tbuckley/cabot-search huggingface dataset:
<i>HER2</i>and Responsiveness of Breast Cancer to Adjuvant Chemotherapy
Authors: Kathleen I. Pritchard, Lois E. Shepherd, Frances P. O'Malley, Irene L. Andrulis, Dongsheng Tu, Vivien H. Bramwell, Mark N. Levine
Journal: New England Journal of Medicine (2006)

Amplification of the human epidermal growth factor receptor type 2 (HER2, also called HER2/neu) gene and overexpression of its product in breast-cancer cells may be associated with responsiveness to anthracycline-containing chemotherapy regimens.In the randomized, controlled Mammary.5 trial, we studied 639 formalin-fixed paraffin-embedded specimens obtained from 710 premenopausal women with node-positive breast cancer who had received either cyclophosphamide, epirubicin, and fluorouracil (CEF) or cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant chemotherapy. HER2 amplification or overexpression was evaluated with the use of fluorescence in situ hybridization, immunohistochemical analysis, and polymerase-chain-reaction analysis.Amplification of HER2 was associated with a poor prognosis regardless of the type of treatment. In patients whose tumors showed amplification of HER2, CEF was superior to CMF when assessed on the basis of relapse-free survival (hazard ratio, 0.52; 95 percent confidence interval, 0.34 to 0.80; P=0.003) and overall survival (hazard ratio, 0.65; 95 percent confidence interval, 0.42 to 1.02; P=0.06). For women whose tumors lacked amplification of HER2, CEF did not improve relapse-free survival (hazard ratio for relapse, 0.91; 95 percent confidence interval, 0.71 to 1.18; P=0.49) or overall survival (hazard ratio for death, 1.06; 95 percent confidence interval, 0.83 to 1.44; P=0.68). The adjusted hazard ratio for the interaction between treatment and HER2 amplification was 1.96 for relapse-free survival (95 percent confidence interval, 1.15 to 3.36; P=0.01) and 2.04 for overall survival (95 percent confidence interval, 1.14 to 3.65; P=0.02).Amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracycline-containing chemotherapy. (cancer.gov number, NCI-V90-0027.).
Inhibition of STAT3Tyr705 Phosphorylation by Smad4 Suppresses Transforming Growth Factor β–Mediated Invasion and Metastasis in Pancreatic Cancer Cells
Authors: Shujie Zhao, Kolaparthi Venkatasubbarao, Jillian W. Lazor, Jane Sperry, Changqing Jin, Lin Cao, James W. Freeman
Journal: Cancer Research (2008)

Abstract The role of Smad4 in transforming growth factor β (TGFβ)–mediated epithelial-mesenchymal transition (EMT), invasion, and metastasis was investigated using isogenically matched pancreatic cancer cell lines that differed only in expression of Smad4. Cells expressing Smad4 showed an enhanced TGFβ-mediated EMT as determined by increased expression of vimentin and decreased expression of β-catenin and E-cadherin. TGFβ-mediated invasion was suppressed in Smad4-intact cells as determined by in vitro assays, and these cells showed a reduced metastasis in an orthotopic model of pancreatic cancer. Interestingly, TGFβ inhibited STAT3Tyr705 phosphorylation in Smad4-intact cells. The decrease in STAT3Tyr705 phosphorylation was linked to a TGFβ/Smad4-dependent and enhanced activation of extracellular signal-regulated kinases, which caused an increase in serine phosphorylation of STAT3Ser727. Down-regulating signal transducer and activator of transcription 3 (STAT3) expression by short hairpin RNA in Smad4-deficient cells prevented TGFβ-induced invasion. Conversely, expressing a constitutively activated form of STAT3 (STAT3-C) in Smad4-intact cells enhanced invasion. This study indicates the requirement of STAT3 activity for TGFβ-induced invasion in pancreatic cancer cells and implicates Smad4-dependent signaling in regulating STAT3 activity. These findings further suggest that loss of Smad4, leading to aberrant activation of STAT3, contributes to the switch of TGFβ from a tumor-suppressive to a tumor-promoting pathway in pancreatic cancer. [Cancer Res 2008;68(11):4221–8]
Evaluation of derivatives of 3-(2-oxo-1-pyrrolidine) hexahydro-1H-azepine-2-one as dermal penetration enhancers: side chain length variation and molecular modeling
Authors: N Kim, A.F El-Kattan, C.S Asbill, R.J Kennette, J.W Sowell, R Latour, B.B Michniak
Journal: Journal of Controlled Release (2001)
Abstract P5-14-02: Women's responses to changes in US Preventive Services Task Force mammography screening guidelines: results from focus groups among ethnically diverse women
Authors: SM Bluethmann, JD Allen, C Hernandez, KM Opdyke, K Gates-Ferris, M Hurlbert, E Harden
Journal: Cancer Research (2012)

Abstract Introduction: In 2009, the US Preventive Services Task Force (USPSTF) changed its recommendations on the age and frequency for routine mammography. To this point, responses to this change among ethnically diverse women have been not been well examined. The objective of this qualitative study is to describe women's awareness of the change in mammography screening guidelines by the U.S. Preventive Services Task Force and to describe their attitudes toward this change. Methods: White, Black and Hispanic women ages 40–49 years were recruited from a variety of community settings in the Greater Boston, MA area to participate in focus groups (k = 10; N=73). Groups were segmented by race/ethnicity (Black = 29%; White=29%; Hispanic=15%). Women were asked if they were aware of the change in USPSTF guidelines, and if so, their understanding about reasons for this change and intention to comply. Focus groups were audio-taped and transcribed verbatim. Thematic content analysis was used to cull recurring discussion themes. Results: Most women in this study were not aware of changes in the USPSTF mammography screening guidelines. Those who were aware of the guideline change were highly suspicious that it was motivated by a desire for cost savings on the part of insurance companies and/or providers. Concerns regarding the accuracy of mammography, pain associated with screening, and fear of receiving positive test results were prevalent. Nevertheless, most said that they did not intend to comply with changes in guidelines; many believed that regular (yearly) mammography should start at a young age (40 or before) and continue indefinitely. Conclusion: Most women in this sample were unaware about changes in mammography screening guidelines and lacked understanding regarding underlying reasons for the change. Communication about the rationale for changes in mammography screening guidelines has left many women unconvinced about the potential downsides of screening and has generated a high degree of mistrust of insurance companies and medical providers. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-14-02.
THE TREATMENT OF ACUTE ALCOHOLISM BY LARGE DOSES OF DIGITALIS.
Authors: HENRY P. LOOMIS
Journal: JAMA (1900)

Suggestions for the use of large doses of digitalis in the treatment of acute alcoholism came from Sweden and England. Fothergill and Jones, of Jersey, England, were the first to introduce its use to the medical profession. Both recommended it very highly. The latter publishes a report of over seventy cases treated by this method alone. He claims that he never saw any alarming symptoms following the use of one-half ounce doses of the tincture. A few clinicians in this country have tried the remedy with varying success; among them Dr. Horatio C. Wood, of Philadelphia, who speaks highly of its effect in a certain class of cases. It is interesting to note that a drug whose use even in moderately large doses is supposed to be fraught with some danger, can be given in one-half ounce doses without producing any of the ordinary symptoms of digitalis poisoning. Various explanations
Contributions of Loss of Lung Recoil and of Enhanced Airways Collapsibility to the Airflow Obstruction of Chronic Bronchitis and Emphysema
Authors: D. G. Leaver, A. E. Tattersfield, N. B. Pride
Journal: Journal of Clinical Investigation (1973)

We investigated the contributions of intrinsic disease of the airways, loss of lung recoil and enhanced airway collapsibility to the airflow obstruction of 17 patients with chronic bronchitis and emphysema. Airways conductance at low flow (G(aw)), maximum expiratory flow (V(E, MAX)) and static lung recoil pressure [P(st) (l)] were measured at different lung volumes, and conductance-static recoil pressure and maximum flow-static recoil pressure curves constructed. Low values of DeltaG(aw)/DeltaP(st) (l) and DeltaV(E), max/DeltaP(st) (l) were attributed to intrinsic airways disease. Airway collapsibility was assessed by comparing G(aw) with upstream conductance on forced expiration and by the intercept of the maximum flow-static recoil curve on the static recoil pressure axis (P(tm)'). All patients had reduced G(aw) at all volumes but in seven DeltaG(aw)/DeltaP(st) (l) was normal. On forced expiration, maximum flow in all patients was reduced more than could be accounted for by loss of lung recoil. DeltaV(E, MAX)/DeltaP(st) (l) was reduced in the patients in whom DeltaG(aw)/P(st) (l) was low. In contrast DeltaV(E, MAX)/DeltaP(st) (l) was normal in three and only slightly reduced in another three of the seven patients with normal DeltaG(aw)/DeltaP(st) (l). In these patients G(aw) greatly exceeded upstream conductance and P(tm)' was increased.We conclude that loss of lung recoil could account for the reduction in resting airways dimensions in 7 of the 17 patients. Enhanced airway collapsibility commonly contributed to reduction in maximum flow. In three patients the airflow obstruction could be entirely accounted for by loss of lung recoil and enhanced airway collapsibility.
Searching for Signs of Life
Authors: None Jiminy
Journal: JAMA (1980)

The planet Jupiter was once a miniature sun, according to Richard C. Hoagland, PhD, a space scientist. During that period, a rich stream of electromagnetic and cosmic ray energy bathed the Jovian satellites, including Europa, Jupiter's third-largest moon. Hoagland believes that photochemical formation of organic molecules, which are the precursors to life, occurred in a global ocean 65 miles deep on Europa's surface. When Jupiter's stellar phase ended, a crust of ice five miles thick formed on the moon's surface. Life evolved under this canopy of ice, sustained by internal heat sources. This information is taken from a story that was clipped from my newspaper months ago. I have picked the story up, reread it, and pondered my peculiar fascination for it almost daily ever since. Why did this unusual thesis, the scientific validity of which I strongly doubted, continue to fasten my attention? It dutifully occurs to me, as
Smoking, Sex, and Pregnancy-Reply
Authors: Donna Day Baird
Journal: JAMA (1986)

<h3>In Reply.—</h3> Rosenberg and Spira raise three questions. First, does our method of counting cycles overestimate the effect of smoking on fertility? Counting cycles with sporadic birth control might result in either an overestimate or an underestimate. The direction of error (if any) depends simply on whether the risk of pregnancy in those cycles is more or less than half the usual risk. The most conservative approach is to exclude all cycles with sporadic use of birth control. In that case, substantially reduced fertility still remains in smokers (pregnancy rate for smokers is estimated to be 0.78 of that for nonsmokers using the Cox proportional hazard model). Second, does inclusion of women who were recently pregnant or nursing lead to an overestimate of the smoking effect? As stated in the original report, this factor was controlled in the effect measure we reported (smokers had an estimated pregnancy rate of 72%
"Casualty overload" from the Southall riots.
Authors: N A Shenouda, A D Greig, A P Dignan
Journal: BMJ (1980)

On 23 April 1979 riots occurred in Southall, Middlesex.Forty-seven casualties were subsequently admitted to the accident and emergency department of Ealing Hospital.We discuss the casualties, their management, and the problems that might arise in an accident and emergency department because of a riot. Casualties and their injuriesOf the 47 casualties, 22 were policemen and 25 civilians.Of the four patients with major injuries, one had a head injury and subsequently died, one had head and facial injuries, one had an eye injury, and one a jaw injury.The remaining 43 patients had minor injuries, which included 24 contusions, 21 lacerations, and two penetrating wounds; 31 of these were to the head,
Recurrence of hepatitis B after liver transplantation is associated with intrahepatic HBcAg and serum IgM anti-HBc
Authors: M.R. Brunetto, P. Ciccorossi, F. Filipponi, A. Giannotti, F. Oliveri, B. Coco, F. Bonino, M. Campa, F. Mosca
Journal: Journal of Hepatology (2001)
Does the extent of ST-segment depression predict short- and long-term mortality in patients with non-ST segment elevation acute coronary syndromes? Insights from the GUSTO IV
Authors: Yuling Fu, Michael Lauer, Wei-Ching Chang, Robert M. Califf, Maarten L. Simoons, Lars Wallentin, Eric J. Topol, Paul W. Armstrong
Journal: Journal of the American College of Cardiology (2003)
Assessing exposure to disinfection by-products in women of reproductive age living in Corpus Christi, Texas, and Cobb county, Georgia: descriptive results and methods.
Authors: M Lynberg, J R Nuckols, P Langlois, D Ashley, P Singer, P Mendola, C Wilkes, H Krapfl, E Miles, V Speight, B Lin, L Small, A Miles, M Bonin, P Zeitz, A Tadkod, J Henry, M B Forrester
Journal: Environmental Health Perspectives (2001)

We conducted a field study in Corpus Christi, Texas, and Cobb County, Georgia, to evaluate exposure measures for disinfection by-products, with special emphasis on trihalomethanes (THMs). Participants were mothers living in either geographic area who had given birth to healthy infants from June 1998 through May 1999. We assessed exposure by sampling blood and water and obtaining information about water use habits and tap water characteristics. Two 10-mL whole blood samples were collected from each participant before and immediately after her shower. Levels of individual THM species (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) were measured in whole blood [parts per trillion (pptr)] and in water samples (parts per billion). In the Corpus Christi water samples, brominated compounds accounted for 71% of the total THM concentration by weight; in Cobb County, chloroform accounted for 88%. Significant differences in blood THM levels were observed between study locations. For example, the median baseline blood level of bromoform was 0.3 pptr and 3.5 pptr for participants in Cobb County and Corpus Christi, respectively (p = 0.0001). Differences were most striking in blood obtained after showering. For bromoform, the median blood levels were 0.5 pptr and 17 pptr for participants in Cobb County and Corpus Christi, respectively (p = 0.0001). These results suggest that blood levels of THM species vary substantially across populations, depending on both water quality characteristics and water use activities. Such variation has important implications for epidemiologic studies of the potential health effects of disinfection by-products.
ISOKINETIC RELATIVE STRENGTH PROFILE OF POLISH ELITE AND SUB-ELITE FEMALE AND MALE SOCCER PLAYERS – A CROSS SECTIONAL STUDY
Authors: M Grygorowicz, R Hojszyk, T Piontek, W Dudzinski
Journal: British Journal of Sports Medicine (2014)

Background However the isokinetic strength is well described in the literature, there is still little know about the relative isokinetic strength values in sub-elite and elite soccer players of both sexes. One has to remember that this value should be regarded as one of critical sport-return criteria in case of the injury. Objective To describe distribution of isokinetic relative strength value in Polish elite female and male soccer players. We hypothesize that there will be no differences in relative isokinetic strength between players in different soccer level group. Design Cross sectional study. Setting Elite and sub-elite division. Participants 41 young sub-elite (YSMS), 27 elite male (EMS) and 30 elite female soccer (EFS) players from Polish Ekstraklasa and Youth Division. Interventions All soccer players performed concentric-concentric knee extension-flexion movements on Biodex System 3 Pro dynamometer at 60°/s of angular isokinetic velocity. Alignment axis of dynamometer rotation, thigh, hip and trunk stabilization as well as gravity correction and the range of motion was then set for each participant according to standard procedures. Values of relative isokinetic strength for were recorded. The one-way ANOVA with post hoc Tukey T test were used to assess differences between three groups. t-Test for two independent samples was used to analyze gender effects. Statistical significance was set at P&lt;.05. Main outcomes measurements Relative knee extensors and flexors isokinetic strength (Nm/kg). Results EFS had significantly higher results in isokinetic quadriceps and hamstring strength comparing to YSMS (2.64 vs. 2.31; P&lt;.001 and 1.39 vs. 1.27; P=.0207, respectively) and significantly lower results comparing EMS group (2.64 vs. 3.11; P&lt;.0001 and 1.39 vs. 1.78; P&lt;.0001, respectively). However there were no differences between groups regarding sex (P=.8881 for extension and P=.0839 for flexion). Conclusions Observed differences may be related to soccer skill level and not gender.
Assisted suicide and euthanasia in Switzerland: Doctors occupy special position
Authors: G. Bosshard
Journal: BMJ (2003)

EDITOR—I agree with Hurst and Mauron that the Swiss penal code illustrates how important it is to separate the issue of whether assisting death should be allowed in some circumstances from that of whether doctors should do it.1 Assistance in dying raises questions that cannot be answered from the perspective of medicine alone. …
Abstract 1774: Development of potent trimeric DR4 agonist Atrimers with therapeutic potential
Authors: Roger Ferrini, Daniela I. Oltean, Mark W. Renshaw, Elise Chen, Glenda Batzer, Maria J. Gonzalez, Bing Lin, Jean da Silva Correia, Martha A. Wild, Weiguang Zhu, Katherine S. Bowdish, Anke Kretz-Rommel
Journal: Cancer Research (2011)

Abstract TRAIL death receptor DR4 is a promising therapeutic target in oncology with expression in a wide variety of tumors. DR4 agonists, including TRAIL and monoclonal antibodies, can induce p53-independent apoptosis and are currently being evaluated in clinical trials in combination with chemotherapy. We aimed to surpass currently available therapeutics by developing trimeric death receptor agonists with properties expected to significantly exceed that of recombinant human TRAIL. The agonists can mimic the natural trimer-trimer interaction of the native ligand/receptor, but do not cross-react with the decoy receptors. Potent DR4 agonist AtrimersTM were engineered using human tetranectin, a trimeric human serum protein of 60 kDa, as a scaffold. A panel of unique DR4 binders was selected from novel phage libraries displaying the C-type lectin domain (CTLD) of tetranectin containing randomized loop sequences. DR4 Atrimers have sub-nanomolar affinity to recombinant DR4-Fc and showed no detectable binding to recombinant forms of DR5 or the decoy receptors. In vitro, the DR4 Atrimers efficiently killed DR4-positive cancer cell lines with sub-nanomolar EC50, but did not kill DR4-negative cell lines. DR4 Atrimers induced cell death of DR4-expressing tumor cells through the caspase pathway, but did not kill primary human B cells and hepatocytes. Interestingly, DR4 Atrimers have differential activities on various cell lines, and also vary in their degree of internalization. While some Atrimers show potent killing of Colo-205 and are rapidly internalized, other agonist Atrimers did not show measurable internalization. These unique properties open the possibility of developing potent naked Atrimers with prolonged half-lives due to lack of internalization, as well as leveraging rapidly internalizing DR4 Atrimers for design of Atrimer-drug conjugates. Further characterization of DR4 Atrimers is ongoing in Colo-205 xenograft models. DR4 agonist AtrimersTM with their superior potency and expected improvement in tumor penetration (vs. antibodies) represent a novel class of targeted cancer therapeutics for efficient induction of apoptosis and provide a promising approach for the treatment of a broad range of cancer types. 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 1774. doi:10.1158/1538-7445.AM2011-1774
PTU-115 Efficacy of mycophenolate mofetil therapy in the management of inflammatory bowel disease
Authors: M R Smith, L Wood, J Slater, S C Cooper
Journal: Gut (2012)

<h3>Introduction</h3> The role of Mycophenolate mofetil (MMF) as an immunomodulatory drug in managing inflammatory bowel disease is yet to be fully defined. We reviewed our experience of the efficacy, safety and tolerability of MMF in treating patients with refractory inflammatory bowel disease. <h3>Methods</h3> A retrospective analysis was performed of the case records of all patients treated with MMF for inflammatory bowel disease at our institution between 2003 and 2011. Remission was assessed by reviewing clinical, endoscopic and laboratory indices. <h3>Results</h3> We identified 36 patients, 23 male (64%) with a median age 46 yrs (range 19–75). Disease was classified as Crohn9s disease in 19, ulcerative colitis 16, indeterminate colitis.1 33 patients (92%) had previously received azathioprine; 32 discontinued this due to side-effects. Five patients had undergone surgery for small bowel Crohn9s disease. The starting dose of MMF was between 500 mg and 2 g daily, titrated to a dose of 2 g daily as tolerated. 26 patients (72%) were concurrently taking oral corticosteroids, and 18 (50%) were taking an oral 5-aminosalicylate. At 8 weeks, 29 patients (81%) had either achieved acute remission or maintained previous remission. Drug side-effects were experienced by eight patients (22%)—these symptoms were managed successfully by dose reduction in six patients (75%), with discontinuation in two patients. There were no serious haematological or other adverse drug effects. After 6 months of treatment, 33 patients continued to take MMF of which 19 patients (58%) had achieved sustained steroid-free remission. Median length of MMF treatment observed was 21.5 months (IQR 9.7–31.6). At the end of the observation period, 29 patients (81%) remained on MMF. 13 patients (36% of the original treatment group; UC 7, Crohn9s 5) remained in steroid-free remission with median time of remission 21.4 months (IQR 11.0–30.0). A further 13 patients achieved sustained remission with the addition of corticosteroids and/or anti-TNF therapy. Five patients (14% overall) were refractory to all medical therapy and underwent surgery: colectomy for UC 3, right hemicolectomy for Crohn9s.<sup>2</sup> <h3>Conclusion</h3> From our experience, MMF may represent a promising alternative treatment for inducing and maintaining remission in patients intolerant of or unable to receive thiopurines. It appears well tolerated with a good safety profile in thiopurine intolerant subjects. <h3>Competing interests</h3> None declared.