gebhart/patrepeval huggingface dataset:
Impact of the COVID-19 pandemic on care delivery and outcomes for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). (2021)

4137 Background: The coronavirus disease 2019 (COVID-19) pandemic has caused abrupt changes to the US health system and disruption in cancer care delivery. Little has been reported on the impact of COVID-19 on patients with mPDAC and the care delivery. Our study aimed to characterize the impact of COVID-19 on healthcare utilization and outcomes for patients with mPDAC in the US in the community oncology setting. Methods: We performed a retrospective cohort study of adult patients diagnosed with mPDAC between March – September 2019 and March – September 2020 using the nationwide Flatiron Health EHR database, comprising data from over 280 (largely community based) cancer clinics. Patients were stratified into two cohorts based on the year of diagnosis (2019 vs. 2020). Clinical characteristics were summarized including age at metastatic diagnosis, stage at initial diagnosis, and ECOG performance score (PS). Overall survival (OS) from metastatic diagnosis was estimated using Kaplan-Meier methods. A sensitivity analysis limiting the follow-up time to November of each year was conducted. Results: Overall, 1,719 patients were included in the study (2019: n = 923, 2020: n = 796); both cohorts had similar demographic compositions in terms of age and sex (2019: median age = 70 (IQR: 62 – 76), 52.2% male; 2020: median age = 70 [IQR: 62 – 76], 53.5% male). In 2020, the number of newly diagnosed mPDAC patients decreased by 13.8% compared to 2019. A slightly higher proportion of patients were initially diagnosed with stage IV disease in 2020 (69.7%) vs 2019 (62.3%). A similar proportion of patients with ECOG PS 0-1 was observed between the two cohorts (2019: 48.5%; 2020: 47.9%). The number of visits recorded within the first 90 days after metastatic diagnosis was similar between the two cohorts (2019: median 8 [IQR: 3 – 14]; 2020: median 9 [IQR: 4 – 14]). For both cohorts, the proportion of patients who received 1L treatment was similar (2019: 75.8%; 2020: 76.5%), and the most common 1L treatment regimen was gemcitabine plus nab-paclitaxel (2019: 37.6%; 2020: 40.9%). Of the 1L treated populations, 37.6% of patients diagnosed in 2019 received second line (2L) compared to 17.9% of the 2020 cohort; 16.9% of 1L treated patients in 2019 received 2L in the sensitivity analysis. Patients diagnosed in 2020 had a significantly lower median OS of 6.1 months (95% CI: 5.4 – 6.9) compared to patients diagnosed in 2019: 8.4 months (7.5 – 9.0) (p &lt; 0.001). Conclusions: During the COVID-19 pandemic era, the diagnoses of de novo mPDAC appears to have been impacted, with a higher number of patients diagnosed with advanced stage at presentation. Our analysis suggests that while patients diagnosed in 2020 received a similar level of care as those in 2019, their survival outcomes were adversely affected. Further research is necessary to characterize the impact of the COVID-19 pandemic on cancer care and outcomes.
ChemInform Abstract: Synthesis of Sugar‐Modified Derivatives of the Unusual Nucleoside Oxanosine and Its Carbocyclic Analogues as Potential Inhibitors of HIV. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations (2017)

A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, which works by converting cells that are heterozygous for the drive construct into homozygotes, thereby enabling super-Mendelian inheritance. Although CRISPR gene drive activity has already been demonstrated, a key obstacle for current systems is their propensity to generate resistance alleles, which cannot be converted to drive alleles. In this study, we developed two CRISPR gene drive constructs based on the nanos and vasa promoters that allowed us to illuminate the different mechanisms by which resistance alleles are formed in the model organism Drosophila melanogaster. We observed resistance allele formation at high rates both prior to fertilization in the germline and post-fertilization in the embryo due to maternally deposited Cas9. Assessment of drive activity in genetically diverse backgrounds further revealed substantial differences in conversion efficiency and resistance rates. Our results demonstrate that the evolution of resistance will likely impose a severe limitation to the effectiveness of current CRISPR gene drive approaches, especially when applied to diverse natural populations.
The Past as Prologue? Business Cycles and Forecasting since the 1960s (2010)

This paper examines how successfully economic forecasts as covered in public media foreshadow major real estate and financial crises. Building from existing research on the accuracy of economic forecasts, we focus on real estate crises and the portrayal of forecasts in the press. We utilize textual analysis to identify articles on specific topics and to track coverage over time, both in the print media, as well as the larger internet-based news world; we also use the Google tool, âInsights for Search,â to gauge public âforecastingâ and popular beliefs. We find that the use of real-time data limits the accuracy of forecasts, that there appears to be a reluctance in the press to forecast bad news, and that when bad news is forecast, the report is often cushioned with counterbalancing observations. Preliminary results based on review of specific sets of articles show that articles reporting on academic forecasts have tended to be more accurate in hindsight than those relying on other sources. Reviews of two periods of real estate crises, the mid-1980s and the 2007-2009 crisis show that many of the serious problems were described in the press as early as two years in advance, but that interest and concern tended to taper off before the crisis occurred, leading to a sense of surprise. Our results suggest while the recent past is not always a good predictor of future trends, it can be very useful to be familiar with long term history that spans several cycles.
Synthesis, structure, and structure‐activity relationships of divalent thrombin inhibitors containing an α‐keto‐amide transition‐state mimetic (1996)

A new class of divalent thrombin inhibitors is described that contains an alpha-keto-amide transition-state mimetic linking an active site binding group and a group that binds to the fibrinogen-binding exosite. The X-ray crystallographic structure of the most potent member of this new class, CVS995, shows many features in common with other divalent thrombin inhibitors and clearly defines the transition-state-like binding of the alpha-keto-amide group. The structure of the active site part of the inhibitor shows a network of water molecules connecting both the side-chain and backbone atoms of thrombin and the inhibitor. Direct peptide analogues of the new transition-state-containing divalent thrombin inhibitors were compared using in vitro assays of thrombin inhibition. There was no direct correlation between the binding constants of the peptides and their alpha-keto-amide counterparts. The most potent alpha-keto-amide inhibitor, CVS995, with a Ki = 1 pM, did not correspond to the most potent divalent peptide and contained a single amino acid deletion in the exosite binding region with respect to the equivalent region of the natural thrombin inhibitor hirudin. The interaction energies of the active site, transition state, and exosite binding regions of these new divalent thrombin inhibitors are not additive.
New scaling guidelines for MNOS nonvolatile memory devices (1991)

New phenomena in MNOS retention characteristics that originate from stored charge distribution are described and new scaling guidelines are indicated. The most significant phenomenon is that write-state retentivity is less dependent on the programmed depth, and is improved by reducing silicon nitride thickness. This behavior suggests that write-state charges are distributed rectangularly, while erase-state charges are distributed exponentially. The lower limit of the programming voltage is determined by write-state retentivity and not erase-state retentivity, and the write-state charge distribution depth determines the lower limit of silicon nitride thickness. The upper limit of the programming voltage is determined by erase-state retentivity after erase/write cycles. The scaling guidelines indicate that 16-Mb EEPROMs can be designed using MNOS memory devices.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
VP35 Knockdown Inhibits Ebola Virus Amplification and Protects against Lethal Infection in Mice (2006)

Phosphorodiamidate morpholino oligomers (PMO) are a class of uncharged single-stranded DNA analogs modified such that each subunit includes a phosphorodiamidate linkage and morpholine ring. PMO antisense agents have been reported to effectively interfere with the replication of several positive-strand RNA viruses in cell culture. The filoviruses, Marburg virus and Ebola virus (EBOV), are negative-strand RNA viruses that cause up to 90% lethality in human outbreaks. There is currently no commercially available vaccine or efficacious therapeutic for any filovirus. In this study, PMO conjugated to arginine-rich cell-penetrating peptide (P-PMO) and nonconjugated PMO were assayed for the ability to inhibit EBOV infection in cell culture and in a mouse model of lethal EBOV infection. A 22-mer P-PMO designed to base pair with the translation start site region of EBOV VP35 positive-sense RNA generated sequence-specific and time- and dose-dependent inhibition of EBOV amplification in cell culture. The same oligomer provided complete protection to mice when administered before or after an otherwise lethal infection of EBOV. A corresponding nonconjugated PMO, as well as nonconjugated truncated versions of 16 and 19 base residues, provided length-dependent protection to mice when administered prophylactically. Together, these data suggest that antisense PMO and P-PMO have the potential to control EBOV infection and are promising therapeutic candidates.
Coiled perimysial fibers of papillary muscle in rat heart: morphology, distribution, and changes in configuration. (1988)

The morphology, distribution, and configuration of coiled perimysial fibers of rat heart papillary muscle were studied. Methods included bright-field light microscopy of silver-stained sections, scanning and transmission electron microscopy, and differential interference contrast light microscopy of unfixed and unstained specimens. Coiled fibers, elliptical in cross section, are arranged in a branched network that diverges from the muscle-tendon junction and is continuous throughout the length of the muscle and into the ventricle wall. Most fibers range in diameter from less than 1 micron to 10 micron and are parallel with the long axis of the muscle, although branching is common and oblique orientations are seen. Several myocytes are associated with each coiled perimysial fiber. Constituent fibrils (diameter, 40-50 nm) occur in bundles twisted within the fiber. Small satellite elastic fibers are parallel to the collagen fiber axes. Stereo analysis of the coiled perimysial fibers reveals helical configurations, as opposed to planar waviness, that become less convoluted or even straighten as the resting muscle is stretched. Calculations based on cross-sectional areas of fibers, changes in fiber configurations, and tensile moduli reported for collagen fibers of other tissues show that the potential tensile strength of the network of coiled perimysial fibers is sufficient to contribute significantly to the mechanical properties of papillary muscle. Detailed evaluations of possible roles of the coiled perimysial collagen fiber system as a function of passive stretch and contraction in ventricular wall, as well as in papillary muscle, warrant further study.
Radio Continuum Studies of Wolf-Rayet Galaxies (2009)

Wolf-Rayet galaxies have a large population of massive WR stars which dominate the optical spectra of these galaxies. Some of these galaxies have been observed in the radio continuum at frequencies >1 GHz which reveal a variety of spectra ranging from power law to flat spectra. A small subset has also been observed at lower frequencies which suggest that there is no single combination of physical mechanisms that can explain all the observed spectra. However a larger sample at the low GMRT frequencies may help discriminate between the various physical models. In this ongoing study, we have observed & detected emission at 610, 240 and 150 MHz from two WR galaxies: Mrk 008 and Mrk 1089. In this poster paper we present the integrated spectra of these galaxies and the preliminary results from our study.
Photoacoustic Imaging: Opening New Frontiers in Medical Imaging (2011)

In today's world, technology is advancing at an exponential rate and medical imaging is no exception. During the last hundred years, the field of medical imaging has seen a tremendous technological growth with the invention of imaging modalities including but not limited to X-ray, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. These tools have led to better diagnosis and improved patient care. However, each of these modalities has its advantages as well as disadvantages and none of them can reveal all the information a physician would like to have. In the last decade, a new diagnostic technology called photoacoustic imaging has evolved which is moving rapidly from the research phase to the clinical trial phase. This article outlines the basics of photoacoustic imaging and describes our hands-on experience in developing a comprehensive photoacoustic imaging system to detect tissue abnormalities.
Air agglomeration of hydrophobic particles (1995)

The agglomeration of hydrophobic particles in an aqueous suspension was accomplished by introducing small amounts of air into the suspension while it was agitated vigorously. The extent of aggregation was proportional both to the air to solids ratio and to the hydrophobicity of the solids. For a given air/solids ratio, the extent of aggregation of different materials increased in the following order: graphite, gilsonite, coal coated with heptane, and Teflon. The structure of agglomerates produced from coarse Teflon particles differed noticeably from the structure of bubble-particle aggregates produced from smaller, less hydrophobic particles.
Integrated voice and data communications overview (1988)

The author reviews architectures and traffic characteristics for voice and data communications, and addresses important issues in integrated voice and data communications. He discusses some possible methods of integrating voice and data and presents an example of implementing integrated voice and data communications. He considers ISDN (integrated services digital network) as a vehicle for supporting integrated services including voice and data as well as image and video. Although the concern is mainly with switched networks, some of the concepts discussed are applicable to both switched and special-services networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Immobilization of plasmid DNA on an anti‐DNA antibody modified coronary stent for intravascular site‐specific gene therapy (2008)

For the first time, our group reports the successful use of anti-DNA antibody-immobilized metal stent as plasmid gene delivery system that possess high efficiency and site-specificity in vitro and in vivo.
Activation of Early Gene Expression in T Lymphocytes by Oct-1 and an Inducible Protein, OAP 40 (1991)

After antigenic stimulation of T lymphocytes, genes essential for proliferation and immune function, such as the interleukin-2 (IL-2) gene, are transcriptionally activated. In both transient transfections and T lymphocyte-specific in vitro transcription, the homeodomain-containing protein Oct-1 participated in the inducible regulation of transcription of the IL-2 gene. Oct-1 functioned in this context with a 40-kilodalton protein called Oct-1-associated protein (OAP40). In addition to interacting specifically with DNA, OAP40 reduced the rate of dissociation of Oct-1 from its cognate DNA-binding site, suggesting that a direct interaction exists between Oct-1 and OAP40.
Comparative Analysis of Binding Kinetics and Thermodynamics of Dipeptidyl Peptidase-4 Inhibitors and Their Relationship to Structure (2016)

The binding kinetics and thermodynamics of dipeptidyl peptidase (DPP)-4 inhibitors (gliptins) were investigated using surface plasmon resonance and isothermal titration calorimetry. Binding of gliptins to DPP-4 is a rapid electrostatically driven process. Off-rates were generally slow partly because of reversible covalent bond formation by some gliptins, and partly because of strong and extensive interactions. Binding of all gliptins is enthalpy-dominated due to strong ionic interactions and strong solvent-shielded hydrogen bonds. Using a congeneric series of molecules which represented the intermediates in the lead optimization program of linagliptin, the onset of slow binding kinetics and development of the thermodynamic repertoire were analyzed in the context of incremental changes of the chemical structures. All compounds rapidly associated, and therefore the optimization of affinity and residence time is highly correlated. The major contributor to the increasing free energy of binding was a strong increase of binding enthalpy, whereas entropic contributions remained low and constant despite significant addition of lipophilicity.
Processor with 4.9-&#x03BC;s break-even time in power gating using crystalline In-Ga-Zn-oxide transistor (2013)

A processor having a power management unit (PMU) and an 8-bit CPU including flip-flops with shadow memories is fabricated by 0.5-μm Si and 0.8-μm c-axis-aligned crystalline In-Ga-Zn-oxide (CAAC-IGZO) technology. The shadow memories hold data without power supply utilizing low off-state current of CAAC-IGZO FETs. A break-even time (BET) of 4.9μs has been obtained. Good scalability of the processor in writing data to shadow memories and in area (5.7% overhead or less) is also confirmed through simulation and layout, based on flip-flops using 30-nm Si FETs combined with 0.3-μm CAAC-IGZO FETs which show good electronic characteristics and no overhead in area.
Arginine behaviour after arginine or citrulline administration in older subjects (2015)

Arginine (ARG) and its precursor citrulline (CIT) are popular dietary supplements, especially for the elderly. However, age-related reductions in lean body mass and alterations in organ functions could change their bioavailability. Pharmacokinetics and tolerance to amino acid (AA) loads are poorly documented in elderly subjects. The objective here was to characterise the plasma kinetics of CIT and ARG in a single-dosing study design. Eight fasting elderly men underwent two separate isomolar oral loading tests (10 g of CIT or 9·94 g of ARG). Blood was withdrawn over an 8-h period to measure plasma AA concentrations. Only CIT, ornithine and ARG plasma concentrations were changed. Volume of distribution was not dependent on AA administered. Conversely, parameters related to ARG kinetics were strongly dependent on AA administered: after ARG load, elimination was higher (ARG>CIT; P=0·041) and admission period+time at peak concentration was lower (ARG<CIT; P=0·033), and the combination of both phenomena results in a marked increase in ARG availability when CIT was administered (ARG<CIT; P=0·033) compared with ARG administration itself. In conclusion, a single CIT administration in the elderly is safe and well tolerated, and CIT proves to be a better in vivo ARG precursor than ARG itself in healthy elderly subjects.
Targeting radiation-resistant hypoxic tumour cells through ATR inhibition (2012)

These findings suggest that ATR inhibition represents a novel strategy to target tumour cells in conditions relevant to pathophysiology and enhance the efficacy of radiotherapy.
Lymph Node Ratio for Postoperative Staging of Laryngeal Squamous Cell Carcinoma with Lymph Node Metastasis (2014)

R classification is a significant prognostic factor of laryngeal cancer and should be used as a complementary staging system of N classification.
Possible Implication of FcγReceptor-Mediated Trogocytosis in Susceptibility to Systemic Autoimmune Disease (2013)

Leukocytes can "gnaw away" the plasma membrane of other cells. This phenomenon, called trogocytosis, occurs subsequent to cell-to-cell adhesion. Currently, two mechanisms of trogocytosis, adhesion molecule-mediated trogocytosis and Fc γ receptor-(Fc γ R-) mediated trogocytosis, have been identified. In our earlier study, we established an in vitro model of Fc γ R-mediated trogocytosis, namely, CD8 translocation model from T cells to neutrophils. By using this model, we demonstrated that the molecules transferred to neutrophils via Fc γ R-mediated trogocytosis were taken into the cytoplasm immediately. This result suggests that the chance of molecules transferred via Fc γ R-mediated trogocytosis to play a role on the cell surface could be time-limited. Thus, we consider the physiological role of Fc γ R-mediated trogocytosis as a means to remove antibodies (Abs) that bind with self-molecules rather than to extract molecules from other cells. This concept means that Fc γ R-mediated trogocytosis can be a defense mechanism to Ab-mediated autoimmune response. Moreover, the activity of Fc γ R-mediated trogocytosis was revealed to be parallel to the endocytotic activity of neutrophils, which was critically related to the susceptibility to systemic autoimmune diseases. The collective findings suggest that Fc γ R-mediated trogocytosis could physiologically play a role in removal of Abs bound to self-antigens and prevent autoimmune diseases.
Vitreous Substitutes: The Present and the Future (2014)

Vitreoretinal surgery has advanced in numerous directions during recent years. The removal of the vitreous body is one of the main characteristics of this surgical procedure. Several molecules have been tested in the past to fill the vitreous cavity and to mimic its functions. We here review the currently available vitreous substitutes, focusing on their molecular properties and functions, together with their adverse effects. Afterwards we describe the characteristics of the ideal vitreous substitute. The challenges facing every ophthalmology researcher are to reach a long-term intraocular permanence of vitreous substitute with total inertness of the molecule injected and the control of inflammatory reactions. We report new polymers with gelification characteristics and smart hydrogels representing the future of vitreoretinal surgery. Finally, we describe the current studies on vitreous regeneration and cell cultures to create new intraocular gels with optimal biocompatibility and rheological properties.