Miracle-dz/UniFAR-FTUs huggingface dataset:
DeepSynergy: predicting anti-cancer drug synergy with Deep Learning

Abstract Motivation While drug combination therapies are a well-established concept in cancer treatment, identifying novel synergistic combinations is challenging due to the size of combinatorial space. However, computational approaches have emerged as a time- and cost-efficient way to prioritize combinations to test, based on recently available large-scale combination screening data. Recently, Deep Learning has had an impact in many research areas by achieving new state-of-the-art model performance. However, Deep Learning has not yet been applied to drug synergy prediction, which is the approach we present here, termed DeepSynergy. DeepSynergy uses chemical and genomic information as input information, a normalization strategy to account for input data heterogeneity, and conical layers to model drug synergies. Results DeepSynergy was compared to other machine learning methods such as Gradient Boosting Machines, Random Forests, Support Vector Machines and Elastic Nets on the largest publicly available synergy dataset with respect to mean squared error. DeepSynergy significantly outperformed the other methods with an improvement of 7.2% over the second best method at the prediction of novel drug combinations within the space of explored drugs and cell lines. At this task, the mean Pearson correlation coefficient between the measured and the predicted values of DeepSynergy was 0.73. Applying DeepSynergy for classification of these novel drug combinations resulted in a high predictive performance of an AUC of 0.90. Furthermore, we found that all compared methods exhibit low predictive performance when extrapolating to unexplored drugs or cell lines, which we suggest is due to limitations in the size and diversity of the dataset. We envision that DeepSynergy could be a valuable tool for selecting novel synergistic drug combinations. Availability and implementation DeepSynergy is available via www.bioinf. jku.at/software/DeepSynergy. Supplementary information Supplementary data are available at Bioinformatics online.
Contact-force-guided vs. contact-force-blinded catheter ablation of typical atrial flutter: a prospective study

Aims It remains unknown whether contact force (CF) sensing technology is of value for cavotricuspid isthmus (CTI) ablation. We prospectively evaluated procedural parameters and outcomes of CF-guided vs. CF-blinded CTI ablation for typical atrial flutter (AFL). Methods and results A total of 70 consecutive patients (62.5 ± 10.9 years) undergoing CTI ablation for AFL were prospectively enrolled, 35 in CF-blinded and 35 in CF-guided groups. A CF-sensing catheter (power 25-35 W) was used in all. In the CF-guided group, CF target range was 10-25 g, whereas in the CF-blinded group, the operator was blinded to CF. The isthmus was divided into anterior, middle, and posterior segments for region-specific CF analysis. The procedural endpoint of bidirectional isthmus block following a 20-min observation period was achieved in all. A trend towards lower fluoroscopy and procedure duration was observed when the CF-guided group was compared with the CF-blinded group. The total radiofrequency (RF) energy delivery time required to achieve bidirectional block was significantly lower in the CF-guided vs. CF-blinded group [10.0 min (IQR 8.3;15.1) vs. 15.9 min (IQR 9.6;24.7), P= 0.0020], with a significant inverse correlation between CF and total RF delivery time (r = -0.36; P= 0.0027). Mean CF measurements significantly increased from anterior to posterior anatomical zones of CTI in the CF-blinded group (ANOVA P= 0.0466). Conclusions Catheter ablation of AFL guided by real-time CF assessment results in a significant reduction in total RF delivery time. Real-time CF measurements facilitate the maintenance of homogenous efficient contact all along the CTI, particularly in the anterior segment where CF is generally lower.
Parent ratings of working memory are uniquely related to performance-based measures of secondary memory but not primary memory

ABSTRACT Introduction: Existing evidence suggests that performance- and rating-based measures of working memory (WM) correlate poorly. Although some researchers have interpreted this evidence as suggesting that these measures may be assessing distinct cognitive constructs, another possibility is that rating-based measures are related to some but not all theoretically motivated performance-based measures. The current study distinguished between performance-based measures of primary memory (PM) and secondary memory (SM), and examined the relation between each of these components of WM and parent-ratings on the WM subscale of the Behavior Rating Inventory of Executive Function (BRIEF–WM). Because SM and BRIEF–WM scores have both been associated with group differences in attention-deficit/hyperactivity disorder (ADHD), it was hypothesized that SM scores would be uniquely related to parent-rated BRIEF–WM scores. Method: Participants were a sample of 77 adolescents with and without an ADHD diagnosis, aged 11 to 15 years, from a midwestern school district. Participant scores on verbal and spatial immediate free recall tasks were used to estimate both PM and SM capacities. Partial correlation analyses were used to evaluate the extent to which estimates of PM and SM were uniquely related parent-rated BRIEF–WM scores. Results: Both verbal and spatial SM scores were significantly related to parent-rated BRIEF–WM scores, when corresponding PM scores were controlled. Higher verbal and spatial SM scores were associated with less frequent parent-report of WM-related failures in their child’s everyday life. However, neither verbal nor spatial PM scores significantly related to parent-rated BRIEF–WM scores, when corresponding SM scores were controlled. Conclusion: The current study suggested that previously observed low correlations between performance- and rating-based measures of WM may result from use of performance-based WM measures that do not capture the unique contributions of PM and SM components of WM.
Diffuse correlation spectroscopy with a fast Fourier transform-based software autocorrelator

Abstract. Diffuse correlation spectroscopy (DCS) is an emerging noninvasive technique that probes the deep tissue blood flow, by using the time-averaged intensity autocorrelation function of the fluctuating diffuse reflectance signal. We present a fast Fourier transform (FFT)-based software autocorrelator that utilizes the graphical programming language LabVIEW (National Instruments) to complete data acquisition, recording, and processing tasks. The validation and evaluation experiments were conducted on an in-house flow phantom, human forearm, and photodynamic therapy (PDT) on mouse tumors under the acquisition rate of ∼400 kHz. The software autocorrelator in general has certain advantages, such as flexibility in raw photon count data preprocessing and low cost. In addition to that, our FFT-based software autocorrelator offers smoother starting and ending plateaus when compared to a hardware correlator, which could directly benefit the fitting results without too much sacrifice in speed. We show that the blood flow index (BFI) obtained by using a software autocorrelator exhibits better linear behavior in a phantom control experiment when compared to a hardware one. The results indicate that an FFT-based software autocorrelator can be an alternative solution to the conventional hardware ones in DCS systems with considerable benefits.
Safety and Effectiveness of Repeat Treatment With VYC-15L for Lip and Perioral Enhancement: Results From a Prospective Multicenter Study.

Background VYC-15L (Juvéderm Volbella XC) is a non-animal crosslinked hyaluronic acid (HA) gel with lidocaine. Objective To evaluate safety and effectiveness of repeat treatment with VYC-15L administered 1 year after treatment for lip and perioral enhancement. Methods In this prospective multicenter study, 124 subjects with minimal, mild, or moderate lip fullness on the validated 5-point Allergan Lip Fullness Scale (LFS) who received initial/touch-up treatment with VYC-15L received repeat treatment with VYC-15L 1 year after initial treatment. Effectiveness endpoints included LFS responder rates (≥1-point improvement from baseline) and scores on the FACE-Q Satisfaction With Lips and Appraisal of Lip Lines scales at 1 month after repeat treatment. Subjects completed safety diaries for 30 days after repeat treatment. Results LFS responder rates were 86.2%, 80.3%, and 61.8% at months 1 and 3 and 1 year, respectively, after initial/touch-up treatment. The responder rate improved to 94.3% 1 month after repeat treatment with VYC-15L and required less median volume vs initial/touchup treatment (1.5 vs 2.6 mL). FACE-Q scores doubled from baseline at 3 months, remained high through 1 year, and doubled from baseline after repeat treatment. At 1 month after repeat treatment, 96.7% and 89.3% of subjects showed improvement over baseline in FACE-Q Satisfaction With Lips and Appraisal of Lip Lines, respectively. Severe injection site responses were less frequent after repeat treatment than initial/touch-up treatment. Conclusion Repeat treatment with VYC-15L at 1 year was safe and effective for lip and perioral enhancement, and required less product volume to achieve similar effectiveness to initial/touch-up treatment.
DFNA5 promoter methylation a marker for breast tumorigenesis

Background Identification of methylation markers that are sensitive and specific for breast cancer may improve early detection. We hypothesize that DFNA5 promoter methylation can be a valuable epigenetic biomarker, based upon strong indications for its role as tumor suppressor gene and its function in regulated cell death. Results Statistically different levels of methylation were seen, with always very low levels in healthy breast reduction samples, very high levels in part of the adenocarcinoma samples and slightly increased levels in part of the normal tissue samples adjacent the tumor. One of the CpGs (CpG4) showed the best differentiation. A ROC curve for DFNA5 CpG4 methylation showed a sensitivity of 61.8% for the detection of breast cancer with a specificity of 100%. Materials and Methods We performed methylation analysis on four CpGs in the DFNA5 promoter region by bisulfite pyrosequencing on 123 primary breast adenocarcinomas and 24 healthy breast reductions. For 16 primary tumors, corresponding histological normal tissue adjacent to the tumor was available. Conclusions We conclude that DFNA5 methylation shows strong potential as a biomarker for detection of breast cancer. Slightly increased methylation in histologically normal breast tissue surrounding the tumor suggests that it may be a good early detection marker.
Reduction of radiation exposure in cryoballoon ablation procedures: a single-centre study applying intracardiac echocardiography and other radioprotective measures

Aims The population treated with cryoballoon (CB) ablation is relatively young, and radiation protection is of major importance. We aimed to demonstrate that radiation exposure can be markedly reduced by intracardiac echocardiography (ICE) and optimized settings of the X-ray system. Methods and results We analysed 100 patients undergoing CB pulmonary vein isolation (PVI) for treatment of paroxysmal atrial fibrillation. In 50 consecutive patients (25 male, 59 ± 13 years; Group 1), we used ICE, skipped PV angiography prior to CB inflation, and avoided fluoroscopy whenever possible. Furthermore, we reduced the frame rate, minimized distance between patient and detector, and consequently applied collimation. These patients were compared with 50 similar preceding patients in Group 2 (29 male, 61 ± 12 years). Total fluoroscopy time was reduced from 18 ± 6 min in Group 2 to 12 ± 5 min in Group 1 (P < 0.001). Moreover, the dose area product was significantly lower (1555 ± 1219 vs. 4935 ± 2094 cGycm2, P < 0.001), total freezing time was significantly shortened (1855 ± 399 vs. 2121 ± 756 s, P = 0.031), and contrast media use was significantly reduced (66 ± 25 vs. 109 ± 27 mL, P < 0.001). At the same time, total procedure duration and complication rates did not differ significantly between both groups. After a 12 months follow-up, a similar percentage of patients was free from recurrences (74% in Group 1 vs. 78% in Group 2, P = 0.640). Conclusion Radiation exposure in CB PVI can be markedly reduced without prolonging procedure times, affecting the outcome or complication rates. Moreover, ICE seems to shorten total freezing time.
Characterization of Dielectric Nanocomposites with Electrostatic Force Microscopy

Nanocomposites physical properties unexplainable by general mixture laws are usually supposed to be related to interphases, highly present at the nanoscale. The intrinsic dielectric constant of the interphase and its volume need to be considered in the prediction of the effective permittivity of nanodielectrics, for example. The electrostatic force microscope (EFM) constitutes a promising technique to probe interphases locally. This work reports theoretical finite-elements simulations and experimental measurements to interpret EFM signals in front of nanocomposites with the aim of detecting and characterizing interphases. According to simulations, we designed and synthesized appropriate samples to verify experimentally the ability of EFM to characterize a nanoshell covering nanoparticles, for different shell thicknesses. This type of samples constitutes a simplified electrostatic model of a nanodielectric. Experiments were conducted using either DC or AC-EFM polarization, with force gradient detection method. A comparison between our numerical model and experimental results was performed in order to validate our predictions for general EFM-interphase interactions.
The role of land use change on the development and evolution of the west coast trough, convective clouds, and precipitation in southwest Australia

Land clearing for agricultural purposes in southwest Australia has created a landscape where a 750 km rabbit-proof fence separates 13 million hectares of croplands from the remnant native vegetation to the east. The Bunny Fence Experiment (BuFex) was conducted in the vicinity of the intended vermin-proof boundary in December 2005 and August 2007. The experiment examined the role of land cover change (LCC) on the preferential formation of clouds over the native vegetation that often terminates along the vermin-proof fence as well as the regional rainfall reduction observed in this region. Observations and numerical model analysis show that the formation and development of the west coast trough (WCT), which is a synoptic-scale feature that initiates spring and summertime convection, is impacted by land cover change and that the cloud fields induced by the WCT would extend further west in the absence of the LCC. The surface convergence patterns associated with the wintertime WCT circulation is substantially altered by LCC, due to changes in both WCT dynamics and surface aerodynamic roughness, leading to a rainfall decrease to the west of the rabbit fence. It is found that the LCC in southwest Australia is indeed responsible for preferential formation of clouds over native vegetation and contributes to the observed rainfall reduction in this region. ”
Core competencies for UK occupational health nurses: a Delphi study

Background Occupational health nurses (OHNs) play a pivotal role in the delivery of occupational health (OH) services. Specific competency guidance has been developed in a number of countries, including the UK. While it is acknowledged that UK OHN practice has evolved in recent years, there has been no formal research to capture these developments to ensure that training and curricula remain up-to-date and reflect current practice. Aims To identify current priorities among UK OHNs of the competencies required for OH practice. Methods A modified Delphi study undertaken among representative OHN networks in the UK. This formed part of a larger study including UK and international occupational physicians. The study was conducted in two rounds using a questionnaire based on available guidance on training competencies for OH practice, the published literature, expert panel reviews and conference discussions. Results Consensus among OHNs was high with 7 out of the 12 domains scoring 100% in rating. ‘Good clinical care’ was the principal domain ranked most important, followed by ‘general principles of assessment & management of occupational hazards to health’. ‘Research methods’ and ‘teaching & educational supervision’ were considered least important. Conclusions This study has established UK OHNs’ current priorities on the competencies required for OH practice. The timing of this paper is opportune with the formal launch of the Faculty of Occupational Health Nursing planned in 2018 and should inform the development of competency requirements as part of the Faculty’s goals for standard setting in OHN education and training.
Cadm3 (Necl‐1) interferes with the activation of the PI3 kinase/Akt signaling cascade and inhibits Schwann cell myelination in vitro

Axo‐glial interactions are critical for myelination and the domain organization of myelinated fibers. Cell adhesion molecules belonging to the Cadm family, and in particular Cadm3 (axonal) and its heterophilic binding partner Cadm4 (Schwann cell), mediate these interactions along the internode. Using targeted shRNA‐mediated knockdown, we show that the removal of axonal Cadm3 promotes Schwann cell myelination in the in vitro DRG neuron/Schwann cell myelinating system. Conversely, over‐expressing Cadm3 on the surface of DRG neuron axons results in an almost complete inability by Schwann cells to form myelin segments. Axons of superior cervical ganglion (SCG) neurons, which do not normally support the formation of myelin segments by Schwann cells, express higher levels of Cadm3 compared to DRG neurons. Knocking down Cadm3 in SCG neurons promotes myelination. Finally, the extracellular domain of Cadm3 interferes in a dose‐dependent manner with the activation of ErbB3 and of the pro‐myelinating PI3K/Akt pathway, but does not interfere with the activation of the Mek/Erk1/2 pathway. While not in direct contradiction, these in vitro results shed lights on the apparent lack of phenotype that was reported from in vivo studies of Cadm3−/− mice. Our results suggest that Cadm3 may act as a negative regulator of PNS myelination, potentially through the selective regulation of the signaling cascades activated in Schwann cells by axonal contact, and in particular by type III Nrg‐1. Further analyses of peripheral nerves in the Cadm−/− mice will be needed to determine the exact role of axonal Cadm3 in PNS myelination. GLIA 2016;64:2247–2262
The effectiveness of influenza vaccination in preventing hospitalisations of elderly individuals in two influenza seasons: a multicentre case–control study, Spain, 2013/14 and 2014/15

Influenza vaccination may limit the impact of influenza in the community. The aim of this study was to assess the effectiveness of influenza vaccination in preventing hospitalisation in individuals aged ≥ 65 years in Spain. A multicentre case–control study was conducted in 20 Spanish hospitals during 2013/14 and 2014/15. Patients aged ≥ 65 years who were hospitalised with laboratory-confirmed influenza were matched with controls according to sex, age and date of hospitalisation. Adjusted vaccine effectiveness (VE) was calculated by multivariate conditional logistic regression. A total of 728 cases and 1,826 matched controls were included in the study. Overall VE was 36% (95% confidence interval (CI): 22–47). VE was 51% (95% CI: 15–71) in patients without high-risk medical conditions and 30% (95% CI: 14–44) in patients with them. VE was 39% (95% CI: 20–53) in patients aged 65–79 years and 34% (95% CI: 11–51) in patients aged ≥ 80 years, and was greater against the influenza A(H1N1)pdm09 subtype than the A(H3N2) subtype. Influenza vaccination was effective in preventing hospitalisations of elderly individuals.
Posttraumatic Stress Disorder and Depression Symptom Severities Are Differentially Associated With Hippocampal Subfield Volume Loss in Combat Veterans

Background Two decades of human neuroimaging research have associated volume reductions in the hippocampus with posttraumatic stress disorder. However, little is known about the distribution of volume loss across hippocampal subfields. Recent advances in neuroimaging methods have made it possible to accurately delineate 10 gray matter hippocampal subfields. Here, we apply a volumetric analysis of hippocampal subfields to data from a group of combat-exposed Veterans. Method Veterans (total, n = 68, posttraumatic stress disorder, n = 36; combat control, n = 32) completed high-resolution structural magnetic resonance imaging. Based on previously validated methods, hippocampal subfield volume measurements were conducted using FreeSurfer 6.0. The Clinician-Administered PTSD Scale assessed posttraumatic stress disorder symptom severity; Beck Depression Inventory assessed depressive symptom severity. Controlling for age and intracranial volume, partial correlation analysis examined the relationship between hippocampal subfields and symptom severity. Correction for multiple comparisons was performed using false discovery rate. Gender, intelligence, combat severity, comorbid anxiety, alcohol/substance use disorder, and medication status were investigated as potential confounds. Results In the whole sample, total hippocampal volume negatively correlated with Clinician-Administered PTSD Scale and Beck Depression Inventory scores. Of the 10 hippocampal subfields, Clinician-Administered PTSD Scale symptom severity negatively correlated with the hippocampus–amygdala transition area (HATA). Beck Depression Inventory scores negatively correlated with dentate gyrus, cornu ammonis 4 (CA4), HATA, CA2/3, molecular layer, and CA1. Follow-up analysis limited to the posttraumatic stress disorder group showed a negative correlation between Clinician-Administered PTSD Scale symptom severity and each of HATA, CA2/3, molecular layer, and CA4. Conclusion This study provides the first evidence relating posttraumatic stress disorder and depression symptoms to abnormalities in the HATA, an anterior hippocampal region highly connected to prefrontal-amygdala circuitry. Notably, dentate gyrus abnormalities were associated with depression severity but not posttraumatic stress disorder symptoms. Future confirmatory studies should determine the extent to which dentate gyrus volume can differentiate between posttraumatic stress disorder- and depression-related pathophysiology.
Crosstalk noise and bit error rate analysis for optical network-on-chip

Crosstalk noise is an intrinsic characteristic of photonic devices used by optical networks-on-chip (ONoCs) as well as a potential issue. For the first time, this paper analyzed and modeled the crosstalk noise, signal-to-noise ratio (SNR), and bit error rate (BER) of optical routers and ONoCs. The analytical models for crosstalk noise, minimum SNR, and maximum BER in mesh-based ONoCs are presented. An automated crosstalk analyzer for optical routers is developed. We find that crosstalk noise significantly limits the scalability of ONoCs. For example, due to crosstalk noise, the maximum BER is 10−3 on the 8×8 mesh-based ONoC using an optimized crossbar-based optical router. To achieve the BER of 10−9 for reliable transmissions, the maximum ONoC size is 6×6. A novel compact high-SNR optical router is proposed to improve the maximum ONoC size to 8×8.