gebhart/patrepeval huggingface dataset:
GENE-04. PEDIATRIC MALIGNANT EPITHELIOID GLIONEURONAL TUMOR: PATHOLOGICAL, CLINICAL, AND MOLECULAR CHARACTERIZATION OF A RARE AND DEADLY MALIGNANCY (2017)

BACKGROUND: Malignant epithelioid glioneuronal tumor (MEGNT) is a rare high-grade brain tumor that exhibits both glial and neuronal differentiation and is not included in the current World Health Organization (WHO) classification. Limited case series describe a highly aggressive tumor with poor survival and have shed little light on MEGNT biology. AIM: The objective of our study was to molecularly characterize a cohort of MEGNTs in order to provide insight into tumor biology and identify potential therapeutic targets. METHODS: An integrated genomic strategy, including exome, transcriptome, and targeted mutation panel sequencing as well as copy number array analysis, was used to evaluate tumor samples obtained from 8 children with MEGNT. Clinical information was obtained by chart review. RESULTS: Outcomes were dismal for these patients despite aggressive surgery (gross total resection x 6) followed by involved field radiation therapy (XRT), with a median event-free survival of 6 months and 4 of 8 patients dead of disease. Frequent and potentially targetable genetic alterations were detected in the MAPK pathway in 4 of 8 cases (BRAF V600E x 3, NTRK2-BEND5) and in PI3K/MTOR pathway genes in 3 of 8 cases (TSC1 x 2, PTEN). Additional aberrations related to the MAPK pathway were identified in 4 patients, including high copy gains in MET and KIT and 2 novel fusions (SOS1-MAP4K3 and MAP3K11-GFAP) which were validated by targeted sequencing and require further functional characterization. Other alterations in known high-grade glioma genes were also detected, including homozygous CDKN2A/B loss (n=3), TP53 mutation (n=2), and amplification events involving MYCN, CDK6, MET, and KIT. CONCLUSION: MEGNT is an aggressive tumor with poor response to conventional therapies. The frequency of potentially-targetable molecular alterations identified in this study indicates an opportunity to test the use of novel targeted agents for children with these tumors.
IFATS Collection: Human Adipose-Derived Stem Cells Seeded on a Silk Fibroin-Chitosan Scaffold Enhance Wound Repair in a Murine Soft Tissue Injury Model (2008)

Soft tissue loss presents an ongoing challenge in reconstructive surgery. Local stem cell application has recently been suggested as a possible novel therapy. In the present study we evaluated the potential of a silk fibroin-chitosan (SFCS) scaffold serving as a delivery vehicle for human adipose-derived stem cells (ASCs) in a murine soft tissue injury model. Green fluorescent protein (GFP)-labeled ASCs were seeded on SFCS scaffolds at a density of 1 x 10(5) ASCs per cm(2) for 48 hours and then suture-inlaid to a 6-mm, full-thickness skin defect in 6-week-old male athymic mice. Wound healing was tracked for 2 weeks by planimetry. Histology was evaluated at 2 and 4 weeks. Our data show that the extent of wound closure was significantly enhanced in the ASC-SFCS group versus SFCS and no-graft controls at postoperative day 8 (90% +/- 3% closure vs. 75% +/- 11% and 55% +/- 17%, respectively). Microvessel density at wound bed biopsy sites from 2 weeks postoperative was significantly higher in the ASC-SFCS group versus SFCS alone (7.5 +/- 1.1 vs. 5.1 +/- 1.0 vessels per high-power field). Engrafted stem cells were positive for the fibroblastic marker heat shock protein 47, smooth muscle actin, and von Willebrand factor at both 2 and 4 weeks. GFP-positive stem cells were also found to differentiate into epidermal epithelial cells at 4 weeks postoperative. In conclusion, human adipose-derived stem cells seeded on a silk fibroin-chitosan scaffold enhance wound healing and show differentiation into fibrovascular, endothelial, and epithelial components of restored tissue.
Pharmacological studies of intravaginally applied dehydroepiandrosterone sulfate(DHA-S). (1991)

The ripening effect of dehydroepiandrosterone sulfate (DHA-S) on the uterine cervix was studied after intravaginal application. A 100-mg suppository containing 0, 5, 10 or 20% (w/w) DHA-S was applied to the vagina of pregnant rats 3 times on days 14-16 of gestation. Wet weight and water content of the uterine cervix increased dose-dependently. To measure the elasticity of the uterine cervix, the tension causing an expansion of 1 mm or 2 mm was determined; this was reduced by the application of 20% DHA-S, and the difference in the length of the cervix produced by tensions of 5 g and 25 g was increased. Application of 20% DHA-S decreased the collagen content of the uterine cervix and the total collagenase activity was increased. Furthermore, histochemical changes, coarsening and edema were observed in the uterine cervix. These findings suggest that intravaginal application of DHA-S would produce ripening effects similar to those after intravenous injection.
Non-Alcoholic Fatty Liver Disease: Current Perspectives and Future Direction in Disease pathogenesis, Treatment and Diagnosis (2012)

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the world. An important implication of this disease is the progression of the disease to a more complicated condition called non-alcoholic steatohepatitis (NASH) and the wide variety of clinical presentations. Over the past 5 years, remarkable progresses have been made in understanding the genetic basis for the disease. Recent clinical trials in pharmacotherapy for the disease have been encouraging as well. It is anticipated that the integration of the wide spectrum information retrieved from genomics, transcriptomics and proteomics studies conducted in NAFLD and NASH will mediate a better understanding of the disease pathogenesis and facilitate the postulation of disease pathobiology pathways. Genetic and biological markers identified from the omics studies may hold promise for diagnosis, personalized treatment, early prevention and new drug development.
Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Stroke Patients (1996)

In stroke patients, high TPA antigen concentrations may indicate an activation of the fibrinolytic system or may be due to a delayed clearance of TPA complexed with inhibitors. High PAI-1 antigen concentrations in patients with cerebral infarction represent increased fibrinolytic inhibition. The findings in this longitudinal study suggest that TPA and PAI-1 antigen concentrations both differ little between the acute and convalescent phases after stroke.
A Randomized Trial Comparing Radical Prostatectomy with Watchful Waiting in Early Prostate Cancer (2002)

In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival.
Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline (2017)

Purpose To make recommendations regarding the use of bisphosphonates and other bone-modifying agents as adjuvant therapy for patients with breast cancer. Methods Cancer Care Ontario and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature. Results Adjuvant bisphosphonates were found to reduce bone recurrence and improve survival in postmenopausal patients with nonmetastatic breast cancer. In this guideline, postmenopausal includes patients with natural menopause or that induced by ovarian suppression or ablation. Absolute benefit is greater in patients who are at higher risk of recurrence, and almost all trials were conducted in patients who also received systemic therapy. Most studies evaluated zoledronic acid or clodronate, and data are extremely limited for other bisphosphonates. While denosumab was found to reduce fractures, long-term survival data are still required. Recommendations It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy. Further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required. Risk factors for osteonecrosis of the jaw and renal impairment should be assessed, and any pending dental or oral health problems should be dealt with prior to starting treatment. Data for adjuvant denosumab look promising but are currently insufficient to make any recommendation. Use of these agents to reduce fragility fractures in patients with low bone mineral density is beyond the scope of the guideline. Recommendations are not meant to restrict such use of bone-modifying agents in these situations. Additional information at www.asco.org/breast-cancer-adjuvant-bisphosphonates-guideline , www.asco.org/guidelineswiki , https://www.cancercareontario.ca/guidelines-advice/types-of-cancer/breast .
IL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines (2008)

The present study is the first to describe in situ expression of IL-17 protein in human breast tumours and to propose a direct association between IL-17 and breast cancer invasion. The precise effectors of IL-17-dependent invasion remain to be characterised but could include a range of proteases such as a disintegrin and metalloproteinase protein or astacins. Nevertheless, this work identifies a novel potential mechanism for breast cancer invasion and tumour progression, the prognostic implication of which is currently under investigation.
Peptide-Derived Antagonists of the Urokinase Receptor. Affinity Maturation by Combinatorial Chemistry, Identification of Functional Epitopes, and Inhibitory Effect on Cancer Cell Intravasation (2001)

The high-affinity interaction between urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays an important role in pericellular plasminogen activation. Since proteolytic degradation of the extracellular matrix has an established role in tumor invasion and metastasis, the uPA-uPAR interaction represents a potential target for therapeutic intervention. By affinity maturation using combinatorial chemistry we have now developed and characterized a 9-mer, linear peptide antagonist of the uPA-uPAR interaction demonstrating specific, high-affinity binding to human uPAR (K(d) approximately 0.4 nM). Studies by surface plasmon resonance reveal that the off-rate for this receptor-peptide complex is comparable to that measured for the natural protein ligand, uPA. The functional epitope on human uPAR for this antagonist has been delineated by site-directed mutagenesis, and its assignment to loop 3 of uPAR domain III (Met(246), His(249), His(251), and Phe(256)) corroborates data previously obtained by photoaffinity labeling and provides a molecular explanation for the extreme selectivity observed for the antagonist toward human compared to mouse, monkey, and hamster uPAR. When human HEp-3 cancer cells were inoculated in the presence of this peptide antagonist, a specific inhibition of cancer cell intravasation was observed in a chicken chorioallantoic membrane assay. These data imply that design of small organic molecules mimicking the binding determinants of this 9-mer peptide antagonist may have a potential application in combination therapy for certain types of cancer.
Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients (2014)

HOXB9 is a novel tumour suppressor that inhibits colon adenocarcinoma progression by inducing differentiation. Elevated expression of HOXB9 predicts a longer survival in colon adenocarcinoma patients.
Progress towards the use of Listeria monocytogenes as a live bacterial vaccine vector for the delivery of HIV antigens (2004)

Listeria monocytogenes is a facultative intracellular bacterium that enters the cell by phagocytosis after which it colonizes the cytosol of the host cell. It is thus a potent vaccine vector for the presentation of passenger antigens to the major histocompatability complex class II and class I pathways of antigen processing and presentation. This article shall review the progress made in developing this unusual bacterium as a vaccine vector. In mouse models, recombinant Listeria carrying a number of different antigens have been shown to provide protective immunity against infectious organisms and therapeutic immunity directed towards tumor-associated antigens. Listeria has been engineered to express a number of HIV/SIV antigens. Measurements of immune responses using these recombinant strains in the mouse, after oral and parenteral immunization, and in the rhesus macaque after oral immunization indicate that strong cell-mediated immunity can be induced against these antigens. This review also discusses safety issues associated with live bacterial vaccine vectors and problems to be overcome in developing Listeria as a HIV vaccine for human use.
Multivariable dimension polynomials and new invariants of differential field extensions (2001)

We introduce a special type of reduction in the ring of differential polynomials and develop the appropriate technique of characteristic sets that allows to generalize the classical Kolchin′s theorem on differential dimension polynomial and find new differential birational invariants of a finitely generated differential field extension.
Lipopolysaccharide Interaction with Cell Surface Toll-like Receptor 4-MD-2 (2003)

Toll-like receptors (TLRs) are innate recognition molecules for microbial products, but their direct interactions with corresponding ligands remain unclarified. LPS, a membrane constituent of gram-negative bacteria, is the best-studied TLR ligand and is recognized by TLR4 and MD-2, a molecule associated with the extracellular domain of TLR4. Although TLR4-MD-2 recognizes LPS, little is known about the physical interaction between LPS and TLR4-MD-2. Here, we demonstrate cell surface LPS-TLR4-MD-2 complexes. CD14 greatly enhances the formation of LPS-TLR4-MD-2 complexes, but is not coprecipitated with LPS-TLR4-MD-2 complexes, suggesting a role for CD14 in LPS loading onto TLR4-MD-2 but not in the interaction itself between LPS and TLR4-MD-2. A tentative dissociation constant (Kd) for LPS-TLR4-MD-2 complexes was approximately 3 nM, which is approximately 10-20 times lower than the reported Kd for LPS-MD-2 or LPS-CD14. The presence of detergent disrupts LPS interaction with CD14 but not with TLR4-MD-2. E5531, a lipid A antagonist developed for therapeutic intervention of endotoxin shock, blocks LPS interaction with TLR4-MD-2 at a concentration 100 times lower than that required for blocking LPS interaction with CD14. These results reveal direct LPS interaction with cell surface TLR4-MD-2 that is distinct from that with MD-2 or CD14.
T3P: A Convenient and Useful Reagent in Organic Synthesis (2007)

This feature focuses on a re-agent chosen by a postgradu-ate, highlighting the uses and preparation of the reagent in current research
Principles and Problems in Physical Chemistry for Biochemists (Second edition) (1981)

The appearance of the second edition of Price and Dwek's well-known book is as timely as was the first.For those of us to whom the phrase 'Physics is fun' was as paradoxical as 'I am now telling a lie', salvation was provided in the arrival of the earlier version of this work.Now the Second Coming, as it were, provides us with the same outstandingly successful format, clarity of treatment, logic of development and thoughtfulness of presentation, together with several new topics.These latter, which fit neatly into the development as though they had always been intended to take their places, include the cooperative binding of ligands to macromolecules, the analysis of ultracentrifugal data, the chemiosmotic theory of oxidative phosphorylation and the kinetics of 2-substrate enzymes.As before, early chapters treat the First and Second Laws of Thermodynamics, leading to the concept of chemical equilibrium and disequilibrium.As such, a natural development to the binding of ligands to macromolecules and the thermodynamics of solutions, both lacking and containing macromolecules, the thermodynamics of acids and bases, electrochemical cells and redox processes, follow sequentially.Two comprehensive chapters on chemical and enzyme kinetics make up the major part of the second half of the book, which finishes off with two short ones covering, respectively, spectrophotometry and radioisotopes.If these are the bones of this useful work, the flesh, indeed the muscle, lies in the large number of worked examples and problems (solutions provided at the back) which illustrate and amplify the text.The student who has worked through the majority of these will have a very thorough grounding in all the important fundamentals which underpin any real understanding of biological processes.At £3.95 it is to be anticipated, as well as hoped, that every student of Biochemistry might purchase a copy.Will there be any topics which (s)he might wish to have had treated more fully?For this reviewer fuller treatments of the effect of temperature on the pK of acids and bases, extended Debye-Hiickel theory, the potentials set up by Gibbs-Donnan equilibria and experimental aspects of potentiometry would have been welcome, but such a view is a purely personal one.I was glad that the authors chose the heretical rebellion against Pascals and Becquerels amongst SI units in favour of atmospheres and Curies, and that the index was helpful and comprehensive.The suggestions for further reading were perhaps a little unadventurous, but these are mere quibbles in a book of such marvellous lucidity and utility, and I have not the slightest hesitation in recommending it to all serious students and teachers of biochemistry and other Life Sciences, who may begin by enjoying the witty dedication -'for the additions between editions'.
The induction of cytotoxic T cells and tumor regression by soluble antigen formulation. (1995)

CTLs specific for tumor antigens play a major role in the immunity against cancer. We have shown that class I-restricted CTLs can be induced by injecting soluble antigens mixed in an antigen formulation (AF) that consists of squalane, Tween 80, and Pluronic L121 (S. Raychaudhuri et al., Proc. Natl. Acad. Sci. USA, 89: 8308-8312, 1992). In this study, using ovalbumin and the ovalbumin-expressing transfectoma (EG7) as a tumor model system, we examined the in vivo antitumor effect of antigen-AF mixture. Vaccination of mice with ovalbumin in AF 2 or 3 days after EG7 tumor challenge showed significant inhibition of tumor growth compared to mice vaccinated with ovalbumin in alum or in saline. Depletion of CD8+ cells at the time of immunization completely abrogated the AF-induced tumor protection, indicating that CD8+ T cells are the major effectors in tumor protection in vivo. Depletion of CD4+ cells led to a marginal loss of tumor protection, which may be the result of inhibition of ovalbumin-specific CTL response due to the lack of T-helper activity. Our results demonstrate that AF can be used in subunit vaccines to stimulate CTLs and tumor regression in vivo.
Mechanism of Phorbol Myristate Acetate-Induced Lymphotoxin Production by a Human T Cell Hybridoma1 (1984)

Various hydroxyl radical scavengers markedly inhibited phorbol myristate acetate (PMA)-induced lymphotoxin (LT) production by a human T cell hybridoma, AC5-8. Among those we tested, tetramethylurea (TMU) was the most potent scavenger, and it was revealed that TMU must be added before 2 h have elapsed after PMA addition in order for LT production to be inhibited. In concordance with this fact, soluble NADPH dependent O2- forming enzyme(s) were activated several fold by PMA. PMA also induced DNA strand breaks, a process markedly inhibited by TMU. As expected, ADP-ribosyl transferase (ADPRT), which is well known to require DNA strand breaks for its enzymatic activity, was activated by PMA treatment. In addition, specific inhibitors for ADPRT, namely 3-amino-benzamide and nicotinamide, inhibited PMA-induced LT production. Taken together, these three successive events, activation of soluble NADPH dependent O2- forming enzyme(s), DNA strand breaks and activation of ADPRT, may be required for PMA-induced LT production by AC5-8.
Inhibition of T cell response with peptides is influenced by both peptide‐binding specificity of major histocompatibility complex molecules and susceptibility of T cells to blocking (1989)

Synthetic peptides corresponding to sequences 46-62 and 51-62 of mouse lysozyme and 46-61 of hen egg-white lysozyme (HEL) were used as competitors in a variety of T cell responses. The competitors, according to their binding specificity for major histocompatibility complex (MHC) were expected to inhibit T cell responses restricted to I-Ak, but not those restricted to I-Ad, I-Ek molecules. In competition experiments with T cell hybridomas, the poor binder I-Ed molecule required 10- to 15-fold higher competitor concentrations than the good binder I-Ak molecule to achieve 50% inhibition of antigen presentation. Similarly, the nonresponder state of H-2d mice to HEL peptide 46-61 could be overcome by increasing the immunizing dose, and proliferative T cell responses to different antigens in association with a variety of class II MHC molecules could be blocked by the mouse lysozyme and HEL peptides. Thus, the capability of some and failure of other MHC molecules to bind certain peptides appeared quantitative, rather than of an all or none nature, in these experimental systems. The susceptibility of uncloned T cell lines to peptide competitors was found to decrease with time. Lines maintained by repeated restimulation with antigen and APC, but without exogenous interleukin 2, acquired resistance within weeks. In contrast, T cell clones retained their susceptibility to peptide competitors over a long period of time. The latter data raise the possibility that a competition between ubiquitous (self) peptides and foreign antigen may result in the selection of T cells that have high avidity for the activating antigen-MHC complex, and are thus relatively resistant to competition at the level of antigen presentation.
Probable Non–Vector-borne Transmission of Zika Virus, Colorado, USA (2011)

Clinical and serologic evidence indicate that 2 American scientists contracted Zika virus infections while working in Senegal in 2008. One of the scientists transmitted this arbovirus to his wife after his return home. Direct contact is implicated as the transmission route, most likely as a sexually transmitted infection.