Storyteller in ADNI4: Application of an early Alzheimer's disease screening tool using brief, remote, and speech-based testing.

INTRODUCTION: Speech-based testing shows promise for sensitive and scalable objective screening for Alzheimer's disease (AD), but research to date offers limited evidence of generalizability. METHODS: Data were taken from the AMYPRED (Amyloid Prediction in Early Stage Alzheimer's Disease from Acoustic and Linguistic Patterns of Speech) studies (N = 101, N = 46 mild cognitive impairment [MCI]) and Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4) remote digital (N = 426, N = 58 self-reported MCI, mild AD or dementia) and in-clinic (N = 57, N = 13 MCI) cohorts, in which participants provided audio-recorded responses to automated remote story recall tasks in the Storyteller test battery. Text similarity, lexical, temporal, and acoustic speech feature sets were extracted. Models predicting early AD were developed in AMYPRED and tested out of sample in the demographically more diverse cohorts in ADNI4 (> 33% from historically underrepresented populations). RESULTS: Speech models generalized well to unseen data in ADNI4 remote and in-clinic cohorts. The best-performing models evaluated text-based metrics (text similarity, lexical features: area under the curve 0.71-0.84 across cohorts). DISCUSSION: Speech-based predictions of early AD from Storyteller generalize across diverse samples. HIGHLIGHTS: The Storyteller speech-based test is an objective digital prescreener for Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4). Speech-based models predictive of Alzheimer's disease (AD) were developed in the AMYPRED (Amyloid Prediction in Early Stage Alzheimer's Disease from Acoustic and Linguistic Patterns of Speech) sample (N = 101). Models were tested out of sample in ADNI4 in-clinic (N = 57) and remote (N = 426) cohorts. Models showed good generalization out of sample. Models evaluating text matching and lexical features were most predictive of early AD.

The ADNI4 Digital Study: A novel approach to recruitment, screening, and assessment of participants for AD clinical research.

INTRODUCTION: We evaluated preliminary feasibility of a digital, culturally-informed approach to recruit and screen participants for the Alzheimer's Disease Neuroimaging Initiative (ADNI4). METHODS: Participants were recruited using digital advertising and completed digital surveys (e.g., demographics, medical exclusion criteria, 12-item Everyday Cognition Scale [ECog-12]), Novoic Storyteller speech-based cognitive test). Completion rates and assessment performance were compared between underrepresented populations (URPs: individuals from ethnoculturally minoritized or low education backgrounds) and non-URPs. RESULTS: Of 3099 participants who provided contact information, 654 enrolled in the cohort, and 595 completed at least one assessment. Two hundred forty-seven participants were from URPs. Of those enrolled, 465 met ADNI4 inclusion criteria and 237 evidenced possible cognitive impairment from ECog-12 or Storyteller performance. URPs had lower ECog and Storyteller completion rates. Scores varied by ethnocultural group and educational level. DISCUSSION: Preliminary results demonstrate digital recruitment and screening assessment of an older diverse cohort, including those with possible cognitive impairment, are feasible. Improving engagement and achieving educational diversity are key challenges. HIGHLIGHTS: A total of 654 participants enrolled in a digital cohort to facilitate ADNI4 recruitment. Culturally-informed digital ads aided enrollment of underrepresented populations. From those enrolled, 42% were from underrepresented ethnocultural and educational groups. Digital screening tools indicate > 50% of participants likely cognitively impaired. Completion rates and assessment performance vary by ethnocultural group and education.

A Protocol for the Inclusion of Minoritized Persons in Alzheimer Disease Research From the ADNI3 Diversity Taskforce.

Importance: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults. Objective: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3. Design, Setting, and Participants: This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease. Exposures: Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board. Main Outcomes and Measures: Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion. Results: A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources). Conclusions and Relevance: In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.

A diffuse, pustular eruption in a neonate: Recognizing SAMD9L-associated autoinflammatory disease (SAAD).

A 3-week-old baby with hydrops fetalis, acute respiratory failure, and shock of unknown etiology developed a diffuse, pustular rash with worsening inflammatory markers and respiratory status despite antimicrobials. Whole exome sequencing revealed a de novo, frameshift mutation in the SAM9DL gene, leading to the diagnosis of SAMD9L-associated autoinflammatory disease.

The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to improve Alzheimer's disease (AD) clinical trials. Since 2006, ADNI has shared clinical, neuroimaging, and cognitive data, and biofluid samples. We used conventional search methods to identify 1459 publications from 2021 to 2022 using ADNI data/samples and reviewed 291 impactful studies. This review details how ADNI studies improved disease progression understanding and clinical trial efficiency. Advances in subject selection, detection of treatment effects, harmonization, and modeling improved clinical trials and plasma biomarkers like phosphorylated tau showed promise for clinical use. Biomarkers of amyloid beta, tau, neurodegeneration, inflammation, and others were prognostic with individualized prediction algorithms available online. Studies supported the amyloid cascade, emphasized the importance of neuroinflammation, and detailed widespread heterogeneity in disease, linked to genetic and vascular risk, co-pathologies, sex, and resilience. Biological subtypes were consistently observed. Generalizability of ADNI results is limited by lack of cohort diversity, an issue ADNI-4 aims to address by enrolling a diverse cohort.

Educating Housekeeping Staff to Encourage a Culture Supportive of Breastfeeding.

Latina women breastfeed at high rates immediately postpartum but also frequently introduce formula. Formula negatively affects breastfeeding, and maternal and child health. The Baby Friendly Hospital Initiative (BFHI) has been shown to improve breastfeeding outcomes. A BFHI-designated hospital must facilitate lactation education for clinical and non-clinical personnel. Housekeepers, often the sole hospital employees sharing the linguistic and cultural heritage of Latina patients, have frequent patient interactions. This pilot project at a community hospital in New Jersey investigated Spanish-speaking housekeeping staff's attitudes and knowledge regarding breastfeeding before and after implementing a lactation education program. After the training the housekeeping staff overall had more positive attitudes toward breastfeeding. This may, in the short-term, contribute to a hospital culture more supportive of breastfeeding.

Comproportionation of CO2 and Cellulose to Formate Using a Floating Semiconductor-Enzyme Photoreforming Catalyst.

Formate production via both CO2 reduction and cellulose oxidation in a solar-driven process is achieved by a semi-artificial biohybrid photocatalyst consisting of immobilized formate dehydrogenase on titanium dioxide (TiO2 |FDH) producing up to 1.16±0.04 mmolformate g TiO 2 ${{_{\ {\rm TiO}{_{2}}}}}$ -1 in 24 hours at 30 °C and 101 kPa under anaerobic conditions. Isotopic labeling experiments with 13 C-labeled substrates support the mechanism of stoichiometric formate formation through both redox half-reactions. TiO2 |FDH was further immobilized on hollow glass microspheres to perform more practical floating photoreforming allowing vertical solar light illumination with optimal light exposure of the photocatalyst to real sunlight. Enzymatic cellulose depolymerization coupled to the floating photoreforming catalyst generates 0.36±0.04 mmolformate per m2 irradiation area after 24 hours. This work demonstrates the synergistic solar-driven valorization of solid and gaseous waste streams using a biohybrid photoreforming catalyst in aqueous solution and will thus provide inspiration for the development of future semi-artificial waste-to-chemical conversion strategies.

Increasing participant diversity in AD research: Plans for digital screening, blood testing, and a community-engaged approach in the Alzheimer's Disease Neuroimaging Initiative 4.

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to validate biomarkers for Alzheimer's disease (AD) clinical trials. To improve generalizability, ADNI4 aims to enroll 50-60% of its new participants from underrepresented populations (URPs) using new biofluid and digital technologies. ADNI4 has received funding from the National Institute on Aging beginning September 2022. METHODS: ADNI4 will recruit URPs using community-engaged approaches. An online portal will screen 20,000 participants, 4000 of whom (50-60% URPs) will be tested for plasma biomarkers and APOE. From this, 500 new participants will undergo in-clinic assessment joining 500 ADNI3 rollover participants. Remaining participants (∼3500) will undergo longitudinal plasma and digital cognitive testing. ADNI4 will add MRI sequences and new PET tracers. Project 1 will optimize biomarkers in AD clinical trials. RESULTS AND DISCUSSION: ADNI4 will improve generalizability of results, use remote digital and blood screening, and continue providing longitudinal clinical, biomarker, and autopsy data to investigators.

Predicting DRESS Syndrome Recurrence-The ReDRESS Score.

This cross-sectional study of DRESS syndrome cases creates a model capable of predicting recurrence to identify patients most at risk.

Microbial Fermentation of Polyethylene Terephthalate (PET) Plastic Waste for the Production of Chemicals or Electricity.

Ideonella sakaiensis (I. sakaiensis) can grow on polyethylene terephthalate (PET) as the major carbon and energy source. Previous work has shown that PET conversion in the presence of oxygen released carbon dioxide and water while yielding adenosine triphosphate (ATP) through oxidative phosphorylation. This study demonstrates that I. sakaiensis is a facultative anaerobe that ferments PET to the feedstock chemicals acetate and ethanol in the absence of oxygen. In addition to PET, the pure monomer ethylene glycol (EG), the intermediate product ethanol, and the carbohydrate fermentation test substance maltose can also serve as fermenting substrates. Co-culturing of I. sakaiensis with the electrogenic and acetate-consuming Geobacter sulfurreducens produced electricity from PET or EG. This newly identified plastic fermentation process by I. sakaiensis provides thus a novel biosynthetic route to produce high-value chemicals or electricity from plastic waste streams.

Engineering Electro- and Photocatalytic Carbon Materials for CO2 Reduction by Formate Dehydrogenase.

Semiartificial approaches to renewable fuel synthesis exploit the integration of enzymes with synthetic materials for kinetically efficient fuel production. Here, a CO2 reductase, formate dehydrogenase (FDH) from Desulfovibrio vulgaris Hildenborough, is interfaced with carbon nanotubes (CNTs) and amorphous carbon dots (a-CDs). Each carbon substrate, tailored for electro- and photocatalysis, is functionalized with positive (-NHMe2+) and negative (-COO-) chemical surface groups to understand and optimize the electrostatic effect of protein association and orientation on CO2 reduction. Immobilization of FDH on positively charged CNT electrodes results in efficient and reversible electrochemical CO2 reduction via direct electron transfer with >90% Faradaic efficiency and -250 µA cm-2 at -0.6 V vs SHE (pH 6.7 and 25 °C) for formate production. In contrast, negatively charged CNTs only result in marginal currents with immobilized FDH. Quartz crystal microbalance analysis and attenuated total reflection infrared spectroscopy confirm the high binding affinity of active FDH to CNTs. FDH has subsequently been coupled to a-CDs, where the benefits of the positive charge (-NHMe2+-terminated a-CDs) were translated to a functional CD-FDH hybrid photocatalyst. High rates of photocatalytic CO2 reduction (turnover frequency: 3.5 × 103 h-1; AM 1.5G) with dl-dithiothreitol as the sacrificial electron donor were obtained after 6 h, providing benchmark rates for homogeneous photocatalytic CO2 reduction with metal-free light absorbers. This work provides a rational basis to understand interfacial surface/enzyme interactions at electrodes and photosensitizers to guide improvements with catalytic biohybrid materials.

What We Have Learned-Milestones in Pediatric Contact Dermatitis.

Purpose of Review: This review highlights recent developments in the field of pediatric allergic contact dermatitis (ACD) and patch testing. We will review updates on the pathophysiology of contact dermatitis, discuss new contact allergens, explore the impact of dupilumab on patch testing, and provide pearls for the diagnosis and management of ACD in children. Recent Findings: ACD is not a single immunologic phenomenon but rather has contributions from multiple inflammatory pathways. Emerging contact allergens include ingredients found in "slime" toys, glucose monitors and insulin pumps, and electronic equipment. Data thus far suggests that patch testing results are generally reliable in the face of concurrent dupilumab use. Summary: ACD is likely underrecognized and underdiagnosed in pediatric patients, including infants and young children. Providers should keep patient-specific factors and emerging trends in mind when addressing suspected ACD, consider contact dermatitis when they encounter challenging cases of atypical, refractory, or chronic dermatitis, and feel comfortable performing patch testing in children.

Characterizing DRESS syndrome recurrence: a systematic review.

Recurrence of DRESS syndrome is poorly characterized, and dermatologists must be prepared to predict, identify, and manage patients after treatment of the initial presentation. In this study, a primary literature search was conducted using PubMed, capturing all articles recording cases of DRESS syndrome recurrence. Forty-two articles were included for review comprising a total of 60 patients. The average age of patients was 46.3 years and time to recurrence was 123 days. Recurrent episodes presented more frequently with a higher fever and eosinophil absolute peak. Relapse was most often attributed to the introduction of a new medication (n = 18). Of the 17 cases in which outcome data were available, the survival rate of those experiencing recurrence was 71%. Viral reactivation with HHV-6 and organ involvement of the liver were frequently recorded complications. In essence, viral reactivation, severe internal organ involvement, and hematological abnormalities all portended a poorer prognosis in those experiencing DRESS syndrome recurrence. An adequate course of treatment should be maintained until clinical and laboratory parameters normalize, with a slow taper to minimize the likelihood of relapse in those most at risk.

Quinoa, potatoes, and llamas fueled emergent social complexity in the Lake Titicaca Basin of the Andes.

The Lake Titicaca basin was one of the major centers for cultural development in the ancient world. This lacustrine environment is unique in the high, dry Andean altiplano, and its aquatic and terrestrial resources are thought to have contributed to the florescence of complex societies in this region. Nevertheless, it remains unclear to what extent local aquatic resources, particularly fish, and the introduced crop, maize, which can be grown in regions along the lakeshores, contributed to facilitating sustained food production and population growth, which underpinned increasing social political complexity starting in the Formative Period (1400 BCE to 500 CE) and culminating with the Tiwanaku state (500 to 1100 CE). Here, we present direct dietary evidence from stable isotope analysis of human skeletal remains spanning over two millennia, together with faunal and floral reference materials, to reconstruct foodways and ecological interactions in southern Lake Titicaca over time. Bulk stable isotope analysis, coupled with compound-specific amino acid stable isotope analysis, allows better discrimination between resources consumed across aquatic and terrestrial environments. Together, this evidence demonstrates that human diets predominantly relied on C3 plants, particularly quinoa and tubers, along with terrestrial animals, notably domestic camelids. Surprisingly, fish were not a significant source of animal protein, but a slight increase in C4 plant consumption verifies the increasing importance of maize in the Middle Horizon. These results underscore the primary role of local terrestrial food resources in securing a nutritious diet that allowed for sustained population growth, even in the face of documented climate and political change across these periods.

Collegian help seeking: the role of self-compassion and self-coldness.

BACKGROUND: Researchers have identified a two-factor structure of self-compassion (i.e. self-compassion and self-coldness). To date, no research has examined each of these constructs' role in collegian professional help-seeking intention. AIM: The current study sought to assess the role of self-compassion and self-coldness in collegian professional help-seeking intention, accounting for other theoretically and empirically-supported help-seeking constructs. METHOD: Participants included 9349 collegians recruited as part of the national 2015-2016 Healthy Minds Study archival dataset. A logistic regression was conducted to examine the unique contributions of self-compassion and self-coldness in predicting professional help-seeking intention, controlling for key help-seeking variables. RESULTS: A test of the full model against a constant only model was statistically significant, which indicated that the predictors collectively distinguished between collegians who intended to seek help from a professional clinician compared to those who did not. The Wald criterion indicated that both self-compassion and self-coldness were uniquely associated with intention to seek professional help. Self-compassion increased and self-coldness decreased the probability of seeking professional help. CONCLUSIONS: The study highlights the importance of self-compassion and self-coldness in collegian help-seeking intention. These findings can inform specific outreach efforts targeting both self-compassion and self-coldness.

A new paraprobiotic-based treatment for control of Haemonchus contortus in sheep.

Haemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat it, giving rise in some areas to multidrug resistant parasites that are very difficult to control. Thus, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B), a naturally occurring protein made by a bacterium widely and safely used around the world as a bioinsecticide, represents a new non-small molecule modality for treating GINs. Cry5B has demonstrated anthelmintic activities against parasites of monogastric animals, including some related to those that infect humans, but has not yet been studied in a ruminant. Here we show that H. contortus adults are susceptible to Cry5B protein in vitro. Cry5B produced in its natural form as a spore-crystal lysate against H. contortus infections in goats had no significant efficacy. However, a new Active Pharmaceutical Ingredient (API) paraprobiotic form of Cry5B called IBaCC (Inactivated Bacterium with Cytosolic Crystals), in which Cry5B crystals are encapsulated in dead Bt cell wall ghosts, showed excellent efficacy in vitro against larval stages of H. contortus and relative protein stability in bovine rumen fluid. When given to sheep experimentally infected with H. contortus as three 60 mg/kg doses, Cry5B IBaCC resulted in significant reductions in fecal egg counts (90%) and parasite burdens (72%), with a very high impact on female parasites (96% reduction). These data indicate that Cry5B IBaCC is a potent new treatment tool for small ruminants in the battle against H. contortus.

Interpreting ancient food practices: stable isotope and molecular analyses of visible and absorbed residues from a year-long cooking experiment.

Chemical analyses of carbonized and absorbed organic residues from archaeological ceramic cooking vessels can provide a unique window into the culinary cultures of ancient people, resource use, and environmental effects by identifying ingredients used in ancient meals. However, it remains uncertain whether recovered organic residues represent only the final foodstuffs prepared or are the accumulation of various cooking events within the same vessel. To assess this, we cooked seven mixtures of C3 and C4 foodstuffs in unglazed pots once per week for one year, then changed recipes between pots for the final cooking events. We conducted bulk stable-isotope analysis and lipid residue analysis on the charred food macro-remains, carbonized thin layer organic patina residues and absorbed lipids over the course of the experiment. Our results indicate that: (1) the composition of charred macro-remains represent the final foodstuffs cooked within vessels, (2) thin-layer patina residues represent a mixture of previous cooking events with bias towards the final product(s) cooked in the pot, and (3) absorbed lipid residues are developed over a number of cooking events and are replaced slowly over time, with little evidence of the final recipe ingredients.