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Educators are instrumental in nurturing students' sense of purpose, particularly in urban schools. Consequently, these educators must not only have a strong sense of purpose but also possess other key virtues. This mixed-methods study explores these virtues among a group of 30 urban Catholic school teachers. They responded to scales measuring purpose, compassion, faith, moral development and agency, and completed a modified Youth Purpose Interview online. Scores were compared to those of the original samples upon which these scales were validated as they were also emerging adults. Participants scored significantly higher on almost all scales than the original samples. These quantitative results and interview data revealed unique sources of purpose such as altruism and compassion towards high-need students. Overall, the participants are strongly disposed to fostering a sense of purpose among their students and respecting the dignity and worth of all persons.

Opinion 130 deals with a Request for an Opinion asking the Judicial Commission to clarify whether the genus name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate. The Request is approved and an answer is given. The name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate because it is a later homonym of the validly published cyanobacterial name Rhodococcus Hansgirg 1884. The Judicial Commission also clarifies that it has the means to resolve such cases by conserving a name over an earlier homonym. It is concluded that the name Rhodococcus Zopf 1891 (Approved Lists 1980) is significantly more important than the name Rhodococcus Hansgirg 1884 and therefore the former is conserved over the latter. This makes the name Rhodococcus Zopf 1891 (Approved Lists 1980) legitimate.

Over the past twenty years, Catholic elementary schools that self identify as "inner-city" have closed at a higher rate than Catholic schools in other locations. These schools have also long been associated with a legacy of effectively serving low-income students, students of color, and recent immigrant students, suggesting that the persistent closure of these schools may have a negative impact on these communities. In this paper, we set out to assess the extent to which there have been demographic or organizational changes over the past twenty years in these "inner-city" schools. We found that while these schools do still serve higher proportions of students of color than Catholic schools nationally, there are distinct organizational and demographic trends that have developed in these schools that merit additional analysis or investigation. We conclude this paper with several suggestions for how to build a research agenda around this up-to-date demographic and organizational analysis of this segment of U.S. Catholic elementary schools.

Abstract Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated the mechanisms through which cancer cells escape treatment, but their relation toward the tumor microenvironment (TME) remains elusive. Here we present a comprehensive transcriptomic landscape of the prostate TME at multiple points in the standard treatment timeline employing single-cell RNA-sequencing and spatial transcriptomics data from 120 patients. We identify club-like cells as a key epithelial cell subtype that acts as an interface between the prostate and the immune system. Tissue areas enriched with club-like cells have depleted androgen signaling and upregulated expression of luminal progenitor cell markers. Club-like cells display a senescence-associated secretory phenotype and their presence is linked to increased polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) activity. Our results indicate that club-like cells are associated with myeloid inflammation previously linked to androgen deprivation therapy resistance, providing a rationale for their therapeutic targeting.

Introduction: Spine fractures occur commonly in the geriatric population. Super-elderly individuals (i.e., those 80 years of age and older) represent a growing segment of the population and are especially prone to these fractures. The contemporary epidemiology of spine fractures in the super-elderly population is incompletely described in the literature. MATERIALS AND METHODS: This descriptive epidemiology study used the National Electronic Injury Surveillance System to examine the incidence and recent trends of spine fractures occurring among super-elderly individuals in the United States (US) from 2011 to 2020. Annual, overall, and age-/sex-specific incidence rates (IRs) were analyzed. Average annual percent change (AAPC) estimates were calculated to indicate the magnitude/direction of trends in annual injury rates. Results: An estimated n = 385,375 super-elderly patients sustained spine fractures over the 10-year study period for an overall IR of 31.5 per 10,000 person-years at-risk. Lumbar fractures (IR = 16.3) were the most common, followed by thoracic (IR = 9.4) and cervical (IR = 6.9) fractures. Incidence was significantly higher in super-elderly females (IR = 35.6) than in males (IR = 24.8). Incidence was significantly higher in nonagenarians (IR = 50.7) and centenarians (IR = 42.6) than in octogenarians (IR = 26.8). Accounting for population growth yielded a significantly increasing incidence over the study period from 20.8 in 2011 to 40.3 in 2020 (AAPC = 8, P < 0.0001). Conclusions: This study suggests that the annual incidence of spine fractures in the oldest cohort of patients in the US (80 + years of age) increased significantly during the recent decade from 2011 to 2020. Increased IRs highlight the need for future research aimed at optimizing outcomes and quality of life in this frail and ever-growing segment of the population.

Abstract Microtubules are essential for various cellular processes. The functional diversity of microtubules is attributed to the incorporation of various α- and β-tubulin isotypes encoded by different genes. In this work, we investigated the functional role of β4B-tubulin isotype (TUBB4B) in hearing and vision as mutations in TUBB4B are associated with sensorineural disease. Using a Tubb4b knockout mouse model, our findings demonstrate that TUBB4B is essential for hearing. Mice lacking TUBB4B are profoundly deaf due to defects in the inner and middle ear. Specifically, in the inner ear, the absence of TUBB4B lead to disorganized and reduced densities of microtubules in pillar cells, suggesting a critical role for TUBB4B in providing mechanical support for auditory transmission. In the middle ear, Tubb4b −/− mice exhibit motile cilia defects in epithelial cells, leading to the development of otitis media. However, Tubb4b deletion does not affect photoreceptor function or cause retinal degeneration. Intriguingly, β6-tubulin levels increase in retinas lacking β4B-tubulin isotype, suggesting a functional compensation mechanism. Our findings illustrate the essential roles of TUBB4B in hearing but not in vision in mice, highlighting the distinct functions of tubulin isotypes in different sensory systems.

The importance placed on passing Senior Secondary School Certificate Examinations (SSCE) in Nigeria has led to the emergence of 'Miracle Examination Centres' (MECs). MECs are schools where candidates get undeserving excellent SSCE results through institutionally enabled malpractice. This undermines the Nigerian education sector and its leadership. But well-researched empirical evidence on MECs in Nigeria is scarce. Through a reconnaissance technique (recce), we provide new evidence on MECs' activities, including their nature and patronage, while providing informed remedial pointers that can be harnessed by the education sector leadership. Interviews were conducted with 97 persons, comprising community members, teachers, and school owners across 16 communities in four study sites (Abuja, Anambra, Edo, and Kogi), and data were supported by observations. Elicited data were thematically analysed. Findings show that MECs were more interested in rents (informal and undue fees) by compromising SSCE standards and less interested in academic training. Community members were aware of the activities of MECs and could readily identify or discuss them. We uncovered the adopted processes in facilitating this kind of malpractice. A feasible strategy to address MECs and similar examination fraud syndicates across countries is for the education sector leadership to strategically focus on the demand and supply sides.

This study aimed to analyze second-semester organic chemistry students' problem-solving strategies, specifically focusing on the resources activated while solving problems on E2, E1, and E1cB elimination reactions. Using the theoretical framework by Elby and Hammer, we defined a resource as a unit of information used in the problem-solving process. The resources activated to solve elimination reaction problems were probed using a mixed-methods approach using survey assessments and think-aloud interviews. The data were analyzed quantitatively and qualitatively following a validated set of scoring criteria. The results align with existing findings that students focus on surface-level structural information and use resources that have been repetitively emphasized over multiple semesters. Resources related to acid-base chemistry were activated more often than reaction-specific resources, such as conformational analyses or carbocation rearrangements. Although acid-base resources aid students in successfully analyzing reaction mechanisms, additional resources must be activated to rationalize specific mechanisms and to explain the products formed. This calls for instructors to provide formative and summative assessments that evaluate the many resources required to elucidate elimination reaction mechanisms and product stereochemistry.

ImportanceProliferative verrucous leukoplakia (PVL) is an aggressive oral precancerous disease characterized by a high risk of transformation to invasive oral squamous cell carcinoma (OSCC), and no therapies have been shown to affect its natural history. A recent study of the PVL immune landscape revealed a cytotoxic T-cell-rich microenvironment, providing strong rationale to investigate immune checkpoint therapy.ObjectiveTo determine the safety and clinical activity of anti-programmed cell death 1 protein (PD-1) therapy to treat high-risk PVL.Design, setting, and participantsThis nonrandomized, open-label, phase 2 clinical trial was conducted from January 2019 to December 2021 at a single academic medical center; median (range) follow-up was 21.1 (5.4-43.6) months. Participants were a population-based sample of patients with PVL (multifocal, contiguous, or a single lesion ≥4 cm with any degree of dysplasia).InterventionPatients underwent pretreatment biopsy (1-3 sites) and then received 4 doses of nivolumab (480 mg intravenously) every 28 days, followed by rebiopsy and intraoral photographs at each visit.Main outcomes and measuresThe primary end point was the change in composite score (size and degree of dysplasia) from before to after treatment (major response [MR]: >80% decrease in score; partial response: 40%-80% decrease). Secondary analyses included immune-related adverse events, cancer-free survival (CFS), PD-1 ligand 1 (PD-L1) expression, 9p21.3 deletion, and other exploratory immunologic and genomic associations of response.ResultsA total of 33 patients were enrolled (median [range] age, 63 [32-80] years; 18 [55%] were female), including 8 (24%) with previously resected early-stage OSCC. Twelve patients (36%) (95% CI, 20.4%-54.8%) had a response by composite score (3 MRs [9%]), 4 had progressive disease (>10% composite score increase, or cancer). Nine patients (27%) developed OSCC during the trial, with a 2-year CFS of 73% (95% CI, 53%-86%). Two patients (6%) discontinued because of toxic effects; 7 (21%) experienced grade 3 to 4 immune-related adverse events. PD-L1 combined positive scores were not associated with response or CFS. Of 20 whole-exome sequenced patients, all 6 patients who had progression to OSCC after nivolumab treatment exhibited 9p21.3 somatic copy-number loss on pretreatment biopsy, while only 4 of the 14 patients (29%) who did not develop OSCC had 9p21.3 loss.Conclusions and relevanceThis immune checkpoint therapy precancer nonrandomized clinical trial met its prespecified response end point, suggesting potential clinical activity for nivolumab in high-risk PVL. Findings identified immunogenomic associations to inform future trials in this precancerous disease with unmet medical need that has been difficult to study.Trial registrationClinicalTrials.gov Identifier: NCT03692325.

BackgroundExisting interventions for co-occurring depression and cannabis use often do not treat both disorders simultaneously and can result in higher rates of symptom relapse. Traditional in-person interventions are often difficult to obtain due to financial and time limitations, which may further prevent individuals with co-occurring depression and cannabis use from receiving adequate treatment. Digital interventions can increase the scalability and accessibility for these individuals, but few digital interventions exist to treat both disorders simultaneously. Targeting transdiagnostic processes of these disorders with a digital intervention—specifically positive valence system dysfunction—may yield improved access and outcomes. ObjectiveRecent research has highlighted a need for the inclusion of individuals with lived experiences to assist in the co-design of interventions to enhance scalability and relevance of an intervention. Thus, the purpose of this study is to describe the process of eliciting feedback from individuals with elevated depressed symptoms and cannabis use and co-designing a digital intervention, Amplification of Positivity—Cannabis Use Disorder (AMP-C), focused on improving positive valence system dysfunction in these disorders. MethodsTen individuals who endorsed moderate to severe depressive symptoms and regular cannabis use (2-3×/week) were recruited online via Meta ads. Using a mixed methods approach, participants completed a 1-hour mixed methods interview over Zoom (Zoom Technologies Inc) where they gave their feedback and suggestions for the development of a mental health app, based on an existing treatment targeting positive valence system dysfunction, for depressive symptoms and cannabis use. The qualitative approach allowed for a broader investigation of participants’ wants and needs regarding the engagement and scalability of AMP-C, and the quantitative approach allowed for specific ratings of intervention components to be potentially included. ResultsParticipants perceived the 13 different components of AMP-C as overall helpful (mean 3.9-4.4, SD 0.5-1.1) and interesting (mean 4.0-4.9, SD 0.3-1.1) on a scale from 1 (not at all) to 5 (extremely). They gave qualitative feedback for increasing engagement in the app, including adding a social component, using notifications, and being able to track their symptoms and progress over time. ConclusionsThis study highlights the importance of including individuals with lived experiences in the development of interventions, including digital interventions. This inclusion resulted in valuable feedback and suggestions for improving the proposed digital intervention targeting the positive valence system, AMP-C, to better match the wants and needs of individuals with depressive symptoms and cannabis use.

Opinion 123 places the epithet of the name Aeromonas punctata on the list of rejected epithets and clarifies the citation of authors of selected names within the genus Aeromonas. Opinion 124 denies the request to place Borreliella on the list of rejected names because the request is based on a misinterpretation of the Code, which is clarified. There are alternative ways to solve the perceived problem. Opinion 125 denies the request to place Lactobacillus fornicalis on the list of rejected names because the provided information does not yield a reason for rejection. Opinion 126 denies the request to place Prolinoborus and Prolinoborus fasciculus on the list of rejected names because a relevant type strain deposit was not examined. Opinion 127 grants the request to assign the strain deposited as ATCC 4720 as the type strain of Agrobacterium tumefaciens, thereby correcting the Approved Lists. These Opinions were ratified by the voting members of the International Committee on Systematics of Prokaryotes.

Judicial Opinion 128 addresses nomenclatural issues related to the names of classes validly published under the International Code of Nomenclature of Prokaryotes. It is confirmed that the common ending -proteobacteria of some class names is not indicative of a joint taxonomic or phylogenetic placement; that the nomenclatural type of Mollicutes Edward and Freundt 1967 (Approved Lists 1980) is Mycoplasmatales Freundt 1955 (Approved Lists 1980); and that the placement of a name on the list of rejected names does not imply that another name with the same spelling but a distinct rank is also placed on that list. The names at the rank of class Anoxyphotobacteria (Gibbons and Murray 1978) Murray 1988, Archaeobacteria Murray 1988, Bacteria Haeckel 1894 (Approved Lists 1980), Firmibacteria Murray 1988, Microtatobiotes Philip 1956 (Approved Lists 1980), Oxyphotobacteria (ex Gibbons and Murray 1978) Murray 1988, Photobacteria Gibbons and Murray 1978 (Approved Lists 1980), Proteobacteria Stackebrandt et al. 1988, Schizomycetes Nägeli 1857 (Approved Lists 1980), Scotobacteria Gibbons and Murray 1978 (Approved Lists 1980) are placed on the list of rejected names. For three common nominative singular suffixes of genus names their genitive singular and nominative plural forms are confirmed: -bacter (-bacteris, -bacteres); -fex (-ficis, -fices); and -genes (-genis, -genes). The class names Aquificae Reysenbach 2002, Chrysiogenetes Garrity and Holt 2002, Chthonomonadetes Lee et al. 2011, Gemmatimonadetes Zhang et al. 2003, Opitutae Choo et al. 2007 and Verrucomicrobiae Hedlund et al. 1998 are orthographically corrected to Aquificia, Chrysiogenia, Chthonomonadia, Gemmatimonadia, Opitutia and Verrucomicrobiia, respectively.

In this paper the Judicial Commission provides general guidance for interpreting the International Code of Nomenclature of Prokaryotes (ICNP) and specific assistance to authors, reviewers and editors of a Request for an Opinion, or of other suggestions related to the ICNP. The role of the Judicial Commission is recapitulated, particularly with respect to the processing of such Requests. Selected kinds of nomenclature-related proposals are discussed that are unsuitable as the basis for a Request. Particular emphasis is put on Requests for placing names or epithets on the list of nomina rejicienda, and a dichotomous identification key is provided to guide potential authors of a Request that targets the name of a species or subspecies because of issues with its type strain. To this end, the criteria for the valid publication of such names under the ICNP are revisited. Aspects of other kinds of Requests are also addressed. The study is based on a comprehensive review of all Judicial Opinions issued since the publication of the Approved Lists in 1980. One goal of this paper is to assist potential authors in deciding whether their concern should be the subject of a Request, and if so, in composing it with the greatest chance of success. It is also clarified how to obtain additional help regarding nomenclature-related issues.

Calcium is important for the growth and development of plants. It serves crucial functions in cell wall and cell membrane structure and serves as a secondary messenger in signaling pathways relevant to nutrient and immunity responses. Thus, measuring calcium levels in plants is important for studies of plant biology and for technology development in food, agriculture, energy, and forest industries. Often, calcium in plants has been measured through techniques such as atomic absorption spectrophotometry (AAS), inductively coupled plasma-mass spectrometry (ICP-MS), and electrophysiology. These techniques, however, require large sample sizes, chemical extraction of samples or have limited spatial resolution. Here, we used near-edge X-ray absorption fine structure (NEXAFS) spectroscopy at the calcium L- and K-edges to measure the calcium to carbon mass ratio with spatial resolution in plant samples without requiring chemical extraction or large sample sizes. We demonstrate that the integrated absorbance at the calcium L-edge and the edge jump in the fluorescence yield at the calcium K-edge can be used to quantify the calcium content as the calcium mass fraction, and validate this approach with onion epidermal peels and ICP-MS. We also used NEXAFS to estimate the calcium mass ratio in hypocotyls of a model plant, Arabidopsis thaliana, which has a cell wall composition that is similar to that of onion epidermal peels. These results show that NEXAFS spectroscopy performed at the calcium edge provides an approach to quantify calcium levels within plants, which is crucial for understanding plant physiology and advancing plant-based materials.

ObjectivesComplex physiological adaptations often involve the coordination of molecular responses across multiple tissues. Establishing transcriptomic resources for non-traditional model organisms with phenotypes of interest can provide a foundation for understanding the genomic basis of these phenotypes, and the degree to which these resemble, or contrast, those of traditional model organisms. Here, we present a one-of-a-kind gene expression dataset generated from multiple tissues of two hibernating brown bears (Ursus arctos).Data descriptionThis dataset is comprised of 26 samples collected from 13 tissues of two hibernating brown bears. These samples were collected opportunistically and are typically not possible to attain, resulting in a highly unique and valuable gene expression dataset. In combination with previously published datasets, this new transcriptomic resource will facilitate detailed investigation of hibernation physiology in bears, and the potential to translate aspects of this biology to treat human disease.

Maternal obesity adversely impacts the in utero metabolic environment, but its effect on fetal hematopoiesis remains incompletely understood. During late development, the fetal bone marrow (FBM) becomes the major site where macrophages and B lymphocytes are produced via differentiation of hematopoietic stem and progenitor cells (HSPCs). Here, we analyzed the transcriptional landscape of FBM HSPCs at single-cell resolution in fetal macaques exposed to a maternal high-fat Western-style diet (WSD) or a low-fat control diet. We demonstrate that maternal WSD induces a proinflammatory response in FBM HSPCs and fetal macrophages. In addition, maternal WSD consumption suppresses the expression of B cell development genes and decreases the frequency of FBM B cells. Finally, maternal WSD leads to poor engraftment of fetal HSPCs in nonlethally irradiated immunodeficient NOD/SCID/IL2rγ-/- mice. Collectively, these data demonstrate for the first time that maternal WSD impairs fetal HSPC differentiation and function in a translationally relevant nonhuman primate model.

Abstract One of the great diagnostic challenges for children with pulmonary arterial hypertension is the need for general anesthesia (GA) to enable successful right heart catheterization. Here, for the first time, we describe how echocardiographic estimates of right ventricular function and pulmonary pressures change in pediatric patients during GA.

Abstract Critical loads (CLs) are frequently used to quantify terrestrial ecosystem impacts from nitrogen (N) deposition using ecological responses such as the growth and mortality of tree species. Typically, CLs are reported as a single value, with uncertainty, for an indicator across a species' entire range. Mediating factors such as climate and soil conditions can influence species' sensitivity to N, but the magnitudes of these effects are rarely calculated explicitly. Here, we quantify the spatial variability and estimation error in N CLs for the growth and survival of 10 different tree species while accounting for key environmental factors that mediate species sensitivity to N (e.g., soil characteristics). We used a bootstrapped machine learning approach to determine the level of N deposition at which a 1% decrease occurs in growth rate or survival probability at forest plot locations across the United States. We found minimal differences (8.5 kg N ha−1 year−1) within these regimes. We also evaluated the most important factors for predicting tree growth rates and mortality and found that climate, competition, and air pollution generally have the greatest influence on growth rates and survival probability. Lastly, we developed a new probability of exceedance metric for each species and found high likelihoods of exceedance across large portions (46%) of some species' ranges. Our analysis demonstrates that machine learning approaches provide a unique capability to: (1) quantify mediating factor influences on N sensitivity of trees, (2) estimate the error in local N CL estimates, and (3) generate localized N CLs with probabilities of exceedance for tree species.

The viscoelasticity of monoclonal antibodies (mAbs) is important during their production, formulation, and drug delivery. High concentration mAbs can provide higher efficacy therapeutics (e.g., during immunotherapy) and improved efficiency during their production (economy of scale during processing). Two humanized mAbs were studied (mAb-1 and mAb-2) with differing isoelectric points. Using high speed particle tracking microrheology, we demonstrated that the mAb solutions have significant viscoelasticities above concentrations of 40 mg/ml. Power law viscoelasticity was observed over the range of time scales ( 10 − 4–1 s) probed for the high concentration mAb suspensions. The terminal viscosity demonstrated an exponential dependence on mAb concentration (a modified Mooney relationship) as expected for charged stabilized Brownian colloids. Gelation of the mAbs was explored by lowering the pH of the buffer and a power law scaling of the gelation transition was observed, i.e., the exponent of the anomalous diffusion of the probe particles scaled inversely with the gelation time.