Miracle-dz/UniFAR-FTUs huggingface dataset:
CRISPR-mediated SOX9 knockout inhibits GFAP expression in retinal glial (Müller) cells

Müller cells, as the predominant glial element in the sensory retina, play a crucial role in healthy and diseased retina. Overactivation of Müller cells in response to damage is detrimental to the retina tissue. Current research shows that inhibiting glial fibrillary acidic protein (GFAP), a sensitive indicator of Müller cell activation, attenuated glial reactions and promoted neuroprotection. Recent evidence suggests that the transcript factor SOX9 (sex-determining region Y box 9), part of the SOX family, regulates GFAP expression of astrocytes in the central nervous system. However, in retina Müller cells, it is still unknown whether GFAP can be downregulated by reduced SOX9 function. The present results show that clustered regularly interspaced short palindromic repeats/Cas9-mediated SOX9 knockout not only inhibited GFAP expression in rat Müller cells but also attenuated cell migration ability. These results suggest that inhibition of SOX9 activity may be a novel therapeutic strategy for reduction of glial cell activity.
Sex-Dependent Impact of Low-Level Lead Exposure during Prenatal Period on Child Psychomotor Functions

The impact of exposure to lead on child neurodevelopment has been well established. However, sex differences in vulnerability are still not fully explained. We aimed at evaluating the effect of a low-level lead exposure, as measured between 20 to 24 weeks of pregnancy and in cord blood, on developmental scores up to 24 months of age in 402 children from the Polish Mother and Child Cohort (REPRO_PL). Additionally, sex-dependent susceptibility to lead at this very early stage of psychomotor development was assessed. The blood lead levels were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). In order to estimate the children’s neurodevelopment, the Bayley Scales of Infant and Toddler Development was applied. The geometric mean (GM) for blood lead level during 20–24 weeks of pregnancy was 0.99 ± 0.15 µg/dL and, in the cord blood, it was 0.96 ± 0.16 µg/dL. There was no statistically significant impact of lead exposure during prenatal period on the girls’ psychomotor abilities. Among the boys, we observed lower scores for cognitive functions, along with increasing cord blood lead levels (β = −2.07; p = 0.04), whereas the results for the language and motor abilities were not statistically significant (p > 0.05). Our findings show that fetal exposure to very low lead levels might affect early cognitive domain, with boys being more susceptible than girls. Education on health, higher public awareness, as well as intervention programs, along with relevant regulations, are still needed to reduce risks for the vulnerable population subgroups.
Dummy Rounds as a DPA Countermeasure in Hardware

This paper describes the technique of Dummy Rounds as a countermeasure against DPA in hardware implementation of round-based ciphers. Its principle is inspired by several well-known countermeasures used in hardware as Hiding and Dynamic Reconfiguration as well as countermeasures used in software implementations as Dummy cycles, Random order execution or Hiding in time. Being inspired by countermeasures based on dynamic reconfiguration, this method combines hiding of power consumption with hiding in time. In this work we also discuss the amount of randomness available for the control of the computation.
Association Between Anxiety and Depression and Gastroesophageal Reflux Disease: Results From a Large Cross-sectional Study

Background/Aims The different clinical manifestations of gastroesophageal reflux disease (GERD) may be influenced by associated psychological factors. We evaluated the psychological status (anxiety and depression) according to each subtype of GERD. Methods Subjects who underwent esophagogastroduodenoscopy and completed a symptom questionnaire between January 2008 and December 2011 were analyzed. The subjects were classified into the following groups: erosive reflux disease (ERD), non-erosive reflux disease (NERD), asymptomatic erosive esophagitis (AEE), and controls. Anxiety and depression were assessed using the State-Trait Anxiety Inventory and Beck Depression Inventory, respectively. Results We analyzed 19 099 subjects: 16 157 (84.6%), 176 (0.9%), 1398 (7.3%), and 1368 (7.2%) in the control, ERD, NERD, and AEE groups, respectively. Multiple multinomial logistic regression revealed a significant association of increased state (adjusted OR, 1.89; 95% CI, 1.53–2.33) and trait anxiety (adjusted OR, 1.78; 95% CI, 1.34–2.35) and depression (adjusted OR, 2.21; 95% CI, 1.75–2.80) with NERD. ERD group showed a significant association only with state anxiety (adjusted OR, 2.20; 95% CI, 1.27–3.81) and depression (adjusted OR, 2.23; 95% CI, 1.18–4.22). The AEE group, however, did not show any significant association with psychological factors. Conclusion This cross-sectional study revealed that anxiety and depression levels were significantly higher in subjects with GERD (notably in the NERD) than in controls.
Disentangling Pre- and Postnatal Maternal Age Effects on Offspring Performance in an Insect with Elaborate Maternal Care

Maternal effect senescence has attracted much recent scientific interest. However, the age-related effects of pre- and postnatal maternal age are often conflated, as these naturally originate from the same individual. Additionally, many maternal effect senescence studies fail to account for potential biases associated with selective disappearance. Here we use a cross-fostered laboratory population of a burying beetle, Nicrophorus vespilloides, to examine both the effects of female pre- and postnatal maternal age on offspring life-history traits and the postcare outcomes of mothers while accounting for selective disappearance of postnatal caregivers. Neither pre- nor postnatal maternal age affected offspring longevity or larval weight at hatching, and postnatal age had no effect on postcare maternal outcomes except to confirm the presence of actuarial senescence. There was weak evidence for concave relationships between two larval traits (dispersal weight and survival) and the age of egg producers. Selective disappearance of caregivers had no clear effect on any of the measured offspring traits. Contrary to predictions from evolutionary theory, maternal effect senescence and reproductive effort increases do not always manifest, and current theory may be insufficient to account for the true diversity of aging patterns relating to maternal care.
Deep Tree Echo State Networks

This work proposes a first study, through empirical assessment, of a deep recursive Neural Network (RecNN) architecture for tree structured data exploiting the efficient design of the Echo State Network (ESN) framework. Three benchmark tasks for trees allow us to assess the potentiality of the novel Deep Tree ESN (DeepTESN) model with respect to the shallow counterpart (Tree ESN) and literature results (including hidden tree Markov models and kernel based approaches) in different conditions and according to both efficiency and predictive performance.
A Fuzzy Approach to Improve an Unsupervised Automatic Keyphrase Extraction Process

The automatic keyphrases extraction is a useful task for many computational applications in the natural language processing and text mining fields. Several solutions to this problem have been reported, but the obtained results still show low rates of accuracy and performance. In this paper, a new unsupervised method for keyphrase extraction from text documents is proposed. The use of lexical-syntactic patterns is combined with a graph-based topic modeling in this approach. The topic modeling is supported by a semantic analysis process carried out from the fuzzy logic perspective. The method was evaluated with the SemEval-2010 and Inspec datasets and compared with other state-of-the-art proposals.
Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response—final results from GeparSixto

Background In the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD). Patients and methods Patients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA). Results A significantly better DFS (hazard ratio 0.56, 95% CI 0.34-0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) [odds ratio (OR) 2.60, 95% CI 1.26-5.37, P = 0.008]. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46-9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17-1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23-1.04, P = 0.059). Conclusions The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.
Seismic Collapse Risk Assessment of Code-Conforming RC Moment Resisting Frame Buildings Designed With 2014 Canadian Standard Association Standard A23.3

This paper presents collapse risk assessment of code-conforming reinforced concrete moment resisting frame (RC MRF) buildings located in Vancouver, Canada. This assessment investigates the three- and six-storey of regular RC MRF building systems, with and without unreinforced masonry infill wall, representing low- to mid-rise structures. These buildings are designed according to the current National Building Code of Canada and detailed based on the 2014 Canadian Standards Association A23.3 standard provision for high seismic regions. Two different ductility classes of seismic building design, namely ductile and moderately ductile, are considered to identify the capability, equality and/or difference of the seismic performance of these designed buildings. Nonlinear dynamic analysis is applied in the performance-based seismic assessment procedures to assess the collapse response of structural for the set of 50 pair ground motion records. Next, the seismic fragility curves are developed through incremental dynamic analysis. Finally, mean annual frequency of collapse is calculated through combination of fragility curve and hazard curve. The results indicate that the bare RC buildings are vulnerable to earthquake-induced collapse when the number of the story increased. The presence of the URM infill walls significantly influence the collapse behavior of the frame structure. Compared to moderately ductile MRF buildings, ductile MRF buildings show a better collapse performance, is strongly influenced by the capacity of the building system.
Gandiva: Introspective Cluster Scheduling for Deep Learning

We introduce Gandiva, a new cluster scheduling framework that utilizes domain-specific knowledge to improve latency and efficiency of training deep learning models in a GPU cluster. One key characteristic of deep learning is feedback-driven exploration, where a user often runs a set of jobs (or a multi-job) to achieve the best result for a specific mission and uses early feedback on accuracy to dynamically prioritize or kill a subset of jobs; simultaneous early feedback on the entire multi-job is critical. A second characteristic is the heterogeneity of deep learning jobs in terms of resource usage, making it hard to achieve best-fit a priori. Gandiva addresses these two challenges by exploiting a third key characteristic of deep learning: intra-job predictability, as they perform numerous repetitive iterations called mini-batch iterations. Gandiva exploits intra-job predictability to time-slice GPUs efficiently across multiple jobs, thereby delivering low-latency. This predictability is also used for introspecting job performance and dynamically migrating jobs to better-fit GPUs, thereby improving cluster efficiency. We show via a prototype implementation and micro-benchmarks that Gandiva can speed up hyper-parameter searches during deep learning by up to an order of magnitude, and achieves better utilization by transparently migrating and time-slicing jobs to achieve better job-to-resource fit. We also show that, in a real workload of jobs running in a 180-GPU cluster, Gandiva improves aggregate cluster utilization by 26%, pointing to a new way of managing large GPU clusters for deep learning.
Facilitating Noncardiac Surgery for the Patient with Left Ventricular Assist Device: A Guide for the Anesthesiologist

The introduction of left ventricular assist device (LVAD) has improved survival rates for patients with end-stage heart failure. Two categories of VADs exist: one generates pulsatile flow and the other produces nonpulsatile continuous flow. Survival is better for patients with continuous-flow LVADs. With improved survival, more of such patients now present for noncardiac surgery (NCS). This review, written for the general anesthesiologists, addresses the perioperative considerations when the patient undergoes NCS. For best outcomes, a multidisciplinary approach is essential in perioperative management of the patient.
Exploring Modern GPU Memory System Design Challenges through Accurate Modeling

This paper explores the impact of simulator accuracy on architecture design decisions in the general-purpose graphics processing unit (GPGPU) space. We perform a detailed, quantitative analysis of the most popular publicly available GPU simulator, GPGPU-Sim, against our enhanced version of the simulator, updated to model the memory system of modern GPUs in more detail. Our enhanced GPU model is able to describe the NVIDIA Volta architecture in sufficient detail to reduce error in memory system even counters by as much as 66X. The reduced error in the memory system further reduces execution time error versus real hardware by 2.5X. To demonstrate the accuracy of our enhanced model against a real machine, we perform a counter-by-counter validation against an NVIDIA TITAN V Volta GPU, demonstrating the relative accuracy of the new simulator versus the publicly available model. We go on to demonstrate that the simpler model discounts the importance of advanced memory system designs such as out-of-order memory access scheduling, while overstating the impact of more heavily researched areas like L1 cache bypassing. Our results demonstrate that it is important for the academic community to enhance the level of detail in architecture simulators as system complexity continues to grow. As part of this detailed correlation and modeling effort, we developed a new Correlator toolset that includes a consolidation of applications from a variety of popular GPGPU benchmark suites, designed to run in reasonable simulation times. The Correlator also includes a database of hardware profiling results for all these applications on NVIDIA cards ranging from Fermi to Volta and a toolchain that enables users to gather correlation statistics and create detailed counter-by-counter hardware correlation plots with minimal effort.
Can computer-aided diagnosis assist in the identification of prostate cancer on prostate MRI? a multi-center, multi-reader investigation

For prostate cancer detection on prostate multiparametric MRI (mpMRI), the Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) and computer-aided diagnosis (CAD) systems aim to widely improve standardization across radiologists and centers. Our goal was to evaluate CAD assistance in prostate cancer detection compared with conventional mpMRI interpretation in a diverse dataset acquired from five institutions tested by nine readers of varying experience levels, in total representing 14 globally spread institutions. Index lesion sensitivities of mpMRI-alone were 79% (whole prostate (WP)), 84% (peripheral zone (PZ)), 71% (transition zone (TZ)), similar to CAD at 76% (WP, p=0.39), 77% (PZ, p=0.07), 79% (TZ, p=0.15). Greatest CAD benefit was in TZ for moderately-experienced readers at PI-RADSv2 <3 (84% vs mpMRI-alone 67%, p=0.055). Detection agreement was unchanged but CAD-assisted read times improved (4.6 vs 3.4 minutes, p<0.001). At PI-RADSv2 ≥ 3, CAD improved patient-level specificity (72%) compared to mpMRI-alone (45%, p<0.001). PI-RADSv2 and CAD-assisted mpMRI interpretations have similar sensitivities across multiple sites and readers while CAD has potential to improve specificity and moderately-experienced radiologists’ detection of more difficult tumors in the center of the gland. The multi-institutional evidence provided is essential to future prostate MRI and CAD development.
The different clinical guideline standards in Brazil: High cost treatment diseases versus poverty-related diseases

Each year, evidence-based clinical guidelines gain more space in the health professionals’ practice and in services organization. Due to the scarcity of scientific publications focused on diseases of poverty, the development of well-founded clinical guidelines becomes more and more important. In view of that, this paper aims to evaluate the quality of Brazilian guidelines for those diseases. The AGREE II method was used to evaluate 16 guidelines for poverty-related diseases (PRD) and 16 guidelines for global diseases whose treatment require high-cost technologies (HCD), with the ultimate aim of comparing the results. It was found that, in general, the guideline development quality standard is higher for the HCD guidelines than for the PRD guidelines, with emphasis on the "rigour of development" (48% and 7%) and "editorial independence" (43% and 1%) domains, respectively, which had the greatest discrepancies. The HCD guidelines showed results close to or above international averages, whereas the PRD guidelines showed lower results in the 6 domains evaluated. It can be concluded that clinical protocol development priorities need some redirecting in order to qualify the guidelines that define the healthcare organization and the care of vulnerable populations.
Protective effect of Anwulignan against D-galactose-induced hepatic injury through activating p38 MAPK–Nrf2–HO-1 pathway in mice

Background Liver aging is a significant risk factor for chronic liver diseases. Oxidative stress has been considered as a conjoint pathological mechanism for the initiation and progression of liver aging. It has been reported that d-galactose (d-gal)-induced hepatic injury is an experimental model well established closely similar to morphological and functional features of liver aging. Schisandra sphenanthera Rehd. et Wils (S. sphenanthera, Schisandraceae), as a famous tradi-tional Chinese medicine, has been used for thousands of years in China to treat various disorders, including liver dysfunctions. This study was aimed to understand whether Anwulignan, one of the monomeric compounds in the lignans from S. sphenanthera, could improve the hepatic injury induced by d-gal in mice and to examine the possible mechanisms. Methods ICR mice were used to produce hepatic injury by 220 mg kg-1 d-gal subcutaneously once daily for 42 days. The effects of oral Anwulignan on liver index; serial AST and ALT levels; histological changes; SOD, GSH-Px, MDA, and 8-OHdG in the liver and peripheral blood; expression of p38 mitogen-activated protein kinase (MAPK), Nrf2, and HO-1 in the liver; and HepG2 cell viability, and decrease caspase-3 contents in liver were examined. Results Anwulignan could significantly increase the liver index, lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the peripheral blood, elevate superoxide dis-mutase (SOD) and glutathione peroxidase (GSH-Px) activities, and decrease malonaldehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) contents in the peripheral blood and liver. Furthermore, Anwulignan could upregulate the expression of p38 mitogen-activated protein kinase (MAPK), Nrf2, and HO-1 in the liver, increase the HepG2 cell viability, and decrease caspase-3 contents in liver. Conclusion Anwulignan has protective effects against the hepatic injury induced by d-gal, which may be related to its antioxidant capacity through activating p38 MAPK–Nrf2–HO-1 pathway, increases the injured cell viability, and decreases the caspase-3 contents in liver.
Incidence rates of narcolepsy diagnoses in Taiwan, Canada, and Europe: The use of statistical simulation to evaluate methods for the rapid assessment of potential safety issues on a population level in the SOMNIA study

Background & objectives Vaccine safety signals require investigation, which may be done rapidly at the population level using ecological studies, before embarking on hypothesis-testing studies. Incidence rates were used to assess a signal of narcolepsy following AS03-adjuvanted monovalent pandemic H1N1 (pH1N1) influenza vaccination among children and adolescents in Sweden and Finland in 2010. We explored the utility of ecological data to assess incidence of narcolepsy following exposure to pandemic H1N1 virus or vaccination in 10 sites that used different vaccines, adjuvants, and had varying vaccine coverage. Methods We calculated incidence rates of diagnosed narcolepsy for periods defined by influenza virus circulation and vaccination campaign dates, and used Poisson regression to estimate incidence rate ratios (IRRs) comparing the periods during which wild-type virus circulated and after the start of vaccination campaigns vs. the period prior to pH1N1 virus circulation. We used electronic health care data from Sweden, Denmark, the United Kingdom, Canada (3 provinces), Taiwan, Netherlands, and Spain (2 regions) from 2003 to 2013. We investigated interactions between age group and adjuvant in European sites and conducted a simulation study to investigate how vaccine coverage, age, and the interval from onset to diagnosis may impact the ability to detect safety signals. Results Incidence rates of narcolepsy varied by age, continent, and period. Only in Taiwan and Sweden were significant time-period-by-age-group interactions observed. Associations were found for children in Taiwan (following pH1N1 virus circulation) and Sweden (following vaccination). Simulations showed that the individual-level relative risk of narcolepsy was underestimated using ecological methods comparing post- vs. pre-vaccination periods; this effect was attenuated with higher vaccine coverage and a shorter interval from disease onset to diagnosis. Conclusions Ecological methods can be useful for vaccine safety assessment but the results are influenced by diagnostic delay and vaccine coverage. Because ecological methods assess risk at the population level, these methods should be treated as signal-generating methods and drawing conclusions regarding individual-level risk should be avoided.