The Physics of Cellular Decision Making During Epithelial-Mesenchymal Transition.

The epithelial-mesenchymal transition (EMT) is a process by which cells lose epithelial traits, such as cell-cell adhesion and apico-basal polarity, and acquire migratory and invasive traits. EMT is crucial to embryonic development and wound healing. Misregulated EMT has been implicated in processes associated with cancer aggressiveness, including metastasis.

Integrating Neural Networks with a Quantum Simulator for State Reconstruction.

We demonstrate quantum many-body state reconstruction from experimental data generated by a programmable quantum simulator by means of a neural-network model incorporating known experimental errors. Specifically, we extract restricted Boltzmann machine wave functions from data produced by a Rydberg quantum simulator with eight and nine atoms in a single measurement basis and apply a novel regularization technique to mitigate the effects of measurement errors in the training data. Reconstructions of modest complexity are able to capture one- and two-body observables not accessible to experimentalists, as well as more sophisticated observables such as the Rényi mutual information.

Sustained Coevolution in a Stochastic Model of Cancer-Immune Interaction.

The dynamic interactions between an evolving malignancy and the adaptive immune system generate diverse evolutionary trajectories that ultimately result in tumor clearance or immune escape. Here, we create a simple mathematical model coupling T-cell recognition with an evolving cancer population that may randomly produce evasive subclones, imparting transient protection against the effector T cells. T-cell turnover declines and evasion rates together explained differences in early incidence data across almost all cancer types.

Anticipating critical transitions in epithelial-hybrid-mesenchymal cell-fate determination.

In the vicinity of a tipping point, critical transitions occur when small changes in an input condition cause sudden, large, and often irreversible changes in the state of a system. Many natural systems ranging from ecosystems to molecular biosystems are known to exhibit critical transitions in their response to stochastic perturbations. In diseases, an early prediction of upcoming critical transitions from a healthy to a disease state by using early-warning signals is of prime interest due to potential application in forecasting disease onset.

Echoes from the past- changing associations between brain tumors and ethnicity.

Background: cranial X radiation therapy was the standard of care for treating dermatological conditions until the 1960s, when its association to cancer and particularly high rates of brain tumors was discovered. This study examines associations found between incidence of brain tumor and ethnicity.

Methods: This study analyzed two cohorts who underwent examination at age 17 and were followed by linkage to the national cancer registry.

Differential Contributions of Pre- and Post-EMT Tumor Cells in Breast Cancer Metastasis.

Metastases are responsible for the majority of breast cancer-associated deaths. The contribution of epithelial-to-mesenchymal transition (EMT) in the establishment of metastases is still controversial. To obtain evidence of EMT in metastasis, we established an EMT lineage tracing (Tri-PyMT) model, in which tumor cells undergoing EMT would irreversibly switch their fluorescent marker from RFP to GFP due to mesenchymal-specific Cre expression.

CDX-2 Expression in Esophageal Biopsies Without Goblet Cell Intestinal Metaplasia May Be Predictive of Barrett's Esophagus.

Background: CDX-2 is a nuclear homeobox transcription factor not normally expressed in esophageal and gastric epithelia, reported to highlight intestinal metaplasia (IM) in the esophagus. Pathological absence of goblet cells at initial screening via hematoxylin and eosin (HE) and alcian blue (AB) staining results in patient exclusion from surveillance programs.

Aims: This study aimed to determine whether non-goblet cell IM, as defined by CDX-2 positivity, can be considered to be a precursor to Barrett's esophagus (BE).

Pericytes enable effective angiogenesis in the presence of proinflammatory signals.

Angiogenesis frequently occurs in the context of acute or persistent inflammation. The complex interplay of proinflammatory and proangiogenic cues is only partially understood. Using an experimental model, permitting exposure of developing blood vessel sprouts to multiple combinations of diverse biochemical stimuli and juxtacrine cell interactions, we present evidence that a proinflammatory cytokine, tumor necrosis factor (TNF), can have both proangiogenic and antiangiogenic effects, depending on the dose and the presence of pericytes.

Histone deacetylases, Mbd3/NuRD, and Tet2 hydroxylase are crucial regulators of epithelial-mesenchymal plasticity and tumor metastasis.

An epithelial-mesenchymal transition (EMT) represents a basic morphogenetic process of high cell plasticity underlying embryogenesis, wound healing, cancer metastasis and drug resistance. It involves a profound transcriptional and epigenetic reprogramming of cells. A critical role of epigenetic modifiers and their specific chromatin modifications has been demonstrated during EMT.

A CTC-Cluster-Specific Signature Derived from OMICS Analysis of Patient-Derived Xenograft Tumors Predicts Outcomes in Basal-Like Breast Cancer.

Circulating tumor cell clusters (CTCcl) have a higher metastatic potential compared to single CTCs and predict long-term outcomes in breast cancer (BC) patients. Because of the rarity of CTCcls, molecular characterization of primary tumors that give rise to CTCcl hold significant promise for better diagnosis and target discovery to combat metastatic BC. In our study, we utilized the reverse-phase protein array (RPPA) and transcriptomic (RNA-Seq) data of 10 triple-negative BC patient-derived xenograft (TNBC PDX) transplantable models with CTCs and evaluated expression of upregulated candidate protein Bcl2 (B-cell lymphoma 2) by immunohistochemistry (IHC).

Computational Modeling of Collective Cell Migration: Mechanical and Biochemical Aspects.

Collective cell migration plays key roles in various physiological and pathological processes in multicellular organisms, including embryonic development, wound healing, and formation of cancer metastases. Such collective migration involves complex crosstalk among cells and their environment at both biochemical and mechanical levels. Here, we review various computational modeling strategies that have been helpful in decoding the dynamics of collective cell migration.

Door To Detorsion Time Determines Testicular Survival.

Objective: To determine the importance of the duration of in-hospital management of patients with testicular torsion for testes survival. The time from onset of symptoms until surgery is a well-known factor determining testicular survival but there is no data regarding the contribution of in-hospital management duration to testicular survival. Unlike the time from onset of symptoms until seeking medical attention, the time from registration to the emergency department (ED) to the time of detorsion-"Door To Detorsion time" (DTD) is dependent on medical providers and should be minimized.

Generation and manipulation of Schrödinger cat states in Rydberg atom arrays.

Quantum entanglement involving coherent superpositions of macroscopically distinct states is among the most striking features of quantum theory, but its realization is challenging because such states are extremely fragile. Using a programmable quantum simulator based on neutral atom arrays with interactions mediated by Rydberg states, we demonstrate the creation of "Schrödinger cat" states of the Greenberger-Horne-Zeilinger (GHZ) type with up to 20 qubits. Our approach is based on engineering the energy spectrum and using optimal control of the many-body system.

Incidence time trends and socioeconomic factors in the observed incidence of autism spectrum disorder in israel: A nationwide nested case-control study.

Autism spectrum disorder (ASD) trends have been gaining a great deal of focus in recent decades, as many studies worldwide show a continued rise in incidence rates. Many researchers have begun analyzing socioeconomic data in relation to ASD in an effort to understand the source of these changing rates and the role of awareness and access to resources. In this study, we aim to contribute to this body of knowledge by examining incidence time trends of ASD in Israel according to socioeconomic factors.

A possible role for epigenetic feedback regulation in the dynamics of the epithelial-mesenchymal transition (EMT).

The epithelial-mesenchymal transition (EMT) often plays a critical role in cancer metastasis and chemoresistance, and decoding its dynamics is crucial to design effective therapeutics. EMT is regulated at multiple levels-transcriptional, translational, protein stability and epigenetics; the mechanisms by which epigenetic regulation can alter the dynamics of EMT remain elusive. Here, to identify the possible effects of epigenetic regulation in EMT, we incorporate a feedback term in our previously proposed model of EMT regulation of the miR-200/ZEB/miR-34/SNAIL circuit.

NRF2 activates a partial epithelial-mesenchymal transition and is maximally present in a hybrid epithelial/mesenchymal phenotype.

The epithelial-mesenchymal transition (EMT) is a key process implicated in cancer metastasis and therapy resistance. Recent studies have emphasized that cells can undergo partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype - a cornerstone of tumour aggressiveness and poor prognosis. These cells can have enhanced tumour-initiation potential as compared to purely epithelial or mesenchymal ones and can integrate the properties of cell-cell adhesion and motility that facilitates collective cell migration leading to clusters of circulating tumour cells (CTCs) - the prevalent mode of metastasis.

Healthcare utilization in infants and toddlers with asthma-like symptoms.

Background: Recurrent asthma-like symptoms are common in infants, but few population studies describe diagnostic and treatment practice.

Methods: Using the electronic data repository of Clalit Health Services, the largest integrated health care provider in Israel, we evaluated children born 2005-2012, who before 3 years of age had >3 episodes of asthma-like symptoms and/or >2 bronchodilator purchases within a year. We described health care utilization and the odds ratio for subsequent utilization after 3 and 12 months' controller therapy.

Syringe disposal among people who inject drugs before and after the implementation of a syringe services program.

Introduction: Due to the increase in people who use opioids in the US, there has been a steady increase in injection drug use. Without access to safe syringe disposal locations, people who inject drugs (PWID) have few options other than improper disposal, including in public places. In 2016, Florida's first legal Syringe Services Program (SSP) was established in Miami.

Feasibility of a text-messaging smoking cessation program for soldiers in Israel.

Background: Cigarette smoking is a main cause of preventable morbidity and mortality. Many young adults begin smoking in the military, with smoking rates higher among soldiers than in the general population. Among other health effects, smoking impairs performance among soldiers.

Large-scale uniform optical focus array generation with a phase spatial light modulator.

In this Letter, to the best of our knowledge, we report a new method to generate uniform large-scale optical focus arrays (LOFAs). By identifying and removing undesired phase rotation in the iterative Fourier transform algorithm (IFTA), our approach rapidly produces computer-generated holograms of highly uniform LOFAs. The new algorithm also shows a faster compensation of system-induced LOFA intensity inhomogeneity than the conventional IFTA.

Cell motility, contact guidance, and durotaxis.

Mechanical properties of the substrate play a vital role in cell motility. In particular, cells have been shown to migrate along aligned fibers in the substrate (contact guidance) and up stiffness gradients (durotaxis). Here we present a simple mechanical model for cell migration coupled to substrate properties, by placing a simulated cell on a lattice mimicking biopolymer gels or hydrogels.

Association Between Type of Educational System and Prevalence and Severity of Myopia Among Male Adolescents in Israel.

Importance: A substantial portion of the public is diagnosed with myopia, which increases the risk of potential sight-threatening complications. The association between study style and the development of myopia is unclear.

Objective: To analyze the association between studying in different educational systems and the prevalence and severity of myopia among Jewish male adolescents in Israel.