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PURPOSE: Multiple studies have indicated that cyclooxygenase-2 (COX-2) inhibitors may prevent colon cancer, which is one of the leading causes of cancer death in the western world. Recent studies, however, [...]

Five-year survival of patients with stage IV epithelial ovarian carcinoma not treated after recurrence is almost non-existent in oncological literature. The authors report a patient almost 30 years after surgery of the primary epithelial ovarian carcinoma lesion and 15 years after recurrent disease and incomplete chemotherapy who is alive without evidence of disease. She received no conventional oncological therapy during the past 15 years but rather used many types of alternative medicine, predominantly mind body therapies. The authors review the relevant literature on this subject and describe what they believe to be the first report of long-term survival of such a patient. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic SARS-CoV-2 infection can significantly increase the spread of the COVID-19 pandemic. We aimed to investigate the epidemiological and clinical predictors of occult serologically confirmed SARS-CoV-2 cases among the general population during the fourth vaccination era in Israel. Methods: We conducted a cross-sectional study among individuals aged ≥18 years who had not been tested for COVID-19 in the preceding 5 months. Occult serologically confirmed cases were based on the presence of anti-N IgG antibodies. Potential risk factors were examined. Multivariable regression analysis identified independent predictors of subclinical SARS-CoV-2 infection. Results: This study included 504 participants. The prevalence of occult serologically confirmed SARS-CoV-2 was 12.5%. Chronic disease was found to be an independent predictor for the absence of occult disease (aOR) 0.4 [95% (CI): 0.18-0.87], p -value = 0.02). No significant differences were observed in age, sex, marital status, number of children, vaccination status, or exposure to COVID-19 infection between participants with and without SARS-CoV-2 sub-infection. Conclusions: We found a lower prevalence of occult serologically confirmed SARS-CoV-2 cases, compared to previous reports, and a negative correlation between chronic disease and occult SARS-CoV-2. Continued research, surveillance, and intervention strategies are needed to optimize long-term health outcomes and provide valuable insights for public health policymakers and clinicians.

Categorization is the foundation of many cognitive functions. Importantly, the categories we use to structure the world are informed by the language we speak. For example, whether we perceive dark blue, light blue, and green to be shades of one, two, or three different colors depends on whether we speak Berinmo, English, or Russian, respectively. Different languages, then, differ by how granular their categories are, but the source of these differences is still poorly understood. Understanding the source of cross-linguistic differences in linguistic categorization is important because categorization influences communicative efficiency and cognitive performance. Here we use computational simulations to show that community structure and specifically community size and community interconnectivity influence the categorization systems that communities create. In particular, the simulations show that the obstacles for diffusion that large communities encounter push them to develop categorization systems that are more expressive and better understood, but only if they have sufficiently long memory to do so. The simulations also show that larger communities are better at creating useful references to rarely communicated meanings, thus further boosting communication in these cases. These findings demonstrate how taking social structure, and especially community size, into account can illuminate why languages evolved to have their current forms. They further show how social constraints, such as those encountered by large communities, can drive the creation of better and more robust systems. As categorization is a building block for many cultural products, these results also have implications for our understanding of cultural evolution more broadly. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m 2 , autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%-smokers, 30.4%-non-White, 22.8%-elderly, 20.8%-ECOG PS ≥ 2, 15.7%-history of AIDs, and 4.7%-history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, p < 0.001). An ECOG PS of ≥2 (HR = 2.01, p < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, p < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.

Amid the COVID-19 outbreak, Israel and numerous other governments closed schools as a precaution, leading to a sudden shift to online learning. The aim of the current study is to provide foundational insight into the perceived readiness of the school system to withstand future adversities, based on the challenges, complexities, as well as successes in adaptation faced by stakeholders during COVID-19. In this cross-sectional study, we assess the perceived levels of functional resilience of the school system among the key stakeholders of the Israeli education system-high school students, parents, teachers, and principals, as well as a composite functional resilience scale. The composite functional resilience consists of 10 main indexes: communication during distance learning (DL) and frontal learning (FL); Perceived stress scale-4 (PSS); psychosocial aspects during distance learning (DL) and frontal learning (FL); digital literacy; pedagogic support; resources; infrastructure; and distance versus frontal learning. The study findings demonstrate differences according to the stakeholders with regard to the perceived functional resilience and the composite functional resilience scores (e.g., students with respect to both of these scores exhibit the lowest results, while teachers display the highest scores). Furthermore, no one variable was significant across the board for all stakeholders in predicting the perceived functional resilience, with the most common predictors among the stakeholders being digital literacy, pedagogic support, PSS, as well as communication during distance and frontal learning. The findings of this study reveal areas for recommended priority actions to be conducted among school system stakeholders., (© 2024. The Author(s).)

The following narrative review embarks on a comprehensive exploration of the role played by the gut microbiome within the Diet-Microbiota-Immunity (DMI) tripartite, aiming to enhance anti-cancer immunotherapy efficacy. While revolutionizing cancer treatment, resistance to immunotherapy and immune-related adverse events (irAEs) remain challenges. The tumor microenvironment (TME), shaped by cancer cells, influences immunotherapy resistance. The gut microbiome, influenced by genetics, environment, diet, and interventions, emerges as a critical player in TME reshaping, thereby modulating immune responses and treatment outcomes. Dietary patterns like the Mediterranean diet, caloric restriction modifications, and specific nutritional components show promise in influencing the tumor microenvironment and gut microbiome for better treatment outcomes. Antibiotics, disrupting gut microbiota diversity, may compromise immunotherapy efficacy. This review emphasizes the need for tailored nutritional strategies to manipulate microbial communities, enhance immune regulation, and improve immunotherapy accessibility while minimizing side effects. Ongoing studies investigate the impact of dietary interventions on cancer immunotherapy, pointing toward promising developments in personalized cancer care. This narrative review synthesizes existing knowledge and charts a course for future investigations, presenting a holistic perspective on the dynamic interplay between dietary interventions, the gut microbiome, and cancer immunotherapy within the DMI tripartite., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest regarding the research, authorship, and/or publication of this article.

Despite decades of stress research, there still exist substantial gaps in our understanding of how social, environmental, and biological factors interact and combine with developmental stressor exposures, cognitive appraisals of stressors, and psychosocial coping processes to shape individuals' stress reactivity, health, and disease risk. Relatively new biological profiling approaches, called multi-omics, are helping address these issues by enabling researchers to quantify thousands of molecules from a single blood or tissue sample, thus providing a panoramic snapshot of the molecular processes occurring in an organism from a systems perspective. In this review, we summarize two types of research designs for which multi-omics approaches are best suited, and describe how these approaches can help advance our understanding of stress processes and the development, prevention, and treatment of stress-related pathologies. We first discuss incorporating multi-omics approaches into theory-rich, intensive longitudinal study designs to characterize, in high-resolution, the transition to stress-related multisystem dysfunction and disease throughout development. Next, we discuss how multi-omics approaches should be incorporated into intervention research to better understand the transition from stress-related dysfunction back to health, which can help inform novel precision medicine approaches to managing stress and fostering biopsychosocial resilience. Throughout, we provide concrete recommendations for types of studies that will help advance stress research, and translate multi-omics data into better health and health care.

Despite great interest in how dynamic fluctuations in psychological states such as mood, social safety, energy, present-focused attention, and burnout impact stress, well-being, and health, most studies examining these constructs use retrospective assessments with relatively long time-lags. Here, we discuss how ecological momentary assessments (EMAs) address methodological issues associated with retrospective reports to help reveal dynamic associations between psychological states at small timescales that are often missed in stress and health research. In addition to helping researchers characterize daily and within-day fluctuations and temporal dynamics between different health-relevant processes, EMAs can elucidate mechanisms through which interventions reduce stress and enhance well-being. EMAs can also be used to identify changes that precede critical health events, which can in turn be used to deliver ecological momentary interventions, or just-in-time interventions, to help prevent such events from occurring. To enable this work, we provide examples of scales and single-item questions used in EMA studies, recommend study designs and statistical approaches that capitalize on EMA data, and discuss limitations of EMA methods. In doing so, we aim to demonstrate how, when used carefully, EMA methods are well poised to greatly advance our understanding of how intrapersonal dynamics affect stress levels, well-being, and human health.

Introduction: Preparing the school system for a future crisis requires the ability to examine the effectiveness of schools' functioning during distant learning and their level of preparedness for future crises. Functional resilience (FR) is defined as the ability to maintain vital operational continuity in the face of disturbance. The study objectives included to develop a FR index of schools and to evaluate and validate it., Methods: To enable examination of the study objectives, the study design included tool development, followed by a validation process among 20 content experts. Concurrently, an eDelphi process for building an inclusive index, based on various components of resilience was conducted. The final study tool consists of four tailored questionnaires to examine perceptions of key stakeholders, i.e.- teachers, principals, parents, and highschool students regarding communication, psychosocial aspects, perceived stress, infrastructure, resources, pedagogic support, digital literacy, and perceived FR. Using an internet panel, the tool was disseminated cross-sectionally among the four groups of stakeholders., Results: The results showed high reliability of most of the scales developed. Furthermore, a high consensus level was reached on the relative importance of each component/ stakeholder to the schools FR. The findings further suggest that there were no significant differences in the composite FR score based on characteristics such as school type/ size/geographic location. However, the findings revealed interesting variations among stakeholders, with findings suggesting greater vulnerability among some., Discussion: To increase resilience and preparedness for future adversities that school systems may face, it is recommended to periodically incorporate an assessment based on a structured tool., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kaim, Siman-Tov, Adini and Lev-ari.)

Mental health disorders are an increasing global public health concern that contribute to morbidity, mortality, disability, and healthcare costs across the world. Biomedical and psychological research has come a long way in identifying the importance of mental health and its impact on behavioral risk factors, physiological health, and overall quality of life. Despite this, access to psychological and psychiatric services remains widely unavailable and is a challenge for many healthcare systems, particularly those in developing countries. This review article highlights the strengths and opportunities brought forward by digital mental health in narrowing this divide. Further, it points to the economic and societal benefits of effectively managing mental illness, making a case for investing resources into mental healthcare as a larger priority for large non-governmental organizations and individual nations across the globe.

The distribution of word order across languages is skewed with SOV order (e.g., researchers sentences write) and SVO order (e.g., researchers write sentences) being >100 times more common than OSV order (sentences researchers write). It is commonly assumed that cross-linguistic preferences reflect cognitive biases, but it is unknown why some languages exhibit dispreferred patterns, or why languages settle on a specific pattern out of several preferred ones. This paper tests whether larger communities are more likely to rely on cross-linguistically preferred patterns as a way to overcome the greater communicative challenges they encounter. Participants played a communication game in large groups, small groups, or alone. Results support the hypothesis that community size influences word order as well as suggest that SOV and SVO orders are prevalent for different reasons with SVO specifically addressing communicative pressures. The studies thus show how community structure can give rise to cross-linguistic preferences, when these preferences can be overridden, and suggest how language might change with changes in social structure., (Copyright © 2023 The Author. Published by Elsevier B.V. All rights reserved.)

Background: Immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) are often managed via immunosuppressive agents (ISAs); however, their impact on ICI efficacy is not well studied. The impact of the use of ISAs on ICI efficacy in patients with advanced melanoma was therefore investigated., Methods: This is a real-world, multicenter, retrospective cohort study of patients with advanced melanoma who received ICIs (n = 370). Overall survival (OS) and time to treatment failure (TTF) from the time of ICI initiation were compared among patients in subgroups of interest by unadjusted and 12-week landmark sensitivity-adjusted analyses. The association of irAEs and their management with OS and TTF were evaluated using univariate and multivariable Cox proportional hazards regression models., Results: Overall, irAEs of any grade and of grade ≥3 occurred in 57% and 23% of patients, respectively. Thirty-seven percent of patients received steroids, and 3% received other ISAs. Median OS was longest among patients receiving both (not reached [NR]), shorter among those receiving only systemic steroids (SSs) (84.2 months; 95% CI, 40.2 months to NR), and shortest among those who did not experience irAEs (10.3 months; 95% CI, 6-20.1 months) (p < .001). Longer OS was significantly associated with the occurrence of irAEs and the use of SSs with or without ISAs upon multivariable-adjusted analysis (p < .001). Similar results were noted with anti-programmed death 1 (PD-1) monotherapy and combination anti-PD-1 plus anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) therapy, and with 12-week landmark sensitivity analysis (p = .01)., Conclusions: These findings in patients with melanoma who were treated with ICIs suggest that the use of SSs or ISAs for the management of irAEs is not associated with inferior disease outcomes, which supports the use of these agents when necessary., (© 2023 American Cancer Society.)

Why do swear words sound the way they do? Swear words are often thought to have sounds that render them especially fit for purpose, facilitating the expression of emotion and attitude. To date, however, there has been no systematic cross-linguistic investigation of phonetic patterns in profanity. In an initial, pilot study we explored statistical regularities in the sounds of swear words across a range of typologically distant languages. The best candidate for a cross-linguistic phonemic pattern in profanity was the absence of approximants (sonorous sounds like l, r, w and y). In Study 1, native speakers of various languages (Arabic, Chinese, Finnish, French, German, Spanish; N = 215) judged foreign words less likely to be swear words if they contained an approximant. In Study 2 we found that sanitized versions of English swear words - like darn instead of damn - contain significantly more approximants than the original swear words. Our findings reveal that not all sounds are equally suitable for profanity, and demonstrate that sound symbolism - wherein certain sounds are intrinsically associated with certain meanings - is more pervasive than has previously been appreciated, extending beyond denoting single concepts to serving pragmatic functions., (© 2022. The Author(s).)

Purpose: Cancer is the second leading cause of death globally. However, by implementing evidence-based prevention strategies, 30%-50% of cancers can be detected early with improved outcomes. At the integrated cancer prevention center (ICPC), we aimed to increase early detection by screening for multiple cancers during one visit., Methods: Self-referred asymptomatic individuals, age 20-80 years, were included prospectively. Clinical, laboratory, and epidemiological data were obtained by multiple specialists, and further testing was obtained based on symptoms, family history, individual risk factors, and abnormalities identified during the visit. Follow-up recommendations and diagnoses were given as appropriate., Results: Between January 1, 2006, and December 31, 2019, 8,618 men and 8,486 women, average age 47.11 ± 11.71 years, were screened. Of 259 cancers detected through the ICPC, 49 (19.8%) were stage 0, 113 (45.6%) stage I, 30 (12.1%) stage II, 25 (10.1%) stage III, and 31(12.5%) stage IV. Seventeen cancers were missed, six of which were within the scope of the ICPC. Compared with the Israeli registry, at the ICPC, less cancers were diagnosed at a metastatic stage for breast (none v 3.7%), lung (6.7% v 11.4%), colon (20.0% v 46.2%), prostate (5.6% v 10.5%), and cervical/uterine (none v 8.5%) cancers. When compared with the average stage of detection in the United States, detection was earlier for breast, lung, prostate, and female reproductive cancers. Patient satisfaction rate was 8.35 ± 1.85 (scale 1-10)., Conclusion: We present a proof of concept study for a one-stop-shop approach to cancer screening in a multidisciplinary outpatient clinic. We successfully detected cancers at an early stage, which has the potential to reduce morbidity and mortality as well as offer substantial cost savings.[Media: see text].

Background: Early in the COVID-19 pandemic, reports about a possible protective effect of nicotine on COVID-19 conflicted with messaging by public health organizations about increased risks of COVID-19 due to smoking. The ambiguous information the public received, combined with COVID-19-induced anxiety, may have led to changes in tobacco or other nicotine product use. This study examined changes in use of combustible cigarettes (CCs), nargila (hookah/waterpipe), e-cigarettes, and IQOS and home-smoking behaviors. We also assessed COVID-19 related anxiety and perceptions regarding changes in risk of COVID-19 severity due to smoking., Methods: We used cross-sectional data from a population telephone survey that was conducted in Israel in the early phase of the COVID-19 pandemic (May-June 2020) and included 420 adult (age 18+) individuals who reported having ever used CCs (n = 391), nargila (n = 193), and/or electronic cigarettes (e-cigarettes)/heated tobacco products (e.g., IQOS) (n = 52). Respondents were asked about the effect that COVID-19 had on their nicotine product use (quit/reduced use, no change, increased use). We assessed changes in product use, risk perceptions, and anxiety using adjusted multinomial logistic regression analyses., Results: Most respondents did not change their frequency of product use (CCs: 81.0%, nargila: 88.2%, e-cigarettes/IQOS: 96.8%). A small percentage either decreased use (CCs: 7.2%, nargila: 3.2%, e-cigarettes/IQOS:2.4%) or increased use (CCs:11.8%, nargila:8.6%, e-cigarettes/IQOS:+ 0.9%). 55.6% of respondents used a product in the home prior to COVID-19; but during the first lockdown COVID-19 period, a greater percentage increased (12.6%) than decreased (4.0%) their home use. Higher levels of anxiety due to COVID-19 were associated with increased home smoking (aOR = 1.59, 95% CI:1.04-2.42, p = 0.02). Many respondents believed that increased severity of COVID-19 illness was associated with CCs (62.0%) and e-cigarettes/vaping (45.3%), with uncertainty about the association being lower for CCs (20.5%) than for vaping (41.3%)., Conclusions: While many respondents believed that nicotine product use (particularly CCs and e-cigarettes) was associated with increased risk of COVID-19 disease severity, the majority of users did not change their tobacco/nicotine use. The confusion about the relationship between tobacco use and COVID-19 calls for clear evidence-based messaging from governments. The association between home smoking and increased COVID-19-related stress suggests the need for campaigns and resources to prevent smoking in the home, particularly during times of stress., (© 2023. The Author(s).)

A classic example of the arbitrary relation between the way a word sounds and its meaning is that microorganism is a very long word that refers to a very small entity, whereas whale is a very short word that refers to something very big. This example, originally presented in Hockett's list of language's design features, has been often cited over the years, not only by those discussing the arbitrary nature of language, but also by researchers of sound symbolism. While the two groups disagreed regarding the role of arbitrariness and sound symbolism in language, they both agreed there is a nonsound symbolic relation between word length and entity size in this case. This paper shows that the length of the words whale and microorganism in fact reflects a sound symbolic pattern. An analysis of >600 languages from >100 language families shows that languages use longer words to denote the concept small than they do to denote the concept big. The paper thus shows how explicit judgments might differ from implicit cognitive association and the problem of relying on these in sound symbolism research., (© 2023 The Authors. Cognitive Science published by Wiley Periodicals LLC on behalf of Cognitive Science Society (CSS).)

In response to the COVID-19 pandemic, many governments ordered school closures as a containment measure, with Israel being among over 100 countries to do so. This resulted in the abrupt shift to online and remote education for many students. Despite attempts to minimize the effects of disrupted education and create a dynamic virtual learning environment, the literature highlights various challenges including lack of communication with implications of distress faced by key stakeholders (students and their parents, teachers, and principals). In this cross-sectional study, we assess the perceived levels of communication and psychosocial aspects during both distance and frontal learning, as well as the long-term impacts (following over two and a half years of an ongoing pandemic) on distress among the key stakeholders of the Israeli education system- high school students, parents, teachers, and principals. The study findings demonstrate severe implications of distance learning on communication and psychosocial aspects, with lingering long-term impacts on distress, among all stakeholders (particularly among students). This reveals the need for tailored capacity building and resilience intervention programs to be integrated in the long-term response to the current ongoing pandemic to improve well-being and reduce distress among the various stakeholders, with particular attention to those that are most vulnerable and were hit the hardest.

(1) Background: Multiple Sclerosis (MS) is a chronic, progressive, immune-mediated disorder that affects the Central Nervous System and is the most common cause of non-traumatic neurological disability in young adults. The study aimed to assess the levels of stress, resilience, well-being, sleep quality, and fatigue in Israeli people with MS (PwMS), and to examine the associations between these factors and the sociodemographic and clinical characteristics. These factors had never before been studied in conjunction in PwMS, nor had they been systematically addressed in Israel, the unique geopolitical situation of which may pose unique challenges. (2) Methods: This was a survey-based, cross-sectional study conducted through an Internet platform. (3) Results: Israeli PwMS who participated in the study were experiencing relatively high levels of stress and low resilience, poor sleep quality, and severe fatigue. The analysis revealed significant associations between resilience and stress, well-being, and anxiety, as well as stress and well-being, resilience, sleep quality, fatigue, and Clinically Isolated Syndrome (CIS). (4) Conclusions: the Israeli PwMS who participated in the study were experiencing higher levels of stress, lower resilience and worse sleep quality than PwMS in other countries, as compared to results previously reported in literature. The findings of this study ought to serve as a call to action for the MS care providers in Israel and warrant further research into the possible causes of the phenomenon and strategies to address it.

A small but significant proportion of COVID-19 patients develop life-threatening cytokine storm. We have developed a new anti-inflammatory drug, EXO-CD24, a combination of an immune checkpoint (CD24) and a delivery platform (exosomes). CD24 inhibits the NF-kB pathway and the production of cytokines/chemokines. EXO-CD24 discriminates damage-from pathogen-associated molecular patterns (DAMPs and PAMPs) therefore does not interfere with viral clearance. EXO-CD24 was produced and purified from CD24-expressing 293-TREx™ cells. Exosomes displaying murine CD24 (mCD24) were also created. EXO-CD24/mCD24 were characterized and examined, for safety and efficacy, in vitro and in vivo. In a phase Ib/IIa study, 35 patients with moderate-high severity COVID-19 were recruited and given escalating doses, 10 8 -10 10 , of EXO-CD24 by inhalation, QD, for 5 days. No adverse events related to the drug were observed up to 443-575 days. EXO-CD24 effectively reduced inflammatory markers and cytokine/chemokine, although randomized studies are required. EXO-CD24 may be a treatment strategy to suppress the hyper-inflammatory response in the lungs of COVID-19 patients and further serve as a therapeutic platform for other pulmonary and systemic diseases characterized by cytokine storm., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Immune-related adverse events (irAEs) often require treatment with high-dose systemic steroids (SS) and other immunosuppressive agents (ISAs). NCCN Guidelines recommend prophylactic antibiotics for Pneumocystis jirovecii pneumonia (PJP) for patients receiving prolonged SS/ISAs. However, there is a paucity of evidence regarding the incidence of opportunistic infections (OIs) and non-OIs and the role of prophylactic antibiotics in patients on SS/ISAs for irAEs., Methods: A retrospective analysis was conducted of patients treated using immune checkpoint inhibitor (ICI) therapy at 5 MedStar Health hospitals from January 2011 to April 2018. OIs were defined per the Infectious Diseases Society of America guidelines for the prevention and treatment of OIs in patients with HIV. The study cohort included patients who received ≥20 mg daily of a prednisone equivalent for ≥4 weeks to manage irAEs., Results: The study cohort identified 112 (15%) of 758 total patients treated using ICIs. Baseline characteristics included the following: median age was 64 years, 74% (n=82) of patients were White, 89% (n=100) had an ECOG performance status ≤1, 61% (n=68) had melanoma, 19% (n=21) had non-small cell lung cancer, 45% (n=50) were treated using an anti-PD-(L)1 ICI, and 33% (n=37) were treated using an anti-PD-1/anti-CTLA-4 combination. The median starting SS dose was 100 mg of a prednisone equivalent, and 25% of patients required additional ISAs, with infliximab (n=15) and mycophenolate mofetil (n=9) being the most common. We found that 20% (n=22) of patients developed any infection, including 7% (n=8) with OIs (oral candidiasis [n=4], nondisseminated varicella zoster infection [n=2], PJP [n=1], and Listeria monocytogenes endophthalmitis [n=1]) and 13% (n=14) with non-OIs (most common: Clostridium difficile and pneumonia [n=5 each]). PJP prophylaxis with sulfamethoxazole/trimethoprim was given to 13% (n=14) patients, of whom 43% (n=6) developed OIs/non-OIs., Conclusions: Our study highlights the fundamental issues for patients on ICI therapy who require SS/ISAs for irAEs: the degree of immunosuppression and the relative risk of OI. We noted a low incidence of OIs overall and breakthrough infections despite PJP prophylaxis. We question whether PJP prophylaxis is efficacious or necessary. Prospective trials are required to answer these questions.

(1) Background: Social distancing became a central strategy employed to limit the spread of the SARS-CoV-2 virus. We explore self-reported adherence (SRA) and factors associated with SRA among Israeli adults at the end of the first national lockdown in Israel. (2) Methods: We conducted a cross-sectional consumer panel survey of 820 Israeli adults aged 18 to 70 in May and June 2020. We collected data on the SRA to the social distancing measures, sociodemographic variables, perceptions of pandemic-related danger and of protection provided by the social distancing measures, as well as Sense of Coherence (SoC). (3) Results: 60% of respondents reported complying with 7 measures. Higher SoC was associated with higher SRA (p = 0.04), and was related to income, marital status, age, profession, and education. The SRA was higher among Jews than Arabs (Jews: Mean = 10.5, SD = 4.5; Arabs: Mean = 9.1, SD = 4.1, p < 0.001) and among males (Males: Mean = 10.8, SD = 4.7; Females: Mean = 9, SD = 4.1; p = 0.003). SoC, perception of protection and perception of danger were associated with higher SRA (p = 0.42, p < 0.001 and p = 0.005 respectively). Single people reported higher levels of SRA than people in relationships (Partnered: Mean = 9.7, SD = 4.2, Non-partnered: Mean = 10.9, SD = 4.7, p = 0.033). (4) Conclusions: At the time of exit from the first lockdown, compliance with social distancing measures was high, with Jewish, single and male Israelis more likely to adhere to the guidelines. We identified the populations at risk for non-adherence and associated factors, reporting for the first time the correlation between SoC and SRA. Further research is needed to assess the role of these factors in Jewish and Arab populations.

Purpose: Compare recovery rates between active young (Y) and middle-aged (MA) males up to 48H post aerobically based, exercise-induced muscle damage (EIMD) protocol. A secondary aim was to explore the relationships between changes in indices associated with EIMD and recovery throughout this timeframe. Methods: Twenty-eight Y ( n = 14, 26.1 ± 2.9y, 74.5 ± 9.3 kg) and MA ( n = 14, 43.6 ± 4.1y, 77.3 ± 12.9 kg) physically active males, completed a 60-min downhill running (DHR) on a treadmill at -10% incline and at 65% of maximal heart rate (HR). Biochemical, biomechanical, psychological, force production and muscle integrity (using MRI diffusion tensor imaging) markers were measured at baseline, immediately-post, and up to 48H post DHR. Results: During the DHR, HR was lower ( p < 0.05) in MA compared to Y, but running pace and distance covered were comparable between groups. No statistical or meaningful differences were observed between groups for any of the outcomes. Yet, Significant ( p < 0.05) time-effects within each group were observed: markers of muscle damage, cadence and perception of pain increased, while TNF-a, isometric and dynamic force production and stride-length decreased. Creatine-kinase at 24H-post and 48H-post were correlated ( p < 0.05, r range = -0.57 to 0.55) with pain perception, stride-length, and cadence at 24H-post and 48H-post. Significant ( p < 0.05) correlations were observed between isometric force production at all time-points and IL-6 at 48H-post DHR ( r range = -0.62 to (-0.74). Conclusion: Y and MA active male amateur athletes recover in a comparable manner following an EIMD downhill protocol. These results indicate that similar recovery strategies can be used by trainees from both age groups following an aerobic-based EIMD protocol., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Markus, Constantini, Goldstein, Amedi, Bornstein, Stolkovsky, Vidal, Lev-Ari, Balaban, Leibou, Blumenfeld-Katzir, Ben-Eliezer, Peled, Assaf, Jensen, Constantini, Dubnov-Raz, Halperin and Gepner.)

The way we process language is influenced by our experience. We are more likely to attend to features that proved to be useful in the past. Importantly, the size of individuals' social network can influence their experience, and consequently, how they process language. In the case of voice recognition, having a larger social network might provide more variable input and thus enhance the ability to recognise new voices. On the other hand, learning to recognise voices is more demanding and less beneficial for people with a larger social network as they have more speakers to learn yet spend less time with each. This paper tests whether social network size influences voice recognition, and if so, in which direction. Native Dutch speakers listed their social network and performed a voice recognition task. Results showed that people with larger social networks were poorer at learning to recognise voices. Experiment 2 replicated the results with a British sample and English stimuli. Experiment 3 showed that the effect does not generalise to voice recognition in an unfamiliar language suggesting that social network size influences attention to the linguistic rather than non-linguistic markers that differentiate speakers. The studies thus show that our social network size influences our inclination to learn speaker-specific patterns in our environment, and consequently, the development of skills that rely on such learned patterns, such as voice recognition.

The objective of this study was to estimate the probability of long-term overall survival based on total number of risk factors (RF). We also sought to examine the role of midlife clinical, behavioral, and psychosocial predictors of longevity in a large cohort of Israeli men. This study was based on the Israeli Ischemic Heart Disease (IIHD) cohort that included over 10,000 men who were followed up for mortality over more than four decades. During the 43 years of follow-up, 4634 (46.1%) men survived to 80 years of age or older. We considered cigarette smoking, diabetes mellitus, high systolic blood pressure, hypercholesterolemia, low socioeconomic status, and serious family problems as RF at ages 40-65. Cox proportional hazards regression models, with age as the time scale, were constructed to estimate the hazard ratios (HRs) for failure to survive 80 years of age. Compared with men free of all the above RF, those with one identified RF (HR = 1.58, 95% CI: 1.42-1.75) and counterparts with two identified RF (HR = 2.18, 95% CI: 1.96-2.43) were at a significantly greater risk of death before 80. Additional RF further increased the risk of early mortality (HR = 3.62, 95% CI: 1.50-8.73 for men with 5 RF). The results suggest a role of physiological, behavioral, and psychological risk factors at midlife in predicting longevity.

Importance: The high risk for breast and ovarian cancers conferred by being a carrier of BRCA1 or BRCA2 germline variant can negatively impact physical and psychological well-being. Novel nonpharmacological interventions on well-being in women with BRCA variants have rarely been reported., Objective: To determine the effect of a 12-week inquiry-based stress reduction (IBSR) program on psychological well-being, sleep quality, psychosocial variables, and attitudes toward risk-reducing surgical procedures among women in Israel who carried BRCA variants., Design, Setting, and Participants: This randomized clinical trial had a 12-week intervention period and a 12-week follow-up period. It was conducted between April 1, 2017, and July 31, 2020. Participants were recruited from the Meirav Breast Center at the Sheba Medical Center, Israel, and the intervention was conducted in Tel Aviv, Israel. The cohort included women with BRCA variants. Data were analyzed from August 1 to December 1, 2020., Interventions: Women were randomly assigned to the 12-week IBSR program or standard care. The IBSR technique is based on the skills of mindfulness, inquiry, and cognitive reframing. The intervention included standardized, weekly group meetings conducted throughout 12 weeks. Standard care included semi-annual breast examinations and breast magnetic resonance imaging (alternating), a gynecological examination, a transvaginal ultrasonographic examination, and CA-125 serum determination. Differences between the groups were tested using mixed-effects models in an intent to treat analysis., Main Outcomes and Measures: The primary outcome was psychological well-being, including 6 parameters: autonomy, personal growth, positive relationships, control of the environment, goals in life, and self-acceptance. Secondary outcomes included sleep quality, attitudes toward risk-reducing surgical procedures, and psychosocial variables. Questionnaires were administered at baseline (T1), at completion of the 12-week intervention (T2), and 12 weeks after completion of the intervention (T3)., Results: Overall, 100 women (mean [SD] age, 41.37 [11.06] years) completed the study, with 50 randomized to the intervention group and 50 randomized to the control group. Mean (SD) time from variant discovery was 4.7 (3.3) years. There were no differences between the intervention and control groups in baseline mean (SD) scores of psychological well-being parameters (autonomy: 55.20 [11.12] vs 56.77 [9.90]; environmental control: 56.30 [11.98 vs 58.51 [11.41]; positive relationships: 63.10 [15.91] vs 68.10 [9.86]; goals in life: 60.00 [14.12] vs 64.82 [10.57]; self-acceptance: 55.02 [16.62] vs 60.32 [13.50]) except personal growth (63.70 [14.66] vs 68.85 [8.07]). The IBSR group, compared with the control group, experienced better mean (SD) scores on all psychological well-being parameters at T2 (autonomy: 63.64 [8.35] vs 54.73 [10.41]; environmental control: 63.95 [10.05] vs 57.45 [11.43]; personal growth: 73.00 [8.34] vs 65.76 [10.95]; positive relationships 71.17 [9.99] vs 65.06 [12.58]; goals in life: 67.57 [8.88] vs 61.18 [12.87]; self-acceptance: 66.93 [11.15] vs 58.09 [15.55]) and at T3 (autonomy: 62.68 [9.05] vs 56.12 [10.64]; environmental control: 64.55 [10.28] vs 59.35 [12.98]; personal growth: 72.00 [8.06] vs 67.15 [11.82]; positive relationships: 71.24 [9.78] vs 66.92 [12.37]; goals in life: 68.33 [8.54] vs 62.92 [13.24]; self-acceptance: 66.84 [11.35] vs 58.97 [17.03]). Individuals in the IBSR group also experienced statistically significant improvements in sleep quality (mean [SD]: T1, 7.35 [3.97]; T3, 4.63 [3.21], P < .001), whereas the control group experienced no statistically significant difference. Women in the intervention group had a more favorable consideration of risk-reducing oophorectomy, from 7 women (14%) who refused to consider oophorectomy at T1 to 1 woman (2%) who refused to consider it at T3 (P = .04), and similar change in consideration of mastectomy: from 23 women (46%) who refused to consider mastectomy at T1 to 13 women (29%) who refused to consider it at T3 (P < .001)., Conclusions and Relevance: This randomized clinical trial found that IBSR improved psychological well-being and led to a more favorable view on risk-reducing surgical procedures for at least 6 months among women in Israel who carried BRCA variants. These results suggest that IBSR may be implemented as a self-practice tool to enhance the well-being of individuals who carry BRCA variants and support them in their decision-making processes., Trial Registration: ClinicalTrials.gov Identifier: NCT03162276.

The COVID-19 pandemic imposed extreme living conditions of social distancing, which triggered negative mental health problems and created challenges in seeking mental health support. Mindfulness-based interventions (MBIs) have been found to enhance wellbeing and mental health by reducing stress and anxiety and improving emotion regulation. Preliminary evidence suggests that online, synchronous MBIs may produce beneficial effects similar to face-to-face programs. However, the effectiveness of such online-MBIs to support mental health in highly stressful times, such as a global pandemic, requires further study. To this end, we investigated the effect of an online 8-week Mindfulness-Based Stress Reduction (MBSR) program on aspects of mental health during the first wave of the COVID-19 pandemic. Participants ( N =92) who expressed interest in discounted online-MBSR programs were recruited for the study. The division into experimental and control groups was based on actual enrollment to the courses. Those who enrolled in a program were assigned to the experimental condition and those who decided not to enroll served as controls. Participants were assessed pre-intervention, post-intervention, and 1-month post-intervention for levels of mindfulness, perceived stress, anxiety, emotion regulation, and intolerance of uncertainty. Differences between the groups were tested using the general linear mixed effects model (GLMM) and Individual Growth Curve Models (IGCM) in intent to treat analysis. The findings indicated that, relative to the control group, MBSR improved mindfulness abilities ( p <0.001), decreased anxiety ( p <0.001), and stress ( p <0.001) and increased emotion regulation ( p <0.001). These effects were found to persist 1 month after the end of the program, despite the increased governmental public-health restrictions due to COVID-19 at that time. The ability to tolerate uncertainty, a central characteristic of the pandemic, was not found to be affected by the program. A mediation analysis revealed that the effect of the intervention on mental health improvement was partially mediated by the improvement in emotion regulation. Overall, the findings provide positive evidence for the feasibility of an online-MBSR program to support the mental health of individuals from the general population through the mediation of emotion regulation in challenging times, such as a global pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sanilevici, Reuveni, Lev-Ari, Golland and Levit-Binnun.)

Larger communities face more communication barriers. We propose that languages spoken by larger communities adapt and overcome these greater barriers by increasing their reliance on sound symbolism, as sound symbolism can facilitate communication. To test whether widely spoken languages are more sound symbolic, participants listened to recordings of the words big and small in widely spoken and less common languages and guessed their meanings. Accuracy was higher for words from widely spoken languages providing evidence that widely spoken languages harbor more sound symbolism. Preliminary results also suggest that widely spoken languages rely on different sound symbolic patterns than less common languages. Community size can thus shape linguistic forms and influence the tools that languages use to facilitate communication., (© 2021 Cognitive Science Society LLC.)

People are more likely to believe things that are easier to process. Foreign-accented speech is relatively difficult to process, and prior research shows that, correspondingly, people believe information less when it is delivered in a foreign accent rather than a native accent. Here we show that a short exposure to foreign accent can reduce this bias, and that the reduction in bias is due to improvement in the processing of the accent. These results demonstrate how cognitive aspects of language processing can influence attitudes. The results also suggest that ensuring exposure to foreign accent can reduce discrimination against nonnative speakers., (© 2021 Cognitive Science Society LLC.)

(1) Background: Self-esteem plays an important role in developing emotional resilience and wellbeing in children. Yet, there has been little related research on Cognitive Behavioral Group Therapy on this topic. Our aims were to assess the effect of the Child Self-Esteem CBT (CSE-CBT) protocol on children's self-esteem in grades five and six; to assess the effect of the CSE-CBT protocol on the therapeutic process; and to explore the feasibility of delivering the CSE-CBT protocol in a school setting. (2) Methods: Eighty elementary school children in grades five and six, divided into four intervention and four control groups, attended 12 structured sessions using the CSE-CBT protocol, led by specially trained teachers. The children completed questionnaires to assess their self-esteem at the beginning and at the end of the study, and answered weekly questionnaires that assessed therapeutic process. Hierarchical linear modeling was used to analyze the data. (3) Results: The CSE-CBT protocol had a significant effect on improving children's self-esteem over the course of the study, regardless of the children's working alliance with the teacher leading the group. (4) Conclusions: The findings suggest that the CSE-CBT protocol has the potential to benefit children's self-esteem and indicate that school teachers can be trained to administer the CBT-protocol.

Most evidence for an association between excess body weight and cancer risk has been derived from studies of relatively short duration with little reference to the effect on tumor site. This study was designed to evaluate the association between categories of body mass index (BMI: <20, 20-25, 25-30, and >30 kg/m 2 ) and the incidence of colon and lung cancer over 43 years of follow-up (1963-2006), in 10,043 men from the Israeli Ischemic Heart Disease (IIHD) prospective cohort (mean age at baseline 49.3 years, mean BMI 25.7 kg/m 2 ). Data from the Israel National Cancer Registry was linked with the IIHD, and the Cox proportional hazards regression model was applied to analyze the relative risks for lung and colon cancer across BMI categories at baseline. Three hundred cases of lung cancer (2.9%) and 328 cases of colon cancer (3.3%) were diagnosed in the total population. Applying a multivariate model adjusted for age, smoking intensity, and total cholesterol, higher BMI category was associated with an increased risk of colon cancer [HR = 1.22 (95% CI 1.02-1.45)], and with a decreased risk for lung cancer [HR = 0.66 (95% CI 0.56-0.77)]. In this long-term follow-up study over four decades, we observed a consistent dose-response pattern between BMI and increased risk for colon cancer, but decreased risk for lung cancer. Specific associations between excess body weight and cancer risk may suggest different patterns of body fat and cancer incidence at a given site.

The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a biomarker for the early detection of cancer. There are currently no studies that assess predictors of CD24 in blood tests among healthy individuals. Our aims were (1) to evaluate predictors of the CD24/CD11b biomarker among healthy subjects and (2) to assess CD24/CD11b levels of participants with and without benign tumors. Our cohort included 1640 healthy subjects, aged 20-85, recruited at the Health Promotion and Integrated Cancer Prevention Center (ICPC) in the Tel Aviv Medical Center. Eligible subjects completed a detailed questionnaire on medical history and other epidemiologic information. CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results showed that the average levels of CD24/CD11b in healthy patients (22.8 ± 9.3) was statistically significant lower compared to subjects with benign cancers (26.1 ± 10.5, p < 0.001). Our multivariable analysis demonstrated that elevated levels of CRP (coefficient β: 1.98, p = 0.011) were significantly associated with high levels of CD24/CD11b expression among healthy participants. Other risk factors of cancer were not associated with elevated CD24 levels among healthy subjects. In conclusion, our findings may assist in further development and optimization of the CD24/CD11b biomarker to serve as a cancer screening test for early detection of cancer among the healthy population.

Background and Objective: While there are multiple studies on the anti-tumoral effects of Panax ginseng as active ingredients (one or more ginsenosides derived from the extract) or as a whole plant extract, there is a lack of studies to assess the effects Panax ginseng's of active ingredients combined with the whole plant extract. Our aim was to study the effect of whole ginseng, enriched in the anti-tumoral Rh2 component and other ginsenosides (Ginseng Rh2+), on the metastatic capacity of non-small cell lung cancer (NSCLC)., Methods: We evaluated the effects of Ginseng Rh2+ on survival, migration and motility, induction of apoptosis, and expression of its apoptosis-related proteins in non-small cell lung cancer (NSCLC) cells in vitro and on primary tumor growth and metastatic capacity in a syngeneic mouse lung cancer model in vivo. The effects of Ginseng Rh2+ on NSCLC cells were studied in vitro using: a colorimetric tetrazolium salt (XTT) assay, annexin V-FITC/PI, western blotting, wound healing motility assay, Transwell migration and cell adhesion assays. In vivo, mice were inoculated with Lewis mouse lung carcinoma cells subcutaneously to evaluate local tumor growth, or intravenously to evaluate the effects of Ginseng Rh2+ on development of experimental metastases. Mice were treated by intraperitoneal administration of Ginseng Rh2+ (0.005-0.5 g kg -1 ) on days 6, 10, and 14 after tumor injection., Results: We found that Ginseng Rh2+ increased the apoptosis of NSCLC cells in vitro, demonstrating dose dependent down-regulation of the Bcl-2 anti-apoptotic gene and concurrent up-regulation of the Bax pro-apoptotic gene. Ginseng Rh2+ inhibited the tumor cells' capacity to attach to the ECM-related matrix and reduced cell migration. In vivo, Ginseng Rh2+ inhibited local tumor growth and reduced the development of experimental lung metastases., Conclusion: Our study suggests that Ginseng Rh2+ may potentially be used as a therapeutic agent for treatment of NSCLC.

An estimated 1.24 million blood cancer cases occur annually worldwide, accounting for approximately 6% of all cancer cases. Currently, there are no standardized hematology cancer screening tests that are recommended for the general population. CD24 is a mucin-like cell surface molecule and P-selectin ligand, which plays a significant role in the maturation of B-lymphocytes and was found to be overexpressed in a number of hematological malignancies. Our primary aim was to assess the sensitivity and specificity of the CD24/CD11b-based blood test for the detection of hematological malignancies. Our cohort included 488 subjects with positive hematological cancer diagnosis ( n = 122) and healthy subjects ( n = 366). CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results demonstrated that the average levels of CD24/CD11b in healthy patients (21.7 ± 9.0) were statistically significantly lower compared to levels of CD24/CD11b in cancer patients (29.5 ± 18.7, p < 0.001). The highest levels of CD24/CD11b were found in multiple myeloma (39.1 ± 23.6), followed by chronic myeloid leukemia (33.0 ± 13.7) and non-Hodgkin lymphoma (32.3 ± 13.3). The test had an overall sensitivity for hematologic cancers of 78.5% (95% CI, 70.7-86.3%) and specificity of 80.2% (95% CI, 76.1-84.3%). In conclusion, our findings indicate the feasibility of a CD24/CD11b-based blood test as a screening test of hematological malignancies.