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Abstract: The idea of using the lytic power of viruses against malignant cells has been entertained for many decades. However, oncolytic viruses gained broad attention as an emerging anti-cancer therapy only recently with the successful implementation of several oncolytic viruses to treat advanced melanoma. Here we review the history of oncolytic viruses in the Russian Federation and recent biotechnological advances in connection with the perspectives of their practical use against aggressive tumors such as glioblastoma or pancreatic cancer. A particular emphasis is made on novel applications of safe non-lytic virus-derived vectors armed with prodrug-converting enzyme transgenes. Rational improvement of oncotropism by conjugation with biopolymers and nanoformulations is also discussed.

Reactive oxygen species (ROS) induce multiple signaling cascades in the cell and hence play an important role in the regulation of the cell's fate. ROS can cause irreversible damage to DNA and proteins resulting in cell death. Therefore, finely tuned regulatory mechanisms exist in evolutionarily diverse organisms that are aimed at the neutralization of ROS and its consequences with respect to cellular damage. The SET domain-containing lysine methyltransferase Set7/9 (KMT7, SETD7, SET7, SET9) post-translationally modifies several histones and non-histone proteins via monomethylation of the target lysines in a sequence-specific manner. In cellulo, the Set7/9-directed covalent modification of its substrates affects gene expression, cell cycle, energy metabolism, apoptosis, ROS, and DNA damage response. However, the in vivo role of Set7/9 remains enigmatic. In this review, we summarize the currently available information regarding the role of methyltransferase Set7/9 in the regulation of ROS-inducible molecular cascades in response to oxidative stress. We also highlight the in vivo importance of Set7/9 in ROS-related diseases.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize anabundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.

Fatigue is one of the most common and debilitating symptoms of multiple sclerosis (MS) but is challenging to assess and has not been comprehensively characterized in patients with progressive MS. This study aimed to (1) obtain qualitative evidence from patients with progressive MS to characterize MS-related fatigue concepts and their impacts on health-related quality of life (HRQoL), and (2) evaluate the conceptual frameworks of existing MS-specific fatigue patient-reported outcome (PRO) instruments using study data to determine the most suitable PRO instrument in this population.Qualitative interviews were conducted with 30 US participants with confirmed progressive MS and fatigue in the last 6 months to assess their MS-related fatigue. Data were compared with concepts in existing PRO instruments to evaluate their relevance in progressive MS.Physical and mental concepts of fatigue were identified and characterized distinctly from patients with progressive MS. Most patients characterized fatigue as occurring daily and lasting several hours, with negative impacts on HRQoL. Concept mapping to existing MS-specific fatigue PRO instruments supported the Fatigue Severity Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) as the most suitable existing option for assessing fatigue in patients with progressive MS, as it separates physical and mental aspects of fatigue and includes every highly endorsed concept reported by the interviewed patients.This qualitative study identified meaningful physical and mental fatigue concepts in patients with progressive MS and preliminarily supports the use of the FSIQ-RMS for this population. More research is needed to fully validate this instrument for progressive MS.

Aims\ud \ud Accurately estimating mean survival after solid organ transplant (SOT) is crucial for efficient healthcare resource allocation decisions. However, registry-based post-transplant recipient survival estimates vary greatly and are incomplete. Often, the methods used in lifetime survival extrapolation may not fit complex transplant data and therefore alternative methods are required. We aimed to explore the flexible cubic spline methodology as a meaningful alternative for estimating lifetime survival following SOT.\ud \ud \ud \ud Methods\ud \ud Survival analyses were conducted in kidney, liver, heart, and lung transplant recipients. Mean survival was estimated using flexible cubic splines on the hazard scale fitted with three knots, based on where hazards changed direction, clinical advice, and best-fit curve using Akaike and Bayesian information criterion. The tail was extrapolated when data were no longer available. Extrapolation tails were compared with general population mortality, using age-matched life table hazards, and the highest hazards were taken at all times.\ud \ud \ud \ud Results\ud \ud We found that mean survival post-transplant was longest for kidney (US: 22.79 years; UK: 26.58 years), followed by liver (US: 20.90 years; UK: 20.38 years), heart (US: 14.82 years; UK: 15.85 years) and lung (US: 9.28 years; UK: 9.21 years). A sensitivity analysis using two knots found differences in survival ranging from −1.30 to +4.83 years across SOTs examined.\ud \ud \ud \ud Limitations\ud \ud This study does not represent individual patient survival, survival by age groups, multiple-organ transplants, or assess factors that may impact overall or organ survival.\ud \ud \ud \ud Conclusions\ud \ud Our study estimates reflect real-world survival following SOTs and demonstrate the importance of including long-term hazards in survival estimations. These lifetime survival estimates can be used by decision makers in situations where means are preferred over medians (e.g. population projections, budgetary estimates, and cost-effectiveness models) and can thus offer a meaningful alternative to the estimates used and accepted in current practice.

Overweight and obese (“heavyweight”) people devalue themselves because, it has been proposed, they are socially devalued. However, for women, social valuation depends not only on how much weight they carry but also on where on their bodies they carry it. Here, we investigated whether weight-based self-valuation and perceived social valuation similarly depend on body shape. Study 1, using a nationally representative sample from National Health and Nutrition Examination Survey (NHANES; N = 1,093 reproductive-aged women), showed that, controlling for body fat, weight labeling (by self and others) and wanting to lose weight depended on body shape. Study 2, in a direct test of predictions using an undergraduate sample of women ( N = 215), showed that with increased body fat, women with an abdominal weight distribution reported more self-devaluation (e.g., lower self-esteem) and perceived social devaluation (e.g., higher perceived weight discrimination); women with a gluteofemoral weight distribution, however, were shielded—partially or fully—from these adverse effects of increased body fat.

Molecularly imprinted polymers - MIPs - denote synthetic polymeric structures that selectively recognize the molecule of interest against which MIPs are templated. A number of works have demonstrated that MIPs can exceed the affinity and selectivity of natural antibodies, yet operating by the same principle of "lock and key". In contrast to antibodies, which have certain limitations related to the minimal size of the antigen, nanoMIPs can be fabricated against almost any target molecule irrespective of its size and low immunogenicity. Furthermore, the cost of MIP production is much lower compared to the cost of antibody production. Excitingly, MIPs can be used as nanocontainers for specific delivery of therapeutics both

Autophagy is a highly conserved process of cellular self-digestion that involves the formation of autophagosomes for the delivery of intracellular components and dysfunctional organelles to lysosomes. This process is induced by different signals including starvation, mitochondrial dysfunction, and DNA damage. The molecular link between autophagy and DNA damage is not well understood yet. Importantly, tumor cells utilize the mechanism of autophagy to cope with genotoxic anti-cancer drug therapy. Another mechanism of drug resistance is provided to cancer cells via the execution of the EMT program. One of the critical transcription factors of EMT is Zeb1. Here we demonstrate that Zeb1 is involved in the regulation of autophagy in several breast cancer cell models. On the molecular level, Zeb1 likely facilitates autophagy through the regulation of autophagic genes, resulting in increased LC3-II levels, augmented staining with Lysotracker, and increased resistance to several genotoxic drugs. The attenuation of Zeb1 expression in TNBC cells led to the opposite effect. Consequently, we propose that Zeb1 augments the resistance of breast cancer cells to genotoxic drugs, at least partially, via autophagy. Collectively, we have uncovered a novel function of Zeb1 in the regulation of autophagy in breast cancer cells.

Supplementary Figure 3. BTK and apoptosis.

p53 is a tumor suppressor that prevents the emergence of transformed cells by inducing apoptosis or senescence, among other responses. Its functions are regulated tightly by posttranslational modifications. Here we show that Bruton's tyrosine kinase (BTK) is a novel modulator of p53. We found that BTK is induced in response to DNA damage and p53 activation. BTK induction leads to p53 phosphorylation, which constitutes a positive feedback loop that increases p53 protein levels and enhances the transactivation of its target genes in response to stress. Inhibiting BTK reduced both p53-dependent senescence and apoptosis. Further, BTK expression also upregulated DNA damage signals and apoptosis. We conclude that despite being involved in oncogenic signals in blood malignancies, BTK has antineoplastic properties in other contexts, such as the enhancement of p53's tumor suppressor responses. Along with evidence that BTK expression correlates with good prognosis in some epithelial tumors, our findings may encourage a reevaluation of the clinical uses of BTK inhibitors in cancer therapy. Cancer Res; 76(18); 5405–14. ©2016 AACR.

Supplementary Figure 2. p53 phosphorylation.

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Supplementary Figure 1.p53 expression and phosphorylation.

Researchers increasingly recognize that the mind and culture interact at many levels to constitute our lived experience, yet we know relatively little about the extent to which culture shapes the way people appraise their experiences and the likelihood that a given experience will be reported. Experiences that involve claims regarding deities, extraordinary abilities, and/or psychopathology offer an important site for investigating the interplay of mind and culture at the population level. However, the difficulties inherent in comparing culture-laden experiences, exacerbated by the siloing of research on experiences based on discipline-specific theoretical constructs, have limited our ability to do so. We introduce the Inventory of Nonordinary Experiences (INOE), which allows researchers to compare experiences by separating the phenomenological features from how they are appraised and asking about both. It thereby offers a new means of investigating the potentially universal (etic) and culture-specific (emic) aspects of lived experiences. To ensure that the INOE survey items are understood as intended by English speakers in the US and Hindi speakers in India, and thus can serve as a basis for cross-cultural comparison, we used the Response Process Evaluation (RPE) method to collect evidence of item-level validity. Our inability to validate some items drawn from other surveys suggests that they are capturing a wider range of experiences than researchers intend. Wider use of the RPE method would increase the likelihood that survey results are due to the differences that researchers intend to measure.

Two related tumor suppressor genes, Brca1 and Brca2, attract a lot of attention from both fundamental and clinical points of view. Oncogenic hereditary mutations in these genes are firmly linked to the early onset of breast and ovarian cancers. However, the molecular mechanisms that drive extensive mutagenesis in these genes are not known. In this review we hypothesize that one of the potential mechanisms behind this phenomenon can be mediated by Alu mobile genomic elements. Linking mutations in the BRCA1 and BRCA2 genes to the general mechanism(s) of genome stability and DNA repair is critical to ensure the rationalized choice of anti-cancer therapy. Accordingly, we review the literature available on mechanisms of DNA damage repair where these proteins are involved in and how the inactivating mutations in these genes (BRCAness) can be exploited in anti-cancer therapy. We also propose a hypothesis that explains why breast and ovarian epithelial tissues are preferentially susceptible to mutations in BRCA genes. Finally, we discuss perspectives of novel therapeutic approaches for treating BRCAness cancers.

Virus-induced CNS diseases impose a considerable human health burden worldwide. For many viral CNS infections, neither antiviral drugs nor vaccines are available. In this study, we examined whether the synthesis of glycosphingolipids, major membrane lipid constituents, could be used to establish an antiviral therapeutic target. We found that neuroinvasive Sindbis virus altered the sphingolipid levels early after infection in vitro and increased the levels of gangliosides GA1 and GM1 in the sera of infected mice. The alteration in the sphingolipid levels appears to play a role in neuroinvasive Sindbis virus replication, as treating infected cells with UDP-glucose ceramide glucosyltransferase (UGCG) inhibitors reduced the replication rate. Moreover, the UGCG inhibitor GZ-161 increased the survival rates of Sindbis-infected mice, most likely by reducing the detrimental immune response activated by sphingolipids in the brains of Sindbis virus-infected mice. These findings suggest a role for glycosphingolipids in the host immune response against neuroinvasive Sindbis virus and suggest that UGCG inhibitors should be further examined as antiviral therapeutics for viral infections of the CNS.

How much cultural variation is explained by the physical and social ecologies people inhabit? Here, we provide an answer using nine ecological variables and 66 cultural variables (including personality traits, values and norms) drawn from the EcoCultural Dataset. We generate a range of estimates by using different statistical metrics (e.g. current levels, average levels across time, unpredictability across time) of each of the ecological variables. Our results suggest that, on average, ecology explains a substantial amount of human cultural variation above and beyond spatial and cultural autocorrelation. The amount of variation explained depended on the metrics used, with current levels and average levels of ecological conditions explaining the greatest amounts of variance in human culture on average (16% and 20%, respectively).

The SET domain containing lysine-specific methyltransferase, Set7/9, covalently attaches methyl moieties to a variety of histone and non-histone substrates. Among the substrates of Set7/9 are: p53, NF-kB, PARP1, E2F1, and other transcription factors that regulate many vital processes in the cell. Through the post-translational regulation of these critical master-regulators Set7/9 is involved in regulation of cell proliferation, cancer progression, and DNA damage response. Noteworthy, the role of Set7/9 in tumorigenesis is contradictory and apparently depends on the cellular context. In this study, we investigated the effect of Set7/9 on tumorigenic characteristics of lung cancer cells. We showed that CRISPR/Cas9-mediated knock-out of Set7/9 in A549 and its shRNA-mediated knock-down in H1299 NSCLC cell lines both augment the proliferation rate of tumor cells compared to the matching wild-type cells. Mechanistically, ablation of Set7/9 increased the expression of cyclin A2 and D1 genes thereby promoting the accumulation of cells in S phase. Furthermore, knockout of Set7/9 decreased the expression of E-cadherin, whose product is critical for cell-cell interactions. Accordingly, this led to the increased migration of lung cancer cells. Finally, both ablation or pharmacological inhibition of Set7/9 enzymatic methyltransferase activity by the selective inhibitor (R)-PFI-2 sensitized NSCLC cells to genotoxic drug, doxorubicin. This effect was also recapitulated on patients-derived NSCLC cell lines. Taken together, our results suggest that Set7/9 plays anti-proliferative and DNA damage-protective roles in NSCLC cells and hence represents an attractive target for anti-cancer chemotherapy.

Background ACTN4 is an actin-binding protein involved in many cellular processes, including cancer development. High ACTN4 expression is often associated with a poor prognosis. However, it has been identified as a positive marker for platinum-based adjuvant chemotherapy for non-small cell lung cancer (NSCLC). The goal of our study was to investigate the involvement of ACTN4 in the NSCLC cells’ response to the genotoxic drugs. Results We generated H1299 cells with the ACTN4 gene knock-out (ACTN4 KO), using the CRISPR/Cas9 system. The resistance of the cells to the cisplatin and etoposide was analyzed with the MTT assay. We were also able to estimate the efficiency of DNA repair through the DNA comet assay and gamma-H2AX staining. Possible ACTN4 effects on the non-homologous end joining (NHEJ) and homologous recombination (HR) were investigated using pathway-specific reporter plasmids and through the immunostaining of the key proteins. We found that the H1299 cells with the ACTN4 gene knock-out did not show cisplatin-resistance, but did display a higher resistance to the topoisomerase II inhibitors etoposide and doxorubicin, suggesting that ACTN4 might be somehow involved in the repair of DNA strand breaks. Indeed, the H1299 ACTN4 KO cells repaired etoposide- and doxorubicin-induced DNA breaks more effectively than the control cells. Moreover, the ACTN4 gene knock-out enhanced NHEJ and suppressed HR efficiency. Supporting the data, the depletion of ACTN4 resulted in the faster assembly of the 53BP1 foci with a lower number of the phospho-BRCA1 foci after the etoposide treatment. Conclusions Thus, we are the first to demonstrate that ACTN4 may influence the resistance of cancer cells to the topoisomerase II inhibitors, and affect the efficiency of the DNA double strand breaks repair. We hypothesize that ACTN4 interferes with the assembly of the NHEJ and HR complexes, and hence regulates balance between these DNA repair pathways.

Why do people hold irrational beliefs? Two accounts predominate. The first spotlights the information ecosystem and how people process this information; this account either casts those who hold irrational beliefs as cognitively deficient or focuses on the reasoning and decision-making heuristics all people use. The second account spotlights an inwardly-oriented and proximate motivation people have to enhance how they think and feel about themselves. Here, we advance a complementary, outwardly-oriented, and more ultimate account—that people often hold irrational beliefs for evolutionarily rational reasons. Under this view, irrational beliefs may serve as rare and valued information with which to rise in prestige, as signals of group commitment and loyalty tests, as ammunition with which to derogate rivals in the eyes of third-parties, or as outrages with which to mobilize the group toward shared goals. Thus, although many beliefs may be epistemically irrational, they may also be evolutionarily rational from the perspective of the functions they are adapted to serve. We discuss the implications of this view for puzzling theoretical phenomena and for changing problematic irrational beliefs.

Originally discovered by Nielsen in 1991, peptide nucleic acids and other artificial genetic polymers have gained a lot of interest from the scientific community. Due to their unique biophysical features these artificial hybrid polymers are now being employed in various areas of theranostics (therapy and diagnostics). The current review provides an overview of their structure, principles of rational design, and biophysical features as well as highlights the areas of their successful implementation in biology and biomedicine. Finally, the review discusses the areas of improvement that would allow their use as a new class of therapeutics in the future.

Scholars interested in cultural diversity have long suggested that similarities and differences across human populations might be understood, at least in part, as stemming from differences in the social and physical ecologies individuals inhabit. Here, we describe the EcoCultural Dataset (ECD), the most comprehensive compilation to date of country-level ecological and cultural variables around the globe. ECD covers 220 countries, 9 ecological variables operationalized by 11 statistical metrics (including measures of variability and predictability), and 72 cultural variables (including values, personality traits, fundamental social motives, subjective well-being, tightness-looseness, indices of corruption, social capital, and gender inequality). This rich dataset can be used to identify novel relationships between ecological and cultural variables, to assess the overall relationship between ecology and culture, to explore the consequences of interactions between different ecological variables, and to construct new indices of cultural distance.

Autophagy is a special catabolic cellular program that is induced in response to deprivation of nutrients and energy starvation. During the execution of this program, cellular components, including aggregates, as well as damaged organelles and some proteins are encapsulated in special vesicles known as autophagosomes and subsequently are degraded after fusion of autophagosomes with lysosomes. Importantly, at late stages of tumorigenesis cancer cells employ autophagy to sustain proliferation in unfavorable conditions, including anti-cancer drug therapy. E3 ubiquitin ligases play an important role in controlling autophagy. Here we demonstrate that the E3 ligase, a p53-induced RING-H2 protein (Pirh2), is involved in the regulation of autophagy in non-small cell lung cancer cells. Knockdown of Pirh2 decreased the expression of genes involved in all steps of autophagy. Concomitantly, Pirh2 knockdown cell lines exhibited much less of the processed form of LC3 compared to the respective cell lines with normal levels of Pirh2. These results were confirmed by the immune fluorescence microscopy using LC3 antibody and the LysoTracker dye. In agreement with the protective role of autophagy, cells with attenuated expression of Pirh2 were more sensitive to the treatment with doxorubicin. Collectively, we have uncovered a novel function of Pirh2 in the regulation of autophagy in lung cancer cells.

Scholars interested in cultural diversity have long suggested that similarities and differences across human populations might be understood, at least in part, as stemming from differences in the social and physical ecologies individuals inhabit—culture is an emergent property of many individual-level effects. Here, we describe the EcoCultural Dataset (ECD), the most comprehensive compilation to date of country-level ecological and cultural variables around the globe. ECD covers, covering 220 countries, 9 ecological variables operationalized by 11 statistical metrics (including measures of variability and predictability), and 72 cultural variables (including values, personality traits, fundamental social motives, subjective well-being, tightness-looseness, indices of corruption, social capital, and gender inequality). This rich dataset can be used to identify novel relationships between ecological and cultural variables, to assess the overall relationship between ecology and culture, to explore the consequences of interactions between different ecological variables, and to construct new indices of cultural distance.

The current monkeypox virus global spread and lack of data regarding clinical specimens’ infectivity call for examining virus infectivity, and whether this correlates with results from PCR, the available diagnostic tool. We show strong correlation between viral DNA amount in clinical specimens and virus infectivity toward BSC-1 cell line. Moreover, we define a PCR threshold value (Cq ≥ 35, ≤ 4,300 DNA copies/mL), corresponding to negative viral cultures, which may assist risk-assessment and decision-making regarding protective-measures and guidelines for patients with monkeypox.

The goal of this project is to explore the effects of ecological unpredictability on culture. Past research on the impact of ecology on culture has focused on how present or past levels of ecological dimensions like resource availability (e.g., resource scarcity versus abundance) are linked to patterns of cultural variation. However, in behavioral ecology, the unpredictability of these dimensions is considered at least as important. Here, we propose that ecological unpredictability should be linked with certain patterns of cultural variation; in particular, variations in levels of tightness-looseness, relational mobility, and innovation. Cultural looseness allows individuals to deviate from social norms in response to the shifting demands of unpredictable environments. Thus, looser societies should be better able to adapt to unpredictable changes by fostering flexible responses. Relational mobility – or ease of movement in and out of social relationships – should be greater in less predictable ecologies, as this should enable people to better choose interaction partners whose affordances best fit changing environmental demands. Finally, in changing environments, we should see more innovation and the development of new technological adaptations to those environmental changes. Ecological unpredictability can be measured along different dimensions. Here, we focus on four: climate (indexed by rainfall, natural disasters, and temperature), resource availability (indexed via GDP per capita, unemployment rates, rates of malnourishment, and famine), resource distribution (index by GINI), extrinsic mortality (indexed via mortality rates due to various causes). We do not have strong predictions about what domain of ecology or which variables will best predict the cultural outcomes of interest. We will use a novel method of operationalizing ecological unpredictability on these dimensions using time series methodology and the auto.ARIMA algorithm (implemented in R packages TSA & forecast). Both pre-registered and exploratory hypotheses are included.

The goal of this project is to explore the effects of ecological unpredictability on culture. Past research on the impact of ecology on culture has focused on how average levels (either at present or in the past) of ecological dimensions are linked to patterns of cultural variation. However, in behavioral ecology, the unpredictability over time of these dimensions is considered at least as important. Here, we propose that ecological unpredictability should push for variation in cultural outcomes. Specifically, we predict that unpredictability should push for greater flexibility to adaptively respond to changing threats and opportunities in the environment. Cultural variations that promote flexibility, like loose cultural norms, high relational mobility, and greater creativity and innovation should persist because they allow individuals within an unpredictable environment to change in response to their ever-changing environment. Specifically, cultural looseness allows for cultures to change social norms in response to the demands of an environment. Thus, more frequent changes should encourage a looser environment. Relational mobility – or movement in and out of social groups – should increase in response to changes in the demands of environment to maximize the benefits of social relationships. At times, it may be beneficial to be in many social groups and at others, like during times of high disease threat, socialization could increase risk to oneself. Finally, in changing environments, we should see more innovation and the development of new technological adaptations to those environmental changes. Ecological unpredictability can be measured along different dimensions. Here, we focus on a few: resource availability, factors related to resource availability (i.e. climate, resource distribution), and mortality, each indexed by a variety of variables. We do not have strong predictions about what domain of ecology or which variables will best predict the cultural outcomes of interest. We propose a novel method of operationalizing ecological unpredictability on these dimensions using time series methodology and the auto.ARIMA algorithm. Both pre-registered and exploratory hypotheses are included.

A memory experiment testing a hypothesis from epistemic vigilance theory

We are testing a computational model of causal judgment, using the 2020 US presidential election as a case study.

In light of the alarming global spread of Monkeypox and the lack of data regarding virus infectivity in clinical specimens, we examined virus infectivity and its correlation with PCR results, the currently available diagnostic tool. Due to the high risk of Monkeypox virus infection, only a limited number of approved BSL-3 laboratories employed with vaccinated staff, including ourselves, are capable of determining Monkeypox virus infectivity. We show strong correlation between viral DNA content and virus infectivity in clinical specimens. Moreover, we define a PCR threshold value which correspond to non-infectious virus, and suggest that our data can be translated into informed decision-making regarding risk assessment, protective measures and guidelines for Monkeypox patients.

20-Hydroxyecdysone (20E) is an arthropod hormone which is synthesized by some plants as part of their defense mechanism. In humans, 20E has no hormonal activity but possesses a number of beneficial pharmacological properties including anabolic, adaptogenic, hypoglycemic, and antioxidant properties, as well as cardio-, hepato-, and neuroprotective features. Recent studies have shown that 20E may also possess antineoplastic activity. In the present study, we reveal the anticancer properties of 20E in Non-Small Cell Lung Cancer (NSCLC) cell lines. 20E displayed significant antioxidant capacities and induced the expression of antioxidative stress response genes. The RNA-seq analysis of 20E-treated lung cancer cells revealed the attenuation of genes involved in different metabolic processes. Indeed, 20E suppressed several enzymes of glycolysis and one-carbon metabolism, as well as their key transcriptional regulators—c-Myc and ATF4, respectively. Accordingly, using the SeaHorse energy profiling approach, we observed the inhibition of glycolysis and respiration mediated by 20E treatment. Furthermore, 20E sensibilized lung cancer cells to metabolic inhibitors and markedly suppressed the expression of Cancer Stem Cells (CSCs) markers. Thus, in addition to the known beneficial pharmacological activities of 20E, our data uncovered novel antineoplastic properties of 20E in NSCLC cells.

This report presents novel results on the involvement of epithelial to mesenchymal transition (EMT) in the process of autophagy. Autophagy is a highly conserved process of cellular self-digestion that involves the formation of autophagosomes for the delivery of intracellular components and dysfunctional organelles to lysosomes. This process is induced by different signals including starvation, mitochondrial dysfunction, and DNA damage. The molecular link between autophagy and DNA damage is not well understood yet. Importantly, tumor cells utilize the mechanism of autophagy to cope with genotoxic anti-cancer drug therapy. Another mechanism of drug resistance is provided to cancer cells via the execution of the EMT program. One of the critical transcription factors of EMT is Zeb1. Here we demonstrate that Zeb1 is involved in the regulation of autophagy in several breast cancer cell models. On the molecular level, forced expression of Zeb1 in otherwise epithelial cells likely facilitates autophagy through the regulation of several autophagic genes, resulting in increased LC3-II levels, augmented staining with Lysotracker, and increased resistance to genotoxic drugs. On the contrary, the attenuation of Zeb1 expression in TNBC cells led to the opposite effect. Consequently, we propose that Zeb1 augments the resistance of breast cancer cells to genotoxic drugs, at least partially, by promoting autophagy. Collectively, we have uncovered a novel function of Zeb1 in the regulation of autophagy in breast cancer cells. Citation Format: Nick A. Barlev, Olga Fedorova, Alexandra Daks, Eugene M. Tulchinsky. Zeb1-mediated autophagy enhances resistance of breast cancer cells to genotoxic drugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1237.

Public health experts emphasize the need for quick, point-of-care SARS-CoV-2 detection as an effective strategy for controlling virus spread. To this end, many “antigen” detection devices were developed and commercialized. These devices are mostly based on detecting SARS-CoV-2’s nucleocapsid protein. Recently, alerts issued by both the FDA and the CDC raised concerns regarding the devices’ tendency to exhibit false positive results. In this work we developed a novel alternative spike-based antigen assay, comprised of four high-affinity, specific monoclonal antibodies, directed against different epitopes on the spike’s S1 subunit. The assay’s performance was evaluated for COVID-19 detection from nasopharyngeal swabs, compared to an in-house nucleocapsid-based assay, composed of antibodies directed against the nucleocapsid. Detection of COVID-19 was carried out in a cohort of 284 qRT-PCR positive and negative nasopharyngeal swab samples. The time resolved fluorescence (TRF) ELISA spike-assay displayed very high specificity (99%) accompanied with a somewhat lower sensitivity (66% for CtAbstract FigureGraphic abstractSchematic representation of sample collection and analysis. The figure was created using BioRender.com

The socialization process of media use begins in the first year ofa child’s life. Infants and toddlers are exposed to media in thebackground, they learn from screens, and acquire media-related skills from watching their family members’ behavior. Hence, it is of great importance to examine the family context in which young children develop their initial media habits, as well as how they learn from screens during a critical period of their lives. This article explores how young children are socialized into becoming media users in a longitudinal study that closely followed the development of the media habits and preferences of children from the age of three months to two years old. A combination of two qualitative methods was applied: observations at the families’ homes were conducted every three months; and in- depth interviews with parents were conducted at the beginning, the middle, and at the end of the study. Families expecting their second or third child were recruited for the study, to create comparable familial circumstances of having older siblings. The study’s findings expose parents’ limited awareness of the importance of instructive and technological mediation, as well asthe need to facilitate proper conditions that would maximize thebenefits of these forms of mediation. Therefore, there is a need for enhancing parental media literacy, which would enable parents to support children’s media uses and lead to the development ofricher and healthier children’s media experiences.

A common chemotherapy regimen in post-transplant lymphoproliferative disease (PTLD) following solid organ transplants (SOT) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). This study reviews the quantitative evidence for long-term consequences associated with components of CHOP identified from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cited references were screened using prespecified criteria (English, systematic review, randomized controlled trial

Physical violence was a recurrent selection pressure in ancestral social environments. The psychology of partner choice may have partially been shaped by this. Here, we investigate whether people prefer partners who are willing and able to protect them from violence. In a series of 7 studies (N = 4,508), we systematically varied the willingness and ability of a date or friend to physically protect you from a violent attack, compared to scenarios in which you do not have this information. Independent of their physical strength (ability to protect), discovering that a person is willing to protect you greatly increased their attractiveness as a partner; this held for both women and men, and when evaluating both opposite- and same-sex partners of both sexes. In fact, partners who were willing to protect you were attractive even if they tried to do so but failed, and even if you were harmed because of their failure. Discovering that a partner is unwilling to protect you decreased their attractiveness. However, this effect varied with the sex of raters (greater decrease for women versus men) and targets (greater decrease for male than female targets); moreover, the decrease was greater for dates than friends. Indeed, discovering that a male date was unwilling to protect them was a deal-breaker for women. We found only weak evidence that ability to physically protect, independent of willingness, increases the attractiveness of a date or friend. We discuss the implications of this ancestrally evolved psychology for social decision-making in the modern world.

The central role of an aberrantly activated EMT program in defining the critical features of aggressive carcinomas is well documented and includes cell plasticity, metastatic dissemination, drug resistance, and cancer stem cell-like phenotypes. The p53 tumor suppressor is critical for leashing off all the features mentioned above. On the molecular level, the suppression of these effects is exerted by p53 via regulation of its target genes, whose products are involved in cell cycle, apoptosis, autophagy, DNA repair, and interactions with immune cells. Importantly, a set of specific mutations in the TP53 gene (named Gain-of-Function mutations) converts this tumor suppressor into an oncogene. In this review, we attempted to contrast different regulatory roles of wild-type and mutant p53 in the multi-faceted process of EMT.

Introduction There are no validated patient-reported outcome (PRO) instruments for Epstein–Barr virus-driven post-transplant lymphoproliferative disease (EBV+ PTLD). The aim of this study was to assess the content applicability for three frequently used PRO instruments from the perspective of patients with EBV+ PTLD. Methods A moderated focus group comprising adult patients with EBV+ PTLD was conducted using a concept confirmation and an open-ended concept elicitation approach. The domains of the EuroQoL Group-5 Dimension (EQ-5D) instrument, Short Form Health Survey-Version 2 (SF-36v2) questionnaire, and Functional Assessment of Chronic Illness Therapy–Lymphoma (FACT-LYM) questionnaire were discussed. The concept elicitation portion was a general discussion of symptoms and patient burden of EBV+ PTLD. Results Six patients participated in this study: five women and one man. Most participants reported acute pain in the location of their EBV+ PTLD. All participants reported significant physical fatigue and experienced productivity loss. Patients reported emotional fatigue, feelings of dissociation, lack of motivation, and persistent fear of disease progression, including mortality. Patients described their social functioning as disjointed, behaving differently with loved ones/caregivers than when alone. The EQ-5D was relevant for the pain/discomfort and anxiety/depression domains; most SF-36v2 domains were relevant, with the exception of the general health perception domain, which was not applicable; all domains in the FACT-LYM were relevant. The open-ended portion drew no new content. Conclusions This qualitative research identified meaningful concepts in patients with EBV+ PTLD, with physical, emotional, and social functioning being impacted. The FACT-LYM questionnaire was the most relevant of the three PROs studied, with all domains relevant to this population. It is important to properly analyze PRO data in patients with EBV+ PTLD.

Cancer testis antigens SEMG1 and SEMG2 (semenogelins 1 and 2) are the main proteins of human seminal fluid and are also expressed in malignant neoplasms of various origins. The biological role of semenogelins in the reproductive process is well understood, but almost nothing is known about their functions in tumor cells. In the present study, we used Mia-Paca2 cell line with overexpression of SEMG1 and SEMG2a as a cell model of human pancreatic cancer. Mia-Paca2 cells transduced with the corresponding vector served as control. Using flow cytometry and dihydroethidium (DHE) fluorescent agent detecting predominantly superoxide anion, we have shown that overexpression of SEMG1 and SEMG2 increases the ROS level. In addition, both semenogelins increased the susceptibility of tumor cells to the widely used chemotherapeutic genotoxic drugs doxorubicin and cisplatin. These findings showed that oncosuppressive properties are possessed by SEMG1 and SEMG2 in the cell model of pancreatic cancer.

While left-sided colonic diverticular disease is common in Western Caucasian populations, right-sided colonic disease (RCD) is rare. The present study aimed to determine the rate of RCD and to identify the symptoms, clinical features, treatment, and outcomes in a single medical center in Israel.Data for this descriptive retrospective analysis were collected from the electronic medical records of all patients diagnosed with colonic diverticulitis from January 2014 to June 2019.During the study period, 1000 patients with diverticulitis were admitted to our institution, of which 99 had RCD (10%). Mean age was 50.2 years. The main presenting symptom was acute onset of right-sided abdominal pain. The diagnosis was made almost exclusively by computed tomography scan and the cecum was the most frequent site. The clinical course was benign, without major complications for most patients (90.1%). Nine patients presented with abscess (n = 1), covered perforation (n = 7), or partial obstruction (n = 1). All patients were treated with intravenous antibiotics with a median length of hospital stay of 3 days and a median 9 days of antibiotic treatment. Only 1 patient underwent diagnostic laparoscopy due to suspected intestinal perforation. Three patients experienced disease recurrence after a median follow-up of 48 months. Upon recovery, half of the patients underwent colonoscopy; no further pathology was found in any.Unlike sigmoid colon diverticulitis, the incidence of RCD in Western populations is low. The clinical course is benign, with conservative treatment without the need for surgery. The complication and recurrence rates are low.

At the turn of the 20th century, researchers and clinicians compared case studies of patients diagnosed with hysteria and mediums who claimed to channel spirits based on alterations they observed in their sense of self. Yet, notwithstanding its early promise, this comparative approach to such "nonordinary experiences" (NOEs) was never fully realized due to disciplinary siloing and the challenges involved in comparing culture-laden accounts. Today, psychologists tend to reify constructs, such as religious or spiritual, extraordinary (e.g., psychical, paranormal, anomalous, or exceptional), and psychopathological. In doing so, they face an unresolved challenge: experiences with phenomenologically distinct features may be appraised similarly within a culture (i.e., viewed as evidence for the same culturally specific construct) and experiences that share phenomenological features may be appraised differently across cultures. Here, we call for a renewed approach to comparing NOEs across cultures that prioritizes subjectively recognizable features instead of constructs. First, we review the history of the comparative approach in psychology and where it is today. Second, we introduce a feature-based approach, building on the event cognition literature, in which "lived experiences" are broken down into their phenomenological features and the claims made about them. Third, we propose ways in which cultural learning shapes experiences, and possibly the ordinary-nonordinary distinction itself. We conclude by highlighting that by building on and shifting the focus of previous efforts, the feature-based approach provides a way to compare experiences at the population level. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

SARS-CoV-2 Omicron strain emergence raised concerns that its enhanced infectivity is partly due to altered spread/contamination modalities. We therefore sampled high-contact surfaces and air in close proximity to patients who were verified as infected with the Omicron strain, using identical protocols applied to sample patients positive to the original or Alpha strains. Cumulatively, for all 3 strains, viral RNA was detected in 90 of 168 surfaces and 6 of 49 air samples (mean cycle threshold [Ct]=35.2±2.5). No infective virus was identified. No significant differences in prevalence were found between strains.

When explaining why an event occurred, people intuitively highlight some causes while ignoring others. How do people decide which causes to select? Models of causal judgment have been evaluated in simple and controlled laboratory experiments, but they have yet to be tested in a complex real-world setting. Here, we provide such a test, in the context of the 2020 U.S. presidential election. Across tens of thousands of simulations of possible election outcomes, we computed, for each state, an adjusted measure of the correlation between a Biden victory in that state and a Biden election victory. These effect size measures accurately predicted the extent to which U.S. participants (N = 207, preregistered) viewed victory in a given state as having caused Biden to win the presidency. Our findings support the theory that people intuitively select as causes of an outcome the factors with the largest standardized causal effect on that outcome across possible counterfactual worlds.