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Objective: Adults with rheumatic disease (RD) experience high levels of fatigue. Regular physical activity has been shown to reduce fatigue among adults. Despite this evidence, adults with RD are more likely to be physically inactive compared with those without RD. Little information is known about the association of physical activity level and fatigue among adults with RD. This study investigated the association of physical activity level and fatigue among adults with and without RD. Methods: Adults (≥18 y) who participated in the 2018 National Health Interview Survey (unweighted n = 25,471) were included in this cross-sectional study. Physical activity and fatigue were self-reported. Statistical analyses were weighted to account for complex survey sampling design. Results: Significantly more adults with RD experience fatigue compared with adults without RD (26.19% vs 13.23%). Adults with RD who were inactive had 2.81 times (95% CI, 2.37–3.34) higher odds of experiencing fatigue compared to adults with RD who were sufficiently active, after adjusting for covariates. Conclusions: Overall, fatigue was more common among adults with RD than it was in the population without RD. [ABSTRACT FROM AUTHOR]

Employers face many dilemmas in effectively implementing work–life flexibility to support employees' personal lives. A key issue is that some employees hold jobs with limited opportunities for work–life flexibility, making them susceptible to burnout; yet most employers believe they can do little to mitigate this dynamic. Furthermore, even when employees hold jobs with greater access to work–life flexibility, some do not take advantage of their flexibility to more fully engage in work and/or home roles. These issues are further exacerbated when supervisors are unsure of their role in supporting work–life flexibility. We identify work–life supportive context as a key factor that provides solutions to these dilemmas. Drawing on job demands resources theory, we posit that, when organizations provide work–life supportive training to supervisors, it promotes a work–life supportive context (i.e., signaling that the organization is supportive of employees' managing their work–life interface), which mitigates burnout for those with limited work–life flexibility and promotes engagement in work and home roles for those with greater work–life flexibility. Results from a year‐long randomized field experiment suggest that, in contexts with trained supervisors and lower employee control over work schedules and boundaries (i.e., lower work–life flexibility), emotional exhaustion is reduced. In contexts with trained supervisors and higher employee control over work boundaries (i.e., higher work–life flexibility), family engagement increases. Surprisingly, irrespective of job access to work‐life flexibility, supervisor participation in work–life support training did not enhance employee work engagement. Implications of our findings for fostering work–life supportive contexts are considered. [ABSTRACT FROM AUTHOR]

Burnout, characterized by exhaustion, reduced accomplishment, and devaluation, can have substantial negative implications for athletes. Notably, researchers continue to examine burnout from multiple perspectives, commonly focusing on stress-, motivation-, or commitment-related factors, with limited efforts to consider these perspectives together. In contrast, this study aimed to assess the utility of these multiple perspectives and the key predictors of burnout in the same athlete sample. Data on burnout, stress, motivation, motivational climate, and sport commitment were gathered from 370 Gaelic games athletes. Separate structural equation models incorporating stress, motivation, and commitment factors as predictors of burnout dimensions were assessed. All models showed adequate fit. However, differences in effect size suggest that stress is more strongly associated with exhaustion, while commitment and motivation showed a stronger relationship with reduced accomplishment and devaluation. Evidence of significant predictors across perspectives also supports an integrated approach and may inform integration efforts and targeted intervention strategies. [ABSTRACT FROM AUTHOR]

Drawing on theories from the sociology of work and organizations, such as Leiter and Maslach's concept of burnout and Siegrist's model of effort–reward imbalance, this paper argues that burnout symptoms in elite sport are related to a mismatch of investment and gratification. Building on data from a sample of German elite athletes (N = 312), findings show that high time investments for training and competitions, the experience of time and role conflicts and negative emotions related to daily training are associated with more burnout symptoms, while sporting success, social support and training-related positive emotions are associated with lower burnout scores. Vulnerability to burnout is increased in situations that qualify as gratification crises, in which athletes perceive that high time commitment does not pay off in terms of sporting success. [ABSTRACT FROM AUTHOR]

The concept of immune cell exhaustion/dysfunction has developed mainly to understand impaired type 1 immune responses, especially by CD8 T-cells against tumors or virus-infected cells, and has been applied to other lymphocytes. Natural killer (NK) cells and CD4 T cells support the efficient activation of CD8 T cells but exhibit dysfunctional phenotypes in tumor microenvironments and in chronic viral infections. In contrast, the concept of type 2 immune cell exhaustion/dysfunction is poorly established. Group 2 innate lymphoid cells (ILC2s) and T-helper 2 (Th2) cells are the major lymphocyte subsets that initiate and expand type 2 immune responses for antiparasitic immunity or allergy. In mouse models of chronic parasitic worm infections, Th2 cells display impaired type 2 immune responses. Chronic airway allergy induces exhausted-like ILC2s that quickly fall into activation-induced cell death to suppress exaggerated inflammation. Thus, the modes of exhaustion/dysfunction are quite diverse and rely on the types of inflammation and the cells. In this review, we summarize current knowledge of lymphocyte exhaustion/dysfunction in the context of type 1 and type 2 immune responses and discuss ILC2-specific regulatory mechanisms during chronic allergy. [ABSTRACT FROM AUTHOR]

A large number of humans entering the world of adults sign the symptoms of the phenomenon burnout between the first and fifth years of their working life shows research for Bulgaria. Manifested symptoms are grouped and form as the most typical the resistance phase of the phenomenon. A predomination of the symptom widening of the sphere of emotions saving establish the data for women. [ABSTRACT FROM AUTHOR]

Adoptive cell therapy (ACT) using in vitro expanded tumor-infiltrating lymphocytes (TILs) has inconsistent clinical responses. To better understand determinants of therapeutic success, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients using single-cell RNA and T cell receptor (TCR) sequencing. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, and these were more effectively mobilized upon in vitro expansion, yielding products enriched in tumor-specific CD8+ cells that preferentially infiltrated tumors post-ACT. Conversely, lack of clinical responses was associated with tumors devoid of tumor-reactive resident clonotypes and with cell products mostly composed of blood-borne clonotypes that persisted in blood but not in tumors post-ACT. Upon expansion, tumor-specific TILs lost tumor-associated transcriptional signatures, including exhaustion, and responders exhibited an intermediate exhausted effector state after TIL engraftment in the tumor, suggesting functional reinvigoration. Our findings provide insight into the nature and dynamics of tumor-specific clonotypes associated with clinical response to TIL-ACT, with implications for treatment optimization. [Display omitted] • Patients with clinical responses have baseline tumors enriched in tumor-reactive TILs • Tumor-reactive TILs are more effectively mobilized upon in vitro expansion • Non-responders' ACT products are mostly composed of blood-borne clonotypes • TIL-ACT promotes T cell reprogramming, suggesting functional reinvigoration Adoptive cell therapy (ACT) using in vitro expanded tumor-infiltrating lymphocytes (TILs) can be curative in melanoma but has inconsistent clinical responses. Chiffelle, Barras, et al. track TIL clonotypes in melanoma patients through ACT therapy and provide insight into the profiles and dynamics of tumor-specific clonotypes associated with clinical response and features related to non-responsiveness. [ABSTRACT FROM AUTHOR]

Scientific knowledge evolves in small steps, with occasional backsteps to correct inaccuracies, all occurring within a competitive environment. This perspective for the first time looks at the history of latency-related RNA (LR-RNA) that was later renamed latency-associated transcript (LAT). At the 1986 International Herpesvirus Workshop (IHW) meeting in Leeds, England, Daniel L Rock and Anthony B Nesburn first reported the discovery of human herpes virus 1 (HSV-1) latency-related (LR) RNA that is antisense to ICP0. Less than a month after the IHW meeting, a paper was submitted to Science magazine and 8 months later appeared in print thanking "D. Rock for suggesting RNA complementary to the ICP0 message may be present in latently infected cells". This perspective is not a review of the LAT literature but intends to clarify the timeline of LAT discovery and subsequent breakthroughs such as reactivation, apoptosis, CD8+ T cell exhaustion, and LAT expression in different cell types detected during latency. While many review articles have been written about LAT since 1987, the most comprehensive and balanced review about LAT was written by Dr. David Bloom's group. In this overview, I will discuss our original collaboration with Dr. Dan Rock and subsequent work that our group performed, which is still ongoing. Finally, I will discuss the controversies associated with LAT from its inception to current times. [ABSTRACT FROM AUTHOR]

This study uses a resource perspective that combines theories used commonly to explore recovery experiences as a theoretical framework and investigate the effects of recovery at the beginning of the workday on exhaustion and vigour at the end of the workday, with workflow in the morning as a mediator. An experience sampling method was used to collect data from 84 fulltime employees. Participants received three survey links each workday over a 2‐week period, resulting in 837 days‐level and 2517 data points. Hierarchical linear regression was used to test hypotheses, with results suggesting that greater recovery at the beginning of the workday correlated negatively with exhaustion and positively with vigour at the end of the workday. Recovery at the beginning correlated positively with flow state in the morning, and flow state correlated positively with vigour at the end of the workday. Flow state in the morning mediated the relationship between recovery level at the beginning and vigour at the end of the workday. These findings suggest the importance of recovery and the effects of flow state on employees' vigour. [ABSTRACT FROM AUTHOR]

The adverse effects observed in some cancer patients treated with erythropoiesis‐stimulating agents such as erythropoietin (EPO) might be due to the latter's well‐known immunosuppressive functions. Here, we used a mouse model of syngeneic triple‐negative breast cancer to explore EPO's immunomodulatory role in a tumour setting. Our results showed that EPO treatment promotes tumour growth, exacerbates the 'immune desert', and results in a 'cold tumour'. EPO treatment changed the immune cell distribution in peripheral blood, secondary lymphoid organs, and the tumour microenvironment (TME). Our in‐depth analysis showed that EPO mainly impacts CD4 T cells by accelerating their activation in the spleen and thus their subsequent exhaustion in the TME. This process is accompanied by a general elevation of CD39 expression by several immune cells (notably CD4 T cells in the tumour and spleen), which promotes an immunosuppressive TME. Lastly, we identified a highly immunosuppressive CD39+ regulatory T cell population (ICOS+, CTLA4+, Ki67+) as a potential biomarker of the risk of EPO‐induced tumour progression. EPO displays pleiotropic immunosuppressive functions and enhances mammary tumour progression in mice. [ABSTRACT FROM AUTHOR]

Techno-overload represents a new job demand arising from information and communication technologies (ICTs) application in the workplace but its impact on task performance is still controversial. The purpose of this paper is to investigate how and when techno-overload affects task performance through two different processes (i.e., the energy depletion process and the motivational process). Based on the job demands-resources (JD-R) model, we developed a moderated mediation model examining the moderating role of mastery climate in the indirect relationship between techno-overload and task performance through exhaustion and work engagement. We collected data from 275 employees in China and tested the model using conditional process modeling. The findings show that mastery climate weakens the negative indirect effect of techno-overload on task performance through exhaustion and strengthens the positive indirect effect of techno-overload on task performance through work engagement. Our paper not only contributes to the techno-overload literature by integrating two competing perspectives and identifying one critical contingency to the influence of techno-overload, but also provides knowledge that can be used for technology, stress, and performance management in organizations. [ABSTRACT FROM AUTHOR]

While employees use information and communication technology (ICT) to support hybrid work, such ICT can result in technostressors. Drawing upon the challenge-hindrance stressor framework, we conceptualise availability and efficient communication as the challenge technostressors, and interruption as the hindrance technostressor. We then develop a theoretical model based on conservation of resources theory to assess their effects on behavioural and psychological outcomes in both work and non-work domains. Survey data were collected from 437 Chinese employees who engaged in hybrid work. The results show that availability and efficient communication enhance perceived location/schedule flexibility, while interruption reduces perceived schedule flexibility. Furthermore, while perceived location flexibly only increased work performance, perceived schedule flexibility increased work/non-work performance and reduced work/non-work exhaustion. Lastly, significant differences were found between those under high and those under low hybrid work. Our study contributes to the literature by clarifying the antecedents and outcomes of location/schedule flexibility in the context of hybrid work. Our study provides important practical suggestions related to the management of hybrid work. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a common gynecological malignancy, and its treatment remains challenging. Although ovarian cancer may respond to immunotherapy because of endogenous immunity at the molecular or T cell level, immunotherapy has so far not had the desired effect. The functional status of preexisting T cells is an indispensable determinant of powerful antitumor immunity and immunotherapy. T cell exhaustion and senescence are two crucial states of T cell dysfunction, which share some overlapping phenotypic and functional features, but each status possesses unique molecular and developmental signatures. It has been widely accepted that exhaustion and senescence of T cells are important strategies for cancer cells to evade immunosurveillance and maintain the immunosuppressive microenvironment. Herein, this review summarizes the phenotypic and functional features of exhaust and senescent T cells, and describes the key drivers of the two T cell dysfunctional states in the tumor microenvironment and their functional roles in ovarian cancer. Furthermore, we present a summary of the molecular machinery and signaling pathways governing T cell exhaustion and senescence. Possible strategies that can prevent and/or reverse T cell dysfunction are also explored. An in-depth understanding of exhausted and senescent T cells will provide novel strategies to enhance immunotherapy of ovarian cancer through redirecting tumor-specific T cells away from a dysfunctional developmental trajectory. [ABSTRACT FROM AUTHOR]

• Fatigue is a symptom frequently complained with advancing age. • The lack of a gold-standard for its assessment make fatigue poorly understood. • Identifying the most appropriate fatigue scale can help in its better understanding. Fatigue is a symptom frequently complained about by older people but unfortunately poorly understood given its subjectivity and the lack of a gold standard for its assessment. The purpose of this study was therefore to preliminarily explore agreement among four different fatigue scales in a sample of persons with extreme longevity (PEL), their direct offsprings (DO), and controls (CO) matched for age and sex with DO. κ statistics was used to quantify agreement among four different fatigue scales. The agreement ranged from mild to substantial and almost perfect agreement depending on the group considered. The highest agreement was found between the Multidimensional Assessment of Fatigue scale and the Short Form Health Survey-36-Vitality Subscale in the PEL group (κ 0.820; 95 % CI 0.471–0.947). These preliminary findings may serve as a guide in selecting the most feasible instrument to assess fatigue in future large-scale research and clinical activities involving older people. [ABSTRACT FROM AUTHOR]

Prior work on supervisor bottom-line mentality (SBLM) has suggested it represents a static, unbending focus, with supervisors so focused on the bottom line that they discount ethical considerations. We propose that SBLM varies, within-person, given various factors in a supervisor's work life that pull and push their attention to and away from the bottom line across their workweeks. We theorize that the varying nature of SBLM elicits anxiety in employees that is exhausting because, on the days supervisors give greater emphasis to the bottom line, employees must abandon the comfort of their routines to produce bottom-line results. Ultimately, this experience motivates employee unethical behavior (i.e., coworker undermining). We also predict that, by providing employees support and guidance, supervisors' steadfast commitment to ethics (i.e., between-person ethical leadership perceptions) influences the degree to which exhausted employees undermine their coworkers. Results from three experience-sampling methodology studies using diverse samples of working adults support our predictions. In Study 3, we also test assumptions in our theorizing with research questions about potential antecedents of SBLM variability and the moderating effects of ethical leadership. These results revealed that supervisor daily ratings of their leader's BLM and the supervisor's own job demands prompted SBLM variation. In addition, supervisor daily ratings of their own BLM were related to employee-rated daily SBLM. Second, while ethical leadership varies within-person, within-person perceptions did not moderate effects; only between-person perceptions (or employee perceptions of their supervisor's general commitment to ethics) did. Implications for theory and research are provided. [ABSTRACT FROM AUTHOR]

Understanding the labor market participation shift associated with an aging population and the challenges of employees who provide care to old-age relatives is essential to ensure progress toward the Sustainable Development Goals. The current study focuses on the decision of employees who combine paid work with unpaid care to relatives aged 65 and above to stay or leave their jobs. We draw on the Turnover Model and the Informal Caregivers Integrative Model (ICIM) to examine how two primary stressors—care burden and work demand—one secondary stressor—work–family conflict—and emotional exhaustion increase the turnover intentions of employees who combine paid work with eldercare to their old relatives aged 65 and over. By synthesizing these two models and using a survey with three chronological waves among 356 Israeli employees, we analyze a mediation model within a Structural Equation Modeling framework. The findings underscore the fact that work–family conflict (a secondary stressor) and the sense of exhaustion act as key mediators in the relationship between employees' primary stressors and turnover intentions. The presence of primary stressors in themselves does not increase turnover intentions. Our findings imply that, rather than providing sporadic adaptations at work, policymakers, organizations, and human resource management systems should respond proactively to prevent the process from undermining employees' ability to achieve equilibrium between their desire to work and care for their old-age relatives. Such a proactive stance would reduce their exhaustion and turnover intention. [ABSTRACT FROM AUTHOR]

The objective of this study is to develop cotton fabrics that are capable of reversible color change in response to temperature changes and of providing an opportunity for thermal management. To achieve this objective, chitosan/sodium alginate natural polymer-walled microcapsules with a thermochromic phase change system core, produced by the complex coacervation method were applied to cotton fabrics by impregnation and exhaustion processes. The thermochromic system contains crystal violet lactone (dye), phenolphthalein (developer), and 1-tetradecanol (solvent) and offers a temperature regulation function thanks to 1-tetradecanol which act as a phase change material. The second objective of this study is to examine the performance characteristics of the microcapsules when applied to cotton fabric via the impregnation and exhaustion method. The visual photographs and colorimetric measurement results indicated that the fabrics treated with microcapsules exhibited thermochromic properties with both application methods. The performance of fabric (Fabric 2) treated with microcapsules by the exhaustion method was superior in terms of color change compared to fabric (Fabric 1) treated by the impregnation method. However, the T-history results demonstrated that the thermoregulation effect of Fabric 1 and Fabric 2 was comparable. The results of the air and water permeability tests on the fabrics indicated that both microcapsule application methods resulted in the pores of the fabrics being filled, thereby significantly reducing the permeability values. In addition, the bending rigidity of the fabrics increased with the addition of microcapsules to the fabrics, while the tear strength decreased. As a result, microcapsules can be effectively applied to cotton fabric by both methods. Moreover, the exhaustion method provided superior performance in relation to the affinity effect of the polymers forming the capsule wall structure against cotton cellulose molecules. [ABSTRACT FROM AUTHOR]

The increased proportion of women in the workplace and the labor force aging have been demanding investigations of the link between menopause and occupational health issues, especially in healthcare settings. Evidence on the association between menopause and occupational burnout in healthcare settings is still inconclusive. Therefore, we aimed to evaluate the association between menopause and burnout among clinical and non-clinical workers in different occupational health environments. A multi-center, cross-sectional study, applying the Oldenburg Burnout Inventory (OBI) was conducted from September 2021 to March 2023 in University Medical Center (UMC) hospitals in Astana, Kazakhstan. The study involved 125 physicians and nurses and 82 non-clinical administrative and service staff. We found that 63.9% of respondents had disengagement and 61.7% had exhaustion. The affiliated clinical setting was associated with disengagement (p = 0.034), with the highest prevalence among employees in surgical departments (76.9%), while a higher prevalence of exhaustion was found in individuals with different work experience (p = 0.023) and among those who were dissatisfied with their work environment (74.3%). While burnout was identified in almost two-thirds of respondents, the self-reported menopause status of participants was not significantly related to either disengagement (p = 0.34) or exhaustion (p = 0.73), even though a higher prevalence of both was revealed among the postmenopausal group. We propose that healthcare management should understand the importance of burnout among postmenopausal healthcare workers and facilitate open communication and a supportive work environment.

Schimke immuno-osseous dysplasia is a rare multisystemic disorder caused by biallelic loss of function of the SMARCAL1 gene that plays a pivotal role in replication fork stabilization and thus DNA repair. Individuals affected from this disease suffer from disproportionate growth failure, steroid resistant nephrotic syndrome leading to renal failure and primary immunodeficiency mediated by T cell lymphopenia. With infectious complications being the leading cause of death in this disease, researching the nature of the immunodeficiency is crucial, particularly as the state is exacerbated by loss of antibodies due to nephrotic syndrome or immunosuppressive treatment. Building on previous findings that identified the loss of IL-7 receptor expression as a possible cause of the immunodeficiency and increased sensitivity to radiation-induced damage, we have employed spectral cytometry and multiplex RNA-sequencing to assess the phenotype and function of T cells ex-vivo and to study changes induced by in-vitro UV irradiation and reaction of cells to the presence of IL-7. Our findings highlight the mature phenotype of T cells with proinflammatory Th1 skew and signs of exhaustion and lack of response to IL-7. UV light irradiation caused a severe increase in the apoptosis of T cells, however the expression of the genes related to immune response and regulation remained surprisingly similar to healthy cells. Due to the disease’s rarity, more studies will be necessary for complete understanding of this unique immunodeficiency. [ABSTRACT FROM AUTHOR]

Burnout among nurses is a pervasive concern in healthcare, with profound implications for patient care and nurse well-being. While research has highlighted the detrimental effects of burnout on many aspects of nursing, including patient safety and quality of care, the underlying mechanisms driving burnout warrant further investigation. In this cross-sectional study, we surveyed 196 nurses from diverse Italian hospitals using an online questionnaire via Qualtrics. Our findings revealed significant negative correlations between psychological safety climate and both relational stressors and emotional exhaustion. Conversely, relational stressors positively correlated with emotional exhaustion, and a significant negative indirect effect of psychological safety climate was found for emotional exhaustion through relational stressors, emphasizing the pivotal role of psychological safety climate in mitigating nurse burnout. Our study underscores the potential effectiveness of interventions targeting psychological safety climate and relational stressors in alleviating emotional exhaustion and burnout among nurses. Theoretical implications underscore the importance of deepening the role of psychological safety climate in mitigating emotional exhaustion, while practical implications emphasize the need for fostering a positive psychological safety climate and implementing targeted interventions to support nurses' well-being.

Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a risk factor for immunological non-response to antiretroviral therapy. In cases of immunological non-response, HIV viral load suppression occurs without an increase in CD4⁺ T-cell counts, heightening the risk of morbidity and mortality in infected individuals. T-cell exhaustion may hinder their regeneration in immunological non-responders. This study aimed to identify markers of CD4⁺ and CD8⁺ T-cell exhaustion in HIV/HCV coinfected immunological non-responders. The study examined three clinical groups: 1) HIV/HCV coinfected immunological non-responders (CD4⁺ T-cells 350/µl blood; n = 9), 2) HIV/HCV coinfected individuals with a standard response to therapy (CD4⁺ T-cells 500/µl blood; n = 9), and 3) relatively healthy volunteers without HIV and HCV infections (n = 9). Ex vivo, the number of CD4⁺ and CD8⁺ T-cells expressing the inhibitory receptor PD-1 was determined using multi-color flow cytometry. In the 7-day in vitro experiment, cell cultures were stimulated with phytohemagglutinin. The number of dying proliferated CD4⁺ and CD8⁺ T-cells (CFSElowZombieUV+) was determined using multi-color flow cytometry. The amount of interleukin-2 in the culture supernatants was measured using an enzyme-linked immunosorbent assay. It was found that in HIV/HCV coinfected immunological non-responders, there was a higher number of CD4⁺ and CD8⁺ T-cells expressing PD-1, a phenotypic marker of exhaustion, compared to the other two groups. Furthermore, the frequency of dying dividing T-cells was higher in immunological non-responders, with an increase in CD4⁺ T-cells but not CD8⁺ T-lymphocytes. Similarly, a decrease in interleukin-2 production was found in stimulated T-cells of HIV/HCV coinfected immunological non-responders in the CD4⁺ T-cell pool, but not in CD8⁺ T-lymphocytes. Thus, in HIV/HCV coinfected immunological non-responders, CD4⁺ T-cells appear exhausted both phenotypically and functionally. While CD8⁺ T-cells express inhibitory receptors, they do not show functional impairments. It appears that the specialized therapy for HIV/HCV coinfected immunological non-responders should aim to improve CD4⁺ T-cell function.

Abstract Acute myeloid leukemia (AML) is an aggressive and genetically heterogeneous disease with poor clinical outcomes. Refractory AML is common, and relapse remains a major challenge, attributable to the presence of therapy-resistant leukemic stem cells (LSCs), which possess self-renewal and repopulating capability. Targeting LSCs is currently the most promising avenue for long-term management of AML. Likewise, chimeric antigen receptor (CAR)-natural killer (NK) cells have emerged as a promising alternative to CAR-T cells due to their intrinsic potential as off-the-shelf products and safer clinical profiles. Here, we introduced a third-generation CAR harboring TIM3 scFv, CD28, 4-1BB, and CD3ζ (CAR-TIM3) into human NK-92 cells, the only FDA-approved NK cell line for clinical trials. TIM3 was chosen as a target antigen owing to its differential expression in LSCs and normal hematopoietic stem/progenitor cells (HSPCs). The established CAR-TIM3 NK-92 cells effectively targeted TIM3 and displayed potent anti-tumor activity against various primitive AML cells, subsequently causing a reduction in leukemic clonogenic growth in vitro, while having minimal effects on HSPCs. CAR-TIM3 NK-92 cells significantly reduced leukemic burden in vivo and interestingly suppressed the engraftment of AML cells into the mouse liver and bone marrow. Surprisingly, we found that CAR-TIM3 NK-92 cells expressed relatively low surface TIM3, leading to a low fratricidal effect. As TIM3 and PD-1 are immune checkpoints involved in NK cell dysfunction, we further tested and found that CAR-TIM3 NK-92 cells are beneficial for alleviating NK cell exhaustion. Our findings highlight the potential application of CAR-TIM3 NK cells for cellular immunotherapy for TIM3+ AML.

Abstract Backgrounds Cognitive problems are common symptoms among individuals with stress-related exhaustion. It is still unknown whether these individuals are at a higher risk of developing dementia later. This study aims to examine the relationship between midlife stress-related exhaustion and dementia incidence. Methods A population sample of 777 women (aged 38, 46, 50 and 54 years) without dementia at baseline was followed over 50 years, from 1968 to 2019. Stress-related exhaustion was based on information from the psychiatric examination in 1968/69. Information on dementia incidence between 1968 and 2019 was obtained from neuropsychiatric examinations, key-informant interviews, and hospital registry. Dementia was diagnosed according to the DSM-III-R criteria. A subgroup of non-demented women (n = 284) was examined for cognitive functions by the Gottfries-Bråne-Steen scale 24 years after baseline. Results Stress-related exhaustion in midlife was associated with higher risk for development of dementia before age 75 (Hazard ratio and 95% confidence interval: 2.95 and 1.35–6.44). The association remained after adjustment for age, major depression, and anxiety disorder. Mean age of dementia onset was younger for women with stress-related exhaustion than women without stress (mean ± SD, 76 ± 9 vs. 82 ± 8 . p = 0.009). Women with stress-related exhaustion in midlife still showed more cognitive impairments 24 years later compared with women without stress (Odds ratio and 95% confidence interval: 2.64 and 1.15–6.06). Conclusions We found that women with stress-related exhaustion in midlife were at a higher risk to develop dementia at relatively younger age. These women showed persistently lower cognitive functions over years even without dementia. Present study results need to be interpreted with caution due to small sample size and should be confirmed in future studies with larger sample size. Our study findings may imply the importance of long-term follow-up regarding cognitive function among individuals with stress-related exhaustion.

Background: This study aimed to investigate the impact of Kinesio tape (KT) on the viscoelastic properties of the lower limb, specifically stiffness and damping, before and after a fatigue protocol. KT is a commonly used therapeutic intervention believed to prevent injury, yet the available evidence on its effectiveness remains limited. Methods: In this pre-post study, fifty healthy participants underwent countermovement jumps before and after a fatigue protocol. The study assessed the body's viscoelastic behavior under two conditions: with and without Kinesio tape (KT) applied to the gastrocnemius muscle, in both fatiguing conditions. Results: The findings revealed a notable reduction in lower limb damping among male participants after fatigue in the condition without tape. Conversely, in the condition with tape, there was no significant change in damping, indicating that KT may prevent the significant decrease in lower limb damping induced by fatigue. Conclusion: The study offers evidence supporting the beneficial effects of KT in maintaining shock absorption capacity post-fatigue. These benefits may stem from KT's potential to enhance muscular activity and contraction force. Given that muscles act as primary shock absorbers, KT application could bolster their ability to dampen sudden impact forces post-exhaustion, potentially lowering the risk of impact-related injuries. These findings advocate for the use of KT as a preventive measure.

Cervical cancer (CC) poses a significant health burden, particularly in low- and middle-income countries. NK cells play a crucial role against CC; however, they can become exhausted and lose their cytotoxic capacity. This work explores the expression of costimulatory receptors (ICOS, 4-1BB, OX-40) in exhausted NK cells from CC patients. Peripheral blood and tumor biopsies were collected, and flow cytometry was used to evaluate the expression of costimulatory receptors in exhausted NK cells. There is an increase of peripheral exhausted NK cells (PD-1+TIGIT+) in CC patients; this subpopulation has a selectively increased expression of the costimulatory receptors ICOS and 4-1BB. An exhausted population is also highly increased in tumor-infiltrating NK cells, and it shows a dramatically increased expression of the costimulatory receptors ICOS (>15×) and 4-1BB (>10×) compared to peripheral NK cells. The exhausted cells, both in the periphery and in the tumor infiltrating lymphocytes (TILs), are also more likely than non-exhausted NK cell populations (PD-1−TIGIT−) to express these costimulatory receptors; increases ranging from 2.0× ICOS, 2.4× 4-1BB, and 2.6× OX-40 in CD56dim PBMCs to 1.5× ICOS, 5× 4-1BB, and 10× OX-40 in TILs were found. Our study demonstrates for the first time the increased expression of the costimulatory receptors ICOS, 4-1BB, and OX-40 in peripheral CD56dim, CD56bright, and tumor-infiltrating NK cells in CC. Targeting these receptors for stimulation could reverse exhaustion and be a promising immunotherapy strategy. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of tumor-induced death worldwide and remains a primary global health concern. In homeostasis, due to its unique structure and physiological function, the lung microenvironment is in a state of immune tolerance and suppression, which is beneficial to tumor development and metastasis. The lung tumor microenvironment is a more complex system that further enhances the immunosuppressive features in the lungs. NK cells are abundantly located in the lungs and play crucial roles in lung tumor surveillance and antitumor immunity. However, the immunosuppressive microenvironment promotes significant challenges to NK cell features, leading to their hypofunction, exhaustion, and compromised antitumor activity. Thus, understanding the complex interactions among the lung microenvironment, lung tumor microenvironment, and NK cell exhaustion is critical for the development of effective cancer immunotherapeutic strategies. The present review will discuss NK cell hypofunction and exhaustion within the lung microenvironment and lung tumor microenvironment, focusing on lung tissue-specific factors, including key cytokines and unique environmental components, that modulate NK cell activation and function. Understanding the functional mechanisms of key factors would help to design strategies to reverse NK cell exhaustion and restore their antitumor function within the lung tumor microenvironment. [ABSTRACT FROM AUTHOR]

Introduction: While the effectiveness of cognitive-behavioral stress management trainings (SMTs) is well-documented, the underlying mechanisms, especially in an occupational context, are not fully understood. We tested whether SMT-induced improvements in stress management skills, particularly in the mastery of changing cognitions, may explain beneficial SMT effects. Methods: Our non-randomized controlled trial comprised 108 employees of a German health insurance company, with 65 of them participating in a cognitive-behavioral SMT and 43 participating in an alternative control training (AT). As outcome variables, we repeatedly assessed stress-related (functional stress management skills, relaxation, stress reactivity, exhaustion), work-related (job dissatisfaction), and specific-context-related (social support, trait anger) measures at baseline, 2 weeks, and 3 months after the trainings. Functional stress management skills and, in particular, a subscale assessing perceived mastery of changing cognitions ("cognitive-strategies-and-problem-solving") were tested as mediators of change. Results: Repeated measures (M)AN(C)OVAs and complementary multigroup latent difference models confirmed improvements in all outcomes in the SMT-group compared to the AT-group (p's ≤ 0.015). Multivariate mediation path analyses revealed that, regarding mechanisms of change, the subscale cognitive-strategies-and-problem-solving was identified as the most important mediator for all outcomes (95% CIs for expected increases in SMT- vs. AT-group = [lower limits (LLs) ≥ 0.004]; 95% CIs for expected decreases in the SMT- vs. AT-group = [upper limits(ULs) ≤ -0.078]) except for job dissatisfaction. Discussion: Our findings confirm that employees can effectively learn to master stress reduction techniques and consequently lower the resulting burden. Moreover, beneficial SMT effects seem to result from improvements in functional stress management skills, particularly in the ability to change cognitions. This points to the importance of training cognitive techniques. [ABSTRACT FROM AUTHOR]

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Copyright of Zeitschrift für Psychodrama und Soziometrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Psychodrama und Soziometrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Psychodrama und Soziometrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Psychodrama und Soziometrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Psychodrama und Soziometrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Backgrounds: Cognitive problems are common symptoms among individuals with stress-related exhaustion. It is still unknown whether these individuals are at a higher risk of developing dementia later. This study aims to examine the relationship between midlife stress-related exhaustion and dementia incidence. Methods: A population sample of 777 women (aged 38, 46, 50 and 54 years) without dementia at baseline was followed over 50 years, from 1968 to 2019. Stress-related exhaustion was based on information from the psychiatric examination in 1968/69. Information on dementia incidence between 1968 and 2019 was obtained from neuropsychiatric examinations, key-informant interviews, and hospital registry. Dementia was diagnosed according to the DSM-III-R criteria. A subgroup of non-demented women (n = 284) was examined for cognitive functions by the Gottfries-Bråne-Steen scale 24 years after baseline. Results: Stress-related exhaustion in midlife was associated with higher risk for development of dementia before age 75 (Hazard ratio and 95% confidence interval: 2.95 and 1.35–6.44). The association remained after adjustment for age, major depression, and anxiety disorder. Mean age of dementia onset was younger for women with stress-related exhaustion than women without stress (mean ± SD, 76 ± 9 vs. 82 ± 8. p = 0.009). Women with stress-related exhaustion in midlife still showed more cognitive impairments 24 years later compared with women without stress (Odds ratio and 95% confidence interval: 2.64 and 1.15–6.06). Conclusions: We found that women with stress-related exhaustion in midlife were at a higher risk to develop dementia at relatively younger age. These women showed persistently lower cognitive functions over years even without dementia. Present study results need to be interpreted with caution due to small sample size and should be confirmed in future studies with larger sample size. Our study findings may imply the importance of long-term follow-up regarding cognitive function among individuals with stress-related exhaustion. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is an aggressive and genetically heterogeneous disease with poor clinical outcomes. Refractory AML is common, and relapse remains a major challenge, attributable to the presence of therapy-resistant leukemic stem cells (LSCs), which possess self-renewal and repopulating capability. Targeting LSCs is currently the most promising avenue for long-term management of AML. Likewise, chimeric antigen receptor (CAR)-natural killer (NK) cells have emerged as a promising alternative to CAR-T cells due to their intrinsic potential as off-the-shelf products and safer clinical profiles. Here, we introduced a third-generation CAR harboring TIM3 scFv, CD28, 4-1BB, and CD3ζ (CAR-TIM3) into human NK-92 cells, the only FDA-approved NK cell line for clinical trials. TIM3 was chosen as a target antigen owing to its differential expression in LSCs and normal hematopoietic stem/progenitor cells (HSPCs). The established CAR-TIM3 NK-92 cells effectively targeted TIM3 and displayed potent anti-tumor activity against various primitive AML cells, subsequently causing a reduction in leukemic clonogenic growth in vitro, while having minimal effects on HSPCs. CAR-TIM3 NK-92 cells significantly reduced leukemic burden in vivo and interestingly suppressed the engraftment of AML cells into the mouse liver and bone marrow. Surprisingly, we found that CAR-TIM3 NK-92 cells expressed relatively low surface TIM3, leading to a low fratricidal effect. As TIM3 and PD-1 are immune checkpoints involved in NK cell dysfunction, we further tested and found that CAR-TIM3 NK-92 cells are beneficial for alleviating NK cell exhaustion. Our findings highlight the potential application of CAR-TIM3 NK cells for cellular immunotherapy for TIM3+ AML. [ABSTRACT FROM AUTHOR]

With growing numbers of workers relying on the digital workplace to get work done, attention is increasingly focused on the well-being impacts of digital working. This study explored the stress, burnout and mental health implications of employees' digital workplace experience. Using the Job Demands-Resources model as a theoretical foundation, 142 workers were surveyed about their experiences of dark side of digital working effects (stress, overload, anxiety, and Fear of Missing Out) and well-being (exhaustion and mental health). Results from regression analyses indicated that the fear of missing out on information (IFoMO) is a risk factor for employee mental health and, along with information overload (IO), may lead to greater exhaustion. Additionally, both IFoMO and IO elevate digital workplace stress, further impacting well-being negatively. The results suggest that organizations need to optimize the flow of work-related information in the digital workplace and support employees to leverage information effectively. Plain language summary: Impacts to employee well-being due to information in the digital workplace With growing numbers of workers relying on the digital workplace to get work done, attention is increasingly focused on the well-being impacts of digital working. This study explored stress, burnout and mental health issues that can arise for employees as a result of demands they experience when using technology at work. A total of 142 workers were surveyed about stress, overload, anxiety, and Fear of Missing Out relating to technology use. They were also asked about negative well-being impacts namely exhaustion and mental health issues. Results indicated that the fear of missing out on information is a risk factor for employee mental health and, along with information overload, may lead to greater exhaustion. In addition, both of these information related issues were found to elevate digital workplace stress, further impacting well-being negatively. The results suggest that organizations need to optimize the flow of work-related information in the digital workplace and support employees to leverage information effectively. [ABSTRACT FROM AUTHOR]

Burnout among nurses is a pervasive concern in healthcare, with profound implications for patient care and nurse well-being. While research has highlighted the detrimental effects of burnout on many aspects of nursing, including patient safety and quality of care, the underlying mechanisms driving burnout warrant further investigation. In this cross-sectional study, we surveyed 196 nurses from diverse Italian hospitals using an online questionnaire via Qualtrics. Our findings revealed significant negative correlations between psychological safety climate and both relational stressors and emotional exhaustion. Conversely, relational stressors positively correlated with emotional exhaustion, and a significant negative indirect effect of psychological safety climate was found for emotional exhaustion through relational stressors, emphasizing the pivotal role of psychological safety climate in mitigating nurse burnout. Our study underscores the potential effectiveness of interventions targeting psychological safety climate and relational stressors in alleviating emotional exhaustion and burnout among nurses. Theoretical implications underscore the importance of deepening the role of psychological safety climate in mitigating emotional exhaustion, while practical implications emphasize the need for fostering a positive psychological safety climate and implementing targeted interventions to support nurses' well-being. [ABSTRACT FROM AUTHOR]

Introduction: School burnout remains a prevalent problem among adolescents; it is associated with low academic achievement and school dropout risk, in turn linked to a whole host of deleterious developmental outcomes. The current longitudinal study sought to better understand the developmental course of school burnout by testing whether poor sleep and problematic internet use each uniquely and additively explained the variance in school burnout over time. Method: Data were collected four times over 18 months, 6 months apart from N = 405 adolescents, grades 9 to 11. Results: Sleep quality, but not quantity, was significantly associated with the school burnout intercept (β = −0.29); no effects were found for the slope. Problematic internet use was also significantly associated with the intercept (β =.44), but not the slope. In a combined model, both sleep quality and problematic internet use significantly predicted the school burnout intercept. The slope was only predicted by age (β = −0.21). Conclusions: The study found partial support for the hypotheses that both poor sleep quality and problematic internet use predicted school burnout, intercept only, not the rate of change. The evidence suggests that school burnout increased across high school; however, the rate of increase slowed with age. In contrast to some previous work, study findings highlight the importance of separately considering both poor sleep and problematic internet use in understanding the development of school burnout during adolescence. N = 229 [ABSTRACT FROM AUTHOR]

This study aims to contribute to an analysis of the well-being of military personnel who are deployed on humanitarian aid missions, taking their work-family (personal life) boundary management into consideration by analyzing the relationship between their preferences and enacted boundaries and military personnel' well-being. Specifically, this study analyzed the boundary fit approach, positing that it is the adjustment between individuals' preferences and enacted boundaries that influences their well-being. Using a sample of 327 military personnel, boundary management profiles were performed, considering the fit between their segmentation preferences and enactment. Furthermore, the relationship between these profiles and the military personnel' well-being was established. The results indicated that misfit profiles were found where the soldiers enacted less segmentation than desired or, on the contrary, more integration than desired, and a profile with a fit between the work-family segmentation they desired and enacted. The military personnel in the fit profile had significantly higher levels of well-being (i.e.,less exhaustion and more work engagement) than those in the misfit profile, who enacted less segmentation than desired. The findings have implications for the design of boundary management literature and future military missions. [ABSTRACT FROM AUTHOR]

In this study, a quantitative diary design was used to examine within-person relationships among daily negative events, emotional intelligence facets, and levels of academic exhaustion and engagement. The research was conducted with a sample of 63 Portuguese health science students (48 females and Mage = 22.3 years) from medicine (n = 33) and psychology (n = 30) degrees who completed a daily survey for 2 weeks (550 diary entries). The results showed a positive association between daily negative events and exhaustion, whereas daily negative events were not associated with academic engagement. Furthermore, the use of emotions emerged as a key emotional intelligence facet associated with reduced exhaustion and enhanced engagement over and above negative events. Taken together, these data highlight the use of emotions as a salient emotional intelligence facet in the context of daily academic exhaustion and engagement. Although preliminary, these findings have the potential to inform emotional intelligence facets that could be improved through training intervention as a means to enhance positive functioning within the higher education environment. [ABSTRACT FROM AUTHOR]

Clinical Question: In physicians and athletic trainers, is burnout associated with self-reported medical errors (MEs)? Clinical Bottom Line: Burnout directly increased the odds of self-reported ME. Physicians and surgeons with burnout had a higher risk of an self-reported ME than athletic trainers with burnout. This disparity may reflect the different definitions, oversight, and opportunities to commit MEs in the respective fields. Emotional exhaustion and personnel accomplishment appear to drive MEs within clinically practicing athletic trainers, whereas emotional exhaustion and depersonalization are indicative of MEs within practicing physicians. Understanding the mechanism behind burnout within practice settings may provide insights into mitigation strategies to reduce MEs and improve patient outcomes. Strength of Recommendation Taxonomy B. [ABSTRACT FROM AUTHOR]

Summary: The weekend constitutes an important recovery period for employees. However, psychologically reattaching to work on Monday can be difficult because employees must transition from their private to their work role. Building on boundary theory and integrating a sleep and circadian perspective, we shed light on this transition by investigating antecedents and outcomes of Monday reattachment. We propose that three weekend sleep characteristics differentially relate to reattachment on Monday: weekend sleep quality, catch‐up sleep (extended sleep duration on the weekend), and social sleep lag (differences in sleep times workweek vs. weekend). Successful reattachment on Monday should, in turn, be related to lower levels of exhaustion and higher task performance during the workweek. We conducted a weekly diary study with 310 employees (933 weeks) over four workweeks. Two‐level path models demonstrated that higher weekend sleep quality was indirectly related to lower levels of workweek exhaustion via higher levels of Monday reattachment. In contrast, higher catch‐up sleep was related to higher levels of workweek exhaustion via lower levels of Monday reattachment. Accordingly, we demonstrate that Monday reattachment can set the tone for the entire workweek, but the capability to reattach can depend on weekend sleep as a core recovery process. [ABSTRACT FROM AUTHOR]

Introduction: Higher education students experience significant levels of exhaustion in their studies, yet there are limited evidence-based support programs available. Therefore, this study evaluated a novel intervention approach by testing the effectiveness of two online interventions based on the study demands-resources framework. These interventions aimed to balance demands and resources. Derived from the theoretical assumptions of the framework, we hypothesized that the interventions would increase study and personal resources, engagement, and study crafting, and decrease study demands, exhaustion, and self-undermining. Additionally, we hypothesized that demands and resources would mediate the effects of the intervention on engagement, exhaustion, study crafting, and self-undermining. Methods: Conducted as a randomized controlled trial with a waitlist control group (n = 71), the study involved participants in two intervention groups who engaged with the interventions for 2 weeks. Intervention group 1 (n = 64) focused on adapting demands, while intervention group 2 (n = 70) focused on increasing resources. The design allowed for a comparison of the effectiveness of these different approaches. Participants completed questionnaires before and after the intervention, and at a 5-week follow-up. Results: Results of the analyses of variance with repeated measures revealed that the interventions had significant positive effects on the personal resource mindfulness, two study crafting strategies, self-undermining, and exhaustion. Notably, intervention group 2 exhibited more positive outcomes. The hypothesized mediation effects through mindfulness were partially supported. Discussion: The study demonstrates the considerable potential of interventions based on the study demands-resources framework for higher education institutions in supporting student well-being. [ABSTRACT FROM AUTHOR]

CD8 + T cells exert a critical role in eliminating cancers and chronic infections, and can provide long-term protective immunity. However, under the exposure of persistent antigen, CD8 + T cells can differentiate into terminally exhausted CD8 + T cells and lose the ability of immune surveillance and disease clearance. New insights into the molecular mechanisms of T-cell exhaustion suggest that it is a potential way to improve the efficacy of immunotherapy by restoring the function of exhausted CD8 + T cells. Transforming growth factor-β (TGF-β) is an important executor of immune homeostasis and tolerance, inhibiting the expansion and function of many components of the immune system. Recent studies have shown that TGF-β is one of the drivers for the development of exhausted CD8 + T cells. In this review, we summarized the role and mechanisms of TGF-β in the formation of exhausted CD8 + T cells and discussed ways to target those to ultimately enhance the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

Background: In young adults, there is evidence that free arm movements do not help to compensate muscle fatigue-induced deteriorations in dynamic balance performance. However, the postural control system in youth is immature, and as a result, the use of arm movements may provide a compensatory "upper body strategy" to correct fatigue-related balance impairments. Thus, the purpose of the present study was to compare the effects of free vs. restricted arm movement on dynamic balance performance prior and following exercise-induced muscle fatigue. Methods: Forty-three healthy youth (19 females; mean age: 12.8 ± 1.9 years) performed the Y Balance Test-Lower Quarter before and immediately after a fatiguing exercise (i.e., repetitive vertical bipedal box jumps until failure) using two different arm positions: free (move the arms freely) and restricted (keep the arms akimbo) arm movement. Results: Muscle fatigue (p ≤ 0.033; 0.10 ≤ ηp² ≤ 0.33) and restriction of arm movement (p ≤ 0.005; 0.17 ≤ ηp² ≤ 0.46) resulted in significantly deteriorated dynamic balance performance. However, the interactions between the two did not reach the level of significance (p ≥ 0.091; 0.01 ≤ ηp² ≤ 0.07). Conclusion: Our findings indicate that the use of an "upper body strategy" (i.e., free arm position) has no compensatory effect on muscle fatigue-induced dynamic balance deteriorations in healthy youth. [ABSTRACT FROM AUTHOR]

The abrupt transition to remote learning during the first year of the COVID-19 pandemic created considerable work-life boundary challenges for college students. Grounded in boundary management theory, this study utilizes an explanatory sequential mixed-methods approach, incorporating both a survey and subsequent focus groups, to explore the dynamics of boundary permeability, communication, work-life conflict, and exhaustion. Both traditional and underrepresented students were included, highlighting the experiences of these distinct populations. Our findings underscore that underrepresented students are particularly susceptible to work-life conflicts and exhaustion, a realization that points towards the critical need for supportive interventions tailored to their specific needs. Furthermore, this research addresses the paucity of studies focusing on students in the boundary management literature and offers valuable insights into diversity, equity, inclusion, and justice (DEIJ) research. By emphasizing the necessity of differentiating support strategies for diverse student populations, the study aids in formulating effective practices for institutions to enhance student well-being in the context of remote work and learning. [ABSTRACT FROM AUTHOR]

Bladder cancer is a heterogenous disease, and molecular subtyping is a promising method to capture this variability. Currently, the immune compartment in relation to subtypes is poorly characterized. Here, we analyzed the immune compartment in bladder tumors and normal bladder urothelium with a focus on T cell subpopulations using flow cytometry and RNA sequencing. The results were investigated in relation to tumor invasiveness (NMIBC/MIBC) and molecular subtypes according to the Lund Taxonomy system. Whereas the NMIBC/MIBC differed in the overall immune infiltration only, the molecular subtypes differed both in terms of immune infiltration and immune compartment compositions. The Basal/Squamous (Ba/Sq) and genomically unstable (GU) tumors displayed increased immune infiltration compared to urothelial-like (Uro) tumors. Additionally, the GU tumors had a higher proportion of regulatory T cells within the immune compartment compared to Uro tumors. Furthermore, sequencing showed higher levels of exhaustion in CD8+ T cells from GU tumors compared to both Uro tumors and the control. Although no such difference was detected at the transcriptomic level in Uro tumors compared to the controls, CD8+ T cells in Uro tumors showed higher expression of several exhaustion markers at the protein level. Taken together, our findings indicate that depending on the molecular subtype, different immunotherapeutic interventions might be warranted. [ABSTRACT FROM AUTHOR]