Explore the vast range of titles available.

Middle school principals are essential to creating a successful learning environment. They should possess expertise in adolescent development, foster a diverse and equitable school community, and invest in teacher development. This review searched, organized, and analyzed the literature between 2019 and 2024 specifically regarding middle school principal preparation programs and leadership approaches. We sought to identify any alignment with the leadership and organization characteristics outlined in the Association of Middle Level Education’s The Successful Middle School: This We Believe framework The findings revealed a slight relationship between principal preparation programs and the leadership and organizational characteristics outlined by Bishop and Harrison. Our findings also revealed that many states lack specific credentialing requirements for middle school principals. To strengthen the field of middle school education, specifically principal preparation, further research will help educational leaders align their practices with middle school characteristics and advocate for the required credentials in this field.

The purpose of our research was to identify challenges middle grades educators face as they strive to disrupt for justice in their predominantly white schools/districts. Developmentally and culturally responsive education for all middle grades students calls on educators to embrace justice-oriented teaching. Yet middle grades teachers attempting to disrupt unjust practices and policies are often met with significant challenges that can undermine their efforts. Research illustrating these challenges could help justice-oriented middle grades teachers and leaders prepare for and proactively address these challenges. This article draws on the experiences of a group of middle grades educators to illustrate the numerous challenges they faced while leading and engaging in justice-oriented initiatives in the predominantly white state of Vermont. We describe four categories of challenges faced by the group: (a) institutional challenges; (b) interpersonal challenges; (c) pedagogic challenges; and (d) inner challenges. Drawn from the findings, we offer implications for justice-oriented middle grades teachers, administrators, and teacher educators.

U.S. school achievement has been the subject of much discussion. In the case of science, technology, engineering, arts, and mathematics (STEAM), the national underperformance across the country, as well as the underrepresentation of minorities are key issues (Anderson et al., 2023; Handelsman & Smith, 2016; National Research Council, 2015; The White House, 2017). Particularly, there is a small, but growing body of research on the low numbers of Black women in STEAM, and the Black girl’s STEAM pipeline. Extracurricular STEAM programs have shown some success in increasing minority STEAM participation. As such, this dissertation seeks to investigate the following research questions: RQ1: How do online extracurricular STEAM programs created for Black girls serve as a potential space to increase STEAM identity? RQ2: Are there identifiable features that exist in online extracurricular STEAM programs that are important for creating a counterspace for adolescent Black girls? Through a qualitative case study, this dissertation explored Black girls’ participation in online STEAM programs. The findings of the study reveal that the extracurricular STEAM programs helped to foster STEAM identities in young Black girls. The programs also help students build a sense of community and create a safe space for Black girls. The study provides implications and recommendations for educators and policymakers who are interested in increasing minority STEAM participation.

The Human Connectome Projects in Development (HCP-D) and Aging (HCP-A) are two large-scale brain imaging studies that will extend the recently completed HCP Young-Adult (HCP-YA) project to nearly the full lifespan, collecting structural, resting-state fMRI, task-fMRI, diffusion, and perfusion MRI in participants from 5 to 100+ years of age. HCP-D is enrolling 1300+ healthy children, adolescents, and young adults (ages 5–21), and HCP-A is enrolling 1200+ healthy adults (ages 36–100+), with each study collecting longitudinal data in a subset of individuals at particular age ranges. The imaging protocols of the HCP-D and HCP-A studies are very similar, differing primarily in the selection of different task-fMRI paradigms. We strove to harmonize the imaging protocol to the greatest extent feasible with the completed HCP-YA (1200+ participants, aged 22–35), but some imaging-related changes were motivated or necessitated by hardware changes, the need to reduce the total amount of scanning per participant, and/or the additional challenges of working with young and elderly populations. Here, we provide an overview of the common HCP-D/A imaging protocol including data and rationales for protocol decisions and changes relative to HCP-YA. The result will be a large, rich, multi-modal, and freely available set of consistently acquired data for use by the scientific community to investigate and define normative developmental and aging related changes in the healthy human brain. •The Lifespan HCP in Development and Aging aim to characterize brain connectivity changes in human childhood and aging.•Here, we report on the multimodal brain imaging protocol being used for both projects.•We report pilot and ancillary data that informed the selection of hardware and imaging parameters.•The resulting data will be publicly released in unprocessed and minimally processed formats.

Defects in DNA single-strand break repair are associated with neurodevelopmental and neurodegenerative disorders. One such disorder is that resulting from mutations in XRCC1 , a scaffold protein that plays a central role in DNA single-strand base repair. XRCC1 is recruited at sites of single-strand breaks by PARP1, a protein that detects and is activated by such breaks and is negatively regulated by XRCC1 to prevent excessive PARP binding and activity. Loss of XRCC1 leads to the toxic accumulation and activity of PARP1 at single-strand breaks leading to base excision repair defects, a mechanism that may underlie pathological changes in patients carrying deleterious XRCC1 mutations. Here, we demonstrate that xrcc1 knockdown impairs development of the cerebellar plate in zebrafish. In contrast, parp1 knockdown alone does not significantly affect neural development, and instead rescues the cerebellar defects observed in xrcc1 mutant larvae. These findings support the notion that PARP1 inhibition may be a viable therapeutic candidate in neurological disorders.

The discovery of the genetic cause of an inflammatory disorder shows that, in winnowing down candidate variants obtained by DNA sequencing screens, geneticists have been (so to speak) throwing the baby out with the bath water.

Background Recombinant human pentraxin-2 (rhPTX-2) significantly decreased decline in percent predicted forced vital capacity (FVC) and stabilized 6-min walk distance (6MWD) in patients with idiopathic pulmonary fibrosis (IPF) during the 28-week, placebo-controlled, randomized period of the Phase II PRM-151–202 study. Interim (76-week) data from the open-label extension (OLE) demonstrated sustained safety and efficacy with rhPTX-2 treatment. Here, we present the entire long-term OLE safety and efficacy data to 128 weeks. Methods Patients who completed the randomized PRM-151–202 study period were eligible for the OLE, during which all patients received rhPTX-2, having started rhPTX-2 (i.e., crossed from placebo) or continued rhPTX-2 after Week 28. rhPTX-2 was administered in 28-week cycles, with 10 mg/kg intravenous infusions (60 min) on Days 1, 3, and 5 in the first week of each cycle, then one infusion every 4 weeks up to Week 128. The OLE primary objective was to assess the long-term safety and tolerability of rhPTX-2. Other outcomes included FVC, 6MWD, and patient-reported outcomes (descriptive analysis). Results All 111 patients who completed the randomized period entered the OLE (n = 37 started rhPTX-2; n = 74 continued rhPTX-2); 57 (51.4%) completed to Week 128. The treatment-emergent adverse event (TEAE) profile was consistent with the randomized period, with the majority of TEAEs graded mild or moderate. Serious TEAEs occurred in 47 patients (42.3%), most frequently IPF (n = 11; 9.9%), pneumonia (n = 7; 6.3%), and acute respiratory failure (n = 3; 2.7%). Three patients underwent lung transplantation. Most serious TEAEs (and all 14 fatal events) were considered unrelated to rhPTX-2 treatment. For patients starting vs continuing rhPTX-2, mean (95% confidence interval) changes from baseline to Week 128 were, respectively, − 6.2% (− 7.7; − 4.6) and − 5.7% (− 8.0; − 3.3) for percent predicted FVC and − 36.3 m (− 65.8; − 6.9) and − 28.9 m (− 54.3; − 3.6) for 6MWD; however, conclusions were limited by patient numbers at Week 128. Conclusions Long-term treatment (up to 128 weeks) with rhPTX-2 was well tolerated in patients with IPF, with no new safety signals emerging in the OLE. The limited efficacy data over 128 weeks may suggest a trend towards a treatment effect. Trial registration NCT02550873; EudraCT 2014-004782-24.

Metastatic neuroendocrine tumors secrete serotonin and other vasoactive substances that are responsible for carcinoid syndrome and carcinoid heart disease. We sought to evaluate the discriminatory utility of diagnostic biomarkers in determining the presence and severity of carcinoid heart disease in patients with metastatic neuroendocrine tumors. A cross-sectional study of patients with neuroendocrine tumors with documented liver metastases and/or carcinoid syndrome between April 2009-October 2012 in 5 tertiary referral centers. Serum was analyzed for Chromogranin A, Chromogranin B and N-terminal pro Brain Natriuretic Peptide (NT-proBNP). Plasma was analyzed for Neurokinin A and 5-Hydroxyindoleacetic acid (5HIAA). Echocardiography was used to determine the presence and severity of carcinoid heart disease. Non-parametric receiver operating characteristic curves were constructed for biomarkers, and the area under the curve determined. The severity of cardiac involvement was correlated with the concentration of each biomarker. A total of 187 patients were identified of whom 37 (20%) had carcinoid heart disease. Significantly higher median values of all biomarkers were found in the patients with cardiac involvement. NT-proBNP and plasma 5HIAA had the highest areas under the curve for the prediction of carcinoid heart disease [NT-proBNP 0.82 (95% confidence interval 0.74-0.90, p<0.0001) and 5HIAA 0.85 (95% confidence interval 0.78-0.92, p<0.0001]. NT-proBNP was moderately correlated (r = 0.48, p<0.001) whereas plasma 5HIAA was only weakly correlated (r = 0.34, p<0.001) with the echocardiographic severity score. NT-proBNP and plasma 5HIAA are both sensitive and specific biomarkers for the presence of carcinoid heart disease whereas only NT-proBNP is moderately correlated with disease severity.

Middle grades teachers and middle grades teacher educators are practicing in a complex sociocultural and sociopolitical moment. As part of the recent critical turn in middle grades education, antiracist teaching and equity pedagogies have gained momentum in the middle grades education literature. Calls to engage in these practices, however, have been met with education legislation and policies intended to forestall equity-oriented teaching. In this context, middle grades teacher educators have an especially important role to play in helping prepare and support justice-oriented preservice and in-service middle grades teachers. In this collaborative self-study of teacher education practices, the authors looked closely at the experiences of five facilitators of a critical professional development institute and also engaged the perspectives of professional development leaders. Together, the authors sought to understand both the strategies and tensions in their work to engage middle grades teachers in critically conscious practice. Study findings describe both teacher educator strategies for the implementation of critical professional development and the possible tensions in this work.

Targeting cell division by chemotherapy is a highly effective strategy to treat a wide range of cancers. However, there are limitations of many standard-of-care chemotherapies: undesirable drug toxicity, side-effects, resistance and high cost. New small molecules which kill a wide range of cancer subtypes, with good therapeutic window in vivo, have the potential to complement the current arsenal of anti-cancer agents and deliver improved safety profiles for cancer patients. We describe results with a new anti-cancer small molecule, WEHI-7326, which causes cell cycle arrest in G2/M, cell death in vitro, and displays efficacious anti-tumor activity in vivo. WEHI-7326 induces cell death in a broad range of cancer cell lines, including taxane-resistant cells, and inhibits growth of human colon, brain, lung, prostate and breast tumors in mice xenografts. Importantly, the compound elicits tumor responses as a single agent in patient-derived xenografts of clinically aggressive, treatment-refractory neuroblastoma, breast, lung and ovarian cancer. In combination with standard-of-care, WEHI-7326 induces a remarkable complete response in a mouse model of high-risk neuroblastoma. WEHI-7326 is mechanistically distinct from known microtubule-targeting agents and blocks cells early in mitosis to inhibit cell division, ultimately leading to apoptotic cell death. The compound is simple to produce and possesses favorable pharmacokinetic and toxicity profiles in rodents. It represents a novel class of anti-cancer therapeutics with excellent potential for further development due to the ease of synthesis, simple formulation, moderate side effects and potent in vivo activity. WEHI-7326 has the potential to complement current frontline anti-cancer drugs and to overcome drug resistance in a wide range of cancers.