Articles

Dr. Dana Atzil-Slonim – Therapeutic Technique Diversity is Linked to Quality of Working Alliance and Client Functioning Following Alliance Ruptures

Abstract Objective: The current investigation aimed to examine the possible association between therapists’ flexibility in use of therapeutic techniques from different therapy orientations (i.e. therapeutic technique diversity; TTD) and subsequent improvement in client-reported (a) global functioning, as well as (b) quality of the working alliance, following sessions in which alliance ruptures occurred. Method: Clients (n…

Prof. Ron Unger – Cervical dilation at the time of epidural catheter insertion is not associated with the degree of prolongation of the first or second stages of labor, or the rate of instrumental vaginal delivery

Abstract Introduction Epidural analgesia (EA) is an established option for efficient intrapartum analgesia. Meta‐analyses have shown that EA differentially affects the first stage of labor but prolongs the second. The question of EA timing remains open. We aimed to investigate whether EA prolongs delivery in total and whether the EA administration timing vis‐à‐vis cervical dilation…

Prof. Ron Unger – Prediction of vaginal birth after cesarean deliveries using machine learning

Background Efforts to reduce cesarean delivery rates to 12–15% have been undertaken worldwide. Special focus has been directed towards parturients who undergo a trial of labor after cesarean delivery to reduce the burden of repeated cesarean deliveries. Complication rates are lowest when a vaginal birth is achieved and highest when an unplanned cesarean delivery is…

Dr. Orly Avni – Schistosomal extracellular vesicle-enclosed miRNAs modulate host T helper cell differentiation

Abstract During the chronic stage of Schistosoma infection, the female lays fertile eggs, triggering a strong anti‐parasitic type 2 helper T‐cell (Th2) immune response. It is unclear how this Th2 response gradually declines even though the worms live for years and continue to produce eggs. Here, we show that Schistosoma mansoni downregulates Th2 differentiation in an antigen‐presenting cell‐independent manner,…

Prof. Cyrille Cohen – A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function

Abstract Background Tumors can employ different mechanisms to evade immune surveillance and function. Overexpression of co-inhibitory ligands that bind to checkpoint molecules on the surface of T-cells can greatly impair the function of latter. TIGIT (T cell immunoreceptor with Ig and ITIM domains) is such a co-inhibitory receptor expressed by T and NK cells which, upon…

Dr. Evan Elliott – Gene network analysis reveals a role for striatal glutamatergic receptors in dysregulated riskassessment behavior of autism mouse models

Abstract Autism spectrum disorder (ASD) presents a wide, and often varied, behavioral phenotype. Improper assessment of risks has been reported among individuals diagnosed with ASD. Improper assessment of risks may lead to increased accidents and self-injury, also reported among individuals diagnosed with ASD. However, there is little knowledge of the molecular underpinnings of the impaired…

Dr. Meital Gal-Tanamy – Hepatitis C Virus Enhances the Invasiveness of Hepatocellular Carcinoma via EGFR-Mediated Invadopodia Formation and Activation

Abstract Hepatocellular carcinoma (HCC) represents the fifth most common cancer worldwide and the third cause of cancer-related mortality. Hepatitis C virus (HCV) is the leading cause of chronic hepatitis, which often results in liver fibrosis, cirrhosis, and eventually HCC. HCV is the most common risk factor for HCC in western countries and leads to a…

Dr. Omry Koren – Deep microbial analysis of multiple placentas shows no evidence for a placental microbiome

Abstract Objectives To resolve the controversy regarding the presence of a microbiota in the placenta. Design Classical and molecular microbiological study. Setting All samples were collected during caesarean section. Population A total of 28 human placentas and six murine placentas. Methods All 28 human placentas were checked for 16S rRNA gene amplification products. Three locations…

Dr. Itay Onn – The chromatin remodeler Chd1 regulates cohesin in budding yeast and humans

Abstract Chd1 is a chromatin remodeler that is involved in nucleosome positioning and transcription. Deletion of CHD1 is a frequent event in prostate cancer. The Structural Maintenance of Chromosome (SMC) complex cohesin mediates long-range chromatin interactions and is involved in maintaining genome stability. We provide new evidence that Chd1 is a regulator of cohesin. In…

Dr. Meital Gal-Tanamy – Hepatitis C virus leaves an epigenetic signature post cure of infection by directacting antivirals

Abstract The increasing worldwide prevalence of Hepatocellular carcinoma (HCC), characterized by resistance to conventional chemotherapy, poor prognosis and eventually mortality, place it as a prime target for new modes of prevention and treatment. Hepatitis C Virus (HCV) is the predominant risk factor for HCC in the US and Europe. Multiple epidemiological studies showed that sustained…

Prof. Ron Unger – Contemporary patterns of labor in nulliparous and multiparous women

Background Controversy surrounds the definition of “normal” and “abnormal” labor. Objective In this study, we used contemporary labor charts to explore labor patterns in large obstetric population (2011–2016). Study Design Detailed information from electronic medical records of live singleton deliveries at term (≥37 weeks of gestation) was extracted. Cases of elective cesarean deliveries, nonvertex presentation,…

Dr. Omry Koren – Modulation of cytokine patterns and microbiome during pregnancy in IBD

Abstract Objective Pregnancy may affect the disease course of IBD. Both pregnancy and IBD are associated with altered immunology and intestinal microbiology. However, to what extent immunological and microbial profiles are affected by pregnancy in patients with IBD remains unclear. Design Faecal and serum samples were collected from 46 IBD patients (31 Crohn’s disease (CD) and 15…
Dr. Ayal Hendel

Dr. Ayal Hendel – Primary immunodeficiencies – from early diagnosis and gene discovery to personalized therapy

Biology and medicine are undergoing a tremendous revolution where the use of advanced technologies, sophisticated bioinformatics and big data, revealing immediate impact on translation to medicine including disease diagnosis, treatment and outcome. Thus the main objective of this proposal that combines clinical and scientific skills is to extend our knowledge on pathways controlling human immunity…

Prof. Michaeli Shulamit

Nucleic Acids Research, 2019 1–15 doi: 10.1093/nar/gkz477 Pseudouridines on Trypanosoma brucei spliceosomal small nuclear RNAs and their implication for RNA and protein interactions K. Shanmugha Rajan1, Tirza Doniger 1, Smadar Cohen-Chalamish1, Dana Chen1, Oz Semo1, Saurav Aryal1, Efrat Glick Saar2, Vaibhav Chikne1, Doron Gerber 1, Ron Unger1, Christian Tschudi3 and Shulamit Michaeli 1,* 1The Mina…

Prof. Cyrille Cohen – Level of neo-epitope predecessor and mutation type determine T cell activation of MHC binding peptides

Abstract Background Targeting epitopes derived from neo-antigens (or “neo-epitopes”) represents a promising immunotherapy approach with limited off-target effects. However, most peptides predicted using MHC binding prediction algorithms do not induce a CD8 + T cell response, and there is a crucial need to refine the predictions to readily identify the best antigens that could mediate T-cell responses. Such…

Prof. Doron Gerber – An Integrated Microfluidics Approach for Personalized Cancer Drug Sensitivity and Resistance Assay

Abstract Cancer is the second leading cause of death globally. Matching proper treatment and dosage is crucial for a positive outcome. Any given drug may affect patients with similar tumors differently. Personalized medicine aims to address this issue. Unfortunately, most cancer samples cannot be expanded in culture, limiting conventional cell‐based testing. Herein, presented is a…

Dr. Orly Avni – Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells

ABSTRACT Stressful life events are considered a risk factor for autoimmune disorders, though the mechanisms are unclear. Here we demonstrate that chronic social stress induces virulence-associated transcriptional patterns in the murine gut microbiota. The stress-influenced microbiota increased the presence of effector T helper cells in the mesenteric lymph nodes, including myelin-autoreactive cells. Inhibition of the…

Dr. Omry Koren – Progesterone Increases Bifidobacterium Relative Abundance during Late Pregnancy

Highlights Bifidobacterium abundance increases in the gut during pregnancy in women and mice Progesterone supplementation alters gut microbial composition in mice and in vitro Progesterone supplementation increases Bifidobacterium abundance in mice and in vitro We suggest that progesterone promotes Bifidobacterium growth during late pregnancy Summary Gestation is accompanied by alterations in the microbial repertoire; however, the mechanisms driving these changes are unknown. Here, we…

Dr. Evan Elliot – Antidepressants affect gut microbiota and Ruminococcus flavefaciens is able to abolish their effects on depressive-like behavior

Abstract Accumulating evidence demonstrates that the gut microbiota affects brain function and behavior, including depressive behavior. Antidepressants are the main drugs used for treatment of depression. We hypothesized that antidepressant treatment could modify gut microbiota which can partially mediate their antidepressant effects. Mice were chronically treated with one of five antidepressants (fluoxetine, escitalopram, venlafaxine, duloxetine…

Dr. Meital Gal-Tanamy -Dysregulation of the cohesin subunit RAD21 by Hepatitis C virus mediates host–virus interactions

Abstract Hepatitis C virus (HCV) infection is the leading cause of chronic hepatitis, which often results in liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCV possesses an RNA genome and its replication is confined to the cytoplasm. Yet, infection with HCV leads to global changes in gene expression, and chromosomal instability (CIN) in the host…

Prof. Ron Unger – Unplanned Cesarean Delivery in the Second Stage of Labor Holds Higher Odds of Complications than in the First Stage, while Similar in Primiparas and Multiparas

Abstract Background: While endeavors to reduce cesarean delivery (CD) rates are given priority worldwide, it is important to evaluate if these efforts place parturients and neonates at risk. CD performed in the second stage of labor carries higher risks of maternal and fetal complications and is a more challenging surgical procedure than that performed in the…

Prof. Eitan Okun – Restoring microglial and astroglial homeostasis using DNA immunization in a Down Syndrome mouse model

Abstract Down Syndrome (DS), the most common cause of genetic intellectual disability, is characterized by over-expression of the APP and DYRK1A genes, located on the triplicated chromosome 21. This chromosomal abnormality leads to a cognitive decline mediated by Amyloid-β (Aβ) overproduction and tau hyper-phosphorylation as early as the age of 40. In this study, we used the Ts65Dn mouse…

Dr. Meital Gal-Tanamy – Antibody Repertoire Analysis of Hepatitis C Virus Infections Identifies Immune Signatures Associated With Spontaneous Clearance

Hepatitis C virus (HCV) is a major public health concern, with over 70 million people infected worldwide, who are at risk for developing life-threatening liver disease. No vaccine is available, and immunity against the virus is not well-understood. Following the acute stage, HCV usually causes chronic infections. However, ~30% of infected individuals spontaneously clear the…

Prof. Dror Fixler – Self calibration iso-pathlength point in cylindrical tissue geometry: solution of steady-state photon diffusion based on the extrapolated zero-boundary

Abstract Near-infrared optical techniques permit tissue diagnosis by surface measurement. However, the geometrical shape of this interface profiles the intensity of the surface measurement, which is found to have an iso-pathlength (IPL) point allowing for absorption identification independent of tissue scattering. The IPL point was projected in Monte Carlo (MC) simulation, validated experimentally in cylindrical…

Dr. Dana Atzil-Slonim – Therapists’ Empathic Accuracy Toward Their Clients’ Emotions

Abstract Objective: Therapists’ empathic accuracy (EA) toward their clients’ fluctuating emotions is a crucial clinical skill that underlies many therapeutic interventions. In contrast to the subjective components of empathy, limited empirical work has addressed EA or its effect on the outcomes of psychotherapy. Here, we differentiate between the components of EA (tracking accuracy, directional discrepancy) as…

Prof. Ron Unger – Iatrogenic hypertension a bioinformatic analysis

Abstract It is well known that a myriad of medications and substances can induce side effects that are related to blood pressure (BP) regulation. This study aims to investigate why certain drugs tend to cause iatrogenic hypertension (HTN) and focus on drug targets that are implicated in these conditions. Databases and resources such as SIDER,…

Dr David Enshell-Seijffers – The Serine Protease Activity of Corin Is Required for Normal Pigment Type Switching

To the Editor The production and deposition of pigment in mouse skin are confined to the hair follicle and hair shaft, respectively. Hair pigmentation in mice involves the deposition of two types of pigment, black (eumelanin) and yellow (pheomelanin), in a very specific pattern (Barsh et al., 2000). Pigment, either black or yellow, is synthesized during…

Prof. Ron Unger – An Integrative Scoring System for Survival Prediction Following Umbilical Cord Blood Transplantation in Acute Leukemia

Abstract Purpose: Survival of acute leukemia (AL) patients following umbilical cord blood transplantation (UCBT) is dependent on an array of individual features. Integrative models for risk assessment are lacking. We sought to develop a scoring system for prediction of overall survival (OS) and leukemia-free survival (LFS) at 2 years following UCBT in AL patients. Experimental Design: The…

Prof. Ron Unger – Dietary patterns are positively associated with semen quality

Objective To study association of semen quality with a priori whole dietary pattern indexes, which reflect real-world dietary practices and the numerous combinations by which foods are consumed: Healthy Eating Index (HEI), Dietary Approaches to Stop Hypertension (DASH), alternate Mediterranean Diet score (aMED), and Alternative Healthy Eating Index (AHEI). Design A cross-sectional single-center study. Setting Hospital fertility…

Prof. Ron Unger – Sonographic large fetal head circumference and risk of cesarean delivery

Background Background Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patient’s risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier…

Prof. Cyrille Cohen – Fast Image-Guided Stratification Using Anti- Programmed Death Ligand 1 Gold Nanoparticles for Cancer Immunotherapy

Abstract Cancer immunotherapy has made enormous progress in offering safer and more effective treatments for the disease. Specifically, programmed death ligand 1 antibody (αPDL1), designed to perform immune checkpoint blockade (ICB), is now considered a pillar in cancer immunotherapy. However, due to the complexity and heterogeneity of tumors, as well as the diversity in patient…

Prof. Ron Unger – Machine learning for prediction of 30-day mortality after ST elevation myocardial infraction An Acute Coronary Syndrome Israeli Survey data mining study

Abstract Background Risk scores for prediction of mortality 30-days following a ST-segment elevation myocardial infarction (STEMI) have been developed using a conventional statistical approach. Objective To evaluate an array of machine learning (ML) algorithms for prediction of mortality at 30-days in STEMI patients and to compare these to the conventional validated risk scores. Methods This was a…

Prof. Cyrille Cohen – The mutational status of p53 can influence its recognition by human T-cells

ABSTRACT p53 was reported to be an attractive immunotherapy target because it is mutated in approximately half of human cancers, resulting in its inactivation and often accumulation in tumor cells. Peptides derived from p53 are presented by class I MHC molecules and may act as tumor-associated epitopes which could be targeted by p53-specific T cells.…

Prof. Ron Unger – Validation of the acute leukemia-EBMT score for prediction of mortality following allogeneic stem cell transplantation in a multi-center GITMO cohort

Abstract Predictive models may help in determining the risk/benefit ratio of allogeneic hematopoietic stem cell transplantation (HSCT) in acute leukemia (AL). Using a machine‐learning algorithm we have previously developed the AL‐ European Society for Blood and Marrow Transplantation (EBMT) score for prediction of mortality following transplantation. We report here the first external validation of the…
The Dangoor Centre For Personalized Medicine

Kaposi’s sarcoma genetic predisposition and personalized therapy

Familial Kaposi’s sarcoma and genetic whole exome analysis Background: Kaposi’s sarcoma (KS) is a rare malignancy most commonly appearing in HIV carriers. In addition to HIV carriers, there are rare families with genetic predisposition for KS, some are Jewish descent from Morocco. Professor Moshe Schaffer identified a few such families in his service as oncologist…

First Dangoor Centre Research Grant Awarded

The first grant of the Dangoor Center for Personalized Medicine has been awarded to a project using innovative epigenetic methods in order to enhance diagnosis and treatment of patients with acute coronary disease. Cardiovascular diseases are defined by the patient’s loss of flexibility in his or her blood vessels or his or her obstructed and…

Prof. Ron Unger – Prediction of Allogeneic Hematopoietic Stem-Cell Transplantation Mortality 100 Days After Transplantation Using a Machine Learning Algorithm A European Group for Blood and Marrow Transplantation Acute Leukemia Working Party Retrospective Data Mining Study

Purpose Allogeneic hematopoietic stem-cell transplantation (HSCT) is potentially curative for acute leukemia (AL), but carries considerable risk. Machine learning algorithms, which are part of the data mining (DM) approach, may serve for transplantation-related mortality risk prediction.Patients and Methods This work is a retrospective DM study on a cohort of 28,236 adult HSCT recipients from the…