing Factors for Any and Major Hypoglycemia With Saxagliptin Versus Placebo and Overall: Analysis From the SAVOR-TIMI 53 Trial
Authors: Avivit Cahn, Itamar Raz, Ofri Mosenzon, Gil Leibowitz, Ilan Yanuv, Aliza Rozenberg, Nayyar Iqbal, Boaz Hirshberg, Mikaela Sjostrand, Christina Stahre, KyungAh Im, Estella Kanevsky, Benjamin M. Scirica, Deepak L. Bhatt, Eugene Braunwald
Journal: Diabetes Care (2016)

OBJECTIVE To analyze the impact of adding saxagliptin versus placebo on the risk for hypoglycemia and to identify predictors of any and major hypoglycemia in patients with type 2 diabetes included in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) study. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes (n = 16,492) were randomized to saxagliptin or placebo and followed for a median of 2.1 years. Associations between any hypoglycemia (symptomatic or glucose measurement &amp;lt;54 mg/dL) or major hypoglycemia (requiring extended assistance) and patient characteristics overall and by treatment allocation were studied. RESULTS At least one hypoglycemic event was reported in 16.6% of patients, and 1.9% reported at least one major event. Patients allocated to saxagliptin versus placebo experienced higher rates of any (hazard ratio [HR] 1.16 [95% CI 1.08, 1.25]; P &amp;lt; 0.001) or major (HR 1.26 [1.01, 1.58]; P = 0.038) hypoglycemia. Hypoglycemia rates (any or major) were increased with saxagliptin in patients taking sulfonylureas (SURs) but not in those taking insulin. Rates were increased with saxagliptin in those with baseline HbA1c ≤7.0% and not in those with baseline HbA1c &amp;gt;7.0%. Multivariate analysis of the overall population revealed that independent predictors of any hypoglycemia were as follows: allocation to saxagliptin, long duration of diabetes, increased updated HbA1c, macroalbuminuria, moderate renal failure, SUR use, and insulin use. Predictors of major hypoglycemia were allocation to saxagliptin, advanced age, black race, reduced BMI, long duration of diabetes, declining renal function, microalbuminuria, and use of short-acting insulin. Among SURs, glibenclamide was associated with increased risk of major but not any hypoglycemia. CONCLUSIONS The identification of patients at risk for hypoglycemia can guide physicians to better tailor antidiabetic therapy.