David Gur

• Israel Institute for Biological Research

We present the investigation of a Burkholderia pseudomallei strain isolated from the urine of a 56-year-old male returning from a recreational trip to Thailand. The patient initially presented with fever and chills, and lobar as well as bladder and prostate involvement was demonstrated on imaging. Treatment first involved trimethoprim-sulfamethoxaz...

Objective Burkholderia pseudomallei , the etiological cause of melioidosis, is a soil saprophyte endemic in South-East Asia, where it constitutes a public health concern of high-priority. Melioidosis cases are sporadically identified in nonendemic areas, usually associated with travelers or import of goods from endemic regions. Due to extensive int...

In a recent study, we demonstrated that vaccination with the polymeric F1 capsule antigen of the plague pathogen Yersinia pestis led to the rapid induction of a protective humoral immune response via the pivotal activation of innate-like B1b cells. Conversely, the monomeric version of F1 failed to promptly protect vaccinated animals in this model o...

SARS-CoV-2 is evolving with increased transmission, host range, pathogenicity, and virulence. The original and mutant viruses escape host innate (Interferon) immunity and adaptive (Antibody) immunity, emphasizing unmet needs for high-yield, commercial-scale manufacturing to produce inexpensive vaccines/boosters for global/equitable distribution. We...

In this study, we evaluated bacterial growth rates of Francisella tularensis strains in iron (Fe)-enriched blood cultures as a means of improving and accelerating bacterial growth. The shortening of the culturing time should facilitate rapid pathogen detection and isolation, positively impacting clinical diagnosis and enabling prompt onset of effic...

Longevity of the immune response following viral exposure is an essential aspect of SARS-CoV-2 infection. Mild SARS-CoV-2 infection of K18-hACE2 mice was implemented for evaluating the mounting and longevity of a specific memory immune response. We show that the infection of K18-hACE2 mice induced robust humoral and cellular immunity (systemic and...

Plague pandemics and outbreaks have killed millions of people during the history of humankind. The disease, caused by the bacteria Yersinia pestis, is currently treated effectively with antibiotics. However, in the case of multidrug-resistant (MDR) bacteria, alternative treatments are required. Bacteriophage (phage) therapy has shown efficient anti...

Plague, caused by the human pathogen Yersinia pestis, is a severe and rapidly progressing lethal disease that has caused millions of deaths globally throughout human history and still presents a significant public health concern, mainly in developing countries. Owing to the possibility of its malicious use as a bio-threat agent, Y. pestis is classi...

Plague pandemics and outbreaks have killed millions of people during the history of humankind. The disease, caused by Yersinia pestis bacteria, can currently be treated efficiently with antibiotics. However, in the case of multidrug-resistant (MDR) bacteria, alternative treatments are required. Bacteriophage (phage) therapy has shown efficient anti...

The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficacious in-v...

Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing lethal infection. The various phases of pneumonic plague are yet to be fully understood. A well-established way to address the pathology of infectious diseases in general, and pneumonic plague in particular, is to conduct concomitant transcriptomic analysis of the bacteria and th...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The continued spread of SARS-CoV-2 increases the probability of influenza/SARS-CoV-2 coinfection, which may result in severe disease. In this study, we examine the disease outcome of influenza A virus (IAV) and SARS...

The COVID-19 pandemic initiated a worldwide race toward the development of treatments and vaccines. Small animal models included the Syrian golden hamster and the K18-hACE2 mice infected with SARS-CoV-2 to display a disease state with some aspects of human COVID-19. A group activity of animals in their home cage continuously monitored by the HCMS10...

A wide range of SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) were reported, most of which target the spike glycoprotein. Therapeutic implementation of these antibodies has been challenged by emerging SARS-CoV-2 variants harboring mutated spike versions. Consequently, re-assessment of previously identified mAbs is of high priority. Four prev...

HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was the implementation of an adenovirus-mediated infection protocol for human ACE2 expr...

According to the WHO, 75% of the world’s plague cases are found in Madagascar, with an average of 200–700 suspected cases annually (mainly bubonic plague). In 2017, a pneumonic plague epidemic of unusual proportions occurred, which raised several challenges for laboratory confirmation of cases, pointing to the need for the development of Yersinia p...

Rapid antibiotic susceptibility tests, performed directly on whole blood samples, will offer great clinical advantages. This issue is of considerable importance when it comes to bioterror pathogens where prompt antibiotic treatment should be offered to infected patients as well as prophylaxis to suspected exposed individuals. Herein, we describe a...

COVID-19 pandemic initiated a worldwide race toward the development of treatments and vaccines. Small animal models were the Syrian golden hamster and the K18-hACE2 mice infected with SARS-CoV-2 to display a disease state with some aspects of the human COVID-19. Group activity of animals in their home cage continuously monitored by the HCMS100 was...

Objective For breast US interpretation, to assess impact of computer-aided diagnosis (CADx) in original mode or with improved sensitivity or specificity. Methods In this IRB approved protocol, orthogonal-paired US images of 319 lesions identified on screening, including 88 (27.6%) cancers (median 7 mm, range 1–34 mm), were reviewed by 9 breast ima...

The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficacious in v...

Rapid determination of bacterial antibiotic susceptibility is important for proper treatment of infections. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has recently published guidelines for rapid antimicrobial susceptibility testing (RAST) performed directly from positive blood culture vials. These guidelines, however, w...

Mice are normally unaffected by SARS-CoV-2 infection since the virus does not bind effectively to the murine version of the ACE2 receptor molecule. Here we report that induced mild pulmonary morbidities render SARS-CoV-2 refractive CD-1 mice to be susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low-doses of the ac...

Neutralizing antibodies represent a valuable therapeutic approach to countermeasure the current COVID-19 pandemic. Emergence of SARS-CoV-2 variants emphasizes the notion that antibody treatments need to rely on highly neutralizing monoclonal antibodies (mAbs), targeting several distinct epitopes for circumventing therapy escape-mutants. Previously,...

The current global COVID-19 pandemic led to an unprecedented effort to develop effective vaccines against SARS-CoV-2. mRNA vaccines were developed very rapidly during the last year, and became the leading immunization platform against the virus, with highly promising phase-3 results and remarkable efficacy data. Since most animal models are not sus...

Mouse monoclonal antibodies were raised against plague disease biomarkers: the bacterial capsular protein fraction 1 (F1) and the low-calcium response—LcrV virulence factor (Vag). A novel tandem assay, employing BioLayer Interferometry (BLI), enabled the isolation of antibodies against four different epitopes on Vag. The tandem assay was carried ou...

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits high levels of mortality and morbidity and has dramatic consequences on human life, sociality and global economy. Neutralizing antibodies constitute a highly promising approach for treating and preventing infection...

Since the onset of the current COVID-19 pandemic, high priority is given to the development of neutralizing antibodies, as a key approach for the design of therapeutic strategies to countermeasure and eradicate the disease. Previously, we reported the development of human therapeutic monoclonal antibodies (mAbs) exhibiting very high protective abil...

Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits high levels of mortality and morbidity and has dramatic consequences on human life, sociality and global economy. Neutralizing antibodies constitute a highly promising approach for treating and preventing infection by t...

Yersinia pestis is a Gram-negative pathogen that causes plague, a devastating disease that kills millions worldwide. Although plague is efficiently treatable by recommended antibiotics, the time of antibiotic therapy initiation is critical, as high mortality rates have been observed if treatment is delayed for longer than 24 h after symptom onset....

Severe manifestations of COVID-19 are mostly restricted to people with comorbidities. Here we report that induced mild pulmonary morbidities render SARS-CoV-2-refractive CD-1 mice to be susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low-doses of the acute-lung-injury stimulants bleomycin or ricin caused a severe...

Antibiotic resistance of bio-threat agents holds major concerns especially in light of advances in methods for engineering pathogens with antibiotic resistance. Preparedness means for rapid identification and prompt proper medical treatment are of need to contain the event and prevent morbidity and spreading of the disease by properly treating expo...

Various respiratory viral infections in general and seasonal influenza in particular may increase the susceptibility to bacterial infections. Plague caused by Yersinia pestis endangers large populations during outbreaks or bioterrorism attacks. Recommended antibiotic countermeasures include well-established protocols based on animal studies and cor...

High-throughput DNA sequencing (HTS) of pathogens in whole blood samples is hampered by the high host/pathogen nucleic acids ratio. We describe a novel and rapid bacterial enrichment procedure whose implementation is exemplified in simulated bacteremic human blood samples. The procedure involves depletion of the host DNA, rapid HTS and bioinformati...

Objective To assess prospectively the interpretative performance of automated breast ultrasound (ABUS) as a supplemental screening after digital breast tomosynthesis (DBT) or as a standalone screening of women with dense breast tissue. Methods Under an IRB-approved protocol (written consent required), women with dense breasts prospectively underwe...

Introduction Most animal handling procedures are associated with injuries among veterinary staff and laboratory animal researchers. However, much of the currently available animal handling equipment is inadequate, limiting access to the treated animal or making workflow cumbersome. Moreover, restraining animals to perform procedures, such as blood...

Background Staging newly diagnosed breast cancer by using dynamic contrast material-enhanced MRI is limited by access, high cost, and false-positive findings. The utility of contrast-enhanced mammography (CEM) and 99mTc sestamibi-based molecular breast imaging (MBI) in this setting is largely unknown. Purpose To compare extent-of-disease assessment...

Rationale and objectives: To preliminarily asses if Contrast Enhanced Digital Mammography (CEDM) can accurately reduce biopsy rates for soft tissue BI-RADS 4A or 4B lesions. Materials and methods: Eight radiologists retrospectively and independently reviewed 60 lesions in 54 consenting patients who underwent CEDM under Health Insurance Portabili...

We have previously shown that the cell morphogenesis NlpD lipoprotein is essential for virulence of the plague bacteria, Yersinia pestis. To elucidate the role of NlpD in Y. pestis pathogenicity, we conducted a whole-genome comparative transcriptome analysis of the wild-type Y. pestis strain and an nlpD mutant under conditions mimicking early stage...

Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing contagious disease. In the plague mouse model, a single immunization with the EV76 live attenuated Y. pestis strain rapidly induced the expression of hemopexin and haptoglobin in the lung and serum, both of which are important in iron sequestration. Immunization against a concomi...

Great efforts are being made to develop new rapid antibiotic susceptibility tests to meet the demand for clinical relevance versus disease progression. This is important especially in diseases caused by bacteria such as Yersinia pestis, the causative agent of plague, which grows rapidly in vivo but relatively slow in vitro. This compromises the abi...

Background Digital breast tomosynthesis (DBT) is replacing digital mammography (DM) in the clinical workflow. Currently, there are limited prospective studies comparing the diagnostic accuracy of both examinations and the role of synthetic mammography (SM) and computer-aided detection (CAD). Purpose To compare the accuracy of DM versus DM + DBT i...

Bubonic plague: Mechanisms of a rapid antibody response Full acquired immunity normally takes weeks to develop, however it’s possible to raise rapid (days) protective antibody responses against the bubonic plague bacterium Yersinia pestis by targeting its F1 capsular antigen. Emanuelle Mamroud and colleagues at the Institute of Biological Research...

Rapid antimicrobial susceptibility tests (ASTs) are essential tool for proper treatment of patients infected by Yersinia pestis (Y. pestis), the causative agent of plague, or for post-exposure prophylaxis of a population exposed to a naturally acquired or deliberately prepared resistant variant. The standard AST of Y. pestis is based on bacterial g...

Purpose: The National Mammography Database (NMD) contains nearly 20 million examinations from 693 facilities; it is the largest information source for use and effectiveness of breast imaging in the United States. NMD collects demographic, imaging, interpretation, biopsy, and basic pathology results, enabling facility and physician comparison for q...

Purpose: Digital breast tomosynthesis (DBT) has the potential to overcome limitations of conventional mammography. This study investigated the effects of addition of DBT on interval and detected cancers in population-based screening. Methods: Oslo Tomosynthesis Screening Trial (OTST) was a prospective, independent double-reading trial inviting w...

Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, Yersinia pestis (Y. pestis), is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therap...

Therapeutic efficacy of parenteral treatment with Gentamicin and ciprofloxacin. Groups of 8 CD-1 mice were exposed intranasally to 100LD50 of Y. pestis Kim53. Mice were treated s.c. with 20 mg/kg/q24 h gentamicin (blue) or with 40 mg/kg/q24 h ciprofloxacin (green) for 5 days starting 48 h after exposure to Y. pestis. Control mice were not treated (...

Multiplexed detection technologies are becoming increasingly important given the possibility of bioterrorism attacks, where the range of suspected pathogens can vary considerably. In this work, we describe the use of Luminex MagPlex magnetic microspheres for the construction of two multiplexed diagnostic suspension arrays, enabling the antibody-bas...

Assessing performance of diagnostic markers is a necessary step for their use in decision making regarding various conditions of interest in diagnostic medicine and other fields. Globally useful markers could, however, have ranges of values that are “diagnostically non-informative”. This paper demonstrates that the presence of marker values from di...

Prompt and effective elicitation of protective immunity is highly relevant for cases of rapidly deteriorating fatal diseases, such as plague, which is caused by Yersinia pestis. Here, we assessed the potential of a live vaccine to induce rapid protection against this infection. We demonstrated that the Y. pestis EV76 live vaccine protected mice aga...

We investigated automated quantitative measures of background parenchymal enhancement (BPE) derived from an early versus delayed post-contrast sequence in breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for association with breast cancer presence in a case-control study. DCE-MRIs were retrospectively analyzed for 51 cancer cas...

Rationale and objectives: The "binormal" model is the most frequently used tool for parametric receiver operating characteristic (ROC) analysis. The binormal ROC curves can have "improper" (non-concave) shapes that are unrealistic in many practical applications, and several tools (eg, PROPROC) have been developed to address this problem. However,...

Background We investigated dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) contrast enhancement kinetic variables quantified from normal breast parenchyma for association with presence of breast cancer, in a case-control study. Methods Under a Health Insurance Portability and Accountability Act compliant and Institutional Review Boa...

Background: Plague is initiated by Yersinia pestis, a highly virulent bacterial pathogen. In late stages of the infection, bacteria proliferate extensively in the internal organs despite the massive infiltration of neutrophils. The ineffective inflammatory response associated with tissue damage may contribute to the low efficacy of anti-plague the...

Standard antimicrobial susceptibility tests used to determine bacterial susceptibility to antibiotics are growth dependent and time consuming. The long incubation time required for standard tests may render susceptibility results irrelevant, particularly for patients infected with lethal bacteria that are slow growing on agar but progress rapidly i...

Performance changes in a binary environment when using additional information is affected only when changes in recommendations are made due to the additional information in question. In a recent study, we have shown that, contrary to general expectation, introducing prior examinations improved recall rates, but not sensitivity. In this study, we as...

The purpose of this study is to develop and test a new computerized model for predicting near-term breast cancer risk based on quantitative assessment of bilateral mammographic image feature variations in a series of negative full-field digital mammography (FFDM) images. The retrospective dataset included series of four sequential FFDM examinations...

Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs. Because neutrophils are the first immune cells recruited to sites of infection, we investigated the mechanisms responsible for their delayed homing to the lung. During the first 24 hr after pulmonary infection with a fully v...

Purpose Fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) estimated from breast dynamic contrast enhanced MRI (DCE-MRI) have been correlated with breast cancer risk. We performed a preliminary study assessing in a small cohort of breast cancer patients the relationship between FGT and BPE both quantified from cancer-unaffecte...

Purpose Background parenchymal enhancement (BPE) estimated from breast dynamic contrast enhanced MRI (DCE-MRI) has been correlated with breast cancer risk. Multiple time-point post-contrast-subtracted sequences are acquired in typical clinical breast DCE-MRI protocols. We quantitatively assessed BPE using fully automated computer algorithms and inv...

To assess radiologists' perceptions of how the new Breast Density Notification Act (BDNA) of Pennsylvania would affect their breast density reporting and their actual reporting patterns after implementation. Under an institutional review board-approved protocol, we surveyed 21 radiologists about how they believe the new law affected their breast de...

Breast magnetic resonance imaging (MRI) is recommended as an adjunct to mammography for women who are considered at elevated risk of developing breast cancer. As a key component of breast MRI, dynamic contrast-enhanced MRI (DCE-MRI) uses a contrast agent to provide high intensity contrast between breast tissues, making it sensitive to tissue compos...

Purpose: To assess the effect of and interaction between the availability of prior images and digital breast tomosynthesis (DBT) images in decisions to recall women during mammogram interpretation. Materials and methods: Verbal informed consent was obtained for this HIPAA-compliant institutional review board-approved protocol. Eight radiologists...

To investigate the underlying relationship between obesity and the extent of emphysema depicted at CT. A dataset of 477 CT examinations was retrospectively collected from a study of chronic obstructive pulmonary disease (COPD). The low attenuation areas (LAAs; ≤950 HU) of the lungs were identified. The extent of emphysema (denoted as %LAA) was defi...

Evaluation of diagnostic performance is typically based on the receiver operating characteristic (ROC) curve and the area under the curve (AUC) as its summary index. The partial area under the curve (pAUC) is an alternative index focusing on the range of practical/clinical relevance. One of the problems preventing more frequent use of the pAUC is t...

To investigate the association between emphysema heterogeneity in spatial distribution, pulmonary function and disease severity. We ascertained a dataset of anonymized Computed Tomography (CT) examinations acquired on 565 participants in a COPD study. Subjects with chronic bronchitis (CB) and/or bronchodilator response were excluded resulting in 19...

Receiver operating characteristic analysis provides an important methodology for assessing traditional (e.g., imaging technologies and clinical practices) and new (e.g., genomic studies, biomarker development) diagnostic problems. The area under the clinically/practically relevant part of the receiver operating characteristic curve (partial area or...

The authors describe where we are in terms of using computer-aided detection (CADe) systems during clinical mammographic interpretations, what are the issues that we face, and why they believe that, despite disappointment in terms of verified added value when it comes to detection of soft tissue abnormalities, we need to continue to explore new app...

To investigate whether lung function in patients with chronic obstructive pulmonary disease (COPD) can be directly predicted using CT densitometric measures and assess the underlying prediction errors as compared with the traditional spirometry-based measures. A total of 600 CT examinations were collected from a COPD study. In addition to the entir...

Full-field digital mammography (FFDM) is the most common screening procedure for detecting early breast cancer. However, due to complications such as overlapping breast tissue in projection images, the efficacy of FFDM reading is reduced. Recent studies have shown that digital breast tomosynthesis (DBT), in combination with FFDM, increases detectio...

In this paper we present a simple technique that can be employed to filter the output of the computerized mass detection schemes. The sensitivity of computer-aided detection (CAD) systems is high; nevertheless specificity is not due to high false positive (FP) detection rates. Our approach is based on Histogram of Oriented Gradients (HOG) descripto...

In a rapidly changing clinical environment, assessment of imaging-based technologies and practices for periodic screening for the early detection of breast cancer is constrained by cost, complexity, and professional resources, particularly concerning supplementary imaging of subgroups constituting a large fraction of the screened population. Relati...

This study investigated association between bilateral mammographic density asymmetry and near-term breast cancer risk. A data base of digital mammograms acquired from 690 women was retrospectively collected. All images were originally interpreted as negative by radiologists. During the next subsequent screening examinations (between 12 and 36 month...

A registration scheme termed as B-spline affine transformation (BSAT) is presented in this study to elastically align two images. We define an affine transformation instead of the traditional translation at each control point. Mathematically, BSAT is a generalized form of the affine transformation and the traditional B-spline transformation (BST)....

Plague, initiated by Yersinia pestis infection, is a rapidly progressing disease with a high mortality rate if not quickly treated. The existence of antibiotic-resistant Y. pestis strains emphasizes the need for the development of novel countermeasures against plague. We previously reported the generation of a recombinant Y. pestis strain (Kim53ΔJ+...

To assess the interaction between the availability of prior examinations and digital breast tomosynthesis (DBT) in decisions to recall a woman during interpretation of mammograms. Eight radiologists independently interpreted twice 36 mammography examinations, each of which had current and prior full-field digital mammography images (FFDM) and DBT u...