gebhart/patrepeval huggingface dataset:
Effective Hemostasis in Cardiac Surgery (1988)

This informative resource focuses on ways to control hemostasis in the cardiac surgical patient. The text covers all important aspects of coagulation management, defines the role of platelets and their abnormalities, reviews the use of heparin and shotgun therapy, and more. With 18 expert contributors.
Safety, Immunogenicity and Duration of Protection of the RTS,S/AS02D Malaria Vaccine: One Year Follow-Up of a Randomized Controlled Phase I/IIb Trial (2010)

ClinicalTrials.gov NCT00197028.
Characterization of Endogenous Sodium Channels in the ND7-23 Neuroblastoma Cell Line: Implications for Use as a Heterologous Ion Channel Expression System Suitable for Automated Patch Clamp Screening (2016)

The rodent neuroblastoma cell line, ND7-23, is used to express voltage-dependent sodium (Nav) and other neuronal ion channels resistant to heterologous expression in Chinese hamster ovary (CHO) or human embryonic kidney (HEK) cells. Their advantage is that they provide endogenous factors and signaling pathways to promote ion channel peptide folding, expression, and function at the cell surface and are also amenable to automated patch clamping. However, ND7-23 cells exhibit endogenous tetrodotoxin (TTX)-sensitive Nav currents, and molecular profiling has revealed the presence of Nav1.2, Nav1.3, Nav1.6, and Nav1.7 transcripts, but no study has determined which subtypes contribute to functional channels at the cell surface. We profiled the repertoire of functional Nav channels endogenously expressed in ND7-23 cells using the QPatch automated patch clamp platform and selective toxins and small molecules. The potency and subtype selectivity of the ligands (Icagen compound 68 from patent US-20060025415-A1-20060202, 4,9 anhydro TTX, and Protoxin-II) were established in human Nav1.3, Nav1.6, and Nav1.7 channel cell lines before application of selective concentrations to ND7-23 cells. Our data confirm previous studies that >97% of macroscopic Nav current in ND7-23 cells is carried by TTX-sensitive channels (300 nM TTX) and that Nav1.7 is the predominant channel contributing to this response (65% of peak inward current), followed by Nav1.6 (∼20%) and negligible Nav1.3 currents (∼2%). In addition, our data are the first to assess the Nav1.6 potency (50% inhibitory concentration [IC50] of 33 nM) and selectivity (50-fold over Nav1.7) of 4,9 anhydro TTX in human Nav channels expressed in mammalian cells, confirming previous studies of rodent Nav channels expressed in oocytes and HEK cells.
Resectability of Presymptomatic Pancreatic Cancer and Its Relationship to Onset of Diabetes: A Retrospective Review of CT Scans and Fasting Glucose Values Prior to Diagnosis (2007)

Pancreatic cancer is frequently undetectable or resectable on CT scans done >/=6 months prior to clinical diagnosis. At onset of diabetes, pancreatic cancers are generally resectable.
PET/CT in the Evaluation of Relapsed or Refractory Hodgkin Lymphoma. (2016)

18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) has been the most important advance in the assessment of Hodgkin lymphoma (HL) since the introduction of computed tomography (CT). In the frontline management of HL, FDG-PET combined with low-dose CT has emerged as the modality of choice for staging and treatment response assessment. Substantial data have accumulated over the past several years supporting the use of PET/CT in the evaluation and management of relapsed or refractory HL, as well. In this article, we review the role of PET/CT after the frontline treatment of HL, as well as the prognostic utility of PET/CT before autologous and allogeneic stem cell transplantation. We also review the use of PET/CT as a part of response-adapted treatment strategies in relapsed or refractory HL and implications for current and future clinical practice.
An advanced video camera system with robust AF, AE, and AWB control (2001)

This paper presents an advanced video camera system which has robust automatic focus (AF), automatic exposure (AE), and automatic white-balance (AWB) control. The proposed AF algorithm decides the correct moving direction of the lens and detects the accurate in-focus state even though the scene is interfered with by the high light intensity. Experimental results demonstrate that the proposed system can be an effective alternative to conventional systems using the hill-climbing method.
A randomized prospective clinical trial of adjuvant C. parvum immunotherapy in 260 patients with clinically localized melanoma (Stage I):Prognostic factors analysis and preliminary results of immunotherayp (1982)

A total of 260 patients with clinically localized melanoma (Stage I) from 18 medical institutions in the Southeastern Cancer Study Group were randomized to receive either surgical treatment alone, or surgery plus Corynebacterium parvum immunotherapy. A multivariant analysis (Cox regression model) of nine prognostic factors was performed on 110 patients with a minimum of two years follow-up. The dominant prognostic variables were thickness (P = 0.0007) and anatomic location of the melanoma (trunk versus other, P = 0.015). Disease-free survival curves were then calculated for 204 surgically evaluable patients. Overall, there was no significant difference in three-year survival for the two-treatment arms, which was 81% for the adjuvant immunotherapy group compared to 67% for the surgical control group (P = 0.10). The median follow-up period was 24 months (range, 1-60 months). However, when the data was subgrouped by tumor thickness, an apparent benefit of immunotherapy was observed in 49 patients with melanomas greater than 3 mm in thickness. Only five of 23 such patients relapsed after receiving C. parvum. Their three-year disease-free survival was 73%. In contrast, 13 of 26 patients who did not receive immunotherapy have relapsed so far and their three-year disease-free survival was only 33% (P = 0.01). In the 175 patients with melanomas less than 3 mm in thickness, both treatment arms had identical three-year disease-free survival rates of 83%. No significant differences between the treatment arms were observed using other prognostic variables, including the level of invasion. Toxicity to C. parvum injections was minimal in most patients. It is concluded that a prognostic factor analysis is critically important in adjunctive trials of melanoma to determine which dominant variables should be used for analyzing patient subgroups; that C. parvum immunotherapy appears to be associated with an improved disease-free survival rate in the subgroup of patients with melanomas greater than 3 mm thickness (this early encouraging data must still be confirmed with continued patients accrual and a longer observation period); and that patients with melanomas less than 3 mm thickness have a relatively favorable prognosis after appropriate surgical treatment, and immunotherapy does not improve their survival rates.
Single-Molecule Analyte Recognition with ClyA Nanopores Equipped with Internal Protein Adaptors (2015)

Nanopores have been used to detect molecules, to sequence DNA, or to investigate chemical reactions at the single-molecule level. Because they approach the absolute limit of sensor miniaturization, nanopores are amenable to parallelization and could be used in single-cell measurements. Here we show that single enzymes can be functionally and reversibly trapped inside the confined space of a ClyA nanopore. Remarkably, the binding of ligands to the internalized proteins is mirrored by specific changes to the nanopore conductance. Conveniently, the manipulation of the charge of the protein allowed increasing of the residence time of the protein inside the nanopore. Nanopores with internalized protein adaptors can be used to study proteins in real time or can be incorporated into inexpensive portable devices for the detection of analytes with high selectivity.
The evolution of clonality testing in the diagnosis and monitoring of hematological malignancies (2014)

Currently, distinguishing between benign and malignant lymphoid proliferations is based on a combination of clinical characteristics, cyto/histomorphology, immunophenotype and the identification of well-defined chromosomal aberrations. However, such diagnoses remain challenging in 10-15% of cases of lymphoproliferative disorders, and clonality assessments are often required to confirm diagnostic suspicions. In recent years, the development of new techniques for clonality detection has allowed researchers to better characterize, classify and monitor hematological neoplasms. In the past, clonality was primarily studied by performing Southern blotting analyses to characterize rearrangements in segments of the IG and TCR genes. Currently, the most commonly used method in the clinical molecular diagnostic laboratory is polymerase chain reaction (PCR), which is an extremely sensitive technique for detecting nucleic acids. This technique is rapid, accurate, specific, and sensitive, and it can be used to analyze small biopsies as well as formalin-fixed paraffin-embedded samples. These advantages make PCR-based approaches the current gold standard for IG/TCR clonality testing. Since the completion of the first human genome sequence, there has been a rapid development of technologies to facilitate high-throughput sequencing of DNA. These techniques have been applied to the deep characterization and classification of various diseases, patient stratification, and the monitoring of minimal residual disease. Furthermore, these novel approaches have the potential to significantly improve the sensitivity and cost of clonality assays and post-treatment monitoring of B- and T-cell malignancies. However, more studies will be required to demonstrate the utility, sensitivity, and benefits of these methods in order to warrant their adoption into clinical practice. In this review, recent developments in clonality testing are examined with an emphasis on highly sensitive systems for improving diagnostic workups and minimal residual disease assessments.
Maximizing the Therapeutic Window of an Antimicrobial Drug by Imparting Mitochondrial Sequestration in Human Cells (2011)

The number of antimicrobial agents available for use in humans is limited by the difficulty of discovering chemical agents with selective toxicity to bacterial targets. Numerous small molecule inhibitors have potential as antimicrobial agents, yet their use has been prevented by high levels of toxic cross-reactivity in human cells. For example, methotrexate (Mtx) is an effective antimetabolite that exerts its effects by inhibiting DHFR. It is a potent antibacterial when accumulated intracellularly, but toxicity in human cells limits clinical utility in infectious disease treatment. Here, we describe peptide conjugates of Mtx that are sequestered into the mitochondria of human cells (mt-Mtx). This alteration in localization of Mtx, which directs it away from its enzyme target, decreases its toxicity in human cells by a factor of 10(3). Mt-Mtx, however, maintains activity against a variety of pathogenic gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The results from this proof-of-principle study describe a novel methodology for augmenting the antibacterial efficacy of drugs amenable to peptide conjugation while simultaneously decreasing their toxicity to the host organism.
A Fully Human Recombinant IgG-like Bispecific Antibody to Both the Epidermal Growth Factor Receptor and the Insulin-like Growth Factor Receptor for Enhanced Antitumor Activity (2005)

Both the epidermal growth factor receptor (EGFR) and the insulin-like growth factor receptor (IGFR) have been implicated in the tumorigenesis of a variety of cancers. Here we propose that simultaneous targeting of both receptors with a bispecific antibody would lead to enhanced antitumor activity. To this end, we produced a recombinant human IgG-like bispecific antibody, a Di-diabody, using the variable regions from two antagonistic antibodies: IMC-11F8 to EGFR and IMC-A12 to IGFR. The Di-diabody binds to both EGFR and IGFR and effectively blocked both EGF- and IGF-stimulated receptor activation and tumor cell proliferation. The Di-diabody also inherited the biological properties from both of its parent antibodies; it triggers rapid and significant IGFR internalization and degradation and mediates effective antibody-dependent cellular cytotoxicity in a variety of tumor cells. Finally, the Di-diabody strongly inhibited the growth of two different human tumor xenografts in vivo. Our results underscore the benefits of simultaneous targeting of two tumor targets with bispecific antibodies.
Serotype-specific outbreak of group B meningococcal disease in Iquique, Chile (1990)

From 1979 to August 1987, there have been 178 cases of meningococcal disease in Iquique, Chile, a city of about 140,000. The attack rate for the last 5 years has been in excess of 20/100,000 per year, more than 20 times greater than for the country overall. The mortality rate was 6%. The disease occurred in patients with ages from 4 months to 60 years, but 89% of cases were in patients less than 21 years. The largest number of cases were in the age group 5-9 years (n = 54), but the highest incidence occurred in children less than 1 year of age (72.8/100,000 per year). The male/female ratio was 1.2. Cases occurred all year round with little seasonal variation. Of the 178 cases, 173 were biologically confirmed. Serogroup analysis of strains from 135 patients revealed A = 1, B = 124, C = 10. Forty-four group B strains from 1985-7 were serotyped: 15:P1.3 = 36, 15:NT = 4, 4:P1.3 = 2, NT:NT = 2. Ten of 11 of the outbreak strains tested were sulfadiazine-resistant. This is the first recognized outbreak caused by a Gp B:15 strain in South America. It shares many of the characteristics of outbreaks caused by closely related strains in Europe, such as a predilection for older children and adolescents, sulfadiazine-resistance, and sustained high attack rates. The Iquique strain (B:15:P1.3) belongs to the same genetic clone (ET-5 complex) as the Norway (B:15:P1.16) and the Cuban (B:4:P1.15) strains.
Sensorimotor Gating and Schizophrenia (1990)

Human and animal model studies of sensorimotor gating allow us to understand the functional significance of attentional abnormalities and monoaminergic alterations in patients with schizophrenic disorders. Clinically, schizophrenic patients report oversensitivity to sensory stimulation that theoretically correlates with stimulus overload and leads to cognitive fragmentation. Paradigms using cortical event-related potentials and the prepulse inhibition of startle responses show that schizophrenic patients also have impaired central nervous system inhibition (sensorimotor gating). Animal model studies demonstrate that increased systemic aminergic activity and increased nucleus accumbens dopamine tone causes sensorimotor gating failure, similar to that seen in schizophrenic patients. The time course of the observed schizophrenic and animal model deficits is compatible with the "temporal map" of monoaminergic neuron functions (le, several hundred milliseconds). Studies of sensorimotor gating allow investigators to comment on the spatial and temporal mapping of neurons, trait and state deficits, and vulnerability factors in the schizophrenic spectrum of disorders. By translating attentional theories into testable hypotheses, the neurobiology of schizophrenic disorders becomes clearer.
Introduction to the human gut microbiota (2017)

The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host-microbe interactions.
Statistical Thermodynamics of Polymer Solutions (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStatistical Thermodynamics of Polymer SolutionsIsaac C. Sanchez and Robert H. LacombeCite this: Macromolecules 1978, 11, 6, 1145–1156Publication Date (Print):November 1, 1978Publication History Published online1 May 2002Published inissue 1 November 1978https://pubs.acs.org/doi/10.1021/ma60066a017https://doi.org/10.1021/ma60066a017research-articleACS PublicationsRequest reuse permissionsArticle Views4451Altmetric-Citations1127LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Use of peracetic acid to sterilize human donor skin for production of acellular dermal matrices for clinical use (2004)

We previously reported methods for sterilizing human skin for clinical use. In a comparison of gamma-irradiation, glycerol, and ethylene oxide, sterilization with ethylene oxide after treatment with glycerol provided the most satisfactory dermis in terms of structure and its ability to produce reconstructed skin with many of the characteristics of normal skin. However, the use of ethylene oxide is becoming less common in the United Kingdom due to concerns about its possible genotoxicity. The aim of this study was to evaluate peracetic acid as an alternative sterilizing agent. Skin sterilized with peracetic acid was compared with skin sterilized using glycerol alone or glycerol with ethylene oxide. The effect of subsequently storing peracetic acid sterilized skin in glycerol or propylene glycol was also examined. Acellular dermal matrices were produced after removal of the epidermis and cells in the dermis, processed for histological and ultrastructural analysis, and the biological function was evaluated by reconstitution with keratinocytes and fibroblasts. Results showed that sterilized acellular matrices retained the integrity of dermal structure and major components of the basement membrane. There were no overall significant differences in the ability of these matrices to form reconstructed skin, but peracetic acid alone gave a lower histologic score than when combined with glycerol or propylene glycol. We conclude that peracetic acid sterilization followed by preservation in glycerol or propylene glycol offers a convenient alternative protocol for processing of human skin. It is suggested that this sterile acellular dermis may be suitable for clinical use.
The DNA secondary structure of theBacillus subtilisgenome (2003)

The entire genomic DNA sequence of the Gram-positive bacterium Bacillus subtilis reported in the SubtiList database has been subjected in this work to a complete bioinformatic analysis of the potential formation of secondary DNA structures such as hairpins and bending. The most significant of these structures have been mapped with respect to their genomic location and compared to those structures already known to have a physiological role, such as the rho-independent transcription terminators. The distribution of these structures along the bacterial chromosome shows two major features: (i). the concentration of the most curved DNA in the intergenic regions rather than within the ORFs, and (ii). a decreasing gradient of large hairpins from the origin towards the terC end of chromosomal DNA replication. Given the increasing biological relevance of secondary DNA structures, these findings should facilitate further studies on the evolution, dynamics and expression of the genetic information stored in bacterial genomes.
Further Analysis of Trials With Azacitidine in Patients With Myelodysplastic Syndrome: Studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B (2006)

Azacitidine provides important clinical benefits for patients with high-risk MDS.
Phosphotyrosine-independent Binding of SHC to the NPLH Sequence of Murine Protein-tyrosine Phosphatase-PEST (1996)

The phosphotyrosine binding (PTB) or phosphotyrosine interaction (PI) domain of the proto-oncoprotein p52SHC binds to an NPXpY consensus sequence found in several growth factor receptors (Kavanaugh, W. M., Turck, C. W., and Williams, L. T. (1994) Science 268, 1177-1179). The amino-terminal region of p52SHC, which includes the PTB/PI domain, has been previously shown to associate with protein-tyrosine phosphatase-PEST (PTP-PEST) in vivo (Habib, T. , Herrera, R., and Decker, S. J. (1994) J. Biol. Chem. 269, 25243-25246). We report here the detailed mapping of this interaction in a murine context using glutathione S-transferase fusion protein binding studies and peptide competition assays. We show that the interaction between murine SHC and murine PTP-PEST is mediated through the PTB/PI domain of murine SHC and an NPLH sequence found in the carboxyl terminus of murine PTP-PEST. Since this interaction is not dependent on the presence of a tyrosine-phosphorylated residue in the target sequence, this reveals that the PTB/PI domain of SHC can recognize both tyrosine-phosphorylated sequences and non-tyrosine-based recognition motifs.
Mechanism of In vitro Pancreatic Cancer Cell Growth Inhibition by Melanoma Differentiation–Associated Gene-7/Interleukin-24 and Perillyl Alcohol (2008)

The death rate for pancreatic cancer approximates the number of new cases each year, and when diagnosed, current therapeutic regimens provide little benefit in extending patient survival. These dire statistics necessitate the development of enhanced single or combinatorial therapies to decrease the pathogenesis of this invariably fatal disease. Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a potent cancer gene therapeutic because of its broad-spectrum cancer-specific apoptosis-inducing properties as well as its multipronged indirect antitumor activities. However, pancreatic cancer cells show inherent resistance to mda-7/IL-24 that is caused by a block of translation of mda-7/IL-24 mRNA in these tumor cells. We now reveal that a dietary agent perillyl alcohol (POH) in combination with Ad.mda-7 efficiently reverses the mda-7/IL-24 "protein translational block" by inducing reactive oxygen species, thereby resulting in mda-7/IL-24 protein production, growth suppression, and apoptosis. Pharmacologic inhibitor and small interfering RNA studies identify xanthine oxidase as a major source of superoxide radical production causing these toxic effects. Because both POH and Ad.mda-7 are being evaluated in clinical trials, combining a dietary agent and a virally delivered therapeutic cytokine provides an innovative approach for potentially treating human pancreatic cancer.