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Given that tap dance offers so much Afrocentric history and expressive potential for today, shouldn’t it have a more solid presence in universities as a foundational American dance form?

Preventing the biogenesis of disease-relevant proteins is an attractive therapeutic strategy, but attempts to target essential protein biogenesis factors have been hampered by excessive toxicity. Here we describe KZR-8445, a cyclic depsipeptide that targets the Sec61 translocon and selectively disrupts secretory and membrane protein biogenesis in a signal peptide-dependent manner. KZR-8445 potently inhibits the secretion of pro-inflammatory cytokines in primary immune cells and is highly efficacious in a mouse model of rheumatoid arthritis. A cryogenic electron microscopy structure reveals that KZR-8445 occupies the fully opened Se61 lateral gate and blocks access to the lumenal plug domain. KZR-8445 binding stabilizes the lateral gate helices in a manner that traps select signal peptides in the Sec61 channel and prevents their movement into the lipid bilayer. Our results establish a framework for the structure-guided discovery of novel therapeutics that selectively modulate Sec61-mediated protein biogenesis.

Healthcare professionals experience negative behaviors such as incivility from various sources within the hospital environment. However, little is known regarding the experience of unlicensed assistive personnel with these behaviors. Using a cross-sectional survey design, the research team aimed to examine the presence, sources, and impact of negative behaviors among registered nurses and unlicensed assistive personnel within a US hospital. Descriptive and inferential statistics were used to analyze quantitative data, while thematic analysis was used to analyze the qualitative responses. A total of 309 participants completed the survey, and 135 participants responded to three qualitative questions. Most respondents identified inadequate staffing/resources to handle workload (87%) and job stress leading to loss of control over behavior as contributing factors to lateral/vertical aggression in the work environment (71%). Impacts of negative behavior on job performance were related to both personal well-being and the work environment. Demoralization was identified as a common consequence of negative behaviors for individuals and within the work environment. The results suggested that registered nurses, unlicensed assistive personnel, and nursing leadership may benefit from system-wide approaches addressing negative behaviors such as incivility within the clinical environment. Specifically, efforts and policies aimed at aiding clinicians in responding to negative behaviors could potentially improve the clinical environment.

Introduction: SMARCA4/SMARCA2 deficiencies have been linked to a variety of neoplasms and have been mainly described in cases of thoracic non-small cell lung cancers. Case Presentation: Here we present a case of SMARCA4/SMARCA2-deficient undifferentiated metastatic malignant tumor with carcinoma of unknown primary. The staining on pathology as well as the unremarkable size of the lung masses raises the possibility of dedifferentiated tumor of unknown primary. Conclusion: This case highlights the need for more routine testing of SMARCA4/SMARCA2 deficiencies as well as the development of more targeted therapies as these mutations are often associated with an aggressive course and poor outcomes.

Abstract Background Integrating complex interventions within healthcare settings can be challenging. Mentoring can be embedded within a randomised controlled trial (RCT) to upskill and support those delivering the intervention. This study aimed to understand, from a realist perspective, how mentoring worked to support implementation fidelity for occupational therapists (OTs) delivering a vocational rehabilitation (VR) intervention within the context of an RCT. Methods A realist evaluation using secondary data (emails, mentoring record forms, interviews) collected as part of an RCT. Three researchers coded the data following content analysis, focused on refining or refuting an initial programme theory by exploring the interactions between context, mechanisms, and outcomes. The research team met to further refine the programme theories. Results Data from 584 emails, 184 mentoring record forms, and 25 interviews were analysed following a realist approach. We developed a programme theory consisting of two contexts (trial set-up, ongoing mentoring), nine mechanisms (collective understanding, monitoring, timely support, positive reinforcement, reflective practice, support data completeness, facilitation strategy, shared learning experience, management of research and clinical duties), and three outcomes (improved confidence, improved fidelity, reduced contamination). Conclusions Offering mentoring support to OTs delivering a VR intervention as part of an RCT improves intervention fidelity and reduces the risk of contamination. It improves OTs’ understanding of the differences between their clinical and research roles and increases their confidence and competence in trial paperwork completion and identification of potential contamination issues.

Introduction: Lemierre’s syndrome is septic thrombophlebitis of the internal jugular vein, most commonly associated with head and neck infections. While central catheters are associated with venous thromboembolism and catheter-associated bacterial infections, cases of Lemierre’s syndrome caused by central catheters are extraordinarily rare.Case Report: We detail a case of Lemierre’s syndrome resulting from a peripherally inserted central catheter in a pregnant female patient. Diagnosis of this rare and potentially life-threatening disease process was expedited using point-of-care ultrasound.  Conclusion: Diagnosis of rare but potentially life- or limb-threatening pathologies is paramount to the successful practice of emergency medicine. Identifying these rare disease processes requires a high index of suspicion and a work-up strategy that includes consideration of medical history in combination with lab and imaging findings to determine appropriate interventions.

This study investigated the association between psychological stamina (grit, mindset and hardiness) and thinking style preferences among South African university students. Data were collected from 369 first-year university students using measures of grit, mindset, hardiness and thinking style preferences. The results indicated that different thinking style preferences were related to grit, mindset and hardiness. We argue that thinking styles should be considered as an important variable when supporting first-year students. Additionally, the role of grit and hardiness in student success should be considered in conjunction with the thinking style preferences of students. Avenues for further research are considered.

Aims To evaluate the myopia control efficacy of Diffusion Optics Technology (DOT) spectacle lenses in children over a 4-year treatment period.Methods CYPRESS Part 1 (NCT03623074) was a 3-year multicentre, randomised, controlled, double-masked trial comparing two investigational spectacle lens DOT designs (Test 1, Test 2) and standard single vision Control lenses in 256 North American children aged 6–10 years. Children completing Part 1 (n=200) were invited to enrol in CYPRESS Part 2 (NCT04947735) for an additional 1-year period. In Part 2, Test 1 (n=35) and Control groups (n=42) continued with their original lens assignment and the Test 2 group (n=21) were crossed over to Test 1 (DOT 0.2) lenses. The co-primary endpoints were change from baseline in axial length (AL) and cycloplegic spherical equivalent refraction (cSER).Results Test 1 spectacle lenses demonstrated superiority to the Control in both co-primary endpoints: with a difference between means (Test 1−Control) of −0.13 mm for AL (p=0.018) and 0.33 D for cSER (p=0.008) in Part 1 and −0.05 mm for AL (p=0.038) and 0.13 D for cSER (p=0.043) in Part 2. Comparing treatment effects in Part 1 and 2 suggests that COVID-19 public health restrictions negatively impacted treatment efficacy in study years 2 and 3.Conclusion DOT 0.2 spectacle lenses are safe and effective at reducing myopia progression, with additional benefit evident in year 4 of wear. These results support the hypothesis that a mild reduction in retinal contrast can slow myopia progression in young children. The unprecedented disruption in participant schooling and lifestyle during the COVID-19 pandemic may have depressed treatment efficacy in Part 1.

IntroductionElementary teachers face many challenges when including reform-based science instruction in their classrooms, and some teachers have chosen to enhance their science instruction by introducing students to citizen science (CS) projects. When CS projects are incorporated in formal school settings, students have an opportunity to engage in real-world projects as they collect and make sense of data, yet relatively few CS projects offer substantial guidance for teachers seeking to implement the projects, placing a heavy burden on teacher learning.MethodsFramed in theory on teacher relationships with curricula, we prepared science standards-aligned educative support materials for two CS projects. We present convergent mixed methods research that examines two teachers’ contrasting approaches to including school-based citizen science (SBCS) in their fifth-grade classrooms, each using support materials for one of the two CS projects. Both are veteran teachers at under-resourced Title 1 (an indicator of the high percentage of the students identified as economically disadvantaged) rural schools in the southeastern United States. We document the teachers’ interpretations and use of SBCS materials for the CS projects with data from classroom observations, instructional logs, teacher interviews, and student focus groups.ResultsOne teacher adapted the materials to include scaffolding to position students for success in data collection and analysis. In contrast, the second teacher adapted the SBCS support materials to maintain a teacher-centered approach to instruction, identifying perceptions of students’ limited abilities and limited instructional time as constraining factors.DiscussionWe discuss the intersection of CS projects in formal education and opportunities for engaging students in authentic science data collection, analysis, and sense-making. The two teachers’ stories identify the influences of school context and the need for teacher support to encourage elementary teachers’ use of SBCS instruction to supplement their science instruction.

BackgroundChild and Family Health Nursing (CFHN) services provide universal care to families during the first 2000 days (conception: 5 years) to support optimal health and developmental outcomes of children in New South Wales, Australia. The use of technology represents a promising means to encourage family engagement with CFHN services and enable universal access to evidenced-based age and stage information. Currently, there is little evidence exploring the acceptability of various models of technology-based support provided during the first 2000 days, as well as the maternal characteristics that may influence this. ObjectiveThis study aims to describe (1) the acceptability of technology-based models of CFHN support to families in the first 6 months, and (2) the association between the acceptability of technology-based support and maternal characteristics. MethodsA cross-sectional survey was undertaken between September and November 2021 with women who were 6-8 months post partum within the Hunter New England Local Health District of New South Wales, Australia. Survey questions collected information on maternal demographics and pregnancy characteristics, perceived stress, access to CFHN services, as well as preferences and acceptability of technology-based support. Descriptive statistics were used to describe the characteristics of the sample, the proportion of women accessing CFHN services, maternal acceptability of technology-based support from CFHN services, and the appropriateness of timing of support. Multivariable logistic regression models were conducted to assess the association between maternal characteristics and the acceptability of technology-based CFHN support. ResultsA total of 365 women participated in the study, most were 25 to 34 years old (n=242, 68%), had completed tertiary level education or higher (n=250, 71%), and were employed or on maternity leave (n=280, 78%). Almost all (n=305, 89%) women reported accessing CFHN services in the first 6 months following their child’s birth. The majority of women (n=282-315, 82%-92%) “strongly agreed or agreed” that receiving information from CFHN via technology would be acceptable, and most (n=308) women “strongly agreed or agreed” with being provided information on a variety of relevant health topics. Acceptability of receiving information via websites was significantly associated with maternal employment status (P=.01). The acceptability of receiving support via telephone and email was significantly associated with maternal education level (adjusted odds ratio 2.64, 95% CI 1.07-6.51; P=.03 and adjusted odds ratio 2.90, 95% CI 1.20-7.00; P=.02, respectively). Maternal age was also associated with the acceptability of email support (P=.04). ConclusionsTechnology-based CFHN support is generally acceptable to mothers. Maternal characteristics, including employment status, education level, and age, were found to modify the acceptability of specific technology modalities. The findings of this research should be considered when designing technology-based solutions to providing universal age and stage child health and developmental support for families during the first 2000 days.

Gestational thrombocytopenia, preeclampsia, and immune thrombocytopenia are commonly recognized etiologies of low platelet counts representing the vast majority of encountered gestational cases (86-100%). However, there are many other rare causes. The following case details a patient with three prior pregnancies, each remarkable for profound unexplained thrombocytopenia, which promptly normalized following delivery. It further details her fourth pregnancy, similar thrombocytopenia, an investigation into the causes, balancing platelet transfusion against the risk of alloimmunization, in-hospital treatment, and her eventual anesthetic, resuscitation, and delivery.

BackgroundCommon, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability among research and quality improvement efforts, to ensure findings are generalizable, and can be pooled to establish best practices.Research questionCan we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches?Study design and methodsA panel of 26 international experts in pediatric ventilator liberation, two methodologists, and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions that were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions.ResultsIn eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥ 80% agreement for all 16 definitions in the following areas: what constitutes respiratory support (invasive mechanical ventilation and noninvasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of noninvasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28 ventilator-free days, and planned vs rescue use of post-extubation noninvasive respiratory support.InterpretationWe propose that these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability and facilitate comparison.

Abstract Background Prognostic indicators for equine multinodular pulmonary fibrosis (EMPF), an interstitial fibrosing lung disease, are poorly described. Hypothesis/Objectives Describe diagnostic findings and outcome predictors for EMPF. Animals Forty‐six adult horses with EMPF. Methods Retrospective multicenter case series from 2009 to 2019. Radiographic (n = 27) and ultrasonographic studies (n = 19) from EMPF horses and bronchoalveolar lavage fluid (BALF) cytology from 6 EMPF and 13 asthma cases were independently reviewed and blinded to diagnosis and outcome. Associations between predictor variables and survival were assessed by predictor screening followed by Fisher's exact and Wilcoxon rank sum tests. Results Primary clinical findings were weight loss (36/46, 78%), increased respiratory effort (33/46, 72%), tachypnea (32/46, 70%), and fever (18/46, 39%). Macrophage atypia was seen in more EMPF than asthmatic horse BALF (67% vs. 8%; P = .02). Equine herpesvirus 5 (EHV‐5) was detected in 24 of 30 (80%) and hyperfibrinogenemia in 25 of 28 (89%) cases. Twenty‐seven of 46 horses (59%) and 11 of 45 (24%) survived to discharge and to 3 months, respectively. Three‐month survival was associated with lower median (range) respiratory rates (30 [24‐36] vs. 41 [30‐60] breaths per minute; P = .04), and higher BALF lymphocyte:neutrophil ratios (4.7 [1.4‐22] vs. 0.47 [0.11‐1.9]; P = .01) and blood lymphocyte counts (1.25 [0.93‐2.55] vs. 0.90 [0.70‐1.24] × 109/L; P = .03). Imaging findings, EHV‐5 detection, and corticosteroid treatment were not associated with survival. Conclusions and Clinical Importance Fever is not a sensitive clinical sign of EMPF. Diagnostic testing should be pursued for horses with increased respiratory rate and effort and weight loss. The prognosis for EMPF horses is poor. Corticosteroid treatment does not improve 3‐month survival.

Abstract Background Exoskeletons are increasingly applied during overground gait and balance rehabilitation following neurological impairment, although optimal parameters for specific indications are yet to be established. Objective This systematic review aimed to identify dose and dosage of exoskeleton-based therapy protocols for overground locomotor training in spinal cord injury/disease. Methods A systematic review was conducted in accordance with the Preferred Reporting Items Systematic Reviews and Meta-Analyses guidelines. A literature search was performed using the CINAHL Complete, Embase, Emcare Nursing, Medline ALL, and Web of Science databases. Studies in adults with subacute and/or chronic spinal cord injury/disease were included if they reported (1) dose (e.g., single session duration and total number of sessions) and dosage (e.g., frequency of sessions/week and total duration of intervention) parameters, and (2) at least one gait and/or balance outcome measure. Results Of 2,108 studies identified, after removing duplicates and filtering for inclusion, 19 were selected and dose, dosage and efficacy were abstracted. Data revealed a great heterogeneity in dose, dosage, and indications, with overall recommendation of 60-min sessions delivered 3 times a week, for 9 weeks in 27 sessions. Specific protocols were also identified for functional restoration (60-min, 3 times a week, for 8 weeks/24 sessions) and cardiorespiratory rehabilitation (60-min, 3 times a week, for 12 weeks/36 sessions). Conclusion This review provides evidence-based best practice recommendations for overground exoskeleton training among individuals with spinal cord injury/disease based on individual therapeutic goals – functional restoration or cardiorespiratory rehabilitation. There is a need for structured exoskeleton clinical translation studies based on standardized methods and common therapeutic outcomes.

Abstract Effects of plant diversity on grassland productivity, or overyielding, are found to be robust to nutrient enrichment. However, the impact of cumulative nitrogen (N) addition (total N added over time) on overyielding and its drivers are underexplored. Synthesizing data from 15 multi-year grassland biodiversity experiments with N addition, we found that N addition decreases complementarity effects and increases selection effects proportionately, resulting in no overall change in overyielding regardless of N addition rate. However, we observed a convex relationship between overyielding and cumulative N addition, driven by a shift from complementarity to selection effects. This shift suggests diminishing positive interactions and an increasing contribution of a few dominant species with increasing N accumulation. Recognizing the importance of cumulative N addition is vital for understanding its impacts on grassland overyielding, contributing essential insights for biodiversity conservation and ecosystem resilience in the face of increasing N deposition.

Abstract Plant diversity effects on community productivity often increase over time. Whether the strengthening of diversity effects is caused by temporal shifts in species-level overyielding (i.e., higher species-level productivity in diverse communities compared with monocultures) remains unclear. Here, using data from 65 grassland and forest biodiversity experiments, we show that the temporal strength of diversity effects at the community scale is underpinned by temporal changes in the species that yield. These temporal trends of species-level overyielding are shaped by plant ecological strategies, which can be quantitatively delimited by functional traits. In grasslands, the temporal strengthening of biodiversity effects on community productivity was associated with increasing biomass overyielding of resource-conservative species increasing over time, and with overyielding of species characterized by fast resource acquisition either decreasing or increasing. In forests, temporal trends in species overyielding differ when considering above- versus belowground resource acquisition strategies. Overyielding in stem growth decreased for species with high light capture capacity but increased for those with high soil resource acquisition capacity. Our results imply that a diversity of species with different, and potentially complementary, ecological strategies is beneficial for maintaining community productivity over time in both grassland and forest ecosystems.

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of ⩾80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ⩾80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.

Drought disrupts soil microbial activity and many biogeochemical processes. Although plant-associated fungi can support plant performance and nutrient cycling during drought, their effects on nearby drought-exposed soil microbial communities are not well resolved. We used H218O quantitative stable isotope probing (qSIP) and 16S rRNA gene profiling to investigate bacterial community dynamics following water limitation in the hyphospheres of two distinct fungal lineages (Rhizophagus irregularis and Serendipita bescii) grown with the bioenergy model grass Panicum hallii. In uninoculated soil, a history of water limitation resulted in significantly lower bacterial growth potential and growth efficiency, as well as lower diversity in the actively growing bacterial community. In contrast, both fungal lineages had a protective effect on hyphosphere bacterial communities exposed to water limitation: bacterial growth potential, growth efficiency, and the diversity of the actively growing bacterial community were not suppressed by a history of water limitation in soils inoculated with either fungus. Despite their similar effects at the community level, the two fungal lineages did elicit different taxon-specific responses, and bacterial growth potential was greater in R. irregularis compared to S. bescii-inoculated soils. Several of the bacterial taxa that responded positively to fungal inocula belong to lineages that are considered drought susceptible. Overall, H218O qSIP highlighted treatment effects on bacterial community structure that were less pronounced using traditional 16S rRNA gene profiling. Together, these results indicate that fungal-bacterial synergies may support bacterial resilience to moisture limitation.