gebhart/patrepeval huggingface dataset:
Search for metabolites of ecteinascidin 743, a novel, marine-derived, anti-cancer agent, in man (2001)

Ecteinascidin 743 (ET-743) is a potent anti-tumoral agent of a marine origin. It is currently being tested in phase II clinical trials using a 3-weekly 24-h i.v. infusion of 1500 microg/m(2) and 3-h infusions of 1650 microg/m(2). Knowledge of the metabolism of ET-743 is, however, still scarce. In the present study, a qualitative chromatographic discovery of metabolites of ET-743 in man is reported. ET-743 and its demethylated analog ET-729 were incubated at 37 degrees C in the presence of enzyme systems, pooled human microsomes, pooled human plasma and uridine 5'-diphosphoglucuronyltransferase, respectively, in appropriate media. Reaction products were investigated chromatographically using photodiode array and ion spray-mass spectrometric detection (LC-MS). The main reaction products in microsomal incubations of ET-743 resulted from a remarkable breakdown of the molecule. In plasma the drugs were deacetylated, and the transferase did actually yield a glucuronide of both ET-743 and ET-729. In contrast, screening of urine, plasma and bile, collected from patients treated with ET-743 at the highest dose levels, using a sensitive LC-MS assay, did not result in detection of ET-729 and metabolites which were generated in vitro. The urinary excretion of ET-743 in man was lower than 0.7% of the administered dose for a 24-h infusion.
Rates of cholesterol, ubiquinone, dolichol and dolichyl‐P biosynthesis in rat brain slices (1990)

Slices from the brain and liver of rats were prepared and upon incubation exhibited a continuous and high capacity for incorporation of radioactive precursors into proteins and lipids. Using [3H]mevalonate as precursor, the rates of biosynthesis of cholesterol, ubiquinone, dolichol and dolichyl-P in brain slices were determined and found to be 5.5, 0.25, 0.0093 and 0.0091 nmol/h/g, respectively. Dolichol and dolichyl-P accumulate to a limited extent, but almost all of these lipids in the brain originate from de novo synthesis. The calculated half-lives for cholesterol, ubiquinone, dolichol and dolichyl-P were 4076, 90, 1006 and 171 h, respectively. The results indicate that lipids formed via the mevalonate pathway in the brain have an active and independently regulated biosynthesis.
Convolutional neural networks for face recognition (1996)

Faces represent complex, multidimensional, meaningful visual stimuli and developing a computational model for face recognition is difficult. We present a hybrid neural network solution which compares favorably with other methods. The system combines local image sampling, a self-organizing map neural network, and a convolutional neural network. The self-organizing map provides a quantization of the image samples into a topological space where inputs that are nearby in the original space are also nearby in the output space, thereby providing dimensionality reduction and invariance to minor changes in the image sample, and the convolutional neural network provides for partial invariance to translation, rotation, scale, and deformation. The method is capable of rapid classification, requires only fast, approximate normalization and preprocessing, and consistently exhibits better classification performance than the eigenfaces approach on the database considered as the number of images per person in the training database is varied from 1 to 5. With 5 images per person the proposed method and eigenfaces result in 3.8% and 10.5% error respectively. The recognizer provides a measure of confidence in its output and classification error approaches zero when rejecting as few as 10% of the examples. We use a database of 400 images of 40 individuals which contains quite a high degree of variability in expression, pose, and facial details.
lnterleukin-6 and Tumour Necrosis Factor Levels Decrease in the Suction Blister Fluids of Psoriatic Patients during Effective Therapy (1994)

These results are in agreement with a functional involvement of these two cytokines in the pathogenesis of the disease and their possible use as follow-up markers.
Disease contact tracing in random and clustered networks (2005)

The efficacy of contact tracing, be it between individuals (e.g. sexually transmitted diseases or severe acute respiratory syndrome) or between groups of individuals (e.g. foot-and-mouth disease; FMD), is difficult to evaluate without precise knowledge of the underlying contact structure; i.e. who is connected to whom? Motivated by the 2001 FMD epidemic in the UK, we determine, using stochastic simulations and deterministic 'moment closure' models of disease transmission on networks of premises (nodes), network and disease properties that are important for contact tracing efficiency. For random networks with a high average number of connections per node, little clustering of connections and short latency periods, contact tracing is typically ineffective. In this case, isolation of infected nodes is the dominant factor in determining disease epidemic size and duration. If the latency period is longer and the average number of connections per node small, or if the network is spatially clustered, then the contact tracing performs better and an overall reduction in the proportion of nodes that are removed during an epidemic is observed.
Towards a theory of modern human origins: Geography, demography, and diversity in recent human evolution (1998)

The origins of modern humans have been the central debate in palaeoanthropology during the last decade. We examine the problem in the context of the history of anthropology, the accumulating evidence for a recent African origin, and evolutionary mechanisms. Using a historical perspective, we show that the current controversy is a continuation of older conflicts and as such relates to questions of both origins and diversity. However, a better fossil sample, improved dates, and genetic data have introduced new perspectives, and we argue that evolutionary geography, which uses spatial distributions of populations as the basis for integrating contingent, adaptive, and demographic aspects of microevolutionary change, provides an appropriate theoretical framework. Evolutionary geography is used to explore two events: the evolution of the Neanderthal lineage and the relationship between an ancestral bottleneck with the evolution of anatomically modern humans and their diversity. We argue that the Neanderthal and modern lineages share a common ancestor in an African population between 350,000 and 250,000 years ago rather than in the earlier Middle Pleistocene; this ancestral population, which developed mode 3 technology (Levallois/Middle Stone Age), dispersed across Africa and western Eurasia in a warmer period prior to independent evolution towards Neanderthals and modern humans in stage 6. Both lineages would thus share a common large-brained ancestry, a technology, and a history of dispersal. They differ in the conditions under which they subsequently evolved and their ultimate evolutionary fate. Both lineages illustrate the repeated interactions of the glacial cycles, the role of cold-arid periods in producing fragmentation of populations, bottlenecks, and isolation, and the role of warmer periods in producing trans-African dispersals. Yrbk Phys Anthropol 41:137–176, 1998. © 1998 Wiley-Liss, Inc.
On techniques for detecting circumscribed masses in mammograms (1989)

A method for detecting one type of breast tumor, circumscribed masses, in mammograms is presented. It relies on a combination of criteria used by experts, including the shape, brightness contrast, and uniform density of tumor areas. The method uses modified median filtering to enhance mammogram images and template matching to detect the tumors. In the template matching step, suspicious areas are identified by thresholding the cross-correlation values, and a percentile method is used to determine a threshold for each film. In addition, two tests are used to remove false alarms from the resulting candidates. The results obtained by applying these techniques to a set of test images are described. They are judged encouraging.
Computational Chemical Imaging for Cardiovascular Pathology: Chemical Microscopic Imaging Accurately Determines Cardiac Transplant Rejection (2015)

Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a stain-less approach using an emerging technology, Fourier transform infrared (FT-IR) spectroscopic imaging to identify different components of cardiac tissue by their chemical and molecular basis aided by computer recognition, rather than by visual examination using optical microscopy. We studied this technique in assessment of cardiac transplant rejection to evaluate efficacy in an example of complex cardiovascular pathology. We recorded data from human cardiac transplant patients' biopsies, used a Bayesian classification protocol and developed a visualization scheme to observe chemical differences without the need of stains or human supervision. Using receiver operating characteristic curves, we observed probabilities of detection greater than 95% for four out of five histological classes at 10% probability of false alarm at the cellular level while correctly identifying samples with the hallmarks of the immune response in all cases. The efficacy of manual examination can be significantly increased by observing the inherent biochemical changes in tissues, which enables us to achieve greater diagnostic confidence in an automated, label-free manner. We developed a computational pathology system that gives high contrast images and seems superior to traditional staining procedures. This study is a prelude to the development of real time in situ imaging systems, which can assist interventionists and surgeons actively during procedures.
Randomized phase II trial of S-1 versus S-1 plus irinotecan (IRIS) in patients with gemcitabine-refractory pancreatic cancer. (2013)

263 Background: Gemcitabine (Gem) monotherapy or Gem-based combination therapy is a standard first-line therapy for advanced pancreatic cancer (PC). There is no consensus on second-line therapy in patients (pts) with disease progression (PD) after Gem-based therapy. S-1, an oral fluoropyrimidine derivative, is commonly used for the second-line treatment of PC in Japan. Shitara et al previously reported that IRIS regimen showed that 44% of response rate (RR), 4.9 mo of median progression free survival (PFS), and 11.3 mo of median overall survival (OS), respectively. Therefore a randomized phase II trial was conducted to evaluate the efficacy and safety of IRIS compared with S-1 alone in the second-line setting. Methods: The inclusion criteria were as follows: (1) histologically or cytologically proven pancreatic adenocarcinoma or adenosquamous carcinoma; (2) confirmed PD after Gem treatment; (3) ECOG PS, 0-1; (4) measurable metastatic lesion based on RECIST criteria; (5) age ≥ 20 years; (6) total bilirubin &lt; 2.0 mg/dL. Patients were randomized to receive either IRIS (CPT-11 100 mg/m 2 , iv, d1,15 plus S-1 80/100/120 mg/day based on BSA, po, d1-14, q4w; Arm A) or S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w; Arm B). The primary endpoint was to compare PFS in Arm A and Arm B. Results: Of a total of 137 pts enrolled between Nov 2008 and Mar 2011, 127 were eligible (60 randomized to Arm A and 67 to B). Median PFS in Arm A and B was 107 and 58 days, respectively (HR= 0.767; 95% CI, 0.527-1.114; p=0.1750). Median OS in Arm A and B was 208 and 176 days, respectively (HR=0.749; 95% CI, 0.512-1.093; p=0.1338). RR was 18.3% in Arm A (11/60; 95% CI, 9.5-30.4) and 6.0% in Arm B (4/67; 95% CI, 1.7-14.6)(p=0.0311). The incidences of grade 3/4 toxicities were as follows: neutropenia (15.6% and 4.3%), anorexia (23.4% and 17.3%), nausea (6.3% and 2.9%), and diarrhea (3.1% and 2.9%) in Arm A and B, respectively. Both regimens were tolerable. Conclusions: Although IRIS showed no significant improvement in PFS or OS compared with S-1 alone in this study, it showed significant advantage in RR, and favorable HR in both of PFS and OS. IRIS might have potential power to treat second-line PC patients. Further study is warranted. Clinical trial information: JapicCTI-080657.
Intravenous immunoglobulin and Alzheimer's disease immunotherapy. (2007)

Amyloid-beta peptide (Abeta) contributes to the acute progression of Alzheimer's disease (AD) and has become the main target for therapeutics. Active immunization with Abeta in individuals with AD has been efficacious; however, some patients developed side effects, possibly related to an autoimmune response. Evidence that intravenous immunoglobulin (IVIg), an FDA-approved purified immunoglobulin fraction from normal human donor blood, shows promise of passive immunotherapy for AD is reviewed. Investigations into the molecular effects of IVIg on Abeta clearance, using the BV-2 cellular microglia line, demonstrate that IVIg dissolves Abeta fibrils in vitro, increases cellular tolerance to Abeta, enhances microglial migration toward Abeta deposits, and mediates phagocytosis of Abeta. Preliminary clinical results indicate that IVIg, which contains natural antibodies against the Abeta, warrants further study into its potential to deliver a controlled immune attack on the peptide, avoiding the immune toxicities that have had a negative impact on the first clinical trials of vaccine against Abeta.
Decline in Blood Pressure Over Time and Risk of Dementia (2004)

Blood pressure starts to decrease only 3 years before dementia diagnosis and continues to decline afterward. A greater decline in systolic pressure occurring 3 to 6 years before diagnosis is associated with an increased risk of dementia only in older people with already low blood pressure or affected by vascular disorders.
Sterile-Insect Methods for Control of Mosquito-Borne Diseases: An Analysis (2009)

Effective vector control, and more specifically mosquito control, is a complex and difficult problem, as illustrated by the continuing prevalence (and spread) of mosquito-transmitted diseases. The sterile insect technique and similar methods control certain agricultural insect pest populations in a species-specific, environmentally sound, and effective manner; there is increased interest in applying this approach to vector control. Such an approach, like all others in use and development, is not a one-size-fits-all solution, and will be more appropriate in some situations than others. In addition, the proposed release of pest insects, and more so genetically modified pest insects, is bound to raise questions in the general public and the scientific community as to such a method's efficacy, safety, and sustainability. This article attempts to address these concerns and indicate where sterile-insect methods are likely to be useful for vector control.
The presence of mast cells in agar cultures. (1980)

Using a specific stain and electron microscopy, small numbers of mast cells were detected in human bone marrow cultures. However, they were not detected in agar cultures containing murine bone marrow cells. In bone marrow cultures from three patients with acute myeloid leukemia the number of mast cells was elevated.
Computer-generated holograms fabricated by direct write of positive electron-beam resist (1993)

An e-beam lithographic technique is described that produces multiple discrete phase levels as a surface-relief structure directly in positive e-beam resist. Processing techniques are presented for two positive e-beam resists: EBR-9 and polymethyl methacrylate (PMMA). This fabrication technology is experimentally applied to produce sawtooth (blazed) gratings and multiphase-level numeric-type computer-generated holograms (i.e., kinoforms).
The N-End Rule Pathway (2012)

The N-end rule pathway is a proteolytic system in which N-terminal residues of short-lived proteins are recognized by recognition components (N-recognins) as essential components of degrons, called N-degrons. Known N-recognins in eukaryotes mediate protein ubiquitylation and selective proteolysis by the 26S proteasome. Substrates of N-recognins can be generated when normally embedded destabilizing residues are exposed at the N terminus by proteolytic cleavage. N-degrons can also be generated through modifications of posttranslationally exposed pro-N-degrons of otherwise stable proteins; such modifications include oxidation, arginylation, leucylation, phenylalanylation, and acetylation. Although there are variations in components, degrons, and hierarchical structures, the proteolytic systems based on generation and recognition of N-degrons have been observed in all eukaryotes and prokaryotes examined thus far. The N-end rule pathway regulates homeostasis of various physiological processes, in part, through interaction with small molecules. Here, we review the biochemical mechanisms, structures, physiological functions, and small-molecule-mediated regulation of the N-end rule pathway.
L-selectin inhibition does not reduce injury in a rabbit model of transient focal cerebral ischemia (2001)

Neutrophils are known to mediate injury in acute ischemic stroke especially during reperfusion. Migration of neutrophils into regions of ischemic injury involves binding to the endothelial cells via interactions with various adhesion molecules. One adhesion molecule, L-selectin, is found on the surface of leukocytes, and is shed prior to leukocyte infiltration. We studied whether a humanized antibody to L-selectin (HuDREG200) might limit ischemic injury in an experimental stroke model. New Zealand White rabbits underwent transorbital occlusion of the left middle cerebral, anterior cerebral and internal carotid arteries using aneurysm clips for 2 h followed by 6 h of reperfusion. Treatment with a saturating dose (4 mg kg-1) of HuDREG200 (n = 8) or vehicle (n = 8) was administered 20 min after occlusion and given as a single i.v. bolus. Hemispheric ischemic neuronal damage (IND) as seen on hematoxylin and eosin stained sections was no different between groups (HuDREG200, 23.3% +/- 6%; vehicle, 19.6% +/- 6%; mean +/- SEM, n.s., t-test). Immunohistochemical staining with neutrophil elastase confirmed the presence of neutrophils within regions of IND in control brains, but treatment did not alter their numbers within ischemic tissue. We conclude that antagonism of neutrophil adhesion at the level of L-selectin does not alter ischemic injury in experimental stroke.
Effect of antibody to transforming growth factor beta on bleomycin induced accumulation of lung collagen in mice. (1993)

These results suggest that TGF-beta has an important role in the aetiology of bleomycin induced lung fibrosis; the neutralisation of TGF-beta by systemic treatment with its antibodies offers a new mode of pharmacological intervention which may be useful in treating lung fibrosis.
The treatment of solid tumors by alpha emitters released from224Ra-loaded sources—internal dosimetry analysis (2010)

Diffusing alpha-emitters radiation therapy (DART) is a proposed new form of brachytherapy, allowing the treatment of solid tumors by alpha particles. DART utilizes implantable sources carrying small activities of radium-224, which continually release into the tumor radon-220, polonium-216 and lead-212 atoms, while radium-224 itself remains fixed to the source. The released atoms disperse inside the tumor by diffusive and convective processes, creating, through their alpha emissions, a high-dose region measuring several mm in diameter about each source. The efficacy of DART has been demonstrated in preclinical studies on mice-borne squamous cell carcinoma and lung tumors and the method is now being developed toward clinical trials. This work studies DART safety with respect to the dose delivered to distant organs as a result of lead-212 leakage from the tumor through the blood, relying on a biokinetic calculation coupled to internal dose assessments. It is found that the dose-limiting organs are the kidneys and red bone marrow. Assuming a typical source spacing of approximately 5 mm and a typical radium-224 activity density of 0.4-0.8 MBq g(-1) of tumor tissue, it is predicted that tumors weighing up to several hundred grams may be treated without reaching the tolerance dose in any organ.
A new member of acid-sensing ion channels from pituitary gland (2000)

Acid-sensing ion channels (ASICs) constitute a branch of the super-gene family of amiloride-sensitive sodium channels. So far five different ASICs have been cloned from mammalian tissues. They are activated by a drop of extracellular pH but differ with respect to effective agonist concentration, desensitization and mRNA expression pattern. Here we report cloning of ASIC4, a new protein showing about 45% identity to other ASICs. ASIC4 is 97% identical between rat and human and shows strongest expression in pituitary gland. Moreover, we detected expression throughout the brain, in spinal cord, and inner ear. ASIC4 cannot be activated by a drop of extracellular pH in Xenopus oocytes, suggesting association with other subunits or activation by a ligand different from protons. Our results suggest a role for ASICs also in endocrine glands.
Vibrational spectra of water molecules at quartz/water interfaces (1994)

Optical sum-frequency generation was used to study OH stretch vibrations of water molecules at fused quartz-water interfaces. The results indicate that orientations and bond ordering of interfacial water molecules are strongly affected by electrostatic interaction and hydrogen bonding of the molecules with the quartz surface.
Pathology Consultation on Transfusion-Related Acute Lung Injury (TRALI) (2012)

Transfusion-related acute lung injury (TRALI) is a serious condition characterized by respiratory distress, hypoxia, and bilateral pulmonary infiltrates, which occur within 6 hours of transfusion. Several theories have been proposed to explain the underlying pathologic mechanisms of TRALI. Immune-mediated TRALI accounts for over 80% of reported cases and is mediated by donor antibodies to HLAs and/or human neutrophil antigens (HNA). Immune-mediated TRALI is most commonly associated with donor plasma transfusion or other blood products from multiparous women, which has led many countries to reduce or exclude women from donating high-volume plasma products. This policy change has resulted in a decrease in the incidence of TRALI and highlighted the importance of nonimmune-mediated TRALI, which is thought to be caused by bioreactive lipids and other biologic response modifiers that accumulate during storage of blood products. When TRALI is suspected, clinical consultation with a transfusion medicine specialist helps differentiate it from other transfusion reactions with similar characteristics.
Determination of burn depth by polarization-sensitive optical coherence tomography (2004)

An assessment of burn depth is a key step in guiding the treatment of patients who have sustained thermal injuries. Polarization-sensitive optical coherence tomography (PS-OCT) might eventually provide the physician with a quantitative estimate of actual burn depth. Burns of various depths were induced by contacting rat skin with a brass rod preheated to 75 degrees C for 5, 15, or 30 s. Thermal injury denatured the collagen in the skin, and PS-OCT imaged the resulting reduction of birefringence through the depth-resolved changes in the polarization state of light propagated and reflected from the sample. Stokes vectors were calculated for each point in the PS-OCT images and the reduction in the rate of phase retardation between two orthogonal polarizations of light (deg/microm) was found to show a consistent trend with burn exposure time. PS-OCT is a noninvasive technique with potential to give the physician the information needed to formulate an optimal treatment plan for burn patients.