The Covid-19 pandemic greatly disrupted educational systems around the world. Given their extensive stakeholder network, Schools and Colleges of Education played an important role in providing leadership across all dimensions of education throughout the pandemic. This paper presents results from an interview based study of Deans of Schools of Education in the United States with a special focus on how they sought to address issues of diversity, equity and inclusion throughout the pandemic. Results show that while there was a great deal of variability in the responses of Deans and Schools of Education many promising practices emerged that are potentially scalable and shareable to other institutions. La pandemia de Covid-19 interrumpió en gran medida los sistemas educativos de todo el mundo. Dada su extensa red, las Escuelas y Facultades de Educación desempeñaron un papel importante al brindar liderazgo en todas las dimensiones de la educación durante la pandemia. Este documento presenta los resultados de un estudio basado en entrevistas a decanos de escuelas de Educación en los Estados Unidos con un enfoque especial en cómo trataron de abordar cuestiones de diversidad, equidad e inclusión durante la pandemia. Los resultados muestran que, si bien hubo una gran variabilidad en las respuestas de los decanos y las escuelas de educación, surgieron muchas prácticas prometedoras que son potencialmente escalables y compartibles con otras instituciones.

Abstract: Students who are engaged writers are likely to produce better writing and to enjoy writing more than students who are disengaged writers. Yet, we are unaware of any existing tool that validly and reliably measures writing engagement. In this article, we describe what writing engagement is and why it is important. Then, we present the Writing Engagement Scale, a valid and reliable tool for measuring writing engagement, and outline how teachers can use this tool to better inform writing instruction in their classrooms.

This article reports on the implementation of a formative assessment tool (the Writing Engagement Scale, or WES) in grades 3–5 in schools in the United States. We used confirmatory factor analysis (CFA) to collect validity evidence for the WES for our population. Results demonstrated acceptable validity and reliability. In addition, survey results indicated that teachers perceived the WES to be useful as a formative writing assessment. We make the case that the WES provides an opportunity to inform teachers’ practice and help researchers understand the dimensions of students’ engagement in writing.

Antibody-dependent cellular cytotoxicity (ADCC) is a key effector mechanism of natural killer (NK) cells that is mediated by therapeutic monoclonal antibodies (mAbs). This process is facilitated by the Fc receptor CD16a on human NK cells. CD16a appears to be the only activating receptor on NK cells that is cleaved by the metalloprotease a disintegrin and metalloproteinase-17 upon stimulation. We previously demonstrated that a point mutation of CD16a prevents this activation-induced surface cleavage. This noncleavable CD16a variant is now further modified to include the high-affinity noncleavable variant of CD16a (hnCD16) and was engineered into human induced pluripotent stem cells (iPSCs) to create a renewable source for human induced pluripotent stem cell-derived NK (hnCD16-iNK) cells. Compared with unmodified iNK cells and peripheral blood-derived NK (PB-NK) cells, hnCD16-iNK cells proved to be highly resistant to activation-induced cleavage of CD16a. We found that hnCD16-iNK cells were functionally mature and exhibited enhanced ADCC against multiple tumor targets. In vivo xenograft studies using a human B-cell lymphoma demonstrated that treatment with hnCD16-iNK cells and anti-CD20 mAb led to significantly improved regression of B-cell lymphoma compared with treatment utilizing anti-CD20 mAb with PB-NK cells or unmodified iNK cells. hnCD16-iNK cells, combined with anti-HER2 mAb, also mediated improved survival in an ovarian cancer xenograft model. Together, these findings show that hnCD16-iNK cells combined with mAbs are highly effective against hematologic malignancies and solid tumors that are typically resistant to NK cell-mediated killing, demonstrating the feasibility of producing a standardized off-the-shelf engineered NK cell therapy with improved ADCC properties to treat malignancies that are otherwise refractory.

Germline SAMD9 and SAMD9L mutations cause a spectrum of multisystem disorders that carry a markedly increased risk of developing myeloid malignancies with somatic monosomy 7. Here, we describe 16 siblings, the majority of which were phenotypically normal, from 5 families diagnosed with myelodysplasia and leukemia syndrome with monosomy 7 (MLSM7; OMIM 252270) who primarily had onset of hematologic abnormalities during the first decade of life. Molecular analyses uncovered germline SAMD9L (n = 4) or SAMD9 (n = 1) mutations in these families. Affected individuals had a highly variable clinical course that ranged from mild and transient dyspoietic changes in the bone marrow to a rapid progression of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with monosomy 7. Expression of these gain-of-function SAMD9 and SAMD9L mutations reduces cell cycle progression, and deep sequencing demonstrated selective pressure favoring the outgrowth of clones that have either lost the mutant allele or acquired revertant mutations. The myeloid malignancies of affected siblings acquired cooperating mutations in genes that are also altered in sporadic cases of AML characterized by monosomy 7. These data have implications for understanding how SAMD9 and SAMD9L mutations contribute to myeloid transformation and for recognizing, counseling, and treating affected families.

The development of immunotherapeutic monoclonal antibodies targeting checkpoint inhibitory receptors, such as programmed cell death 1 (PD-1), or their ligands, such as PD-L1, has transformed the oncology landscape. However, durable tumor regression is limited to a minority of patients. Therefore, combining immunotherapies with those targeting checkpoint inhibitory receptors is a promising strategy to bolster antitumor responses and improve response rates. Natural killer (NK) cells have the potential to augment checkpoint inhibition therapies, such as PD-L1/PD-1 blockade, because NK cells mediate both direct tumor lysis and T cell activation and recruitment. However, sourcing donor-derived NK cells for adoptive cell therapy has been limited by both cell number and quality. Thus, we developed a robust and efficient manufacturing system for the differentiation and expansion of high-quality NK cells derived from induced pluripotent stem cells (iPSCs). iPSC-derived NK (iNK) cells produced inflammatory cytokines and exerted strong cytotoxicity against an array of hematologic and solid tumors. Furthermore, we showed that iNK cells recruit T cells and cooperate with T cells and anti-PD-1 antibody, further enhancing inflammatory cytokine production and tumor lysis. Because the iNK cell derivation process uses a renewable starting material and enables the manufacturing of large numbers of doses from a single manufacture, iNK cells represent an "off-the-shelf" source of cells for immunotherapy with the capacity to target tumors and engage the adaptive arm of the immune system to make a "cold" tumor "hot" by promoting the influx of activated T cells to augment checkpoint inhibitor therapies.