Bimodal aphasia and dysgraphia: Phonological output buffer aphasia and orthographic output buffer dysgraphia in spoken and sign language.

We report a case of crossmodal bilingual aphasia-aphasia in two modalities, spoken and sign language-and dysgraphia in both writing and fingerspelling. The patient, Sunny, was a 42 year-old woman after a left temporo-parietal stroke, a speaker of Hebrew, Romanian, and English and an adult learner, daily user of Israeli Sign language (ISL). We assessed Sunny's spoken and sign languages using a comprehensive test battery of naming, reading, and repetition tasks, and also analysed her spontaneous-speech and sign.

Targeting CD4+ T cell Exhaustion to Improve Future Immunotherapy Strategies.

As of late, reinvigoration of exhausted T cells as a form of immunotherapy against cancer has been a promising strategy. However, inconsistent results highlight the uncertainties in the current understanding of cellular exhaustion and the need for research and better treatment design. In our previous work, we utilized mathematical modeling and analysis to recapitulate and complement the biological understanding of exhaustion in response to growing tumors.

A Mathematical Model of TCR-T Cell Therapy for Cervical Cancer.

Engineered T cell receptor (TCR)-expressing T (TCR-T) cells are intended to drive strong anti-tumor responses upon recognition of the specific cancer antigen, resulting in rapid expansion in the number of TCR-T cells and enhanced cytotoxic functions, causing cancer cell death. However, although TCR-T cell therapy against cancers has shown promising results, it remains difficult to predict which patients will benefit from such therapy. We develop a mathematical model to identify mechanisms associated with an insufficient response in a mouse cancer model.

Modeling the Development of Cellular Exhaustion and Tumor-Immune Stalemate.

Cellular exhaustion in various immune cells develops in response to prolonged stimulation and overactivation during chronic infections and in cancer. Marked by an upregulation of inhibitory receptors and diminished effector functions, exhausted immune cells are unable to fully eradicate the antigen responsible for the overexposure. In cancer settings, this results in a relatively small but constant tumor burden known as a localized tumor-immune stalemate.

The Effectiveness of Case-management Rehabilitation Intervention in Facilitating Return to Work and Maintenance of Employment After Myocardial Infarction: Results of a Randomized Controlled Trial.

Objective: To study the long-term effectiveness of case-management rehabilitation intervention on vocational reintegration of patients after myocardial infarction (MI).

Design: Blinded simple randomization was used to construct an intervention and control groups that were followed up for two years.

Subjects And Setting: 151 patients, aged 50.

Mining Marine Metagenomes Revealed a Quorum-Quenching Lactonase with Improved Biochemical Properties That Inhibits the Food Spoilage Bacterium Pseudomonas fluorescens.

The marine environment presents great potential as a source of microorganisms that possess novel enzymes with unique activities and biochemical properties. Examples of such are the quorum-quenching (QQ) enzymes that hydrolyze bacterial quorum-sensing (QS) signaling molecules, such as -acyl-homoserine lactones (AHLs). QS is a form of cell-to-cell communication that enables bacteria to synchronize gene expression in correlation with population density.

Dysnumeria in Sign Language: Impaired Construction of the Decimal Structure in Reading Multidigit Numbers in a Deaf ISL Signer.

We report on the first in-depth analysis of a specific type of dysnumeria, number-reading deficit, in sign language. The participant, Nomi, is a 45-year-old signer of Israeli Sign Language (ISL). In reading multidigit numbers (reading-then-signing written numbers, the counterpart of reading aloud in spoken language), Nomi made mainly decimal, number-structure errors- reading the correct digits in an incorrect (smaller) decimal class, mainly in longer numbers of 5-6-digits.

Modeling LSD1-Mediated Tumor Stagnation.

LSD1 (KDMA1) has gained attention in the last decade as a cancer biomarker and drug target. In particular, recent work suggests that LSD1 inhibition alone reduces tumor growth, increases T cell tumor infiltration, and complements PD1/PDL1 checkpoint inhibitor therapy. In order to elucidate the immunogenic effects of LSD1 inhibition, we develop a mathematical model of tumor growth under the influence of the adaptive immune response.

Modeling the Effect of Memory in the Adaptive Immune Response.

It is well understood that there are key differences between a primary immune response and subsequent responses. Specifically, memory T cells that remain after a primary response drive the clearance of antigen in later encounters. While the existence of memory T cells is widely accepted, the specific mechanisms that govern their function are generally debated.

Study of dose-dependent combination immunotherapy using engineered T cells and IL-2 in cervical cancer.

Adoptive T cell based immunotherapy is gaining significant traction in cancer treatment. Despite its limited efficacy so far in treating solid tumors compared to hematologic cancers, recent advances in T cell engineering render this treatment increasingly more successful in solid tumors, demonstrating its broader therapeutic potential. In this paper we develop a mathematical model to study the efficacy of engineered T cell receptor (TCR) T cell therapy targeting the E7 antigen in cervical cancer cell lines.

Universal response in the RKO colon cancer cell line to distinct antimitotic therapies.

Both classic and newer antimitotics commonly induce a prolonged mitotic arrest in cell culture. During arrest, cells predominantly undergo one of two fates: cell death by apoptosis, or mitotic slippage and survival. To refine this binary description, a quantitative understanding of these cell responses is needed.

Modeling the Dynamics of Heterogeneity of Solid Tumors in Response to Chemotherapy.

In this paper, we extend the model of the dynamics of drug resistance in a solid tumor that was introduced by Lorz et al. (Bull Math Biol 77:1-22, 2015). Similarly to the original, radially symmetric model, the quantities we follow depend on a phenotype variable that corresponds to the level of drug resistance.

Modeling Cancer Cell Growth Dynamics in Response to Antimitotic Drug Treatment.

Investigating the role of intrinsic cell heterogeneity emerging from variations in cell-cycle parameters and apoptosis is a crucial step toward better informing drug administration. Antimitotic agents, widely used in chemotherapy, target exclusively proliferative cells and commonly induce a prolonged mitotic arrest followed by cell death via apoptosis. In this paper, we developed a physiologically motivated mathematical framework for describing cancer cell growth dynamics that incorporates the intrinsic heterogeneity in the time individual cells spend in the cell-cycle and apoptosis process.

Modeling the Transfer of Drug Resistance in Solid Tumors.

ABC efflux transporters are a key factor leading to multidrug resistance in cancer. Overexpression of these transporters significantly decreases the efficacy of anti-cancer drugs. Along with selection and induction, drug resistance may be transferred between cells, which is the focus of this paper.

Stability Analysis of a Model of Interaction Between the Immune System and Cancer Cells in Chronic Myelogenous Leukemia.

We describe here a simple model for the interaction between leukemic cells and the autologous immune response in chronic phase chronic myelogenous leukemia (CML). This model is a simplified version of the model we proposed in Clapp et al. (Cancer Res 75:4053-4062, 2015).

[THE IMPACT OF A COMMUNITY INTERVENTION PROGRAM IN ISRAELI WORKSITES TO REDUCE THE RISK OF CARDIOVASCULAR DISEASES].

Introduction: Atherosclerosis is the main cause of cardiovascular (CV) morbidity and mortality in the western world. Detection and treatment of risk factors (such as hypertension, dyslipidemia and diabetes mellitus) reduce CV events. We have shown cost utility in reducing these CV risk factors in community clinics and community centers.

BCR-ABL transcript variations in chronic phase chronic myelogenous leukemia patients on imatinib first-line: Possible role of the autologous immune system.

Many chronic myelogenous leukemia (CML) patients in chronic phase who respond well to imatinib therapy show fluctuations in their leukemic loads in the long-term. We developed a mathematical model of CML that incorporates the intervention of an autologous immune response. Our results suggest that the patient's immune system plays a crucial role in imatinib therapy in maintaining disease control over time.

Mathematical models of breast and ovarian cancers.

Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review, we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women.

Modeling the Dynamics of High-Grade Serous Ovarian Cancer Progression for Transvaginal Ultrasound-Based Screening and Early Detection.

High-grade serous ovarian cancer (HGSOC) represents the majority of ovarian cancers and accounts for the largest proportion of deaths from the disease. A timely detection of low volume HGSOC should be the goal of any screening studies. However, numerous transvaginal ultrasound (TVU) detection-based population studies aimed at detecting low-volume disease have not yielded reduced mortality rates.

Mathematical Modeling Reveals That Changes to Local Cell Density Dynamically Modulate Baseline Variations in Cell Growth and Drug Response.

Cell-to-cell variations contribute to drug resistance with consequent therapy failure in cancer. Experimental techniques have been developed to monitor tumor heterogeneity, but estimates of cell-to-cell variation typically fail to account for the expected spatiotemporal variations during the cell growth process. To fully capture the extent of such dynamic variations, we developed a mechanistic mathematical model supported by in vitro experiments with an ovarian cancer cell line.

A Review of Mathematical Models for Leukemia and Lymphoma.

Recently, there has been significant activity in the mathematical community, aimed at developing quantitative tools for studying leukemia and lymphoma. Mathematical models have been applied to evaluate existing therapies and to suggest novel therapies. This article reviews the recent contributions of mathematical modeling to leukemia and lymphoma research.

Implication of the Autologous Immune System in BCR-ABL Transcript Variations in Chronic Myelogenous Leukemia Patients Treated with Imatinib.

Imatinib and other tyrosine kinase inhibitors (TKI) have improved treatment of chronic myelogenous leukemia (CML); however, most patients are not cured. Deeper mechanistic understanding may improve TKI combination therapies to better control the residual leukemic cell population. In analyzing our patients' data, we found that many patients who otherwise responded well to imatinib therapy still showed variations in their BCR-ABL transcripts.

Modeling intrinsic heterogeneity and growth of cancer cells.

Intratumoral heterogeneity has been found to be a major cause of drug resistance. Cell-to-cell variation increases as a result of cancer-related alterations, which are acquired by stochastic events and further induced by environmental signals. However, most cellular mechanisms include natural fluctuations that are closely regulated, and thus lead to asynchronization of the cells, which causes intrinsic heterogeneity in a given population.