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  • Open Access English
    Authors: 
    Olalekan O. Oluwole; Krimo Bouabdallah; Javier Munoz; Sophie de Guibert; Julie M. Vose; Nancy L. Bartlett; Yi Lin; Abhinav Deol; Peter A. McSweeney; Andre Goy; +17 more
    Country: Netherlands

    Summary ZUMA‐1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi‐cel), an autologous CD19‐directed chimaeric antigen receptor (CAR)‐T cell therapy, in refractory large B‐cell lymphoma. To reduce treatment‐related toxicity, several exploratory safety management cohorts were added to ZUMA‐1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end‐points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days −5 through −3), 2 × 106 CAR‐T cells/kg (day 0) and once‐daily oral dexamethasone [10 mg, day 0 (before axi‐cel) through day 2]. Forty patients received axi‐cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty‐eight per cent of patients did not experience CRS or NEs within 72 h of axi‐cel. With a median follow‐up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.

  • Open Access English
    Authors: 
    Meysam Alizamir; Ozgur Kisi; Ali Najah Ahmed; Cihan Mert; Chow Ming Fai; Sungwon Kim; Nam-Won Kim; Ahmed El-Shafie;
    Publisher: Public Library of Science

    Soil temperature has a vital importance in biological, physical and chemical processes of terrestrial ecosystem and its modeling at different depths is very important for land-atmosphere interactions. The study compares four machine learning techniques, extreme learning machine (ELM), artificial neural networks (ANN), classification and regression trees (CART) and group method of data handling (GMDH) in estimating monthly soil temperatures at four different depths. Various combinations of climatic variables are utilized as input to the developed models. The models’ outcomes are also compared with multi-linear regression based on Nash-Sutcliffe efficiency, root mean square error, and coefficient of determination statistics. ELM is found to be generally performs better than the other four alternatives in estimating soil temperatures. A decrease in performance of the models is observed by an increase in soil depth. It is found that soil temperatures at three depths (5, 10 and 50 cm) could be mapped utilizing only air temperature data as input while solar radiation and wind speed information are also required for estimating soil temperature at the depth of 100 cm.

  • Closed Access English
    Authors: 
    Jensen Reckhow; Orit Kaidar-Person; Merav A Ben-David; Anna Ostrovski; Dina Ilinsky; Jeffrey Goldstein; Zvi Symon; Shira Galper;
    Country: Netherlands

    A dosimetric study to evaluate the use of continuous positive airway pressure (CPAP), with free-breathing (CPAP-FB) or with deep inspiration breath hold (DIBH-CPAP) an adjunct and alternative to DIBH to reduce heart and lung dose in the radiation therapy (RT) of breast cancer planned for left side RT with regional nodes and internal mammary. A retrospective analysis of 10 left-sided breast cancer patients whose heart or lung dose constraints were not met after RT planning based on FB or DIBH simulations and were referred for CPAP-based planning. All patients were simulated using FB, DIBH, CPAP-FB, and CPAP-DIBH. Treatment plans were calculated to cover the breast/chest wall and regional nodes using tangential field-in-field technique (FiF). Dose-volume parameters for heart, ipsilateral lung, and contralateral breast were compared using the Wilcoxon signed-rank test. For all RT plans, mean heart dose (Gy) was lower for treatment plans with CPAP: CPAP-FB (mean 3.4 vs 7.4, p = 0.001) and CPAP-DIBH (mean 2.5 vs 7.4, p = 0.006) compared to FB alone. CPAP-DIBH also significantly reduced MHD as compared to DIBH alone (mean 2.5 vs 4.3 Gy, p = 0.013). CPAP-DIBH significantly reduced mean lung dose as compared to both FB (mean 14.4 vs 20.1, p = 0.005) and DIBH alone (mean 14.4 vs 17.4, p = 0.007). Eight of 10 patients did not meet ipsilateral lung V20Gy dose constraints ( ?35% of lung receiving 20 Gy) in either the free breathing or DIBH plans, whereas 8 out of 10 met lung V20Gy goal constraints ( ?30% of lung receiving 20 Gy) in the CPAP-DIBH plans. Based on the outcomes of our study, CPAP could be a strategy for reducing lung and heart dose, both in patients not able to execute DIBH and as an adjunct in those not deriving sufficient dose reduction from DIBH alone. ? 2020 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  • Open Access English
    Authors: 
    Uria Moran; Uri Gottlieb; Arnon Gam; Shmuel Springer;
    Publisher: BioMed Central

    Abstract Background Inadequate quadriceps strength following anterior cruciate ligament reconstruction (ACLR) often results in alterations in gait pattern that are usually reported during loading response. Neuro-muscular electrical stimulation (NMES) is frequently used to overcome this quadriceps weakness. Despite the beneficial effects of NMES, persistent deficits in strength and gait are reported. The aim of this study was to investigate the feasibility of applying quadriceps functional electrical stimulation (FES) during walking in addition to standard rehabilitation, in the initial stage of ACLR rehabilitation. Methods Subjects were randomized to quadriceps FES synchronized with walking group (n = 10) or quadriceps NMES (duty cycle of 10 s on/10 s off) group (n = 13). Both interventions were performed for 10 min three days a week, in addition to a standard rehabilitation program. Assessments were performed up to 2 weeks before the ACLR (pre-ACLR), and 4 weeks postoperatively. Outcomes measured were gait speed, single limb stance gait symmetry, quadriceps isometric peak strength ratio (peak strength at 4 weeks/peak strength pre-ACLR) and peak strength inter-limb symmetry. Gait outcomes were also assessed 1-week post-surgery. Results Subjects in both groups regained pre-ACLR gait speed and symmetry after 4 weeks of rehabilitation, with no difference between groups. However, although pre-ACLR quadriceps peak strength was similar between groups (FES - 205 Nm, NMES − 225 Nm, p = 0.605), subjects in the FES group regained 82% of their pre-quadriceps strength compared to 47% in the NMES group (p = 0.02). In addition, after 4 weeks, the FES group had significantly better inter-limb strength symmetry 0.63 ± 0.15 vs. 0.39 ± 0.18 in the NMES group (p = 0.01). Conclusions Quadriceps FES combined with traditional rehabilitation is a feasible, early intervention treatment option, post-ACLR. Furthermore, at 4 weeks post-surgery, FES was more effective in recovering quadriceps muscle strength than was NMES. While spatiotemporal gait parameters did not differ between groups, kinetic and kinematic studies may be useful to further understand the effects of quadriceps FES post-ACLR. The promising results of this preliminary investigation suggest that such studies are warranted. Trial registration ISRCTN 02817399. First posted June 29, 2016.

  • Open Access English
    Authors: 
    Adi Eindor Abarbanel; Timna Naftali; Nahum Ruhimovich; Ariella Bar-Gil Shitrit; Fabiana Sklerovsky-Benjaminov; Fred M. Konikoff; Shay Matalon; Haim Shirin; Yael Milgrom; Tomer Ziv-Baran; +1 more
    Publisher: BMJ Publishing Group

    IntroductionAnxiety and depression are common disturbances in patients with inflammatory bowel diseases (IBD), and were found to impact the disease course. Illness perceptions (IPs), self-efficacy (SE) and sense of coherence (SOC) are important psychological functions, used by the individual to cope with his chronic disease.Aimsto investigate the association of IP, SE and SOC on anxiety and depression among patients with IBD.Patients and methodsPatients filled questionnaires including: demographic, socioeconomic and clinical features. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. IP, SE and SOC were assessed using the Brief Illness perception Questionnaire, IBD-SE and SOC scales.ResultsThe study sample consisted of 299 patients with IBD, median age 34.15, 63% females, 70.9% had Crohn’s disease, filled the questionnaires. In the multivariate analysis, lower results in IP, SE and SOC were found to be associated with significantly increase anxiety (OR 8.35, p<0.001; OR 4.18, p=0.001; OR 4.67, p<0.001, respectively) and depression (OR 15.8, p=0.001; OR 10.99, p=0.029; OR 6.12, p=0.014ConclusionsAnxiety and depression are associated with IP, SE and SOC in patients with IBD. Clinicians should be aware of this impact, recognise their patients’ psychological abilities to cope with the disease and improve those abilities, when needed, in order to achieve a better coping with the disease and to prevent the development of anxiety and depression.

  • Open Access English
    Authors: 
    Trafton Drew; Lauren Williams; Christopher Michael Jones; Roy Luria;
    Publisher: Frontiers Media S.A.
    Project: NSF | Graduate Research Fellows... (1747505)

    Recent evidence has suggested that visual working memory (VWM) plays an important role in representing the target prior to initiating a visual search. The more familiar we are with the search target, the more refined the representation of the target (or ‘target template’) becomes. This sharpening of the target template is thought to underlie the reduced response time and increased accuracy associated with repeatedly searching for the same target. Perhaps target representations transition from limited-capacity VWM to Long-Term Memory (LTM) as targets repeat. In prior work, amplitude of an event-related potential (ERP) component associated with VWM representation decreased with target repetition, broadly supporting this notion. However, previous research has focused on artificial stimuli (Landolt Cs) that are far removed from search targets in the real world. The current study extends this work by directly comparing target representations for artificial stimuli and common object images. We found VWM representation follows the same pattern for real and artificial stimuli. However, the initial selection of the real world objects follows a much different pattern than more typical artificial stimuli. Further, the morphology of nonlateralized waveforms was substantially different for the two stimulus categories. This suggests that the two types of stimuli were processed in fundamentally different ways. We conclude that object type strongly influences how we deploy attentional and mnemonic resources prior to search. Early attentional selection of familiar objects may facilitate additional long-term memory processes that lead to behavioral benefits not seen with more simplistic stimuli.

  • Open Access English
    Authors: 
    Irena Voinsky; David Gurwitz;
    Publisher: John Wiley & Sons, Inc.

    Abstract Uncertainties remain concerning the pathophysiology, epidemiology, and potential therapeutics for COVID‐19. Among unsettled controversies is whether tobacco smoking increases or protects from severe COVID‐19. Several epidemiological studies reported reduced COVID‐19 hospitalizations among smokers, while other studies reported the opposite trend. Some authors assumed that smokers have elevated airway expression of ACE2, the cell recognition site of the SARS‐Cov‐2 spike protein, but this suggestion remains unverified. We therefore performed data mining of two independent NCBI GEO genome‐wide RNA expression files (GSE7894 and GSE994) and report that in both data sets, current smokers and never smokers have, on average, closely similar bronchial epithelial cell mRNA levels of ACE2, as well as TMPRSS2, coding for a serine protease priming SARS‐Cov‐2 for cell entry, and ADAM17, coding for a protease implicated in ACE2 membrane shedding. In contrast, the expression levels of TMPRSS4, coding for a protease that primes SARS‐CoV‐2 for cell entry similarly to TMPRSS2, were elevated in bronchial epithelial cells from current smokers compared with never smokers, suggesting that higher bronchial TMPRSS4 levels in smokers might put them at higher SARS‐Cov‐2 infection risk. The effects of smoking on COVID‐19 severity need clarification with larger studies. Additionally, the postulated protective effects of nicotine and nitric oxide, which may presumably reduce the risk of a “cytokine storm” in infected individuals, deserve assessment by controlled clinical trials.

  • Publication . Conference object . Preprint . Article . 2020
    Open Access English
    Authors: 
    Jingfei Du; Edouard Grave; Beliz Gunel; Vishrav Chaudhary; Onur Celebi; Michael Auli; Veselin Stoyanov; Alexis Conneau;

    Unsupervised pre-training has led to much recent progress in natural language understanding. In this paper, we study self-training as another way to leverage unlabeled data through semi-supervised learning. To obtain additional data for a specific task, we introduce SentAugment, a data augmentation method which computes task-specific query embeddings from labeled data to retrieve sentences from a bank of billions of unlabeled sentences crawled from the web. Unlike previous semi-supervised methods, our approach does not require in-domain unlabeled data and is therefore more generally applicable. Experiments show that self-training is complementary to strong RoBERTa baselines on a variety of tasks. Our augmentation approach leads to scalable and effective self-training with improvements of up to 2.6% on standard text classification benchmarks. Finally, we also show strong gains on knowledge-distillation and few-shot learning. 8 pages

  • Open Access English
    Authors: 
    Orna Levran; Einat Peles; Matthew Randesi; Joel Correa da Rosa; Pei-Hong Shen; John Rotrosen; Miriam Adelson; Mary Jeanne Kreek;
    Publisher: Future Medicine Ltd

    Aim: This study assesses whether genetic variants in stress-related genes are associated with prolonged abstinence from heroin in subjects that are not in long-term methadone treatment. Methods: Frequencies of 117 polymorphisms in 30 genes were compared between subjects with history of heroin addiction, either without agonist treatment (n = 129) or in methadone maintenance treatment (n = 923). Results: SNP rs1500 downstream of CRHBP and an interaction of SNPs rs10482672 (NR3C1) and rs4234955 (NPY1R/NPY5R) were significantly associated with prolonged abstinence without agonist treatment. Conclusion: This study suggests that variability in stress-related genes may contribute to the ability of certain subjects to remain in prolonged abstinence from heroin, possibly due to higher resilience to stress.

  • Publication . Other literature type . Article . 2021
    Open Access English
    Authors: 
    Tomer Illouz; Ravit Madar; Tamir Hirsh; Arya Biragyn; Eitan Okun;

    Aging-related decline in immune functions, termed immunosenescence, is a primary cause of reduced protective responses to vaccines in the elderly, due to impaired induction of cellular and humoral responses to new antigens (Ag), especially if the response is T cell dependent. The result is a more severe morbidity following infections, more prolonged and frequent hospitalization, and a higher mortality rate than in the general population. Therefore, there is an increasing need to develop vaccination strategies that overcome immunosenescence, especially for aging-related diseases such as Alzheimer's disease (AD). Here we report a new vaccination strategy harnessing memory-based immunity, which is less affected by aging. We found that aged C57BL/6 and 5xFAD mice exhibit a dramatic reduction in anti-Amyloid-β (Aβ) antibody (Ab) production. We aimed to reverse this process by inducing memory response at a young age. To this end, young mice were primed with the vaccine carrier Hepatitis B surface antigen (HBsAg). At an advanced age, these mice were immunized with an Aβ1-11 fused to HBsAg. This vaccination scheme elicited a markedly higher Aβ-specific antibody titer than vaccinating aged unprimed mice with the same construct. Importantly, this vaccine strategy more efficiently reduced cerebral Aβ levels and altered microglial phenotype. Overall, we provide evidence that priming with an exogenous Ag carrier can overcome impaired humoral responses to self-antigens in the elderly, paving the route for a potent immunotherapy to AD.

Advanced search in
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24,117 Research products, page 1 of 2,412
  • Open Access English
    Authors: 
    Olalekan O. Oluwole; Krimo Bouabdallah; Javier Munoz; Sophie de Guibert; Julie M. Vose; Nancy L. Bartlett; Yi Lin; Abhinav Deol; Peter A. McSweeney; Andre Goy; +17 more
    Country: Netherlands

    Summary ZUMA‐1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi‐cel), an autologous CD19‐directed chimaeric antigen receptor (CAR)‐T cell therapy, in refractory large B‐cell lymphoma. To reduce treatment‐related toxicity, several exploratory safety management cohorts were added to ZUMA‐1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end‐points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days −5 through −3), 2 × 106 CAR‐T cells/kg (day 0) and once‐daily oral dexamethasone [10 mg, day 0 (before axi‐cel) through day 2]. Forty patients received axi‐cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty‐eight per cent of patients did not experience CRS or NEs within 72 h of axi‐cel. With a median follow‐up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.

  • Open Access English
    Authors: 
    Meysam Alizamir; Ozgur Kisi; Ali Najah Ahmed; Cihan Mert; Chow Ming Fai; Sungwon Kim; Nam-Won Kim; Ahmed El-Shafie;
    Publisher: Public Library of Science

    Soil temperature has a vital importance in biological, physical and chemical processes of terrestrial ecosystem and its modeling at different depths is very important for land-atmosphere interactions. The study compares four machine learning techniques, extreme learning machine (ELM), artificial neural networks (ANN), classification and regression trees (CART) and group method of data handling (GMDH) in estimating monthly soil temperatures at four different depths. Various combinations of climatic variables are utilized as input to the developed models. The models’ outcomes are also compared with multi-linear regression based on Nash-Sutcliffe efficiency, root mean square error, and coefficient of determination statistics. ELM is found to be generally performs better than the other four alternatives in estimating soil temperatures. A decrease in performance of the models is observed by an increase in soil depth. It is found that soil temperatures at three depths (5, 10 and 50 cm) could be mapped utilizing only air temperature data as input while solar radiation and wind speed information are also required for estimating soil temperature at the depth of 100 cm.

  • Closed Access English
    Authors: 
    Jensen Reckhow; Orit Kaidar-Person; Merav A Ben-David; Anna Ostrovski; Dina Ilinsky; Jeffrey Goldstein; Zvi Symon; Shira Galper;
    Country: Netherlands

    A dosimetric study to evaluate the use of continuous positive airway pressure (CPAP), with free-breathing (CPAP-FB) or with deep inspiration breath hold (DIBH-CPAP) an adjunct and alternative to DIBH to reduce heart and lung dose in the radiation therapy (RT) of breast cancer planned for left side RT with regional nodes and internal mammary. A retrospective analysis of 10 left-sided breast cancer patients whose heart or lung dose constraints were not met after RT planning based on FB or DIBH simulations and were referred for CPAP-based planning. All patients were simulated using FB, DIBH, CPAP-FB, and CPAP-DIBH. Treatment plans were calculated to cover the breast/chest wall and regional nodes using tangential field-in-field technique (FiF). Dose-volume parameters for heart, ipsilateral lung, and contralateral breast were compared using the Wilcoxon signed-rank test. For all RT plans, mean heart dose (Gy) was lower for treatment plans with CPAP: CPAP-FB (mean 3.4 vs 7.4, p = 0.001) and CPAP-DIBH (mean 2.5 vs 7.4, p = 0.006) compared to FB alone. CPAP-DIBH also significantly reduced MHD as compared to DIBH alone (mean 2.5 vs 4.3 Gy, p = 0.013). CPAP-DIBH significantly reduced mean lung dose as compared to both FB (mean 14.4 vs 20.1, p = 0.005) and DIBH alone (mean 14.4 vs 17.4, p = 0.007). Eight of 10 patients did not meet ipsilateral lung V20Gy dose constraints ( ?35% of lung receiving 20 Gy) in either the free breathing or DIBH plans, whereas 8 out of 10 met lung V20Gy goal constraints ( ?30% of lung receiving 20 Gy) in the CPAP-DIBH plans. Based on the outcomes of our study, CPAP could be a strategy for reducing lung and heart dose, both in patients not able to execute DIBH and as an adjunct in those not deriving sufficient dose reduction from DIBH alone. ? 2020 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  • Open Access English
    Authors: 
    Uria Moran; Uri Gottlieb; Arnon Gam; Shmuel Springer;
    Publisher: BioMed Central

    Abstract Background Inadequate quadriceps strength following anterior cruciate ligament reconstruction (ACLR) often results in alterations in gait pattern that are usually reported during loading response. Neuro-muscular electrical stimulation (NMES) is frequently used to overcome this quadriceps weakness. Despite the beneficial effects of NMES, persistent deficits in strength and gait are reported. The aim of this study was to investigate the feasibility of applying quadriceps functional electrical stimulation (FES) during walking in addition to standard rehabilitation, in the initial stage of ACLR rehabilitation. Methods Subjects were randomized to quadriceps FES synchronized with walking group (n = 10) or quadriceps NMES (duty cycle of 10 s on/10 s off) group (n = 13). Both interventions were performed for 10 min three days a week, in addition to a standard rehabilitation program. Assessments were performed up to 2 weeks before the ACLR (pre-ACLR), and 4 weeks postoperatively. Outcomes measured were gait speed, single limb stance gait symmetry, quadriceps isometric peak strength ratio (peak strength at 4 weeks/peak strength pre-ACLR) and peak strength inter-limb symmetry. Gait outcomes were also assessed 1-week post-surgery. Results Subjects in both groups regained pre-ACLR gait speed and symmetry after 4 weeks of rehabilitation, with no difference between groups. However, although pre-ACLR quadriceps peak strength was similar between groups (FES - 205 Nm, NMES − 225 Nm, p = 0.605), subjects in the FES group regained 82% of their pre-quadriceps strength compared to 47% in the NMES group (p = 0.02). In addition, after 4 weeks, the FES group had significantly better inter-limb strength symmetry 0.63 ± 0.15 vs. 0.39 ± 0.18 in the NMES group (p = 0.01). Conclusions Quadriceps FES combined with traditional rehabilitation is a feasible, early intervention treatment option, post-ACLR. Furthermore, at 4 weeks post-surgery, FES was more effective in recovering quadriceps muscle strength than was NMES. While spatiotemporal gait parameters did not differ between groups, kinetic and kinematic studies may be useful to further understand the effects of quadriceps FES post-ACLR. The promising results of this preliminary investigation suggest that such studies are warranted. Trial registration ISRCTN 02817399. First posted June 29, 2016.

  • Open Access English
    Authors: 
    Adi Eindor Abarbanel; Timna Naftali; Nahum Ruhimovich; Ariella Bar-Gil Shitrit; Fabiana Sklerovsky-Benjaminov; Fred M. Konikoff; Shay Matalon; Haim Shirin; Yael Milgrom; Tomer Ziv-Baran; +1 more
    Publisher: BMJ Publishing Group

    IntroductionAnxiety and depression are common disturbances in patients with inflammatory bowel diseases (IBD), and were found to impact the disease course. Illness perceptions (IPs), self-efficacy (SE) and sense of coherence (SOC) are important psychological functions, used by the individual to cope with his chronic disease.Aimsto investigate the association of IP, SE and SOC on anxiety and depression among patients with IBD.Patients and methodsPatients filled questionnaires including: demographic, socioeconomic and clinical features. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. IP, SE and SOC were assessed using the Brief Illness perception Questionnaire, IBD-SE and SOC scales.ResultsThe study sample consisted of 299 patients with IBD, median age 34.15, 63% females, 70.9% had Crohn’s disease, filled the questionnaires. In the multivariate analysis, lower results in IP, SE and SOC were found to be associated with significantly increase anxiety (OR 8.35, p<0.001; OR 4.18, p=0.001; OR 4.67, p<0.001, respectively) and depression (OR 15.8, p=0.001; OR 10.99, p=0.029; OR 6.12, p=0.014ConclusionsAnxiety and depression are associated with IP, SE and SOC in patients with IBD. Clinicians should be aware of this impact, recognise their patients’ psychological abilities to cope with the disease and improve those abilities, when needed, in order to achieve a better coping with the disease and to prevent the development of anxiety and depression.

  • Open Access English
    Authors: 
    Trafton Drew; Lauren Williams; Christopher Michael Jones; Roy Luria;
    Publisher: Frontiers Media S.A.
    Project: NSF | Graduate Research Fellows... (1747505)

    Recent evidence has suggested that visual working memory (VWM) plays an important role in representing the target prior to initiating a visual search. The more familiar we are with the search target, the more refined the representation of the target (or ‘target template’) becomes. This sharpening of the target template is thought to underlie the reduced response time and increased accuracy associated with repeatedly searching for the same target. Perhaps target representations transition from limited-capacity VWM to Long-Term Memory (LTM) as targets repeat. In prior work, amplitude of an event-related potential (ERP) component associated with VWM representation decreased with target repetition, broadly supporting this notion. However, previous research has focused on artificial stimuli (Landolt Cs) that are far removed from search targets in the real world. The current study extends this work by directly comparing target representations for artificial stimuli and common object images. We found VWM representation follows the same pattern for real and artificial stimuli. However, the initial selection of the real world objects follows a much different pattern than more typical artificial stimuli. Further, the morphology of nonlateralized waveforms was substantially different for the two stimulus categories. This suggests that the two types of stimuli were processed in fundamentally different ways. We conclude that object type strongly influences how we deploy attentional and mnemonic resources prior to search. Early attentional selection of familiar objects may facilitate additional long-term memory processes that lead to behavioral benefits not seen with more simplistic stimuli.

  • Open Access English
    Authors: 
    Irena Voinsky; David Gurwitz;
    Publisher: John Wiley & Sons, Inc.

    Abstract Uncertainties remain concerning the pathophysiology, epidemiology, and potential therapeutics for COVID‐19. Among unsettled controversies is whether tobacco smoking increases or protects from severe COVID‐19. Several epidemiological studies reported reduced COVID‐19 hospitalizations among smokers, while other studies reported the opposite trend. Some authors assumed that smokers have elevated airway expression of ACE2, the cell recognition site of the SARS‐Cov‐2 spike protein, but this suggestion remains unverified. We therefore performed data mining of two independent NCBI GEO genome‐wide RNA expression files (GSE7894 and GSE994) and report that in both data sets, current smokers and never smokers have, on average, closely similar bronchial epithelial cell mRNA levels of ACE2, as well as TMPRSS2, coding for a serine protease priming SARS‐Cov‐2 for cell entry, and ADAM17, coding for a protease implicated in ACE2 membrane shedding. In contrast, the expression levels of TMPRSS4, coding for a protease that primes SARS‐CoV‐2 for cell entry similarly to TMPRSS2, were elevated in bronchial epithelial cells from current smokers compared with never smokers, suggesting that higher bronchial TMPRSS4 levels in smokers might put them at higher SARS‐Cov‐2 infection risk. The effects of smoking on COVID‐19 severity need clarification with larger studies. Additionally, the postulated protective effects of nicotine and nitric oxide, which may presumably reduce the risk of a “cytokine storm” in infected individuals, deserve assessment by controlled clinical trials.

  • Publication . Conference object . Preprint . Article . 2020
    Open Access English
    Authors: 
    Jingfei Du; Edouard Grave; Beliz Gunel; Vishrav Chaudhary; Onur Celebi; Michael Auli; Veselin Stoyanov; Alexis Conneau;

    Unsupervised pre-training has led to much recent progress in natural language understanding. In this paper, we study self-training as another way to leverage unlabeled data through semi-supervised learning. To obtain additional data for a specific task, we introduce SentAugment, a data augmentation method which computes task-specific query embeddings from labeled data to retrieve sentences from a bank of billions of unlabeled sentences crawled from the web. Unlike previous semi-supervised methods, our approach does not require in-domain unlabeled data and is therefore more generally applicable. Experiments show that self-training is complementary to strong RoBERTa baselines on a variety of tasks. Our augmentation approach leads to scalable and effective self-training with improvements of up to 2.6% on standard text classification benchmarks. Finally, we also show strong gains on knowledge-distillation and few-shot learning. 8 pages

  • Open Access English
    Authors: 
    Orna Levran; Einat Peles; Matthew Randesi; Joel Correa da Rosa; Pei-Hong Shen; John Rotrosen; Miriam Adelson; Mary Jeanne Kreek;
    Publisher: Future Medicine Ltd

    Aim: This study assesses whether genetic variants in stress-related genes are associated with prolonged abstinence from heroin in subjects that are not in long-term methadone treatment. Methods: Frequencies of 117 polymorphisms in 30 genes were compared between subjects with history of heroin addiction, either without agonist treatment (n = 129) or in methadone maintenance treatment (n = 923). Results: SNP rs1500 downstream of CRHBP and an interaction of SNPs rs10482672 (NR3C1) and rs4234955 (NPY1R/NPY5R) were significantly associated with prolonged abstinence without agonist treatment. Conclusion: This study suggests that variability in stress-related genes may contribute to the ability of certain subjects to remain in prolonged abstinence from heroin, possibly due to higher resilience to stress.

  • Publication . Other literature type . Article . 2021
    Open Access English
    Authors: 
    Tomer Illouz; Ravit Madar; Tamir Hirsh; Arya Biragyn; Eitan Okun;

    Aging-related decline in immune functions, termed immunosenescence, is a primary cause of reduced protective responses to vaccines in the elderly, due to impaired induction of cellular and humoral responses to new antigens (Ag), especially if the response is T cell dependent. The result is a more severe morbidity following infections, more prolonged and frequent hospitalization, and a higher mortality rate than in the general population. Therefore, there is an increasing need to develop vaccination strategies that overcome immunosenescence, especially for aging-related diseases such as Alzheimer's disease (AD). Here we report a new vaccination strategy harnessing memory-based immunity, which is less affected by aging. We found that aged C57BL/6 and 5xFAD mice exhibit a dramatic reduction in anti-Amyloid-β (Aβ) antibody (Ab) production. We aimed to reverse this process by inducing memory response at a young age. To this end, young mice were primed with the vaccine carrier Hepatitis B surface antigen (HBsAg). At an advanced age, these mice were immunized with an Aβ1-11 fused to HBsAg. This vaccination scheme elicited a markedly higher Aβ-specific antibody titer than vaccinating aged unprimed mice with the same construct. Importantly, this vaccine strategy more efficiently reduced cerebral Aβ levels and altered microglial phenotype. Overall, we provide evidence that priming with an exogenous Ag carrier can overcome impaired humoral responses to self-antigens in the elderly, paving the route for a potent immunotherapy to AD.

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