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There is debate regarding whether most articulatory planning occurs offline (rather than online) and whether the products of off-line processing are stored in a separate articulatory buffer until a large enough chunk is ready for production. This hypothesis predicts that delayed naming conditions should reduce not only onset RTs but also word durations because articulatory plans will be buffered and kept ready. We have tested this hypothesis with young control speakers, an aphasic speaker , and an age and education-matched speaker, using repetition, reading and picture-naming tasks. Contrary to the off-line hypothesis, delayed conditions strongly reduced onset RTs, but had no benefit for word durations. In fact, we found small effects in the opposite direction. Moreover, frequency and imageability affected word durations even in delayed conditions, consistent with articulatory processing continuing on-line. The same pattern of results was found in CS and in control participants, strengthening confidence in our results. There is debate regarding whether most articulatory planning occurs offline (rather than online) and whether the results of off-line processing are stored in a separate articulatory buffer until a large enough chunk is ready for production. This hypothesis predicts that delayed naming conditions should reduce not only onset RTs but also word durations because articulatory plans will be buffered and kept ready. We have tested young control speakers, an aphasic speaker, and an age and education matched speaker, using repetition, reading and picture naming tasks. Contrary to the off-line hypothesis, delayed conditions strongly reduced onset RTs, but had no benefit for word durations. In fact, we found small effects in the opposite direction. Moreover, frequency and imageability affected word durations even in delayed conditions, consistent with articulatory processing continuing on-line. The same pattern of results was found in CS and in control participants, strengthening confidence in our results.

Sepsis carries a high mortality in the United States. Hospitals across the country are working to find new ways to recognize, treat, and streamline care for patients with sepsis. At an academic medical center in the Midwest, a quality improvement project was developed using a sepsis rapid response team with physician associates/assistants (PAs) and NPs. This improved hospital adherence to sepsis evaluation and order set use from 48% to 86%. The added evaluation of the patient by a PA or NP, along with ensuring adherence to the sepsis order set, made an effective first step to improve care of patients with sepsis in this hospital.

Phenylketonuria (PKU) is a metabolic disease where Phenylalanine (Phe) rises much above normal levels. Cross-sectional and correlational studies provide valuable information on the importance of maintaining low blood-Phe to achieve good outcomes, but they may be confounded, at least partially, by differences in participant demographics. Moreover, the effect of Phe at older ages is difficult to ascertain because of strong associations between Phe levels across ages. Within-participant studies avoid confounding issues. We have reviewed these studies. We followed PRISMA guidelines to search the literature for studies reporting the impact of Phe changes within participants. Phe was either increased or decreased through diet relaxation/resumption or through pharmacological interventions. Forty-six separate articles reported, singly or in combination, results on cognition (N = 37), well-being (N = 22) and neurophysiological health (N = 14). For all studies, we established, in a binary way, whether a benefit of lower Phe was or was not demonstrated and compared numbers showing benefit versus a null or negative outcome. We then analyzed whether critical parameters (e.g., length of the study/condition for the change, size of Phe change achieved) influenced presence or absence of benefit. For a subset of studies that reported quantitative cognitive outcomes, we carried out a meta-analysis to estimate the size of change in cognitive performance associated with a change in Phe and its significance. There were significantly more studies with benefits than no benefits, both for cognitive and well-being outcomes, and a trend in this direction for neurophysiological outcomes. The meta-analysis showed a highly significant effect size both overall (0.55) and when studies with adults/adolescents were considered separately (0.57). There was some indication that benefits were easier to demonstrate when differences in Phe were larger and achieved across a longer period, but these effects were not always consistent. These results reinforce results from the literature by demonstrating the importance of lower Phe in children as well as in adolescents and adults, even when confounding factors in group composition are eliminated. The field would benefit from further studies where Phe levels are contrasted within-participants to ascertain how much Phe needs to be changed and for how long to see a difference and which measures demonstrate a difference (e.g., which cognitive tasks).

Background: In aphasia, impairments affecting stages after lexical access have been subdivided into three types: 1. impairments specifying a sequence of phonemes after lexical access (the reproduction variety of conduction aphasia, CA); 2. impairments holding on to these representations during articulatory planning (the short-term memory (STM) variety of CA); and 3. Impairments specifying integrated articulatory/motor plans for clusters of phonemes (apraxia of speech, AoS). Models of speech production, however, suggest more articulated possibilities (i.e., different subtypes of articulatory impairments). Aims: We investigated the impairment in a person with aphasia whose preliminary assessment revealed mixed speech characteristics, combining features typically used to identify CA – phonological errors across tasks and repeated attempts at the target – with features typically used to identify AoS – phonetic errors and word dysfluencies (phoneme elongations and syllabifications). Our preliminary hypothesis was that there was a difficulty transferring information from an (intact) phonological output buffer to articulatory planning. Slow/noisy transfer would predict dysfluencies, errors selecting motor programs, but also repeated attempts (RA) at revising the output in the face of intact feedback and intact original representations. This hypothesis also predicts effects of position and phonological complexity. Method and Procedure: We tested CS’s word and nonword repetition, word reading, and picture naming. We quantified lexical and non-lexical errors, repeated attempts, phonetic errors, and syllabifications. We assessed effects of word frequency, word length, phoneme position, and syllabic and phonological complexity. Results: CS made similar errors across tasks, consistent with a post-lexical impairment. His RAs most often built up a correct target from fragments and/or previously incorrect attempts, similar to a conduite d’approche. He also produced more errors in later positions, and more repeated attempts on longer words. However, inconsistent with decay from an output buffer, phonological errors did not increase with word length. Finally, frequency mattered, consistent with easier/faster access to simpler/more practiced motor plans. Conclusions: CS’s speech characteristics and anatomical lesion are consistent with transfer limitations between phonology and articulatory planning. However, CS has more difficulties in computing articulatory plans than in selecting and retaining phonological representations, as commonly attributed to CA. CS’s case suggests that different varieties of phonological and articulatory disorders need to be distinguished, beyond a strict dichotomy AoS/CA (e.g., involving transfer limitations and difficulties in computing, selecting,, and/or initiating articulatory plans).

ObjectivesThe quest to measure and improve diagnosis has proven challenging; new approaches are needed to better understand and measure key elements of the diagnostic process in clinical encounters. The aim of this study was to develop a tool assessing key elements of the diagnostic assessment process and apply it to a series of diagnostic encounters examining clinical notes and encounters’ recorded transcripts. Additionally, we aimed to correlate and contextualise these findings with measures of encounter time and physician burnout.DesignWe audio-recorded encounters, reviewed their transcripts and associated them with their clinical notes and findings were correlated with concurrent Mini Z Worklife measures and physician burnout.SettingThree primary urgent-care settings.ParticipantsWe conducted in-depth evaluations of 28 clinical encounters delivered by seven physicians.ResultsComparing encounter transcripts with clinical notes, in 24 of 28 (86%) there was high note/transcript concordance for the diagnostic elements on our tool. Reliably included elements were red flags (92% of notes/encounters), aetiologies (88%), likelihood/uncertainties (71%) and follow-up contingencies (71%), whereas psychosocial/contextual information (35%) and mentioning common pitfalls (7%) were often missing. In 22% of encounters, follow-up contingencies were in the note, but absent from the recorded encounter. There was a trend for higher burnout scores being associated with physicians less likely to address key diagnosis items, such as psychosocial history/context.ConclusionsA new tool shows promise as a means of assessing key elements of diagnostic quality in clinical encounters. Work conditions and physician reactions appear to correlate with diagnostic behaviours. Future research should continue to assess relationships between time pressure and diagnostic quality.

The plant-sourced polyketide triacetic acid lactone (TAL) has been recognized as a promising platform chemical for the biorefinery industry. However, its practical application was rather limited due to low natural abundance and inefficient cell factories for biosynthesis. Here, we report the metabolic engineering of oleaginous yeast Rhodotorula toruloides for TAL overproduction. We first introduced a 2-pyrone synthase gene from Gerbera hybrida (GhPS) into R. toruloides and investigated the effects of different carbon sources on TAL production. We then systematically employed a variety of metabolic engineering strategies to increase the flux of acetyl-CoA by enhancing its biosynthetic pathways and disrupting its competing pathways. We found that overexpression of ATP-citrate lyase (ACL1) improved TAL production by 45% compared to the GhPS overexpressing strain, and additional overexpression of acetyl-CoA carboxylase (ACC1) further increased TAL production by 29%. Finally, we characterized the resulting strain I12-ACL1-ACC1 using fed-batch bioreactor fermentation in glucose or oilcane juice medium with acetate supplementation and achieved a titer of 28 or 23 g/L TAL, respectively. This study demonstrates that R. toruloides is a promising host for the production of TAL and other acetyl-CoA-derived polyketides from low-cost carbon sources.

Early in the SARS-CoV-2 pandemic, the M Health Fairview Hospital System established dedicated hospitals for establishing cohorts and caring for patients with COVID-19, yet the association between treatment at COVID-19-dedicated hospitals and mortality and complications is not known.To analyze the mortality rate and complications associated with treatment at the COVID-19-dedicated hospitals.This retrospective cohort study evaluated data prospectively collected from March 1, 2020, through June 30, 2021, from 11 hospitals in Minnesota, including 2 hospitals created solely to care for patients with COVID-19. Data obtained included demographic characteristics, treatments, and outcomes of interest for all patients with a confirmed COVID-19 infection admitted to this hospital system during the study period.Patients were grouped based on whether they received treatment from 1 of the 2 COVID-19-dedicated hospitals compared with the remainder of the hospitals within the hospital system.Multivariate analyses, including risk-adjusted logistic regression and propensity score matching, were performed to evaluate the primary outcome of in-hospital mortality and secondary outcomes, including complications and use of COVID-specific therapeutics.There were 5504 patients with COVID-19 admitted during the study period (median age, 62.5 [IQR, 45.0-75.6] years; 2854 women [51.9%]). Of these, 2077 patients (37.7%) (median age, 63.4 [IQR, 50.7-76.1] years; 1080 men [52.0%]) were treated at 1 of the 2 COVID-19-dedicated hospitals compared with 3427 (62.3%; median age, 62.0 [40.0-75.1] years; 1857 women (54.2%) treated at other hospitals. The mortality rate was 11.6% (n = 241) at the dedicated hospitals compared with 8.0% (n = 274) at the other hospitals (P .001). However, risk-adjusted in-hospital mortality was significantly lower for patients in the COVID-19-dedicated hospitals in both the unmatched group (n = 2077; odds ratio [OR], 0.75; 95% CI, 0.59-0.95) and the propensity score-matched group (n = 1317; OR, 0.78; 95% CI, 0.58-0.99). The rate of overall complications in the propensity score-matched group was significantly lower (OR, 0.81; 95% CI, 0.66-0.99) and the use of COVID-19-specific therapeutics including deep vein thrombosis prophylaxis (83.9% vs 56.9%; P .001), high-dose corticosteroids (56.1% vs 22.2%; P .001), remdesivir (61.5% vs 44.5%; P .001), and tocilizumab (7.9% vs 2.0; P .001) was significantly higher.In this cohort study, COVID-19-dedicated hospitals had multiple benefits, including providing high-volume repetitive treatment and isolating patients with the infection. This experience suggests improved in-hospital mortality for patients treated at dedicated hospitals owing to improved processes of care and supports the use of establishing cohorts for future pandemics.

Gramene (http://www.gramene.org), a knowledgebase founded on comparative functional analyses of genomic and pathway data for model plants and major crops, supports agricultural researchers worldwide. The resource is committed to open access and reproducible science based on the FAIR data principles. Since the last NAR update, we made nine releases; doubled the genome portal's content; expanded curated genes, pathways and expression sets; and implemented the Domain Informational Vocabulary Extraction (DIVE) algorithm for extracting gene function information from publications. The current release, #63 (October 2020), hosts 93 reference genomes—over 3.9 million genes in 122 947 families with orthologous and paralogous classifications. Plant Reactome portrays pathway networks using a combination of manual biocuration in rice (320 reference pathways) and orthology-based projections to 106 species. The Reactome platform facilitates comparison between reference and projected pathways, gene expression analyses and overlays of gene–gene interactions. Gramene integrates ontology-based protein structure–function annotation; information on genetic, epigenetic, expression, and phenotypic diversity; and gene functional annotations extracted from plant-focused journals using DIVE. We train plant researchers in biocuration of genes and pathways; host curated maize gene structures as tracks in the maize genome browser; and integrate curated rice genes and pathways in the Plant Reactome.

Children with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD) have 2–3 times increased healthcare utilization and annual costs once diagnosed, but little is known about their utilization patterns early in life. Quantifying their early health system utilization could uncover condition-specific health trajectories to facilitate earlier detection and intervention. Patients born 10/1/2006–10/1/2016 with ≥ 2 well-child visits within the Duke University Health System before age 1 were grouped as ASD, ADHD, ASD + ADHD, or No Diagnosis using retrospective billing codes. An additional comparison group was defined by later upper respiratory infection diagnosis. Adjusted odds ratios (AOR) for hospital admissions, procedures, emergency department (ED) visits, and outpatient clinic encounters before age 1 were compared between groups via logistic regression models. Length of hospital encounters were compared between groups via Mann–Whitney U test. In total, 29,929 patients met study criteria (ASD N = 343; ADHD N = 1175; ASD + ADHD N = 140). ASD was associated with increased procedures (AOR = 1.5, p p p p p p p p p p p p = 0.003). Each condition was associated with increased health system utilization and distinctive patterns of utilization before age 1. Recognizing these patterns may contribute to earlier detection and intervention.

Background: Hospital referral regions (HRRs) are often used to characterize inpatient referral patterns, but it is unknown how well these geographic regions are aligned with variation in Medicare-financed hospice care, which is largely provided at home. Objective: Our objective was to characterize the variability in hospice use rates among elderly Medicare decedents by HRR and county. Methods: Using 2014 Master Beneficiary File for decedents 65 and older from North and South Carolina, we applied Bayesian mixed models to quantify variation in hospice use rates explained by HRR fixed effects, county random effects, and residual error among Medicare decedents. Results: We found HRRs and county indicators are significant predictors of hospice use in NC and SC; however, the relative variation within HRRs and associated residual variation is substantial. On average, HRR fixed effects explained more variation in hospice use rates than county indicators with a standard deviation (SD) of 10.0 versus 5.1 percentage points. The SD of the residual error is 5.7 percentage points. On average, variation within HRRs is about half the variation between regions (52%). Conclusions: The magnitude of unexplained residual variation in hospice use for NC and SC suggests that novel, end-of-life-specific service areas should be developed and tested to better capture geographic differences and inform research, health systems, and policy.

Contains fulltext : 288017.pdf (Publisher’s version ) (Open Access) Our study estimated size of impairment for different cognitive functions in early-treated adults with PKU (AwPKU) by combining literature results in a meta-analytic way. We analysed a large set of functions (N = 19), each probed by different measures (average = 12). Data were extracted from 26 PKU groups and matched controls, with 757 AwPKU contributing 220 measures. Effect sizes (ESs) were computed using Glass' ∆ where differences in performance between clinical/PKU and control groups are standardized using the mean and standard deviation of the control groups. Significance was assessed using measures nested within independent PKU groups as a random factor. The weighted Glass' ∆ was - 0.44 for all functions taken together, and - 0.60 for IQ, both highly significant. Separate, significant impairments were found for most functions, but with great variability (ESs from -1.02 to -0.18). The most severe impairments were in reasoning, visual-spatial attention speed, sustained attention, visuo-motor control, and flexibility. Effect sizes were larger with speed than accuracy measures, and with visuo-spatial than verbal stimuli. Results show a specific PKU profile that needs consideration when monitoring the disease. 01 december 2022

Main conclusion SorghumBase provides a community portal that integrates genetic, genomic, and breeding resources for sorghum germplasm improvement. Abstract Public research and development in agriculture rely on proper data and resource sharing within stakeholder communities. For plant breeders, agronomists, molecular biologists, geneticists, and bioinformaticians, centralizing desirable data into a user-friendly hub for crop systems is essential for successful collaborations and breakthroughs in germplasm development. Here, we present the SorghumBase web portal (https://www.sorghumbase.org), a resource for the sorghum research community. SorghumBase hosts a wide range of sorghum genomic information in a modular framework, built with open-source software, to provide a sustainable platform. This initial release of SorghumBase includes: (1) five sorghum reference genome assemblies in a pan-genome browser; (2) genetic variant information for natural diversity panels and ethyl methanesulfonate (EMS)-induced mutant populations; (3) search interface and integrated views of various data types; (4) links supporting interconnectivity with other repositories including genebank, QTL, and gene expression databases; and (5) a content management system to support access to community news and training materials. SorghumBase offers sorghum investigators improved data collation and access that will facilitate the growth of a robust research community to support genomics-assisted breeding.

ImportanceAutism detection early in childhood is critical to ensure that autistic children and their families have access to early behavioral support. Early correlates of autism documented in electronic health records (EHRs) during routine care could allow passive, predictive model-based monitoring to improve the accuracy of early detection.ObjectiveTo quantify the predictive value of early autism detection models based on EHR data collected before age 1 year.Design, Setting, and ParticipantsThis retrospective diagnostic study used EHR data from children seen within the Duke University Health System before age 30 days between January 2006 and December 2020. These data were used to train and evaluate L2-regularized Cox proportional hazards models predicting later autism diagnosis based on data collected from birth up to the time of prediction (ages 30-360 days). Statistical analyses were performed between August 1, 2020, and April 1, 2022.Main Outcomes and MeasuresPrediction performance was quantified in terms of sensitivity, specificity, and positive predictive value (PPV) at clinically relevant model operating thresholds.ResultsData from 45 080 children, including 924 (1.5%) meeting autism criteria, were included in this study. Model-based autism detection at age 30 days achieved 45.5% sensitivity and 23.0% PPV at 90.0% specificity. Detection by age 360 days achieved 59.8% sensitivity and 17.6% PPV at 81.5% specificity and 38.8% sensitivity and 31.0% PPV at 94.3% specificity.Conclusions and RelevanceIn this diagnostic study of an autism screening test, EHR-based autism detection achieved clinically meaningful accuracy by age 30 days, improving by age 1 year. This automated approach could be integrated with caregiver surveys to improve the accuracy of early autism screening.

OBJECTIVE Individuals with dyslexia do not only show deficits with reading but are also less accurate in naming pictures. This has mainly been linked to prevalent phonological deficits. However, deficits in lexical retrieval of picture names could also be due to increased lexical-semantic competition. The present study tested whether adults with dyslexia (AwDs) are more affected by a competitive lexical-semantic context than control participants. METHOD Twenty-seven AwD and 34 control participants completed the blocked-cyclic picture-naming paradigm and the Hayling sentence completion task. RESULTS In the blocked-cyclic naming task, AwDs showed a larger semantic interference effect than controls in terms of errors, especially producing competitor errors. In the Hayling sentence completion task, AwDs made more errors than controls when asked to complete sentences with semantically unrelated words, that is, in the competitive condition. They especially produced semantically related words or antonyms to target words. CONCLUSIONS We found that AwDs experience difficulties with resolving lexical competition that go beyond their phonological deficits. Future studies will need to establish the mechanisms behind the increased lexical competition that AwDs exhibit. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

After discovering a low incidence of delirium for hip fracture patients at our institution, we evaluated if this was due to underreporting and, if so, where process errors occurred.Hip fracture patients aged ≥60 with a diagnosis of delirium were identified. Chart-Based Delirium Identification Instrument (CHART-DEL) identified missed diagnoses of delirium. Process maps were created based off staff interviews and observations.The incidence of delirium was 15.3% (N = 176). Within a random sample (n = 98), 15 patients (15.5%) were diagnosed, while 20 (24.7%) went undiagnosed despite evidence of delirium. Including missed diagnoses, delirium prevalence was higher in the sample compared to all patients (35.7% vs 15.3%, p 0.001). Most missed diagnoses were due to failure in identifying delirium (60%) or failure in documenting/coding diagnosis (20%). The prevalence of baseline cognitive impairment was higher in undiagnosed delirium patients versus correctly diagnosed patients (80% vs 20%, p = 0.001).Our institution significantly underreports delirium among hip fracture patients mainly due to; (1) failure to identify delirium by the clinical staff, and (2) failure to document/code diagnosis despite correct identification. Baseline cognitive impairment can render delirium diagnosis challenging. These serve as targets for quality improvement and hip fracture care enhancement.

Plant Reactome (https://plantreactome.gramene.org) is an open-source, comparative plant pathway knowledgebase of the Gramene project. It uses Oryza sativa (rice) as a reference species for manual curation of pathways and extends pathway knowledge to another 82 plant species via gene-orthology projection using the Reactome data model and framework. It currently hosts 298 reference pathways, including metabolic and transport pathways, transcriptional networks, hormone signaling pathways, and plant developmental processes. In addition to browsing plant pathways, users can upload and analyze their omics data, such as the gene-expression data, and overlay curated or experimental gene-gene interaction data to extend pathway knowledge. The curation team actively engages researchers and students on gene and pathway curation by offering workshops and online tutorials. The Plant Reactome supports, implements and collaborates with the wider community to make data and tools related to genes, genomes, and pathways Findable, Accessible, Interoperable and Re-usable (FAIR).

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of interfaces to genomic data across the tree of life, including reference genome sequence, gene models, transcriptional data, genetic variation and comparative analysis. Data may be accessed via our website, online tools platform and programmatic interfaces, with updates made four times per year (in synchrony with Ensembl). Here, we provide an overview of Ensembl Genomes, with a focus on recent developments. These include the continued growth, more robust and reproducible sets of orthologues and paralogues, and enriched views of gene expression and gene function in plants. Finally, we report on our continued deeper integration with the Ensembl project, which forms a key part of our future strategy for dealing with the increasing quantity of available genome-scale data across the tree of life.

Significance Tumor-associated microglia and macrophages (TAMs) constitute up to one half of the cells in glioblastoma multiforme (GBM) and are known to promote tumor growth. Therefore, modulation and reeducation of the TAM pool is a promising antitumor strategy against GBMs. We recently showed that disruption of the SIRPα-CD47 signaling axis is efficacious against various brain tumors including GBM primarily by inducing tumor phagocytosis. Here, we show that tumor-associated microglia are capable of in vivo tumor cell phagocytosis in response to anti-CD47 blockade. The activation of microglia was associated with distinct morphological and transcriptional changes. In fact, microglia show a dampened inflammatory response upon anti-CD47 therapy compared with macrophages, making them an attractive target for clinical applications especially in the confined regions of the brain., Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with fatal outcome. Tumor-associated macrophages and microglia (TAMs) have been found to be major tumor-promoting immune cells in the tumor microenvironment. Hence, modulation and reeducation of tumor-associated macrophages and microglia in GBM is considered a promising antitumor strategy. Resident microglia and invading macrophages have been shown to have distinct origin and function. Whereas yolk sac-derived microglia reside in the brain, blood-derived monocytes invade the central nervous system only under pathological conditions like tumor formation. We recently showed that disruption of the SIRPα-CD47 signaling axis is efficacious against various brain tumors including GBM primarily by inducing tumor phagocytosis. However, most effects are attributed to macrophages recruited from the periphery but the role of the brain resident microglia is unknown. Here, we sought to utilize a model to distinguish resident microglia and peripheral macrophages within the GBM-TAM pool, using orthotopically xenografted, immunodeficient, and syngeneic mouse models with genetically color-coded macrophages (Ccr2RFP) and microglia (Cx3cr1GFP). We show that even in the absence of phagocytizing macrophages (Ccr2RFP/RFP), microglia are effector cells of tumor cell phagocytosis in response to anti-CD47 blockade. Additionally, macrophages and microglia show distinct morphological and transcriptional changes. Importantly, the transcriptional profile of microglia shows less of an inflammatory response which makes them a promising target for clinical applications.

Background: High intensity, one-to-one rehabilitation therapy is effective in the treatment of poststroke aphasia, but it can put strain on public health providers, as well as lead to high attrition. Working within a group of peers may be efficient for professional speech and language therapists, as well as reduce feelings of isolation and lack of confidence in patients, which can negatively affect progress. Evidence-based, structured group-based approaches, however, are lacking. Aims: We wanted to assess the feasibility a new group-delivered game-based intervention, designed to provide efficacious word-retrieval rehabilitation, in a cost-effective and motivating environment. Method & Procedure: Two cohorts of six participants took part. Each was split into two teams to play language games where pictures were named with the help of team members and facilitation from a speech and language therapist. Facilitation was varied in three different cueing conditions: phonemic, gesture + phonemic, and semantic + phonemic. Overall, 180 words were practiced (90 nouns and 90 verbs). Therapy was delivered 3 days per week, for 6 weeks (for a total of 54 hr). Outcomes & Results: Our intervention was equally effective across the three cueing conditions and for nouns and verbs. Gains were demonstrated in naming the pictures used in training, but also in the description of pictured scenes designed to elicit the same words. With these tasks, there were improvements of 25% and 18% from base-line accuracy, which compares well with gains reported in the literature using individually delivered speech and language therapy based on picture naming. Improvements were mostly maintained at both 4–7 weeks and 6-months post-therapy and were significant in all but the two most severely affected participants. There was some generalization of gains to narrative production, but not to other language tasks, nor to untreated words in picture naming. These positive language outcomes were combined with a high level of engagement and satisfaction (with participants stating a preference for games over standard therapy). Conclusions: Our results support embedding theoretically and empirically based techniques for aphasia rehabilitation within games with a strong social aspect, which may promote linguistic recovery in a way that is both time and cost-efficient and engaging. Future research should explore more formally outcomes in terms of increased well-being and reduced social isolation, as well as language proficiency.

We report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The data indicate that the number of pan-genes exceeds 103,000 and that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres further reveal the locations and internal structures of major cytological landmarks. We show that combining structural variation with SNPs can improve the power of quantitative mapping studies. Finally, we document variation at the level of DNA methylation, and demonstrate that unmethylated regions are enriched for cis-regulatory elements that overlap QTL and contribute to changes in gene expression.One sentence summaryA multi-genome analysis of maize reveals previously unknown variation in gene content, genome structure, and methylation.

An a-maize-ing set of genomes Maize is an important crop cultivated worldwide. As maize spread across the world, selection for local environments resulted in variation, but the impact on differences between the genome has not been quantified. By producing high-quality genomic sequences of the 26 lines used in the maize nested association mapping panel, Hufford et al . map important traits and demonstrate the diversity of maize. Examining RNA and methylation of genes across accessions, the authors identified a core set of maize genes. Beyond this core set, comparative analysis across lines identified high levels of variation in the total set of genes, the maize pan-genome. The value of this resource was further exemplified by mapping quantitative traits of interest, including those related to pathogen resistance. —LMZ

Sorghum bicolor, one of the most important grass crops around the world, harbors a high degree of genetic diversity. We constructed chromosome-level genome assemblies for two important sorghum inbred lines, Tx2783 and RTx436. The final high-quality reference assemblies consist of 19 and 18 scaffolds, respectively, with contig N50 values of 25.6 and 20.3 Mb. Genes were annotated using evidence-based and de novo gene predictors, and RAMPAGE data demonstrate that transcription start sites were effectively captured. Together with other public sorghum genomes, BTx623, RTx430, and Rio, extensive structural variations (SVs) of various sizes were characterized using Tx2783 as a reference. Genome-wide scanning for disease resistance (R) genes revealed high levels of diversity among these five sorghum accessions. To characterize sugarcane aphid (SCA) resistance in Tx2783, we mapped the resistance region on chromosome 6 using a recombinant inbred line (RIL) population and found a SV of 191 kb containing a cluster of R genes in Tx2783. Using Tx2783 as a backbone, along with the SVs, we constructed a pan-genome to support alignment of resequencing data from 62 sorghum accessions, and then identified core and dispensable genes using this population. This study provides the first overview of the extent of genomic structural variations and R genes in the sorghum population, and reveals potential targets for breeding of SCA resistance.

SummaryGenome sequencing projects annotate protein-coding gene models with multiple transcripts, aiming to represent all of the available transcript evidence. However, downstream analyses often operate on only one representative transcript per gene locus, sometimes known as the canonical transcript. To choose canonical transcripts, TRaCE (Transcript Ranking and Canonical Election) holds an ‘election’ in which a set of RNA-seq samples rank transcripts by annotation edit distance. These sample-specific votes are tallied along with other criteria such as protein length and InterPro domain coverage. The winner is selected as the canonical transcript, but the election proceeds through multiple rounds of voting to order all the transcripts by relevance. Based on the set of expression data provided, TRaCE can identify the most common isoforms from a broad expression atlas or prioritize alternative transcripts expressed in specific contexts.Availability and ImplementationTranscript ranking code can be found on GitHub at {{https://github.com/warelab/TRaCE}}Contactolson@cshl.edu, ware@cshl.eduSupplementary informationAdditional data are available in the github repository.

Microbial synthesis of wax esters (WE) from low-cost renewable and sustainable feedstocks is a promising path to achieve cost-effectiveness in biomanufacturing. WE are industrially high-value molecules, which are widely used for applications in chemical, pharmaceutical, and food industries. Since the natural WE resources are limited, the WE production mostly rely on chemical synthesis from rather expensive starting materials, and therefore solution are sought from development of efficient microbial cell factories. Here we report to engineer the yeast Yarrowia lipolytica and bacterium Escherichia coli to produce WE at the highest level up to date. First, the key genes encoding fatty acyl-CoA reductases and wax ester synthase from different sources were investigated, and the expression system for two different Y. lipolytica hosts were compared and optimized for enhanced WE production and the strain stability. To improve the metabolic pathway efficiency, different carbon sources including glucose, free fatty acid, soybean oil, and waste cooking oil (WCO) were compared, and the corresponding pathway engineering strategies were optimized. It was found that using a lipid substrate such as WCO to replace glucose led to a 60-fold increase in WE production. The engineered yeast was able to produce 7.6 g/L WE with a yield of 0.31 (g/g) from WCO within 120 h and the produced WE contributed to 57% of the yeast DCW. After that, E. coli BL21(DE3), with a faster growth rate than the yeast, was engineered to significantly improve the WE production rate. Optimization of the expression system and the substrate feeding strategies led to production of 3.7–4.0 g/L WE within 40 h in a 1-L bioreactor. The predominant intracellular WE produced by both Y. lipolytica and E. coli in the presence of hydrophobic substrates as sole carbon sources were C36, C34 and C32, in an order of decreasing abundance and with a large proportion being unsaturated. This work paved the way for the biomanufacturing of WE at a large scale.

BACKGROUND The increasing incidence of COVID-19 infection has challenged health care systems to increase capacity while conserving personal protective equipment (PPE) supplies and minimizing nosocomial spread. Telemedicine shows promise to address these challenges but lacks comprehensive evaluation in the inpatient environment. OBJECTIVE The aim of this study is to evaluate an intrahospital telemedicine program (virtual care), along with its impact on exposure risk and communication. METHODS We conducted a natural experiment of virtual care on patients admitted for COVID-19. The primary exposure variable was documented use of virtual care. Patient characteristics, PPE use rates, and their association with virtual care use were assessed. In parallel, we conducted surveys with patients and clinicians to capture satisfaction with virtual care along the domains of communication, medical treatment, and exposure risk. RESULTS Of 137 total patients in our primary analysis, 43 patients used virtual care. In total, there were 82 inpatient days of use and 401 inpatient days without use. Hospital utilization and illness severity were similar in patients who opted in versus opted out. Virtual care was associated with a significant reduction in PPE use and physical exam rate. Surveys of 41 patients and clinicians showed high rates of recommendation for further use, and subjective improvements in communication. However, providers and patients expressed limitations in usability, medical assessment, and empathetic communication. CONCLUSIONS In this pilot natural experiment, only a subset of patients used inpatient virtual care. When used, virtual care was associated with reductions in PPE use, reductions in exposure risk, and patient and provider satisfaction.

The United States produces more than 10 million tons of waste oils and fats each year. This paper aims to establish a new biomanufacturing platform that convert waste oils or fats into a series of value-added products. Our research employs the oleaginous yeast Yarrowia lipolytica as a case study for citrate production from waste oils. First, we conducted the CFD simulation of the bioreactor system and identified that the extracellular mixing and mass transfer is the first limiting factor of an oil fermentation process due to the insolubility of oil in water. Based on the CFD simulation results, bioreactor design and operating conditions were optimized and successfully enhanced oil uptake and bioconversion in fed-batch fermentation experiments. After that, we investigated the impacts of cell morphology on oil uptake, intracellular lipid accumulation, and citrate formation by overexpressing and deleting the MHY1 gene in the wild type Y. lipolytica. Fairly good correlations were achieved between cell morphology and productivities of biomass, lipid, and citrate. Finally, fermentation kinetics with both glucose and oil substrates were compared and the oil fermentation process was carefully evaluated. Our research results suggest that waste oils or fats can be economical feedstocks for biomanufacturing of many high-value products.

Maps of the synapses made and neurotransmitters released by all neurons in model systems, such as Caenorhabditis elegans have left still unresolved how neural circuits integrate and respond to neurotransmitter signals. Using the egg-laying circuit of C. elegans as a model, we mapped which cells express each of the 26 neurotransmitter GPCRs of this organism and also genetically analyzed the functions of all 26 GPCRs. We found that individual neurons express many distinct receptors, epithelial cells often express neurotransmitter receptors, and receptors are often positioned to receive extrasynaptic signals. Receptor knockouts reveal few egg-laying defects under standard laboratory conditions, suggesting that the receptors function redundantly or regulate egg-laying only in specific conditions; however, increasing receptor signaling through overexpression more efficiently reveals receptor functions. This map of neurotransmitter GPCR expression and function in the egg-laying circuit provides a model for understanding GPCR signaling in other neural circuits. SIGNIFICANCE STATEMENT Neurotransmitters signal through GPCRs to modulate activity of neurons, and changes in such signaling can underlie conditions such as depression and Parkinson's disease. To determine how neurotransmitter GPCRs together help regulate function of a neural circuit, we analyzed the simple egg-laying circuit in the model organism C. elegans. We identified all the cells that express every neurotransmitter GPCR and genetically analyzed how each GPCR affects the behavior the circuit produces. We found that many neurotransmitter GPCRs are expressed in each neuron, that neurons also appear to use these receptors to communicate with other cell types, and that GPCRs appear to often act redundantly or only under specific conditions to regulate circuit function.

Haplotype phasing maize genetic variants is important for genome interpretation, population genetic analysis and functional analysis of allelic activity. We performed an isoform-level phasing study using two maize inbred lines and their reciprocal crosses, based on single-molecule, full-length cDNA sequencing. To phase and analyze transcripts between hybrids and parents, we developed IsoPhase. Using this tool, we validated the majority of SNPs called against matching short-read data from embryo, endosperm and root tissues, and identified allele-specific, gene-level and isoform-level differential expression between the inbred parental lines and hybrid offspring. After phasing 6907 genes in the reciprocal hybrids, we annotated the SNPs and identified large-effect genes. In addition, we identified parent-of-origin isoforms, distinct novel isoforms in maize parent and hybrid lines, and imprinted genes from different tissues. Finally, we characterized variation in cis- and trans-regulatory effects. Our study provides measures of haplotypic expression that could increase accuracy in studies of allelic expression., Bo Wang et al. report an isoform-level phasing study in maize using long-read cDNA sequencing and a new method, IsoPhase, to annotate allele-specific, gene-level and isoform-level expression. They identify novel gene isoforms, imprinted genes, and variation in cis- and trans-regulatory effects.