Secure tumor classification by shallow neural network using homomorphic encryption

Disclosure of patients genetic information in the process of applying machine learning techniques for tumor classification hinders the privacy of personal information. Homomorphic Encryption (HE), which supports operations between encrypted data, can be used as one of the tools to perform such computation without information leakage, but it brings great challenges for directly applying general machine learning algorithms due to the limitations of operations supported by HE. In particular, non-polynomial activation functions, including softmax functions, are difficult to implement with HE and require a suitable approximation method to minimize the loss of accuracy. In the secure genome analysis competition called iDASH 2020, it is presented as a competition task that a multi-label tumor classification method that predicts the class of samples based on genetic information using HE. We develop a secure multi-label tumor classification method using HE to ensure privacy during all the computations of the model inference process. Our solution is based on a 1-layer neural network with the softmax activation function model and uses the approximate HE scheme. We present an approximation method that enables softmax activation in the model using HE and a technique for efficiently encoding data to reduce computational costs. In addition, we propose a HE-friendly data filtering method to reduce the size of large-scale genetic data. We aim to analyze the dataset from The Cancer Genome Atlas (TCGA) dataset, which consists of 3,622 samples from 11 types of cancers, genetic features from 25,128 genes. Our preprocessing method reduces the number of genes to 4,096 or less and achieves a microAUC value of 0.9882 (85% accuracy) with a 1-layer shallow neural network. Using our model, we successfully compute the tumor classification inference steps on the encrypted test data in 3.75 minutes. As a result of exceptionally high microAUC values, our solution was awarded co-first place in iDASH 2020 Track 1: Secure multi-label Tumor classification using Homomorphic Encryption. Our solution is the first result of implementing a neural network model with softmax activation using HE. Also, HE optimization methods presented in this work enable machine learning implementation using HE or other challenging HE applications.This work was supported by Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korea government(MSIT) (No.2020-0-00840, Development and Library Implementation of Fully Homomorphic ML Algorithms supporting Neural Network Learning over Encrypted Data)

A randomized, phase II study of gefitinib alone versus nimotuzumab plus gefitinib after platinum-based chemotherapy in advanced non-small cell lung cancer (KCSG LU12-01)

We aimed to evaluate the efficacy of dual inhibition of epidermal growth factor receptor (EGFR) with nimotuzumab (EGFR monoclonal antibody) plus gefitinib (EGFR-tyrosine kinase inhibitor) in advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. An open label, randomized, phase II trial was conducted at 6 centers; 160 patients were randomized (1:1) to either gefitinib alone or nimotuzumab (200 mg, i. v. weekly) plus gefitinib (250 mg p. o. daily) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) at 3 months. Of the total 160 enrolled patients, 155 (77: gefitinib, 78: nimotuzumab plus gefitinib) received at least one dose and could be evaluated for efficacy and toxicity. The majority had adenocarcinoma (65.2%) and ECOG performance status of 0 to 1 (83.5%). The median follow-up was 22.1 months, and the PFS rate at 3 months was 48.1% in gefitinib and 37.2% in nimotuzumab plus gefitinib (P = not significant, NS). The median PFS and OS were 2.8 and 13.2 months in gefitinib and 2.0 and 14.0 months in nimotuzumab plus gefitinib. Combined treatment was not associated with superior PFS to gefitinib alone in patients with EGFR mutation (13.5 vs. 10.2 months in gefitinib alone, P=NS) or those with wild-type EGFR (0.9 vs. 2.0 months in gefitinib alone, P=NS). Combined treatment did not increase EGFR inhibition-related adverse events with manageable toxicities. The dual inhibition of EGFR with nimotuzumab plus gefitinib was not associated with better outcomes than gefitinib alone as a second-line treatment of advanced NSCLC (NCT01498562).

Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients With Diabetes Mellitus The DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy With Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients)

ObjectivesWe sought to evaluate the impact of cilostazol on neointimal hyperplasia after drug-eluting stent (DES) implantation in patients with diabetes mellitus (DM).BackgroundAlthough cilostazol has reduced the extent of neointimal hyperplasia and restenosis in patients after bare-metal stent implantation, it is not known whether this effect occurs after DES implantation in diabetic patients.MethodsThis randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol, triple group, n = 200) and dual antiplatelet therapy (aspirin and clopidogrel, standard group, n = 200) for 6 months in patients with DM receiving DES. The primary end point was in-stent late loss at 6 months.ResultsThe 2 groups had similar baseline clinical and angiographic characteristics. The in-stent (0.25 ± 0.53 mm vs. 0.38 ± 0.54 mm, p = 0.025) and in-segment (0.42 ± 0.50 mm vs. 0.53 ± 0.49 mm, p = 0.031) late loss were significantly lower in the triple versus standard group, as were 6-month in-segment restenosis (8.0% vs. 15.6%, p = 0.033) and 9-month target lesion revascularization (TLR) (2.5% vs. 7.0%, p = 0.034). At 9 months, major adverse cardiac events, including death, myocardial infarction, and TLR, tended to be lower in the triple than in the standard group (3.0% vs. 7.0%, p = 0.066). Multivariate analysis showed that sirolimus-eluting stents and the use of cilostazol were strong predictors of reduced restenosis or TLR.ConclusionsTriple antiplatelet therapy after DES implantation decreased angiographic restenosis and extent of late loss, resulting in a reduced risk of 9-month TLR compared with dual antiplatelet therapy in diabetic patients

Efficacy of two different self-expanding nitinol stents for atherosclerotic femoropopliteal arterial disease (SENS-FP trial): study protocol for a randomized controlled trial

BACKGROUND: There have been few randomized control trials comparing the incidence of stent fracture and primary patency among different self-expanding nitinol stents to date. The SMART™ CONTROL stent (Cordis Corp, Miami Lakes, Florida, United States) has a peak-to-valley bridge and inline interconnection, whereas the COMPLETE™-SE stent (Medtronic Vascular, Santa Rosa, California, United States) crowns have been configured to minimize crown-to-crown interaction, increasing the stent's flexibility without compromising radial strength. Further, the 2011 ESC (European society of cardiology) guidelines recommend that dual antiplatelet therapy with aspirin and a thienopyridine such as clopidogrel should be administered for at least one month after infrainguinal bare metal stent implantation. Cilostazol has been reported to reduce intimal hyperplasia and subsequent repeat revascularization. To date, there has been no randomized study comparing the safety and efficacy of two different antiplatelet regimens, clopidogrel and cilostazol, following successful femoropopliteal stenting. METHODS/DESIGN: The primary purpose of our study is to examine the incidence of stent fracture and primary patency between two different major representative self-expanding nitinol stents (SMART™ CONTROL versus COMPLETE™-SE) in stenotic or occlusive femoropopliteal arterial lesion. The secondary purpose is to examine whether there is any difference in efficacy and safety between aspirin plus clopidogrel versus aspirin plus cilostazol for one month following stent implantation in femoropopliteal lesions. This is a prospective, randomized, multicenter trial to assess the efficacy of the COMPLETE™-SE versus SMART™ CONTROL stent for provisional stenting after balloon angioplasty in femoropopliteal arterial lesions. The study design is a 2x2 randomization design and a total of 346 patients will be enrolled. The primary endpoint of this study is the rate of binary restenosis in the treated segment at 12 months after intervention as determined by catheter angiography or duplex ultrasound. DISCUSSION: This trial will provide powerful insight into whether the design of the COMPLETE™-SE stent is more fracture-resistant or effective in preventing restenosis compared with the SMART™ CONTROL stent. Also, it will determine the efficacy and safety of aspirin plus clopidogrel versus aspirin plus cilostazol in patients undergoing stent implantation in femoropopliteal lesions. TRIAL REGISTRATION: Registered on 2 April 2012 with the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT01570803)

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

New Era of Air Quality Monitoring from Space: Geostationary Environment Monitoring Spectrometer (GEMS)

GEMS will monitor air quality over Asia at unprecedented spatial and temporal resolution from GEO for the first time, providing column measurements of aerosol, ozone and their precursors (nitrogen dioxide, sulfur dioxide and formaldehyde). Geostationary Environment Monitoring Spectrometer (GEMS) is scheduled for launch in late 2019 - early 2020 to monitor Air Quality (AQ) at an unprecedented spatial and temporal resolution from a Geostationary Earth Orbit (GEO) for the first time. With the development of UV-visible spectrometers at sub-nm spectral resolution and sophisticated retrieval algorithms, estimates of the column amounts of atmospheric pollutants (O3, NO2, SO2, HCHO, CHOCHO and aerosols) can be obtained. To date, all the UV-visible satellite missions monitoring air quality have been in Low Earth orbit (LEO), allowing one to two observations per day. With UV-visible instruments on GEO platforms, the diurnal variations of these pollutants can now be determined. Details of the GEMS mission are presented, including instrumentation, scientific algorithms, predicted performance, and applications for air quality forecasts through data assimilation. GEMS will be onboard the GEO-KOMPSAT-2 satellite series, which also hosts the Advanced Meteorological Imager (AMI) and Geostationary Ocean Color Imager (GOCI)-2. These three instruments will provide synergistic science products to better understand air quality, meteorology, the long-range transport of air pollutants, emission source distributions, and chemical processes. Faster sampling rates at higher spatial resolution will increase the probability of finding cloud-free pixels, leading to more observations of aerosols and trace gases than is possible from LEO. GEMS will be joined by NASA&apos;s TEMPO and ESA&apos;s Sentinel-4 to form a GEO AQ satellite constellation in early 2020s, coordinated by the Committee on Earth Observation Satellites (CEOS)

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat