Recent Publications
Lilach Malatskey: Preferences and barriers to the utilization of primary health care by sick physicians: a nationwide survey (Fam Pract . )
Physicians are often dissatisfied with their own medical care. Self-prescribing is common despite established guidelines that discourage this practice. From a pilot study, we know primary care physicians' (PCP) preferences, but we lack information regarding other specialties and work places. The goal of this study was to examine whether physicians are satisfied with their personal primary care and how this could be improved.
Tomer Meirson: Structural basis of SARS-CoV-2 spike protein induced by ACE2 (Bioinformatics . )
The recent emergence of the novel SARS-coronavirus 2 (SARS-CoV-2) and its international spread pose a global health emergency. The spike (S) glycoprotein binds ACE2 and promotes SARS-CoV-2 entry into host cells. The trimeric S protein binds the receptor using the receptor-binding domain (RBD) causing conformational changes in S protein that allow priming by host cell proteases. Unraveling the dynamic structural features used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal novel therapeutic targets.
Tzipora C Falik-Zaccai: Sedaghatian-type spondylometaphyseal dysplasia: Whole exome sequencing in neonatal dry blood spots enabled identification of a novel variant in GPX4 (Eur J Med Genet .)
Accumulation of lipid peroxides causes membrane damage and cell death. Glutathione peroxidase 4 (GPX4) acts as a hydroperoxidase which prevents accumulation of toxic oxidized lipids and blocks ferroptosis, an iron-dependent, non-apoptotic mode of cell death. GPX4 deficiency causes Sedaghatian-type spondylo-metaphyseal dysplasia (SSMD), a lethal autosomal recessive disorder, featuring skeletal dysplasia, cardiac arrhythmia and brain anomalies with only three pathogenic GPX4 variants reported in two SSMD patients. Our objective was to identify the underlying genetic cause of neonatal death of two siblings presenting with hypotonia, cardiorespiratory failure and SSMD. (Ayalla Fedida, Shani Ben Harouch, Limor Kalfon, Zahi Abunassar, Hussam Omari, Hanna Mandel, Tzipora C Falik-Zaccai)
Tzipora Falik-Zaccai, Limor Kalfon, Hagay Ladany: De novo STXBP1 mutation in a child with developmental delay and spasticity reveals a major structural alteration in the interface with syntaxin 1A (Am J Med Genet B Neuropsychiatr Genet . )
STXBP1, also known as Munc-18, is a master regulator of neurotransmitter release and synaptic function in the human brain through its direct interaction with syntaxin 1A. STXBP1 binds syntaxin 1A is an inactive conformational state. This study provides a direct link between the outcome of a novel variant in STXBP1 and protein structure and dynamics. The structural change upon mutation drives an alteration in synaptic function.
Tomer Meirson: Real World Outcomes of Ipilimumab and Nivolumab in Patients with Metastatic Melanoma (Cancers (Basel) .)
Immunotherapy has drastically changed the outlook for melanoma patients over the past decade. Specifically, the dual blockade of immune checkpoints using ipilimumab and nivolumab has shown unprecedented response rates and survival outcomes. This immense achievement, though, is at the cost of toxicity, with 60% of the patients experiencing high-grade adverse events (AEs). Our study aims to report the efficacy and toxicity outcomes of an out-of-trial, real-life population.
O Oron, E Elliott: Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B (Mol Autism .)
Partial or an entire deletion of SHANK3 are considered as major drivers in the Phelan-McDermid syndrome, in which 75% of patients are diagnosed with autism spectrum disorder (ASD). During the recent years, there was an increasing interest in stem cell therapy in ASD, and specifically, mesenchymal stem cells (MSC). Moreover, it has been suggested that the therapeutic effect of the MSC is mediated mainly via the secretion of small extracellular vesicle that contains important molecular information of the cell and are used for cell-to-cell communication. Within the fraction of the extracellular vesicles, exosomes were highlighted as the most effective ones to convey the therapeutic effect.
Gabby Elbaz-Greener, Guy Rozen, Fabio Kusniec, Ibrahim Marai, Diab Ghanim, Shemy Carasso, Offer Amir:Trends in Utilization and Safety of In-Hospital Coronary Artery Bypass Grafting During a Non-ST-Segment Elevation Myocardial Infarction (Am J Cardiol .)
Up to 10% of non-ST-segment elevation myocardial infarction (NSTEMI) patients require coronary artery bypass graft (CABG) surgery during their hospitalization. Contemporary, real-world, data regarding CABG utilization and safety in NSTEMI patients are lacking. Our objectives were to investigate the contemporary trends in utilization and outcomes of CABG in patients admitted for NSTEMI.
Wisam Sbeit, Anas Kadah, Amir Mari, Tawfik Khoury: A state-of-the-art comprehensive review summarizing the emerging data on endoscopic ultrasound-guided liver diseases management (Eur J Gastroenterol Hepatol . )
Liver diseases are among the most common diseases worldwide accounting for substantial morbidity and mortality. Most liver diseases necessitate radiological evaluation or accurate diagnosis and recently for management as well. In the last decade, the application of therapeutic endoscopic ultrasound (EUS) procedure has been increasingly utilized for the management of various liver diseases. In this comprehensive narrative review article, we provide systematic overview on EUS-guided therapeutic interventions in various liver diseases summarizing most updated data regarding technical success, outcomes and safety profiles.
Ekaterina Shlush: Potential antigenic cross-reactivity between SARS-CoV-2 and Dengue viruses (Clin Infect Dis .)
COVID-19 and dengue fever are difficult to distinguish given shared clinical and laboratory features. Failing to consider COVID-19 due to false-positive dengue serology can have serious implications. We aimed to assess this possible cross reactivity.
Mizied Falah: Lauryl Gallate Activity and Streptococcus mutans: Its Effects on Biofilm Formation, Acidogenicity and Gene Expression (Molecules .)
Streptococcus mutans bacterium is implicated in the pathogenesis of dental caries due to the production of biofilm and organic acids from dietary sucrose. Despite the availability of various means of prophylaxis, caries still has a high worldwide prevalence. Therefore, it is important to find new pharmaceuticals to inhibit S. mutans biofilm formation and acidogenicity. The aim of the current study was to evaluate the activity of lauryl gallate (dodecyl gallate) against S. mutans acidogenicity, the expression of biofilm-associated genes, and biofilm development on solid surfaces (polystyrene, glass)
Amiel A Dror, Netanel Eisenbach, Matti Mizrachi, Asaf Zigron, Samer Srouji, Eyal Sela: Vaccine hesitancy: the next challenge in the fight against COVID-19 (Eur J Epidemiol .)
Vaccine hesitancy remains a barrier to full population inoculation against highly infectious diseases. Coincident with the rapid developments of COVID-19 vaccines globally, concerns about the safety of such a vaccine could contribute to vaccine hesitancy. We analyzed 1941 anonymous questionnaires completed by healthcare workers and members of the general Israeli population, regarding acceptance of a potential COVID-19 vaccine. Our results indicate that healthcare staff involved in the care of COVID-19 positive patients, and individuals considering themselves at risk of disease, were more likely to self-report acquiescence to COVID-19 vaccination if and when available. In contrast, parents, nurses, and medical workers not caring for SARS-CoV-2 positive patients expressed higher levels of vaccine hesitancy. Interventional educational campaigns targeted towards populations at risk of vaccine hesitancy are therefore urgently needed to combat misinformation and avoid low inoculation rates.
Mycoplasma and Ureaplasma carriage in pregnant women: the prevalence of transmission from mother to newborn (BMC Pregnancy Childbirth .)
Mycoplasma and Ureaplasma have been extensively studied for their possible impact on pregnancy, and their involvement in newborn diseases. This work examined Mycoplasma and Ureaplasma carriage among gravidas women and newborns in Israel, as well as associations between carriage and demographic characteristics, risk factors, pregnancy outcomes, and newborn morbidity rates. (Avi Peretz, Oran Tameri, Maya Azrad, Shay Barak, Yuri Perlitz, Wadie Abu Dahoud, Moshe Ben-Ami, Amir Kushnir)
David Karasik: The Musculoskeletal Knowledge Portal: Making Omics Data Useful to the Broader Scientific Community J Bone Miner Res . )
The development of high-throughput genotyping technologies and large biobank collections, complemented with rapid methodological advances in statistical genetics, has enabled hypothesis-free genome-wide association studies (GWAS), which have identified hundreds of genetic variants across many loci associated with musculoskeletal conditions. Similarly, basic scientists have valuable molecular cellular and animal data based on musculoskeletal disease that would be enhanced by being able to determine the human translation of their findings. By further synthesizing these large scale human genomic musculoskeletal datasets with complementary evidence from model organisms, new and existing genetic loci can be statistically fine-mapped to plausibly causal variants, candidate genes and biological pathways. Genes and pathways identified using this approach can be further prioritized as drug targets including side-effect profiling and the potential for new indications. To bring together these big data, and to realize the vision of creating a knowledge portal, the International Federation of Musculoskeletal Research Societies (IFMRS) established a working group to collaborate with scientists from the Broad Institute to create the Musculoskeletal Knowledge Portal (MSK-KP) that would consolidate -omics datasets from humans, cellular experiments, and model organisms into a central repository that can be accessed by researchers. The vision of the MSK-KP is to enable better understanding of the biological mechanisms underlying musculoskeletal disease and apply this knowledge to identify and develop new disease interventions.