gebhart/patrepeval huggingface dataset:
Influence of Host Factors on Survival in Dogs with Malignant Mammary Gland Tumors (2003)

Abstract The purpose of our study was to determine if specific host factors, such as age at diagnosis, obesity, and hormone status, influence the prognosis of canine mammary gland carcinomas and to confirm if previously reported risk factors (ie, histologic subtype, tumor size, and World Health Organization [WHO] stage) were important in a large series of affected dogs. Ninety-nine female dogs with mammary gland carcinomas, no previous therapy, an excisional biopsy, and known cause of death were studied. No significant association with survival was noted for age at diagnosis (chronologic or physiologic), obesity, or hormone status (ie, spayed versus intact, regardless of time of being spayed). Of the tumor factors analyzed, the histologic subtype anaplastic carcinoma (P= .02), WHO stage I (P= .01), evidence of metastasis at the time of diagnosis (P= .004), and tumor size of 3 cm or smaller (P= .005) all significantly influenced survival. Dogs that were classified as having tumor-related mortality had a shorter postoperative survival compared to dogs that died of other causes (14 months versus 23 months; P= .03). In conclusion, histologic subtype, WHO stage, and tumor size remain important prognostic factors in canine mammary gland tumors. Further study of other prognostic factors is needed to determine which tumors are adequately addressed with local therapy only and which dogs may require adjuvant treatment with chemotherapy.
Overview of Flow Cytometry and Microbiology (2004)

Although in recent years flow cytometry has become commonplace in hematology and immunology laboratories, application of the technology to microbiology remains largely unrealized. This overview presents the historical background, discusses applications in various areas of the field, and speculates on the directions of future developments. The availability of high-quality methods should be a prime factor in convincing microbiologists that flow cytometry may have certain advantages over traditional methods and that it does indeed have much to contribute to microbiology.
Alternative routes of mucosal immunization in large animals (2004)

Mucosal immunization regimes that employ the oral route of delivery are often compromised by antigen degradation in the stomach. Moreover, tolerance or immunological unresponsiveness to orally delivered vaccine antigens is also a major problem associated with this route of immunization. Immunization by alternative routes including intrarectal (i.r.) and intranasal (i.n.) is becoming increasingly recognized in large animals for generating protective antibody responses at mucosal surfaces. These approaches are particularly useful in ruminant species which have four stomachs that can potentially interfere with antigen presentation to mucosal inductive sites of the gut. Modifications to enhance existing mucosal immunization regimes have also been explored through the use of alternative antigen delivery systems and mucosal adjuvants. The combination of alternative immunization routes and the use of appropriate antigen delivery systems appear to be a rational approach for providing protective immunity at mucosal surfaces. There has been a considerable amount of research conducted on evaluating the efficacy of emerging antigen delivery systems and novel adjuvants for improved immunity to mucosal immunization but very little of this work has been specific to the mucosal compartment of large animals. The aim of this review is therefore to assess the feasibility and practicality of using large animals (particularly sheep, cattle and pigs) for inducing and detecting specific immune responses to alternative mucosal routes of immunization.
Spatially and temporally local spike-timing-dependent plasticity rule (2006)

Recent neurophysiological research has focused on the temporal relationships between neuronal firing and plasticity, and has shown the phenomenon of spike-timing-dependent plasticity (STDP). Various models were suggested to implement the STDP-like learning rule in artificial networks based on spiking neuronal representations. Here we present and analyze a simple rule that only depends on the information that is available at the synapse at the time of synaptic modification. This rule is further extended by addition of four different types of gating derived from conventionally used types of gated decay in learning rules for continuous firing rate neural networks. The results show that the advantages of using these gatings are transferred to the new rule without sacrificing its dependency on spike-timing.
Phase I study using continuous intravenous (CI) KOS-862 (Epothilone D) in patients with solid tumors (2004)

2024 Background: Similar to taxanes, epothilones are a class of naturally occurring cytotoxic macrolides that stabilize microtubules and induce mitotic arrest, retaining potency in P-glycoprotein MDR cell lines. 6 schedules of KOS-862 were investigated in phase I trials. Methods: As the optimal schedule in the mouse xenograft model used prolonged exposure (6-hr IV infusion at 30 mg/kg) to reach plasma steady state Css=425 ng/mL, two CI schedules were attempted: a 24-hr CI (Schedule A) and up to 72-hr CI (Schedule B) q 2 weeks. Steady state is difficult to maintain for a drug with a rapid alpha distribution, hence a loading dose (75 mg/hr for 30 min) was incorporated, followed by maintenance dose. Results: 24 pts have been enrolled (median age 62 yrs, range 28–86 yrs; 7 F/17 M; median KPS 80; median prior regimens 3, range 0–10): 17 on Schedule A, 7 on Schedule B. Eighty total infusions have been administered. 4 dose levels have been tested on Schedule A (1, 2, 4 and 6 mg/hr rates); 2 dose levels on Schedule B (1 and 1.7 mg/hr). Drug-related toxicity includes mild-to-moderate fatigue, nausea/abdominal pain, dizziness, and neurosensory. One episode of grade 3 neurosensory occurred at 6 mg/hr x 24-hr CI; this dose group is being expanded. AUC=Css(SD) at this dose was 12300 ng/mL*h; constant dosing at 7 mg/h for 23.5 h would theoretically achieve a Css=423 ng/mL (Css=AUCSDτ n →τ n+1 /τ ). Pts dosed at 4 mg/h for 23.5h achieved Css=200 ng/mL. Comparison of PK between short infusion and CI showed similar results (mean±SD) CL=6.7±2.7 v 8.7±2.9 L/h/m2; half-life 10.3±2.9 v 10.8±2.3 hours; Vz 96±41 v136±59 L/m2; MRT 10.0±3.6 v 17.1±4.5 hours. As a marker of biologic activity, PBMCs were examined for microtubule bundle formation at the end of the CI. On Schedule A, 15 and 20% bundle formation at 4 and 6 mg/h was observed, respectively, indicating that there was significant polymerization over this period of time. Signs of antitumor activity included 1 pt with bladder ca (shrinkage of primarily nodal disease) and 1 pt with prostate ca (25% decline in PSA). Conclusions: Biologic activity at tolerable doses has been noted and accrual continues to define the recommended dose. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Kosan Biosciences, Inc. Kosan Biosciences, Inc. Kosan Biosciences, Inc. Kosan Biosciences, Inc. Kosan Biosciences, Inc.
Unanticipated transient sciatic nerve deficits from intra-wound liposomal bupivacaine injection during total hip arthroplasty (2015)

Liposomal bupivacaine (Exparel<sup>®</sup>) is a novel formulation of local anesthetic used to provide extended postoperative analgesia as part of a multimodal pain control regimen in patients undergoing total joint arthroplasty. In the three total hip arthroplasty cases described, all patients exhibited a transient loss of neurologic function in the sciatic nerve distribution of the operated extremity lasting between 24 and 72 h during the immediate postoperative period. Due to the nature and duration of the deficits, it was concluded that they likely occurred as a result of unintended injection of the medication in close proximity to the sciatic nerve. To the best of our knowledge, these events have yet to be reported in the current literature. We recommend orthopaedic surgeons pay special attention during infiltration of the medication at the surgical site to avoid postoperative neurological deficits.
In Vivo Targeting of Tumor Endothelial Cells by Systemic Delivery of Lentiviral Vectors (2003)

Tumor angiogenesis is a rate-limiting factor for tumor growth, and the endothelial cells of tumor vessels display specific features that can be exploited for the selective delivery of cancer therapeutics. To specifically target exogenous genes to angiogenic tumor vessels, we generated a panel of vesicular stomatitis virus-pseudotyped lentiviral vectors (LVs) engineered for endothelial cell (EC)-specific expression. We cloned a wide repertoire of transcription regulatory sequences from genes preferentially expressed in ECs (Tie1, Tie2, Flk-1, VE-Cad, and ICAM-2) into self-inactivating LVs to drive expression of the marker gene encoding green fluorescent protein (GFP) or of the conditionally toxic gene encoding nitroreductase, and compared them with the ubiquitously expressing phosphoglycerate kinase (PGK) and cytomegalovirus (CMV) promoters. We evaluated the efficiency and specificity of vector expression in vitro in a panel of human primary cultures, including ECs, fibroblasts, neurons, lymphocytes, and hematopoietic progenitors, and in tumor cell lines. We found that vectors containing promoter and enhancer sequences from the Tie2 gene achieved remarkable specificity of expression in ECs in vitro and in vivo. On intravenous delivery into tumor-bearing mice, the Tie2 vector targeted expression to the ECs of tumor vessels. In contrast, LVs carrying the PGK or CMV promoter gave widespread GFP marking in ECs and non-ECs of tumors and other organs. The previously reported upregulation of the Tie2 gene in ECs activated for angiogenesis may explain the remarkable selectivity of expression of the Tie2 vector in ECs of tumor vessels. The new vector provides the means for selective delivery of gene therapy to tumor sites in vivo.
On the role of interference in laser‐based mid‐infrared widefield microspectroscopy (2018)

A laser's high degree of coherence leads to interferences, which-in the absence of precautions-can cause severe image distortions such as fringes and speckles and which thereby strongly hamper a meaningful interpretation of hyperspectral images in laser-based widefield microspectroscopy. While images and spectra of homogenous samples may already suffer from interferences, any structured object such as a tissue thin section will add to these distortions due to wavelength- and, in particular, sample-dependent phase shifts (structure sizes, absorption coefficients, refractive indices). This effect is devastating for the universal applicability of laser-based microspectroscopy especially in the mid-infrared (MIR), where cell sizes are of the same dimension as the wavelength of the illumination source. Here, we show that the impact of interferences is strongly mitigated by reducing the time-averaged spatiotemporal coherence properties of the illumination using a moving plus a stationary scatterer. In this case, the illumination path provides a pseudothermal radiation source and spatially resolved spectra can be obtained at the quality of the reference method, that is, Fourier-transform infrared microspectroscopy, without compromising spectral or spatial resolution.
Complete androgen blockade as treatment for advanced prostate cancer: clinical response and side-effects. (1989)

Treatment of advanced prostatic cancer is currently based on hormonal manipulation. In 1982 Labrié supported a new concept of hormonal treatment based on complete androgen blockade. The objective of this study was to evaluate the effects of total androgen suppression, achieved by the combination of a LHRH agonist (buserelin) plus a pure anti-androgen (flutamide) in the long-term treatment of advanced prostate cancer. Forty-seven untreated consenting patients with advanced prostatic cancer entered in the study, and 41 of these proved evaluable for response and toxicity. Buserelin and Flutamide were administered three times daily, intranasally and orally respectively, at a dose of 1.2 mg and 750 mg for twelve months. Circulating testosterone levels, regularly measured during the study, were reduced by the treatment to castrated levels. Clinical results are encouraging for the high rate of objective and clinical responses PR + SD = 37 (90%), for its duration (12 months), for the significant improvement of urological symptoms and for the decrease of cancer-related pain, even in cases with detectable bone metastases. Compliance was excellent in all the subjects and no patient was forced to interrupt treatment because of cardiovascular toxicity or severe side-effects, which were limited to occasional loss of libido and potency, hot-flashes, mild diarrhea and nausea.
The Psychopharmacology of Agitation: Consensus Statement of the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup (2012)

Agitation is common in the medical and psychiatric emergency department, and appropriate management of agitation is a core competency for emergency clinicians. In this article, the authors review the use of a variety of first-generation antipsychotic drugs, second-generation antipsychotic drugs, and benzodiazepines for treatment of acute agitation, and propose specific guidelines for treatment of agitation associated with a variety of conditions, including acute intoxication, psychiatric illness, delirium, and multiple or idiopathic causes. Pharmacologic treatment of agitation should be based on an assessment of the most likely cause of the agitation. If agitation results from a delirium or other medical condition, clinicians should first attempt to treat the underlying cause instead of simply medicating with antipsychotics or benzodiazepines.
Analysis of a subclass-restricted HIV-1 gp41 epitope by omission peptides. (1989)

To define the amino acids involved in IgG subclass reactivity to two overlapping HIV-1 gp41 (E34/32; amino acid positions 582-613) peptides, sera from 18 HIV-infected individuals were studied. Peptides mimicking E34 but with single amino acid deletions or glycine substitutions were used to define the amino acid residues necessary for antibody binding. Two dominating immunogenic epitopes, containing highly hydrophilic amino acids, were found on the original peptide. Further analysis was undertaken with two corresponding omission sets of dodecapeptides representing halves of the complete E34 plus a terminal cystein peptide. The subclass reactivities usually differed between the patients with regard to the epitopes with which the different IgG subclasses reacted and also to the importance of different amino acids in antibody binding. The 600 glycine and the 601 lysine were involved in the binding of all IgG1, 2 and 4 and most IgG3. The development of E34/32-reactive IgM and IgG subclasses showed different patterns in four patients with primary HIV infections, contradicting the existence of a general pattern for the development of IgG subclasses to this peptide. The findings suggest that different progenitor clones are selected for synthesis of the different subclasses.
Review and Recent Development of Angle-Resolved Low-Coherence Interferometry for Detection of Precancerous Cells in Human Esophageal Epithelium (2008)

The combination of low-coherence interferometry with angle-resolved light scattering measurements has been shown to be a powerful method for determining the structure of cell nuclei within intact tissue samples. The nuclear morphology data have been used as a biomarker of neoplastic change in a wide range of settings. Here, we review the development of angle-resolved low-coherence interferometry (a/LCI) for assessing the health status of human esophageal epithelial tissues based on depth-resolved measurements of the morphology of cell nuclei. The design and implementation of clinical instrumentation are reviewed, and results from ex vivo human tissue measurements are presented to validate the capabilities of the technique. In addition to the review of earlier papers, new results are presented, which demonstrate the first application of a portable a/LCI system with a flexible endoscopic probe to assessing depth-resolved nuclear morphology in a clinical setting. High sensitivity for the detection of precancerous tissues is demonstrated.
Digital networks in the automotive vehicle (1999)

Automotive electronic systems are piggybacking on the exponential growth of the computer industry. This article takes a look at the progressive innovations which have shaped the electrical architecture of today&apos;s vehicles and which will mould tomorrow&apos;s. It discusses: why networks are necessary in vehicles; special attributes of these networks; examples of automotive control network protocols; importance of software in modern vehicles; and future automotive system trends.
Targeted and Armed Oncolytic Poxviruses for Cancer: the Lead Example of JX-594 (2012)

Oncolytic viruses (OVs) are designed to replicate in, and subsequently lyse cancer cells. Numerous oncolytic virus platforms are currently in development. Here we review preclinical and clinical experience with JX-594, the lead candidate from the targeted and armed oncolytic poxvirus class. JX-594 is derived from a vaccinia vaccine strain that has been engineered for 1) enhanced cancer targeting and 2) has been "armed" with the therapeutic transgene granulocytemacrophage colony stimulating factor (GM-CSF) to stimulate anti-tumoral immunity. Poxviruses have many ideal features for use as oncolytic agents. The development of oncolytic vaccinia viruses is supported by a large safety database accumulated in the smallpox eradication program. In addition, poxviruses have evolved unique capabilities for systemic spread through the blood that can be harnessed for the treatment of metastatic disease. JX-594 demonstrates a high degree of cancer selectivity and systemic efficacy by multiple mechanisms-of-action (MOAs) in preclinical testing. Data from Phase 1 and 2 clinical trials has confirmed that these features result in potent and systemic efficacy in patients with treatment refractory metastatic cancers.
Virus Particles as Templates for Materials Synthesis (1999)

Virus protein cages, capsids, which display a wide range of sizes and shapes, can be used for constrained materials synthesis. The authors briefly review recent work involving capsids, including the use of spherical viruses for inorganic mineralization and organic polymer encapsulation and the mineralization of anisotropic structures such as the tobacco mosaic virus, which can lead to mineralized fibers of iron oxide or silica with very high aspect ratios. The topic of gating—which enables the selective entrapment and release of materials from within the central cavity—is briefly touched upon.
Escape from Human Monoclonal Antibody Neutralization Affects In Vitro and In Vivo Fitness of Severe Acute Respiratory Syndrome Coronavirus (2010)

These data provide a mechanism for overcoming neutralization escape by use of broadly cross-reactive cocktails of cross-neutralizing MAbs that recognize residues within the receptor-binding domain that are critical for virus replication and virulence.
Near Net Shaping with Bimodal Powders on Shaped Membranes via EPD (2009)

The electrophoretic deposition (EPD) is a very promising process for shaping compacts, especially for nanopowders. Up till now EPD is not used on a large-scale production of ceramic products. Additionally, the higher cost of nanopowders was also a barrier for the development of new products. As the deposition rate at EPD is independent of particle size, it is an ideal process for shaping compacts of powder mixtures with nanopowders. Silica and zirconia powders were used as model systems to demonstrate the advantages of EPD. Applications might be the preparation of high-purity silica glass for processing of semiconductors and zirconia ceramics for near net-shaped dental crowns. In both cases the optimum green density was achieved for approx. 10 % addition of nanopowders to a coarser matrix powder. The compacts were homogenous. Alternatively, compacts of different powders can be prepared in a two-step process. Examples are shown for the electrophoretic impregnation (EPI) and a reactive forming of nanoparticles inside the pore volume of a compact consisting of coarser particles.
Aprotinin-like isoinhibitors in bovine organs. (1988)

Previous studies have shown that bovine spleen contains, besides aprotinin (bovine pancreatic trypsin inhibitor, BPTI), three iso-inhibitors (I-III), which are structurally and functionally very similar to BPTI. The primary structure of inhibitors I and II indicates that they are not post-translational products of BPTI, in agreement with independent findings on two homologous genes reported to be present in the bovine genome, which encode BPTI and inhibitors I and II, respectively. A careful reinvestigation on the occurrence of these inhibitors in various bovine organs is presented in this paper, based on their isolation with standard biochemical techniques and on functional and structural studies. All data indicate that the same isoinhibitors found in spleen are also present, besides BPTI, in organs such as lung, liver and pituitary gland, where they were never found before. BPTI and inhibitor II always prevail.
Uncouplers of Oxidative Phosphorylation (1990)

Uncouplers of oxidative phosphorylation in mitochondria inhibit the coupling between the electron transport and phosphorylation reactions and thus inhibit ATP synthesis without affecting the respiratory chain and ATP synthase (H(+)-ATPase). Miscellaneous compounds are known to be uncouplers, but weakly acidic uncouplers are representative because they show very potent activities. The most potent uncouplers discovered so far are the hindered phenol SF 6847, and hydrophobic salicylanilide S-13, which are active in vitro at concentrations in the 10 nM range. For induction of uncoupling, an acid dissociable group, bulky hydrophobic moiety and strong electron-withdrawing group are required. Weakly acidic uncouplers are considered to produce uncoupling by their protonophoric action in the H(+)-impermeable mitochondrial membrane. For exerting these effects, the stability of the respective uncoupler anions in the hydrophobic membrane is very important. High stability is achieved by delocalization of the polar ionic charge through uncoupler (chemical)-specific mechanisms. Such an action of weakly acidic uncouplers is characteristic of the highly efficient membrane targeting action of a nonsite-specific type of bioactive compound.
Gene Transfer for Angiogenesis in Coronary Artery Disease (2001)

Angiogenesis is a promising novel therapeutic strategy to provide new venues for blood flow in patients with severe ischemic heart and peripheral vascular disease, who are not candidates for standard revascularization strategies. We describe the underlying mechanisms involved in physiologic and therapeutic angiogenesis, underscoring the relative importance of vasculogenesis, angiogenesis, and arteriogenesis. We then present the various gene transfer vectors including plasmid, viral, and cell-based vectors, and various delivery modalities. The available preclinical data are presented, followed by a description of preliminary clinical experience, with an emphasis on the preliminary nature of these results, which address safety and not efficacy. Finally, we discuss the promises and pitfalls of clinical angiogenesis and gene transfer studies, stressing the importance of proper design of clinical trials and adequate protection of research subjects.