Exploring van der Waals materials with high anisotropy: geometrical and optical approaches.

The emergence of van der Waals (vdW) materials resulted in the discovery of their high optical, mechanical, and electronic anisotropic properties, immediately enabling countless novel phenomena and applications. Such success inspired an intensive search for the highest possible anisotropic properties among vdW materials. Furthermore, the identification of the most promising among the huge family of vdW materials is a challenging quest requiring innovative approaches. Here, we suggest an easy-to-use method for such a survey based on the crystallographic geometrical perspective of vdW materials followed by their optical characterization. Using our approach, we found As2S3 as a highly anisotropic vdW material. It demonstrates high in-plane optical anisotropy that is ~20% larger than for rutile and over two times as large as calcite, high refractive index, and transparency in the visible range, overcoming the century-long record set by rutile. Given these benefits, As2S3 opens a pathway towards next-generation nanophotonics as demonstrated by an ultrathin true zero-order quarter-wave plate that combines classical and the Fabry-Pérot optical phase accumulations. Hence, our approach provides an effective and easy-to-use method to find vdW materials with the utmost anisotropic properties.

Impact of Vaccination Rates, Pre-Pandemic Life Expectancy, Economic Status and Age on COVID-19 Excess Mortality Across United States.

Aim: This study investigates factors influencing pandemic mortality rates across U.S. states during different waves of SARS-CoV-2 infection from February 2020 to April 2023, given that over one million people died from COVID-19 in the country. Methods: We performed statistical analyses and used linear regression models to estimate age-adjusted and unadjusted excess mortality as functions of life expectancy, vaccination rates, and GDP per capita in U.S. states. Results and Discussion: States with lower life expectancy and lower GDP per capita experienced significantly higher mortality rates during the pandemic, underscoring the critical role of underlying health conditions and healthcare infrastructure, as reflected in these factors. When categorizing states by vaccination rates, significant differences in GDP per capita and pre-pandemic life expectancy emerged between states with lower and higher vaccination rates, likely explaining mortality disparities before mass vaccination. During the Delta and Omicron BA.1 waves, when vaccines were widely available, the mortality gap widened, and states with lower vaccination rates experienced nearly double the mortality compared to states with higher vaccination rates (Odds Ratio 1.8, 95% CI 1.7-1.9, p < 0.01). This disparity disappeared during the later Omicron variants, likely because the levels of combined immunity from vaccination and widespread infection across state populations became comparable. We showed that vaccination rates were the only significant factor influencing age-adjusted mortality, highlighting the substantial impact of age-specific demographics on both life expectancy and GDP across states. Conclusion: The study underscores the critical role of high vaccination rates in reducing excess deaths across all states, regardless of economic status. Vaccination rates proved more decisive than GDP per capita in reducing excess deaths. Additionally, states with lower pre-pandemic life expectancy faced greater challenges, reflecting the combined effects of healthcare quality, demographic variations, and social determinants of health. These findings call for comprehensive public health strategies that address both immediate interventions, like vaccination, and long-term improvements in healthcare infrastructure and social conditions.

Chronic Inflammation Disrupts Circadian Rhythms in Splenic CD4+ and CD8+ T Cells in Mice.

Internal circadian clocks coordinate 24 h rhythms in behavior and physiology. Many immune functions show daily oscillations, and cellular circadian clocks can impact immune functions and disease outcome. Inflammation may disrupt circadian clocks in peripheral tissues and innate immune cells. However, it remains elusive if chronic inflammation impacts adaptive immune cell clock, e.g., in CD4+ and CD8+ T lymphocytes. We studied this in the experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis, as an established experimental paradigm for chronic inflammation. We analyzed splenic T cell circadian clock and immune gene expression rhythms in mice with late-stage EAE, CFA/PTx-treated, and untreated mice. In both treatment groups, clock gene expression rhythms were altered with differential effects for baseline expression and peak phase compared with control mice. Most immune cell marker genes tested in this study did not show circadian oscillations in either of the three groups, but time-of-day- independent alterations were observed in EAE and CFA/PTx compared to control mice. Notably, T cell effects were likely independent of central clock function as circadian behavioral rhythms in EAE mice remained intact. Together, chronic inflammation induced by CFA/PTx treatment and EAE immunization has lasting effects on circadian rhythms in peripheral immune cells.

Comparison of vaccination and booster rates and their impact on excess mortality during the COVID-19 pandemic in European countries.

Aim: To evaluate the effect of vaccination/booster administration dynamics on the reduction of excess mortality during COVID-19 infection waves in European countries. Methods: We selected twenty-nine countries from the OurWorldInData project database according to their population size of more than one million and the availability of information on dominant SARS-CoV-2 variants during COVID-19 infection waves. After selection, we categorized countries according to their "faster" or "slower" vaccination rates. The first category included countries that reached 60% of vaccinated residents by October 2021 and 70% by January 2022. The second or "slower" category included all other countries. In the first or "faster" category, two groups, "boosters faster'' and "boosters slower" were created. Pearson correlation analysis, linear regression, and chi-square test for categorical data were used to identify the association between vaccination rate and excess mortality. We chose time intervals corresponding to the dominance of viral variants: Wuhan, Alpha, Delta, and Omicron BA.1/2. Results and discussion: The "faster" countries, as opposed to the "slower" ones, did better in protecting their residents from mortality during all periods of the SARS-CoV-2 pandemic and even before vaccination. Perhaps higher GDP per capita contributed to their better performance throughout the pandemic. During mass vaccination, when the Delta variant prevailed, the contrast in mortality rates between the "faster" and "slower" categories was strongest. The average excess mortality in the "slower" countries was nearly 5 times higher than in the "faster" countries, and the odds ratio (OR) was 4.9 (95% CI 4.4 to 5.4). Slower booster rates were associated with significantly higher mortality during periods dominated by Omicron BA.1 and BA.2, with an OR of 2.6 (CI 95%. 2.1 to 3.3). Among the European countries we analyzed, Denmark, Norway, and Ireland did best, with a pandemic mortality rate of 0.1% of the population or less. By comparison, Bulgaria, Serbia, and Russia had a much higher mortality rate of up to 1% of the population. Conclusion: Thus, slow vaccination and booster administration was a major factor contributing to an order of magnitude higher excess mortality in "slower" European countries compared to more rapidly immunized countries.

Comparison of Vaccination and Booster Rates and Their Impact on Excess Mortality During the COVID-19 Pandemic in European Countries.

Aim To evaluate the effect of vaccination/booster administration dynamics on the reduction of excess mortality during COVID-19 infection waves in European countries. Methods We selected twenty-nine countries from the OurWorldInData project database according to their population size of more than one million and the availability of information on dominant SARS-CoV-2 variants during COVID-19 infection waves. After selection, we categorized countries according to their ″faster″ or ″slower″ vaccination rates. The first category included countries that reached 60% of vaccinated residents by October 2021 and 70% by January 2022. The second or ″slower″ category included all other countries. In the first or ″faster″ category, two groups, ″boosters faster'' and ″boosters slower″ were created. Pearson correlation analysis, linear regression, and chi-square test for categorical data were used to identify the association between vaccination rate and excess mortality. We chose time intervals corresponding to the dominance of viral variants: Wuhan, Alpha, Delta, and Omicron BA.1/2. Results The ″faster″ countries, as opposed to the ″slower″ ones, did better in protecting their residents from mortality during all periods of the SARS-CoV-2 pandemic and even before vaccination. Perhaps higher GDP per capita contributed to their better performance throughout the pandemic. During mass vaccination, when the Delta variant prevailed, the contrast in mortality rates between the ″faster″ and ″slower″ categories was strongest. The average excess mortality in the ″slower″ countries was nearly 5 times higher than in the ″faster″ countries, and the odds ratio (OR) was 4.9 (95% CI 4.4 to 5.4). Slower booster rates were associated with significantly higher mortality during periods dominated by Omicron BA.1 and BA.2, with an OR of 2.6 (CI 95%. 2.1 to 3.3). Among the European countries we analyzed, Denmark, Norway, and Ireland did best, with a pandemic mortality rate of 0.1% of the population or less. By comparison, Bulgaria, Serbia, and Russia had a much higher mortality rate of up to 1% of the population. Thus, slow vaccination and booster administration was a major factor contributing to an order of magnitude higher excess mortality in ″slower″ European countries compared to more rapidly immunized countries.

SARS-CoV-2 infection of phagocytic immune cells and COVID-19 pathology: Antibody-dependent as well as independent cell entry.

Our review summarizes the evidence that COVID-19 can be complicated by SARS-CoV-2 infection of immune cells. This evidence is widespread and accumulating at an increasing rate. Research teams from around the world, studying primary and established cell cultures, animal models, and analyzing autopsy material from COVID-19 deceased patients, are seeing the same thing, namely that some immune cells are infected or capable of being infected with the virus. Human cells most vulnerable to infection include both professional phagocytes, such as monocytes, macrophages, and dendritic cells, as well as nonprofessional phagocytes, such as B-cells. Convincing evidence has accumulated to suggest that the virus can infect monocytes and macrophages, while data on infection of dendritic cells and B-cells are still scarce. Viral infection of immune cells can occur directly through cell receptors, but it can also be mediated or enhanced by antibodies through the Fc gamma receptors of phagocytic cells. Antibody-dependent enhancement (ADE) most likely occurs during the primary encounter with the pathogen through the first COVID-19 infection rather than during the second encounter, which is characteristic of ADE caused by other viruses. Highly fucosylated antibodies of vaccinees seems to be incapable of causing ADE, whereas afucosylated antibodies of persons with acute primary infection or convalescents are capable. SARS-CoV-2 entry into immune cells can lead to an abortive infection followed by host cell pyroptosis, and a massive inflammatory cascade. This scenario has the most experimental evidence. Other scenarios are also possible, for which the evidence base is not yet as extensive, namely productive infection of immune cells or trans-infection of other non-immune permissive cells. The chance of a latent infection cannot be ruled out either.

Retrospective Cohort Study of the Effectiveness of the Sputnik V and EpiVacCorona Vaccines against the SARS-CoV-2 Delta Variant in Moscow (June-July 2021).

The goal of this study was to evaluate the epidemiological effectiveness of the Sputnik V and EpiVacCorona vaccines against COVID-19. This work is a retrospective cohort study of COVID-19 patients. The cohort created by the Moscow Health Department included more than 300,000 infected people who sought medical care in June and July 2021. Analysis of data revealed a tendency for the increase in the Sputnik V vaccine effectiveness (VE) as the severity of the disease increased. Protection was the lowest for mild disease, and it was more pronounced for severe disease. We also observed a decrease in VE with increasing age. For the youngest group (18-50 years old), the estimated VE in preventing death in June 2021 was 95% (95% CI 64-100), and for the older group (50+ years old), it was 74% (95% CI 67-87). The estimated protection against a severe form of the disease in the 18-50-year-old group was above 81% (CI 95% 72-93), and in the 50+ years-old group, it was above 68% (CI 95% 65-82). According to our analysis, EpiVacCorona proved to be an ineffective vaccine and therefore cannot protect against COVID-19.

The Role of Acidosis in the Pathogenesis of Severe Forms of COVID-19.

COVID-19 has specific characteristics that distinguish this disease from many other infections. We suggest that the pathogenesis of severe forms of COVID-19 can be associated with acidosis. This review article discusses several mechanisms potentially linking the damaging effects of COVID-19 with acidosis and shows the existence of a vicious cycle between the development of hypoxia and acidosis in COVID-19 patients. At the early stages of the disease, inflammation, difficulty in gas exchange in the lungs and thrombosis collectively contribute to the onset of acidosis. In accordance with the Verigo-Bohr effect, a decrease in blood pH leads to a decrease in oxygen saturation, which contributes to the exacerbation of acidosis and results in a deterioration of the patient's condition. A decrease in pH can also cause conformational changes in the S-protein of the virus and thus lead to a decrease in the affinity and avidity of protective antibodies. Hypoxia and acidosis lead to dysregulation of the immune system and multidirectional pro- and anti-inflammatory reactions, resulting in the development of a "cytokine storm". In this review, we highlight the potential importance of supporting normal blood pH as an approach to COVID-19 therapy.

Prospects for Using Expression Patterns of Paramyxovirus Receptors as Biomarkers for Oncolytic Virotherapy.

The effectiveness of oncolytic virotherapy in cancer treatment depends on several factors, including successful virus delivery to the tumor, ability of the virus to enter the target malignant cell, virus replication, and the release of progeny virions from infected cells. The multi-stage process is influenced by the efficiency with which the virus enters host cells via specific receptors. This review describes natural and artificial receptors for two oncolytic paramyxoviruses, nonpathogenic measles, and Sendai viruses. Cell entry receptors are proteins for measles virus (MV) and sialylated glycans (sialylated glycoproteins or glycolipids/gangliosides) for Sendai virus (SeV). Accumulated published data reviewed here show different levels of expression of cell surface receptors for both viruses in different malignancies. Patients whose tumor cells have low or no expression of receptors for a specific oncolytic virus cannot be successfully treated with the virus. Recent published studies have revealed that an expression signature for immune genes is another important factor that determines the vulnerability of tumor cells to viral infection. In the future, a combination of expression signatures of immune and receptor genes could be used to find a set of oncolytic viruses that are more effective for specific malignancies.

Directed evolution as a tool for the selection of oncolytic RNA viruses with desired phenotypes.

Viruses have some characteristics in common with cell-based life. They can evolve and adapt to environmental conditions. Directed evolution can be used by researchers to produce viral strains with desirable phenotypes. Through bioselection, improved strains of oncolytic viruses can be obtained that have better safety profiles, increased specificity for malignant cells, and more efficient spread among tumor cells. It is also possible to select strains capable of killing a broader spectrum of cancer cell variants, so as to achieve a higher frequency of therapeutic responses. This review describes and analyses virus adaptation studies performed with members of four RNA virus families that are used for viral oncolysis: reoviruses, paramyxoviruses, enteroviruses, and rhabdoviruses.

Defects in interferon pathways as potential biomarkers of sensitivity to oncolytic viruses.

Increased sensitivity of cancer cells to viruses is a prerequisite for the success of oncolytic virotherapy. One of the major causes of such a phenotype is the disruption of innate antiviral defenses associated with dysfunction of type 1 interferons (IFNs) that permits unlimited replication of viruses in cancer cells. Defects in IFN pathways help cancer progression by providing additional advantages to tumor cells. However, while these defects promote the survival and accelerated proliferation of malignant cells, they facilitate viral replication and thus enhance the efficiency of viral oncolysis. This review describes a broad spectrum of defects in genes that participate in IFN induction and IFN response pathways. Expression levels and/or functional activities of these genes are frequently low or absent in cancer cells, making them sensitive to virus infection. Therefore, certain specific defects in IFN signaling cascades might serve as potential biomarkers to help in identifying individual cancer patients who are likely to benefit from oncolytic virotherapy.

Oncolytic Sendai Virus Therapy of Canine Mast Cell Tumors (A Pilot Study).

Background: Canine mastocytomas (mast cell tumors) represent a common malignancy among many dog breeds. A typical treatment strategy for canine mastocytomas includes surgery, chemo- and radio-therapy, although in many cases the therapy fails and the disease progression resumes. New treatment approaches are needed. Aims: The goal of this pilot study was to examine safety and efficacy of oncolytic Sendai virus therapy administered to canine patients with cutaneous or subcutaneous mastocytomas. Materials and Methods: Six canine patients, with variable grades and stages of the disease, received virus therapy, either as a monotherapy, or in combination with surgery. The therapy included two or more virus applications administered weekly or biweekly. Each application of Sendai virus (107-108.6 EID50) consisted of multiple individual 0.01-0.1 ml injections delivered intratumorally, intradermally around a tumor, and under a tumor bed. Results: The treatment was well tolerated, with minor transitory side effects. Of the six dogs, two did not receive surgery or any other treatment besides the virus injections. The other four animals underwent radical or debulking surgeries, and in three of them the subsequent administration of Sendai virus completely cleared locally recurrent or/and remaining tumor masses. Five dogs demonstrated a complete response to the treatment, the animals remained disease free during the time of observation (2-3 years). One dog responded only partially to the virotherapy; its after-surgical recurrent tumor and some, but not all, metastases were cleared. This dog had the most advanced stage of the disease with multiple enlarged lymph nodes and cutaneous metastases. Conclusion: The results of the pilot study suggest that Sendai virus injections could be safe and efficient for the treatment of dogs affected by mastocytomas.They also suggest the need of further studies for finding optimal schemes and schedules for this kind of therapy.

Sequence characteristics define trade-offs between on-target and genome-wide off-target hybridization of oligoprobes.

Off-target oligoprobe's interaction with partially complementary nucleotide sequences represents a problem for many bio-techniques. The goal of the study was to identify oligoprobe sequence characteristics that control the ratio between on-target and off-target hybridization. To understand the complex interplay between specific and genome-wide off-target (cross-hybridization) signals, we analyzed a database derived from genomic comparison hybridization experiments performed with an Affymetrix tiling array. The database included two types of probes with signals derived from (i) a combination of specific signal and cross-hybridization and (ii) genomic cross-hybridization only. All probes from the database were grouped into bins according to their sequence characteristics, where both hybridization signals were averaged separately. For selection of specific probes, we analyzed the following sequence characteristics: vulnerability to self-folding, nucleotide composition bias, numbers of G nucleotides and GGG-blocks, and occurrence of probe's k-mers in the human genome. Increases in bin ranges for these characteristics are simultaneously accompanied by a decrease in hybridization specificity-the ratio between specific and cross-hybridization signals. However, both averaged hybridization signals exhibit growing trends along with an increase of probes' binding energy, where the hybridization specific signal increases significantly faster in comparison to the cross-hybridization. The same trend is evident for the S function, which serves as a combined evaluation of probe binding energy and occurrence of probe's k-mers in the genome. Application of S allows extracting a larger number of specific probes, as compared to using only binding energy. Thus, we showed that high values of specific and cross-hybridization signals are not mutually exclusive for probes with high values of binding energy and S. In this study, the application of a new set of sequence characteristics allows detection of probes that are highly specific to their targets for array design and other bio-techniques that require selection of specific probes.

Western lifestyle and immunopathology of multiple sclerosis.

There is increasing evidence for a sudden and unprecedented rise in the incidence of multiple sclerosis (MS) in Westernized countries over the past decades, emphasizing the role of environmental factors. Among many candidates, rapid changes in dietary habits seem to play a role in the pathogenesis of MS. Here, we summarize and discuss the available evidence for the role of dietary nutrients, such as table salt, fatty acids, and flavonoids, in the development and pathogenesis of MS. We also discuss new and emerging risk factors accompanying Western lifestyle, such as shift work, sleep, and circadian disruption.

Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses.

Lymphocytes circulate through lymph nodes (LN) in search for antigen in what is believed to be a continuous process. Here, we show that lymphocyte migration through lymph nodes and lymph occurred in a non-continuous, circadian manner. Lymphocyte homing to lymph nodes peaked at night onset, with cells leaving the tissue during the day. This resulted in strong oscillations in lymphocyte cellularity in lymph nodes and efferent lymphatic fluid. Using lineage-specific genetic ablation of circadian clock function, we demonstrated this to be dependent on rhythmic expression of promigratory factors on lymphocytes. Dendritic cell numbers peaked in phase with lymphocytes, with diurnal oscillations being present in disease severity after immunization to induce experimental autoimmune encephalomyelitis (EAE). These rhythms were abolished by genetic disruption of T cell clocks, demonstrating a circadian regulation of lymphocyte migration through lymph nodes with time-of-day of immunization being critical for adaptive immune responses weeks later.

Dissociation of Molecular and Endocrine Circadian Rhythms in Male Mice Lacking Bmal1 in the Adrenal Cortex.

The circadian rhythm of glucocorticoids affects diverse physiological systems, including stress responses and the coordination of rhythmic functions in peripheral and central tissues. Circadian clocks are considered to be important coordinators of glucocorticoid release and loss of the core clock component Brain and muscle Arnt-like protein-1 leads to ablation of behavioral and physiological rhythms, hypocortisolism, impaired ACTH, and behavioral stress responses. Transplantation and conditional clock gene knock-down studies in mice suggest an important role of local adrenocortical clock function in this context. Here, we present a Cre-loxP-mediated conditional knockout of Bmal1 in the steroidogenic cells of the adrenal cortex in mice. Mutant animals show a loss of molecular clock gene activity rhythms in this tissue with subsequent disruption of rhythmic steroidogenic gene expression. However, despite this loss of normal clock rhythmicity in the adrenal cortex, behavioral and physiological rhythms and acute stress responses persist in mutant mice. These findings reveal a dissociation of transcriptional and endocrine rhythm regulation in the adrenal cortex, arguing for a less pivotal function of the local clock machinery in the regulation of circadian and acute glucocorticoid outputs.

Optimization of signal-to-noise ratio for efficient microarray probe design.

MOTIVATION: Target-specific hybridization depends on oligo-probe characteristics that improve hybridization specificity and minimize genome-wide cross-hybridization. Interplay between specific hybridization and genome-wide cross-hybridization has been insufficiently studied, despite its crucial role in efficient probe design and in data analysis. RESULTS: In this study, we defined hybridization specificity as a ratio between oligo target-specific hybridization and oligo genome-wide cross-hybridization. A microarray database, derived from the Genomic Comparison Hybridization (GCH) experiment and performed using the Affymetrix platform, contains two different types of probes. The first type of oligo-probes does not have a specific target on the genome and their hybridization signals are derived from genome-wide cross-hybridization alone. The second type includes oligonucleotides that have a specific target on the genomic DNA and their signals are derived from specific and cross-hybridization components combined together in a total signal. A comparative analysis of hybridization specificity of oligo-probes, as well as their nucleotide sequences and thermodynamic features was performed on the database. The comparison has revealed that hybridization specificity was negatively affected by low stability of the fully-paired oligo-target duplex, stable probe self-folding, G-rich content, including GGG motifs, low sequence complexity and nucleotide composition symmetry. CONCLUSION: Filtering out the probes with defined 'negative' characteristics significantly increases specific hybridization and dramatically decreasing genome-wide cross-hybridization. Selected oligo-probes have two times higher hybridization specificity on average, compared to the probes that were filtered from the analysis by applying suggested cutoff thresholds to the described parameters. A new approach for efficient oligo-probe design is described in our study. CONTACT: shabalin@ncbi.nlm.nih.gov or olga.matveeva@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Complete Genome Sequence of the Oncolytic Sendai virus Strain Moscow.

We report here the complete genome sequence of Sendai virus Moscow strain. Anecdotal evidence for the efficacy of oncolytic virotherapy exists for this strain. The RNA genome of the Moscow strain is 15,384 nucleotides in length and differs from the nearest strain, BB1, by 18 nucleotides and 11 amino acids.

Circadian Clocks, Stress, and Immunity.

In mammals, molecular circadian clocks are present in most cells of the body, and this circadian network plays an important role in synchronizing physiological processes and behaviors to the appropriate time of day. The hypothalamic-pituitary-adrenal endocrine axis regulates the response to acute and chronic stress, acting through its final effectors - glucocorticoids - released from the adrenal cortex. Glucocorticoid secretion, characterized by its circadian rhythm, has an important role in synchronizing peripheral clocks and rhythms downstream of the master circadian pacemaker in the suprachiasmatic nucleus. Finally, glucocorticoids are powerfully anti-inflammatory, and recent work has implicated the circadian clock in various aspects and cells of the immune system, suggesting a tight interplay of stress and circadian systems in the regulation of immunity. This mini-review summarizes our current understanding of the role of the circadian clock network in both the HPA axis and the immune system, and discusses their interactions.

Oncolysis by paramyxoviruses: preclinical and clinical studies.

Preclinical studies demonstrate that a broad spectrum of human malignant cells can be killed by oncolytic paramyxoviruses, which include cells of ecto-, endo-, and mesodermal origin. In clinical trials, significant reduction in size or even complete elimination of primary tumors and established metastases are reported. Different routes of viral administration (intratumoral, intravenous, intradermal, intraperitoneal, or intrapleural), and single- versus multiple-dose administration schemes have been explored. The reported side effects are grade 1 and 2, with the most common among them being mild fever. Some advantages in using para-myxoviruses as oncolytic agents versus representatives of other viral families exist. The cytoplasmic replication results in a lack of host genome integration and recombination, which makes paramyxoviruses safer and more attractive candidates for widely used therapeutic oncolysis in comparison with retroviruses or some DNA viruses. The list of oncolytic paramyxovirus representatives includes attenuated measles virus (MV), mumps virus (MuV), low pathogenic Newcastle disease (NDV), and Sendai (SeV) viruses. Metastatic cancer cells frequently overexpress on their surface some molecules that can serve as receptors for MV, MuV, NDV, and SeV. This promotes specific viral attachment to the malignant cell, which is frequently followed by specific viral replication. The paramyxoviruses are capable of inducing efficient syncytium-mediated lyses of cancer cells and elicit strong immunomodulatory effects that dramatically enforce anticancer immune surveillance. In general, preclinical studies and phase 1-3 clinical trials yield very encouraging results and warrant continued research of oncolytic paramyxoviruses as a particularly valuable addition to the existing panel of cancer-fighting approaches.