Search

As an instructor of the developmental reading and writing course at Texas State University, Barrie McGee is required per state mandate to design a course as an accelerated version of an integrated reading and writing (IRW) course. Furthermore, she is uniquely positioned as a student enrolled in the program in developmental education to access literature on theory and research relevant to integrating reading and writing to help inform her instructional choices. For example, Bartholemae and Petrosky's (1986) seminal work, "Facts, Artifacts, and Counterfacts," has done much to help her envision what such a course would look like including, assignments and reflections on student writing and insights of the difficulty underprepared students have imagining themselves as readers and writers. However, it is Salvatori's (1996) difficulty paper assignment, the topic discussed in her article, "Conversations with Texts: Reading in the Teaching of Composition," which resonates with McGee as paving a way for students to engage in conversation with the text and to prepare for class discussions by writing a one-page description of any difficulty they noted in a given reading. Drawing from Salvatori's (1996) article, McGee argues that the difficulty paper assignment provides a flexible framework for instruction in the IRW course that reflects the features of Rosenblatt's transactional theory of reading and writing and which perceives what she terms "leaning into difficulty" as a way to build new knowledge. In this article, she begins broadly with a short discussion on the fundamentals of an IRW course according to Bartholemae and Petrosky (1986), and then moves into a more specific focus on Salvatori's (1996) rationale for and particulars of the difficulty paper assignment. McGee expands this view of the difficulty paper by examining its use in Sweeney and McBride's (2015) study to further highlight the flexibility of the assignment to gain insight into student experiences with reading. Final thoughts conclude the article.

In this mixed-methods study, we performed content analysis on openended survey items to reveal primary themes related to how PhD students are responding to the Trump policies and the COVID-19 pandemic. In our data set, 40.7% of the respondents reported that their career plans have been affected by Trump's antiscience policies, 54.5% by the COVID-19 pandemic. Our study revealed three themes, which were (1) awareness of the reduced funding for STEM (science, engineering, technology, and mathematics) and higher education, (2) heightened awareness of and commitment to the pursuit of social and racial justice, (3) interest in seeking job opportunities abroad. The top three themes for the COVID-19 pandemic were (1) shifting graduation timelines and adjusting research to the virtual campus life; (2) losing jobs, concerning about hiring freezes and fewer job openings; and (3) reconsidering their place in a STEM field postpandemic, including a possible complete change in career plans; thoughts of leaving the country for international jobs.

"Remedial Trap." "Bridge to Nowhere." "Completion Divide." Such language used to describe the field of Developmental Education (DE), especially by those outside the field, is undeniably deficit oriented. In this manuscript, we initiate a dialog that critiques such portrayals of DE, particularly those that appear in key documents that have had great influence on policy and legislation impacting DE. The manuscript is written symposium style, beginning with a coauthored reflection on the current terminology used to shape the narrative of a field, followed by responses by three professionals within the field. Respondents: Darolyn A. Flaggs, Assistant Professor of Education, Kennesaw State University; Michelle A. Francis, Reading Instructor, West Valley College; and Concetta A. Williams, Director of Composition, Chicago State University.

Challenges arising from the classroom behavioral management of students with social, emotional and behavioral difficulties are a concern for educational professionals. The purpose of this study is to review common elements of behavior interventions for the disruptive behaviors of children with social, emotional and behavioral difficulties. A systematic review was conducted through an electronic search of studies (from 2000 to 2017) on ERIC, Web of Science, FRANCIS, and MEDLINE databases. The inclusion criteria involved: (i) an intervention improving behaviors at school of children with disruptive behaviors; (ii) elementary school children with the majority of the sample or average age between 6-11 years old; (iii) at least one measurable outcome focusing on social/emotional/behavioral outcomes; (iv) single-case designs. Of the 5339 articles that were identified in the initial screening, 27 met the criteria to be included in the review. Common characteristics of successful interventions are discussed to make recommendations for future implementation.

In the hopes of deepening Basic Writing instructors' critical awareness of their authority in assigning meaning to student experience, we present a case study of two adult-arrival immigrant students. We explore the ways that writing instructors and tutors encourage students' personal narratives of persistence--rather than actual persistence habits--and shape their academic and person identities, at times in ways beyond students' choosing. We call into question the relevance and utility of applying the popular theoretical framework of symbolic capital (Bourdieu) to Basic Writing and college literacy pedagogy. Instead, we call for Basic Writing instructors to respond to students' personal narratives as a form of participation within a specific academic discourse community. This work requires refocusing the learning environment as a community of practice to center student agency alongside educators' and students' participation goals, while providing students with an explicit introduction to participation expectations so that they can make informed decisions about how and when they choose to share personal stories.

Abstract Background This study evaluates the implementation and running costs of an HIV self-testing (HIVST) distribution program in Eswatini. HIVST kits were delivered through community-based and workplace models using primary and secondary distribution. Primary clients could self-test onsite or offsite. This study presents total running economic costs of kit distribution per model between April 2019 and March 2020, and estimates average cost per HIVST kit distributed, per client self-tested, per client self-tested reactive, per client confirmed positive, and per client initiating antiretroviral therapy (ART). Methods Distribution data and follow-up phone interviews were analysed to estimate implementation outcomes. Results were presented for each step of the care cascade using best-case and worst-case scenarios. A top-down incremental cost-analysis was conducted from the provider perspective using project expenditures. Sensitivity and scenario analyses explored effects of economic and epidemiological parameters on average costs. Results Nineteen thousand one hundred fifty-five HIVST kits were distributed to 13,031 individuals over a 12-month period, averaging 1.5 kits per recipient. 83% and 17% of kits were distributed via the community and workplace models, respectively. Clients reached via the workplace model were less likely to opt for onsite testing than clients in the community model (8% vs 29%). 6% of onsite workplace testers tested reactive compared to 2% of onsite community testers. Best-case scenario estimated 17,458 (91%) clients self-tested, 633 (4%) received reactive-test results, 606 (96%) linked to confirmatory testing, and 505 (83%) initiated ART. Personnel and HIVST kits represented 60% and 32% of total costs, respectively. Average costs were: per kit distributed US$17.23, per client tested US$18.91, per client with a reactive test US$521.54, per client confirmed positive US$550.83, and per client initiating ART US$708.60. Lower rates for testing, reactivity, and linkage to care in the worst-case scenario resulted in higher average costs along the treatment cascade. Conclusion This study fills a significant evidence gap regarding costs of HIVST provision along the client care cascade in Eswatini. Workplace and community-based distribution of HIVST accompanied with effective linkage to care strategies can support countries to reach cascade objectives.

Abstract Widespread adoption of mirror-image biological systems presents difficulties in accessing the requisite D-protein substrates. In particular, mirror-image phage display has the potential for high-throughput generation of biologically stable macrocyclic D-peptide binders with potentially unique recognition modes but is hindered by the individualized optimization required for D-protein chemical synthesis. We demonstrate a general mirror-image phage display pipeline that utilizes automated flow peptide synthesis to prepare D-proteins in a single run. With this approach, we prepare and characterize 12 D-proteins – almost one third of all reported D-proteins to date. With access to mirror-image protein targets, we describe the successful discovery of six macrocyclic D-peptide binders: three to the oncoprotein MDM2, and three to the E3 ubiquitin ligase CHIP. Reliable production of mirror-image proteins can unlock the full potential of D-peptide drug discovery and streamline the study of mirror-image biology more broadly.

Abstract Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Admixed American ancestry group. Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies in many genes were consistent with the data from the public gnomAD database, with some notable exceptions resolved using gnomAD subsets. Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence. This work will allow targeted precision medicine efforts at revealed disparities.

Abstract Background Viviparity—live birth—is a complex and innovative mode of reproduction that has evolved repeatedly across the vertebrate Tree of Life. Viviparous species exhibit remarkable levels of reproductive diversity, both in the amount of care provided by the parent during gestation, and the ways in which that care is delivered. The genetic basis of viviparity has garnered increasing interest over recent years; however, such studies are often undertaken on small evolutionary timelines, and thus are not able to address changes occurring on a broader scale. Using whole genome data, we investigated the molecular basis of this innovation across the diversity of vertebrates to answer a long held question in evolutionary biology: is the evolution of convergent traits driven by convergent genomic changes? Results We reveal convergent changes in protein family sizes, protein-coding regions, introns, and untranslated regions (UTRs) in a number of distantly related viviparous lineages. Specifically, we identify 15 protein families showing evidence of contraction or expansion associated with viviparity. We additionally identify elevated substitution rates in both coding and noncoding sequences in several viviparous lineages. However, we did not find any convergent changes—be it at the nucleotide or protein level—common to all viviparous lineages. Conclusions Our results highlight the value of macroevolutionary comparative genomics in determining the genomic basis of complex evolutionary transitions. While we identify a number of convergent genomic changes that may be associated with the evolution of viviparity in vertebrates, there does not appear to be a convergent molecular signature shared by all viviparous vertebrates. Ultimately, our findings indicate that a complex trait such as viviparity likely evolves with changes occurring in multiple different pathways.

Abstract We describe here an individual from a fourth family with germline compound heterozygous MSH3 germline variants and its observed biological consequences. The patient was initially diagnosed with invasive moderately-differentiated adenocarcinoma of the colon at the age of 43. Germline multigene panel testing revealed a pathogenic variant MSH3 c.2436-1 G > A and a variant of (initial) uncertain significance MSH3 c.3265 A > T (p.Lys1089*). Germline genetic testing of family members confirm the variants are in trans with the c.2436-1 G > A variant of paternal and the c.3265 A > T variant of maternal origin. Tumor DNA exhibits low levels of microsatellite instability and elevated microsatellite alterations at selected tetranucleotide repeats (EMAST). Tissue immunohistochemical staining for MSH3 demonstrated variant MSH3 protein is present in the cytoplasm and cell membrane but not in the nucleus of normal and tumor epithelial cells. Furthermore, variant MSH3 is accompanied by loss of nuclear MSH6 and a reduced level of nuclear MSH2 in some tumor cells, suggesting that the variant MSH3 protein may inhibit binding of MSH6 to MSH2.

Abstract There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. The role of amyloid beta 42 (Aβ42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ42, which is increased from adipose tissue of male mice with obesity and is associated with higher plasma Aβ42. Increasing circulating Aβ42 levels in male mice without obesity has no effect on systemic glucose homeostasis but has obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. The closely related Aβ40 isoform does not have these same effects on the heart. Administration of an Aβ-neutralising antibody prevents obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aβ-neutralising antibody administration in established obesity prevents further deterioration of cardiac function. Multi-contrast transcriptomic analyses reveal that Aβ42 impacts pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aβ42 inhibits mitochondrial complex I. These data reveal a role for systemic Aβ42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure.

Abstract Methane (CH4) emissions from ruminants are of a significant environmental concern, necessitating accurate prediction for emission inventories. Existing models rely solely on dietary and host animal-related data, ignoring the predicting power of rumen microbiota, the source of CH4. To address this limitation, we developed novel CH4 prediction models incorporating rumen microbes as predictors, alongside animal- and feed-related predictors using four statistical/machine learning (ML) methods. These include random forest combined with boosting (RF-B), least absolute shrinkage and selection operator (LASSO), generalized linear mixed model with LASSO (glmmLasso), and smoothly clipped absolute deviation (SCAD) implemented on linear mixed models. With a sheep dataset (218 observations) of both animal data and rumen microbiota data (relative sequence abundance of 330 genera of rumen bacteria, archaea, protozoa, and fungi), we developed linear mixed models to predict CH4 production (g CH4/animal·d, ANIM-B models) and CH4 yield (g CH4/kg of dry matter intake, DMI-B models). We also developed models solely based on animal-related data. Prediction performance was evaluated 200 times with random data splits, while fitting performance was assessed without data splitting. The inclusion of microbial predictors improved the models, as indicated by decreased root mean square prediction error (RMSPE) and mean absolute error (MAE), and increased Lin’s concordance correlation coefficient (CCC). Both glmmLasso and SCAD reduced the Akaike information criterion (AIC) and Bayesian information criterion (BIC) for both the ANIM-B and the DMI-B models, while the other two ML methods had mixed outcomes. By balancing prediction performance and fitting performance, we obtained one ANIM-B model (containing 10 genera of bacteria and 3 animal data) fitted using glmmLasso and one DMI-B model (5 genera of bacteria and 1 animal datum) fitted using SCAD. This study highlights the importance of incorporating rumen microbiota data in CH4 prediction models to enhance accuracy and robustness. Additionally, ML methods facilitate the selection of microbial predictors from high-dimensional metataxonomic data of the rumen microbiota without overfitting. Moreover, the identified microbial predictors can serve as biomarkers of CH4 emissions from sheep, providing valuable insights for future research and mitigation strategies.

Abstract Lipotoxicity, the accumulation of lipids in non-adipose tissues, alters the metabolic transcriptome and mitochondrial metabolism in skeletal muscle. The mechanisms involved remain poorly understood. Here we show that lipotoxicity increased histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5), which reduced the expression of metabolic genes and oxidative metabolism in skeletal muscle, resulting in increased non-oxidative glucose metabolism. This metabolic reprogramming was also associated with impaired apoptosis and ferroptosis responses, and preserved muscle cell viability in response to lipotoxicity. Mechanistically, increased HDAC4 and 5 decreased acetylation of p53 at K120, a modification required for transcriptional activation of apoptosis. Redox drivers of ferroptosis derived from oxidative metabolism were also reduced. The relevance of this pathway was demonstrated by overexpression of loss-of-function HDAC4 and HDAC5 mutants in skeletal muscle of obese db/db mice, which enhanced oxidative metabolic capacity, increased apoptosis and ferroptosis and reduced muscle mass. This study identifies HDAC4 and HDAC5 as repressors of skeletal muscle oxidative metabolism, which is linked to inhibition of cell death pathways and preservation of muscle integrity in response to lipotoxicity.

Despite evidence from clinical trials showing the efficacy of shorter durations of therapy, most HER2-positive early breast cancer (EBC) patients receive a year of anti-HER2 therapy. A survey of Canadian oncologists was conducted online, with electronic data collection, and the analysis is reported descriptively. Measures collected included current practices with respect to the duration of adjuvant anti-HER2 therapy, perspectives on data regarding shorter durations of treatment, and interest in further trials on this subject. Responses were received from 42 providers across Canada. Half (50%, 21/42) reported having never recommended 6 months of anti-HER2 therapy. The primary reason physicians consider a shorter duration is in response to treatment-related toxicities (76%, 31/41). Most participants (79%, 33/42) expressed the need for more data to determine which patients can be safely and effectively treated with shorter durations. Patient factors such as young age, initial stage, hormone receptor status, and type of neoadjuvant chemotherapy were attributed to reluctance to offer shorter durations of treatment. Many respondents (83%, 35/42) expressed interest in participating in the proposed clinical trial of 6 months of anti-HER2 therapy. In contemporary Canadian practice, 12 months of anti-HER2 therapy remains the primary practice. Future trials are required to better define the role of shorter treatment durations.

Abstract Group A streptococcal strains potentially acquire new M protein gene types through genetic recombination (emm switching). To detect such variants, we screened 12,596 invasive GAS genomes for strains of differing emm types that shared the same multilocus sequence type (ST). Through this screening we detected a variant consisting of 16 serum opacity factor (SOF)-positive, emm pattern E, emm82 isolates that were ST36, previously only associated with SOF-negative, emm pattern A, emm12. The 16 emm82/ST36 isolates were closely interrelated (pairwise SNP distance of 0–43), and shared the same emm82-containing recombinational fragment. emm82/ST36 isolates carried the sof12 structural gene, however the sof12 indel characteristic of emm12 strains was corrected to confer the SOF-positive phenotype. Five independent emm82/ST36 invasive case isolates comprised two sets of genetically indistinguishable strains. The emm82/ST36 isolates were primarily macrolide resistant (12/16 isolates), displayed at least 4 different core genomic arrangements, and carried 11 different combinations of virulence and resistance determinants. Phylogenetic analysis revealed that emm82/ST36 was within a minor (non-clade 1) portion of ST36 that featured almost all ST36 antibiotic resistance. This work documents emergence of a rapidly diversifying variant that is the first confirmed example of an emm pattern A strain switched to a pattern E strain.

Imaging of proteoforms in human tissues is hindered by low molecular specificity and limited proteome coverage. Here, we introduce proteoform imaging mass spectrometry (PiMS), which increases the size limit for proteoform detection and identification by fourfold compared to reported methods and reveals tissue localization of proteoforms at

BackgroundImmune reconstitution bone loss (IRBL) is a common side-effect of antiretroviral therapy (ART) in people with human immunodeficiency virus (PWH). Immune reconstitution bone loss acts through CD4+ T-cell/immune reconstitution-induced inflammation and is independent of antiviral regimen. Immune reconstitution bone loss may contribute to the high rate of bone fracture in PWH, a cause of significant morbidity and mortality. Although IRBL is transient, it remains unclear whether bone recovers, or whether it is permanently denuded and further compounds bone loss associated with natural aging.MethodsWe used a validated IRBL mouse model involving T-cell reconstitution of immunocompromised mice. Mice underwent cross-sectional bone phenotyping of femur and/or vertebrae between 6 and 20 months of age by microcomputed tomography (µCT) and quantitative bone histomorphometry. CD4+ T cells were purified at 20 months to quantify osteoclastogenic/inflammatory cytokine expression.ResultsAlthough cortical IRBL in young animals recovered with time, trabecular bone loss was permanent and exacerbated skeletal decline associated with natural aging. At 20 months of age, reconstituted CD4+ T cells express enhanced osteoclastogenic cytokines including RANKL, interleukin (IL)-1β, IL-17A, and tumor necrosis factor-α, consistent with elevated osteoclast numbers.ConclusionsImmune reconstitution bone loss in the trabecular compartment is permanent and further exacerbates bone loss due to natural aging. If validated in humans, interventions to limit IRBL may be important to prevent fractures in aging PWH.

Reconstructing hydroclimate over the Common Era is essential for understanding the dominant mechanisms of precipitation change and improving climate model projections, which currently suggest Northeast Mexico will become drier in the future. Tree-ring reconstructions have suggested regional rainfall is primarily controlled by Pacific sea-surface temperatures (SSTs). However, tree ring records tend to reflect winter-spring rainfall, and thus may not accurately record total annual precipitation. Using the first multiproxy speleothem record spanning the last millennium, combined with results from an atmospheric general circulation model, we demonstrate mean annual rainfall in Northeast Mexico is highly sensitive to Atlantic SST variability. Our findings suggest future precipitation in Northeast Mexico is more dependent upon the warming of Tropical Atlantic SSTs relative to the Tropical Pacific.

President Trump's education policies continue to marginalize Black STEM students at the highest levels of education. Responding to a survey on their racialized educational experiences and future career trajectories, an ethnically diverse group of Black STEM doctoral students expressed anxiety about trying to pursue a STEM career during the Trump presidency. Their responses reflected their heightened sense of urgency to be change agents for racial justice in both the STEM arena and the wider society. These survey findings demonstrate that the Trump administration has created anxiety among minoritized people about pursuing STEM careers and triggered an activist spirit in this group of future STEM PhDs. In this paper, I discuss the ways the racist ideologies, practices, and policies of the Trump administration are impairing scientific innovation and increasing activism among Black STEMers. The findings reveal a vital need to continue discussing the consequences of the Trump administration's assault on Blacks in the STEM disciplines.

Background/Context: The United States invests in STEM education, but this investment is racialized and political. The country wants to maintain global economic domination, but there are also calls to diversify the STEM workforce (Baber, 2015; Basile & Lopez, 2015; Vakil & Ayers, 2019). This context leaves Black and Brown people to navigate racially hostile, toxic, and oppressive STEM learning and working environments (Bullock, 2017; Erete et al., 2020; Wright & Riley, 2021). Purpose/Objective/Research Question/Focus of Study: This conceptual paper offers strategies for institutionalizing equity ethics in STEM higher education. The paper attends to the core components of equity ethics and its possibilities while identifying structural constraints. Equity ethics is an equity-minded perspective that focuses on leveraging the multiple forms of knowledge associated with understanding and engaging the natural world to foster an oppression-free society that specifically enhances the lives of Black and Brown people. We also examine specific cases of STEM education and research scholars and practitioners who are committed to engaging and uplifting racially minoritized communities through the intersection of STEM and justice. Research Design: This conceptual paper takes a qualitative approach. It uses the existing literature to review the current state of diversity in STEM, the major components of an equity ethic, the structural and institutional barriers people of color face in STEM higher education, and how equity ethics may be institutionalized. In particular, we highlight examples of equity ethics in action to provide models for action and policy change. Conclusions/Recommendations: Institutionalized equity ethics at the mid-institutional level (e.g., departments and units) would require all faculty to mentor Black and Brown STEM students through critical transitions. We also recommend revising department- and unit-level policies and practices around access to resources that are critical for STEM achievement and knowledge production. Although expanding and sustaining financial investments in equity-focused endeavors is required, these investments must also come with the power and agency to transform institutional structures around STEM access, learning, and innovation. Transformation of top-level policies and practices could include changes to institutional admissions processes and ensuring that racist gatekeeping mechanisms are removed, while also requiring senior-level administrators to have training in racial justice ideologies and praxes. Building equity ethics into STEM higher education is essential to creating a more just and equitable STEM ecosystem.

Black women in graduate school can experience stress due to blatant and subtle acts of gendered racism. However, we do not know how such stressors are navigated over time among those who successfully complete their PhDs. The current study used a Black feminist thought framework and narrative analysis to conduct a longitudinal exploration of how three successful Black women biomedical graduate students make sense of and respond to gendered racism they experienced and the coping strategies they employ as they persist. When interacting with others, the women experienced low expectations and doubts about being legitimate scientists. These experiences contributed to feelings of isolation, impacted their networking opportunities, and dampened their view of the desirability of an academic career postgraduation. Over time, their coping strategies for dealing with negative racial and gendered racial stereotypes and biases shifted from opting to "prove others wrong" or working harder, to leaning on their social networks for camaraderie and advice as well as choosing to not exert energy to form a response. Implications for mentoring and mentoring programs at the graduate level and science, technology, engineering, and mathematics programming are discussed.

The experiences of underrepresented women and ethnic minorities in computer science (CS) fields are at the heart of understanding the factors that impact the critical transitions students face when entering into Science, Technology, Engineering, or Mathematics (STEM) careers. The research, conducted using a grounded theory approach, gauges student and teacher perspectives, specifically investigating minoritized student perspectives that influence their entrance and continuation into an educational pathway. The study’s outcomes underscore the crucial roles of (1) Student Family Encouragement, (2) School and Community Engagement, and (3) Professional/Teacher Mentorship as critical junctions that school districts should be aware of when creating student pathways into college and career, particularly for underrepresented groups.

The adoption of a blended learning approach is increasing among higher education institutions with a significant amount of research that focuses on linear relationships. However, there is limited research on how the blended learning environment functions and interacts as a complex system. There is a need for more research that explores the relationships that exist within a blended learning environment using a system-based framework, such as the Complex Adaptive Blended Learning Systems (CABLS) framework. The purpose of this qualitative phenomenological study was to explore the perceived relationships that exist within the CABLS in a higher education blended learning environment. Interviews were conducted with the learner, teacher, institutional administrators, and learning support staff. A thematic analysis was used to identify themes to better understand stakeholder relationships within the CABLS framework. The results of this study seek to provide all stakeholders with a better understanding of the complex interdependent relationships within the CABLS framework to optimize a collaborative approach to blended learning.