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Mental health is a significant concern among young people, particularly during the COVID-19 pandemic. Notably, mental health problems can significantly reduce student performance in school, including both engagement and achievement. Both mental health problems and reduced student performance often arise due to "peer victimization," which can include teasing, racial- or gender-based discrimination, and/or physical assault. Stress has been proposed as one mechanism through which victimization influences mental health, and stress can also interfere with academic performance at school, including engagement and achievement. To date, however, no research has evaluated longitudinal associations between victimization and stress, and how these longitudinal patterns may impact adolescent behavior and mental health. In this study, we used data from a 2-year cluster randomized trial of cooperative learning to evaluate an etiological process model that includes (1) longitudinal reciprocal effects between victimization and stress, and (2) the effects of both victimization and stress on student mental health and academic engagement. We hypothesized that victimization and stress would have significant reciprocal effects, and that both would predict greater mental health problems and lower academic engagement. We further hypothesized that cooperative learning would have significant effects on all constructs. We found partial support for this model, whereby stress predicted greater victimization, but victimization did not predict increased stress. While both factors were linked to student outcomes, stress was a more powerful predictor. We also found significant salutary effects of cooperative learning on all constructs. The implications of these results for student behavioral and mental health are discussed.

Abstract Obesity is associated with an increased risk of developing multiple myeloma (MM). The molecular mechanisms causing this association is complex and incompletely understood. Whether obesity affects bone marrow immune cell composition in multiple myeloma is not characterized. Here, we examined the effect of diet-induced obesity on bone marrow immune cell composition and tumor growth in a Vk*MYC (Vk12653) transplant model of multiple myeloma. We find that diet-induced obesity promoted tumor growth in the bone marrow and spleen and reduced the relative number of T and B cells in the bone marrow. Our results suggest that obesity may reduce MM immune surveillance and thus may contribute to increased risk of developing MM.

Infections are common in plasma cell cancer multiple myeloma (MM) due to disease-related immune deficiencies and cancer treatment. Myeloma cells express Toll-like receptors (TLRs), and TLR activation has been shown to induce proliferative and pro-survival signals in cancer cells. MM is a complex and heterogeneous disease, and expression levels of TLRs as well as downstream signaling components are likely to differ between patients. Here, we show that in a large cohort of patients, TLR1, TLR4, TLR6, TLR9, and TLR10 are the most highly expressed in primary CD138+ cells. Using an MM cell line expressing TLR4 and TLR9 as a model, we demonstrate that TLR4 and TLR9 activation promoted the expression of well-established pro-survival and oncogenes in MM such as MYC, IRF4, NFKB, and BCL2. TLR4 and TLR9 activation inhibited the efficacy of proteasome inhibitors bortezomib and carfilzomib, drugs used in the treatment of MM. Inhibiting the autophagosome–lysosome protein degradation pathway by hydroxychloroquine (HCQ) diminished the protective effect of TLR activation on proteasome inhibitor-induced cytotoxicity. We also found that TLR signaling downregulated the expression of TNFRSF17, the gene encoding for B-cell maturation antigen (BCMA). MYC, BCL2, and BCL2L1 were upregulated in approximately 50% of primary cells, while the response to TLR signaling in terms of TNFRSF17 expression was dichotomous, as an equal fraction of patients showed upregulation and downregulation of the gene. While proteasome inhibitors are part of first-line MM treatment, several of the new anti-MM immune therapeutic drugs target BCMA. Thus, TLR activation may render MM cells less responsive to commonly used anti-myeloma drugs.

The purpose of this survey study was to explore the relationships between well-being and adaptability among music teacher educators in the United States during the 2020-2021 academic year. We used an online questionnaire to collect data related to demographics, well-being, adaptability, and academic year events. The 85 participants reported relatively high levels of psychological well-being and adaptability. Specific adaptability attributes (e.g., ability to draw on positive feelings and emotions when confronted with new situations in the classroom) were found to be significant predictors of overall well-being.

The primary purpose of this study was to design a reliable and valid continuous-time coding tool for measuring teacher use of space and teacher interactions based on prior research (Hesler, 1972; Martin, 2002). The tool captured teachers' use of space as they moved through 14 identified areas of the large instrumental ensemble classroom and engaged in 10 types of verbal and musical interactions with students. Evidence for content validity is presented, and the tool was found to have high inter-rater reliability. The secondary purpose of the study was to explore the effect of a brief expository lesson on preservice instrumental music teachers' use of classroom space and proximity while teaching, with specific emphasis on teachers moving away from the podium and toward and among students. The expository intervention changed teachers' use of space during the lesson immediately following the intervention (i.e., teachers spent less time on the podium and more time moving toward and among students), but the behaviors did not persist over time.

Peer victimization represents a pervasive problem, particularly for students in middle school. Although curriculum-based prevention programs have generated small to moderate effects on victimization, these effects tend to weaken beginning with the transition to middle school. In this study, we evaluated cooperative learning (CL) as a mechanism to prevent victimization, and evaluated reciprocated friendships as a mediator of these effects. Using four waves of data from a cluster randomized trial of CL (7 intervention and 8 control middle schools; N = 1,890 students, 47.1% female, 75.2% White), we found that CL significantly reduced victimization after two years, and these effects were mediated by growth in the ratio of reciprocated friendship in the first year. We conclude that CL can reduce victimization by providing a means for students to engage in extended social interactions with a wider range of peers and thus creating opportunities for students to forge stronger (i.e., reciprocated) friendships.

Scores from computer-based tests are increasingly used to inform a variety of school- and student-level decisions. An underlying assumption is that the associated scores represent effortful responding by each student with respect to the tasks presented. An innovative method for examining evidence for this assumption involves an examination of item response times to detect rapid guessing behavior. If such behavior is present for a particular student across many items, the score is considered invalid due to low test-taking effort (TTE). Drawing on Eccles' expectancy-value theory, this study explored the prevalence of low TTE among middle school students during a computer adaptive test in reading, as well as demographic and motivational correlates of low TTE. Results suggested a prevalence rate of low TTE of 7%. Low TTE was particularly common among males and those with high cost value perceptions. Implications for research and practice are discussed.

Adolescents, particularly early adolescents, are vulnerable to stress created by negative peer interactions. Stress, in turn, can lead to increased mental health problems and reduced academic engagement, in addition to negative long-term consequences for cognitive development and physical health. Using four waves (2 years) of data from a cluster randomized trial (N = 15 middle schools, 1,890 students, 47.1% female, 75.2% White), we evaluated whether enhancements to peer relations, brought about through carefully structured small-group learning activities (i.e., cooperative learning), could reduce stress and emotional problems and promote academic engagement. We hypothesized that the increased social contact created by cooperative learning would promote greater peer relatedness, reducing student stress and, in turn, reducing emotional problems and promoting academic engagement. Our results confirmed these hypotheses. We conclude that cooperative learning can provide social, behavioral, academic, and mental health benefits for students.

Para la administración de empresas productivas metalúrgicas es importante desarrollar procesos de gestión de la calidad y brinda solvencia en el mercado minero metalúrgico y su proyección. En tal sentido, la presente investigación tiene como objetivo Diseñar un sistema de gestión de la calidad con la aplicación de la norma NB/ISO 9001:2015 para optimizar los procesos productivos en la empresa Tecnología en Fundición Careaga Campos “TECFUCCA SRL” de la ciudad de Potosí. Para lograrlo se planteó una investigación de tipo descriptiva con paradigma mixto, a través de un cuestionario, entrevista semiestructurada y guía de observación. Estos instrumentos fueron aplicados a empleados y gerentes; así como la observación de los procesos en la empresa objeto de estudio. Los resultados arrojaron que la empresa no cuenta con una estructura organizacional adecuada, ni manual de gestión de la calidad. Para ello se diseñó una propuesta en base a los lineamientos de la norma NB/ISO 9001:2015, esto contempla: Manual de Gestión de la Calidad; Manual de Procedimientos; Manual de Funciones y Presupuesto de Implementación.

Abstract Multiple myeloma (MM) is an incurable cancer of terminally differentiated plasma cells that proliferate in the bone marrow. miRNAs are promising biomarkers for risk stratification in MM and several miRNAs are shown to have a function in disease pathogenesis. However, to date, surprisingly few miRNA-mRNA interactions have been described for and functionally validated in MM. In this study, we performed miRNA-seq and mRNA-seq on CD138 + cells isolated from bone marrow aspirates of 86 MM patients to identify novel interactions between sRNAs and mRNAs. We detected 9.8% significantly correlated miRNA-mRNA pairs of which 5.17% were positively correlated and 4.65% were negatively correlated. We found that miRNA-mRNA pairs that were predicted by in silico target-prediction algorithms were more negatively correlated than non-target pairs, indicating functional miRNA targeting and that correlation between miRNAs and mRNAs from patients can be used to identify miRNA-targets. mRNAs for negatively correlated miRNA-mRNA target pairs were associated with gene ontology terms such as autophagy, protein degradation and endoplasmic stress response, reflecting important processes in MM. Targets for two specific miRNAs, miR-125b-5p and miR-365b-3p, were functionally validated in MM cell line transfection experiments followed by RNA-sequencing and qPCR. In summary, we identified functional miRNA-mRNA target pairs by correlating miRNA and mRNA data from primary MM cells. We identified several target pairs that are of potential interest for further studies. The data presented here may serve as a hypothesis-generating knowledge base for other researchers in the miRNA/MM field. We also provide an interactive web application that can be used to exploit the miRNA-target interactions as well as clinical parameters associated to these target-pairs.

IL-32 is a pro-inflammatory cytokine expressed by several types of cancer cells and immune cells. Currently, no treatment targeting IL-32 is available, and its intracellular and exosomal localization make IL-32 less accessible to drugs. We previously showed that hypoxia promotes IL-32 expression through HIF1α in multiple myeloma cells. Here, we demonstrate that high-speed translation and ubiquitin-dependent proteasomal degradation lead to a rapid IL-32 protein turnover. We find that IL-32 protein half-life is regulated by the oxygen-sensing cysteine-dioxygenase ADO and that deubiquitinases actively remove ubiquitin from IL-32 and promote protein stability. Deubiquitinase inhibitors promoted the degradation of IL-32 and may represent a strategy for reducing IL-32 levels in multiple myeloma. The fast turnover and enzymatic deubiquitination of IL-32 are conserved in primary human T cells; thus, deubiquitinase inhibitors may also affect T-cell responses in various diseases.

The purpose of this study was to survey secondary band and orchestra teachers (N = 436) in Colorado and Indiana regarding their self-reported immediacy behaviors, ensemble setups, and use of classroom space when teaching. Immediacy "refers to nonverbal teacher behaviors which increase nonverbal interaction with students and which communicate closeness." Female teachers and teachers of young ensembles reported higher levels of overall immediacy. Among component immediacy behaviors, teachers reported using proximity-related behaviors the least; females reported using proximity behaviors at higher rates than males. The majority of teachers reported using "closed" ensemble setups (i.e., setups that limit teacher movement among students) and remained in these setups for the majority of the school year. Teachers of young ensembles reported greater use of "opened" setups (i.e., setups that help facilitate teacher movement among students). Although teachers reported spending the majority of rehearsal time on the podium, female teachers, teachers of young ensembles, and teachers who used opened setups reported less time on the podium and more time moving among students. Implications for immediacy, ensemble setup, and teacher use of space in music education are discussed.

This small-scale field experiment tests whether an adapted values-affirmation intervention enhances youths' academic achievement and mitigates social identity threat while simultaneously raising capacity to promote social change via the development of "critical consciousness" (CC). CC is the critical analysis of inequitable social conditions, motivation to effect change, and the action taken to change perceived inequities. Participants included 53 ninth and tenth grade students from the Midwestern United States (M[subscript age] = 14.97). Results suggested that the intervention may bolster academic performance and raise critical motivation, a subcomponent of CC. Because CC has been thought to be slow to develop, this study provides new insight into how CC can be fostered to support the social mobility and inclusion of youth experiencing marginalization.

Despite "Brown vs. Board of Education," prejudice still exists in the American school system. These attitudes can give rise to negative social experiences for students of color (i.e., discrimination), negatively impacting their mental and physical health and creating disparities in educational outcomes. Rather than seeking to ameliorate these negative experiences, our approach attempts to address the underlying prejudices and, in so doing, reduce these disparities. Using 4 waves of data from a cluster randomized trial (N = 15 middle schools, 1,890 students, 47.1% female, 75.2% White), we hypothesized that cooperative learning, which has been shown to reduce prejudice in previous research, would create positive gains in peer relatedness, perceptions of academic support, and engagement in learning, and that gains would be larger for students of color; our results confirmed these hypotheses. Our findings highlight the potential role of cooperative learning in reducing disparities and creating greater equity in education.

Multiple myeloma (MM) is a hematological cancer characterized by accumulation of malignant plasma cells in the bone marrow. The patients are immune suppressed and suffer from recurrent and chronic infections. Interleukin-32 is a non-conventional, pro-inflammatory cytokine expressed in a subgroup of MM patients with a poor prognosis. IL-32 has also been shown to promote proliferation and survival of the cancer cells. Here we show that activation of toll-like receptors (TLRs) promotes expression of IL-32 in MM cells through NFκB activation. In patient-derived primary MM cells, IL-32 expression is positively associated with expression of TLRs. Furthermore, we found that several TLR genes are upregulated from diagnosis to relapse in individual patients, predominantly TLRs sensing bacterial components. Interestingly, upregulation of these TLRs coincides with an increase in IL-32. Taken together, these results support a role for IL-32 in microbial sensing in MM cells and suggest that infections can induce expression of this pro-tumorigenic cytokine in MM patients.

Infections are common in plasma cell cancer multiple myeloma (MM) due to disease-related immune deficiencies and cancer treatment. Myeloma cells express Toll-like receptors (TLRs), and TLR activation has been shown to induce proliferative and pro-survival signals in cancer cells. MM is a complex and heterogeneous disease, and expression levels of TLRs as well as downstream signaling components are likely to differ between patients. Here, we show that in a large cohort of patients, TLR1, TLR4, TLR6, TLR9, and TLR10 are the most highly expressed in primary CD138+ cells. Using an MM cell line expressing TLR4 and TLR9 as a model, we demonstrate that TLR4 and TLR9 activation promoted the expression of well-established pro-survival and oncogenes in MM such as MYC, IRF4, NFKB, and BCL2. TLR4 and TLR9 activation inhibited the efficacy of proteasome inhibitors bortezomib and carfilzomib, drugs used in the treatment of MM. Inhibiting the autophagosome–lysosome protein degradation pathway by hydroxychloroquine (HCQ) diminished the protective effect of TLR activation on proteasome inhibitor-induced cytotoxicity. We also found that TLR signaling downregulated the expression of TNFRSF17, the gene encoding for B-cell maturation antigen (BCMA). MYC, BCL2, and BCL2L1 were upregulated in approximately 50% of primary cells, while the response to TLR signaling in terms of TNFRSF17 expression was dichotomous, as an equal fraction of patients showed upregulation and downregulation of the gene. While proteasome inhibitors are part of first-line MM treatment, several of the new anti-MM immune therapeutic drugs target BCMA. Thus, TLR activation may render MM cells less responsive to commonly used anti-myeloma drugs. [ABSTRACT FROM AUTHOR]

Summary: Interleukin-32 (IL-32) is a nonclassical cytokine expressed in cancers, inflammatory diseases, and infections. Its expression is regulated by two different oxygen sensing systems; HIF1α and cysteamine dioxygenase (ADO), indicating that IL-32 may be involved in the response to hypoxia. We here demonstrate that endogenously expressed, intracellular IL-32 interacts with components of the mitochondrial respiratory chain and promotes oxidative phosphorylation. Knocking out IL-32 in three myeloma cell lines reduced cell survival and proliferation in vitro and in vivo. High-throughput transcriptomic and MS-metabolomic profiling of IL-32 KO cells revealed that cells depleted of IL-32 had perturbations in metabolic pathways, with accumulation of lipids, pyruvate precursors, and citrate. IL-32 was expressed in a subgroup of myeloma patients with inferior survival, and primary myeloma cells expressing IL-32 had a gene signature associated with immaturity, proliferation, and oxidative phosphorylation. In conclusion, we demonstrate a previously unrecognized role of IL-32 in the regulation of plasma cell metabolism.