Tel Aviv University
  • Tel Aviv, Israel
Recent publications
Background Israel is a multiethnic society with a population of 9.8 million at the end of 2023. Israeli Arabs (i.e., Arab Palestinian citizens of Israel) account for 21% of the Israel’s overall population, 22% of its working age population and 16% of the employed population. This study has several objectives: (1) To provide an overview of the current representation of Israeli Arabs in four key health care professions (medicine, nursing, dentistry, and pharmacy) in terms of employment, licensure, and professional studies; (2) To document changes in those parameters over the past decade, subject to limitations of data availability; (3) To provide a broader context on the employment of Israeli Arabs; (4) To explore the policy implications of the key findings. Methods Estimates of employment levels are based on the Labor Force Survey (LFS) of the Central Bureau of Statistics (CBS). Data on licensure (i.e., professional qualification) and place of professional studies were extracted from the Ministry of Health report series entitled “The Health Care Professions”. Data on enrollment in degree programs in Israel was provided by the Council of Higher Education. Important background information was elicited from relevant policy documents and policy experts. Results In 2023, among employed Israelis up to age 67, Arabs constituted approximately one-quarter of Israel’s physicians (25%), nurses (27%), and dentists (27%), and half of Israel’s pharmacists (49%). These percentages are substantially higher than they were in 2010, with the increase being particularly marked in the case of physicians (25% versus 8%). The number of new licenses granted annually increased significantly between 2010 and 2022 for both Arabs and Jews in each of the professions covered. The percentage of newly licensed professionals who are Arab increased substantially among physicians and nurses, while remaining stable among dentists and pharmacists. In medicine, dentistry, and pharmacy, many of the licensed Arab health professionals had studied outside of Israel; this phenomenon also exists for nursing but is less widespread there. In the 2022/3 academic year, the percentage of first-degree students in Israeli colleges and universities who were Arab was 70% in pharmacy, 33% in nursing, 23% in dentistry, and 9% in medicine. Between 2012/3 and 2022/3 the percentage of first-degree students who are Arab increased substantially for pharmacy, declined slightly for nursing, and declined substantially for medicine and dentistry. Conclusions Arab professionals play a substantial and recently increased role in the provision of health care services in Israel. It is important to recognize, appreciate, and maintain this substantial role. Moreover, its potential as a model for sectors other than health care should be explored. To build on achievements to date, and to promote continued progress, policymakers should expand access to health professional education within Israel, upgrade the skills of graduates of non-Israeli universities, promote diversity in leadership positions and key specialties, and expand specialty care services in Arab localities.
The impact of the European Union (EU) in strengthening nanotechnology risk regulation in non-EU countries is still an under-researched topic. This article focuses on the EU’s influence on its trading partners, using the case study of Israel, which in 2023 adopted restrictions on nanotechnology in cosmetics products following the EU. It is argued that EU risk regulation have been both a trigger and a formative factor for the development of Israeli nanomaterials restrictions. The importance and economic interdependence in the EU market for cosmetics has prompted a response from Israeli policymakers. In addition, the EU regulatory capacity through its expertise and sanctioning authority have influenced the Israeli regulatory agenda. The article shows that the impact of EU regulation also coincided with domestic economic factors, concerns about technology policy and policymakers’ preference for stringent standards. Israel’s risk regulation of nanomaterials in cosmetics provides a useful case study for analyzing the EU’s regulatory impact on its trading partners. Once again, stricter EU’s health and safety regulation drives those of its trading partner upward.
Copy number variants (CNVs) are an important source of genetic variation underlying rapid adaptation and genome evolution. Whereas point mutation rates vary with genomic location and local DNA features, the role of genome architecture in the formation and evolutionary dynamics of CNVs is poorly understood. Previously, we found the GAP1 gene in Saccharomyces cerevisiae undergoes frequent amplification and selection in glutamine-limitation. The gene is flanked by two long terminal repeats (LTRs) and proximate to an origin of DNA replication (autonomously replicating sequence, ARS), which likely promote rapid GAP1 CNV formation. To test the role of these genomic elements on CNV-mediated adaptive evolution, we evolved engineered strains lacking either the adjacent LTRs, ARS, or all elements in glutamine-limited chemostats. Using a CNV reporter system and neural network simulation-based inference (nnSBI) we quantified the formation rate and fitness effect of CNVs for each strain. Removal of local DNA elements significantly impacts the fitness effect of GAP1 CNVs and the rate of adaptation. In 177 CNV lineages, across all four strains, between 26% and 80% of all GAP1 CNVs are mediated by Origin Dependent Inverted Repeat Amplification (ODIRA) which results from template switching between the leading and lagging strand during DNA synthesis. In the absence of the local ARS, distal ones mediate CNV formation via ODIRA. In the absence of local LTRs, homologous recombination can mediate gene amplification following de novo retrotransposon events. Our study reveals that template switching during DNA replication is a prevalent source of adaptive CNVs.
Purpose of Review Gambling disorder (GD) presents significant psychiatric challenges, particularly for vulnerable populations like military veterans, who often also face mental health comorbidities. Recovery is a crucial issue in the gambling field, representing a transition from illness to health. Currently, there is no consensus regarding its definition. This scoping review aimed to map the characteristics of studies on recovery in veterans with GD, explore how it is defined and measured, identify the dominate recovery approach, and the main research topics. Recent Findings This review identified 13 scientific articles. Findings showed minimal explicit use of the term “recovery” by researchers. The main recovery approach is the deficit based. Most studies focused on treatment programs and their effectiveness, neglecting the unique characteristics of veterans and alternative recovery pathways. Summary Future studies should explore and conceptualize recovery in veterans, and inquire into the specific recovery needs of veterans living with GD.
Objective To evaluate the effectiveness of a cesarean delivery (CD) bundle including preoperative vaginal preparation, cefazolin and azithromycin administration, compared with cefazolin alone, in reducing postoperative infections, among women undergoing CD during the second stage of labor. Methods In August 2016, our departmental protocol for preventing infectious morbidity in second‐stage CD was revised from preoperative intravenous 2 g cefazolin alone, to preoperative intravenous 2 g cefazolin, intravenous 500 mg azithromycin, and vaginal cleansing with povidone‐iodine. In this before‐and‐after study, the medical records of women who underwent CD during the second stage of labor were reviewed, comparing two time periods: January 2014 to August 2016 (control group, cefazolin alone) and November 2016 to January 2021 (CD bundle group). Obstetric characteristics, postoperative infections, and neonatal outcomes were compared between groups. Composite infectious morbidity was defined as one or more of: endometritis, surgical‐site infection (SSI), abscess, urinary tract infection, and postpartum fever. Results During the study period, there were 5265 intrapartum CD, among them 457 were during the second stage of labor. The CD bundle group (n = 331) had lower rates of endometritis, SSI, and composite infectious morbidity compared with the control group (n = 126, 1.2% vs. 4.8%, P = 0.030; 3.0% vs. 7.1%, P = 0.049, 6.9% vs. 14.3%, P = 0.014, respectively). Neonatal outcomes did not differ between groups. Multivariable regression analysis adjusted for confounders revealed that the CD bundle reduced the risk for the composite infectious outcome, with adjusted odds ratio 0.08 (95% confidence interval 0.01–0.50). Conclusions In second‐stage CD, adding preoperative azithromycin and vaginal cleansing to cefazolin was efficacious in reducing postoperative infections.
745 Background: In a Phase 2 trial, treatment of non-resectable locally advanced pancreatic cancer (LAPC) patients harboring the KRAS G12D or G12V mutations, with SiG12DLoder combined with chemotherapy resulted in superior median overall survival (OS) of 9.3 months over chemotherapy (not statistically significant) and Objective Response Rate of 55% (35% over the chemotherapy control), when administered once every 3 months (Clinical trial # NCT01676259, ESMO 2023, abstract FPN: 1626). SIL-204 which is a modified version of siRNA siG12D is composed of a 21-base sense and 23-base antisense strands, both chemically modified and linked to a lipid. SIL-204 is encapsulated in biodegradable PLGA microparticles (MP), for direct release and injection into KRAS mutated solid tumors using an endoscopic ultrasound procedure. The strategy of preventing the synthesis of KRAS mutated protein may have an advantage over other approaches targeting KRAS function using small molecules. Methods: Methods are presented in results section. Results: SIL-204 has an increase stability over siG12D.To enhance stability, base modifications and phosphorothiate bonds at cleavage sites were implemented. SIL-204 exhibited a half-life of more than 48 hours in human serum. SIL-204 has robust KRAS silencing . When tested in Hepa1-6 cells transfected with individual human KRAS mutations, SIL-204 effectively silenced the various G12x mutations found in pancreatic cancer (D,V,R,C) at sub-nanomolar concentration (IC50 range=0.19-0.59) as well as G13D (IC50 =0.37). Addition of a hydrophobic tail to a prototype of SIL-204, SIL-101, increased the silencing of KRAS. Using PANC-1 cells (KRAS G12D mutation), lipid conjugation of the siRNA doubled the siRNA’s silencing efficiency in these cells. In addition, release of SIL-204 from the MP was tested in rats and indicates a prolong and sustained release over our intended treatment regimen SIL-204-MP was administered to tumors from human pancreatic tumor cell lines Capan-1 (KRAS G12V mutation and labelled with luciferase) grown in NSG mice and Panc-1 (grown in Athymic Nude mice). Bioluminescence imaging of tumor growth showed that SIL-204-MP significantly reduced Capan-1 tumor growth compared to vehicle controls, p<0.0005. Furthermore, histopathological analyses of tumor center slices from Capan-1 and Panc-1 models showed induction of significant tumor necrosis with SIL-204 compared to vehicle controls. Conclusions: The preclinical results of SIL-204-MP are promising and as the potential to further enhance the anti-tumor effect demonstrated by siG12DLoder in pancreatic patients. SIL-204 is now in toxicology studies as preparation for clinical trials in non-resectable pancreatic cancer.
Helicobacter pylori (HP) is a Gram-negative bacterium that infects approximately fifty percent (50%) of individuals worldwide. The coccoid form of HP, a dormant state with altered morphology, has been associated with persistent infections and antibiotic resistance. This study aimed to investigate the prevalence of the coccoid form of HP in patients living with obesity. Sleeve gastrectomy specimens from obese patients and gastric biopsies from non-obese individuals were analyzed. Immunohistochemistry (IHC) staining and histopathological examination were performed to identify and quantify the coccoid forms of HP. Statistical analysis was conducted to compare the results between the two groups. The study included 53 obese patients and 62 non-obese individuals. The percentage of coccoid forms of HP was significantly higher in obese patients compared to non-obese individuals (median 50% vs. 10%, p < 0.001). Type of gastritis was also significantly different between the groups. Obese patients exhibited a higher prevalence of the coccoid form of HP in their gastric mucosa. This finding suggests that the gastric microenvironment in obesity may favor the formation of the coccoid form, potentially impacting the colonization and pathogenicity of HP. The higher prevalence of the coccoid form in obese patients has important clinical implications, as it is more resistant to antibiotics and difficult to eradicate. Alternative treatment strategies may be necessary to effectively manage HP infections in this population. Furthermore, the presence of the coccoid form may increase the risk of HP-associated diseases in obese individuals. Further research is needed to elucidate the underlying mechanisms and explore novel treatment approaches for HP infection in the context of obesity.
The aim of the present systematic review was to evaluate the efficacy of surgical techniques for the preservation of a tooth with VRF. We included case series presenting techniques for the treatment of VRFs. Both electronic sources (MEDLINE, EMBASE, Cochrane Central) and reference lists/table of contents of pertinent journals were screened. Eight articles (six studies) were included. Four of the studies bonded the fractured fragments with 4‐META/MMA‐TBB resin, one adopted MTA, and in one study the authors used resin‐ionomer cement. There was significant heterogeneity in the results regarding teeth survival rate and it was not possible to perform a quantitative synthesis. Scientific evidence concerning the treatment of vertically fractured roots is sparse and of low quality. Consequently, it is not possible to draw conclusions regarding the efficacy of the reported techniques. More studies with higher scientific standards may add validity to the techniques described here. Trial Registration: CRD42024524356 in PROSPERO
Background Although most melanomas develop de novo, about 30% are nevus-associated melanomas, where the prognostic value is unclear. Our study aimed to determine whether nevus-associated melanoma is associated with sentinel lymph node (SLN) status and prognosis in patients with melanoma. Methods The Sentinel Lymph Node Working Group database, which includes comprehensive clinicopathological and outcome data, was utilized to investigate the association of nevus-associated melanoma with SLN status as well as relapse-free (RFS), melanoma-specific (MSS), and overall survival (OS) using multivariable logistic regression and Cox regression modeling. Results A total of 3447 adult patients with a median follow-up of 2.6 years (interquartile range 0.9–6.9) were evaluable. Compared with de novo melanomas, nevus-associated melanomas showed a significant correlation with younger age as well as favorable histological features. The presence of a nevus-associated melanoma was not identified as an independent factor for SLN status (odds ratio 1.06, 95% confidence interval [CI] 0.80–1.41; p = 0.68). Compared with de novo melanomas, nevus-associated melanomas provided independent prognostic information for a favorable RFS (hazard ratio [HR] 0.67, 95% CI 0.53–0.84; p < 0.001), MSS (HR 0.54, 95% CI 0.34–0.85; p = 0.008), and OS (HR 0.42, 95% CI 0.30–0.57; p < 0.001). Conclusion Melanomas associated with pre-existing nevi appear to be an independent favorable prognostic factor for recurrence and survival and may potentially be used as a clinical parameter for identifying patients with lower risk of recurrence.
Background Endurance athletes tend to accumulate large training volumes, the majority of which are performed at a low intensity and a smaller portion at moderate and high intensity. However, different training intensity distributions (TID) are employed to maximize physiological and performance adaptations. Objective The objective of this study was to conduct a systematic review and network meta-analysis of individual participant data to compare the effect of different TID models on maximal oxygen uptake (VO2max) and time-trial (TT) performance in endurance-trained athletes. Methods Studies were included if: (1) they were published in peer reviewed academic journals, (2) they were in English, (3) they were experimental or quasi-experimental studies, (4) they included trained endurance athletes, (5) they compared a polarized (POL) TID intervention to a comparator group that utilized a different TID model, (6) the duration in each intensity domain could be quantified, and (7) they reported VO2max or TT performance. Medline and SPORTDiscus were searched from inception until 11 February 2024. Results We included 13 studies with 348 (n = 296 male, n = 52 female) recreational (n = 150) and competitive (n = 198) endurance athletes. Mean age ranged from 17.6 to 41.5 years and VO2max ranged from 46.6 to 68.3 mL·kg⁻¹·min⁻¹, across studies respectively. Based on the time in heart rate zone approach, there was no difference in VO2max (SMD = − 0.06, p = 0.68) or TT performance (SMD = − 0.05, p = 0.34) between POL and pyramidal (PYR) interventions. There were no statistically significant differences between POL and any of the other TID interventions. Subgroup analysis showed a statistically significant difference in the response of VO2max between recreational and competitive athletes for POL and PYR (SMD = − 0.63, p < 0.05). Competitive athletes may have greater improvements to VO2max with POL, while recreational athletes may improve more with a PYR TID. Conclusions Our results indicate that the adaptations to VO2max following different TID interventions are dependent on performance level. Athletes at a more competitive level may benefit from a POL TID intervention and recreational athletes from a PYR TID intervention.
Background Artificial intelligence (AI) models analyzing embryo time-lapse images have been developed to predict the likelihood of pregnancy following in vitro fertilization (IVF). However, limited research exists on methods ensuring AI consistency and reliability in clinical settings during its development and validation process. We present a methodology for developing and validating an AI model across multiple datasets to demonstrate reliable performance in evaluating blastocyst-stage embryos. Methods This multicenter analysis utilizes time-lapse images, pregnancy outcomes, and morphologic annotations from embryos collected at 10 IVF clinics across 9 countries between 2018 and 2022. The four-step methodology for developing and evaluating the AI model include: (I) curating annotated datasets that represent the intended clinical use case; (II) developing and optimizing the AI model; (III) evaluating the AI’s performance by assessing its discriminative power and associations with pregnancy probability across variable data; and (IV) ensuring interpretability and explainability by correlating AI scores with relevant morphologic features of embryo quality. Three datasets were used: the training and validation dataset (n = 16,935 embryos), the blind test dataset (n = 1,708 embryos; 3 clinics), and the independent dataset (n = 7,445 embryos; 7 clinics) derived from previously unseen clinic cohorts. Results The AI was designed as a deep learning classifier ranking embryos by score according to their likelihood of clinical pregnancy. Higher AI score brackets were associated with increased fetal heartbeat (FH) likelihood across all evaluated datasets, showing a trend of increasing odds ratios (OR). The highest OR was observed in the top G4 bracket (test dataset G4 score ≥ 7.5: OR 3.84; independent dataset G4 score ≥ 7.5: OR 4.01), while the lowest was in the G1 bracket (test dataset G1 score < 4.0: OR 0.40; independent dataset G1 score < 4.0: OR 0.45). AI score brackets G2, G3, and G4 displayed OR values above 1.0 (P < 0.05), indicating linear associations with FH likelihood. Average AI scores were consistently higher for FH-positive than for FH-negative embryos within each age subgroup. Positive correlations were also observed between AI scores and key morphologic parameters used to predict embryo quality. Conclusions Strong AI performance across multiple datasets demonstrates the value of our four-step methodology in developing and validating the AI as a reliable adjunct to embryo evaluation.
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Eric A. Ben-David
  • Material Science and Engineering
Zvi Wollberg
  • Department of Zoology
Yoav Leiser
  • Faculty of Medicine
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Tel Aviv, Israel
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Prof. Yosef Klafter