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Background: Youth mental health has declined since the COVID-19 pandemic began. Health coaching and mindfulness-based intervention may support therapeutic processes that promote resilience in the face of risk factors for adverse mental health outcomes. Building Resilience for Healthy Kids (HK) is a school-based intervention designed to support mental health through targeting these processes. Objective: In this study, we tested HK in a pilot randomized controlled trial. Specifically, we examined intervention effects on the theoretically-informed therapeutic processes of emotion regulation, mindfulness, self-efficacy, and resilience and the clinical outcomes of depression and anxiety symptoms. The trial took place between April and June 2021, offering an opportunity to assess the impact of HK in the context of COVID-19. Methods: Participants were early adolescents (N = 230), randomized to HK or assessment-only. Participants in the intervention condition received weekly one-on-one sessions with health coaches. All youth completed validated self-report measures at baseline and post-intervention. Results: Linear mixed effects models indicated that participants who received HK had a greater reduction in emotion regulation difficulties, relative to assessment-only controls (d = 0.84, large effect). Follow-up analyses revealed that youth who endorsed negative affectivity at baseline experienced more benefits than those who did not, and youth who attended more HK sessions increased in self-efficacy, in addition to improved emotion regulation. Intervention effects did not reach significance for other outcomes. Conclusions: Findings suggest that HK may support youth in reducing difficulties in emotion regulation, which are precursors to the development of mental health concerns in adolescence.

Hypertext comprehension often suffers from inadequate representation of the text's structure. Explication of the local paragraph macrostructure within each node might help to overcome this obstacle. As headings show several deficits, especially in digital text, marginalia are considered a promising alternative in signaling hypertext structure as they should foster interactive processing. 41 participants learned with a hypertext with identical macropropositions presented as either macropropositional marginalia (EG1), paragraph-initial topic sentences (EG2) or with an unsignaled placing of the macropropositions at the end of each paragraph (CG). All three experimental texts contained identical information. Results revealed increased inference performance for marginalia and increased factual recognition for topic sentences, confirming the assumptions that marginalia foster interactive processing but suffer the same oversignaling deficit as headings concerning the processing of factual information.

The incidence of HIV infection in rural African youth remains high despite widespread knowledge of the disease within the region and increasing funds allocated to programs aimed at its prevention and treatment. This suggests that program efficacy requires a more nuanced understanding of the profiles of the most at-risk individuals. To evaluate the explanatory power of novel psychographic variables in relation to high-risk sexual behaviors, we conducted a survey to assess the effects of psychographic factors, both behavioral and attitudinal, controlling for standard predictors in 546 youth (12-26 years of age) across 8 villages in northern Tanzania. Indicators of high-risk sexual behavior included HIV testing, sexual history (i.e., virgin/non-virgin), age of first sexual activity, condom use, and number of lifetime sexual partners. Predictors in the statistical models included standard demographic variables, patterns of media consumption, HIV awareness, and six new psychographic features identified via factor analyses: personal vanity, family-building values, ambition for higher education, town recreation, perceived parental strictness, and spending preferences. In a series of hierarchical regression analyses, we find that models including psychographic factors contribute significant additional explanatory information when compared to models including only demographic and other conventional predictors. We propose that the psychographic approach used here, in so far as it identifies individual characteristics, aspirations, aspects of personal life style and spending preferences, can be used to target appropriate communities of youth within villages for leading and receiving outreach, and to build communities of like-minded youth who support new patterns of sexual behavior.

The capacity to focus one's attention for an extended period of time can be increased through training in contemplative practices. However, the cognitive processes engaged during meditation that support trait changes in cognition are not well characterized. We conducted a longitudinal wait-list controlled study of intensive meditation training. Retreat participants practiced focused attention (FA) meditation techniques for three months during an initial retreat. Wait-list participants later undertook formally identical training during a second retreat. Dense-array scalp-recorded electroencephalogram (EEG) data were collected during 6 min of mindfulness of breathing meditation at three assessment points during each retreat. Second-order blind source separation, along with a novel semi-automatic artifact removal tool (SMART), was used for data preprocessing. We observed replicable reductions in meditative state-related beta-band power bilaterally over anteriocentral and posterior scalp regions. In addition, individual alpha frequency (IAF) decreased across both retreats and in direct relation to the amount of meditative practice. These findings provide evidence for replicable longitudinal changes in brain oscillatory activity during meditation and increase our understanding of the cortical processes engaged during meditation that may support long-term improvements in cognition.

Technology permeates our daily lives; education has not been untouched. Liaw (2002) points out that "teachers, trainers, and instructional designers of computer-based or Web-based instruction would benefit by being more attentive to learners' perceptions toward Web-based environments." Reviewing the earlier research into student perceptions toward online or blended nonmathematical courses, studies found that students were in general satisfied with their learning experience. Additionally, students believed the courses benefited their learning, increased their motivation, and improved their self-discipline. A main reason mentioned for the satisfaction was the convenience and flexibility offered by the course structure; the courses allowed for self-pacing, learning at any place and any time, and saving time. Students did worry about the lack of traditional teachers, believing that a face-to-face component was still important for the learning experience. In the study described here, researchers sought to describe the thoughts and feelings of students participating in redesigned blended computer-aided sections of college algebra. Results indicated that about 38% of the participants had positive thoughts and perceptions about taking a section of computer-aided college algebra, while about 47% reported negative initial thoughts and perceptions. (Contains 2 tables.)

A mixed-method study was conducted during the Fall 2008 semester to better understand the experiences of students participating in computer-aided instruction of College Algebra using the software MyMathLab. The learning environment included a computer learning system for the majority of the instruction, a support system via focus groups (weekly class meetings), and tutorial services. Emerging themes for the best way to learn College Algebra were (1) use of resources (45.6% indicated View an Example, Video, or Textbook); (2) soliciting help from others (44.7% indicated tutors, time in tutoring lab, or attending Focus Group); and (3) "practice, practice, practice" (approximately 30%). Least beneficial resources identified were textbooks (traditional and electronic), videos, and focus groups. Combining the two most mentioned computer-only resources, View an Example and Help Me Solve This, accounted for 82.3% of the responses; only 14.8% identified these singly. Interestingly, combining the single effects of Help Me Solve This and tutoring, accounted for 21.0% of the responses; students appeared to value a computer resource coupled with a face-to-face resource over strictly computer resources. The results of this study suggested that students preferred resources that directly helped them with individual homework problems, rather than those emphasizing major concepts. (Contains 4 tables.)

Highly pleiotropic and constitutively active protein kinase CK2 is a key target in cancer therapy, but only one small‐molecule inhibitor has reached clinical trials—CX‐4945. In this study, we present the indeno[1,2‐b]indole derivative 5‐isopropyl‐4‐methoxy‐7‐methyl‐5,6,7,8‐tetrahydroindeno[1,2‐b]indole‐9,10‐dione (5a‐2) that decreased the intracellular CK2 activity in A431, A549, and LNCaP tumor cell lines analogous to CX‐4945 (> 75% inhibition at 20 µm) and similarly blocked CK2‐specific Akt phosphorylation in LNCaP cells. Cellular uptake analysis demonstrated higher intracellular concentrations of 5a‐2 (408.3 nm) compared with CX‐4945 (119.3 nm). This finding clarifies the comparable effects of both compounds on the intracellular CK2 activity despite their different inhibitory potency in vitro [IC50 = 25 nm (5a‐2) and 3.7 nm (CX‐4945)]. Examination of the effects of both CK2 inhibitors on cancer cells using live‐cell imaging revealed notable differences. Whereas CX‐4945 showed a stronger pro‐apoptotic effect on tumor cells, 5a‐2 was more effective in inhibiting tumor cell migration. Our results showed that 49% of intracellular CX‐4945 was localized in the nuclear fraction, whereas 71% of 5a‐2 was detectable in the cytoplasm. The different subcellular distribution, and thus the site of CK2 inhibition, provides a possible explanation for the different cellular effects. Our study indicates that investigating CK2 inhibition‐mediated cellular effects in relation to the subcellular sites of CK2 inhibition may help to improve our understanding of the preferential roles of CK2 within different cancer cell compartments. [ABSTRACT FROM AUTHOR]

This activity involved constructing parallelograms on the sides of an arbitrary triangle and discovering a relationship between the areas of the parallelograms. (MP)

Three examples are presented which involve constructions employing a compass, a centimeter ruler, and a calculator. Employing mathematical tools to support understanding and discovery of mathematical principles is viewed as being clearly a desire of mathematics educators, but it is felt such tools are not frequently used to their fullest. (MP)

To establish indices of responsiveness on the Coma Recovery Scale - Revised (CRS-R) for patients with disorders of consciousness (DoC): (1) minimal detectable change with 95% confidence interval (MDC95), (2) conditional MDC95 (cMDC), and (3) distribution-based minimally clinically important difference (MCID). To compare participants' change in CRS-R scores between the control and placebo group of the Amantadine Trial. Retrospective analysis of data collected during a randomized, placebo-controlled clinical trial of participants with DoC. Inpatient rehabilitation facilities. 180 adult participants with DoC resulting from traumatic brain injury (age: mean=36.4 years, SD=15.3; gender: 130 males, 50 females ; condition: 92 Amantadine, 88 placebo). Amantadine or placebo was administered to patients for four weeks. CRS-R was administered to patients at baseline and four weeks later. We transformed CRS-R total raw scores (0 to 23) to a 10-unit equal-interval scale using Rasch analysis. All responsiveness indices are in CRS-R units. For the full sample, MDC95=11, cMDC 95 range=11-42, MCID:.20SD=4,.33SD=6,.50SD=9. Experimental group: Mean CRS-R change (20.4 units) exceeded all MCID values. 63 (68.5%) participants improved beyond MDC 95; 53 (57.6%) participants improved beyond cMDC 95. Control group: Mean CRS-R change (16.8 units) exceeded all MCID values. 54 (61.4%) participants improved beyond MDC 95; 42 (48.9%) participants improved beyond cMDC 95. The experimental group made a mean CRS-R change that was nearly 4 units greater than the control group. The MDC95 and MCID statistics account for differences over the four weeks between the two CRS-R administrations. The cMDC95 accounts for measurement error in change scores on a pair-wise basis and thus provides a more precise index to identify individual patients who are likely to have truly changed. Participants in the amantadine group improved, on average, nearly CRS-R 4 units greater than the control group which represents a small (.20SD) important difference. As none of the distribution-based MCIDs exceed the MDC95 or cMDC95 values, MCIDs should not be applied to interpret individual patient change. N/A. [ABSTRACT FROM AUTHOR]

[Display omitted] Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder characterized by a life-threatening cytokine storm and immunopathology. Familial HLH type 3 (FHL3) accounts for approximately 30% of all inborn HLH cases worldwide. It is caused by mutations in the UNC13D gene that result in impaired degranulation of cytotoxic vesicles and hence compromised T-cell- and natural killer-cell-mediated killing. Current treatment protocols, including allogeneic hematopoietic stem cell (HSC) transplantation, still show high mortality. We sought to develop and evaluate a curative genome editing strategy in the preclinical FHL3 Jinx mouse model. Jinx mice harbor a cryptic splice donor site in Unc13d intron 26 and develop clinical symptoms of human FHL3 upon infection with lymphocytic choriomeningitis virus (LCMV). We employed clustered regularly interspaced short palindromic repeats (CRISPR)-Cas technology to delete the disease-causing mutation in HSCs and transplanted Unc13d -edited stem cells into busulfan-conditioned Jinx recipient mice. Safety studies included extensive genotyping and chromosomal aberrations analysis by single targeted linker-mediated PCR sequencing (CAST-Seq)-based off-target analyses. Cure from HLH predisposition was assessed by LCMV infection. Hematopoietic cells isolated from transplanted mice revealed efficient gene editing (>95%), polyclonality of the T-cell receptor repertoire, and neither signs of off-target effects nor leukemogenesis. Unc13d transcription levels of edited and wild-type cells were comparable. While LCMV challenge resulted in acute HLH in Jinx mice transplanted with mock-edited HSCs, Jinx mice grafted with Unc13d -edited cells showed rapid virus clearance and protection from HLH. Our study demonstrates that transplantation of CRISPR-Cas edited HSCs supports the development of a functional polyclonal T-cell response in the absence of genotoxicity-associated clonal outgrowth. [ABSTRACT FROM AUTHOR]

The production of motors for the electric vehicles requires innovative and systematic quality control approaches to boost efficiency while moving from low volume towards mass production. In this context, end-of-line quality testing methods are usually applied to assess the product functionality at the end of the process chain. However, this approach does not allow process monitoring and the in-line prevention and correction of defects, leading to significant scrap rates and value losses. This paper presents a new system-level strategy for the in-line quality-oriented assembly of rotors in the production of automotive electric drives. The new strategy is based on a new cyber-physical system that optimizes the assembly strategy depending on the quality of magnetized stacks, monitored with data gathered by in-line inspection. For each batch, the magnetic stacks to be assembled and their orientation is selected according to an optimization algorithm, aiming at minimizing the deviation from the target total integral magnetic flux and maximizing the field uniformity in the magnetized rotor. The impact of the proposed strategy on the quality and productivity related performance measures are predicted by analytical methods. Experimental results based on an industrial case study are reported, showing that the application of the proposed strategy yields a significant increase in the production rate of conforming engines. The proposed approach paves the way to innovative zero-defect manufacturing strategies at system level in emerging, high-tech, manufacturing sectors. [ABSTRACT FROM AUTHOR]

Background & Aims: Virus-specific CD8+ T cells are required for the control of hepatitis C virus (HCV) infection. We investigated the extent to which different effector functions of CD8+ T cells contribute to the inhibition of viral replication. Methods: We developed a novel immunologic model by stably transducing the HLA-A2 gene into the replicon system, matching the epitope sequence of the replicon to the sequence targeted by an HCV-specific CD8+ T-cell clone. Luciferase activity was then measured to quantitate HCV RNA replication. Results: HCV-specific CD8+ T cells strongly inhibited viral replication, through cytolytic and noncytolytic mechanisms, in a dose-dependent manner. HCV replication was almost completely inhibited at an effector-to-target ratio of 1:1 with significant cytotoxicity; however, >95% viral inhibition occurred at ratios as low as 1:100. Importantly, no cytotoxicity was observed at low effector-to-target ratios, indicating a dominant effect of noncytolytic effector functions that was confirmed by Transwell experiments. Neutralization experiments revealed that interferon gamma mediates the noncytolytic inhibition. Conclusions: Only a very few HCV-specific CD8+ T cells are required to inhibit HCV replication; inhibition occurs primarily by noncytolytic effector functions. [Copyright &y& Elsevier]