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pwCF carrying the Q359K/T360K variant may have significant clinical benefit from treatment with ETI that may exceed improvements observed with TI treatment. These data support routine clinical use of ETI in this rare patient group. https://bit.ly/45DjFw9., Competing Interests: Conflict of interest: K. Yaacoby-Bianu declares grants and support for attending meetings, receiving fees from Sanofi outside the submitted work. Conflict of interest: D. Prais declares grants, consulting fees and payment for lectures from Vertex, outside the submitted work. Conflict of interest: R. Cohen declares payment for lectures from GSK, and support for attending meetings, receiving fees from Boehringer Ingelheim, AstraZeneca and Kamada, outside the submitted work. Conflict of interest: M. Shteinberg declares grants from GSK, Trudell and the Tel Aviv League for Lung Disease during the conduct of the study; consulting fees from AstraZeneca, Boehringer Ingelheim, Dexcel, Kamada, Synchrony Medical, Trumed, Vertex and Zambon; lecture fees from AstraZeneca, Boehringer Ingelheim, GSK, Kamada, Sanofi and Insmed; support for attending meetings from AstraZeneca, Boehringer Ingelheim, Kamada, Rafa and GSK; participation on advisory boards for Bonus Biotherapeutics, Boehringer Ingelheim and AstraZeneca; board fees from the American Journal of Respiratory and Critical Care Medicine; and receipt of equipment from Trudell, outside the submitted work. Conflict of interest: M. Heching, M.R. Kramer, E. Shmueli, F. Vermeulen, A.S. Ramalho and G. Livnat declare that they have no conflicts of interest., (Copyright ©The authors 2025.) more...

Evidence regarding the high-dose (HD) vaccine's relative vaccine effectiveness (rVE) and absolute benefit in reducing influenza-related hospitalizations compared to the standard-dose (SD) vaccine is warranted. We estimated the adjusted rVE and the number needed to vaccinate (NNV) of the HD vaccine compared to the SD vaccine among Clalit Health Services members aged ≥65 years. Among 418,603 and 393,125 members vaccinated in the 2022-2023 and 2023-2024 influenza seasons, the adjusted rVE was 27% (95% CI: -12% to 61%) for 2022-2023 and 7% (95% CI: -36% to 42%) for 2023-2024, with NNV to prevent one hospitalization event being 2262 (95% CI: 1004 to ∞) and 7662 (95% CI: 1293 to ∞), respectively. Even among the highest-risk subgroup, the NNV was 1289 (95% CI: 571 to ∞) for 2022-2023 and 4719 (95% CI: 797 to ∞) for 2023-2024. The HD vaccine exhibited a limited incremental benefit, even for individuals at the highest risk., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).) more...

Background: Public reluctance to receive COVID-19 vaccination is associated with safety concerns. By contrast, the seasonal influenza vaccine has been administered for decades with a solid safety record and a high level of public acceptance. We compare the safety profile of the BNT162b2 COVID-19 booster vaccine to that of the seasonal influenza vaccine., Methods: We study a prospective cohort of 5079 participants in Israel and a retrospective cohort of 250,000 members of MHS selected randomly. We examine reactions to BNT162b2 mRNA COVID-19 booster and to influenza vaccinations. All prospective cohort participants wore a smartwatch and completed a daily digital questionnaire. We compare pre-vaccination and post-vaccination smartwatch heart-rate data, and a stress measure based on heart-rate variability. We also examine adverse events from electronic health records., Results: In the prospective cohort, 1905 participants receive the COVID-19 booster vaccine; 899 receive influenza vaccination. Focusing on those who receive both vaccines yields a total of 689 participants in the prospective cohort and 31,297 members in the retrospective cohort. Individuals reporting a more severe reaction after influenza vaccination tend to likewise report a more severe reaction after COVID-19 vaccination. In paired analysis, the increase in both heart rate and stress measure for each participant is higher for COVID-19 than for influenza in the first 2 days after vaccination. No elevated risk of hospitalization due to adverse events is found following either vaccine. Except for Bell's palsy after influenza vaccination, no elevated risk of adverse events is found., Conclusions: The more pronounced side effects after COVID-19 vaccination may explain the greater concern associated with it. Nevertheless, our comprehensive analysis supports the safety profile of both vaccines., (© 2024. The Author(s).) more...

Background: Limited knowledge exists regarding behavioral and biomarker shifts during the period from respiratory infection exposure to testing decisions (the diagnostic decision period), a key phase affecting transmission dynamics and public health strategy development. This study aims to examine the changes in behavior and biomarkers during the diagnostic decision period for COVID-19, influenza, and group A streptococcus (GAS)., Methods: We analyzed data from a two-year prospective cohort study involving 4795 participants in Israel, incorporating smartwatch data, self-reported symptoms, and medical records. Our analysis focused on three critical phases: the digital incubation period (from exposure to physiological anomalies detected by smartwatches), the symptomatic incubation period (from exposure to onset of symptoms), and the diagnostic decision period for influenza, COVID-19, and GAS., Findings: The delay between initial symptom reporting and testing was 39 [95% confidence interval (CI): 34-45] hours for influenza, 53 [95% CI: 49-58] hours for COVID-19, and 38 [95% CI: 32-46] hours for GAS, with 73 [95% CI: 67-78] hours from anomalies in heart measures to symptom onset for influenza, 23 [95% CI: 18-27] hours for COVID-19, and 62 [95% CI: 54-68] hours for GAS. Analyzing the entire course of infection of each individual, the greatest changes in heart rates were detected 67.6 [95% CI: 62.8-72.5] hours prior to testing for influenza, 64.1 [95% CI: 61.4-66.7] hours prior for COVID-19, and 58.2 [95% CI: 52.1-64.2] hours prior for GAS. In contrast, the greatest reduction in physical activities and social contacts occurred after testing., Interpretation: These findings highlight the delayed response of patients in seeking medical attention and reducing social contacts and demonstrate the transformative potential of smartwatches for identifying infection and enabling timely public health interventions., Funding: This work was supported by the European Research Council, project #949850, the Israel Science Foundation (ISF), grant No. 3409/19, within the Israel Precision Medicine Partnership program, and a Koret Foundation gift for Smart Cities and Digital Living., Competing Interests: All authors declare no competing interests., (© 2024 The Author(s).) more...

Vaccines stand out as one of the most effective tools in our arsenal for reducing morbidity and mortality. Nonetheless, public hesitancy towards vaccination often stems from concerns about potential side effects, which can vary from person to person. As of now, there are no automated systems available to proactively warn against potential side effects or gauge their severity following vaccination. We have developed machine learning (ML) models designed to predict and detect the severity of post-vaccination side effects. Our study involved 2111 participants who had received at least one dose of either a COVID-19 or influenza vaccine. Each participant was equipped with a Garmin Vivosmart 4 smartwatch and was required to complete a daily self-reported questionnaire regarding local and systemic reactions through a dedicated mobile application. Our XGBoost models yielded an area under the receiver operating characteristic curve (AUROC) of 0.69 and 0.74 in predicting and detecting moderate to severe side effects, respectively. These predictions were primarily based on variables such as vaccine type (influenza vs. COVID-19), the individual's history of side effects from previous vaccines, and specific data collected from the smartwatches prior to vaccine administration, including resting heart rate, heart rate, and heart rate variability. In conclusion, our findings suggest that wearable devices can provide an objective and continuous method for predicting and monitoring moderate to severe vaccine side effects. This technology has the potential to improve clinical trials by automating the classification of vaccine severity., (© 2024. The Author(s).) more...

Background: Studies on post-COVID-19 condition (PCC) in adults have shown deterioration in pulmonary function tests (PFTs), mainly a diffusion limitation. Among the pediatric population, data are scarce. Aim: To characterize PFTs in children with PCC, including changes over time. Methods: A prospective longitudinal study of children with defined PCC and respiratory complaints who were referred to a designated multidisciplinary clinic from 11/2020 to 12/2022. Results: Altogether, 184 children with a mean age of 12.4 years (SD 4.06) were included. A mild obstructive pattern was demonstrated in 19/170 (11%) at presentation, as indicated by spirometry and/or positive exercise challenge test and/or reversibility post bronchodilators, only three had a previous diagnosis of asthma. Lung volumes and diffusion were normal in all but one patient (1/134, 0.7%). Exhaled nitric oxide levels were elevated in 32/144 (22%). A total of 33 children who had repeated PFTs had normal or near-normal PFTs on follow-up testing, including seven (21.2%) who had mild obstructive PFTs at presentation. Multivariate analysis identified older age [OR 1.36 (95% CI:1.07-1.75)], specific imaging findings (prominent bronchovascular markings (OR 43.28 (95% CI: 4.50-416.49)), and hyperinflation (OR 28.42, 95% CI: 2.18-370.84)] as significant predictors of an obstructive pattern on PFTs. Conclusions: In children with PCC and respiratory symptoms, the most common impairment was a mild obstructive pattern; most were without a history of asthma. Improvement was witnessed in long-term follow-up. In contrast to the adult population, no diffusion limitation was found. Empirical periodic inhaler therapy may be considered in children with factors associated with PFT abnormalities. more...

Background: Lung function deterioration in cystic fibrosis (CF) is typically measured by a decline in the forced expiratory volume in one second (FEV 1 %), which is thought to be a late marker of lung disease. Dynamic hyperinflation (DH) is seen in obstructive lung diseases while exercising. Our aim was to assess whether DH could predict pulmonary deterioration in CF; a secondary measure was the peak VO 2 ., Methods: A retrospective study was conducted of people with CF who performed cardiopulmonary exercise tests (CPETs) during 2012-2018. The tests were classified as those demonstrating DH non-DH. Demographic, genetic, and clinical data until 12.2022 were extracted from patient charts., Results: A total of 33 patients aged 10-61 years performed 41 valid CPETs with valid DH measurements; sixteen (39%) demonstrated DH. At the time of the CPETs, there was no difference in the FEV 1 % measurements between the DH and non-DH groups (median 83.5% vs. 87.6%, respectively; p = 0.174). The FEV 1 % trend over 4 years showed a decline in the DH group compared to the non-DH group ( p = 0.009). A correlation was found between DH and the lung clearance index (LCI), as well as the FEV 1 % (r = 0.36 and p = 0.019 and r = -0.55 and p = 0.004, respectively). Intravenous (IV) antibiotic courses during the 4 years after the CPETs were significantly more frequent in the DH group ( p = 0.046). The peak VO 2 also correlated with the FEV 1 % and LCI (r = 0.36 and p = 0.02 and r = -0.46 and p = 0.014, respectively) as well as with the IV antibiotic courses (r = -0.46 and p = 0.014)., Conclusions: In our cohort, the DH and peak VO 2 were both associated with lung function deterioration and more frequent pulmonary exacerbations. DH may serve as a marker to predict pulmonary deterioration in people with CF. more...

Background: Modern wars have a catastrophic effect on the wellbeing of civilians. However, the nature of this effect remains unclear, with most insights gleaned from subjective, retrospective studies., Methods: We prospectively monitored 954 Israelis (>40 years) from two weeks before the May 2021 Israel-Gaza war until four weeks after the ceasefire using smartwatches and a dedicated mobile application with daily questionnaires on wellbeing. This war severely affected civilians on both sides, where over 4300 rockets and missiles were launched towards Israeli cities, and 1500 aerial, land, and sea strikes were launched towards 16,500 targets in the Gaza Strip., Results: We identify considerable changes in all the examined wellbeing indicators during missile attacks and throughout the war, including spikes in heart rate levels, excessive screen-on time, and a reduction in sleep duration and quality. These changes, however, fade shortly after the war, with all affected measures returning to baseline in nearly all the participants. Greater changes are observed in individuals living closer to the battlefield, women, and younger individuals., Conclusions: The demonstrated ability to monitor objective and subjective wellbeing indicators during crises in real-time is pivotal for the early detection of and prompt assistance to populations in need., (© 2023. The Author(s).) more...

Despite proportionality being one of the tenets of data protection laws, we currently lack a robust analytical framework to evaluate the reach of modern data collections and the network effects at play. Here, we propose a graph-theoretic model and notions of node- and edge-observability to quantify the reach of networked data collections. We first prove closed-form expressions for our metrics and quantify the impact of the graph's structure on observability. Second, using our model, we quantify how (1) from 270,000 compromised accounts, Cambridge Analytica collected 68.0M Facebook profiles; (2) from surveilling 0.01% of the nodes in a mobile phone network, a law enforcement agency could observe 18.6% of all communications; and (3) an app installed on 1% of smartphones could monitor the location of half of the London population through close proximity tracing. Better quantifying the reach of data collection mechanisms is essential to evaluate their proportionality., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).) more...

Early childhood dental caries is the most prevalent disease in childhood. Paediatricians are considered by parents as the main authority on prevention and treatment of all the health requirements of their infants., Aim: The aim of this study was to evaluate the knowledge and practice of paediatricians in promoting oral and dental health among young patients (under age 36 months) and their parents., Materials and Methods: 145 anonymous questionnaires were distributed among paediatricians, 130 of them were 90% or above answered and were suitable for analysis for this study.75% of the questionnaires were distributed during the national convention of the Israeli Association of Clinical Paediatrics, 10% in paediatric ambulatory clinics and 15% in paediatric departments in hospitals. Questionnaires were distributed between 2018 and 2020. The inclusion criteria were physicians specialists in paediatrics or residents in paediatrics, all have Israeli licences to practice in Israel. exclusion criteria were partially filled questionnaires. The questionnaire was validated in a pilot study during the years 2010-2012. In addition to demographic variables that included medical training, post-graduate education and clinical practice the questionnaire included 42 questions. Eleven questions on demographics and amount of dental training during academic and clinical training 31 questions belonged to several sections that referred to the participants' awareness of the AAP guidelines regarding oral and dental health and knowledge of oral health. In each section paediatricians were asked to answer or give an opinion on a specific issue, their answers were coded to scores on a scale of 0-5 and summed per section. Correlations between different variables were analysed. The t -test and Mann-Whitney U test were performed for comparing two variables. For comparing more than two variables, we used the Kruskal-Wallis one-way analysis of variance test or ANOVA., Results: The response rate was 89% (130 questionnaires out of 145). The survey showed that most paediatricians (80%) recognized their role in maintaining the oral and dental health of their young patients. Nevertheless, most admitted that they do not perform simple procedures on a regular basis, like dental examinations (64.6%), or asking parents about feeding habits (59.2%) or teeth brushing (75.4%). Only 21% of the participants expressed adequate knowledge of dental care for children younger than age 3 years. Fifty-eight percent of the participants never had any dental training during their entire paediatric medicine training, including medical school. Paediatricians in private or baby clinics received higher scores in practicing caries prevention, 24.15 ± 5.17 (SD), than paediatricians in hospitals, 2.79 ± 0.54 (SD) ( p  = 0.006). Caries prevention practice was not found to correlate with paediatricians' knowledge or attitudes regarding oral and dental caries prevention., Conclusion: Oral and dental knowledge should be incorporated into the paediatric medicine curriculum. With their heavy workload, paediatricians generally do not implement dental caries risk assessment and counselling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Shmueli, Assad-Halloun, Fux-Noy, Halperson, Shmueli, Ram, Moskovitz.) more...

Introduction: Several dry-powder inhalers (DPIs) contain lactose which may be contaminated with milk proteins. Confusion exists pertaining to DPI use in patients with cow's milk protein allergy (CMPA). Methods: A computerized survey sent via e-mail to pediatric pulmonologists and allergologists. Results: A total of 77 out of 232 (33.2%) doctors replied, of whom 80.5% were pediatric pulmonologists. A total of 69 of 77 (89.6%) were specialists, 37.6% with more than 15 years of experience. The most commonly used DPIs were formoterol + budesonide and vilanterol + fluticasone. A total of 62 out of 77 (80.5%) responders knew these DPIs contained lactose. A total of 35 out of 77 (45.5%) doctors who replied did not know that DPI leaflets list CMPA as a contra-indication to DPI administration. Of these, 4 (11.4%) stated that they would instruct patients with CMPA to stop DPIs, and 7 (20%) would avoid recommending DPIs. A total of 42 out of 77 (54.5%) responders were aware of this warning, yet 13 of these 42 (30.9%) continued to recommend lactose-containing DPIs without hesitation and 18 of these 42 (42.8%) responders prescribed DPIs but considered allergy severity. Conclusions: Almost half of certified, experienced pediatric pulmonologists and allergologists were unaware of the warning to administer DPIs to patients with CMPA. Most doctors who do know of this warning still continue to prescribe these DPIs. more...

More than 12 billion COVID-19 vaccination shots have been administered as of August 2022, but information from active surveillance about vaccine safety is limited. Surveillance is generally based on self-reporting, making the monitoring process subjective. We study participants in Israel who received their second or third Pfizer BioNTech COVID-19 vaccination. All participants wore a Garmin Vivosmart 4 smartwatch and completed a daily questionnaire via smartphone. We compare post-vaccination smartwatch heart rate data and a Garmin-computed stress measure based on heart rate variability with data from the patient questionnaires. Using a mixed effects panel regression to remove participant-level fixed and random effects, we identify considerable changes in smartwatch measures in the 72 h post-vaccination even among participants who reported no side effects in the questionnaire. Wearable devices were more sensitive than questionnaires in determining when participants returned to baseline levels. We conclude that wearable devices can detect physiological responses following vaccination that may not be captured by patient self-reporting. More broadly, the ubiquity of smartwatches provides an opportunity to gather improved data on patient health, including active surveillance of vaccine safety., (© 2022. The Author(s).) more...

Background: Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. Therefore, we aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy., Methods: We conducted an observational prospective cohort study to evaluate the level of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement, one serology test was drawn from all patients 4-6 months after the second vaccine dose. In addition a control group matched for age and sex was created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June and August 2021., Results: All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P = 1.0). The anti-fibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [IQR, 207-811] AU/ml vs. 820.75 [IQR, 459-1313] AU/ml; P < 0.001). Only 48.3% (14/29) of patients in the anti-inflammatory arm were seropositive in comparison to 100% (29/29) in the healthy control group (P < 0.001). The anti-inflammatory arm had a significantly lower median antibody titer in comparison to the healthy control group (39.6 [IQR, 4.25-165] AU/ml vs. 970.1 [IQR, 505-1926] AU/ml; P < 0.001)., Conclusion: IPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, and maintain a 100% seropositivity rate 4-6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD treated with anti-inflammatory therapy, 48% were seronegative 4-6 months after the second vaccine dose. Moreover, treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments., (© 2022. The Author(s).) more...

Numerous studies over the past decades established that real-world networks typically follow preferential attachment and detachment principles. Subsequently, this implies that degree fluctuations monotonically increase while rising up the 'degree ladder', causing high-degree nodes to be prone for attachment of new edges and for detachment of existing ones. Despite the extensive study of node degrees (absolute popularity), many domains consider node ranks (relative popularity) as of greater importance. This raises intriguing questions-what dynamics are expected to emerge when observing the ranking of network nodes over time? Does the ranking of nodes present similar monotonous patterns to the dynamics of their corresponding degrees? In this paper, we show that surprisingly the answer is not straightforward. By performing both theoretical and empirical analyses, we demonstrate that preferential principles do not apply to the temporal changes in node ranking. We show that the ranking dynamics follows a non-monotonous curve, suggesting an inherent partition of the nodes into qualitatively distinct stability categories. These findings provide plausible explanations to observed yet hitherto unexplained phenomena, such as how superstars fortify their ranks despite massive fluctuations in their degrees, and how stars are more prone to rank instability., (© 2022 The Authors.) more...

Despite extensive technological advances in recent years, objective and continuous assessment of physiologic measures after vaccination is rarely performed. We conducted a prospective observational study to evaluate short-term self-reported and physiologic reactions to the booster BNT162b2 mRNA (Pfizer-BioNTech, https://www.pfizer.com) vaccine dose. A total of 1,609 participants were equipped with smartwatches and completed daily questionnaires through a dedicated mobile application. The extent of systemic reactions reported after the booster dose was similar to that of the second dose and considerably greater than that of the first dose. Analyses of objective heart rate and heart rate variability measures recorded by smartwatches further supported this finding. Subjective and objective reactions after the booster dose were more apparent in younger participants and in participants who did not have underlying medical conditions. Our findings further support the safety of the booster dose from subjective and objective perspectives and underscore the need for integrating wearables in clinical trials. more...

Halting the rapid clinical deterioration, marked by arterial hypoxemia, is among the greatest challenges clinicians face when treating COVID-19 patients in hospitals. While it is clear that oxygen measures and treatment procedures describe a patient's clinical condition at a given time point, the potential predictive strength of the duration and extent of oxygen supplementation methods over the entire course of hospitalization for a patient death from COVID-19 has yet to be assessed. In this study, we aim to develop a prediction model for COVID-19 mortality in hospitals by utilizing data on oxygen supplementation modalities of patients. We analyzed the data of 545 patients hospitalized with COVID-19 complications admitted to Assuta Ashdod Medical Center, Israel, between 7 March 2020, and 16 March 2021. By solely analyzing the daily data on oxygen supplementation modalities in 182 random patients, we could identify that 75% (9 out of 12) of individuals supported by reservoir oxygen masks during the first two days died 3-30 days following hospital admission. By contrast, the mortality rate was 4% (4 out of 98) among those who did not require any oxygenation supplementation. Then, we combined this data with daily blood test results and clinical information of 545 patients to predict COVID-19 mortality. Our Random Forest model yielded an area under the receiver operating characteristic curve (AUC) score on the test set of 82.5%, 81.3%, and 83.0% at admission, two days post-admission, and seven days post-admission, respectively. Overall, our results could essentially assist clinical decision-making and optimized treatment and management for COVID-19 hospitalized patients with an elevated risk of mortality. more...

Background: Clinical trial guidelines for assessing the safety of vaccines, are primarily based on self-reported questionnaires. Despite the tremendous technological advances in recent years, objective, continuous assessment of physiological measures post-vaccination is rarely performed., Methods: We conducted a prospective observational study during the mass vaccination campaign in Israel. 160 participants >18 years who were not previously found to be COVID-19 positive and who received the BNT162b2 COVID-19 (Pfizer BioNTech) vaccine were equipped with an FDA-approved chest-patch sensor and a dedicated mobile application. The chest-patch sensor continuously monitored 13 different cardiovascular, and hemodynamic vitals: heart rate, blood oxygen saturation, respiratory rate, systolic and diastolic blood pressure, pulse pressure, mean arterial pressure, heart rate variability, stroke volume, cardiac output, cardiac index, systemic vascular resistance and skin temperature. The mobile application collected daily self-reported questionnaires on local and systemic reactions., Results: We identify continuous and significant changes following vaccine administration in nearly all vitals. Markedly, these changes are observed even in presumably asymptomatic participants who did not report any local or systemic reaction. Changes in vitals are more apparent at night, in younger participants, and in participants following the second vaccine dose., Conclusion: the considerably higher sensitivity of wearable sensors can revolutionize clinical trials by enabling earlier identification of abnormal reactions with fewer subjects., Competing Interests: Competing interestsArik Eisenkraft is the Chief Medical Officer of Biobeat Technologies Ltd., the supplier of the chest-patch sensor. The remaining authors declare no competing interests., (© The Author(s) 2022.) more...

Current COVID-19 screening efforts mainly rely on reported symptoms and the potential exposure to infected individuals. Here, we developed a machine-learning model for COVID-19 detection that uses four layers of information: (i) sociodemographic characteristics of the individual, (ii) spatio-temporal patterns of the disease, (iii) medical condition and general health consumption of the individual and (iv) information reported by the individual during the testing episode. We evaluated our model on 140 682 members of Maccabi Health Services who were tested for COVID-19 at least once between February and October 2020. These individuals underwent, in total, 264 516 COVID-19 PCR tests, out of which 16 512 were positive. Our multi-layer model obtained an area under the curve (AUC) of 81.6% when evaluated over all the individuals in the dataset, and an AUC of 72.8% when only individuals who did not report any symptom were included. Furthermore, considering only information collected before the testing episode-i.e. before the individual had the chance to report on any symptom-our model could reach a considerably high AUC of 79.5%. Our ability to predict early on the outcomes of COVID-19 tests is pivotal for breaking transmission chains, and can be used for a more efficient testing policy. more...

Background: During the Coronavirus disease 2019 (COVID-19) pandemic, wearing facemasks became obligatory worldwide., Objectives: The objective of this study was to evaluate the effects of facemasks on gas exchange., Methods: Healthy adults were assessed at rest and during slow and brisk 5-minute walks, with and without masks. We monitored O 2 saturation, end-tidal carbon dioxide (EtCO 2 ), and heart and respiratory rates. Participants graded their subjective difficulty and completed individual sensations questionnaires., Results: Twenty-one participants with a median age of 38 years (range, 29-57 years) were recruited. At rest, all vital signs remained normal, without and with masks. However, during slow and brisk walks, EtCO 2 increased; the rise was significantly higher while wearing masks: slow walk, mean EtCO 2 (mmHg) change +4.5 ± 2.4 versus +2.9 ± 2.3, P = .004; brisk walk EtCO 2 change +8.4 ± 3.0 versus +6.2 ± 4.0, P = .009, with and without masks, respectively. Wearing masks was also associated with higher proportions of participant hypercarbia (EtCO 2 range, 46-49 mmHg) compared with walking without masks, though this was only partially significant. Mean O 2 -saturation remained stable (98%) while walking without masks but decreased by 1.2 % ± 2.2 while walking briskly with a mask ( P = .01). Mild desaturation (O 2 range, 93% to 96%) was noted during brisk walks among 43% of participants with masks, compared with only 14% without masks ( P = .08). Borg's scale significantly increased while walking with a mask, for both slow and brisk walks ( P < .001). Sensations of difficulty breathing and shortness of breath were more common while walking with masks., Conclusion: While important to prevent viral spread, wearing facemasks during brisk 5-minute walks might be associated with mild hypercarbia and desaturation. The clinical significance of these minor gas exchange abnormalities is unclear and should be further investigated., Competing Interests: Conflict of interest: None., (© Copyright 2021 by the American Board of Family Medicine.) more...

Pertussis is a highly contagious bacterial disease that primarily affects infants. To optimize the pertussis vaccination schedule in Israel and evaluate the cost-effectiveness of alternative strategies that add or remove booster doses, we developed an age-structured model for pertussis transmission. Our model was calibrated using 16 years of data from laboratory-confirmed pertussis cases in Israel. Costs and quality-adjusted life years (QALYs) projected by the model within 12 years from the implementation of the considered interventions were compared with the current vaccination schedule. We found that by using the same number of vaccines administered today, the targeting of children at the age of six instead of seven would be predicted to be the optimal schedule to decrease both outpatient visits and hospitalizations. We also found that any increase in maternal vaccination coverage is likely to be cost-effective, with an incremental cost-effectiveness ratio of $77,000-$97,000 per QALY. By contrast, the contribution of the second booster dose is limited, with a probability of only 0.6 to be cost-effective at $110,000/QALY saved. Additional effort should be invested to encourage maternal vaccination against pertussis. We recommend moving the first booster to age six and prudently considering the necessity of the second booster dose. more...

The unprecedented restrictions imposed due to the COVID-19 pandemic altered our daily habits and severely affected our well-being and physiology. The effect of these changes is yet to be fully understood. Here, we analysed highly detailed data on 169 participants for two to six months, before and during the second COVID-19 lockdown in Israel. We extracted 12 well-being indicators from sensory data of smartwatches and from self-reported questionnaires, filled daily using a designated mobile application. We found that, in general, lockdowns resulted in significant changes in mood, sleep duration, sport duration, social encounters, resting heart rate and number of steps. Examining subpopulations, we found that younger participants (aged 20-40 years) suffered from a greater decline in mood and number of steps than older participants (aged 60-80 years). Likewise, women suffered from a higher increase in stress and reduction in social encounters than men. Younger early chronotypes did not increase their sleep duration and exhibited the highest drop in mood. Our findings underscore that while lockdowns severely impacted our well-being and physiology in general, greater damage has been identified in certain subpopulations. Accordingly, special attention should be given to younger people, who are usually not in the focus of social support, and to women. more...

Vaccination has become one of the most prominent measures for preventing the spread of infectious diseases in modern times. However, mass vaccination of the population may not always be possible due to high costs, severe side effects, or shortage. Therefore, identifying individuals with a high potential of spreading the disease and targeted vaccination of these individuals is of high importance. While various strategies for identifying such individuals have been proposed in the network epidemiology literature, the vast majority of them rely solely on the network topology. In contrast, in this paper, we propose a novel targeted vaccination strategy that considers both the static network topology and the dynamic states of the network nodes over time. This allows our strategy to find the individuals with the highest potential to spread the disease at any given point in time. Extensive evaluation that we conducted over various real-world network topologies, network sizes, vaccination budgets, and parameters of the contagion model, demonstrates that the proposed strategy considerably outperforms existing state-of-the-art targeted vaccination strategies in reducing the spread of the disease. In particular, the proposed vaccination strategy further reduces the number of infected nodes by 23-99%, compared to a vaccination strategy based on Betweenness Centrality., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2021.) more...

In this paper, we propose a comprehensive analytics framework that can serve as a decision support tool for HR recruiters in real-world settings in order to improve hiring and placement decisions. The proposed framework follows two main phases: a local prediction scheme for recruitments' success at the level of a single job placement, and a mathematical model that provides a global recruitment optimization scheme for the organization, taking into account multilevel considerations. In the first phase, a key property of the proposed prediction approach is the interpretability of the machine learning (ML) model, which in this case is obtained by applying the Variable-Order Bayesian Network (VOBN) model to the recruitment data. Specifically, we used a uniquely large dataset that contains recruitment records of hundreds of thousands of employees over a decade and represents a wide range of heterogeneous populations. Our analysis shows that the VOBN model can provide both high accuracy and interpretability insights to HR professionals. Moreover, we show that using the interpretable VOBN can lead to unexpected and sometimes counter-intuitive insights that might otherwise be overlooked by recruiters who rely on conventional methods. We demonstrate that it is feasible to predict the successful placement of a candidate in a specific position at a pre-hire stage and utilize predictions to devise a global optimization model. Our results show that in comparison to actual recruitment decisions, the devised framework is capable of providing a balanced recruitment plan while improving both diversity and recruitment success rates, despite the inherent trade-off between the two., Competing Interests: None., (© 2020 Elsevier B.V. All rights reserved.) more...

Global financial crises have led to the understanding that classical econometric models are limited in comprehending financial markets in extreme conditions, partially since they disregarded complex interactions within the system. Consequently, in recent years research efforts have been directed towards modeling the structure and dynamics of the underlying networks of financial ecosystems. However, difficulties in acquiring fine-grained empirical financial data, due to regulatory limitations, intellectual property and privacy control, still hinder the application of network analysis to financial markets. In this paper we study the trading of cryptocurrency tokens on top of the Ethereum Blockchain, which is the largest publicly available financial data source that has a granularity of individual trades and users, and which provides a rare opportunity to analyze and model financial behavior in an evolving market from its inception. This quickly developing economy is comprised of tens of thousands of different financial assets with an aggregated valuation of more than 500 Billion USD and typical daily volume of 30 Billion USD, and manifests highly volatile dynamics when viewed using classic market measures. However, by applying network theory methods we demonstrate clear structural properties and converging dynamics, indicating that this ecosystem functions as a single coherent financial market. These results suggest that a better understanding of traditional markets could become possible through the analysis of fine-grained, abundant and publicly available data of cryptomarkets. more...

Objectives: To evaluate the utilisation (overall and by specialty) and the characteristics of second-opinion seekers by insurance type (either health fund or supplementary insurance) in a mixed private-public healthcare., Design: An observational study., Setting: Secondary care visits provided by a large public health fund and a large supplementary health insurance in Israel., Participants: The entire sample included 1 392 907 patients aged 21 years and above who visited at least one specialist over an 18 months period, either in the secondary care or privately via the supplementary insurance., Outcomes Measures: An algorithm was developed to identify potential second-opinion instances in the dataset using visits and claims data. Multivariate logistic regression was used to identify characteristics of second-opinion seekers by the type of insurance they used., Results: 143 371 (13%) out of 1 080 892 patients who had supplementary insurance sought a single second opinion, mostly from orthopaedic surgeons. Relatively to patients who sought second opinion via the supplementary insurance, second-opinion seekers via the health fund tended to be females (OR=1.2, 95% CI 1.17 to 1.23), of age 40-59 years (OR=1.36, 95% CI 1.31 to 1.42) and with chronic conditions (OR=1.13, 95% CI 1.08 to 1.18). In contrast, second-opinion seekers via the supplementary insurance tended to be native-born and established immigrants (OR=0.79, 95% CI 0.76 to 0.84), in a high socioeconomic level (OR=0.39, 95% CI 0.37 to 0. 4) and living in central areas (OR=0.88, 95% CI 0.85 to 0.9)., Conclusions: Certain patient profiles tended to seek second opinions via the supplementary insurance more than others. People from the centre of the country and with a high socioeconomic status tended to do so, as medical specialists tend to reside in central urban areas. Further research is recommended to examine the availability of medical specialists by specialty and residence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) more...

The concept of "Structural Diversity" of a network refers to the level of dissimilarity between the various agents acting in the system, and it is typically interpreted as the number of connected components in the network. This key property of networks has been studied in multiple settings, including diffusion of ideas in social networks and functional diversity of regions in brain networks. Here, we propose a new measure, "Structural Entropy", as a revised interpretation to "Structural Diversity". The proposed measure relies on the finer-grained network communities (in contrast to the network's connected components), and takes into consideration both the number of communities and their sizes, generating a single representative value. We then propose an approach for monitoring the structure of correlation-based networks over time, which relies on the newly suggested measure. Finally, we illustrate the usefulness of the new approach, by applying it to the particular case of emergent organization of financial markets. This provides us a way to explore their underlying structural changes, revealing a remarkably high linear correlation between the new measure and the volatility of the assets' prices over time. more...

Persuasion is at the core of norm creation, emergence of collective action, and solutions to 'tragedy of the commons' problems. In this paper, we show that the directionality of friendship ties affect the extent to which individuals can influence the behavior of each other. Moreover, we find that people are typically poor at perceiving the directionality of their friendship ties and that this can significantly limit their ability to engage in cooperative arrangements. This could lead to failures in establishing compatible norms, acting together, finding compromise solutions, and persuading others to act. We then suggest strategies to overcome this limitation by using two topological characteristics of the perceived friendship network. The findings of this paper have significant consequences for designing interventions that seek to harness social influence for collective action. more...

CD24 is expressed in 90% of colorectal adenomas and adenocarcinomas. Colorectal cancer (CRC) can be mostly prevented but average risk population screening by stool testing or colonoscopy faces many hurdles. Blood testing is clinically needed. We aimed to evaluate the utility of CD24 expression in peripheral blood leukocytes (PBLs). Two independent case studies were conducted in eligible individuals undergoing colonoscopy. Protein extracted from PBLs was subjected to immunoblotting using anti-CD24 monoclonal antibodies. CD24 sensitivity and specificity were determined using receiver operating characteristic (ROC) analysis. Initially, 150 subjects were examined: 63 had CRC, 19 had adenomas, and 68 had normal colonoscopies. The sensitivity and specificity of CD24 for distinguishing CRC from normal subjects were 70.5% (95% CI, 54.8-83.2%) and 83.8% (95% CI, 74.6-92.7%) and for adenomas 84.2% (95% CI, 60.4-96.4%) and 73.5% (95% CI, 61.4-83.5%), respectively. In the second trial (n = 149), a similar specificity but higher sensitivity was achieved: 80.0% (95% CI, 63.1-91.6%) for CRC and 89.2% (95% CI, 74.6-97%) for adenomas. A simple noninvasive blood test evaluating CD24 levels has high sensitivity and specificity for detecting colorectal adenomas and cancer in patients undergoing colonoscopy at an urban medical center. Larger multicenter studies are warranted to establish the potential of this promising test. more...

The rise of smartphones and web services made possible the large-scale collection of personal metadata. Information about individuals' location, phone call logs, or web-searches, is collected and used intensively by organizations and big data researchers. Metadata has however yet to realize its full potential. Privacy and legal concerns, as well as the lack of technical solutions for personal metadata management is preventing metadata from being shared and reconciled under the control of the individual. This lack of access and control is furthermore fueling growing concerns, as it prevents individuals from understanding and managing the risks associated with the collection and use of their data. Our contribution is two-fold: (1) we describe openPDS, a personal metadata management framework that allows individuals to collect, store, and give fine-grained access to their metadata to third parties. It has been implemented in two field studies; (2) we introduce and analyze SafeAnswers, a new and practical way of protecting the privacy of metadata at an individual level. SafeAnswers turns a hard anonymization problem into a more tractable security one. It allows services to ask questions whose answers are calculated against the metadata instead of trying to anonymize individuals' metadata. The dimensionality of the data shared with the services is reduced from high-dimensional metadata to low-dimensional answers that are less likely to be re-identifiable and to contain sensitive information. These answers can then be directly shared individually or in aggregate. openPDS and SafeAnswers provide a new way of dynamically protecting personal metadata, thereby supporting the creation of smart data-driven services and data science research. more...

Complex problem solving in science, engineering, and business has become a highly collaborative endeavor. Teams of scientists or engineers collaborate on projects using their social networks to gather new ideas and feedback. Here we bridge the literature on team performance and information networks by studying teams' problem solving abilities as a function of both their within-team networks and their members' extended networks. We show that, while an assigned team's performance is strongly correlated with its networks of expressive and instrumental ties, only the strongest ties in both networks have an effect on performance. Both networks of strong ties explain more of the variance than other factors, such as measured or self-evaluated technical competencies, or the personalities of the team members. In fact, the inclusion of the network of strong ties renders these factors non-significant in the statistical analysis. Our results have consequences for the organization of teams of scientists, engineers, and other knowledge workers tackling today's most complex problems. more...

During the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among children were 2× higher than that of the previous 4 influenza seasons; hospitalization rates were 5× higher. Children hospitalized for pandemic (H1N1) 2009 were older and had more underlying chronic diseases than those hospitalized for seasonal influenza. more...

High-frequency, low-intensity electric fields generated by insulated electrodes have previously been shown to inhibit bacterial growth in vitro. In the present study, we tested the effect of these antimicrobial fields (AMFields) on the development of lung infection caused by Pseudomonas aeruginosa in mice. We demonstrate that AMFields (10 MHz) significantly inhibit bacterial growth in vivo, both as a stand-alone treatment and in combination with ceftazidime. In addition, we show that peripheral (skin) heating of about 2 degrees C can contribute to bacterial growth inhibition in the lungs of mice. We suggest that the combination of alternating electric fields, together with the heat produced during their application, may serve as a novel antibacterial treatment modality. more...

Background: Exposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields--TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin., Methods: Three pairs of wild type/MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative (C11) of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line EmtR1; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7/Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231/Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs., Results: TTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields/drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells., Conclusions: The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors. more...

Background: Reports of the risk of colorectal neoplasia associated with a variant of the adenomatous polyposis coli (APC E1317Q) gene are conflicting. Using a case-control design, we investigated this relationship within a clinic-based cohort followed through the Integrated Cancer Prevention Center and the Tel-Aviv Sourasky Medical Center., Materials and Methods: All study subjects were tested for the APC E1317Q variant at enrollment. Subjects underwent colonoscopic evaluation (+/-biopsy and/or polypectomy) and had cancer history and colorectal neoplasia risk factors assessed. The crude and adjusted risks of neoplasia associated with the E1317Q variant were calculated., Results: The prevalence of the E1317Q variant was 1.4% in the entire study sample and 3.2% in Sephardic Jews. E1317Q was more prevalent among cases: 15 of 458 (3.3%) cases were carriers compared with 11 of 1431 (0.8%) controls [odds ratio (OR) 4.4, 95% CI 2.0-9.6]. When stratified by neoplasia type, adenoma risk was significantly elevated in carriers (OR 4.1, 95% CI 1.8-9.4) but colorectal cancer risk was not (OR 2.1, 95% CI 0.8-5.3). After adjustment, the E1317Q variant remained a significant predictor of colorectal adenoma (OR 4.6, 95% CI 2.0-10.8)., Conclusions: The APC E1317Q variant is associated with colorectal neoplasia, particularly colorectal adenomas, but further studies are still needed. Variant prevalence is elevated in Sephardic Jews. more...

Background: The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial., Methods: Cell proliferation in culture was studied in human breast carcinoma (MDA-MB-231) and human glioma (U-118) cell lines, exposed to TTFields, paclitaxel, doxorubicin, cyclophosphamide and dacarbazine (DTIC) separately and in combinations. In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients., Results: The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index more...

Hemorrhagic enteritis virus (HEV) belongs to the Adenoviridae family, a subgroup of adenoviruses (Ads) that infect avian species. In this article, the complete DNA sequence and the genome organization of the virus are described. The full-length of the genome was found to be 26,263 bp, shorter than the DNA of any other Ad described so far. The G + C content of the genome is 34.93%. There are short terminal repeats (39 bp), as described for other Ads. Genes were identified by comparison of the DNA and predicted amino acid sequences with published sequences of other Ads. The organization of the genome in respect to late genes (52K, IIIa, penton base, core protein, hexon, endopeptidase, 100K, pVIII, and fiber), early region 2 genes (polymerase, terminal protein, and DNA binding protein), and intermediate gene IVa2 was found to be similar to that of other human and avian Ad genomes. No sequences similar to E1 and E4 regions were found. Very low similarity to ovine E3 region was found. Open reading frames were identified with no similarity to any published Ad sequence., (Copyright 1998 Academic Press.) more...

It is proposed that an intracellular cycle exists to limit or terminate the insulin signal. The cycle involves increased synthesis of sn-1,2-diacylglycerol (DAG) in response to insulin. The DAG activates protein kinase C (PKC) which phosphorylates glycogen synthase either directly or through other protein kinases to render it inactive. Protein kinase C may also inhibit the insulin receptor by phosphorylation of receptor serine residues. Insulin resistance could then arise as a consequence of a persistent increase in DAG levels. Such an increase could occur in three different ways. Chronic hyperinsulinaemia could increase DAG levels by de-novo synthesis from phosphatidic acid, by hydrolysis of phosphatidylcholine, or by hydrolysis of glycosyl-phosphatidylinositol; DAG is also formed by hydrolysis of phosphatidylinositol 4,5-biphosphate (PIP2). This reaction, known as the 'PI response,' may be the connection between hypertension and insulin resistance. A third mechanism for an increase in DAG involves neural abnormalities. Thus, muscle denervation in the rat is characterized both by a profound insulin resistance and a large increase in DAG. It is possible that a similar increase occurs in humans and may explain the association between denervation, inactivity, and insulin resistance. more...