tbuckley/cabot-search huggingface dataset:
Surgical margins and the risk of local-regional recurrence (LRR) following mastectomy for early-stage breast cancer.
Authors: S. K. Childs, Y. Chen, S. Pochebit, M. Golshan, M. M. Duggan, J. S. Wong, J. R. Harris, J. R. Bellon
Journal: Journal of Clinical Oncology (2011)

95 Background: We sought to clarify the influence of a positive or close superficial or deep mastectomy margin on the risk of LRR. Methods: We reviewed the charts of 561 consecutive women who underwent mastectomy without radiation for newly diagnosed in situ or invasive breast cancer between 1998 and 2005. The study cohort consists of 167 of these women who had a positive or close (≤2 mm) superficial or deep surgical margin. LRR as the site of first recurrence (+/− simultaneous distant disease) and distant metastasis (DM) rates were calculated using the Kaplan-Meier method. The median age was 50 years. Forty-five (27%) had ductal carcinoma in situ (DCIS) only. Of the 122 women with invasive disease, 79% had T1, 18% T2, and 3% T3 tumors, and 25% had positive axillary nodes (range, 1-4; 68% 1 positive node). Twenty-nine (24%) of those with invasive disease had lymphovascular invasion. The superficial margin was positive in 61 (37%) and close in 69 (41%). The deep margin was positive in 28 (17%) and close in 51 (31%). Results: The median follow-up was 6.3 years (range, 1-12.4). The 5-year LRR rate was 5% (95% CI 2-10%) and the DM rate was 3% (95% CI 1-8%). Twelve patients had a LRR; this included the chest wall in 9 and the axilla in 4. Five of the 12 had positive nodes. Four of 92 (4%) with close margins had a LRR vs. 8/75 (11%) with positive margins (log-rank p=0.15). Of the 45 with pure DCIS, 1 (2%) had a LRR. Of those with invasive disease, LRR occurred in 1/28 (4%) who had invasive disease at (positive) or near (close) the superficial margin, 3/38 (8%) with DCIS at or near the superficial margin, 0/12 with invasive disease at or near the deep margin, and 1/12 (8%) with DCIS at or near the deep margin. Both margins were positive or close in 32/122 patients with invasive disease; 6 of these (19%) had a LRR. Conclusions: The risk of LRR in patients with a positive or close surgical margin after mastectomy is generally low. The benefit of post-mastectomy radiation in this population with otherwise favorable features is likely to be small. While there may be a higher risk of LRR in patients with disease at or close to both margins (likely representing extent of disease), numbers in these categories are small and these results should be interpreted with caution.
Development of a Biochemical Diagnosis of Parkinson Disease by Detection of α-Synuclein Misfolded Aggregates in Cerebrospinal Fluid
Authors: Mohammad Shahnawaz, Takahiko Tokuda, Masaaki Waragai, Nicolas Mendez, Ryotaro Ishii, Claudia Trenkwalder, Brit Mollenhauer, Claudio Soto
Journal: JAMA Neurology (2016)

Parkinson disease (PD) is a highly prevalent and incurable neurodegenerative disease associated with the accumulation of misfolded α-synuclein (αSyn) aggregates. An important problem in this disease is the lack of a sensitive, specific, and noninvasive biochemical diagnosis to help in clinical evaluation, monitoring of disease progression, and early differential diagnosis from related neurodegenerative diseases.To develop a novel assay with high sensitivity and specificity to detect small quantities of αSyn aggregates circulating in cerebrospinal fluid (CSF) of patients affected by PD and related synucleinopathies.The strategy evaluated in this proof-of-concept study uses the protein misfolding cyclic amplification (PMCA) technology that detects minute amounts of misfolded oligomers by taking advantage of their ability to nucleate further aggregation, enabling a very high amplification of the signal. The technology was first adapted with synthetic αSyn oligomers prepared in vitro and used to screen in 2 blinded cohorts of CSF samples from German and Japanese patients with PD (n = 76) and individuals serving as controls affected by other neurologic disorders (n = 65), neurodegenerative diseases (n = 18), and Alzheimer disease (n = 14). The kinetics of αSyn aggregation were measured by αSyn-PMCA in the presence of CSF samples from the participants to detect αSyn oligomeric seeds present in this biological fluid. The assays were conducted from November 15, 2013, to August 28, 2015.Kinetic parameters correlated with disease severity at the time of sample collection, measured by the Hoehn and Yahr scale, with the lowest grade indicating unilateral involvement with minimal or no functional impairment, and the highest grade defining patients with complete confinement to wheelchair or bed.Studies with synthetic αSyn aggregates showed that αSyn-PMCA enabled to detect as little as 0.1 pg/mL of αSyn oligomers. The αSyn-PMCA signal was directly proportional to the amount of αSyn oligomers added to the reaction. A blinded study of CSF samples correctly identified patients affected by PD with an overall sensitivity of 88.5% (95% CI, 79.2%-94.6%) and specificity of 96.9% (95% CI, 89.3%-99.6%). The αSyn-PMCA results for different patients correlated with the severity of the clinical symptoms of PD (Japanese cohort: rs = -0.54, P = .006; German cohort: rs = -0.36, P = .02).The findings suggest that detection of αSyn oligomers by αSyn-PMCA in the CSF of patients affected by PD may offer a good opportunity for a sensitive and specific biochemical diagnosis of the disease. Further studies are needed to investigate the usefulness of αSyn-PMCA to monitor disease progression and for preclinical identification of patients who may develop PD.
Laga M., Plummer F.A., Piot P., Data P., Namara W. Ndinya-Achola J.O., Nsanze H., Maitha G., Ronald A.R., Pamba H.O. and Brunham R.: Prophylaxis of Gonococcal and Chlamydia Ophthalmia Neonatorum: Silver Nitrate Versus Tetracycline. New Eng. J. Med. 318: 6
Authors: Pamba Hannington Ouma
Journal: New England Journal of Medicine (1988)
Silvestrol, a Rocaglate Derivative from the Indonesian Plant Aglaia foveolata, Has Significant Bcl-2- and p53-Independent Anti-Tumor Activity against Chronic Lymphocytic Leukemia Cells.
Authors: Ryan B. Edwards, David M. Lucas, Gerard Lozanski, Amy J. Johnson, Bao-Ning Su, Thomas S. Lin, John C. Byrd, A. Douglas Kinghorn, Michael R. Grever
Journal: Blood (2006)
Novel AMKL Chimeric Transcription Factors Are Potent Inducers of Leukemia with Unique Mechanisms of Leukemogenesis
Authors: Jinjun Dang, Stephanie Nance, Amanda Larson Gedman, Jinjun Cheng, Jing Ma, Michael P Walsh, Cary Koss, Peter Vogel, James R Downing, Tanja A Gruber
Journal: Blood (2014)
Dosimetric comparison of targeted high-dose-rate brachytherapy versus whole gland treatment.
Authors: Melody P Chung, Oluwatosin Kayode, Jason Wang, Sang-June Park, Leonard S. Marks, D. Jeffrey Demanes, Mitchell Kamrava
Journal: Journal of Clinical Oncology (2012)

255 Background: To determine potential benefits of focal brachytherapy, we investigated target coverage and magnitude of decreased dose to organs at risk (OARs) with hemigland (HG) compared to whole gland (WG) high dose rate brachytherapy. Methods: 10 WG implants were used to generate 10 WG and 20 HG (left and right) treatment plans using Inverse Planning Simulation Annealing in Oncentra Masterplan (Nucletron). The same distribution of 17-18 catheters was used for WG and HG plans. The same dose constraints were used for all plans (D90 100-115%, V100 97-100%, V150&lt;35%, Rectum D 0.1cc &lt;85%, Bladder D 0.1cc &lt; 95%, and Urethra D 0.1cc &lt;110%). The HG contour was a modification of the WG contour whereby the urethra divided the prostate into hemiglands. Contours for OARs were identical. HG plans were not actually delivered. The prescription dose was 7.25 Gy x 6. A D 90 , V 100 , and V 150 were calculated for HG and WG, along with D 0.1cc , D 1cc , D 2cc, and D avg to OARs. We estimated mean difference and 95% confidence intervals for outcome measures. Bonferroni correction was used to adjust for bias due to multiple comparisons. Statistical analyses were conducted using SAS 9.2 (SAS Institute, Cary, NC), with a significance level set at p=0.003. Results: Compared to WG, HG was associated with a higher D 90 (108 vs 112%, p &lt; 0.0001), lower V 100 (98.8 vs 97.6%, p = 0.0001), and higher V 150 (26.5 vs 33.8%, p = 0.0001). WG therapy resulted in higher tissue doses to OARs. Mean values for the rectum were D 0.1cc (76.0 vs 71.2%, p=.0027), D 1cc (68.4 vs 59.0%, p&lt;0.0001), D 2cc (64.1 vs 53.1%, p&lt;0.0001) and D avg (27.5 vs 20.5%, p&lt;0.0001). Mean values for the bladder were D 0.1cc (83.8 vs 82.2%, p=0.0925), D 1cc (73.4 vs 64.0%, p&lt;0.0001), D 2cc (67.5 vs 55.9%, p&lt;0.0001) and D avg (22.1 vs 16.2%, p&lt;0.0001). Mean values for the urethra were D 0.1cc (106.5 vs 97.7, p&lt;0.0001), D 1cc (103.1 vs 82.9%, p&lt;0.0001), D 2cc (95.2 vs 69.3%, p&lt;0.0001) and D avg (73.5 vs 57.2%, p&lt;0.0001). Conclusions: The catheter distribution used for WG may not be ideal for HG as a higher D 90 and V 150 was noted. HG plans decreased D avg to the rectum, bladder, and urethra by a difference of 7.0, 5.9, and 16.3%. Further research is warranted to determine whether further dose reductions can be achieved and are clinically meaningful.
Phosphoinositide 3’-Kinase (PI3K) Delta Inhibition with CAL-101 Blocks B-Cell Receptor (BCR) Signaling and the Prosurvival Actions of Nurslike Cells (NLC), In Chronic Lymphocytic Leukemia
Authors: Julia Hoellenriegel, Sarah A Meadows, William G. Wierda, Michael J Keating, Brian Lannutti, Jan A. Burger
Journal: Blood (2010)
Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation
Authors: Thiyagaragan M. Achariyar, Baoman Li, Weiguo Peng, Philip B. Verghese, Yang Shi, Evan McConnell, Abdellatif Benraiss, Tristan Kasper, Wei Song, Takahiro Takano, David M. Holtzman, Maiken Nedergaard, Rashid Deane
Journal: Molecular Neurodegeneration (2016)

Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel. We reasoned that this system also serves to distribute essential molecules in CSF into brain. The aim was to establish whether apoE in CSF, secreted by the choroid plexus, is distributed into brain, and whether this distribution pattern was altered by sleep deprivation.We used fluorescently labeled lipidated apoE isoforms, lenti-apoE3 delivered to the choroid plexus, immunohistochemistry to map apoE brain distribution, immunolabeled cells and proteins in brain, Western blot analysis and ELISA to determine apoE levels and radiolabeled molecules to quantify CSF inflow into brain and brain clearance in mice. Data were statistically analyzed using ANOVA or Student's t- test.We show that the glymphatic fluid transporting system contributes to the delivery of choroid plexus/CSF-derived human apoE to neurons. CSF-delivered human apoE entered brain via the perivascular space of penetrating arteries and flows radially around arteries, but not veins, in an isoform specific manner (apoE2 > apoE3 > apoE4). Flow of apoE around arteries was facilitated by AQP4, a characteristic feature of the glymphatic system. ApoE3, delivered by lentivirus to the choroid plexus and ependymal layer but not to the parenchymal cells, was present in the CSF, penetrating arteries and neurons. The inflow of CSF, which contains apoE, into brain and its clearance from the interstitium were severely suppressed by sleep deprivation compared to the sleep state.Thus, choroid plexus/CSF provides an additional source of apoE and the glymphatic fluid transporting system delivers it to brain via the periarterial space. By implication, failure in this essential physiological role of the glymphatic fluid flow and ISF clearance may also contribute to apoE isoform-specific disorders in the long term.
Morphologic Changes Associated With Pantothenic Acid Deficiency in the Mouse&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Stuart W. Lippincott, Harold P. Morris
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article Morphologic Changes Associated With Pantothenic Acid Deficiency in the Mouse Get access Stuart W. Lippincott, Stuart W. Lippincott research fellow Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold P. Morris Harold P. Morris senior nutrition chemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 1, August 1941, Pages 39–46, https://doi.org/10.1093/jnci/2.1.39 Published: 01 August 1941
Cost-Utility of Stepped Care Targeting Psychological Distress in Patients With Head and Neck or Lung Cancer
Authors: Femke Jansen, Anna M.H. Krebber, Veerle M.H. Coupé, Pim Cuijpers, Remco de Bree, Annemarie Becker-Commissaris, Egbert F. Smit, Annemieke van Straten, Guus M. Eeckhout, Aartjan T.F. Beekman, C. René Leemans, Irma M. Verdonck-de Leeuw
Journal: Journal of Clinical Oncology (2017)

Purpose A stepped care (SC) program in which an effective yet least resource-intensive treatment is delivered to patients first and followed, when necessary, by more resource-intensive treatments was found to be effective in improving distress levels of patients with head and neck cancer or lung cancer. Information on the value of this program for its cost is now called for. Therefore, this study aimed to assess the cost-utility of the SC program compared with care-as-usual (CAU) in patients with head and neck cancer or lung cancer who have psychological distress. Patients and Methods In total, 156 patients were randomly assigned to SC or CAU. Intervention costs, direct medical costs, direct nonmedical costs, productivity losses, and health-related quality-of-life data during the intervention or control period and 12 months of follow-up were calculated by using Trimbos and Institute of Medical Technology Assessment Cost Questionnaire for Psychiatry, Productivity and Disease Questionnaire, and EuroQol-5 Dimension measures and data from the hospital information system. The SC program’s value for the cost was investigated by comparing mean cumulative costs and quality-adjusted life years (QALYs). Results After imputation of missing data, mean cumulative costs were ­€3,950 (95% CI, –€8,158 to –€190) lower, and mean number of QALYs was 0.116 (95% CI, 0.005 to 0.227) higher in the intervention group compared with the control group. The intervention group had a probability of 96% that cumulative QALYs were higher and cumulative costs were lower than in the control group. Four additional analyses were conducted to assess the robustness of this finding, and they found that the intervention group had a probability of 84% to 98% that cumulative QALYs were higher and a probability of 91% to 99% that costs were lower than in the control group. Conclusion SC is highly likely to be cost-effective; the number of QALYs was higher and cumulative costs were lower for SC compared with CAU.
Prognostic Impact of the Levels of Expression of Cell Surface Proteins Commonly Expressed by Blasts and Hematopoietic Precursor Cells in De Novo AML Patients: A Report From the Spanish Cetlam Study Group
Authors: Maria Concepcion Garcia-Dabrio, Montserrat Hoyos, Ana Garrido, Salut Brunet, Rafael F Duarte, Josep-Maria Ribera, Jordi Esteve, Andreu Llorente, Mar Tormo, Ramon Guardia, Natalia Lloveras, Antoni Garcia, Inmaculada Heras, Juan Besalduch, M. Paz Queipo De Llano, Javier Bueno, Joan Bargay, Pio Torres, Josep M. Marti-Tutusaus, Llorenç Font, Anna Aventin, Quentin Lecrevisse, Alberto Orfao, Jorge Sierra, Josep F. Nomdedeu
Journal: Blood (2012)
Results of a phase II study of single-agent nab-paclitaxel in platinum-refractory second-line metastatic urothelial carcinoma (UC).
Authors: S. S. Sridhar, C. M. Canil, S. D. Mukherjee, E. Winquist, C. Elser, A. Eisen, M. N. Reaume, L. Zhang, Y. Ko
Journal: Journal of Clinical Oncology (2011)

241 Background: There is currently no standard second-line chemotherapy for platinum- refractory UC. Both paclitaxel and docetaxel are commonly used but response rates are &lt; 20% and no survival advantage has been shown. In this multi-institutional phase II study, we evaluated the efficacy and tolerability of a new albumin-bound nanoparticle formulation of paclitaxel, known as Abraxane (ABI-007) as a single agent in patients with platinum-refractory metastatic UC. Methods: Patients with measurable UC, progressing on or after first-line platinum-based chemotherapy were enrolled onto this two-stage trial. ABI-007 was given at 260 mg/m 2 IV q3weekly until progression. Clinical evaluation, CBC and blood chemistries were performed every cycle with restaging CT scans every 2 cycles. Results: Accrual is now complete with 48 patients enrolled. Baseline characteristics: Male: Female 40:8; median age 68; ECOG Performance Status 0:1:2, 15:24:8. 248 cycles were delivered: median 5.5 cycles/pt with 17/48 pts (35%) requiring dose reductions. Most frequent adverse events (AE) were alopecia (12%), fatigue (12%), pain (12%), neuropathy (9%) and nausea (4%). The most frequent grade 3+ AE were pain (45%), hypertension (14%), fatigue (8%), joint stiffness (5%), neuropathy (4%) and weakness (4%). Forty patients are evaluable for response: 1 (2.5%) complete response (CR), 11 (28%) partial responses (PR), 9 (23%) stable disease (SD) and 20 (49%) progressive disease. One patient was inevaluable for response, 7 patients are too early for evaluation. Conclusions: Single-agent ABI-007 was well tolerated with a response rate (CR+PR) of 33% (12/36) and a clinical benefit rate (CR+PR+SD) of 58% (21/36), representing one of the highest reported response rates to date in the second-line UC setting. These results suggest further study of ABI-007 in urothelial carcinoma is warranted. No significant financial relationships to disclose.
IL-6 Released from BMSCs Suppresses Cytotoxic Effect of Ara-C and IL-6 Mediated Signaling Enhances Re-Growing of HEL Cells Following Ara-C Treatment
Authors: Hyejoo Park, Daeyoon Kim, Chansu Lee, Eunkyung Bae, Kwang-Sung Ahn, Youngil Koh, Hyun Jung Lee, Hyo Jung Kim, Junglim Lee, Hwi-Joong Yoon, Sung-Soo Yoon
Journal: Blood (2015)
PS01.29: The EGFR-mTOR Signaling Axis: a Prognostic Biomarker in Non–Small Cell Lung Carcinoma at the Time of Diagnosis
Authors: Neelu Puri, Zachary Crees, Caleb Shearrow, Leo Lin, Kavin Asari, Aayush Bhoraskar, Andrew Nowak, Gagan Chhabra, Shylendra Sreenivassappa, Connie Vitali, Odile David
Journal: Journal of Thoracic Oncology (2016)
A Clinical Study of Bortezomib in Combination with Dexamethasone and/or Doxorubibcin for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma
Authors: Jie Jin, Jiejing Qian, Haitao Meng, Wenbin Qian, Hongyan Tong, Yin Tong, Liping Mao
Journal: Blood (2008)
OP0008 Structure modification in osteoarthritis with intra-articular sodium hyaluronate of mol. 500–730 kda
Authors: RW Jubb, S Piva, L Beinat, J Dacre, P Gishen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Several Hyaluronan based products are available for intra-articular administration. These products differ in their composition and contain either natural hyaluronan of differing molecular weight or chemically crosslinked hyaluronan. Numerous clinical studies have shown that a series of 3–5 weekly intra-articular injections of hyaluronan of molecular weight 500–730 kDa (Hyalgan) reduces pain and improves function in patients with osteoarthritis of the knee and that this effect can be long lasting (6–12 months). Moreover, there is some evidence from pilot clinical studies to suggest that this product may slow osteoarthritis. <h3>Objectives</h3> The primary objective of the present study was to examine the structure-modifying activity of intra-articular hyaluronan of molecular weight 500–730 kDa.(Hyalgan). <h3>Methods</h3> A multicentre, randomised, placebo-controlled, double-blind (masked observer) study in patients with primary knee osteoarthritis (ACR criteria) was conducted in 17 centres in the UK. The primary end point was the change in radiological joint space between baseline and one year in the medial tibio-femoral compartment, measured by digital image analysis. Weight-bearing antero-posterior radiographs were taken using a standardised technique. Patients were randomly assigned to receive 3 courses of 3 intra-articular injections of hyaluronan or 2 ml of placebo (saline solution) during the one year study. Uncontrolled use of analgesics and NSAIDs were allowed. <h3>Results</h3> 408 patients with knee osteoarthritis (II-III Kellgren-Lawrence) were enrolled in the trial and 319 patients completed the one year study period. Mean patient age was 64.2 yrs (sd = 9.3), 68.4% of patients were female. The two groups, placebo and control, were comparable at entry for disease state and demographics. The change in joint space width between baseline and one year in the two groups was compared by analysis of variance. The group of patients with greater joint space at entry, treated with hyaluronan, showed statistically reduced progression of joint space narrowing. In the hyaluronan group the mean loss was only -0.22 (sd = 1.1), while in the placebo group the mean loss was -0.60 (sd = 1.1). This was statistically significant, p &lt; 0.05. <h3>Conclusion</h3> Repeat treatment cycles of intra-articular hyaluronan of molecular weight 500–730 kDa (Hyalgan) result in a statistically significant delay in radiological joint space narrowing within one year, in patients with osteoarthritis of the knee.
Structure of the 40S ribosomal subunit of Plasmodium falciparum by homology and de novo modeling
Authors: Harrison Ndung'u Mwangi, Peter Wagacha, Peterson Mathenge, Fredrick Sijenyi, Francis Mulaa
Journal: Acta Pharmaceutica Sinica B (2016)

Generation of three dimensional structures of macromolecules using in silico structural modeling technologies such as homology and de novo modeling has improved dramatically and increased the speed by which tertiary structures of organisms can be generated. This is especially the case if a homologous crystal structure is already available. High-resolution structures can be rapidly created using only their sequence information as input, a process that has the potential to increase the speed of scientific discovery. In this study, homology modeling and structure prediction tools such as RNA123 and SWISS–MODEL were used to generate the 40S ribosomal subunit from Plasmodium falciparum. This structure was modeled using the published crystal structure from Tetrahymena thermophila, a homologous eukaryote. In the absence of the Plasmodium falciparum 40S ribosomal crystal structure, the model accurately depicts a global topology, secondary and tertiary connections, and gives an overall root mean square deviation (RMSD) value of 3.9 Å relative to the template׳s crystal structure. Deviations are somewhat larger in areas with no homology between the templates. These results demonstrate that this approach has the power to identify motifs of interest in RNA and identify potential drug targets for macromolecules whose crystal structures are unknown. The results also show the utility of RNA homology modeling software for structure determination and lay the groundwork for applying this approach to larger and more complex eukaryotic ribosomes and other RNA-protein complexes. Structures generated from this study can be used in in silico screening experiments and lead to the determination of structures for targets/hit complexes.