Roosevelt Institute

The auto industry is a central force in the US economy and is in the midst of a profound global transition from gas-powered to electric vehicles. While public investment is necessary for such a complex and urgent transformation of a major sector of the economy, the government's engagement with the auto sector runs into a major challenge: the shareholder primacy orientation in US corporate governance, which allows companies to use the public funding to increase its payments to shareholders rather than invest in its workforce and production innovations. This article considers how past public policy toward the auto industry has held up the industry without shifting corporate practices, and how industrial policy should include corporate guardrails to maximize its success in the future.

<h3>Objective:</h3> To identify dysregulated microRNAs in patients with ALS compared to controls. <h3>Background:</h3> ALS is a neurodegenerative disease characterized by degeneration of upper and lower motor neurons. The diagnosis is challenging and is delayed due to a lack of adequate tools. Currently, circulating microRNAs have evidence in their favor as diagnostic biomarkers in ALS. <h3>Design/Methods:</h3> We performed a systematic review and conducted a database search in PubMed, Embase, Scopus, and Web of Science until July 2021. We included articles about patients with ALS diagnosed by Revised El Escorial Criteria, who measure the expression of microRNA and compare it with controls. On the other hand, we excluded articles based on animal models, reviews, letters, and articles with no complete text. We used two independent reviewers for article selection, quality assessment, and data extraction. We used the BIOCROSS (biomarker-based cross-sectional studies) tool to assess the risk of bias. We conducted the bioinformatic analysis using the DIANA tools mirPath v.3.0 software. <h3>Results:</h3> We included 24 original articles and identified 23 microRNAs repeated twice or more times in the articles, showing consistency and significant expression in ALS patients compared to controls. From these 23 miRNAs, 10 were up-regulated (hsa-miR-338-3p, hsa-miR-100, hsa-miR-206, hsa-miR-133a/b, hsa-miR-31, hsa-miR-34c, hsa-miR-424, hsa-miR-36073p, and hsa-miR-542-3p) and 13 were down-regulated (hsa-miR-451, hsa-miR-638, hsa-miR-149, hsa-miR183, hsa-miR-3613-5p, hsa-miR-425-5p, hsa-miR-30c-5p, hsa-let-7a, hsa-miR-26b-5p, hsa-let-7f-5p, hsa-miR-409-3p, hsa-miR-148b-3p, and hsa-miR584-5p). Bioinformatic analysis suggests these microRNAs are involved with three genetic pathways: prion disease, fatty acid synthesis, and fatty acid metabolism. <h3>Conclusions:</h3> The 23 microRNA we identified might be the beginning of a panel to diagnose ALS in its early stages. The genetic pathways shown in the bioinformatic analysis can provide clues to the pathophysiology of ALS. In addition, there is a need to conduct more studies regarding the potential of miRNAs as biomarkers; these studies should be standardized to avoid variability among them. <b>Disclosure:</b> Dr. Aguilera Peña has nothing to disclose. Dr. Cardenas Cruz has nothing to disclose. Dr. Correa has nothing to disclose.

Digital cultural assets are often thought to exist in separate spheres based on their two principal points of origin: digitized and born digital. Increasingly, advances in digital curation are blurring this dichotomy, by introducing so-called “collections as data,” which regardless of their origination make cultural assets more amenable to the application of new computational tools and methodologies. This paper brings together archivists, scholars, and technologists to demonstrate computational treatments of digital cultural assets using Artificial Intelligence (AI) and Machine Learning (ML) techniques that can help unlock hard-to-reach archival content. It describes an extended, iterative study applied to digitized and datafied WWII-era records housed at the FDR Presidential Library, rich content that is regrettably under-utilized by scholars examining American responses to the Holocaust. Authors detail the benefits of interdisciplinary collaboration for evaluating user needs, identifying and applying tools and methodologies (including ML through object detection and AI through Named Entity Recognition or NER), and reaching the real-world outcome of public access to augmented data. They also discuss issues of digital representation, relational context, and interface design to enable new modes of public and scholarly access. While based on a case study, we believe that this work is a substantial contribution to revealing the strengths and weaknesses of using AI/ML systems in cultural organizations. We give particular care to lessons learned, and generalize the approach taken across broad classes of collections with a focus on responsive iterations, reproducibility, and the relevance of data and its structures to users.

Amyloid-β (Aβ) is a principal cleavage product of amyloid-β protein precursor (AβPP) and is widely recognized as a key pathogenic player in Alzheimer's disease (AD). Yet, there is increasing evidence of a neurotoxic role for the AβPP intracellular domain (AICD) which has been proposed to occur through its nuclear function. Intriguingly, there is a γ-secretase resident at the mitochondria which could produce AICD locally. We examined the potential of AICD to induce neuronal apoptosis when targeted specifically to the mitochondria and compared its mechanism of neurotoxicity to that of Aβ. We utilized transient transfection of HT22 neuronal cells with bicistronic plasmids coding for DsRed and either empty vector (Ires), Aβ, AICD59, or mitochondrial-targeted AICD (mitoAICD) in combination with various inhibitors of pathways involved in apoptosis. AICD induced significant neuronal apoptosis only when targeted to the mitochondria. Apoptosis required functional mitochondria as neither Aβ nor mitoAICD induced significant toxicity in cells devoid of mitochondrial DNA. Both glutathione and a Bax inhibitor protected HT22 cells from either peptide. However, inhibition of the mitochondrial permeability transition pore only protected from Aβ, while pan-caspase inhibitors uniquely rescued cells from mitoAICD. Our results show that AICD displays a novel neurotoxic function when targeted to mitochondria. Moreover, mitoAICD induces apoptosis via a mechanism that is distinct from that of Aβ. These findings suggest that AICD produced locally at mitochondria via organelle-specific γ-secretase could act in a synergistic manner with Aβ to cause mitochondrial dysfunction and neuronal death in AD.

This research presents implications of the global pandemic for local government resiliency in the United States. The authors explore insights from local government officials and managers on the front lines of response and recovery efforts to the biological natural disaster. Findings from the latest nationwide survey of U.S. local governments regarding their preparedness for weather‐related natural disasters also inform responses to the current crisis. Results indicate that local governments are innovating and taking strategic actions to fight the virus, even as COVID‐19 has exposed social inequities that are exacerbated as the virus spreads. Survey findings of disaster readiness of local governments to weather‐related disasters shows that small, resource‐poor governments will not be able to respond well and social inequities will grow. Policy strategies at all levels of government must recognize and account for these inequities as threat of this virus subsides, to support stronger, more effective readiness for the next biological catastrophe.

Amyotrophic lateral sclerosis (ALS) is a devastating disorder characterized by motor neuron apoptosis and subsequent skeletal muscle atrophy caused by oxidative and nitrosative stress, mitochondrial dysfunction, and neuroinflammation. Anthocyanins are polyphenolic compounds found in berries that possess neuroprotective and anti-inflammatory properties. Protocatechuic acid (PCA) is a phenolic acid metabolite of the parent anthocyanin, kuromanin, found in blackberries and bilberries. We explored the therapeutic effects of PCA in a transgenic mouse model of ALS that expresses mutant human Cu, Zn-superoxide dismutase 1 with a glycine to alanine substitution at position 93. These mice display skeletal muscle atrophy, hindlimb weakness, and weight loss. Disease onset occurs at approximately 90 days old and end stage is reached at approximately 120 days old. Daily treatment with PCA (100 mg/kg) by oral gavage beginning at disease onset significantly extended survival (121 days old in untreated vs. 133 days old in PCA-treated) and preserved skeletal muscle strength and endurance as assessed by grip strength testing and rotarod performance. Furthermore, PCA reduced astrogliosis and microgliosis in spinal cord, protected spinal motor neurons from apoptosis, and maintained neuromuscular junction integrity in transgenic mice. PCA lengthens survival, lessens the severity of pathological symptoms, and slows disease progression in this mouse model of ALS. Given its significant preclinical therapeutic effects, PCA should be further investigated as a treatment option for patients with ALS.

Esta revisión buscó identificar la prevalencia de desnutrición en menores de 18 años hospitalizados en instituciones de América Latina, los criterios empleados para su clasificación, así como, la estancia hospitalaria y riesgo nutricional. Para esto, se realizó una búsqueda bibliográfica sistemática siguiendo la metodología PRISMA de artículos sobre prevalencia de desnutrición en niños y adolescentes relacionada con enfermedades en países latinoamericanos, publicados entre 1995 y enero del 2019. Fueron elegibles para su inclusión los estudios que informaron datos sobre la prevalencia de desnutrición en pacientes hospitalizados &lt; de 18 años con un tamaño de muestra mayor a 50 sujetos. La revisión se llevó a cabo por tres revisores independientes que evaluaron la calidad metodológica. Como principal resultado se identifica que la prevalencia informada de desnutrición en pacientes pediátricos hospitalizados varía considerablemente. Esta cifra osciló entre 3,3 y 67%. La diferencia se debe principalmente a la diversidad de las poblaciones evaluadas y a los métodos utilizados para detectar y evaluar el estado nutricional. Se tiene como principal conclusión que la elevada variabilidad reportada en cuanto a evaluación del estado nutricional plantea la necesidad de la unificación de estándares de clasificación que permitan favorecer la toma de decisiones a nivel hospitalario.