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Background: Caregivers of people living with dementia (PLWD) often experience burden based on their care recipients' symptoms of wandering, disorientation, and agitation. Objective: To examine the utilization and perceived value of technology-based solutions for caregiving among caregivers of PLWD. Methods: In collaboration with three Texas sites, PLWD and family caregiver dyads were recruited from clinical and community sites to assess the feasibility of a caregiving technology. PLWDs were asked to wear a GPS-based wearable device, which was paired with caregivers' smartphone application, that enabled location monitoring and was equipped with call functions. After three months, researchers called caregivers to ask about their utilization of the "system" (i.e., wearable paired with smartphone application) and the perceived value of this technology. Forty-one caregivers completed follow-up telephone interviews. Results: About 70% of caregivers reported their care recipient wore the wearable device daily, and 39.1% used the smartphone application daily. Approximately 31% of caregivers reported daily use of the tracking feature, 30.8% reported daily use of the "safe zone" feature (i.e., geo-fencing), and 17.1% reported daily use of the two-way calling feature. About 39% of caregivers were extremely satisfied with the "system," 43.6% found it extremely easy to use, and 46.2% found it extremely useful for caregiving. On average, caregivers with higher baseline Zarit Burden Interview scores found the "system" to be more useful with their caregiving (f = 5.97, p = 0.006) and were more satisfied with the "system" (f = 3.75, p = 0.034). Conclusions: Findings suggest caregiver burden may drive the perceived usefulness of, and satisfaction with, technology-based solutions. [ABSTRACT FROM AUTHOR]

More teachers are trying out the flipped classroom model in which content is delivered outside of class time, typically through online videos and "homework," and follow-up activities are done in class. This model frees up more class time for inquiry and discussion. This article focuses on the self-learning portion of the flipped learning model, in particular, increasing students' intellectual engagement by requiring them to answer embedded questions as they watch math videos. Questions can be embedded to help students gain different types of knowledge. On the basis of a preliminary analysis of 89 embedded questions in 21 videos on geometry and measurement, five types of embedded questions have been identified: (1) factual knowledge; (2) procedural knowledge and skills; (3) conceptual knowledge; (4) task comprehension; and (5) mathematical thinking. An awareness of various pedagogical reasons for embedding a question can expand teachers' repertoire of the kinds of questions they can consider embedding should they wish to assign math videos for their students to watch, especially in a flipped learning model.

BACKGROUND: A major obstacle in translating the therapeutic potential of chimeric antigen receptor (CAR) T cells to children with central nervous system (CNS) tumors is the blood–brain barrier. To overcome this limitation, preclinical and clinical studies have supported the use of repeated, locoregional intracranial CAR T-cell delivery. However, there is limited literature available describing the process for the involvement of an investigational drug service (IDS) pharmacy, particularly in the setting of a children’s hospital with outpatient dosing for CNS tumors. OBJECTIVES: To describe Seattle Children’s Hospital’s experience in clinically producing CAR T cells and the implementation of IDS pharmacy practices used to deliver more than 300 intracranial CAR T-cell doses to children, as well as to share how we refined the processing techniques from CAR T-cell generation to the thawing of fractionated doses for intracranial delivery. METHODS: Autologous CD4+ and CD8+ T cells were collected and transduced to express HER2, EGFR, or B7-H3–specific CAR T cells. Cryopreserved CAR T cells were thawed by the IDS pharmacy before intracranial delivery to patients with recurrent/refractory CNS tumors or with diffuse intrinsic pontine glioma/diffuse midline glioma. RESULTS: The use of a thaw-and-dilute procedure for cryopreserved individual CAR T-cell doses provides reliable viability and is more efficient than typical thaw-and-wash protocols. Cell viability with the thaw-and-dilute protocol was approximately 75% and was always within 10% of the viability assessed at cryopreservation. Cell viability was preserved through 6 hours after thawing, which exceeded the 1-hour time frame from thawing to infusion. CONCLUSION: As the field of adoptive immunotherapy grows and continues to bring hope to patients with fatal CNS malignancies, it is critical to focus on improving the preparatory steps for CAR T-cell delivery. [ABSTRACT FROM AUTHOR]

Recent studies have been conducted in regards to the use of social- media by students and how it can impact his/her academic performance. However, much of this research has been focused on how to use social-media websites in the classroom to facilitate student learning. Therefore, we aimed to address how the use of social-media can be either beneficial or detrimental to undergraduate students, with respect to their academic performance. We distributed a survey to 234 participants, all attending the same four-year university. Throughout the survey, the students self-reported their grade point average (GPA), study habits, and social-media use. We established that female students use social-media websites more often than their male peers, and using a Pearson's correlation, we found that GPA negatively correlated with the number of social-media websites to which students subscribe (p < 0.05). Furthermore, we found that using more social-media websites correlated positively with the amount of time students spend using social-media platforms on a daily basis. Although previous studies indicate that social-media websites should be incorporated into the classroom, our results suggest that this addition may have negative effects on the study habits and academic performance of undergraduate students, particularly those within the field of biological sciences.

Cells rely on activity-dependent protein-protein interactions to convey biological signals. For chimeric antigen receptor (CAR) T cells containing a 4-1BB costimulatory domain, receptor engagement is thought to stimulate the formation of protein complexes similar to those stimulated by T cell receptor (TCR)–mediated signaling, but the number and type of protein interaction–mediating binding domains differ between CARs and TCRs. Here, we performed coimmunoprecipitation mass spectrometry analysis of a second-generation, CD19-directed 4-1BB:ζ CAR (referred to as bbζCAR) and identified 128 proteins that increased their coassociation after target engagement. We compared activity-induced TCR and CAR signalosomes by quantitative multiplex coimmunoprecipitation and showed that bbζCAR engagement led to the activation of two modules of protein interactions, one similar to TCR signaling that was more weakly engaged by bbζCAR as compared with the TCR and one composed of TRAF signaling complexes that was not engaged by the TCR. Batch-to-batch and interindividual variations in production of the cytokine IL-2 correlated with differences in the magnitude of protein network activation. Future CAR T cell manufacturing protocols could measure, and eventually control, biological variation by monitoring these signalosome activation markers. Editor's summary: Chimeric antigen receptor (CAR) T cells are effective therapies against some cancers; however, a better understanding of their signaling pathways would help in enhancing their efficacy. Ritmeester-Loy et al. identified and quantified the protein-protein interactions induced by CAR stimulation in CAR T cells generated from healthy donors. As well as characterizing protein-protein interactions that were induced both by CARs and endogenous T cell receptors, the authors identified a set of protein-protein interactions specific to CARs. The extent of activation of CAR T cells varied from batch to batch but correlated with signaling strength, suggesting that variations in key signaling components may modulate CAR T cell performance. —John F. Foley [ABSTRACT FROM AUTHOR]

Purpose of Review: Correlative studies should leverage clinical trial frameworks to conduct biospecimen analyses that provide insight into the bioactivity of the intervention and facilitate iteration toward future trials that further improve patient outcomes. In pediatric cellular immunotherapy trials, correlative studies enable deeper understanding of T cell mobilization, durability of immune activation, patterns of toxicity, and early detection of treatment response. Here, we review the correlative science in adoptive cell therapy (ACT) for childhood central nervous system (CNS) tumors, with a focus on existing chimeric antigen receptor (CAR) and T cell receptor (TCR)-expressing T cell therapies. Recent Findings: We highlight long-standing and more recently understood challenges for effective alignment of correlative data and offer practical considerations for current and future approaches to multi-omic analysis of serial tumor, serum, and cerebrospinal fluid (CSF) biospecimens. We highlight the preliminary success in collecting serial cytokine and proteomics from patients with CNS tumors on ACT clinical trials. [ABSTRACT FROM AUTHOR]

The benefits of cancer information-seeking may be particularly salient to individuals impacted by childhood cancer, including patients, caregivers, health professionals, and advocates. The purpose of this study was to explore information-seeking patterns for childhood cancer through the National Cancer Institute's Cancer Information Service (CIS), a multi-channel, bilingual resource for cancer information. The study team conducted descriptive analyses on secondary data characterizing 1820 caregivers, health professionals, organizations, and members of the general public who contacted the CIS about childhood cancer between September 2018 and June 2022. Almost 80% of inquiries about childhood cancer were initiated by caregivers, followed by the public, health professionals, and organizations. Although English was the primary language used by individuals to reach the CIS when discussing childhood cancer, there were variations in points of access (i.e., telephone, instant messaging, email, social media) across the four user groups. Most childhood cancer inquiries were about staging and treatment, and the primary cancer sites discussed by CIS users were neurologic or brain, hematologic, and musculoskeletal cancers. Discussion topics included managing and coping with cancer, clinical trials, and treatment side effects. Just over half (54%) of CIS contacts about childhood cancer resulted in a health professional referral. Findings provide direction for the CIS and other public health organizations to deliver, prioritize, and tailor their services to support the information needs of childhood cancer survivors and their families-as well as those who care and advocate for them-who may have a significant need for credible cancer information. [ABSTRACT FROM AUTHOR]

Background and Aims Very early onset inflammatory bowel disease [VEOIBD] is characterized by intestinal inflammation affecting infants and children less than 6 years of age. To date, over 60 monogenic aetiologies of VEOIBD have been identified, many characterized by highly penetrant recessive or dominant variants in underlying immune and/or epithelial pathways. We sought to identify the genetic cause of VEOIBD in a subset of patients with a unique clinical presentation. Methods Whole exome sequencing was performed on five families with ten patients who presented with a similar constellation of symptoms including medically refractory infantile-onset IBD, bilateral sensorineural hearing loss and, in the majority, recurrent infections. Genetic aetiologies of VEOIBD were assessed and Sanger sequencing was performed to confirm novel genetic findings. Western analysis on peripheral blood mononuclear cells and functional studies with epithelial cell lines were employed. Results In each of the ten patients, we identified damaging heterozygous or biallelic variants in the Syntaxin-Binding Protein 3 gene [ STXBP3 ], a protein known to regulate intracellular vesicular trafficking in the syntaxin-binding protein family of molecules, but not associated to date with either VEOIBD or sensorineural hearing loss. These mutations interfere with either intron splicing or protein stability and lead to reduced STXBP3 protein expression. Knock-down of STXBP3 in CaCo2 cells resulted in defects in cell polarity. Conclusion Overall, we describe a novel genetic syndrome and identify a critical role for STXBP3 in VEOIBD, sensorineural hearing loss and immune dysregulation. [ABSTRACT FROM AUTHOR]

Artificial light at night (ALAN) functions as a novel environmental stimulus that has the potential to disrupt interactions among species. Despite recent efforts to explain nocturnal pollinators' responses to this stimulus, the likelihood and associated mechanisms of attraction toward artificial light and potential consequences on fitness for diurnal pollinators are still largely unclear. Here, we took advantage of the obligate mutualism between yucca moths (Tegeticula maculata maculata) and yucca plants (Hesperoyucca whipplei) to understand how direct light exposure and skyglow can influence a pairwise plant–pollinator interaction. To surmise whether adult moths exhibit positive phototaxis, we deployed a set of field-placed light towers during the peak of yucca flowering and compared the number of moths caught in traps between dark-controlled and light-treated trials. Adult moth abundance was much higher when light was present, which suggests that ALAN may alter this diurnal moth's activity patterns to expand their temporal niche into the night. To evaluate ALAN effects on yucca fruit set and moth larva recruitment, we measured skyglow exposure above yucca plants and direct light intensity from a second set of light towers. Both larva and fruit recruitment increased with skyglow, and fruit set also increased with direct lighting, but the relationship was weaker. Contrarily, larva recruitment did not change when exposed to a gradient of direct light, which may instead reflect effects of ALAN on moth physiology, such as disrupted female oviposition, or misdirecting behaviors essential to oviposition activity. Our results suggest that ALAN can positively influence the fitness of both plants and moths in this tightly co-evolved mutualism, but the benefits to each species may depend on whether night lighting is direct or indirect. Whether such effects and mechanisms could relate to susceptibility to the presence of ALAN on this or other plant–pollinator relationships will remain an important focus of future research. [ABSTRACT FROM AUTHOR]

The extent of artificial night light and anthropogenic noise (i.e., "light" and "noise") impacts is global and has the capacity to threaten species across diverse ecosystems. Existing research involving impacts of light or noise has primarily focused on noise or light alone and single species; however, these stimuli often co‐occur and little is known about how co‐exposure influences wildlife and if and why species may vary in their responses. Here, we had three aims: (1) to investigate species‐specific responses to light, noise, and the interaction between the two using a spatially explicit approach to model changes in abundance of 140 prevalent bird species across North America, (2) to investigate responses to the interaction between light exposure and night length, and (3) to identify functional traits and habitat affiliations that explain variation in species‐specific responses to these sensory stimuli with phylogenetically informed models. We found species that responded to noise exposure generally decreased in abundance, and the additional presence of light interacted synergistically with noise to exacerbate its negative effects. Moreover, the interaction revealed negative emergent responses for several species that only reacted when light and noise co‐occurred. Additionally, an interaction between light and night length revealed 47 species increased in abundance with light exposure during longer nights. In addition to modifying behavior with optimal temperature and potential foraging opportunities, birds might be attracted to light, yet suffer inadvertent physiological consequences. The trait that most strongly related to avian response to light and noise was habitat affiliation. Specifically, species that occupy closed habitat were less tolerant of both sensory stressors compared to those that occupy open habitat. Further quantifying the contexts and intrinsic traits that explain how species respond to noise and light will be fundamental to understanding the ecological consequences of a world that is ever louder and brighter. [ABSTRACT FROM AUTHOR]

Because of the COVID-19 pandemic, in-person services for individuals with neurodevelopmental disabilities were disrupted globally, resulting in a transition to remote delivery of services and therapies. For individuals with neurogenetic conditions, reliance on nonclinical caregivers to facilitate all therapies and care was unprecedented. The study aimed to (1) describe caregivers' reported impact on their dependent's services, therapies, medical needs, and impact on themselves as a result of the COVID-19 pandemic and (2) assess the relationship between the extent of disruption of services and the degree of self-reported caregiver burden. Two online questionnaires were completed by caregivers participating in Simons Searchlight in April and May 2020. Surveys were completed by caregivers of children or dependent adults with neurodevelopmental genetic conditions in Simons Searchlight. Caregivers reported that the impact of the COVID-19 pandemic moderately or severely disrupted services, therapies, or medical supports. The majority of caregivers were responsible for providing some aspect of therapy. Caregivers reported "feeling stressed but able to deal with problems as they arise," and reported lower anxiety at follow-up. Caregivers reported that telehealth services were not meeting the needs of those with complex medical needs. Future surveys will assess if and how medical systems, educational programs, therapists, and caregivers adapt to the challenges arising during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

White-nose syndrome is an introduced fungal disease that has reduced the size of hibernating populations of little brown bats Myotis lucifugus by 90% across much of eastern North America since 2007. Herein, we report the recapture of eight banded little brown bats, all males, with minimum ages of 18.6–25.6 y. The recaptures occurred during winter 2019–2020, at a hibernaculum in Michigan where white-nose syndrome likely has been present since 2013–2014, indicating that these old and apparently healthy males are in their seventh season of exposure to the disease. Hence, our data suggest that a long life in little brown bats and existence of white-nose syndrome are not necessarily incompatible. [ABSTRACT FROM AUTHOR]