tbuckley/cabot-search huggingface dataset:
Effect of a spacer on pulmonary aerosol deposition from a jet nebuliser during mechanical ventilation.
Authors: C J Harvey, M J O'Doherty, C J Page, S H Thomas, T O Nunan, D F Treacher
Journal: Thorax (1995)

Several factors have been identified which improve nebulised aerosol delivery in vitro. One of these is the addition of a spacer to the ventilator circuit which improves aerosol delivery from a jet nebuliser to a model lung by approximately 30%. The current study was designed to demonstrate whether similar improvements could be demonstrated in vivo.Ten patients (seven men) were studied during mechanical ventilation (Siemens Servo 900C) after open heart surgery. Aerosol was delivered using a Siemens Servo 945 nebuliser system (high setting) driving a System 22 Acorn jet nebuliser (Medic-Aid) containing 3 ml technetium-99m labelled human serum albumin (99mTc-HSA (50 micrograms); activity in the first nebulisation, 90 MBq; in the second nebulisation, 185 MBq). Central and peripheral lung aerosol deposition and the time to complete deposition were measured using a gamma camera and compared when the nebuliser was connected to the inspiratory limb using a simple T-piece or a 600 ml spacer.The addition of the spacer increased total lung deposition (mean (SD) percentage initial nebuliser activity) from 2.2 (0.7)% to 3 (0.8)%. There was no difference in the time required to complete nebulisation (18.2 min v 18.3 min respectively for T-piece and spacer) or in the retention of activity in the nebuliser (46.2% v 47.1% respectively).The combination of a spacer with a jet nebuliser increased lung deposition by 36% in mechanically ventilated patients and is a simple way of increasing drug deposition or reducing the amount of an expensive drug required for nebulisation.
Screening and outcomes in biliary atresia: Summary of a National Institutes of Health workshop
Authors: Ronald J. Sokol, Ross W. Shepherd, Riccardo Superina, Jorge A. Bezerra, Patricia Robuck, Jay H. Hoofnagle
Journal: Hepatology (2007)

Biliary atresia is the most common cause of end-stage liver disease in the infant and is the leading pediatric indication for liver transplantation in the United States. Earlier diagnosis (<30-45 days of life) is associated with improved outcomes following the Kasai portoenterostomy and longer survival with the native liver. However, establishing this diagnosis is problematic because of its rarity, the much more common indirect hyperbilirubinemia that occurs in the newborn period, and the schedule for routine infant health care visits in the United States. The pathogenesis of biliary atresia appears to involve immune-mediated fibro-obliteration of the extrahepatic and intrahepatic biliary tree in most patients and defective morphogenesis of the biliary system in the remainder. The determinants of the outcome of portoenterostomy include the age at surgery, the center's experience, the presence of associated congenital anomalies, and the postoperative occurrence of cholangitis. A number of screening strategies in infants have been studied. The most promising are early measurements of serum conjugated bilirubin and a stool color card given to new parents that alerts them and their primary care provider to alcholic stools. This report summarizes a National Institutes of Health workshop held on September 12 and 13, 2006, in Bethesda, MD, that addressed the issues of outcomes, screening, and pathogenesis of biliary atresia.
Verbal Toys in the "Otic"-Reply
Authors: Alexander Gode
Journal: JAMA (1964)

Regarding Dr. Ransom's interesting list: Webster describes "-otic" as a suffix "forming adjectives corresponding to nouns ending in -<i>osis</i>... to be distinguished from -ic following stems ending in -<i>ot.</i>" I have often thought of collecting unpaired formations in "-osis" and "-otic" in order to determine whether there is a principle or at least a trend according to which the language chooses or does not choose to make use of the potentially available "-osis/-otic" pattern. Now I have the beginning of such a collection. I confess I too enjoy the not very dignified game of building words like "idiosis" from "idiotic" (by simply not heeding Webster's warning about "-ic" after "-ot"). But my favorite is not "idiosis"; it is "erosis."
Profession, press, and television.
Authors: A M Campbell
Journal: BMJ (1970)

well, flatly denied that a patient with a par- ticular condition was in the hospital.The administrator, however, after several calls, agreed that such a patient was there but that premature publicity might cause her anxiety and hazard her health.I therefore agreed not to write anything.When I challenged the doctor with this information he said, "I just wanted to throw you off the scent."This sort of experience makes the plea that journalists should treat doctors more gently seem rather hollow.Doctors with ex- perience of reputable journalists will know that reporters frequently are asked and agree to keep confidence about something, even if it is only to preserve a doctor's identity to protect him from charges of advertising.But if a doctor has a grievance about in- accurate reporting or unethical behaviour by reporters he has the remedy in his own hands.A complaint to the newspaper or perhaps to the Press Council can have a very sobering effect on the journalist involved.It is significant that the Press Council confirms that complaints from doctors about medical matters are extremely rare.-Iam, etc.,
Abstract 4389: Copper and platinum uptake in cultured rat dorsal root ganglion neurons
Authors: Johnson J. Liu, Yaeseul Kim, Julian F.B. Mercer, Mark J. McKeage
Journal: Cancer Research (2011)

Abstract Peripheral neuropathy is a dose-limiting toxicity of platinum drugs due to their accumulation in the dorsal root ganglia (DRG) and damage to sensory neurons. Our previous studies showed a specific pattern of expression of copper transporters in rat DRG tissue (Liu JJ et al 2009; Ip V et al 2010). Here we aimed to investigate their functional activity in the uptake of copper and platinum in cultured DRG neurons in vitro. Dissociated rat DRG neurons were cultured in N2-supplemented Neurobasal-A medium. Cellular metal levels were measured by the inductively coupled plasma mass spectrometry. The copper content of the cultured DRG neurons increased linearly with time (R2, 0.7952 ∼ 0.8903) during a one hour exposure to 3 ∼ 100 µM of CuCl2. The rate of cellular uptake of copper had nonlinear dependence (R2, 0.9629) on the exposure concentration of CuCl2, with a maximal uptake rate of 0.237 ± 0.041 nmole/min/mg protein and CuCl2 concentration achieving half-maximal uptake of 49.1 µM. The uptake of copper was temperature-dependent, stimulated by ascorbate and inhibited by zinc. CTR1 mRNA was detectable in cultured DRG neurons and its protein co-localised with microtubule-associated protein 2-positive neuronal cell bodies. Oxaliplatin inhibited copper uptake by DRG neurons and their platinum content increased linearly with time (R2, 0.916) during a one hour oxaliplatin exposure. In conclusion, CTR1 is functionally expressed by rat DRG neurons in primary culture. Oxaliplatin accumulates and inhibits copper uptake in DRG neurons. Supported by research grants from Cancer Society of New Zealand and McBeath Child Cancer Trust Fund. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4389. doi:10.1158/1538-7445.AM2011-4389
Abstract 029: Racial Disparities in Coronary Heart Disease Mortality in the Regards Study
Authors: Monika Safford, Todd M Brown, Christopher Gamboa, Raegan W Durant, Stephen P Glasser, Jewell Halanych, James M Shikany, Ronald Prineas
Journal: Circulation (2013)

Background: Coronary heart disease (CHD) mortality has long been higher among US blacks compared with whites, especially among younger individuals. Recent progress on eliminating these disparities has not been reported. Methods: We examined CHD mortality in the REGARDS study, a 30,239-member national prospective cohort study that oversampled blacks (41%) and residents of the southeastern US, recruiting from 2003-7. Baseline data included interviews and in-home collection of physiologic and medication data. Telephone follow-up was conducted every 6 months to detect endpoints, triggering medical record retrieval and expert adjudication. Deaths prompted interviews with next-of-kin or proxies, collection of medical records and death certificates. We examined risks for definite or probable CHD mortality overall, and separately for in-hospital and out-of-hospital CHD death. Cox models stratified on age 65 estimated hazard ratios (HR) for CHD mortality for blacks compared with whites, adjusting for sociodemographics and CHD risk factors. Results: We analyzed 14,992 participants &lt;65 years of age (44% blacks) and 14,678 &gt;65 years of age (38% blacks). There were 126 CHD deaths among those age &lt;65 and 273 among those age &gt;65 over a mean follow-up of 4.2+1.5 SD years. Adjusting for age and region of residence, excess risks among blacks were generally more pronounced for those age &lt;65, but this excess risk attenuated after adding all risk factors, except for in-hospital mortality for those &gt;65 years of age (Table). Conclusions: Risks for CHD mortality were higher among blacks, largely attributable to higher risk factor burden especially among the young, suggesting that targeted intervention efforts are needed to overcome this disparity. The excess risk for in-hospital mortality among older blacks warrants further attention.
P308 HISTOLOGICAL HEPATOCYTE DAMAGE PRECEDES STEATOSIS IN ALD PATIENTS WITH GENETIC VARIANT L148M IN PNPLA3
Authors: V. Rausch, T. Peccerella, H.K. Seitz, F. Stickel, E. Yagmur, S. Herzig, T. Longerich, S. Mueller
Journal: Journal of Hepatology (2014)
Complete Rupture of the Left Main Bronchus With Successful Repair
Authors: John V. Comer
Journal: JAMA (1966)

RUPTURE OF A MAJOR bronchus is now recognized as a complication of severe crushing trauma to the thorax. The first recorded case was seen at autopsy more than 75 years ago, and the first surgical success in the treatment of this condition was 15 years ago. The earliest case report was one by Seuvre<sup>1</sup>in 1873, where at postmortem examination of a 74-year-old woman, the right main-stem bronchus was completely separated from the trachea. Subsequently, necropsy cases are scattered in the literature until 1928 when Krinitzki<sup>2</sup>reported the first instance of survival with this lesion. In his patient, at autopsy 21 years after injury, an occluded right main bronchus was found. It was not until 1949, however, that Griffith<sup>3</sup>reported the first patient to be treated successfully by excision of the strictured segment of bronchus and restoration of bronchial continuity. Since that time, frequent reports of surgical
Dementia strategy should focus on reducing risks and promoting brain health, say experts
Authors: M. Limb
Journal: BMJ (2014)

Leading scientists have backed calls for a fresh policy approach to combat dementia in the United Kingdom by focusing on reducing risk factors and promoting brain health throughout people’s lives. They said that “a substantial proportion of dementia might be delayed or averted if modifiable risk factors are effectively addressed.”

The UK Health Forum and Public Health England launched a consensus statement on 20 May signed by 59 experts and organisations, including practitioners and researchers in dementia, public health, and non-communicable disease (NCD) prevention.1 It said recent evidence showed that the population’s risk might be reduced so that fewer people at particular ages developed dementia. The evolving evidence was now “sufficient” to justify action and further research on dementia risk reduction by “reducing the modifiable risk factors and improving the recognised protective factors,” the statement said.

The experts described a “compelling” case for dementia risk reduction to be incorporated into health policies that are designed to tackle NCDs, to make better use of current efforts and resources. …
Communication—the forgotten palliative care emergency
Authors: Mark Pickering, Rob George
Journal: BMJ (2007)

<h3>AIMS</h3> To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. <h3>METHODS</h3> A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. <h3>RESULTS</h3> The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. <h3>CONCLUSIONS</h3> The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.
Phosphorescent Light–Emitting Iridium Complexes Serve as a Hypoxia-Sensing Probe for Tumor Imaging in Living Animals
Authors: Shaojuan Zhang, Masahiro Hosaka, Toshitada Yoshihara, Kazuya Negishi, Yasuhiko Iida, Seiji Tobita, Toshiyuki Takeuchi
Journal: Cancer Research (2010)

Iridium complex is a promising organic light-emitting diode material for next generation video displays that emits phosphorescence quenched by oxygen. We used this oxygen-quenching feature for imaging tumor hypoxia. Red light-emitting Ir(btp)(2)(acac) (BTP) presented hypoxia-dependent light emission in culture cell lines, whose intensity was in parallel with hypoxia-inducible factor-1alpha images. BTP was further applied to imaging five nude mouse transplanted with tumors. All tumors presented a bright BTP-emitting image even 5 minutes after injection. The minimal image recognition size was approximately 2 mm in diameter. By morphologic examination and phosphorescence lifetime measurement, BTP appeared to localize to the tumor cells. Because BTP is easily modifiable, we synthesized BTP analogues with a longer excitation/emission wavelength. One of them, BTPHSA, depicted clear imaging from tumors transplanted 6 to 7 mm deep from the skin surface. We suggest that iridium complex materials have a vast potential for imaging hypoxic lesions such as tumor tissues.
Grammar and brain
Authors: Helmut Schnelle
Journal: Behavioral and Brain Sciences (2003)

Jackendoff's account of relating linguistic structure and brain structure is too restricted in concentrating on formal features of computational requirements, neglecting the achievements of various types of neuroscientific modelling. My own approaches to neuronal models of syntactic organization show how these requirements could be met. The book's lack of discussion of a sound philosophy of the relation is briefly mentioned.
Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1–infected patients
Authors: Eric G. Meissner, Yu‐Jin Lee, Anu Osinusi, Zayani Sims, Jing Qin, Dan Sturdevant, John McHutchison, Mani Subramanian, Maureen Sampson, Susanna Naggie, Keyur Patel, Alan T. Remaley, Henry Masur, Shyam Kottilil
Journal: Hepatology (2014)

Hepatitis C virus (HCV) modulates intrahepatic cholesterol biosynthetic pathways to promote viral replication. Chronic HCV infection is associated with altered metabolism, including dyslipidemia and insulin resistance (IR), which contributes to disease progression and influences response to therapy. To further understand the impact of HCV infection on host metabolism, we examined changes in serum lipid profiles and intrahepatic expression of lipid-related genes during interferon (IFN)-free treatment of chronic HCV, genotype 1 infection with sofosbuvir and ribavirin (RBV), and explored associations with treatment outcome. Serum lipids (total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], and triglycerides [TGs]) and hemoglobin A1C (HbA1C) were measured during treatment, while gene expression of lipid-related genes was assessed using paired pre- and end-of-treatment (EOT) liver biopsies from 8 patients (n=7 sustained virologic response [SVR]; n=1 relapse) and unpaired EOT liver biopsies from 25 patients (n=17 SVR; n=8 relapse). Serum LDL concentration and particle size increased early in therapy, whereas TG concentration and very-low-density lipoprotein particle size decreased concomitantly, irrespective of treatment outcome. Whereas LDL increased in patients regardless of treatment outcome, average LDL concentration was lower at baseline and post-treatment in patients who relapsed. Analysis of paired liver biopsies revealed altered expression of genes associated with lipid transport, assembly, and signaling. In unpaired EOT liver biopsies, intrahepatic expression of fatty acid metabolism and lipid transport genes was lower in patients who experienced treatment relapse.
Abstract PR5: Therapeutic targeting of oncogene-specific tyrosine kinase networks during prostate cancer progression
Authors: Justin M. Drake, Jiaoti Huang, Thomas G. Graeber, Owen N. Witte, Nicholas A. Graham, Tanya Stoyanova, Amir Sedghi, Andrew S. Goldstein, Houjian Cai, Daniel A. Smith, Hong Zhang, Komisopoulou Evangelia
Journal: Cancer Research (2012)

Abstract Dominant activating mutations or DNA amplification of tyrosine kinases are not readily observed despite the numerous oncogenic alterations implicated in prostate cancer. We demonstrate that castration resistant prostate cancer (CRPC) exhibits increased tyrosine phosphorylation, raising the question of whether enhanced tyrosine kinase activity is observed in this disease in the absence of specific tyrosine kinase mutations. We generated a mouse model of prostate cancer progression using combinations of commonly perturbed non-tyrosine kinase oncogenes and pathways, including myristoylated Akt (Akt), androgen receptor (AR), Erg, and activated Kras (KrasG12V). We recapitulated the different stages of prostate cancer ranging from prostatic intraepithelial neoplasia (PIN) (Akt) to low grade cancer (Akt+Erg) to highly aggressive prostatic adenocarcinoma (Akt+AR or Akt+KrasG12V). We detected a significant upregulation of tyrosine phosphorylation at the advanced adenocarcinoma stage. Phosphotyrosine peptide enrichment and quantitative mass spectrometry identified oncogene-specific tyrosine kinase signatures, including activation of Egfr Y1172 (Akt+Erg), EphA2 Y595 (Akt+KrasG12V), and Jak2 Y1007/08 (Akt+AR). Kinase:substrate relationship analysis of the phosphopeptides also revealed Abl Y245 and Src Y416 tyrosine kinase activation in Akt+AR tumors; known targets of the tyrosine kinase inhibitor Dasatinib. We are currently evaluating the efficacy of tyrosine kinase inhibitors Dasatinib or Erlotinib on non-tyrosine kinase driven tumors Akt+AR or Akt+Erg, respectively. In summary, the observation of elevated phosphotyrosine signaling in advanced prostate cancer and identification of specific tyrosine kinase pathways from genetically-defined tumor models points to new therapeutic approaches using tyrosine kinase inhibitors for advanced prostate cancer. This abstract is also presented as Poster C35. Citation Format: Justin M. Drake, Jiaoti Huang, Thomas G. Graeber, Owen N. Witte, Nicholas A. Graham, Tanya Stoyanova, Amir Sedghi, Andrew S. Goldstein, Houjian Cai, Daniel A. Smith, Hong Zhang, Evangelia Komisopoulou. Therapeutic targeting of oncogene-specific tyrosine kinase networks during prostate cancer progression [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr PR5.
Abstract 4295: Multifunctional nanoconstructs for tumor visualization using contrast enhanced MRI
Authors: Jeyarama Ananta, Richa Sethi, Ayrat Gizzatov, Ghanashyam Acharya, Xuewu Liu, Christof Karmonik, Lon Wilson, Paolo Decuzzi
Journal: Cancer Research (2012)

Abstract New multifunctional nanoconstructs using mesoporous Si particles (SiMPs) and polymeric hydrogel particles (HG) are synthesized with superior MRI efficacy and favorable pharmacokinetic properties. Clinically relevant Gd3+-based contrast agents (CAs) for magnetic resonance imaging (MRI), namely [Gd (DTPA)]2−, [Gd (DOTA)]1- and superparamagnetic iron oxide (SPIO) nanoparticles, were either i) encapsulated within the mesoporous structure of the SiMPs or ii) covalently attached to SiMPs and HGs. The size (from 400 to 2000 nm) and shape (discoidal, cylindrical, etc.) of the nanoconstructs are accurately tailored during the fabrication process to control the in vivo biodistribution. In tumor bearing mouse model, discoidal particles with a characteristic size of 1000 x 400 nm were found to accumulate at the tumor site more than other particles. The incorporation of clinically used, FDA approved CAs into the mesoporous structure of the SiMPs led to magnetic nanoconstructs exhibiting much higher relaxivities as compared to free CAs in solution. In particular, the relaxivity for [Gd (DTPA)]2− and [Gd (DOTA)]−1 loaded SiMPs was measured to be ∼ 25 mM−1s−1, which is more than 6 times larger than the r1 obtained for free CAs (∼ 4 mM−1s−1). The pore size played a dominant role in that the relaxivity was observed to grow with a reduction in pore diameter: r1 ∼ 24 mM−1s−1 for small pore SiMPs (5-10 nm); and r1 ∼ 10 mM−1s−1 for huge pore SiMPs (30-40 nm). CAs covalently attached to SiMPs and HGs, exhibited no such dependence on pore sizes but provided comparable enhancement in r1. For SPIOs encapsulated in mesoporous SiMPs, a much larger enhancement in relaxivity was observed with r2 ∼ 220 mM−1s−1 for the resulting nanoconstructs against r2 ∼ 11.2 mM−1s−1 for free SPIOs. These results suggest that geometrical confinement into mesopores is a general strategy for enhancing the performance of both T1 and T2 MRI CAs. Intravenous injection of SPIO-loaded SiMPs in melanoma bearing mice decreased the contrast (T2-weigthed relaxation), confirming the high level of accumulation of these nanoconstructs at the tumor site. For the enhanced relaxivity and superior localization of imaging agents at the target site, the proposed nanoconstructs provide an ideal platform for early cancer detection by MRI. In addition, the easily functionalizable surface of these nanoconstructs render them the ability to perform cellular and molecular imaging using clinical MRI scanners. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4295. doi:1538-7445.AM2012-4295