pinecone/core-2020-05-10-deduplication huggingface dataset:
PFG NMR diffusion experiments for complex systems

Many practical applications of diffusion NMR, ranging from biomedical to industrial, entail the measurement of low-concentration solutes in non-deuterated, compositionally complex systems. The aim of this article is to present examples of robust, versatile diffusion experiments that can be used with non-deuterated solvents and at non-ambient temperatures. Specifically, three experiments are presented in detail: CONVEX, which combines excitation-sculpting solvent suppression with double-echo convection-compensating PGSE; DQDiff, which implements double-quantum filtered diffusion measurements in a convection-compensating mode; and applications of Oscillating-Gradient Spin-Echo (OGSE) to systems with homonuclear scalar couplings. These examples are based on the recent work by the authors and relate to a variety of systems, ranging from simple solutions to colloidal and polymeric systems. Besides the applied aspects, we review the general methodology used to treat the effects of diffusion and flow in NMR experiments, and apply this theory to derive the diffusion attenuation expression for each of the experiments presented. The paper should be useful to beginners as well as advanced users of general NMR wishing to learn about diffusion measurements
Gradient‐enhanced TROSY described with Cartesian product operators

TROSY, Transverse Relaxation Optimized Spectroscopy, was developed more than a decade ago. Since that time, the  15 N‐ 1 H HSQC‐TROSY experiment has become the standard “fingerprint” correlation spectrum for proteins of high molecular weight. In addition, its implementation in protein triple resonance experiments has pushed the boundaries of NMR assignment up to about 100 kDa, making NMR a highly relevant technique in structural biology. TROSY exploits the dipole‐CSA cross‐correlated relaxation properties of the NH system and selects for the narrowest of the HSQC J‐correlation quartet in both dimensions. The original publications and reviews of TROSY use shift operators and/or single transition product operators to describe the TROSY coherence pathways selections. In this review, we offer a familiar Cartesian product operator approach to comprehensively describe all of the events in the modern TROSY pulse sequence such as multiplet selection, gradient coherence selection, gradient quadrature, and sensitivity enhancement. © 2011 Wiley Periodicals, Inc. Concepts Magn Reson Part A 38: 280–288, 2011
Spatial mapping of translational diffusion coefficients using diffusion tensor imaging: A mathematical description

In this article, we discuss the theoretical background for diffusion weighted imaging and diffusion tensor imaging. Molecular diffusion is a random process involving thermal Brownian motion. In biological tissues, the underlying microstructures restrict the diffusion of water molecules, making diffusion directionally dependent. Water diffusion in tissue is mathematically characterized by the diffusion tensor, the elements of which contain information about the magnitude and direction of diffusion and is a function of the coordinate system. Thus, it is possible to generate contrast in tissue based primarily on diffusion effects. Expressing diffusion in terms of the measured diffusion coefficient (eigenvalue) in any one direction can lead to errors. Nowhere is this more evident than in white matter, due to the preferential orientation of myelin fibers. The directional dependency is removed by diagonalization of the diffusion tensor, which then yields a set of three eigenvalues and eigenvectors, representing the magnitude and direction of the three orthogonal axes of the diffusion ellipsoid, respectively. For example, the eigenvalue corresponding to the eigenvector along the long axis of the fiber corresponds qualitatively to diffusion with least restriction. Determination of the principal values of the diffusion tensor and various anisotropic indices provides structural information. We review the use of diffusion measurements using the modified Stejskal–Tanner diffusion equation. The anisotropy is analyzed by decomposing the diffusion tensor based on symmetrical properties describing the geometry of diffusion tensor. We further describe diffusion tensor properties in visualizing fiber tract organization of the human brain
A single phantom to mimic 1H MR spectra of different tissues

International audienceObjectTo design and build a single phantom, encompassing various elementary tubes, that mimics the 1H magnetic resonance (MR) spectra of liver, prostate, muscle and brain.Materials and MethodsHigh-resolution NMR tubes were filled with water and the metabolite of interest, at a concentration of 50 mM, or with dairy cream or oil. The tubes (5 mm outer diameter) were placed into a plastic support, the ensemble was positioned in the center of a cuboid container filled with water. Simulations of the magnetic field inhomogeneity arising from the susceptibility variations in the current phantom were also performed. MR localized spectroscopy was performed on a 1.5 T clinical scanner.ResultsMR spectra of voxels positioned in four different locations of the phantom closely mimicked the resonance peaks of liver, prostate, muscle and brain in vivo MR spectra. In particular, for the muscle spectrum, the intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) resonances were obtained using dairy cream and oil, respectively. Simulations of the magnetic field inhomogeneity in the phantom showed that in the case of an NMR tube length five times greater than the thickness of the volume of interest, it is not necessary to fill the container with water. However, to ensure a good reception level and shim settings, the NMR tubes were immersed in water.ConclusionsA single phantom of new design, that is easily built and highly reconfigurable, is here presented, to mimic the in vivo MR spectra of liver, prostate, muscle, brain and other models as needed
Activation of Src Kinase in Primary Colorectal Carcinoma

BACKGROUND. The specific activity of the non-receptor protein tyrosine kinase, Src,
is increased in the majority of colon and rectal adenocarcinomas compared to
normal mucosa. However, the prognostic significance of this difference is unknown.
The objective of the current study was to determine if Src activity is a
marker for poor clinical prognosis in colon carcinoma patients. As Src activation
leads to expression of urokinase/plasminogen activator receptor (u-PAR), expression
of Src and u-PAR were correlated with patient survival.
METHODS. Tumors and adjacent normal colonic mucosae from 45 patients with
colorectal carcinoma were screened for Src activity by the immune complex kinase
assay. Expression of u-PAR was determined by enzyme linked immunoabsorbent
assay. The primary tumor-to-normal mucosa ratios of activity were compared
following classification and regression tree (CART) analysis to determine the prognostic
significance of elevated specific Src activity. Expression of u-PAR was correlated
with Src activity.
RESULTS. By CART analysis, Src activity in tumors elevated more than twofold over
normal mucosa was significant. Increased Src activity significantly correlated with
Dukes stage, pT and pN classification, and increased u-PAR levels (P   0.001).
Kaplan Meier analysis showed a significant association between elevated Src
activity and shorter overall survival of all patients (P  0.0004) and of Dukes Stage
A-C patients (P  0.0037). In patients who underwent curative resection, a significant
correlation with a decreased disease-free survival rate was found (P
  0.0001). Multivariate analysis revealed that elevated Src activity was a prognostic
parameter independent of M classification (P  0.0125, relative risk 3.54, 95%
confidence interval 1.31 – 9.76).
CONCLUSIONS. Src activity is an independent indicator of poor clinical prognosis in
all stages of human colon carcinoma. These data suggest that Src-specific inhibitors
may have a therapeutic role in inhibiting tumor progression and metastasis,
and that measurement of Src activity may aid in selection of early stage patients for
adjuvant therapy. CPublishedN/
Role of methalothionein in irradiated human rectal carcinoma.

BACKGROUND. Metallothioneins (MT) are low-molecular weight, metal-binding
proteins that play a role in cellular proliferation and differentiation, as well as in
cellular defense mechanisms. They act as scavengers of free radicals produced by
irradiation. A number of in vitro and in vivo studies have linked overexpression of
cellular MT with tumor cell resistance to radiation. This is the first study that
investigates whether MT expression is involved in the radioresistance of rectal
carcinoma.
METHODS. Using a mouse monoclonal antibody, MT expression was analyzed by
immunohistochemistry on surgical samples (n   85) from 85 patients with locally
advanced rectal carcinoma who were treated preoperatively with a hyperfractionated
and accelerated radiotherapy schedule and on tumor biopsies (n   13)
obtained before treatment. The potential correlations between MT expression and
pathologic variables and survival were examined.
RESULTS. MT were expressed strongly in both the cytoplasm and nucleus of tumor
cells in 7 biopsy and 42 surgical samples. A comparison of MT expression in biopsy
and surgical specimens showed that MT expression did not change after irradiation
in most cases. Against all expectations, MT were expressed more frequently in
tumors from responders than in those from the nonresponders (P   0.02). There
was no correlation between MT expression and tumor stage, histology after radiotherapy,
or survival.
CONCLUSION. These findings do not support the hypothesis that MT overexpression
at the end of radiotherapy is a marker for radiation resistance. Cancer 2002;95:
1003–8. © 2002 American Cancer Society.
DOI 10.1002/cncr.10780Peer reviewe
Distribution of p63, a novel myoepithelial marker, in fine-needle aspiration biopsies of the breast: an analysis of 82 samples

BACKGROUND. The presence of myoepithelial cells (MECs) in fine-needle aspiration
biopsies (FNAB) of the breast constitute an important criterion used to
diagnose benign breast lesions. However, MECs sometimes have a distorted cytomorphology,
and most of the previously evaluated myoepithelial markers do not
have satisfactory sensitivity and specificity. p63, a recently characterized p53
homolog, is a nuclear transcription factor that is expressed in basal cells of
multilayered epithelia and myoepithelial cells of the breast. The authors analyzed
the immunocytochemical distribution of p63 in a series of 82 breast FNABs (30
benign lesions and 52 malignant breast lesions).
METHODS. Eighty-two archival, Papanicolaou-stained smears of breast lesions were
retrieved from the files of the authors’ institutions. Immunocytochemistry was
performed according to the streptavidin-biotin-peroxidase complex technique using
the antibody 4A4 (against all p63 isoforms). Two pathologists evaluated the
distribution of p63 positive cells. Only nuclear reactivity was considered specific.
RESULTS. In benign lesions, p63 decorated the nuclei of MECs in all samples. p63
also stained naked nuclei in fibroadenomas. In malignant lesions, p63 was positive
in MECs overlying malignant cell clusters in all 8 samples of ductal carcinoma in
situ (DCIS), in 9 of 16 samples of pure invasive carcinomas (IC), and in 16 of 20
samples that contained both DCIS and IC. In 18 samples (36%), a variable population
of p63 positive, malignant cells was observed. p63 failed to decorate stromal,
neural, adipocytic, and smooth muscle cells in all samples.
CONCLUSIONS. p63 is a reliable nuclear marker of MECs in breast aspirates. Regardless
of the fact that variable proportions of p63 positive, malignant cells were
observed in 36% of breast carcinoma aspirates, p63 may be a useful adjunct
antibody to confirm the presence of MECs in FNABs of benign breast lesions.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/5386/2001
High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma - A multicenter study of the Intergruppo Italiano Linfomi showing prolonged disease free survival in patients

BACKGROUND. The objective of the current study was to evaluate in a multicenter setting the feasibility and efficacy of a high-dose sequential (HDS) chemotherapy regimen that combined intensive debulking and high-dose therapy (HDT) with peripheral blood progenitor cell (PBPC) autografting in patients with refractory or recurrent Hodgkin lymphoma (HL). METHODS. Data were collected from 102 patients with HL who were treated with the HDS regimen at 14 centers associated with the Intergruppo Italiano Linfomi. Twenty-four patients had primary refractory HL, 59 patients had their first recurrence of HL (within I year in 32 patients and > 1 year in 27 patients), and 19 patients had multiple disease recurrences. The HDS regimen included the sequential delivery of high-dose (hd) cyclophosphamide with PBPC harvesting, methotrexate, etoposide, then HDT (usually hd mitoxantrone plus L-phenylalanine mustard) with PBPC autografting. In addition, radiotherapy was delivered to 36 patients at sites of bulky or persistent disease. RESULTS. Ninety-two patients (90%) completed the HDS program. There were five toxic deaths (treatment-related mortality rate, 4.9%) and six secondary malignancies (five patients developed myelodysplastic syndrome/acute myelogenous leukemia, and one patient developed colorectal carcinoma). At a median follow-up of 5 years, the 5-year overall survival (OS) and event-free survival (EFS) projections were 64% (95% confidence interval [95% Cl], 54-74%) and 53% (95% Cl, 43-63%), respectively. Patients with their first recurrence had the most favorable outcome, with 5-year OS and EFS projections of 77% (95% CI, 66-88%) and 63% (95% CI, 50-76%), respectively. There were no significant differences between patients with early first recurrence and late first recurrence. The poorest outcome was observed in patients with refractory HL, with 5-year OS and EFS projections of 36% (95% Cl, 16-55%) and 33% (95% Cl, 14-52%), respectively. Patients who received HDS chemotherapy after multiple recurrences had an intermediate outcome. Multivariate analysis showed that refractory disease and systemic symptoms at the time of initial presentation were associated significantly associated with poor OS and EFS. CONCLUSIONS. The use of HDS chemotherapy for patients with refractory and/or recurrent HL is feasible at the multicenter level. The combination of intensive debulking and HDT with PBPC autografting offers a good chance of prolonged disease free survival for patients with their first recurrence of HL
Vinblastine, bleomycin, and methotrexate chemotherapy plus irradiation for patients with early-stage, favorable Hodgkin lymphoma - The experience of the gruppo italiano studio linfomi

BACKGROUND. The acknowledged effectiveness of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy in patients with early-stage Hodgkin lymphoma has been associated with conflicting toxicity reports. METHODS. One hundred forty-three patients were evaluated clinically and had favorable Stage IA or IIA Hodgkin lymphoma. Ninety-three patients were treated with the standard VBM schedule combined with extended-field radiotherapy (EFRT), leaving the choice of the therapeutic sequence free. Fifty subsequent patients were treated with a slightly modified VBM schedule (VbMp) combined with RT limited to involved fields (IF-RT) and delivered only after the end of chemotherapy. In the VbMp schedule, intervals between cycles were 21 days instead of 28 days, bleomycin doses were reduced, small doses of prednisone were given orally, and the interval before RT was prolonged. RESULTS. Clinical response was complete in 96% of patients who were treated with VBM plus EF-RT and in 94% of patients who were treated with VbMp plus IF-RT. Recurrence rates were nearly identical (12% and 11%, respectively) over necessarily different follow-up (91 months and 33 months, respectively). Hematologic toxicity was tolerable in both trials, and pulmonary side effects were moderate in the first trial and negligible in the second. On the whole, treatment was tolerated better when RT followed chemotherapy. CONCLUSIONS. The VBM regimen was confirmed to be effective in patients with early-stage Hodgkin lymphoma. Administration of all cycles before RT improved tolerance; pulmonary toxicity probably is mitigated further by reduced bleomycin doses, mild prednisone therapy, and a more prolonged resting interval before RT. A slightly higher recurrence rate was expectable in the VBM plus IF-RT trial despite the actual intensification of vinblastine and methotrexate
Breast Carcinoma Survival in Europe and the United States: A Population-Based Study

BACKGROUND. Breast carcinoma survival rates were found to be higher in the U.S. than in Europe. METHODS. Multiple regression analysis of breast carcinoma survival rates among women diagnosed between 1990 and 1992 was performed using clinical data from population-based case series from the Surveillance, Epidemiogy, and End Results (SEER) program (13,172 women) and the European Concerted Action on survival and Care of Cancer Patients (EUROCARE) project (4478 women). RESULTS. Early-stage tumors (T1N0M0) were more frequent in the SEER data (41% of cases) than in the EUROCARE data (29%). In the SEER data, early tumors were more frequent in women age ≥ 65 years (43%) than in younger women (38%), whereas the reverse was true in the European data (25% vs. 31%). In both case series, > 90% of women underwent surgery and 81-82% underwent lymphadenectomy, but the number of axillary lymph nodes evaluated was higher in the SEER data than in the EUROCARE data. The 5-year survival rate was higher in the U.S. case series (89%) than in the European series (79%). This differential was observed for each stage category evaluated: early (T1N0M0), large lymph node-negative (T2-3N0M0), lymph node-positive (T1-3N+M0), locally advanced (T4M0), and metastatic (M1) tumors. The overall relative excess risk (RER) of death was significantly higher (RER, 1.37; 95% confidence interval [95% CI], 1.25-1.50) among European women compared with U.S. women (referent group). Adjustment for stage, age, surgery, and the number of lymph nodes evaluated explained most of the excess risk (RER, 1.07; 95% CI, 0.98-1.17). CONCLUSIONS. Transatlantic differences in the 5-year survival rates for women diagnosed with breast carcinoma between 1990 and 1992 were attributable mainly to differences in stage of disease. Resources should be invested to achieve earlier diagnosis of breast carcinoma in Europe, especially for elderly women
Clinical relevance of immunophenotype in a retrospective comparative study of 297 peripheral T-cell lymphomas, unspecified, and 496 diffuse large B-cell lymphomas: experience of the Intergruppo Italiano Linformi.

BACKGROUND. To assess the impact of T-cell/B-cell phenotype on clinical outcome, the authors retrospectively compared patients who had peripheral T-cell lymphoma, unspecified (PTCL-U), with patients who had diffuse large B-cell lymphoma (DLBCL). METHODS. Two hundred ninety-seven cases of PTCL-U and 496 cases of DLBCL that had been transferred from the files of the Intergruppo Italiano Linfomi or the Gruppo Italiano Linfomi were integrated into a unique working file and reviewed by the authors. RESULTS. The PTCL-U group and the DLBCL group had significantly different distribution patterns with respect to patient age, gender, disease stage, performance status (PS), the presence or absence of systemic B symptoms, the presence or absence of bulky disease, lactic acid dehydrogenase (LDH) levels, and number of extranodal sites (ENS). A significantly greater number of patients in the DLBCL group experienced complete remission (P < 0.0001). Multinomial logistic regression analysis confirmed that immunophenotype, PS, LDH concentration, and number of ENS were independent predictors of response. At a median follow-tip duration of 43 months, there was no observable difference in disease-free Survival (DFS) between patients with DLBCL and patients with PTCL-U; however, multivariate analysis did reveal that poorer PS and bone marrow involvement were significantly associated with shorter DFS. Furthermore, although the overall survival (OS) curves associated with the T-cell and B-cell ummunophenotypes were significantly different from each other at a median follow-up duration of 37 months (P = 0.0012), Cox multivariate analysis excluded immunophenotype from the final OS model. CONCLUSIONS. The findings made in the current study indicate that the natural history of PTCL-U may differ from that of DLBCL. Patients with PTCL-U tended to have less favorable clinical outcomes, although the observed difference in outcome was only partially attributable to immunophenotype, which was independently associated with response, but not with survival. Differences in prognostic factor distributions between patients with PTCL-U and patients with DLBCL may account for some portion of the expected phenotype-associated risk
Long-term disease-free survival of patients with radically resected thymomas: relevance of cell-cycle protein expression

BACKGROUND. Despite radical Surgical resection, thymomas often recur. The objective of the current retrospective Study was to investigate the prognostic relevance of the expression of cell-cycle proteins in these neoplasms to formulate a possible therapeutic Surveillance strategy for the prevention of recurrence. METHODS. The authors retrospectively reviewed the main clinicopathologic factors, including the World Health Organization (WHO) classification, of patients with thymoma who had undergone radical surgical resection. Specimens were studied using immunohistochemistry and the expression of cell-cycle proteins (i.e., p21, p27, and p53) was assessed. Univariate and multivariate analysis of predicting survival prognostic factors were performed. RESULTS. The authors analyzed 88 patients with thymoma who underwent radical surgical resection at the study institution. According to the Masaoka staging system, 41 patients had Stage I disease, 31 patients had Stage II disease, and 16 patients had Stage III disease. There were 24 tumor recurrences (27.3%), 4 of which were local, 16 of which were distant intrathoracic, and 4 of which were extrathoracic. The second radical resection provided a disease-free Survival rate that was similar to the first. Only Masaoka stage (P=0.001), WHO classification (P=0.001), high expression of p53 (P=0.03), and low expression of p21 (P=0.02) and p27 (P=0.001) were found to he correlated with a reduced disease-free survival. Low p27 expression was found to be the most significant predictive factor of a short disease-free Survival (P=0.001), especially when associated with low p21 expression and high p53 expression (P=0.0001). CONCLUSIONS. Long-term disease-free survival in thymoma patients treated with radical surgical resection Was found to be correlated with Masaoka stage, WHO classification, and expression of cell-cycle proteins, with the latter found to be the most significant predictive factor. Functional cooperation between cell-cycle proteins might constitute another level of regulation in tumor growth. More careful surveillance should be adopted whenever there is negative cell-cycle protein expression. (c) 2005 American Cancer Society