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Objective: The purpose of this study was to compare two pedagogical methods, active learning and passive instruction, to determine which is more useful in helping students to achieve the learning outcomes in a one-hour research skills instructional session.Methods: Two groups of high school students attended an instructional session to learn about consumer health resources and strategies to enhance their searching skills. The first group received passive instruction, and the second engaged in active learning. We assessed both groups’ learning using 2 methods with differing complexity. A total of 59 students attended the instructional sessions (passive instruction, n=28; active learning, n=31).Results: We found that the active learning group scored more favorably in four assessment categories.Conclusions: Active learning may help students engage with and develop a meaningful understanding of several resources in a single session. Moreover, when using a complex teaching strategy, librarians should be mindful to gauge learning using an equally complex assessment method.

Dartmouth College’s demographics have shifted over the past one hundred years, from an almost entirely all male, white, and wealthy student body, to one with gender, racial, ethnic, and socioeconomic diversity. During this time, the College has endeavored to maintain its reputation as an academically exclusive institution for the intellectual elite while simultaneously opening its doors continually wider to a more diverse student population. These aspirations, for broad inclusivity within the bounds of narrow exclusivity, have frequently worked in opposition to one another, and Dartmouth’s administrators have led the College in a delicate balancing act amid shifting alumni demands, student needs, cultural expectations, and institutional priorities. I explore how, at four key points in the College’s history, boundaries of exclusion and inclusion have been enacted and how those boundaries have been defined, redefined, and reshaped. I focus each of the four sections on a time period during which national and local events shaped Dartmouth at multiple levels. I center each time period around a story that exemplifies the changes happening at the time, and I contextualize each story, exploring the circumstances that led up to it and the consequences that followed. I selected the four time periods based not on those the College uses to tell its own history, but by identifying national periods of historical significance in the role of higher education, understandings of gender, cultures of dominant and marginalized groups, individual and institutional identity development, and the evolution of political movements. I use literature from history, cultural studies, women studies, education, sociology, and psychology to interpret and contextualize a myriad of primary source documents from Dartmouth’s past including personal correspondence, student memorabilia books, official publications, presidential speeches, oral histories, student publications, admissions documentation, and meeting notes from Greek organizations. Through my research, I conclude that while significant progress has been made in diversifying Dartmouth—the campus looks markedly different than it did a century ago and the present-day student experience likely would seem foreign to a student from the class of 1917—the College still is steeped in its history in ways that sometimes surprise, and frequently anger, members of Dartmouth’s community who expect and demand more.

Abstract Liquid biopsy, particularly the analysis of circulating tumor DNA (ctDNA), has demonstrated considerable promise for numerous clinical intended uses. Successful validation and commercialization of novel ctDNA tests have the potential to improve the outcomes of patients with cancer. The goal of the Blood Profiling Atlas Consortium (BloodPAC) is to accelerate the development and validation of liquid biopsy assays that will be introduced into the clinic. To accomplish this goal, the BloodPAC conducts research in the following areas: Data Collection and Analysis within the BloodPAC Data Commons; Preanalytical Variables; Analytical Variables; Patient Context Variables; and Reimbursement. In this document, the BloodPAC’s Analytical Variables Working Group (AV WG) attempts to define a set of generic analytical validation protocols tailored for ctDNA-based Next-Generation Sequencing (NGS) assays. Analytical validation of ctDNA assays poses several unique challenges that primarily arise from the fact that very few tumor-derived DNA molecules may be present in circulation relative to the amount of nontumor-derived cell-free DNA (cfDNA). These challenges include the exquisite level of sensitivity and specificity needed to detect ctDNA, the potential for false negatives in detecting these rare molecules, and the increased reliance on contrived samples to attain sufficient ctDNA for analytical validation. By addressing these unique challenges, the BloodPAC hopes to expedite sponsors’ presubmission discussions with the Food and Drug Administration (FDA) with the protocols presented herein. By sharing best practices with the broader community, this work may also save the time and capacity of FDA reviewers through increased efficiency.

Impaired TGF-β signaling due to SMAD4 mutation in PDAC tumors initiates a STAT3-dependent signaling cascade that leads to increased stromal stiffening and disease progression. Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality, yet antistromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor-β (TGF-β) signaling have high epithelial STAT3 activity and develop stiff, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several KRAS-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby STAT3 signaling promotes tumor progression by increasing matricellular fibrosis and tissue tension. In contrast, epithelial STAT3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated STAT3 were associated with SMAD4 mutation and shorter survival. The findings implicate epithelial tension and matricellular fibrosis in the aggressiveness of SMAD4 mutant pancreatic tumors and highlight STAT3 and mechanics as key drivers of this phenotype.

Catalysts consisting of metal particles supported on reducible oxides exhibit promising activity and selectivity for a variety of current and emerging industrial processes. Enhanced catalytic activity can arise from direct contact between the support and the metal or from metal-induced promoter effects on the oxide. Discovering the source of enhanced catalytic activity and selectivity is challenging, with conflicting arguments often presented based on indirect evidence. Here, we separate the metal from the support by a controlled distance while maintaining the ability to promote defects via the use of carbon nanotube hydrogen highways. As illustrative cases, we use this approach to show that the selective transformation of furfural to methylfuran over Pd/TiO 2 occurs at the Pd-TiO 2 interface while anisole conversion to phenol and cresol over Cu/TiO 2 is facilitated by exposed Ti 3+ cations on the support. This approach can be used to clarify many conflicting arguments in the literature. Understanding the location and nature of the catalytic active site is critical for controlling a catalyst’s activity and selectivity. Here, the authors separate the metal from the support by a controlled distance while maintaining the ability to promote defects via the use of carbon nanotube hydrogen highways.

BACKGROUNDInitial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.METHODSWe prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data.RESULTSTwenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C.CONCLUSIONPediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.FUNDINGFinancial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex's Lemonade Stand Foundation for Childhood Cancer; Children's Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA . Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s disease and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition. Whole-genome sequence analysis identifies five independent risk loci for Lewy body dementia and demonstrates overlapping genetic architecture with Alzheimer’s and Parkinson’s diseases.

Motor axon regeneration following peripheral nerve injury is critical for motor recovery but therapeutic interventions enhancing this are not available. We conduct a phenotypic screen on human motor neurons and identified blebbistatin, a non-muscle myosin II inhibitor, as the most effective neurite outgrowth promotor. Despite its efficacy in vitro, its poor bioavailability limits in vivo application. We, therefore, utilize a blebbistatin analog, NMIIi2, to explore its therapeutic potential for promoting axon regeneration. Local NMIIi2 application directly to injured axons enhances regeneration in human motor neurons. Furthermore, following a sciatic nerve crush injury in male mice, local NMIIi2 administration to the axonal injury site facilitates motor neuron regeneration, muscle reinnervation, and functional recovery. NMIIi2 also promotes axon regeneration in sensory, cortical, and retinal ganglion neurons. These findings highlight the therapeutic potential of topical NMII inhibition for treating axon damage. Therapeutic interventions for motor axon regeneration following peripheral nerve injury are currently unavailable. Here authors show local administration of a non-muscle myosin II inhibitor at the injury site increases motor and sensory function recovery in vivo.

In this study, men 65 years of age or older with low serum testosterone and symptoms of hypoandrogenism received testosterone or placebo for a year. Testosterone had a moderate benefit in sexual function and some benefit in mood but no benefit in vitality or walking distance. Testosterone concentrations in men decrease with increasing age. 1 , 2 Many symptoms and conditions similar to those that are caused by low testosterone levels in men with pituitary or testicular disease become more common with increasing age. Such symptoms include decreases in mobility, sexual function, and energy. These parallels suggest that the lower testosterone levels in older men may contribute to these conditions. Previous trials of testosterone treatment in men 65 years of age or older, however, have yielded equivocal results. Although testosterone treatment consistently increased muscle mass and decreased fat mass, 3 , 4 effects on physical performance, 3 , 5 , 6 sexual function, . . .

Taste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types: Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour, and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP.sub.3 R3-KO mouse (does not release calcium (Ca.sup.2+) from internal stores in Type II cells when stimulated with bitter, sweet, or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca.sup.2+ imaging in isolated taste cells from the IP.sub.3 R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLC[beta] signaling pathway to respond to bitter, sweet, and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLC[beta]3-KO mouse confirmed that BR cells use this signaling pathway to respond to bitter, sweet, and umami stimuli. Short term behavioral assays revealed that BR cells make significant contributions to taste driven behaviors and found that loss of either PLC[beta]3 in BR cells or IP.sub.3 R3 in Type II cells caused similar behavioral deficits to bitter, sweet, and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) also demonstrated that functional Type II and BR cells are required for normal stimulus induced expression.