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For stretchable electronics to achieve broad industrial application, they must be reliable to manufacture and must perform robustly while undergoing large deformations. We present a new strategy for creating planar stretchable electronics and demonstrate one such device, a stretchable microelectrode array based on flex circuit technology. Stretchability is achieved through novel, rationally designed perforations that provide islands of low strain and continuous low-strain pathways for conductive traces. This approach enables the device to maintain constant electrical properties and planarity while undergoing applied strains up to 15%. Materials selection is not limited to polyimide composite devices and can potentially be implemented with either soft or hard substrates and can incorporate standard metals or new nano-engineered conductors. By using standard flex circuit technology, our planar microelectrode device achieved constant resistances for strains up to 20% with less than a 4% resistance offset over 120,000 cycles at 10% strain.

Summary: The ability to sense and respond to osmotic fluctuations is critical for the maintenance of cellular integrity. We used gene co-essentiality analysis to identify an unappreciated relationship between TSC22D2, WNK1, and NRBP1 in regulating cell volume homeostasis. All of these genes have paralogs and are functionally buffered for osmo-sensing and cell volume control. Within seconds of hyperosmotic stress, TSC22D, WNK, and NRBP family members physically associate into biomolecular condensates, a process that is dependent on intrinsically disordered regions (IDRs). A close examination of these protein families across metazoans revealed that TSC22D genes evolved alongside a domain in NRBPs that specifically binds to TSC22D proteins, which we have termed NbrT (NRBP binding region with TSC22D), and this co-evolution is accompanied by rapid IDR length expansion in WNK-family kinases. Our study reveals that TSC22D, WNK, and NRBP genes evolved in metazoans to co-regulate rapid cell volume changes in response to osmolarity.

Abstract Background Adult smoking rates in the USA are highest in economically depressed rural Appalachia. Pharmacist-delivered tobacco cessation support that incorporates medication therapy management (such as the QuitAid intervention) is a promising approach to address this need. Methods Twenty-four adult smokers recruited between September and November 2021 through an independent pharmacy in rural Appalachia were randomized in a non-blinded 2 × 2 × 2 factorial design to (1) pharmacist delivered QuitAid intervention (yes vs. no); (2) combination nicotine replacement therapy (NRT) gum + NRT patch (vs. NRT patch); and/or (3) 8 weeks of NRT (vs. standard 4 weeks). Participants received 4 weeks of NRT patch in addition to the components to which they were assigned. Participants completed baseline and 3-month follow-up assessments. Primary outcomes were feasibility of recruitment and randomization, retention, treatment adherence, and fidelity. Results Participants were recruited in 7 weeks primarily through a referral process, commonly referred to as ask-advise-connect (61%). Participants were on average 52.4 years old, 29.2% were male and the majority were white (91.6%) and Non-Hispanic (91.7%). There was a high level of adherence to the interventions, with 85% of QuitAid sessions completed, 83.3% of the patch used, and 54.5% of gum used. Participants reported a high level of satisfaction with the program, and there was a high level of retention (92%). Conclusions This demonstration pilot randomized controlled study indicates that an ask-advise-connect model for connecting rural smokers to smoking cessation support and providing QuitAid for smoking cessation is feasible and acceptable among rural Appalachian smokers and independent pharmacists. Further investigation into the efficacy of a pharmacist-delivered approach for smoking cessation is needed. Trial registration The trial was retrospectively registered at ClinicalTrials.gov. Trial #: NCT05649241.

The emergence of SARS-CoV-2 variants during the COVID-19 pandemic caused frequent global outbreaks that confounded public health efforts across many jurisdictions, highlighting the need for better understanding and prediction of viral evolution. Predictive models have been shown to support disease prevention efforts, such as with the seasonal influenza vaccine, but they require abundant data. For emerging viruses of concern, such models should ideally function with relatively sparse data typically encountered at the early stages of a viral outbreak. Conventional discrete approaches have proven difficult to develop due to the spurious and reversible nature of amino acid mutations and the overwhelming number of possible protein sequences adding computational complexity. We hypothesized that these challenges could be addressed by encoding discrete protein sequences into continuous numbers, effectively reducing the data size while enhancing the resolution of evolutionarily relevant differences. To this end, we developed a viral protein evolution prediction model (VPRE), which reduces amino acid sequences into continuous numbers by using an artificial neural network called a variational autoencoder (VAE) and models their most statistically likely evolutionary trajectories over time using Gaussian process (GP) regression. To demonstrate VPRE, we used a small amount of early SARS-CoV-2 spike protein sequences. We show that the VAE can be trained on a synthetic dataset based on this data. To recapitulate evolution along a phylogenetic path, we used only 104 spike protein sequences and trained the GP regression with the numerical variables to project evolution up to 5 months into the future. Our predictions contained novel variants and the most frequent prediction mapped primarily to a sequence that differed by only a single amino acid from the most reported spike protein within the prediction timeframe. Novel variants in the spike receptor binding domain (RBD) were capable of binding human angiotensin-converting enzyme 2 (ACE2) in silico, with comparable or better binding than previously resolved RBD-ACE2 complexes. Together, these results indicate the utility and tractability of combining deep learning and regression to model viral protein evolution with relatively sparse datasets, toward developing more effective medical interventions.

ABSTRACTChronic Pseudomonas aeruginosa lung infections are a feature of cystic fibrosis (CF) that many patients experience even with the advent of highly effective modulator therapies. Identifying factors that impact P. aeruginosa in the CF lung could yield novel strategies to eradicate infection or otherwise improve outcomes. To complement published P. aeruginosa studies using laboratory models or RNA isolated from sputum, we analyzed transcripts of strain PAO1 after incubation in sputum from different CF donors prior to RNA extraction. We compared PAO1 gene expression in this “spike-in” sputum model to that for P. aeruginosa grown in synthetic cystic fibrosis sputum medium to determine key genes, which are among the most differentially expressed or most highly expressed. Using the key genes, gene sets with correlated expression were determined using the gene expression analysis tool eADAGE. Gene sets were used to analyze the activity of specific pathways in P. aeruginosa grown in sputum from different individuals. Gene sets that we found to be more active in sputum showed similar activation in published data that included P. aeruginosa RNA isolated from sputum relative to corresponding in vitro reference cultures. In the ex vivo samples, P. aeruginosa had increased levels of genes related to zinc and iron acquisition which were suppressed by metal amendment of sputum. We also found a significant correlation between expression of the H1-type VI secretion system and CFTR corrector use by the sputum donor. An ex vivo sputum model or synthetic sputum medium formulation that imposes metal restriction may enhance future CF-related studies.IMPORTANCEIdentifying the gene expression programs used by Pseudomonas aeruginosa to colonize the lungs of people with cystic fibrosis (CF) will illuminate new therapeutic strategies. To capture these transcriptional programs, we cultured the common P. aeruginosa laboratory strain PAO1 in expectorated sputum from CF patient donors. Through bioinformatic analysis, we defined sets of genes that are more transcriptionally active in real CF sputum compared to a synthetic cystic fibrosis sputum medium. Many of the most differentially active gene sets contained genes related to metal acquisition, suggesting that these gene sets play an active role in scavenging for metals in the CF lung environment which may be inadequately represented in some models. Future studies of P. aeruginosa transcript abundance in CF may benefit from the use of an expectorated sputum model or media supplemented with factors that induce metal restriction.

BackgroundChild marriage has been associated with a range of negative maternal and reproductive health outcomes. This study explored these associations in Liberia and Sierra Leone and examined how child marriage intersected with other measures of social disadvantage.MethodsData were derived from 631 and 1,325 married or cohabitating women aged 20-24 interviewed in the 2019-2020 Liberia and 2019 Sierra Leone Demographic and Health Surveys, respectively. Analyses were stratified by country. Regression models examined associations between age at first marriage (ResultsOver half of currently married/cohabitating women aged 20-24 in Liberia (52%) and Sierra Leone (54%) married before age 18, and over one in 10 married before age 15. In both countries, after adjusting for other factors, being married before the age of 18 was significantly associated with early fertility, high fertility, and low fertility control. Associations were particularly strong among women who first married before age 15. In Liberia, women who married at age 15-17 had significantly lower odds of skilled attendance at delivery and institutional delivery if they lived in the North Central region. Sierra Leonean women who married before age 15 had lower odds of institutional delivery and lower odds of four or more ANC visits if they lived in the North Western region.ConclusionThis study found clear associations between child marriage and negative reproductive health outcomes in Liberia and Sierra Leone, with stronger associations among women married in early adolescence. Child marriage and region of residence intersected to shape young women's access to skilled attendance at birth and institutional delivery. These findings call for further investigation and targeted intervention.

ABSTRACTMetagenomics is a powerful method for interpreting the ecological roles and physiological capabilities of mixed microbial communities. Yet, many tools for processing metagenomic data are neither designed to consider eukaryotes nor are they built for an increasing amount of sequence data. EukHeist is an automated pipeline to retrieve eukaryotic and prokaryotic metagenome-assembled genomes (MAGs) from large-scale metagenomic sequence data sets. We developed the EukHeist workflow to specifically process large amounts of both metagenomic and/or metatranscriptomic sequence data in an automated and reproducible fashion. Here, we applied EukHeist to the large-size fraction data (0.8–2,000 µm) from Tara Oceans to recover both eukaryotic and prokaryotic MAGs, which we refer to as TOPAZ (Tara Oceans Particle-Associated MAGs). The TOPAZ MAGs consisted of >900 environmentally relevant eukaryotic MAGs and >4,000 bacterial and archaeal MAGs. The bacterial and archaeal TOPAZ MAGs expand upon the phylogenetic diversity of likely particle- and host-associated taxa. We use these MAGs to demonstrate an approach to infer the putative trophic mode of the recovered eukaryotic MAGs. We also identify ecological cohorts of co-occurring MAGs, which are driven by specific environmental factors and putative host-microbe associations. These data together add to a number of growing resources of environmentally relevant eukaryotic genomic information. Complementary and expanded databases of MAGs, such as those provided through scalable pipelines like EukHeist, stand to advance our understanding of eukaryotic diversity through increased coverage of genomic representatives across the tree of life.IMPORTANCESingle-celled eukaryotes play ecologically significant roles in the marine environment, yet fundamental questions about their biodiversity, ecological function, and interactions remain. Environmental sequencing enables researchers to document naturally occurring protistan communities, without culturing bias, yet metagenomic and metatranscriptomic sequencing approaches cannot separate individual species from communities. To more completely capture the genomic content of mixed protistan populations, we can create bins of sequences that represent the same organism (metagenome-assembled genomes [MAGs]). We developed the EukHeist pipeline, which automates the binning of population-level eukaryotic and prokaryotic genomes from metagenomic reads. We show exciting insight into what protistan communities are present and their trophic roles in the ocean. Scalable computational tools, like EukHeist, may accelerate the identification of meaningful genetic signatures from large data sets and complement researchers’ efforts to leverage MAG databases for addressing ecological questions, resolving evolutionary relationships, and discovering potentially novel biodiversity.

The majority of adult learners of a signed language are hearing and have little to no experience with a signed language. Thus, they must simultaneously learn a specific language and how to communicate within the visual-gestural modality. Past studies have examined modality-unique drivers of acquisition within first and second signed language learners. In the former group, atypically developing signers have provided a unique axis—namely, disability—for analyzing the intersection of language, modality, and cognition. Here, we extend the question of how cognitive disabilities affect signed language acquisition to a novel audience: hearing, second language (L2) learners of a signed language. We ask whether disability status influences the processing of spatial scenes (perspective taking) and short sentences (phonological contrasts), two aspects of the learning of a signed language. For the methodology, we conducted a secondary, exploratory analysis of a data set including college-level American Sign Language (ASL) students. Participants completed an ASL phonological- discrimination task as well as non-linguistic and linguistic (ASL) versions of a perspective-taking task. Accuracy and response time measures for the tests were compared between a disability group with self-reported diagnoses (e.g., ADHD, learning disability) and a neurotypical group with no self-reported diagnoses. The results revealed that the disability group collectively had lower accuracy compared to the neurotypical group only on the non-linguistic perspective-taking task. Moreover, the group of students who specifically identified as having a learning disability performed worse than students who self-reported using other categories of disabilities affecting cognition. We interpret these findings as demonstrating, crucially, that the signed modality itself does not generally disadvantage disabled and/or neurodiverse learners, even those who may exhibit challenges in visuospatial processing. We recommend that signed language instructors specifically support and monitor students labeled with learning disabilities to ensure development of visual-spatial skills and processing in signed language.

Introduction Strokes affects almost 13 million new people each year and while the outcomes of stroke have improved over the past several decades in high income countries, the same cannot be seen in low‐ and lower‐middle‐income countries. This is the first study to identify the availability of diagnostic tools along with the rates of stroke mortality and other post‐stroke complications in the low‐and lower‐middle‐income countries. Methods A systematic review was completed with a search of the MEDLINE, Embase, and Scopus databases with adherence to the PRISMA guidelines. Studies were included if they reported any outcomes of stroke in low‐ and lower‐middle‐income countries as designated by The World Bank classification. Results A total of 24 studies were included, of which seven originated from Ethiopia, three from Zambia, two from Tanzania, Zimbabwe, and Iran. A single study from each of Botswana, Nigeria, Senegal, Ghana, Kenya, Cameroon, Uganda, and Sierra Leone were included. Of these studies the time from symptom onset to diagnosis varied greatly (< 24 hours to 28 days). Out of 20 studies reporting, 95% stated they had access to CT/MRI. Stroke mortality rates differed greatly across included studies with in‐hospital mortality occurring between 5.0%‐35.4% and 30‐day mortality between 11.7%‐60.1%. Good clinical outcomes (mRS score 0–2) was reported by several studies and was found to have a range between 4.9%‐19.6% at 30 days. Conclusions A severe healthcare disparity in access to care is present in low‐ and lower‐middle‐income countries where there is delayed diagnosis of strokes leading to increased rates of poor clinical outcomes for these patients.

The rapid emergence of publicly accessible artificial intelligence platforms such as large language models (LLMs) has led to an equally rapid increase in articles exploring their potential benefits and risks. We performed a bibliometric analysis of ChatGPT literature in medicine and science to better understand publication trends and knowledge gaps. Following title, abstract, and keyword searches of PubMed, Embase, Scopus, and Web of Science databases for ChatGPT articles published in the medical field, articles were screened for inclusion and exclusion criteria. Data were extracted from included articles, with citation counts obtained from PubMed and journal metrics obtained from Clarivate Journal Citation Reports. After screening, 267 articles were included in the study, most of which were editorials or correspondence with an average of 7.5 +/− 18.4 citations per publication. Published articles on ChatGPT were authored largely in the United States, India, and China. The topics discussed included use and accuracy of ChatGPT in research, medical education, and patient counseling. Among non-surgical specialties, radiology published the most ChatGPT-related articles, while plastic surgery published the most articles among surgical specialties. The average citation number among the top 20 most-cited articles was 60.1 +/− 35.3. Among journals with the most ChatGPT-related publications, there were on average 10 +/− 3.7 publications. Our results suggest that managing the inevitable ethical and safety issues that arise with the implementation of LLMs will require further research exploring the capabilities and accuracy of ChatGPT, to generate policies guiding the adoption of artificial intelligence in medicine and science.

A gene expression compendium is a heterogeneous collection of gene expression experiments assembled from data collected for diverse purposes. The widely varied experimental conditions and genetic backgrounds across samples creates a tremendous opportunity for gaining a systems level understanding of the transcriptional responses that influence phenotypes. Variety in experimental design is particularly important for studying microbes, where the transcriptional responses integrate many signals and demonstrate plasticity across strains including response to what nutrients are available and what microbes are present. Advances in high-throughput measurement technology have made it feasible to construct compendia for many microbes. In this review we discuss how these compendia are constructed and analyzed to reveal transcriptional patterns.

ABSTRACT Thousands of Pseudomonas aeruginosa RNA sequencing (RNA-seq) gene expression profiles are publicly available via the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA). In this work, the transcriptional profiles from hundreds of studies performed by over 75 research groups were reanalyzed in aggregate to create a powerful tool for hypothesis generation and testing. Raw sequence data were uniformly processed using the Salmon pseudoaligner, and this read mapping method was validated by comparison to a direct alignment method. We developed filtering criteria to exclude samples with aberrant levels of housekeeping gene expression or an unexpected number of genes with no reported values and normalized the filtered compendia using the ratio-of-medians method. The filtering and normalization steps greatly improved gene expression correlations for genes within the same operon or regulon across the 2,333 samples. Since the RNA-seq data were generated using diverse strains, we report the effects of mapping samples to noncognate reference genomes by separately analyzing all samples mapped to cDNA reference genomes for strains PAO1 and PA14, two divergent strains that were used to generate most of the samples. Finally, we developed an algorithm to incorporate new data as they are deposited into the SRA. Our processing and quality control methods provide a scalable framework for taking advantage of the troves of biological information hibernating in the depths of microbial gene expression data and yield useful tools for P. aeruginosa RNA-seq data to be leveraged for diverse research goals. IMPORTANCE Pseudomonas aeruginosa is a causative agent of a wide range of infections, including chronic infections associated with cystic fibrosis. These P. aeruginosa infections are difficult to treat and often have negative outcomes. To aid in the study of this problematic pathogen, we mapped, filtered for quality, and normalized thousands of P. aeruginosa RNA-seq gene expression profiles that were publicly available via the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA). The resulting compendia facilitate analyses across experiments, strains, and conditions. Ultimately, the workflow that we present could be applied to analyses of other microbial species.

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes difficult-to-treat infections. Two well-studied divergent P. aeruginosa strain types, PAO1 and PA14, have significant genomic heterogeneity, including diverse accessory genes present in only some strains. Genome content comparisons find core genes that are conserved across both PAO1 and PA14 strains and accessory genes that are present in only a subset of PAO1 and PA14 strains. Here, we use recently assembled transcriptome compendia of publicly available P. aeruginosa RNA sequencing (RNA-seq) samples to create two smaller compendia consisting of only strain PAO1 or strain PA14 samples with each aligned to their cognate reference genome. We confirmed strain annotations and identified other samples for inclusion by assessing each sample’s median expression of PAO1-only or PA14-only accessory genes. We then compared the patterns of core gene expression in each strain. To do so, we developed a method by which we analyzed genes in terms of which genes showed similar expression patterns across strain types. We found that some core genes had consistent correlated expression patterns across both compendia, while others were less stable in an interstrain comparison. For each accessory gene, we also determined core genes with correlated expression patterns. We found that stable core genes had fewer coexpressed neighbors that were accessory genes. Overall, this approach for analyzing expression patterns across strain types can be extended to other groups of genes, like phage genes, or applied for analyzing patterns beyond groups of strains, such as samples with different traits, to reveal a deeper understanding of regulation. IMPORTANCE Pseudomonas aeruginosa is a ubiquitous pathogen. There is much diversity among P. aeruginosa strains, including two divergent but well-studied strains, PAO1 and PA14. Understanding how these different strain-level traits manifest is important for identifying targets that regulate different traits of interest. With the availability of thousands of PAO1 and PA14 samples, we created two strain-specific RNA-seq compendia where each one contains hundreds of samples from PAO1 or PA14 strains and used them to compare the expression patterns of core genes that are conserved in both strain types and to determine which core genes have expression patterns that are similar to those of accessory genes that are unique to one strain or the other using an approach that we developed. We found a subset of core genes with different transcriptional patterns across PAO1 and PA14 strains and identified those core genes with expression patterns similar to those of strain-specific accessory genes.

ABSTRACT Objective: Bibliometrics is a group of statistical and mathematical methods employed to measure and analyze the quantity and the quality of scientific articles, books, and other forms of publications. The objective of the present study was to conduct a bibliometric analysis of the Jornal Brasileiro de Psiquiatria (JBP) by listing its 100 most highly cited articles in the scientific literature and identifying their main characteristics in terms of authorship and research topics and design. Methods: The 100 top-cited references in the JBP were identified through a search with Google Scholar. The main author, last author, corresponding author, the total number of authors, gender of the authors, year of publication, research institution, geographic origin, language, and the research design and subject of each reference were recorded and analyzed. Results: A marked increase in the number of citations in the last 15 years, a relatively balanced distribution of publications among the Brazilian states and research centers, absence of gender bias among authors, and a varied range of published topics suggest a good current editorial performance by the JBP. Relative lack of systematic reviews and longitudinal studies, dearth of articles published in the English language, and modest participation of foreign authors were points requiring improvement. Conclusion: The present study suggests that a survey of the 100 most cited articles in the JBP can provide a historical overview of the progress of this journal, as well as highlight the main obstacles, constraints, and challenges faced by its editors and authors.

Background: Large variation exists for out-of-hospital-cardiac-arrest (OHCA) prehospital care, but less is known about variations in post-arrest care. We sought to evaluate variation in post-arrest care in Texas as well as factors associated with higher performing hospitals. Methods: We analyzed data in Texas Cardiac Arrest Registry to Enhance Survival (TX-CARES), including all adult, non-traumatic OHCAs from 1/1/2014 through 12/31/ 2020 that survived to hospital admission. We first evaluated variability in provisions of post-arrest care and outcomes. We then stratified hospitals into quartiles based on their rate of survival and evaluated the association between improving quartiles and care. Lastly, we evaluated for outliers in post-arrest care and outcomes using a mixed-effect regression model. Results: We analyzed 7,842 OHCAs admitted to 146 hospitals. We identified large variations in post-arrest care, including targeted temperature management (TTM) (IQR 7.0–51.1%), left heart catheterization (LHC) (IQ 0–25%), and percutaneous coronary intervention (PCI) (IQR 0–10.3%). Higher performing hospital quartiles were associated with higher rates of TTM (aOR 1.42, 95% CI 1.36–1.49), LHC (aOR 2.07, 95% CI 1.92–2.23), and PCI (aOR 2.02, 95% CI 1.81–2.25); but lower rates of bystander CPR (aOR 0.90, 95% CI 0.87–0.94). We identified numerous performance outlier hospitals; 39 for TTM, 34 for PCI, 9 for survival to discharge, and 24 for survival with good neurologic function. Conclusions: Post-arrest care varied widely across Texas hospitals. Hospitals with higher rates of survival to discharge had increased rates of TTM, LHC, and PCI but not bystander CPR.

Retro-odontoid pseudotumor formation consists of an abnormal growth of granulation tissue typically posterior to the odontoid process, resulting as a manifestation of atlantoaxial instability. This instability can occur as a result of conditions ranging from severe mechanical trauma to metabolic disease or autoimmune conditions such as rheumatoid arthritis. A pseudotumor may impinge on the spinal nerves or even the spinal cord and brainstem, manifesting symptoms from severe neck pain to cervicomedullary compression or myelopathy, and in some cases even sudden death. The objective of this review is to consolidate the findings in published case reports and relevant prior literature reviews regarding the formation of retro-odontoid pseudotumor. We address the pathophysiology involved in acquired and congenital pseudotumor formation, including those associated with rheumatoid arthritis (panni). Additionally, we discuss past and current operative techniques designed to curtail and ultimately regress a retro-odontoid pseudotumor and pannus. Surgical techniques that are addressed include ventral decompression (both transoral and transnasal), dorsal decompression, and indications for posterior instrumentation in pannus formation, particularly in cases that may be sufficiently treated in lieu of an anterior approach. Finally, we will examine the role of external orthoses as both a method of conservative treatment as well as a potential adjunct to the aforementioned surgical procedures.

Rock climbing has evolved from a method for alpine mountaineering into a popular recreational activity and competitive sport. Advances in safety equipment and the rapid growth of indoor climbing facilities has enabled climbers to focus on the physical and technical movements needed to elevate performance. Through improved training methods, climbers can now achieve ascents of extreme difficulty. A critical aspect to further improve performance is the ability to continuously measure body movement and physiologic responses while ascending the climbing wall. However, traditional measurement devices (e.g., dynamometer) limit data collection during climbing. Advances in wearable and non-invasive sensor technologies have enabled new applications for climbing. This paper presents an overview and critical analysis of the scientific literature on sensors used during climbing. We focus on the several highlighted sensors with the ability to provide continuous measurements during climbing. These selected sensors consist of five main types (body movement, respiration, heart activity, eye gazing, skeletal muscle characterization) that demonstrate their capabilities and potential climbing applications. This review will facilitate the selection of these types of sensors in support of climbing training and strategies.

Insulin facilitates renal sodium reabsorption and attenuates gluconeogenesis. Sex differences in this regulation have not been well characterized. Using tetracycline-inducible Cre-lox recombination, we knocked out (KO) the insulin receptor (InsR) from the renal tubule in adult male (M) and female (F) mice (C57Bl6 background) with a paired box 8 (PAX8) promoter. Body weights were not affected by the KO, but mean kidney weights were reduced in the KO mice (13 and 3%, in M and F, respectively, relative to wild-type (WT) mice). A microscopic analysis revealed 25 and 19% reductions in the proximal tubule (PT) and cortical collecting duct cell heights, respectively, in KOMs relative to WTMs. The reductions were 5 and 11% for KOFs. Western blotting of renal cortex homogenates showed decreased protein levels for the β and γ subunits of the epithelial sodium channel (ENaC) and the sodium-potassium-2-chloride cotransporter type 2 (NKCC2) in both sexes of KO mice; however, α-ENaC was upregulated in KOMs and downregulated in KOFs. Both sexes of KO mice cleared exogenously administered glucose faster than the WT mice and had lower semi-fasted, anesthetized blood glucose levels. However, KOMs (but not KOFs) demonstrated evidence of enhanced renal gluconeogenesis, including higher levels of renal glucose-6-phosphatase, the PT’s production of glucose, post-prandial blood glucose, and plasma insulin, whereas KOFs exhibited downregulation of renal high-capacity sodium glucose cotransporter (SGLT2) and upregulation of SGLT1; these changes appeared to be absent in the KOM. Overall, these findings suggest a sex-differential reliance on intact renal tubular InsR signaling which may be translationally important in type 2 diabetes, obesity, or insulin resistance when renal insulin signaling is reduced.

Abstract Genomes computationally inferred from large metagenomic data sets are often incomplete and may be missing functionally important content and strain variation. We introduce an information retrieval system for large metagenomic data sets that exploits the sparsity of DNA assembly graphs to efficiently extract subgraphs surrounding an inferred genome. We apply this system to recover missing content from genome bins and show that substantial genomic sequence variation is present in a real metagenome. Our software implementation is available at https://github.com/spacegraphcats/spacegraphcats under the 3-Clause BSD License.

Background Variation in alternative tobacco product (ATP) constituents, heating potential, and consumer behaviors have made it difficult to characterize their health risks. To date, most toxicity studies of ATPs have used established cigarette endpoints to inform study design. Furthermore, to assess where ATPs fall on the tobacco harm continuum, with cigarettes representing maximum potential risk, studies have tended to compare the relative biological responses to ATPs against those due to cigarettes. Objectives 1) To characterize the exhalation profiles of two popular ATPs: electronic cigarettes (e-cigarettes) and hookah waterpipes (hookah) and 2) to determine if ATP exhalation patterns were representative of cigarette exhalation patterns. Methods Exhalation patterns were recorded (mouth only, nose only, or both mouth and nose) among individuals observed in the New York City tri-state area using a recognizable tobacco product (cigarette, e-cigarette, or hookah). Cigarette smokers and e-cigarette vapers were observed on city streets; water-pipe smokers were observed inside Manhattan hookah bars. Results E-cigarette vapers practiced exclusive nasal exhalation at far higher rates than did cigarette smokers (19.5% vs 4.9%). Among vapers, e-cigarette device type was also significantly associated with exhalation profile. Overall, cigarette smokers exhaled from their nose approximately half to one-third as often as ATP users (hookah and e-cigarettes, respectively). Conclusions Nasal exhalation of tobacco emissions appears to be a shared characteristic across several types of ATPs. It is therefore plausible that ATP-specific consumer behaviors may foster unique upper respiratory health consequences that have not been observed in smokers. Thus, product-specific behaviors should inform the prioritization of biological endpoints used in studies evaluating ATP toxicity and health effects.

Ponte osteotomy is an increasingly popular technique for multiplanar correction of adolescent idiopathic scoliosis. Prior cadaveric studies have suggested that sequential posterior spinal releases increase spinal flexibility. Here we introduce a novel technique involving a sequential approach to the Ponte osteotomy that minimizes spinal canal exposure. One fresh-frozen adult human cadaveric thoracic spine specimen with 4 cm of ribs was divided into three sections (T1–T5, T6–T9, T10–L1) and mounted for biomechanical testing. Each segment was loaded with five Newton meters under four conditions: baseline inferior facetectomy with supra/interspinous ligament release, superior articular process (SAP) osteotomy in situ, spinous process (SP) osteotomy in situ, and complete posterior column osteotomy with SP/SAP excision and ligamentum flavum release (PCO). Compared to baseline, in situ SAP osteotomy alone provided 3.5%, 7.6%, and 7.2% increase in flexion/extension, lateral bending, and axial rotation, respectively. In situ SP osteotomy increased flexion/extension, lateral bending, and axial rotation by 15%, 18%, and 10.3%, respectively. PCO increased flexion/extension, lateral bending, and axial rotation by 19.6%, 28.3%, and 12.2%, respectively. Our report introduces a novel approach where incremental increases in range of motion can be achieved with minimal spinal canal exposure and demonstrates feasibility in a cadaveric model.

In this work, Saccharomyces cerevisiae

Students from underrepresented groups face numerous challenges during their scientific education and training, including discrimination. Research tends to investigate student experiences with discrimination on the basis of a single characteristic, but an intersectional framework is necessary for understanding the complexity of discrimination. Using data from a survey of more than 1,300 U.S. graduate students in five natural and social science disciplines, the authors examine the predictors of reported discrimination across three different characteristics: gender, race, and religion. They find that nearly two thirds of students report discrimination on at least one characteristic, while almost 30 percent report discrimination along multiple characteristics. Multivariate analyses show that a student’s report of discrimination on any one characteristic is significantly associated with increased odds of reporting discrimination on each of the other two characteristics. This suggests that an individual’s experiences within one social location are often intertwined with and influence their experiences with in other social locations.

Competitive indoor climbing has increased in popularity at the youth, collegiate, and Olympic levels. A critical aspect for improving performance is characterizing the physiologic response to different climbing strategies (e.g., work/rest patterns, pacing) and techniques (e.g., body position and movement) relative to location on climbing wall with spatially varying characteristics (e.g., wall inclinations, position of foot/hand holds). However, this response is not well understood due to the limited capabilities of climbing-specific measurement and assessment tools. In this study, we developed a novel method to examine time-resolved sensor-based measurements of multiple personal biometrics at different microlocations (finely spaced positions; MLs) along a climbing route. For the ML-specific biometric system (MLBS), we integrated continuous data from wearable biometric sensors and smartphone-based video during climbing, with a customized visualization and analysis system to determine three physiologic parameters (heart rate, breathing rate, ventilation rate) and one body movement parameter (hip acceleration), which are automatically time-matched to the corresponding video frame to determine ML-specific biometrics. Key features include: (1) biometric sensors that are seamlessly embedded in the fabric of an athletic compression shirt, and do not interfere with climbing performance, (2) climbing video, and (3) an interactive graphical user interface to rapidly visualize and analyze the time-matched biometrics and climbing video, determine timing sequence between the biometrics at key events, and calculate summary statistics. To demonstrate the capabilities of MLBS, we examined the relationship between changes in ML-specific climbing characteristics and changes in the physiologic parameters. Our study demonstrates the ability of MLBS to determine multiple time-resolved biometrics at different MLs, in support of developing and assessing different climbing strategies and training methods to help improve performance.

ABSTRACT Ribosomal DNA amplicon sequencing of grape musts has demonstrated that microorganisms occur nonrandomly and are associated with the vineyard of origin, suggesting a role for the vineyard, grape, and wine microbiome in shaping wine fermentation outcomes. Here, ribosomal DNA amplicon sequencing from grape musts and RNA sequencing of eukaryotic transcripts from primary fermentations inoculated with the wine yeast Saccharomyces cerevisiae RC212 were used to profile fermentations from 15 vineyards in California and Oregon across two vintages. These data demonstrate that the relative abundance of fungal organisms detected by ribosomal DNA amplicon sequencing correlated with neither transcript abundance from those same organisms within the RNA sequencing data nor gene expression of the inoculated RC212 yeast strain. These data suggest that the majority of the fungi detected in must by ribosomal DNA amplicon sequencing were not active during the primary stage of these inoculated fermentations and were not a major factor in determining RC212 gene expression. However, unique genetic signatures were detected within the ribosomal DNA amplicon and eukaryotic transcriptomic sequencing that were predictive of vineyard site and region. These signatures included S. cerevisiae gene expression patterns linked to nitrogen, sulfur, and thiamine metabolism. These genetic signatures of site offer insight into specific environmental factors to consider with respect to fermentation outcomes and vineyard site and regional wine characteristics. IMPORTANCE The wine industry generates billions of dollars of revenue annually, and economic productivity is in part associated with regional distinctiveness of wine sensory attributes. Microorganisms associated with grapes and wineries are influenced by region of origin, and given that some microorganisms play a role in fermentation, it is thought that microbes may contribute to the regional distinctiveness of wine. In this work, as in previous studies, it is demonstrated that specific bacteria and fungi are associated with individual wine regions and vineyard sites. However, this work further shows that their presence is not associated with detectable fungal gene expression during the primary fermentation or the expression of specific genes by the inoculate Saccharomyces cerevisiae strain RC212. The detected RC212 gene expression signatures associated with region and vineyard site also allowed the identification of flavor-associated metabolic processes and environmental factors that could impact primary fermentation outcomes. These data offer novel insights into the complexities and subtleties of vineyard-specific inoculated wine fermentation and starting points for future investigations into factors that contribute to regional wine distinctiveness.

ABSTRACT RNA sequencing (RNA-seq) has matured into a reliable and low-cost assay for transcriptome profiling and has been deployed across a range of systems. The computational tool space for the analysis of RNA-seq data has kept pace with advances in sequencing. Yet tool development has largely centered around the human transcriptome. While eukaryotic and prokaryotic transcriptomes are similar, key differences in transcribed units limit the transfer of wet-lab and computational tools between the two domains. The article by M. Chung, R. S. Adkins, J. S. A. Mattick, K. R. Bradwell, et al. (mSystems 6:e00917-20, 2021, https://doi.org/10.1128/mSystems.00917-20), demonstrates that integrating prokaryote-specific strategies into existing RNA-seq analyses improves read quantification. Unlike in eukaryotes, polycistronic transcripts derived from operons lead to sequencing reads that span multiple neighboring genes. Chung et al. introduce FADU, a software tool that performs a correction for such reads and thereby improves read quantification and biological interpretation of prokaryotic RNA sequencing.

Women and people of color continue to be underrepresented among biomedical researchers to an alarming degree. Research interest and subsequent productivity have been shown to be affected by the research training environment through the mediating effects of research self-efficacy. This article presents the findings of a study to determine whether a short-term research training program coupled with an efficacy enhancing intervention for novice female biomedical scientists of diverse racial backgrounds would increase their research self-efficacy beliefs. Forty-three female biomedical scientists were randomized into a control or intervention group and 15 men participated as a control group. Research self-efficacy significantly increased for women who participated in the self-efficacy intervention workshop. Research self-efficacy within each group also significantly increased following the short-term research training program, but cross-group comparisons were not significant. These findings suggest that educational interventions that target sources of self-efficacy and provide domain-specific learning experiences are effective at increasing research self-efficacy for women and men. Further studies are needed to determine the longitudinal outcomes of this effort. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The sequence and progression of alcohol related life events were investigated in a sample of African Americans and compared with findings from a predominantly Caucasian sample. METHODS: Alcohol dependent participants were recruited from treatment facilities. Participants completed the Semi-Structured Assessment for the Genetics of Alcoholism to assess the physical, psychological and social manifestations of alcoholism and related disorders. RESULTS: The sequence and mean age of appearance of alcohol-related life events were similar for this sample of African-American men and women. While there were similarities in the progression of alcohol related life problems between the African American and the Caucasian samples, the frequency of symptom endorsement for most problems was significantly higher in the Caucasian sample. CONCLUSIONS: Identifying ethnic differences in the clinical course of alcohol dependence may be of importance in developing treatment plans and assist in the development of culturally sensitive intervention and prevention programs. [ABSTRACT FROM AUTHOR]

Manure-derived organic amendments are a cost-effective tool that provide many potential benefits to plant and soil health including fertility, water retention, and disease suppression. A greenhouse experiment was conducted to evaluate how dairy manure compost (DMC), dairy manure compost-derived vermicompost (VC), and dehydrated poultry manure pellets (PP) impact the tripartite relationship among plant growth, soil physiochemical properties, and microbial community composition. Of tomato plants with manure-derived fertilizers amendments, only VC led to vigorous growth through the duration of the experiment, whereas DMC had mixed impacts on plant growth and PP was detrimental. Organic amendments increased soil porosity and soil water holding capacity, but delayed plant maturation and decreased plant biomass. Composition of bacterial communities were affected more by organic amendment than fungal communities in all microhabitats. Composition of communities outside roots (bulk soil, rhizosphere, rhizoplane) contrasted those within roots (endosphere). Distinct microbial communities were detected for each treatment, with an abundance of Massilia, Chryseolinea, Scedosporium, and Acinetobacter distinguishing the control, vermicompost, dairy manure compost, and dehydrated poultry manure pellet treatments, respectively. This study suggests that plant growth is affected by the application of organic amendments not only because of the soil microbial communities introduced, but also due to a synergistic effect on the physical soil environment. Furthermore, there is a strong interaction between root growth and the spatial heterogeneity of soil and root-associated microbial communities.