Privacy-preserving biological age prediction over federated human methylation data using fully homomorphic encryption.

DNA methylation data play a crucial role in estimating chronological age in mammals, offering real-time insights into an individual's aging process. The epigenetic pacemaker (EPM) model allows inference of the biological age as deviations from the population trend. Given the sensitivity of this data, it is essential to safeguard both inputs and outputs of the EPM model. A privacy-preserving approach for EPM computation utilizing fully homomorphic encryption was recently introduced. However, this method has limitations, including having high communication complexity and being impractical for large data sets. The current work presents a new privacy-preserving protocol for EPM computation, analytically improving both privacy and complexity. Notably, we employ a single server for the secure computation phase while ensuring privacy even in the event of server corruption (compared to requiring two noncolluding servers in prior work). Using techniques from symbolic algebra and number theory, the new protocol eliminates the need for communication during secure computation, significantly improves asymptotic runtime, and offers better compatibility to parallel computing for further time complexity reduction. We implemented our protocol, demonstrating its ability to produce results similar to the standard (insecure) EPM model with substantial performance improvement compared to prior work. These findings hold promise for enhancing data security in medical applications where personal privacy is paramount. The generality of both the new approach and the EPM suggests that this protocol may be useful in other applications employing similar expectation-maximization techniques.

A Fast and Reliable Solution to PnP, Using Polynomial Homogeneity and a Theorem of Hilbert.

One of the most-extensively studied problems in three-dimensional Computer Vision is "Perspective-n-Point" (PnP), which concerns estimating the pose of a calibrated camera, given a set of 3D points in the world and their corresponding 2D projections in an image captured by the camera. One solution method that ranks as very accurate and robust proceeds by reducing PnP to the minimization of a fourth-degree polynomial over the three-dimensional sphere S3. Despite a great deal of effort, there is no known fast method to obtain this goal. A very common approach is solving a convex relaxation of the problem, using "Sum Of Squares" (SOS) techniques. We offer two contributions in this paper: a faster (by a factor of roughly 10) solution with respect to the state-of-the-art, which relies on the polynomial's homogeneity; and a fast, guaranteed, easily parallelizable approximation, which makes use of a famous result of Hilbert.

Communication Efficient Algorithms for Bounding and Approximating the Empirical Entropy in Distributed Systems.

The empirical entropy is a key statistical measure of data frequency vectors, enabling one to estimate how diverse the data are. From the computational point of view, it is important to quickly compute, approximate, or bound the entropy. In a distributed system, the representative ("global") frequency vector is the average of the "local" frequency vectors, each residing in a distinct node. Typically, the trivial solution of aggregating the local vectors and computing their average incurs a huge communication overhead. Hence, the challenge is to approximate, or bound, the entropy of the global vector, while reducing communication overhead. In this paper, we develop algorithms which achieve this goal.

Profile trends of non-COVID patients admitted to the cardiac intensive care unit during the 2020 COVID pandemic.

BACKGROUND: During the COVID-19 outbreak, numerous reports indicated a higher mortality rate among cardiovascular patients. We investigated how this trend applied to patients admitted to the cardiac intensive care unit (CICU). METHODS: We retrospectively compared CICU patients admitted during the initial peak of the COVID outbreak between February and May 2020 (Covid Era, CE group) to a control group in pre-pandemic time in 2019. We interviewed patients to determine the symptom onset time and the time interval between symptomology and hospital arrival. RESULTS: The data of 292 patients were used in the analysis (119 patients in the CE group and 173 in the control group). CE patients had a higher incidence of ischemic heart disease (IHD) (p<.03), heart failure (p<.04), and psychiatric disorders (p<.001). During COVID time, more patients were hospitalized with myocarditis (OR: 26.45), arrhythmias (OR: 2.88), and new heart failure (HF) (p<.001) and less with STEMI (OR: 0.39; 95% CI: 0.24-0.63). Fewer PCIs were performed in the CE group (p<.001), with an overall lower success rate (p<.05) than reported in the control group. Patients in the CE group reported a longer period between symptom onset to hospital arrival (p<.001, χ2 = 12.42). The six-month survival rate was significantly lower in CE patients (χ2 = 7.01, P = 0.008). CONCLUSIONS: Among CICU patients admitted to our center during the initial period of the COVID pandemic, STEMI events were less frequent while cases of newly diagnosed HF sharply increased. Patients waited longer after symptom onset before seeking medical care during the pandemic. The delay may have resulted in clinical deterioration that could explain the high mortality rate and the new HF admission rate.

The impact of anxiety level on decision to seek medical care of non-COVID cardiac patients during the pandemic outbreak-single-center experience in Israel.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has significantly the delivery of healthcare all around the world. In part, an abnormal and unexplained high non-COVID-related cardiovascular mortality rate was reported during the outbreak. We assess the correlation between anxiety level and decision to seek medical care (DSMC) during the COVID-19 pandemic. MATERIALS AND METHODS: We recruited patients with cardiovascular complaints admitted to the emergency department in a single institute in Israel between February and September 2020. Anxiety level was measured using available questionnaires. DSMC was assessed with a newly designed questionnaire (DM-19). RESULTS: Two-hundreds seventy patients were included in the study. The mean age was 52.6 ± 14.9 (females represent 36.2%). 23.6% of the patients had at least moderate cardiovascular risk. High anxiety levels were (HAL) reported in nearly half of the patients (57.1% and 49.8% for General Anxiety Disorder Assessment [GAD-7] and Beck Anxiety Inventory [BAI], respectively). It was more prevalent in old, married, and unemployed patients (significant p-value for all in both questionnaires). Age was an independent factor (χ2 = 6.33, p < 0.001, odds-ratio: 4.8) and had a positive correlation on anxiety level (r = 0.81, p < 0.001 and r = 0.62, p < 0.001, for GAD-7 and BAI, respectively). The DM-19 revealed a strong and positive correlation of seeking medical care with anxiety level (R2 linear = 0.44, r = 0.70, p < 0.001 and R2 linear = 0.30, r = 0.58, p < 0.001 for GAD-7 and BAI, respectively) and results in deferring medical care for several days than patient with low anxiety level (p = 0.02). CONCLUSIONS: We observed an abnormal prevalence of a high level of anxiety among non-COVID patients with cardiovascular complaints, which affected the patient's likelihood to seek medical care and resulted in an unreasonable postponement of medical treatment. Our results may explain cardiovascular mortality trends during the outbreak and should be considered in health crisis management. Future studies will involve multi-institutional efforts to address reproducibility of our findings across geographic regions in the state of the global impact. Additionally, it is imperative to understand the effects of the coronavirus vaccine on patient consideration to seek medical care.

Long-distance regulation of shoot gravitropism by Cyclophilin 1 in tomato (Solanum lycopersicum) plants.

MAIN CONCLUSION: The phloem-mobile protein SlCyp1 traffics to distant parts of the shoot to regulate its gravitropic response. In addition, SlCyp1 targets specific cells in the root to promote lateral root development. The tomato (Solanum lycopersicum) Cyclophilin 1 (SlCyp1) gene encodes a peptidyl-prolyl isomerase required for auxin response, lateral root development and gravitropic growth. The SlCyp1 protein is a phloem-mobile signal that moves from shoot to root to regulate lateral root development (Spiegelman et al., Plant J 83:853-863, 2015; J Exp Bot 68:953-964, 2017a). Here, we explored the mechanism of SlCyp1 movement by fusing it to the fluorescent protein mCherry. We found that, once trafficked to the root, SlCyp1 is unloaded from the phloem to the surrounding tissues, including the pericycle and lateral root primordia. Interestingly, SlCyp1 not only moves to the root system, but also to distant parts of the shoot. Grafting of the SlCyp1 mutant diageotropica (dgt) scions on VFN8 control rootstocks resulted in recovery of dgt shoot gravitropism, which was associated with the restoration of auxin-response capacity. Application of the cyclophilin inhibitor cyclosporine A suppressed gravitropic recovery, indicating that SlCyp1 must be active in the target tissue to affect the gravitropic response. These results provide new insights on the mechanism of SlCyp1 transport and functioning as a long-distance signal regulating shoot gravitropism.

Liposomes of Quantum Dots Configured for Passive and Active Delivery to Tumor Tissue.

The majority of developed and approved anticancer nanomedicines have been designed to exploit the dogma of the enhanced permeability and retention (EPR) effect, which is based on the leakiness of the tumor's blood vessels accompanied by impeded lymphatic drainage. However, the EPR effect has been under scrutiny recently because of its variable manifestation across tumor types and animal species and its poor translation to human cancer therapy. To facilitate the EPR effect, systemically injected NPs should overcome the obstacle of rapid recognition and elimination by the mononuclear phagocyte system (MPS). We hypothesized that circulating monocytes, major cells of the MPS that infiltrate the tumor, may serve as an alternative method for achieving increased tumor accumulation of NPs, independent of the EPR effect. We describe here the accumulation of liposomal quantum dots (LipQDs) designed for active delivery via monocytes, in comparison to LipQDs designed for passive delivery (via the EPR effect), following IV administration in a mammary carcinoma model. Hydrophilic QDs were synthesized and entrapped in functionalized liposomes, conferring passive ("stealth" NPs; PEGylated, neutral charge) and active (monocyte-mediated delivery; positively charged) properties by differing in their lipid composition, membrane PEGylation, and charge (positively, negatively, and neutrally charged). The various physicochemical parameters affecting the entrapment yield and optical stability were examined in vitro and in vivo. Biodistribution in the blood, various organs, and in the tumor was determined by the fluorescence intensity and Cd analyses. Following the treatment of animals (intact and mammary-carcinoma-bearing mice) with disparate formulations of LipQDs (differing by their lipid composition, neutrally and positively charged surfaces, and hydrophilic membrane), we demonstrate comparable tumor uptake of QDs delivered by the passive and the active routes (mainly by Ly-6Chi monocytes). Our findings suggest that entrapping QDs in nanosized liposomal formulations, prepared by a new facile method, imparts superior structural and optical stability and a suitable biodistribution profile leading to increased tumor uptake of fluorescently stable QDs.

Down-regulation of SlCyp1 in the phloem reduces auxin response and photosynthetic rate in tomato (Solanum lycopersicum) plants.

The tomato dgt mutant, containing a single mutation in the Cyclophilin1 (SlCyp1) gene, is auxin insensitive and exhibits a pleotropic phenotype that includes lack of lateral roots, malformed xylem structure and reduced root-to-shoot ratio. Recently, we found that the SlCyp1 protein is phloem-mobile and traffic from shoot to root to induce lateral root formation. These processes are achieved through activation of auxin-mediated developmental programs. Inhibition of the trafficked SlCyp1 activity at the target site resulted in inhibition of the auxin response, supporting the hypothesis that this protein is indeed a mobile signal. Here, we show that partial silencing of SlCyp1 in the phloem only resulted in perturbed auxin response in the roots and reduced photosynthetic and transpiration rates. The presented data suggests that expression of SlCyp1 in the phloem is essential for proper auxin response at the whole plant level. We, therefore, propose that this protein acts as a long-distance signaling molecule acting as coordinator between roots and shoot activities.

The DNA2 nuclease/helicase is an estrogen-dependent gene mutated in breast and ovarian cancers.

Genomic instability, a hallmark of cancer, is commonly caused by failures in the DNA damage response. Here we conducted a bioinformatical screen to reveal DNA damage response genes that are upregulated by estrogen and highly mutated in breast and ovarian cancers. This screen identified 53 estrogen-dependent cancer genes, some of which are novel. Notably, the screen retrieved 9 DNA helicases as well as 5 nucleases. DNA2, which functions as both a helicase and a nuclease and plays a role in DNA repair and replication, was retrieved in the screen. Mutations in DNA2, found in estrogen-dependent cancers, are clustered in the helicase and nuclease domains, suggesting activity impairment. Indeed, we show that mutations found in ovarian cancers impair DNA2 activity. Depletion of DNA2 in cells reduces their tumorogenicity in mice. In human, high expression of DNA2 correlates with poor survival of estrogen receptor-positive patients but not of estrogen receptor-negative patients. We also demonstrate that depletion of DNA2 in cells reduces proliferation, while addition of estrogen restores proliferation. These findings suggest that cells responding to estrogen will proliferate despite impaired in DNA2 activity, potentially promoting genomic instability and triggering cancer development.

Towards identifying the roll motion parameters of a motorcycle simulator.

This study aimed at identifying the roll motion parameters of a motorcycle simulator prototype. Experienced motorcyclists tuned the angular physical movement of the mock-up and that of the visual scene to achieve an optimal riding experience during curves. The participants exceeded the rolling angles that would be required in real-world riding, while avoiding leaning the mock-up beyond 10°. In addition, they were more influenced by the speed of the virtual motorcycle than by road curvature, especially in a wide field of view. Heterogeneity was found in the roll applied to the visual scene. The overall patterns suggest that at least when washout is not applied to remove the side forces that in real-world riding are compensated by a centrifugal force, greater roll of the visual at the expense of the mock-up is mandatory to avoid performance biases that might be enhanced due to fear of falling off the simulator. Future roll motion models must take into consideration factors such as riding postures, which might not only influence the forces operating on the rider-motorcycle system, but also how motorcyclists perceive the visual world.

Control of breast cancer growth and initiation by the stem cell-associated transcription factor TCF3.

Regulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote their growth and progression. TCF3 (also known as TCF7L1) is a member of the TCF/LEF transcription factor family that is central in regulating epidermal and embryonic stem cell identity. We found that TCF3 is highly expressed in poorly differentiated human breast cancers, preferentially of the basal-like subtype. This suggested that TCF3 is involved in the regulation of breast cancer cell differentiation state and tumorigenicity. Silencing of TCF3 dramatically decreased the ability of breast cancer cells to initiate tumor formation, and led to decreased tumor growth rates. In culture, TCF3 promotes the sphere formation capacity of breast cancer cells and their self-renewal. We found that in contrast to ES cells, where it represses Wnt-pathway target genes, TCF3 promotes the expression of a subset of Wnt-responsive genes in breast cancer cells while repressing another distinct target subset. In the normal mouse mammary gland, Tcf3 is highly expressed in terminal end buds, structures that lead duct development. Primary mammary cells are dependent on Tcf3 for mammosphere formation, and its overexpression in the developing gland disrupts ductal growth. Our results identify TCF3 as a central regulator of tumor growth and initiation, and a novel link between stem cells and cancer.

Why do car drivers fail to give way to motorcycles at t-junctions?

Studies of accident statistics suggest that motorcyclists are particularly vulnerable to collisions with other vehicles which pull out of side roads onto a main carriageway, failing to give way to the approaching motorcycle. Why might this happen? The typical response of the car driver is that they looked in the appropriate direction but simply failed to see the motorcycle. To assess the visual skills of drivers in such scenarios we compared the behaviour of novice and experienced drivers to a group of dual drivers (with both car and motorcycle experience). Participants watched a series of video clips, displayed across three screens, depicting the approach to various t-junctions. On reaching the junction, participants had to decide when it was safe to pull out. Responses and eye movements were measured. The results confirmed that dual drivers had the safest responses at junctions, especially in the presence of conflicting motorcycles. On a range of visual measures both novice and experienced drivers appeared inferior to dual drivers, though for potentially different reasons. There were however no differences in the time it took all drivers to first fixate approaching motorcycles. Instead the differences appeared to be due to the amount of time spent looking at the approaching motorcycle. The experienced drivers had shorter gazes on motorcycles than cars, suggesting that they either process less salient motorcycles faster than cars, or that they terminated the gaze prematurely perhaps because they did not realise they were fixating a motorcycle. We argue that this is potential evidence for an oculomotor basis for Look But Fail To See errors.

Attending overtaking cars and motorcycles through the mirrors before changing lanes.

Right of way violation crashes are the most common type of accidents that motorcyclists face. This study assessed right of way decisions in scenarios which require noticing whether there is traffic from behind that is about to overtake. A test was created which presents participants clips with a wide field of vision (from a driver's perspective in a moving vehicle), with mirror information inset that allows either cars or motorcycles that are about to overtake, to be attended. Novice and experienced car drivers, and dual drivers (with both car and motorcycle experience), watched these clips while their eye movements were monitored. The results indicated that in the rear-view and the right-side mirrors, and in the right hand lane, conflicting motorcycles garnered more attention than conflicting cars. This pattern however was particularly driven by the dual drivers group. Additionally, novice drivers and dual drivers made more use of the right side mirror than the experienced drivers. Dual drivers also made more use of the rear view mirror than experienced drivers. Finally, significant positive correlations that were found between percentages of safe manoeuvres and measures of visual search provide direct evidence demonstrating that the frequency of risky manoeuvres was indeed larger in those cases where less time was spent gazing at the mirrors, indicating that the additional attention devoted to process conflicting vehicles contributes to reduce risky manoeuvres. The general pattern of results also provides some indirect support that non-motorcyclists drivers are more likely to have Look But Fail To See errors with conflicting motorcycles than motorcyclist drivers.

Applying the motorcyclist's perspective to improve car drivers' attitudes towards motorcyclists.

This study sought to provide a first crucial step in the direction of developing an intervention program aimed at improving safe attitudes and skills among car drivers towards motorcycles. We intended to improve drivers' attitudes towards motorcyclists by exposing them to demands that motorcyclists face on the road. Car drivers were exposed to hazard perception clips taken from a motorcyclist's perspective, and interactive hazards in a motorcycle simulator. Car hazard perception clips and a car simulator were used as control conditions. A questionnaire assessed participant knowledge and attitudes towards motorcyclists before and after the intervention. After the intervention participants had more empathic- and fewer negative-attitudes, as well as safer attitudes towards motorcyclists. Self-reported attitude-change suggested that the use of motorcycle hazard perception clips was more effective than the simulator, and the intervention was most effective for those car drivers who reported the most negative attitudes prior viewing the clips or riding the simulator. Providing car drivers with a perspective of the motorcyclist may prove to be a useful tool for promoting safer attitudes towards motorcyclists.

Hazard perception as a function of target location and the field of view.

A typical hazard perception test presents participants with a single-screen view of the road ahead. This study assessed how increasing this field of view would affect hazard perception abilities. Drivers were shown video clips of driving situations containing at least one hazard either on a single screen, or with the addition of side views on two separate but adjacent screens that extended the perceived worldview to approximately 180 degrees. Mirror information was also included to allow information from behind the vehicle to be attended. Participants were instructed to press a button as soon as they saw a hazard. Faster response times were found for hazards that appeared in the centre of the central screen, than in the periphery of the central screen, with hazards that first appeared in the lateral screens responded to slowest. Additionally, responses to the hazards were faster and were more likely to occur in the three-, as compared to the single-screen condition. These results suggest that providing participants with a wider field of view, which includes more environmental cues that are related to the relevant hazardous situation increases their ability to detect hazards, and some limited support to that providing them with a wider view increases this ability even when all hazard-relevant information appear only in the central screen. A number of reasons for the three-screen advantage are discussed. This study suggests that even responses to central hazards may be under-estimated in a typical single-screen hazard perception test, and that improvements can be made for new hazard perception tests, by including visual information from the side and from behind the driver. This new methodology not only allows testing hazard perception skills in a potentially more immersive and realistic environment, but also enables to create hazard perception clips that cannot be realised in a typical single-screen test.

Approaches of truck drivers and non-truck drivers toward reckless on-road behavior.

The purpose of the study was to compare the reported approaches of truck drivers to those of non-truck drivers toward reckless on-road behaviors. One hundred and sixty-seven adult males, including 70 non-truck drivers, completed the questionnaires voluntarily. The truck drivers were employees of a concrete manufacturing company working at various company plants throughout Israel. Seventy were professional mixer truckers and 27 were tip-truckers. The participants completed the Reckless Driving Self-Report Scale based on Taubman Ben-Ari et al. [Taubman Ben-Ari, O., Florian, V., Mikulincer, M., 1999. The impact of mortality salience on reckless driving: a test of terror management mechanisms. Journal of Personality and Social Psychology 76, 35-45], adapted for truck drivers for this study. It was expected that non-professional, as compared to professional (truck) drivers, would be more permissive regarding reckless driving, since driving risks are less prominent in their daily driving experience. An ANOVA performed on mean reckless-driving scores yielded significant results. The post hoc Schéffe test indicated significantly higher reckless-driving scores for automobile drivers as compared to both mixer-truck driver scores and tip-truck driver scores. In addition, the reckless-driving scores for mixer-truck drivers were significantly higher than the tip-truck driver scores. We discuss various explanations for the findings and consider possible implications for training strategies in organizations as well as for media campaigns focused on mutual safe road use of truck drivers and private vehicle drivers.

Self-reported driving behaviors as a function of trait anxiety.

This study examined self-reported driving behaviors in 120 (Israeli) male drivers as a function of trait anxiety (TA). TA was assessed through the TA scale of the State-Trait Anxiety Inventory. For the analysis of driving behaviors, the present study used the Driver Behavior Questionnaire (DBQ) and adopted previous distinctions between four classes of behaviors within the DBQ: errors, lapses, ordinary violations and aggressive violations. Regression analyses revealed that level of TA had a significant direct positive effect on all dependent variables, suggesting riskier driving behaviors among high-anxious individuals. Significant logarithmic effects for all measures indicate that these aberrant driving behaviors increase more at increasing LTA-, than at increasing HTA-values. Consistent with the general adverse effects of anxiety on performance effectiveness, the present findings as well, are interpreted in the framework of theories which suggest that worries occupy the capacities of working memory, at the expense of the task to be performed. The positive relation between aggressive violations and TA is sought to reflect low levels of emotional adjustment among high-anxious individuals.

Compliance of Ultra-Orthodox and secular pedestrians with traffic lights in Ultra-Orthodox and secular locations.

Following a previous study that revealed the disobedience of Ultra-Orthodox citizens, as compared to secular citizens, of traffic lights at crosswalks, the present study examined the road habits of 995 Ultra-Orthodox and secular pedestrians in neighboring Ultra-Orthodox and secular cities. Using an observation grid designed specially for this study, the pedestrians were observed at two crosswalks--one in an Ultra-Orthodox city and one in a secular city--as far as similar traffic parameters, using a logistic regression. The tendency to cross on a red light was assessed as a function of estimated age, gender, religiosity, location (religious/secular), the duration of the red light, the number of vehicles crossing and the number of pedestrians waiting at the curb. Ultra-Orthodox pedestrians committed more violations than secular pedestrians did, and there were more road violations in the Ultra-Orthodox location than there were in the secular location. Fewer traffic violations were committed by "local" pedestrians (Ultra-Orthodox pedestrians in the Ultra-Orthodox location and secular pedestrians in the secular location) than by "foreigners" (Ultra-Orthodox pedestrians in the secular location and secular pedestrians in the Ultra-Orthodox location). The odds of crossing on a red light decreased as a function of both the number of people waiting at the curb and the number of vehicles. Consistent with previous research, males crossed on red much more than females did, regardless of religiosity and location. Our discussion focuses on theoretical and practical explanations of the findings.

Risk perception of driving as a function of advanced training aimed at recognizing and handling risks in demanding driving situations.

The present study examined in 224 individuals whether an advanced driving training aimed at recognizing, avoiding and handling risks in demanding driving situations, affected perceived risk of driving situations (measured by a questionnaire). The training, which involved both experience and feedback on real performance, specifically intended to emphasize the dangers in loss of control of a vehicle. With that emphasis, it was hypothesized that perceived risk would increase after as compared to before the training. In addition, this study examined whether risk perception was dependent on gender or on age. A mixed ANOVA performed on mean scores on the questionnaire yielded significant main effects for training (before/after), gender, and age. Higher levels of perceived risk were reported after the training as compared to before it, by females than by males, and by older adult drivers than by younger adult drivers. An analysis of the data of a smaller sample showed that the increment in perceived risk was still present 2 months after the training, and that it did not decrease significantly as compared to immediately after the training. These results are discussed in relation to relevant methodological issues and future research.

Success on a practical driver's license test with and without the presence of another testee.

The present study examined whether performance in practical driving tests differed when individuals were tested with and without the presence of another testee. In addition, this study examined whether such differences were dependent on the sex of the tested person, on that of the observer testee, and on the order of tests. It was found that for both males and females, a greater proportion of drivers who were tested alone passed the test as compared to drivers who were tested in pairs. Additionally, proportionately more males than females passed the driving test. Only for males was performance also dependent on the gender of the other tested individual. A greater proportion of males who were tested with an accompanying female passed the test than males who were tested with an accompanying male. These results are discussed in relation to social facilitation, gender differences in driving performance, and differences in testing procedures.