tbuckley/cabot-search huggingface dataset:
Frequent Pathologic Complete Responses in Aggressive Stages II to III Breast Cancers With Every-4-Week Carboplatin and Weekly Paclitaxel With or Without Trastuzumab: A Brown University Oncology Group Study
Authors: William M. Sikov, Don S. Dizon, Rochelle Strenger, Robert D. Legare, Kathy P. Theall, Theresa A. Graves, Jennifer S. Gass, Teresa A. Kennedy, Mary Anne Fenton
Journal: Journal of Clinical Oncology (2009)

To evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel +/- weekly trastuzumab in resectable and locally advanced breast cancer.Women with stages IIA to IIIB disease received carboplatin dosed by six times the area under the curve every 4 weeks and paclitaxel 80 mg/m(2) weekly for 16 weeks, and weekly trastuzumab was added for human epidermal growth factor receptor 2 (HER2) -positive status. The primary end point was the pathologic complete response (pCR) rate, defined as the absence of invasive disease in the breast and axillary nodes. Postoperative therapies were at the discretion of the treating physicians.Fifty-five patients were enrolled, and of these 43 had resectable disease. The median age was 54 years (range, 31 to 74 years). Treatment was well tolerated; there were no episodes of febrile neutropenia or grade 4 thrombocytopenia, and there were only two instances of grade 3 peripheral neuropathy. Overall, the pCR rate was 45%. The pCR rate was 43% (95% CI, 28% to 58%) in patients with resectable disease. Higher pCR rates occurred in patients with HER2-positive tumors (76% v 31% for HER2-negative tumors; P = .003), with estrogen receptor (ER) -negative tumors (75% v 27% for ER-positive tumors; P = .001), or with triple-negative tumors (67% v 12% ER-positive and HER2-negative tumors; P = .002). At a median of 28 months postoperation, recurrence-free survival (RFS) was 88.7%. If patients with ER-positive and HER2-negative tumors are excluded from analysis, patients who achieved a pCR were less likely to experience disease recurrence (RFS, 86%) than those who did not achieve a pCR (RFS, 75%).Neoadjuvant carboplatin and weekly paclitaxel +/- trastuzumab achieve high pCR rates in patients with HER2-positive and triple-negative disease without exposure to an anthracycline. Preliminary RFS results are encouraging but are likely influenced by adjuvant therapy received. Additional study of this regimen in high-risk patients is warranted.
STUDIES WITH BRUCELLA ENDOTOXIN IN HUMANS: THE SIGNIFICANCE OF SUSCEPTIBILITY TO ENDOTOXIN IN THE PATHOGENESIS OF BRUCELLOSIS
Authors: Robert S. Abernathy, Wesley W. Spink
Journal: Journal of Clinical Investigation (1958)

The mechanisms by which patients ill with brucellosis develop their characteristic symptoms of fever, chills, myalgia, asthenia and malaise have not been precisely elucidated. In particular, the contributions of the brucella cell itself to the pathogenesis of these clinical features have not been extensively investigated. An unusual clinical observation (1) suggested that some component of the cell did play a significant role. When patients seriously ill with brucellosis due to Brucella melitensis were treated with chlortetracycline, an unexpected abrupt febrile response often occurred within 8 to 12 hours after the initial dose of the antibiotic. These adverse reactions could be abolished or ameliorated by administering smaller initial doses of the antibiotic. Such effects suggested to the observers that, as a result of the antibrucella activity of the chlortetracycline, brucella cells were killed, thus liberating some cellular component which then produced the febrile response. This component was presumably the endotoxin of the cell.
The measurement of absolute lung volume without plethysmography
Authors: Ori Adam, Robert Shiner, Peter Calverley, Julian Solway, Robert Brown, Jeffrey Fredberg
Journal: European Respiratory Journal (2011)

A basic and important component of pulmonary function testing is determination of absolute lung volumes, including total lung capacity (TLC). However this involves the use of equipment such as a Body Plethysmograph (BP) that is unsuited to routine office practice. To determine TLC, we report here a new mechanical approach – the Partial Volume Method, PVM – that requires neither BP, gas dilution, nor thoracic imaging, yet is simple, compact, rapid, inexpensive, and accurate. With cheeks supported, the subject breathes through a flow interruption valve downstream of a parallel chamber of known gas volume. As a result of respiratory system inertance, respiratory flow continues undiminished for a very short time ( PVM  = 0.981· TLC PLETH , R 2 =0.87; R=0.943 (Pearson), CI: 0.961-0.918.  The coefficient of variation (CV) for repeated PVM trials was 3.44%. Together, these results establish a new method for accurate, rapid, and reproducible determination of TLC in healthy subjects with minimal subject cooperation.  This work was sponsored by PulmOne Ltd., Ra9ananna, Israel.
Increased platelet aggregate formation in patients with chronic airflow obstruction and hypoxaemia.
Authors: J A Wedzicha, D Syndercombe-Court, K C Tan
Journal: Thorax (1991)

Platelet aggregate formation in vivo was assessed by means of the platelet aggregate ratio and from platelet release products (beta thromboglobulin, platelet factor 4, thromboxane B2) in 23 patients with chronic airflow obstruction with and without hypoxaemia and in 10 control subjects without respiratory disease. Eight of the 11 hypoxaemic patients were having long term oxygen therapy. The platelet aggregate ratio was lower in the hypoxaemic patients (0.88 (SE 0.03] than in the non-hypoxaemic (0.97 (0.01] and control groups (1.00 (0.02], and there was a trend to lower aggregate ratios in the more hypoxaemic patients. Platelet release products in the peripheral venous blood were not increased in the patients or control subjects. Platelet behaviour is altered in chronic hypoxaemia and this enhanced platelet activity could contribute to the pulmonary vascular damage found in these patients through direct effects or mediator release.
Design Issues of Randomized Phase II Trials and a Proposal for Phase II Screening Trials
Authors: Lawrence V. Rubinstein, Edward L. Korn, Boris Freidlin, Sally Hunsberger, S. Percy Ivy, Malcolm A. Smith
Journal: Journal of Clinical Oncology (2005)

Future progress in improving cancer therapy can be expedited by better prioritization of new treatments for phase III evaluation. Historically, phase II trials have been key components in the prioritization process. There has been a long-standing interest in using phase II trials with randomization against a standard-treatment control arm or an additional experimental arm to provide greater assurance than afforded by comparison to historic controls that the new agent or regimen is promising and warrants further evaluation. Relevant trial designs that have been developed and utilized include phase II selection designs, randomized phase II designs that include a reference standard-treatment control arm, and phase II/III designs. We present our own explorations into the possibilities of developing “phase II screening trials,” in which preliminary and nondefinitive randomized comparisons of experimental regimens to standard treatments are made (preferably using an intermediate end point) by carefully adjusting the false-positive error rates (α or type I error) and false-negative error rates (β or type II error), so that the targeted treatment benefit may be appropriate while the sample size remains restricted. If the ability to conduct a definitive phase III trial can be protected, and if investigators feel that by judicious choice of false-positive probability and false-negative probability and magnitude of targeted treatment effect they can appropriately balance the conflicting demands of screening out useless regimens versus reliably detecting useful ones, the phase II screening trial design may be appropriate to apply.
The passage of drugs into horse saliva and the suitability of saliva for pre-race testing.
Authors: M. W. Horner
Journal: British Journal of Sports Medicine (1976)

Figure la shows how a saliva sample is taken at the racecourse by swabbing out the horse's mouth with a gauze pad held in forceps. This usually only produces 2 to 3ml of saliva. However, work at these laboratories has been facilitated by use of ponies with explanted parotid papillae. The papilla is the site of the opening of the parotid salivary duct on the inside of the cheek, and in each of these ponies a surgical operation has been performed which brings one papilla through to the outside of the cheek, so that pure parotid saliva can easily be collected.
Benefit of Robotic Assistance in Comparing Outcomes of Minimally Invasive Versus Open Radical Prostatectomy
Authors: Ashutosh K. Tewari, Jay K. Jhaveri, Krishna Surasi, Nishant Patel, Gerald Y. Tan
Journal: Journal of Clinical Oncology (2008)

toxicity by Morel at al 2 , also cited by Deenen et al and already discussed, sex had unfortunately not been taken into account as a separate risk factor, and the sex of the patients experiencing toxicity had not been revealed.Importantly, the female patient alluded to by Deenen et al who experienced lethal toxicity was homozygous for DPYD*2.In conclusion, we thank Deenen et al for their detailed analysis of our data and for pointing out possible alternative explanations.The additional data presented here do not support their hypotheses but they provide additional support to our main findings of low positive predictive value for DPYD*2A genotyping and an intriguing interaction between DPYD genetics and sex for the development of FUrelated toxicity.Together with our additional observation that the patient's genetic background determines to some extent the type of toxicity, value of detailed prospective studies is emphasized and warrants additional investigation into genome-wide determinants as well as nongenetic causes of toxicity.
Plasma "cortisol" response to Synacthen in patients on long-term small-dose prednisone therapy.
Authors: J A Hicklin, M R Wills
Journal: Annals of the Rheumatic Diseases (1968)

In view of the uncertainty about safe limits of steroid dosage and of the particular interest in the 5 mg.per day dose level (de Andrade, McCormick, and Hill, 1964), we studied adrenal cortical respon- siveness in a series of patients with rheumatoid arthritis, who had been on this dose of prednisone for varying periods, by the Synacthen test (Wood, Frankland, James, and Landon, 1965). MaterialPatients.-39patients were studied, all but one of whom had taken prednisone 5 mg./day for periods of from 8 weeks to 8 years.One patient (Case 31) had her dose increased from 5 to 7 mg./day 8 months before the test.With the exception of two who had polymyalgia rheu- matica, all had rheumatoid arthritis.Of these 39 patients, nineteen were selected at random and studied again after a year to discover the effects of continued or altered prednisone dosage upon adrenal function.Control.-Twentynormal hospitalized controls of com- parable age range were studied under the same test conditions as the patients.
Source of Electrocardiographic ST Changes in Subendocardial Ischemia
Authors: Danshi Li, Chuan Yong Li, Ah Chot Yong, David Kilpatrick
Journal: Circulation Research (1998)

Abstract —To clarify the source of electrocardiographic ST depression associated with ischemia, a sheep model of subendocardial ischemia was developed in which simultaneous epicardial and endocardial ST potentials were mapped, and a computer model using the bidomain technique was developed to explain the results. To produce ischemia in different territories of the myocardium in the same animal, the left anterior descending coronary artery and left circumflex coronary artery were partially constricted in sequence. Results from 36 sheep and the computer simulation are reported. The distributions of epicardial potentials from either ischemic source were very similar ( r =0.77±0.14, P &lt;0.0001), with both showing ST depression on the free wall of the left ventricle and no association between the ST depression and the ischemic region. However, endocardial potentials showed that ST elevation was directly associated with the region of reduced blood flow. Insulating the heart from the surrounding tissue with plastic increased the magnitude of epicardial ST potentials, which was consistent with an intramyocardial source. Increasing the percent stenosis of a coronary artery increased epicardial ST depression at the lateral boundary and resulted in ST elevation starting from the ischemic center as ischemia became transmural. Computer simulation using the bidomain model reproduced the epicardial ST patterns and suggested that the ST depression was generated at the lateral boundary between ischemic and normal territories. ST depression on the epicardium reflected the position of this lateral boundary. The boundaries of ischemic territories are shared, and only those appearing on the free wall contribute to external ST potential fields. These effects explain why body surface ST depression does not localize cardiac ischemia in humans.
Effectiveness of Health Education to Increase Screening for Cervical Cancer Among Eastern-Band Cherokee Indian Women in North Carolina
Authors: M. Dignan, R. Michielutte, K. Blinson, H. B. Wells, L. D. Case, P. Sharp, S. Davis, J. Konen, R. P. McQuellon
Journal: JNCI Journal of the National Cancer Institute (1996)

Background:The North Carolina Native American Cervical Cancer Prevention Project was a 5-year, National Cancer Institute-funded trial of health education designed to increase screening for cervical cancer among Native-American women in North Carolina.
The Fab fragment of a directly activating monoclonal antibody that precipitates a disulfide-linked heterodimer from a helper T cell clone blocks activation by either allogeneic Ia or antigen and self-Ia.
Authors: J Kaye, C A Janeway
Journal: The Journal of Experimental Medicine (1984)

We characterize a monoclonal antibody directed against the antigen/Ia receptor of a cloned helper T cell line that induced T cell clone proliferation and T cell clone-dependent B cell proliferation at antibody concentrations as low as 10(-11) M. A Fab fragment of this antibody was not stimulatory, implicating cross-linking of antigen receptors as the primary signal for T cell activation. The Fab fragment inhibited activation of this clone by both allogeneic Ia and antigen plus self-Ia, but not by the nonspecific stimulators concanavalin A and rabbit anti-mouse brain serum. This strongly supports the hypothesis that a single molecule mediates both self-Ia plus antigen and non-self-Ia recognition. This molecule is presumably the disulfide-linked heterodimer comprised of 42,000 mol wt acidic and basic subunits precipitated by this monoclonal antibody. The cell surface and internal precursor forms of this protein are also identified. In addition, the response to allogeneic Ia stimulation was more readily inhibited by the Fab fragment than was the response to antigen plus self-Ia, suggesting that alloreactivity reflects a low affinity interaction with a ligand represented at high frequency on the stimulatory cell.
Metastatic Renal Cancer Treated with Interleukin-2 and Lymphokine-Activated Killer Cells
Authors: RICHARD I. FISHER
Journal: Annals of Internal Medicine (1988)

To confirm the antitumor efficacy of treatment with interleukin-2 and lymphokine-activated killer cells in patients with metastatic renal cancer.Nonrandomized, phase II clinical trial.Tertiary care units in university medical centers.Consecutive trial of 35 patients with metastatic or unresectable renal cell cancer who have bidimensionally measurable disease, performance status 0 or 1, and normal function of all vital organs. Thirty-two patients completed interleukin-2 priming and received at least one lymphokine-activated killer cell infusion. Three patients were removed from the study and did not receive infusion of cells secondary to rapid tumor progression or toxicity.Patients initially received recombinant interleukin-2, 100,000 units/kg body weight every 8 hours, on days 1 to 5 in a priming phase to stimulate lymphokine-activated killer cell precursors and effector activity in vivo. Leukapheresis was done on days 8 to 12 and lymphocytes were cultured in vitro with interleukin-2 for 3 to 4 days to amplify lymphokine-activated killer cell activity. Finally, interleukin-2, 100,000 units/kg every 8 hours, was infused with cultured cells on days 12 to 16. All doses of interleukin-2 and lymphokine-activated killer cells were administered in intensive care units.The mean number of doses of interleukin-2 administered during the priming phase was 12.9 +/- 0.4; the mean number of lymphokine-activated killer cells reinfused was 7.0 +/- 0.6 X 10(10); and the mean number of interleukin-2 doses administered during the last phase was 10.2 +/- 0.6. The overall objective response rate was 16%; two patients had complete responses and three patients had partial responses with greater than 50% reduction of all measurable tumor. The complete responders remain disease-free at 12 and 9 months. Two partial responders have not had tumor regrowth at 16 and 15 months. The third partial responder relapsed at 4 months. Toxicity was severe but generally of short duration and manageable. There were no treatment-related deaths. Hypotension, weight gain, anemia, and elevations of serum creatinine levels and liver enzymes were common. Two patients required intubation; one patient had a myocardial infarction.This phase II study confirms the antitumor activity of interleukin-2 and lymphokine-activated killer cell therapy in patients with metastatic or unresectable renal cell cancer. Response rates, especially complete remission rates, are comparable or better than rates achieved with other forms of therapy.
Acute renal failure induced by contrast medium: steps towards prevention
Authors: R Mathew, K Haque, W Woothipoom
Journal: BMJ (2006)

<h3>Abstract</h3> The complex web of interactions in biological communities is an area of study that requires large multifactorial experiments with sufficient statistical power. The use of automated tools can reduce the time and labor associated with experiment setup, data collection, and analysis in experiments aimed at untangling these webs. Here we demonstrate tools for high-throughput experimentation (HTE) in duckweeds, small aquatic plants that are amenable to autonomous experimental preparation and image-based phenotyping. We showcase the abilities of our HTE system in a study with 6,000 experimental units grown across 1,000 different nutrient environments. The use of our automated tools facilitated the collection and analysis of time-resolved growth data, which revealed finer dynamics of plant-microbe interactions across environmental gradients. Altogether, our HTE system can run experiments of up to 11,520 experimental units and can be adapted to studies with other small organisms.
Evidence-Based Recommendations for Local Therapy for Soft Tissue Sarcomas
Authors: Peter W.T. Pisters, Brian O'Sullivan, Robert G. Maki
Journal: Journal of Clinical Oncology (2007)

There has been a gradual migration in the local treatment of soft tissue sarcomas from amputation and similar radical resectional approaches to more conservative, function-preserving surgery combined with radiotherapy. This progress has been made possible by small, single-institution, randomized trials that demonstrated the superiority of this more conservative, combined-modality approach. In the new millennium, attention has shifted to defining subsets of patients who might be adequately treated by surgery alone and defining the optimal sequence of surgery and radiation for patients who require both types of local therapy. There remains considerable discussion and debate surrounding the issue of pre- and postoperative chemotherapy for patients with localized soft tissue sarcomas. Adjuvant chemotherapy is a standard of care for adults who have the subtypes of soft tissue sarcomas that typically occur in pediatric patients (Ewing sarcoma, rhabdomyosarcoma), and just as clearly, adjuvant chemotherapy is not warranted in patients with low- and intermediate-risk disease (stages I and II). For patients with higher risk disease (stage III), the available randomized trials do not convincingly demonstrate a clinical benefit to adjuvant chemotherapy. As such, a complete accounting of potential risks and benefits is appropriate when discussing adjuvant chemotherapy with patients who have stage III disease.
Genome-wide association analysis in Primary sclerosing cholangitis and ulcerative colitis identifies risk loci at<i>GPR35</i>and<i>TCF4</i>
Authors: David Ellinghaus, Trine Folseraas, Kristian Holm, Eva Ellinghaus, Espen Melum, Tobias Balschun, Jon K. Laerdahl, Alexey Shiryaev, Daniel N. Gotthardt, Tobias J. Weismüller, Christoph Schramm, Michael Wittig, Annika Bergquist, Einar Björnsson, Hanns-Ulrich Marschall, Morten Vatn, Andreas Teufel, Christian Rust, Christian Gieger, H-Erich Wichmann, Heiko Runz, Martina Sterneck, Christian Rupp, Felix Braun, Rinse K. Weersma, Cisca Wijmenga, Cyriel Y. Ponsioen, Christopher G. Mathew, Paul Rutgeerts, Séverine Vermeire, Erik Schrumpf, Johannes R. Hov, Michael P. Manns, Kirsten M. Boberg, Stefan Schreiber, Andre Franke, Tom H. Karlsen
Journal: Hepatology (2012)

Approximately 60%-80% of patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). Previous genome-wide association studies (GWAS) in PSC have detected a number of susceptibility loci that also show associations in UC and other immune-mediated diseases. We aimed to systematically compare genetic associations in PSC with genotype data in UC patients with the aim of detecting new susceptibility loci for PSC. We performed combined analyses of GWAS for PSC and UC comprising 392 PSC cases, 987 UC cases, and 2,977 controls and followed up top association signals in an additional 1,012 PSC cases, 4,444 UC cases, and 11,659 controls. We discovered novel genome-wide significant associations with PSC at 2q37 [rs3749171 at G-protein-coupled receptor 35 ( GPR35 ); P = 3.0 × 10 −9 in the overall study population, combined odds ratio [OR] and 95% confidence interval [CI] of 1.39 (1.24-1.55)] and at 18q21 [rs1452787 at transcription factor 4 ( TCF4 ); P = 2.61 × 10 −8 , OR (95% CI) = 0.75 (0.68-0.83)]. In addition, several suggestive PSC associations were detected. The GPR35 rs3749171 is a missense single nucleotide polymorphism resulting in a shift from threonine to methionine. Structural modeling showed that rs3749171 is located in the third transmembrane helix of GPR35 and could possibly alter efficiency of signaling through the GPR35 receptor. Conclusion : By refining the analysis of a PSC GWAS by parallel assessments in a UC GWAS, we were able to detect two novel risk loci at genome-wide significance levels. GPR35 shows associations in both UC and PSC, whereas TCF4 represents a PSC risk locus not associated with UC. Both loci may represent previously unexplored aspects of PSC pathogenesis. (HEPATOLOGY 2013;58:1074–1083)