93 research outputs found
Generic Intent Representation in Web Search
This paper presents GEneric iNtent Encoder (GEN Encoder) which learns a
distributed representation space for user intent in search. Leveraging large
scale user clicks from Bing search logs as weak supervision of user intent, GEN
Encoder learns to map queries with shared clicks into similar embeddings
end-to-end and then finetunes on multiple paraphrase tasks. Experimental
results on an intrinsic evaluation task - query intent similarity modeling -
demonstrate GEN Encoder's robust and significant advantages over previous
representation methods. Ablation studies reveal the crucial role of learning
from implicit user feedback in representing user intent and the contributions
of multi-task learning in representation generality. We also demonstrate that
GEN Encoder alleviates the sparsity of tail search traffic and cuts down half
of the unseen queries by using an efficient approximate nearest neighbor search
to effectively identify previous queries with the same search intent. Finally,
we demonstrate distances between GEN encodings reflect certain information
seeking behaviors in search sessions
Bio-Guided Fractionation of Papaya Leaf Juice for Delineating the Components Responsible for the Selective Anti-proliferative Effects on Prostate Cancer Cells
Alternative therapies against cancer cells with minimal or no effect on healthy tissues are highly sought after. Prostate cancer (PCa) is the second most frequently diagnosed malignancy in males. The Carica papaya L. leaf extract has been traditionally used by Australian aboriginal people for anticancer properties. In this study, medium polar fraction of papaya leaf extract that had shown anti-proliferative activity in PCa cell lines in vitro, in earlier studies, was further fractionated to 28 fractions by semi-preparative HPLC. Nine of these fractions were identified to possess selective anti-proliferative responses on PCa cells in comparison to non-cancerous cells of prostate gland origin. When these nine sub-fractions were mixed in various combinations, a combination containing six of the specific fractions (FC-3) showed the best potency. FC3 inhibited the growth of BPH-1, PC-3, and LNCaP cells in a concentration-dependent manner with an IC50 value <20 ÎŒg/mL, while (unlike paclitaxel, the positive control) minimal effect was observed on the proliferation of non-cancerous, WPMY-1 and RWPE-1cells. Furthermore, synergistic interaction of FC-3 with paclitaxel was observed with combination index values in the range of 0.89â0.98 and 0.85â1.10 on PC-3 and LNCaP cells, respectively. Untargeted qualitative analysis using UHPLC (Ultra High-Performance Liquid Chromatography)-QToF (Quadrupole Time of-Flight) mass spectrometry and screening against the METLIN database indicated presence of multiple known anticancer compounds in the FC-3 extract. These outcomes show that the potent and selective anti-proliferative effects are due to a range of bio-active compounds within the medium polar fraction of papaya leaf juice
Perceived drivers and barriers in the governance of wastewater treatment and reuse in India : Insights from a two-round Delphi study
Wastewater treatment and reuse practices are limited in India despite the known benefits of preventing water resources pollution and contributing to sustainable production and consumption systems. We identify the perceived key drivers and barriers to wastewater treatment and reuse governance in a two-round Delphi study, including literature and case study analyses and consultation with 75 panelists. Panelists indicated that the most significant driver for wastewater treatment and water reuse is persistent water scarcity that necessitates diversification to alternative water supplies. In contrast, the most significant barriers are the lack of enforcement of pollution monitoring and control, the lack of an umbrella directive for integrated water resources management, and insufficient collaboration between responsible governmental organizations, central and state water authorities. Given the absence of central guidelines, only a few Indian states such as Maharashtra, Gujarat or Punjab have adopted effective governance structures. These states showcase that defined reuse standards can create successful wastewater treatment and reuse practices but require target-based regulations which are enforced and regularly monitored and financing mechanisms for their long-term operation. The new effluent discharge standards by the National Green Tribunal, the government support programmes, and increasing water scarcity in many parts of India will supposedly drive innovative wastewater treatment and reuse structures. Panelists agreed that efforts are needed to develop technology guiding frameworks following the fit-for-purpose principle and that strengthening institutional and monitoring capacity is crucial to increase confidence in the quality of recovered water resources, create demand, and ultimately safeguard human health and the environment
Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1 alpha
Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients
Correction: Aljabali, A.A.A.; et al. Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer via down Regulation of Nuclear p65 and HIF-1α. Cancers 2020, 12, 113
The authors wish to make the following corrections to this paper [...]
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML.
Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes for acute myeloid leukemia (AML) patients. We evaluated 8709 AML patients from the CIBMTR database and, after selection and manual curation of cytogenetics data, 3779 patients in CR1 were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis compared to intermediate-risk patients detected an increased risk of relapse for KMT2A-rearranged and adverse-risk patients (HR 1.27, p = 0.01 and HR 1.71, p < 0.001, respectively). Leukemia-free survival (LFS) was similar for KMT2A and adverse-risk patients (HR 1.26, p = 0.002 and HR 1.47, p < 0.001), as was overall survival (OS) (HR 1.32, p < 0.001 and HR 1.45, p < 0.001). No differences in outcome could be detected when patients were stratified by KMT2A fusion partner. This is the largest study conducted to date on post-HCT outcomes in AML using manually curated cytogenetics for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A rearrangements and adverse-risk disease
Improved Constraints on the 21 cm EoR Power Spectrum and the X-Ray Heating of the IGM with HERA Phase I Observations
We report the most sensitive upper limits to date on the 21 cm epoch of
reionization power spectrum using 94 nights of observing with Phase I of the
Hydrogen Epoch of Reionization Array (HERA). Using similar analysis techniques
as in previously reported limits (HERA Collaboration 2022a), we find at 95%
confidence that Mpc) mK at and that Mpc mK at , an improvement by a factor of 2.1 and 2.6 respectively. These limits are
mostly consistent with thermal noise over a wide range of after our data
quality cuts, despite performing a relatively conservative analysis designed to
minimize signal loss. Our results are validated with both statistical tests on
the data and end-to-end pipeline simulations. We also report updated
constraints on the astrophysics of reionization and the cosmic dawn. Using
multiple independent modeling and inference techniques previously employed by
HERA Collaboration (2022b), we find that the intergalactic medium must have
been heated above the adiabatic cooling limit at least as early as ,
ruling out a broad set of so-called "cold reionization" scenarios. If this
heating is due to high-mass X-ray binaries during the cosmic dawn, as is
generally believed, our result's 99% credible interval excludes the local
relationship between soft X-ray luminosity and star formation and thus requires
heating driven by evolved low-metallicity stars.Comment: 57 pages, 37 figures. Updated to match the accepted ApJ version.
Corresponding author: Joshua S. Dillo
The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy
Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations.
Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (>â90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves.
Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45â85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations >â90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SEâ=â0.013, pââ90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score.
Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care
Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population
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