gebhart/patrepeval huggingface dataset:
Safety and Clinical Activity of Temsirolimus in Combination with Rituximab and DHAP in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma - Results of the Part I Cohort of the STORM Trial (2015)

Abstract Purpose. To evaluate the safety, tolerability and efficacy of the combination of the mTOR inhibitor Temsirolimus and a standard salvage regimen (R-DHAP) in patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL). Patients and Methods. This is a prospective, multicenter, phase II, open-label study. Patients with relapsed or refractory DLBCL with a maximum of two prior treatment lines were eligible. The STORM regimen consisted of Rituximab 375 mg/m² (day 2) and DHAP (Dexamethasone 40mg day 3-6, Cisplatine 100 mg/m² day 3, Cytarabine 2x2 g/m² day 4) with Temsirolimus added on day 1 and 8 of a 21 d cycle, with 2-4 cycles planned. In part I, dose levels for the mTOR inhibitor Temsirolimus from 25, 50, 75 and 100 mg were predefined. Results. Here we report on the preliminary results of part I of this clinical trial. 15 patients were included - 8 patients in the 25 mg cohort and 7 patients in the 50 mg cohort. Median age was 70 (range 49-76) years and median number of prior regimen was 1. Two DLTs (one venous thrombosis in the 25 mg cohort, one esophagus infection in the 50 mg cohort) were observed. The most frequent non-hematologic side effects were nausea (9 pts, 60%), epistaxis (7 pts, 47%), fatigue (6 pts, 40%), increased ALT (6 pts, 40%) and increased creatinine (6 pts, 40%). Frequent grade 3/4 events (n&gt;2) in both cohorts (25mg|50mg) included leukopenia (11 pts, 73% - with a mean duration of 4.4 days | 6.7 days ), thrombocytopenia (11 pts, 73% - with a mean duration of 4.6 days | 11.9 days), lymphopenia (6pts, 40%), anemia (5 pts, 33%), neutropenia (3 pts, 20%), renal failure (3 pts, 20%) and infections (4 pts, 27%, bladder infection, esophagus infection, central venous access infection, soft tissue infection, mucositis). Based on the observed toxicity profile, the independent data safety committee recommended a Temsirolimus dose of 25 mg given on day 1 and 8 for the part II extension cohort of the trial. All but one evaluable patient responded (10/11 pts, 91%), with two CRs and one CRu (27%). Four patients could not be evaluated for response at the time of this report. After a median follow up of 12 (range 5-22) months, no relapse has been documented so far (1 pt lost to follow up). Conclusion. Temsirolimus can be safely added to DHAP and Rituximab with promising activity. Recruitment into part II is ongoing and updated results will be presented. Disclosures Witzens-Harig: Pfizer: Honoraria, Research Funding; Roche: Honoraria. Keller:Roche: Consultancy, Honoraria; Pfizer: Consultancy. Viardot:Roche: Honoraria; CTI: Consultancy; Pfizer: Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy. Buske:Roche: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria. Ho:Sanofi: Research Funding. Hess:Janssen, Roche, Celgene, Novartis: Consultancy; Pfizer, Janssen, Roche, Mundipharma: Honoraria, Research Funding.
Quantile Regression and Its Applications: A Primer for Anesthesiologists (2019)

Multivariable regression analysis is a powerful statistical tool in biomedical research with numerous applications. While linear regression can be used to model the expected value (ie, mean) of a continuous outcome given the covariates in the model, quantile regression can be used to compare the entire distribution of a continuous response or a specific quantile of the response between groups. The advantage of the quantile regression methodology is that it allows for understanding relationships between variables outside of the conditional mean of the response; it is useful for understanding an outcome at its various quantiles and comparing groups or levels of an exposure on those quantiles. We present quantile regression in a 3-step approach: determining that quantile regression is desired, fitting the quantile regression model, and interpreting the model results. We then apply our quantile regression analysis approach using 2 illustrative examples from the 2015 American College of Surgeons National Surgical Quality Improvement Program Pediatric database, and 1 example utilizing data on duration of sensory block in rats.
Isotope Dilution Mass Spectrometry (IDMS) (2016)

This document contains recommendations for terminology in mass spectrometry. Development of standard terms dates back to 1974 when the IUPAC Commission on Analytical Nomenclature issued recommendations on mass spectrometry terms and definitions. In 1978, the IUPAC Commission on Molecular Structure and Spectroscopy updated and extended the recommendations and made further recommendations regarding symbols, acronyms, and abbreviations. The IUPAC Physical Chemistry Division Commission on Molecular Structure and Spectroscopy’s Subcommittee on Mass Spectroscopy revised the recommended terms in 1991 and appended terms relating to vacuum technology. Some additional terms related to tandem mass spectrometry were added in 1993 and accelerator mass spectrometry in 1994. Owing to the rapid expansion of the field in the intervening years, particularly in mass spectrometry of biomolecules, a further revision of the recommendations has become necessary. This document contains a comprehensive revision of mass spectrometry terminology that represents the current consensus of the mass spectrometry community.
A prospective trial to evaluate the performance of the multitarget hepatocellular carcinoma blood test (mt-HBT) for screening at-risk patients: The Altus study. (2022)

TPS486 Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death in the U.S. HCC surveillance is associated with improved early detection and receipt of curative treatment. However, current surveillance strategies suffer from low adherence and suboptimal sensitivity. The multi-target HCC blood test (mt-HBT) is a novel early detection assay that provides a qualitative result based on a multiparametric algorithm that incorporates information from methylation markers ( HOXA1, TSPYL5, and B3GALT6), AFP, and patient sex. Here, we describe the protocol for a prospective, multicenter clinical trial designed to investigate the performance of the mt-HBT in patients at risk for HCC. Methods: ALTernative to U/S (ALTUS) is a longitudinal, multicenter, prospective study with a targeted enrollment of 3,000 participants. The main inclusion and exclusion criteria are described in the table. Participants will receive HCC surveillance imaging (either U/S or CT/MRI) and blood collection for the mt-HBT. Those with positive U/S are anticipated to receive standard-of-care imaging follow-up with a multiphase CT or MRI, and those with a negative U/S will receive a study CT/MRI within 30 days of blood collection. Imaging interpretation is based on the CT/MRI LI-RADS (LR) v2018 categories. The primary endpoints are the overall sensitivity and specificity of the mt-HBT to detect HCC, defined as pathology-confirmed HCC or hepatocellular cholangiocarcinoma (cHCC-CCA), LR-4/5, or LR-TIV/M plus definite/probable HCC or cHCC-CCA. The secondary endpoints are mt-HBT early-stage sensitivity, and performance in a) participants with LR-5 or biopsy-confirmed HCC and b) participants confirmed non-HCC. Participants not diagnosed with a liver malignancy at visit one will continue to receive HCC surveillance, returning for a second visit ̃6 months from first blood collection. Blood will be collected after the second visit for the mt-HBT. Data on treatment will be collected for those diagnosed with HCC. Study participants and providers will be blinded to the mt-HBT results. Participants are currently enrolling across the U.S., with 60 targeted sites and an anticipated 12-month enrollment window. Clinical trial information: NCT05064553. [Table: see text]
Selection of D‐Amino‐Acid Peptides That Bind to Alzheimer's Disease Amyloid Peptide Aβ1–42 by Mirror Image Phage Display (2003)

A mirror image phage display approach was used to identify novel and highly specific ligands for Alzheimer's disease amyloid peptide Abeta(1-42). A randomized 12-mer peptide library presented on M13 phages was screened for peptides with binding affinity for the mirror image of Abeta(1-42). After four rounds of selection and amplification the peptides were enriched with a dominating consensus sequence. The mirror image of the most representative peptide (D-pep) was shown to bind Abeta(1-42) with a dissociation constant in the submicromolar range. Furthermore, in brain tissue sections derived from patients that suffered from Alzheimer's disease, amyloid plaques and leptomeningeal vessels containing Abeta amyloid were stained specifically with a fluorescence-labeled derivative of D-pep. Fibrillar deposits derived from other amyloidosis were not labeled by D-pep. Possible applications of this novel and highly specific Abeta ligand in diagnosis and therapy of Alzheimer's disease are discussed.
Concise Preparation of 2,2-Difluorohomopropargyl Carbonyl Derivatives. Application to the Synthesis of 4,4-Difluoroisoquinolinone Congeners (2008)

A scalable synthesis of 2,2-difluorohomopropargyl esters was achieved using a magnesium-promoted Barbier reaction of substituted difluoropropargyl bromides with alkyl chloroformates. These 2,2-difluorohomopropargyl esters were effective precursors in the synthesis of homopropargylic amides-by aminolysis using AlMe3, as well as of ketones-through the reaction of the corresponding Weinreb amides with Grignard reagents. Ring closing metathesis using difluorinated 1,7-enyne carbonyl compounds furnished six-membered diene products, which were used as susbstrates in a Diels-Alder reaction to afford 4,4-difluoroisoquinolin-3-ones. The [2 + 2 + 2] cycloaddition of alkynes with fluorinated 1,7-diyne amides gave 4,4-difluoro-1,4-dihydro-3(2H)-isoquinolinone derivatives regioselectively.
Salicylate Potentiates Amikacin Therapy in Rodent Models of Klebsiella pneumoniae Infection (1993)

In vitro effects of salicylate on Klebsiella pneumoniae include capsule repression and enhanced aminoglycoside activity. The effects of high-dose salicylate on amikacin therapy were assessed in animal models. In a mouse lethality model, amikacin protective doses were reduced up to 12-fold by salicylate doses of 277 mg/kg. Salicylate alone increased the LD50 for K. pneumoniae in mice by nearly 1 log unit. In a lobar pneumonia model, rats received salicylate-amikacin intravenously 3 days after challenge, and bacteria were quantified from lung tissue on day 7. Rats receiving one-fourth the minimum effective amikacin dose had 1 x 10(6) cfu/g of lung, while no bacteria were detected in those also receiving salicylate (173 mg/kg). At one-eighth the minimum effective dose of amikacin, salicylate prevented the development of pneumonia. Salicylate potentiation of antimicrobial therapy far surpassed that observed in vitro, yet the potentiation was abolished in neutropenic animals. Thus, salicylate may enhance phagocytosis rather than antibiotic action in therapy.
Cermets from molten metal infiltration processing (2023)

New cermets with improved properties and applications are provided. These new cermets have lower density and/or higher hardness than B4C cermet. By incorporating other new ceramics into B4C powders or as a substitute for B4C, lower densities and/or higher hardness cermets result. The ceramic powders have much finer particle size than those previously used which significantly reduces grain size of the cermet microstructure and improves the cermet properties.
Developing a generalized BRDF model from experimental data (2018)

In this paper, we present a model for BRDF that can be developed from a limited set of experimentally observed data, and which then can be used for predictive purposes in scene-generation or sensor-performance applications. The model is physics based and can be as detailed as desired, depending on the scope of experimental data available. Basic input parameters required are the complex refractive index of the material, or the directional hemispherical reflectivity (DHR) for s- and p-polarized radiation. At least one BRDF measurement is needed to determine the angular spread function. Incorporating BRDF measurements at several angles of incidence into the model yields better accuracy for describing behavior such as forward scatter, depolarization, the participation of volumetric and surface-scattering mechanisms in layered surfaces, diffuse-scatter coherence properties, and narrowing of the angular spread function which provides an indication of optical depth. Illustrations and demonstrations of the methodology are drawn from data sets measured on bead-blasted aluminum, automotive paint incorporating a clear-coat layer, and green low-gloss vehicle paint.
Electron Microscopy of Biomolecules (2006)

Electron microscopy (EM) is a method appropriate for examining details of the sizes and shapes of biological macromolecules and is particularly useful in studying isolated or reconstituted macromolecular assemblies. Small amounts of material (often < 1 µg) can be used and prepared in a state suitable for viewing in as short a time as several minutes. The basic procedure involves adsorption of the biomolecules onto a support film, followed by staining or shadowing of the preparation and viewing of the dehydrated molecules in vacuo in an electron beam. A resolution of 1 to 2 nm is routine with conventional microscopes. The basic procedure can be adapted to give information about sites of specific epitopes, location of newly synthesized components, internal structures, and atomic composition. Structures most suitable for EM analysis are nucleoprotein complexes, including ribosomes, spliceosomes, nucleosomes, and virus particles. DNA and RNA molecules are also suitable, and their lengths can be directly related to the number of base pairs or nucleotide residues determined biochemically. In general, it is difficult to visualize small proteins (<50 000 Da), but good detail can be obtained if they are isolated as multimeric complexes or if they can be induced to form filaments or crystalline arrays. A wide range of applications are available using EM techniques, including virus identification, mapping of hybridized regions in heteroduplexes, detailing of macromolecular interaction, and analysis of the organization of molecular components in replication, transcription, splicing, and translation complexes.
Mitogen Stimulation Cooperates with Telomere Shortening To Activate DNA Damage Responses and Senescence Signaling (2004)

Replicative senescence is induced by critical telomere shortening and limits the proliferation of primary cells to a finite number of divisions. To characterize the activity status of the replicative senescence program in the context of cell cycle activity, we analyzed the senescence phenotypes and signaling pathways in quiescent and growth-stimulated primary human fibroblasts in vitro and liver cells in vivo. This study shows that replicative senescence signaling operates at a low level in cells with shortened telomeres but becomes fully activated when cells are stimulated to enter the cell cycle. This study also shows that the dysfunctional telomeres and nontelomeric DNA lesions in senescent cells do not elicit a DNA damage signal unless the cells are induced to enter the cell cycle by mitogen stimulation. The amplification of senescence signaling and DNA damage responses by mitogen stimulation in cells with shortened telomeres is mediated in part through the MEK/mitogen-activated protein kinase pathway. These findings have implications for the further understanding of replicative senescence and analysis of its role in vivo.
Predicting transfusions in cardiac surgery: the easier, the better: the Transfusion Risk and Clinical Knowledge score (2009)

A simple risk model based on five predictors only has a similar or better accuracy and calibration in predicting the transfusion rate in cardiac surgery than more complex models.
Comparison and Mechanism Study of Antibacterial Activity of Cationic and Neutral Oligo-Thiophene-Ethynylene (2021)

Photodynamic therapy (PDT) is a potential approach to resolve antibiotic resistance, and phenylene/thiophene-ethynylene oligomers have been widely studied as effective antibacterial reagents. Oligomers with thiophene moieties usually exhibit good antibacterial activity under light irradiation and dark conditions. In the previous study, we verified that neutral oligo-<i>p</i>-phenylene-ethynylenes (OPEs) exhibit better antibacterial activity than the corresponding cationic ones; however, whether this regular pattern also operates in other kinds of oligomers such as oligo-thiophene-ethynylene (OTE) is unknown. Also, the antibacterial activity comparison of OTEs bearing cyclic and acyclic amino groups will offer useful information to further understand the role of amino groups in the antibacterial process and guide the antibacterial reagent design as amino groups affect the antibacterial activity a lot. We synthesized four OTEs bearing neutral or cationic, cyclic, or acyclic amino groups and studied their antibacterial activity in detail. The experimental results indicated that the OTEs exhibited better antibacterial activity than the OPEs, the neutral OTEs exhibited better antibacterial activity in most cases, and OTEs bearing cyclic amino groups exhibited better antibacterial activity than those bearing acyclic ones in most cases. This study provides useful guidelines for further antibacterial reagent design and investigations.
26.5 A 0.7V 1.5-to-2.3mW GNSS receiver with 2.5-to-3.8dB NF in 28nm FD-SOI (2016)

We are approaching the age of IoE, in which wearable devices such as smart watches will be widespread. Sensing processors play a key role and the Global Navigation Satellite System (GNSS) is considered fundamental. Power consumption is one of the most important characteristics for such sensing processors. However, current GNSS receivers consume around 10mW [1,2] and are difficult to be embedded. GNSS receivers require high supply voltage for low-noise RF, which contributes to large power consumption. We developed 0.7V RF circuits that enable effective use of FD-SOI. Among the RF circuits, an LNA and an LPF are the key to 0.7V operation. We implemented an LNA with DC feedback using an OPAMP and an LPF that is composed of OTAs that have positive feedback as well as a mechanism for adjusting the output common-mode voltage.
Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Alirocumab Treatment in the ODYSSEY OUTCOMES Trial (2019)

A high PRS for CAD is associated with elevated risk for recurrent MACE after acute coronary syndrome and a larger absolute and relative risk reduction with alirocumab treatment, providing an independent tool for risk stratification and precision medicine.
Search forD0−D0mixing and doubly-Cabibbo-suppressed decays of theD0in hadronic final states (1998)

We present results of a search for ${D}^{0}\ensuremath{-}{D}^{0}$ mixing and doubly-Cabibbo-suppressed decays of the ${D}^{0}$ in Fermilab experiment E791, a fixed-target charm hadroproduction experiment. We look for evidence of mixing in the decay chain ${D}^{*}\ensuremath{\rightarrow}\ensuremath{\pi}\stackrel{\ensuremath{\rightarrow}}{D}\ensuremath{\pi}(K\ensuremath{\pi}$ or $K\ensuremath{\pi}\ensuremath{\pi}\ensuremath{\pi})$. If the charge of the pion from the ${D}^{*}$ decay is the same as the charge of the kaon from the $D$ decay (a ``wrong-sign'' event), mixing may have occurred. Mixing can be distinguished from other sources of wrong-sign events (such as doubly-Cabibbo-suppressed decays) by analyzing the distribution of decay times. We see no evidence of mixing. Allowing for $\mathrm{CP}$ violation in the interference between DCS and mixing amplitudes our fitted ratio for mixed to unmixed decay rates is ${r}_{\mathrm{mix}}{=(0.39}_{\ensuremath{-}0.32}^{+0.36}\ifmmode\pm\else\textpm\fi{}0.16)%$. This corresponds to a 90% C.L. upper limit of ${r}_{\mathrm{mix}}&lt;0.85%$. The sensitivity of this result is comparable to that of previous measurements, but the assumptions made in fitting the data are notably more general. We present results from many fits to our data under various assumptions. If we assume ${r}_{\mathrm{mix}}=0$, we find a two-sigma wrong-sign enhancement in the $K\ensuremath{\pi}$ mode which we ascribe to doubly Cabibbo-suppressed decays. The ratios of doubly Cabibbo-suppressed decays to Cabibbo-favored decays are ${r}_{\mathrm{dcs}}(K\ensuremath{\pi}{)=(0.68}_{\ensuremath{-}0.33}^{+0.34}\ifmmode\pm\else\textpm\fi{}0.07)%$ and ${r}_{\mathrm{dcs}}(K\ensuremath{\pi}\ensuremath{\pi}\ensuremath{\pi}{)=(0.25}_{\ensuremath{-}0.34}^{+0.36}\ifmmode\pm\else\textpm\fi{}0.03)%$.
Design study of a brain-dedicated time-of-flight PET system with a hemispherical detector arrangement (2019)

Time-of-flight (TOF) is now a standard technology for positron emission tomography (PET), but its effective use for small diameter PET systems has not been studied well. In this paper, we simulated a brain-dedicated TOF-PET system with a hemispherical detector arrangement. We modeled a Hamamatsu TOF-PET module (C13500-4075LC-12) with 280 ps coincidence resolving time (CRT), in which a 12 × 12 array of multi pixel photon counters (MPPCs) is connected to a lutetium fine silicate (LFS) crystal array of 4.1 × 4.1 mm<sup>2</sup> cross section each, based on one-to-one coupling. On the other hand, spatial resolution degradation due to the parallax error should be carefully addressed for the small diameter PET systems. The ideal PET detector would have both depth-of-interaction (DOI) and TOF capabilities, but typical DOI detectors that are based on light sharing tend to degrade TOF performance. Therefore, in this work, we investigated non-DOI detectors with an appropriate crystal length, which was a compromise between suppressed parallax error and decreased sensitivity. Using GEANT4, we compared two TOF detectors, a 20 mm long non-DOI and a 10 mm long non-DOI, with a non-TOF, 4-layer DOI detector with a total length of 20 mm (i.e. 5 × 4 mm). We simulated a contrast phantom and evaluated the relationship between the contrast recovery coefficient (CRC) and the noise level (the coefficient of variation, COV) for reconstructed images. The 10 mm long non-DOI, which reduces the parallax error at the cost of sensitivity loss, showed better imaging quality than the 20 mm long non-DOI. For example, the CRC value of a 10 mm hot sphere at COV = 20% was 72% for the 10 mm long non-DOI, which was 1.2 times higher than that of the 20 mm long non-DOI. The converged CRC values for the 10 mm long non-DOI were almost equivalent to those of the non-TOF 4-layer DOI, and the 10 mm long non-DOI converged faster than the non-TOF 4-layer DOI did. Based on the simulation results, we evaluated a one-pair prototype system of the TOF-PET detectors with 10 mm crystal length, which yielded the CRT of 250 ± 8 ps. In summary, we demonstrated support for feasibility of the brain-dedicated TOF-PET system with the hemispherical detector arrangement.