Search results for: Yifat Koren Carmi

Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

Abstract:

Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: Nurit Carmi

Abstract:

There are many endangered species that are not popular but whose conservation is, nonetheless, important. The present study deals with sharks who suffer from demonization and, accordingly, from public indifference to the deteriorating state of their conservation. We used the seasonal appearance of sharks in the Israeli coastal zone to study public perceptions and attitudes towards sharks prior to ("control group") and after ("visitors") shark watching during a visit in an information center. We found that shark’s image was significantly more positive among the "visitors" compared to the control group. We found that visiting in the information center was strongly related to a more positive shark image, attitudes toward shark conservation, and willingness to act to preserve them.

Keywords: wildlife tourism, shark conservation, attitudes towards animals, human-animal relationships, Smith's salience index

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Authors: Omar Sorour, Michael Leahy, Thomas Irvine, Vladimir Koren

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Introduction: Covid encephalitis is a rare yet dangerous complication, particularly affecting the older and immunocompromised. Symptoms range from confusion to delirium, coma, and seizures. Although neurological manifestations have become more well-characterized in COVID patients, little is known about whether priorneurological abnormalities may predispose patients to COVID encephalopathy. Case Description: A 73 y.o. male with a CT and MRI-confirmed stable, prior 9 mm cavernoma in the right frontal lobe and no past history of seizures was hospitalized with generalized weakness, abdominal pain, nausea, and shortness of breath with subsequent COVID pneumonia. Three days after the initial presentation, the patient developed a spontaneous generalized tonic-clonic seizure consistent with presumed COVID encephalitis, along with somnolence and confusion. A day later, the patient had two other seizure episodes. Follow-up EEG suggested an inter-ictal epileptic focus with sharp waves corresponding to roughly the same location as the patient’s pre-existing cavernoma. The patient’s seizures stopped shortly thereafter, while his encephalopathy continued for days. Conclusion: We illustrate that a pre-existing anatomic cortical abnormality may act as a potential nidus for new-onset seizure activity in the context of suggested COVID encephalopathy. Future studies may further demonstrate that manifestations of COVIDencephalopathy in certain patients may be more predictable than initially assumed.

Keywords: cavernoma, covid, encephalopathy, seizures

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Authors: Vojko Kilar, Boris Azinović, David Koren

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Recently, an increasing trend of passive and low-energy buildings transferring form non earthquake-prone to earthquake-prone regions has thrown out the question about the seismic safety of such buildings. The paper describes the most commonly used thermal insulating materials and the special details, which could be critical from the point of view of earthquake resistance. The most critical appeared to be the cases of buildings founded on the RC foundation slab lying on a thermal insulation (TI) layer made of extruded polystyrene (XPS). It was pointed out that in such cases the seismic response of such buildings might differ to response of their fixed based counterparts. The main parameters that need special designers’ attention are: the building’s lateral top displacement, the ductility demand of the superstructure, the foundation friction coefficient demand, the maximum compressive stress in the TI layer and the percentage of the uplifted foundation. The analyses have shown that the potentially negative influences of inserting the TI under the foundation slab could be expected only for slender high-rise buildings subjected to severe earthquakes. Oppositely it was demonstrated for the foundation friction coefficient demand which could exceed the capacity value yet in the case of low-rise buildings subjected to moderate earthquakes. Some suggestions to prevent the horizontal shifts are also given.

Keywords: earthquake response, extruded polystyrene (XPS), low-energy buildings, foundations on thermal insulation layer

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Authors: David Koren, Vojko Kilar

Abstract:

The modern energy-efficient houses are often founded on a thermal insulation (TI) layer placed under the building’s RC foundation slab. The purpose of the paper is to identify the potential problems of the buildings founded on TI layer from the seismic point of view. The two main goals of the study were to assess the seismic behavior of such buildings, and to search for the critical structural parameters affecting the response of the superstructure as well as of the extruded polystyrene (XPS) layer. As a test building a multi-storeyed RC frame structure with and without the XPS layer under the foundation slab has been investigated utilizing nonlinear dynamic (time-history) and static (pushover) analyses. The structural response has been investigated with reference to the following performance parameters: i) Building’s lateral roof displacements, ii) Edge compressive and shear strains of the XPS, iii) Horizontal accelerations of the superstructure, iv) Plastic hinge patterns of the superstructure, v) Part of the foundation in compression, and vi) Deformations of the underlying soil and vertical displacements of the foundation slab (i.e. identifying the potential uplift). The results have shown that in the case of higher and stiff structures lying on firm soil the use of XPS under the foundation slab might induce amplified structural peak responses compared to the building models without XPS under the foundation slab. The analysis has revealed that the superstructure as well as the XPS response is substantially affected by the stiffness of the foundation slab.

Keywords: extruded polystyrene (XPS), foundation on thermal insulation, energy-efficient buildings, nonlinear seismic analysis, seismic response, soil–structure interaction

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Authors: Gubair Tarabeh, Ghadir Zriek, David Oppenheim, Avi Sagi-Schwartz, Nina Koren-Karie

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Introduction: Mind-Mindedness (MM) focuses on mothers' attunement to their infant's mental states as reflected in their speech to the infant. Appropriate MM comments are associated with attachment security in individualistic Western societies where parents value their children’s autonomy and independence, and may therefore be more likely to engage in mind-related discourse with their children that highlights individual thoughts, preferences, emotions, and motivations. Such discourse may begin in early infancy, even before infants are likely to understand the semantic meaning of parental speech. Parents in collectivistic societies, by contrast, are thought to emphasize conforming to social norms more than individual goals, and this may lead to parent-child discourse that emphasizes appropriate behavior and compliance with social norms rather than internal mental states of the self and the other. Therefore, the examination of maternal MM and its relationship with attachment in Arab collectivistic culture in Israel was of particular interest. Aims of the study: The goal of the study was to examine whether the associations between MM and attachment in the Arab culture in Israel are the same as in Western samples. An additional goal was to examine whether appropriate and non-attuned MM comments could, together, distinguish among mothers of children in the different attachment classifications. Material and Methods: 76 Arab mothers and their infants between the ages of 12 and 18 months were observed in the Strange Situation Procedure (49 secure (B), 11 ambivalent (C), 14 disorganized (D), and 2 avoidant (A) infants). MM was coded from an 8-minute free-play sequence. Results: Mothers of B infants used more appropriate and less non-attuned MM comments than mothers of D infants, with no significant differences with mothers of C infants. Also, mothers of B infants used less non-attuned MM comments than both mothers of D infants and mothers of C infants. In addition, Mothers of B infants were most likely to show the combination of high appropriate and low non-attuned MM comments; Mothers of D infants were most likely to show the combination of high non-attuned and low appropriate MM comments; and a non-significant trend indicated that mothers of C infants were most likely to show a combination of high appropriate and high non-attuned MM comments. Conclusion: Maternal MM was associated with attachment in the Arab culture in Israel with combinations of appropriate and non-attuned MM comments distinguishing between different attachment classifications.

Keywords: attachment, maternal mind-mindedness, Arab culture, collectivistic culture

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Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

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Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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Authors: Lena Lapidot, Amir Amnon, Rita Nosenko, Veitsman Ella, Cohen-Ezra Oranit, Davidov Yana, Segev Shlomo, Koren Omry, Safran Michal, Ben-Ari Ziv

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Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related mortality worldwide. Liver Cirrhosis is the main predisposing risk factor for the development of HCC. The factor(s) influencing disease progression from Cirrhosis to HCC remain unknown. Gut microbiota has recently emerged as a major player in different liver diseases, however its association with HCC is still a mystery. Moreover, there might be an important association between the gut microbiota, nutrition, life style and the progression of Cirrhosis and HCC. The aim of our study was to characterize the gut microbial signature in association with life style and nutrition of patients with Cirrhosis, HCC-Cirrhosis and healthy controls. Design: Stool samples were collected from 95 individuals (30 patients with HCC, 38 patients with Cirrhosis and 27 age, gender and BMI-matched healthy volunteers). All participants answered lifestyle and Food Frequency Questionnaires. 16S rRNA sequencing of fecal DNA was performed (MiSeq Illumina). Results: There was a significant decrease in alpha diversity in patients with Cirrhosis (qvalue=0.033) and in patients with HCC-Cirrhosis (qvalue=0.032) compared to healthy controls. The microbiota of patients with HCC-cirrhosis compared to patients with Cirrhosis, was characterized by a significant overrepresentation of Clostridium (pvalue=0.024) and CF231 (pvalue=0.010) and lower expression of Alphaproteobacteria (pvalue=0.039) and Verrucomicrobia (pvalue=0.036) in several taxonomic levels: Verrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae and the genus Akkermansia (pvalue=0.039). Furthermore, we performed an analysis of predicted metabolic pathways (Kegg level 2) that resulted in a significant decrease in the diversity of metabolic pathways in patients with HCC-Cirrhosis (qvalue=0.015) compared to controls, one of which was amino acid metabolism. Furthermore, investigating the life style and nutrition habits of patients with HCC-Cirrhosis, we found significant correlations between intake of artificial sweeteners and Verrucomicrobia (qvalue=0.12), High sugar intake and Synergistetes (qvalue=0.021) and High BMI and the pathogen Campylobacter (qvalue=0.066). Furthermore, overweight in patients with HCC-Cirrhosis modified bacterial diversity (qvalue=0.023) and composition (qvalue=0.033). Conclusions: To the best of the our knowledge, we present the first report of the gut microbial composition in patients with HCC-Cirrhosis, compared with Cirrhotic patients and healthy controls. We have demonstrated in our study that there are significant differences in the gut microbiome of patients with HCC-cirrhosis compared to Cirrhotic patients and healthy controls. Our findings are even more pronounced because the significantly increased bacteria Clostridium and CF231 in HCC-Cirrhosis weren't influenced by diet and lifestyle, implying this change is due to the development of HCC. Further studies are needed to confirm these findings and assess causality.

Keywords: Cirrhosis, Hepatocellular carcinoma, life style, liver disease, microbiome, nutrition

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Authors: Iris Alkaher, Nurit Carmi

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It is widely agreed among scientists that population growth (PG) is a major factor that drives the global environmental crisis. Many researchers recognize that explicitly addressing the impact of PG on the environment and human quality of life through education systems worldwide could play a significant role in improving understanding regarding the links between rapid PG and environmental degradation and changing perceptions, attitudes, and behaviors concerning the necessity to reduce the fertility rate. However, the issue of PG is still rarely included in schools' curricula, mainly because of its complexity and controversiality. This study aims to explore the perspectives of teachers with an academic background in environmental and sustainability education (ESEteachers) and teachers with no such background (non-ESE teachers) regarding PG as an environmental risk. The study also explores the teachers’ willingness to include PG in their teaching and identifies what predicts their inclusion of it. In this mixed-methods research study, data were collected using questionnaires and interviews. The findings portray a complex picture concerning the debate aboutPG as a major factor that drives the global environmental crisis in the Israeli context. Consistent with other countries, we found that the deep-rooted pronatalist culture in the Israeli society, as well as a robust national pronatalist agenda and policies, have a tremendous impact on the education system. Therefore, we found that an academic background in ESE had a limited impact on teachers' perceptions concerning PG as a problem and on their willingness to include it in their teaching and discuss its controversiality. Teachers' attitudes related to PG demonstrated social, cultural, and politically oriented disavowal justification regarding the negative impacts of rapid PG, identified in the literature as population-skepticism and population-fatalism. Specifically, factors such as the ongoing Israeli-Palestinian conflict, the Jewish anxiety of destruction, and the religious command to“be fruitful and multiply”influenced the perceptions of both ESE and non-ESE teachers. While these arguments are unique to the Israeli context, pronatalist policies are international. In accordance with the pronatalist policy, we also found that the absence of PG from both school curricula and the Israeli public discourse was reported by ESE and non-ESE teachers as major reasons for their disregarding PG in their teaching. Under these circumstances, the role of the education system to bring the population question to the front stage in Israel and elsewhere is more challenging. To encourage science and social studies teachers to incorporate the controversial issue of PG in their teaching and successfully confront dominant pronatalist cultures, they need strong and ongoing scaffolding and support. In accordance with scientists' agreement regarding the role of PG as a major factor that drives the global environmental crisis, we call on stakeholders and policymakers in the education system to bring the population debate into schools' curricula, the sooner, the better. And not only as part of human efforts to mitigate environmental degradation but also to use this controversial topic as a platform for shaping critical learners and responsible and active citizens who are tolerant of different people’s opinions.

Keywords: population growth, environmental and sustainability education, controversial environmental sustainability issues, pronatalism

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