gebhart/patrepeval huggingface dataset:
A pilot phase II study of digoxin in patients with recurrent prostate cancer as evident by a rising PSA. (2013)

5061 Background: Hypoxia-inducible factor 1α (HIF-1α) is a novel cancer drug target and inhibitors of hypoxia-response pathway are being developed. Digoxin and other cardiac glycosides were found to inhibit prostate cancer (PCa) growth via the inhibition of HIF-1α synthesis in mouse model. Epidemiologic data showed that use of digoxin in men was associated with a significant lower risk of development of PCa. We hypothesized that therapeutic dose of digoxin could inhibit human PCa growth and disease progression. Methods: Open label, non-placebo pilot study. Non-metastatic, biochemically relapsed PCa patients (pts) with prostate specific antigen doubling time (PSADT) of 3 -24 months and no hormonal therapy within the past 6 months were enrolled. All pts had testosterone &gt; 50 ng/dL at baseline. Digoxin was taken daily with dose titration to therapeutic level (0.8 – 2 mg/dl) and pts had routine follow-up that include cardiac monitoring with EKG. The primary endpoint was to evaluate the proportion of patients at 6 month post-treatment that had a PSADT &gt; 200% from the baseline. Results: Fifteen pts were enrolled into the study with 13 pts finishing the planned 6 months of treatment. Twenty percent (3/15) of the pts had PSA decrease &gt;25% from baseline. At 6 months, 7 of 15 (47%) pts had PSADT &gt; 200% of the baseline PSADT and were continued on study for an additional 24 weeks of treatment. Mean duration of digoxin treatment was 34.5 weeks. Digoxin was well tolerated with possible relation of one grade 3 back pain and one grade 2 hyperglycemia. No pts came off study due to cardiac reasons. Pre-and post-treatment PSA kinetics, vascular endothelial growth factors and other cytokines levels are being determined. Conclusions: Digoxin was well tolerated and showed a prolongation in the PSDAT in 47% of the patients. Digoxin may have biologic activity in men with androgen-dependent PCa but further controlled studies are required to confirm the results. Clinical trial information: NCT01162135.
Cancer of Unknown Primary Sites: What Radiologists Need to Know and What Oncologists Want to Know (2013)

With advances in imaging, pathology, and molecular medicine, the diagnosis and management of CUP have evolved into more personalized and site-specific therapies. A multidisciplinary integrated approach among oncologists, pathologists, and radiologists is extremely important.
Production of the Rare Ginsenoside Rh2-MIX (20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3) by Enzymatic Conversion Combined with Acid Treatment and Evaluation of Its Anti-Cancer Activity (2017)

The ginsenoside Rh2 has strong anti-cancer, anti-inflammatory, and anti-diabetic effects. However, the application of ginsenoside Rh2 is restricted because of the small amounts found in Korean white and red ginsengs. To enhance the production of ginsenoside Rh2-MIX (comprising 20(<i>S</i>)-Rh2, 20(<i>R</i>)-Rh2, Rk2, and Rh3 as a 10-g unit) with high specificity, yield, and purity, a new combination of enzymatic conversion using the commercial enzyme Viscozyme L followed by acid treatment was developed. Viscozyme L treatment at pH 5.0 and 50°C was used initially to transform the major ginsenosides Rb1, Rb2, Rc, and Rd into ginsenoside F2, followed by acid-heat treatment using citric acid 2% (w/v) at pH 2.0 and 121°C for 15 min. Scale-up production in a 10-L jar fermenter, using 60 g of the protopanaxadiol-type ginsenoside mixture from ginseng roots, produced 24 g of ginsenoside Rh2-MIX. Using 2 g of Rh2-MIX, 131 mg of 20(<i>S</i>)-Rh2, 58 mg of 20(<i>R</i>)-Rh2, 47 mg of Rk2, and 26 mg of Rh3 were obtained at over 98% chromatographic purity. Then, the anti-cancer effect of the four purified ginsenosides was investigated on B16F10, MDA-MB-231, and HuH-7 cell lines. As a result, these four rare ginsenosides markedly inhibited the growth of the cancer cell lines. These results suggested that rare ginsenoside Rh2-MIX could be exploited to prepare an anti-cancer supplement in the functional food and pharmaceutical industries.
Immediate impact of yogic breathing on pulsatile cerebrospinal fluid dynamics (2022)

Cerebrospinal fluid (CSF), a clear fluid bathing the central nervous system (CNS), undergoes pulsatile movements. Together with interstitial fluid, CSF plays a critical role for the removal of waste products from the brain, and maintenance of the CNS health. As such, understanding the mechanisms driving CSF movement is of high scientific and clinical impact. Since pulsatile CSF dynamics is sensitive and synchronous to respiratory movements, we are interested in identifying potential integrative therapies such as yogic breathing to regulate CSF dynamics, which has not been reported before. Here, we investigated the pre-intervention baseline data from our ongoing randomized controlled trial, and examined the impact of four yogic breathing patterns: (i) slow, (ii) deep abdominal, (iii) deep diaphragmatic, and (iv) deep chest breathing with the last three together forming a yogic breathing called three-part breath. We utilized our previously established non-invasive real-time phase contrast magnetic resonance imaging approach using a 3T MRI instrument, computed and tested differences in single voxel CSF velocities (instantaneous, respiratory, cardiac 1st and 2nd harmonics) at the level of foramen magnum during spontaneous versus yogic breathing. In examinations of 18 healthy participants (eight females, ten males; mean age 34.9 ± 14 (SD) years; age range: 18-61 years), we observed immediate increase in cranially-directed velocities of instantaneous-CSF 16-28% and respiratory-CSF 60-118% during four breathing patterns compared to spontaneous breathing, with the greatest changes during deep abdominal breathing (28%, p = 0.0008, and 118%, p = 0.0001, respectively). Cardiac pulsation was the primary source of pulsatile CSF motion except during deep abdominal breathing, when there was a comparable contribution of respiratory and cardiac 1st harmonic power [0.59 ± 0.78], suggesting respiration can be the primary regulator of CSF depending on the individual differences in breathing techniques. Further work is needed to investigate the impact of sustained training yogic breathing on pulsatile CSF dynamics for CNS health.
Intratracheal injection of endotoxin and cytokines. IX. Contribution of CD11a/ICAM-1 to neutrophil emigration (1995)

Intratracheal injection of endotoxin [lipopolysaccharide (LPS)] in rats causes acute inflammation characterized by the emigration of neutrophils (PMNs) into the bronchoalveolar airspace. Antibody to PMN adhesion molecule CD11a inhibited LPS-initiated PMN accumulation in bronchoalveolar lavage (BAL) fluid by 32% (P < 0.001). Antibody to the endothelial CD11a counterreceptor intercellular adhesion molecule-1 (ICAM-1) inhibited LPS-initiated PMN accumulation in BAL fluid by 66% (P < 0.0001). Combined antibody blockade of ICAM-1 and the C-X-C chemokine cytokine-induced neutrophil chemoattractant (CINC) inhibited LPS-initiated PMN emigration by 80%, significantly more than antibody against either ICAM-1 or CINC alone. To study the relative contribution of alveolar macrophages and PMNs to intra-alveolar tumor necrosis factor (TNF), the LPS-induced TNF in BAL fluid was measured after depletion of circulating PMNs with a cytolytic antibody to CD18. Although the anti-CD18 antibody completely abrogated LPS-initiated PMN emigration into BAL fluid, TNF levels in BAL fluid were unaffected, suggesting that alveolar macrophages are the predominant cellular source of LPS-induced TNF production. In conclusion, 1) CD11a, ICAM-1, and CINC play major roles in the LPS-initiated emigration of PMNs into the bronchoalveolar space, and 2) the TNF that drives ICAM-1 and CINC expression is derived largely from alveolar macrophages rather than PMNs.
A coding artifacts removal algorithm based on spatial and temporal regularization (2004)

In this paper, we propose a new video post-processing algorithm for reducing coding artifacts. The algorithm is based on regularized image restoration technique, in which a nonconvex regularization function is used to enforce smoothness constraints on the spatial image pixels for suppressing coding artifacts while preserving important image attribute. Temporal regularization is carried out along the motion trajectories. We apply half-quadratic regularization and piecewise constraint strategy to simplify the optimization problem. Explicit filtering formulae are obtained and a recursive filtering algorithm is developed. Experimental results demonstrate that the proposed method can significantly improve both subjective and objective quality of MPEG-4 coded video sequences in comparison with the postprocessing technique in MPEG-4.
Bax-induced cytochrome c release from mitochondria depends on alpha-helices-5 and -6 (2004)

The pro-apoptotic protein Bax plays a key role in the mitochondrial signalling pathway. Upon induction of apoptosis, Bax undergoes a conformational change and translocates to mitochondrial membranes, where it inserts and mediates the release of cytochrome c from the intermembrane space into the cytosol. However, the domains of Bax that are essential for the induction of cytochrome c release are still elusive. Therefore various Bax deletion mutants were generated and expressed in Escherichia coli. The proteins were then purified in order to delineate the function of the transmembrane domain, the BH3 (Bcl-2 homology 3) domain and the putative pore-forming alpha-helices-5 and -6. These proteins were used to analyse the mechanism of Bax-induced cytochrome c release from mitochondria. None of the Bax proteins caused cytochrome c release merely through physical perturbation of the mitochondrial outer membrane. The alpha-helices-5 and -6 of Bax were shown to mediate the insertion of the protein into mitochondrial membranes and to be essential for the cytochrome c -releasing activity of Bax. In contrast, neither the transmembrane domain nor a functional BH3 domain is required for the Bax-mediated release of cytochrome c from mitochondria.
Highlighting Functional Mass Spectrometry Imaging Methods in Bioanalysis (2022)

Most mass spectrometry imaging (MSI) methods provide a molecular map of tissue content but little information on tissue function. Mapping tissue function is possible using several well-known examples of "functional imaging" such as positron emission tomography and functional magnetic resonance imaging that can provide the spatial distribution of time-dependent biological processes. These functional imaging methods represent the net output of molecular networks influenced by local tissue environments that are difficult to predict from molecular/cellular content alone. However, for decades, MSI methods have also been demonstrated to provide functional imaging data on a variety of biological processes. In fact, MSI exceeds some of the classic functional imaging methods, demonstrating the ability to provide functional data from the nanoscale (subcellular) to whole tissue or organ level. This Perspective highlights several examples of how different MSI ionization and detection technologies can provide unprecedented detailed spatial maps of time-dependent biological processes, namely, nucleic acid synthesis, lipid metabolism, bioenergetics, and protein metabolism. By classifying various MSI methods under the umbrella of "functional MSI", we hope to draw attention to both the unique capabilities and accessibility with the aim of expanding this underappreciated field to include new approaches and applications.
A cost model for similarity queries in metric spaces (1998)

Article A cost model for similarity queries in metric spaces Share on Authors: Paolo Ciaccia DEIS - CSITE-CNR, Bologna, Italy DEIS - CSITE-CNR, Bologna, ItalyView Profile , Marco Patella DEIS - CSITE-CNR, Bologna, Italy DEIS - CSITE-CNR, Bologna, ItalyView Profile , Pavel Zezula IEI-CNR, Pisa, Italy IEI-CNR, Pisa, ItalyView Profile Authors Info & Claims PODS '98: Proceedings of the seventeenth ACM SIGACT-SIGMOD-SIGART symposium on Principles of database systemsMay 1998 Pages 59–68https://doi.org/10.1145/275487.275495Online:01 May 1998Publication History 104citation586DownloadsMetricsTotal Citations104Total Downloads586Last 12 Months16Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Biomimetic Functionalized Surfaces and the Induction of Bone Formation (2017)

Tissue engineering still needs to assign the molecular basis of pattern formation, tissue induction, and morphogenesis: What next to morphogens and stem cells? Macroporous biomimetic matrices per se, without the addition of the soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β) supergene family, remarkably initiate the induction of bone formation. Carving geometries within different calcium phosphate-based macroporous bioreactors we show that geometric cues imprinted within the macroporous spaces initiate the spontaneous induction of bone. Concavities biomimetize the remodeling cycle of the primate osteonic bone and are endowed with functionalized smart geometric cues that per se initiate osteoblasts' differentiation with the expression and secretion of osteogenic molecular signals that induce bone as a secondary response. To study the role of calcium ions (Ca<sup>++</sup>) and osteoclastogenesis, coral-derived calcium carbonate (CC)/hydroxyapatite (HA) bioreactors with limited conversion to HA (7% HA/CC) were preloaded with 500 μg of the L-type voltage gated calcium channel blocker verapamil hydrochloride. Bioreactors were also loaded with 240 μg of the bisphosphonate zoledronate, an osteoclast inhibitor, and implanted in heterotopic sites of the rectus abdominis muscle of Papio ursinus. Bisphosphonate-treated specimens were characterized by a delayed profoundly inhibited induction of tissue patterning with limited induction of bone. Macroporous constructs pretreated with verapamil hydrochloride yielded limited bone formation. Similarly, 125 or 150 μg human Noggin previously adsorbed onto the macroporous bioreactors resulted in minimal bone formation by induction, indirectly showing that the initiation of bone formation is through the bone morphogenetic protein (BMP) pathway. Downregulation of BMP-2 and osteogenic protein-1 (OP-1) with upregulation of Noggin correlated with limited bone induction. Angiogenesis, capillary sprouting, and Ca<sup>++</sup> provide chemotactic signals for myoendothelial, myoblastic, and pericytic stem cell differentiation into osteoblastic-like cells expressing the osteogenic soluble molecular signals of the TGF-β supergene family. Secreted gene products are embedded directly onto the substratum within its regulatory concavities. The protected microenvironment of the concavities biomimetizes the phylogenetically ancient repetitive multitested designs and topographies of Nature. Migrating cells onto the primed substratum by osteoclastic nanotopographical geometric inductive modifications convert geometrical cues set by osteoclastogenesis into BMP gene expression pathways that ultimately set into motion the spontaneous induction of bone formation.
The prolongation of drug action in the treatment of diseases of the nose and paranasal sinuses. (1993)

In order to prolong drug contact with the mucous membrane, and thus therapeutic action, cellulose polymers have been used. These polymers exert no toxic action on liver function. The release of the drug from the polymer depends on the degree of polymer viscosity. The use of drug-containing polymers in the treatment of nasal diseases and paranasal sinusitis is highly effective.
Water-Solubilizing Hydrophobic ZnAgInSe/ZnS QDs with Tumor-Targeted cRGD-Sulfobetaine-PIMA-Histamine Ligands via a Self-Assembly Strategy for Bioimaging (2017)

Exploring the organic-to-aqueous phase transfer of quantum dots (QDs) is significant for achieving their versatile applications in biomedical fields. In this thematic issue, surface modification, size control, and biocompatibility of QDs and QDs-based nanocomposites are core problems. Herein, the new highly fluorescent tumor-targeted QDs-clusters consisting of ZnAgInSe/ZnS (ZAISe/ZnS) QDs and sulfobetaine-PIMA-histamine (SPH) polymer with the α<sub>ν</sub>β<sub>3</sub> integrin receptor cyclic RGD (c-RGD) were developed via ligand exchange and an accompanying self-assembly process. It was found that the structure of RGD-SPH QDs-clusters was propitious to reduce the capture of reticulo-endothelial system (RES) in virtue of external stealth ligands, and benefit to selectively accumulate at the tumor site after intravenous injection via active tumor targeting cooperated with the enhanced permeability and retention (EPR) effect. In the meantime, those clusters also recognized and enriched the cell surface when cocultured with the α<sub>ν</sub>β<sub>3</sub> integrin receptor overexpressed malignant cells (U87MG tumor). On the basis of the results, fabricating mutil-functional nanocomposites integrated with the long-term circulation and dual-targeting effects should be an interesting strategy for imaging cancer in vitro and in vivo.
Visible volume buffer for efficient hair expression and shadow generation (2003)

Much research has been conducted on hair modeling and hair rendering with considerable success. However, the immense number of hair strands means that memory and CPU time requirements are very severe. To reduce the memory and the time needed for hair modeling and rendering, a visible volume buffer is proposed. Instead of using thousands of thin hairs, the memory usage and hair modeling time can be reduced by using coarse background hairs and fine surface hairs. The background hairs can be constructed by using thick hairs. To improve the look of the hair model, the background hair near the surface is broken down into numerous thin hairs and rendered. The visible volume buffer is used to determine the surface hairs. The rendering time of the background and surface hairs is found to be faster than the conventional hair model by a factor of more than four with little lost in image quality. The visible volume buffer is also used to produce shadows for the hair model.
Intra prediction using in-loop residual coding for the post-HEVC standard (2017)

A few years after standardization of the High Efficiency Video Coding (HEVC), now the Joint Video Exploration Team (JVET) group is exploring post-HEVC video compression technologies. In the intra prediction domain, this effort has resulted in an algorithm with 67 internal modes, new filters and tools which significantly improve HEVC. However, the improved algorithm still suffers from the long distance prediction inaccuracy problem. In this paper, we propose an In-Loop Residual coding Intra Prediction (ILR-IP) algorithm which utilizes inner-block reconstructed pixels as references to reduce the distance from predicted pixels. This is done by using the ILR signal for partially reconstructing each pixel, right after its prediction and before its block-level out-loop residual calculation. The ILR signal is decided in the rate-distortion sense, by a brute-force search on a QP-dependent finite codebook that is known to the decoder. Experiments show that the proposed ILR-IP algorithm improves the existing method in the Joint Exploration Model (JEM) up to 0.45% in terms of bit rate saving, without complexity overhead at the decoder side.
Waiting for the Other Foot to Drop (2013)

A 65-year-old man presented with a 4-month history of fevers, sweats, fatigue, and weakness. He also reported that pain in his feet and calves was sufficiently distracting that he could not enjoy reading.
Hardware-based pointer data prefetcher (2004)

Effective prefetching of data from a lower memory hierarchy to higher level is a helpful way to combat the increasing memory latency that impedes the performance improvement. This paper presents a hardware-based prefetching technique to alleviate load misses caused by irregular access patterns common in linked-list structures. Different from previous works we identify a pointer load using its architecture source register. A table called target register bitmap (TRB) is maintained. By looking up this table we can identify if a load is a pointer load. We remember the base addresses of consumer load operations in a cache and prefetch the data pointed by speculative virtual addresses to a prefetch buffer, which is smaller than the data cache. Whenever a load is encountered, both the prefetch buffer and the data cache are looked up. SPEC2000 and Olden benchmarks are used to evaluate this method. This technique is able to predict accurately over 80% of the pointer load address. A system using this technique having 8KB LI data cache plus a 1KB address cache and a 1KB prefetch buffer gives an average of around 6% performance improvement over a system with 16KB LI data cache.
The use of citrullinated peptides and proteins for the diagnosis of rheumatoid arthritis (2010)

The presence or absence of antibodies to citrullinated peptides/proteins (ACPA) is an important parameter that helps a clinician set a diagnosis of early rheumatoid arthritis and, hence, initiate treatment. There are several commercial tests available to measure ACPA levels, although it can be difficult to decide what the best test for a given clinical question is. We analyzed literature data in which the diagnostic and other properties of various ACPA tests are compared. The results show that for diagnostic purposes the CCP2 test has the highest specificity, the highest sensitivity in stratified studies and the highest positive predictive value. For the prediction of future joint destruction the CCP2, MCV, and CCP3 tests may be used. The ability to predict the likelihood of not achieving sustained disease-modifying antirheumatic drug-free remission was highest for the CCP2 test. Finally, the levels of anti-CCP2 and anti-CCP3 (and possibly anti-mutated citrullinated vimentin) in rheumatoid arthritis patients are not significantly influenced by TNFalpha blocking agents.
Efficient and Accurate Construction of Genetic Linkage Maps from the Minimum Spanning Tree of a Graph (2008)

Genetic linkage maps are cornerstones of a wide spectrum of biotechnology applications, including map-assisted breeding, association genetics, and map-assisted gene cloning. During the past several years, the adoption of high-throughput genotyping technologies has been paralleled by a substantial increase in the density and diversity of genetic markers. New genetic mapping algorithms are needed in order to efficiently process these large datasets and accurately construct high-density genetic maps. In this paper, we introduce a novel algorithm to order markers on a genetic linkage map. Our method is based on a simple yet fundamental mathematical property that we prove under rather general assumptions. The validity of this property allows one to determine efficiently the correct order of markers by computing the minimum spanning tree of an associated graph. Our empirical studies obtained on genotyping data for three mapping populations of barley (Hordeum vulgare), as well as extensive simulations on synthetic data, show that our algorithm consistently outperforms the best available methods in the literature, particularly when the input data are noisy or incomplete. The software implementing our algorithm is available in the public domain as a web tool under the name MSTmap.