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Abstract The link between the oral microbiome and neurodevelopmental disorders remains a compelling hypothesis, still requiring confirmation in large-scale datasets. Leveraging over 7000 whole-genome sequenced salivary samples from 2025 US families with children diagnosed with autism spectrum disorders (ASD), our cross-sectional study shows that the oral microbiome composition can discriminate ASD subjects from neurotypical siblings (NTs, AUC = 0.66), with 108 differentiating species (q

Abstract Millions of United States (U.S.) troops deployed to the Middle East and Southwest Asia were exposed to toxic airborne hazards and/or open-air burn pits. Burn pit emissions contain particulate matter combined with toxic gasses and heavy metals. Ongoing research has demonstrated that exposures to the airborne hazards from military burn pits have profound and lasting health and wellness consequences. Research on the long-term health consequences of exposure to open burn pits has been limited. Work continues to understand the scope of the health impacts and the underlying pathobiology following exposures and to establish care standards. The U.S. Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act was signed into law August 2022. This act expands the benefits and services to U.S. Veterans exposed to toxicants, requires the Veterans Health Administration to provide toxic exposure screening, and supports increased research, education, and treatment due to toxic occupational exposures. This review highlights the state of the science related to military burn pit exposures research with an emphasis on pulmonary health. Clinical data demonstrate areas of reduced or delayed pulmonary ventilation and lung pathologies such as small airways scarring, diffuse collagen deposition and focal areas of ossification. Identification and characterization of foreign matter deposition in lung tissues are reported, including particulate matter, silica, titanium oxides, and polycyclic aromatic hydrocarbons. These data are consistent with toxic exposures and with the symptoms reported by post-deployment Veterans despite near-normal non-invasive pulmonary evaluations. On-going work toward new methods for non-invasive pulmonary diagnoses and disease monitoring are described. We propose various studies and databases as resources for clinical and health outcomes research. Pre-clinical research using different burn pit modeling approaches are summarized, including oropharyngeal aspiration, intranasal inhalation, and whole-body exposure chamber inhalation. These studies focus on the impacts of specific toxic substances as well as the effects of short-term and sustained insults over time on the pulmonary systems.

Abstract Background Few validated brief scales are available to measure constructs that may hinder mpox-related prevention and care engagement, such as knowledge and stigma. Both are highly salient barriers to infectious disease care and disease understanding, precursors to evaluating one’s risk and need to, for example, accept vaccination. To address this gap, we developed and validated the Mpox Stigma Scale (MSS) and Mpox Knowledge Scale (MKS). Methods As part of a full-scale clinical trial, we offered an optional mpox survey to participants who self-identified as African American or Black, were 18–29 years old, and lived in Alabama, Georgia, or North Carolina (2023, N = 330). We calculated psychometric properties through confirmatory factor analyses (CFA) and applied Comparative Fit Index (CFI), Goodness of Fit Index (GFI), and Tucker-Lewis Index (TLI) values equal to or exceeding 0.90 and Root Mean Square Error of Approximation (RMSEA) and Standardized Root Mean Square Residual (SRMR) values less than 0.08 to determine adequate model fit. We computed internal reliability using Cronbach’s alpha and calculated Pearson or Spearman correlation coefficients between the MSS and MKS and related variables. Results For the MSS, CFA results showed that the one-factor model fit the data well (χ2(df = 5, N = 330) = 34.962, CFI = 0.97, GFI = 0.99, TLI = 0.94, RMSEA = 0.13, SRMR = 0.03). For the MKS, the one-factor model provided a good fit to the data (χ2(df = 6, N = 330) = 8.44, CFI = 0.99, GFI = 0.99, TLI = 0.95, RMSEA = 0.15, SRMR = 0.02). Cronbach’s alphas were MSS = 0.91 and MKS = 0.83, suggesting good to excellent reliability. The MSS was correlated with the MKS (r = .55, p

Abstract Obesity impairs tissue insulin sensitivity and signaling, promoting type-2 diabetes. Although improving insulin signaling is key to reversing diabetes, the multi-organ mechanisms regulating this process are poorly defined. Here, we screen the secretome and receptome in Drosophila to identify the hormonal crosstalk affecting diet-induced insulin resistance and obesity. We discover a complex interplay between muscle, neuronal, and adipose tissues, mediated by Bone Morphogenetic Protein (BMP) signaling and the hormone Bursicon, that enhances insulin signaling and sugar tolerance. Muscle-derived BMP signaling, induced by sugar, governs neuronal Bursicon signaling. Bursicon, through its receptor Rickets, a Leucine-rich-repeat-containing G-protein coupled receptor (LGR), improves insulin secretion and insulin sensitivity in adipose tissue, mitigating hyperglycemia. In mouse adipocytes, loss of the Rickets ortholog LGR4 blunts insulin responses, showing an essential role of LGR4 in adipocyte insulin sensitivity. Our findings reveal a muscle-neuronal-fat-tissue axis driving metabolic adaptation to high-sugar conditions, identifying LGR4 as a critical mediator in this regulatory network.

Abstract Natural radiogenic isotopes (primarily 87Sr/86Sr) from hot springs in the Upper Geyser Basin of the Yellowstone Plateau volcanic field and associated rocks were used to evaluate groundwater flow patterns, water‐rock reactions, and the extent of mixing between various groundwater sources. Thermal waters have very low uranium concentrations and 234U/238U activity ratios near 1.0, which limit their utility as tracers in this reducing setting. Thermal waters have higher Sr concentrations (

Large-bore aspiration thrombectomy is emerging as a promising alternative for thrombus removal in acute pulmonary embolism (PE). In this article, we report a successful case with the newly approved AlphaVac F1885 device in a 76-year-old patient presenting with an intermediate- to high-risk acute PE. Preoperative imaging demonstrated bilateral PE with a modified miller index of 30 and an right ventricle-to-left ventricle ratio of 2.1. Mechanical thrombectomy was performed under local anesthesia with mild sedation. The pulmonary artery pressures decreased from 85/27 to 46/13 immediately after thrombectomy. The postoperative course was notable for marked symptom improvement and repeat imaging showed a 63% decrease in clot burden with a decrease in right ventricle-to-left ventricle ratio to 1.3.

Abstract Silicon photonic integrated circuit foundries enable wafer-level fabrication of entire electro-optic systems-on-a-chip for applications ranging from datacommunication to lidar to chemical sensing. However, silicon’s indirect bandgap has so far prevented its use as an on-chip optical source for these systems. Here, we describe a fullyintegrated broadband silicon waveguide light source fabricated in a state-of-the-art 300-mm foundry. A reverse-biased p-i-n diode in a silicon waveguide emits broadband near-infrared optical radiation directly into the waveguide mode, resulting in nanowatts of guided optical power from a few milliamps of electrical current. We develop a one-dimensional Planck radiation model for intraband emission from hot carriers to theoretically describe the emission. The brightness of this radiation is demonstrated by using it for broadband characterization of photonic components including Mach-Zehnder interferometers and lattice filters, and for waveguide infrared absorption spectroscopy of liquid-phase analytes. This broadband silicon-based source can be directly integrated with waveguides and photodetectors with no change to existing foundry processes and is expected to find immediate application in optical systems-on-a-chip for metrology, spectroscopy, and sensing.

Abstract Long-read sequencing offers long contiguous DNA fragments, facilitating diploid genome assembly and structural variant (SV) detection. Efficient and robust algorithms for SV identification are crucial with increasing data availability. Alignment-based methods, favored for their computational efficiency and lower coverage requirements, are prominent. Alternative approaches, relying solely on available reads for de novo genome assembly and employing assembly-based tools for SV detection via comparison to a reference genome, demand significantly more computational resources. However, the lack of comprehensive benchmarking constrains our comprehension and hampers further algorithm development. Here we systematically compare 14 read alignment-based SV calling methods (including 4 deep learning-based methods and 1 hybrid method), and 4 assembly-based SV calling methods, alongside 4 upstream aligners and 7 assemblers. Assembly-based tools excel in detecting large SVs, especially insertions, and exhibit robustness to evaluation parameter changes and coverage fluctuations. Conversely, alignment-based tools demonstrate superior genotyping accuracy at low sequencing coverage (5-10×) and excel in detecting complex SVs, like translocations, inversions, and duplications. Our evaluation provides performance insights, highlighting the absence of a universally superior tool. We furnish guidelines across 31 criteria combinations, aiding users in selecting the most suitable tools for diverse scenarios and offering directions for further method development.

Abstract Premise Traditional methods of ploidal‐level estimation are tedious; using DNA sequence data for cytotype estimation is an ideal alternative. Multiple statistical approaches to leverage sequence data for ploidy inference based on site‐based heterozygosity have been developed. However, these approaches may require high‐coverage sequence data, use inappropriate probability distributions, or have additional statistical shortcomings that limit inference abilities. We introduce nQuack, an open‐source R package that addresses the main shortcomings of current methods. Methods and Results nQuack performs model selection for improved ploidy predictions. Here, we implement expectation maximization algorithms with normal, beta, and beta‐binomial distributions. Using extensive computer simulations that account for variability in sequencing depth, as well as real data sets, we demonstrate the utility and limitations of nQuack. Conclusions Inferring ploidy based on site‐based heterozygosity alone is difficult. Even though nQuack is more accurate than similar methods, we suggest caution when relying on any site‐based heterozygosity method to infer ploidy.

Summary: The lymphatic fluid is the conduit by which part of the tissue “omics” is transported to the draining lymph node for immunosurveillance. Following cannulation of the pre-nodal cervical and mesenteric afferent lymphatics, herein we investigate the lymph proteomic composition, uncovering that its composition varies according to the tissue of origin. Tissue specificity is also reflected in the dendritic cell-major histocompatibility complex class II-eluted immunopeptidome harvested from the cervical and mesenteric nodes. Following inflammatory disruption of the gut barrier, the lymph antigenic and inflammatory loads are analyzed in both mice and subjects with inflammatory bowel diseases. Gastrointestinal tissue damage reflects the lymph inflammatory and damage-associated molecular pattern signatures, microbiome-derived by-products, and immunomodulatory molecules, including metabolites of the gut-brain axis, mapped in the afferent mesenteric lymph. Our data point to the relevance of the lymphatic fluid to probe the tissue-specific antigenic and inflammatory load transported to the draining lymph node for immunosurveillance.

Background: Some studies have suggested the risk of wound complications may be higher using the direct anterior (DA) approach to total hip arthroplasty (THA). This study aimed to compare the risk of early postoperative wound complications between the DA and direct lateral (DL) approaches to THA and to determine patient risk factors that may contribute to this problem. Methods: All patients who underwent primary THA with a single surgeon over a 5-year period were retrospectively reviewed. All patients were treated with either the DA or DL approach. Data collected included patient demographics, surgical approach, and wound status. There was a minimum follow-up of 6 weeks to allow for an adequate assessment of surgical wound healing. Univariate and multivariate analyses were used to compare the 2 approaches. Results: Five hundred seventy-nine patients (77.6%) who underwent DA approach and 167 patients (22.4%) who underwent DL approach were included. Patients who underwent DL approach had a higher body mass index and a higher rate of diabetes than those treated with the DA approach. Forty patients (6.9%) in the DA cohort and 14 (8.4%) in the DL cohort experienced early wound complications, P = .523. After controlling for potential confounding variables, the surgical approach was not an independent risk factor for early postoperative wound complications. Conclusions: While there have been concerns regarding use of the DA approach in patients with higher body mass index and certain medical comorbidities, the results of this study suggest the choice of surgical approach may have minimal effect on the rate of early postoperative wound complications.

In two laboratory trials, natural products, including freshly picked leaves from spearmint, rosemary, and tansy plants, a water extract from soybean plants, peels from a common cucumber, and 1% peppermint oil in hexane, were placed in a moist harborage preferred by Argentine ants, Linepithema humile (Mayr), and the number of ants entering the harborage after two and four hours was counted. None of the recommended home remedies (tansy, cucumber, or soybean extract) deterred ants from an attractive, moist harborage in either trial, even when the quantity of these treatments was increased 4- to 10-fold. Freshly picked leaves from rosemary and spearmint plants deterred ants from harboring, and the 1% peppermint oil was the most deterrent of all treatments.

During the 2021 (n = 15) and 2022 (n = 13) summers, we measured the total and dissolved (

Foldy is a cloud-based application that allows non-computational biologists to easily utilize advanced AI-based structural biology tools, including AlphaFold and DiffDock. With many deployment options, it can be employed by individuals, labs, universities, and companies in the cloud without requiring hardware resources, but it can also be configured to utilize locally available computers. Foldy enables scientists to predict the structure of proteins and complexes up to 6000 amino acids with AlphaFold, visualize Pfam annotations, and dock ligands with AutoDock Vina and DiffDock. In our manuscript, we detail Foldy's interface design, deployment strategies, and optimization for various user scenarios. We demonstrate its application through case studies including rational enzyme design and analyzing proteins with domains of unknown function. Furthermore, we compare Foldy's interface and management capabilities with other open and closed source tools in the field, illustrating its practicality in managing complex data and computation tasks. Our manuscript underlines the benefits of Foldy as a day-to-day tool for life science researchers, and shows how Foldy can make modern tools more accessible and efficient.

Abstract Background: Using a large, geographically diverse, hospital-based database in the United States (Premier PINC AI Healthcare Database), we aimed to describe the proportion and characteristics of patients receiving phenotype-desirable antimicrobial therapy (PDAT) among those hospitalized with Enterobacterales bloodstream infections. Methods: Adult patients with an admission between January 1, 2017 and June 30, 2022 with ≥1 blood culture positive for Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, or Proteus mirabilis and receiving an empiric antibiotic therapy on blood culture collection (BCC) Days 0 or 1 were included. Receiving PDAT (defined as receipt of any antimicrobial categorized as “desirable” for the respective phenotype) on BCC Days 0−2 was defined as receiving early PDAT. Results: Among 35,880 eligible patients, the proportion of patients receiving PDAT increased (from 6.8% to 22.8%) from BCC Day 0−4. Patients who received PDAT (8,193, 22.8%) were more likely to visit large (500 + beds, 36% vs 31%), teaching (45% vs 39%), and urban (85% vs 82%) hospitals in the Northeast (22% vs 13%) compared to patients not receiving PDAT (all P

Disk vortices, seen in numerical simulations of protoplanetary disks and found observationally in Atacama Large Millimeter/submillimeter Array and Very Large Array images of these objects, are promising sites for planet formation given their pebble trapping abilities. Previous works have shown a strong concentration of pebbles in vortices, but gravitational collapse has only been shown in low-resolution, two-dimensional, global models. In this Letter, we aim to study the pebble concentration and gravitational collapse of pebble clouds in vortices via high-resolution, three-dimensional, local models. We performed simulations of the dynamics of gas and solids in a local shearing box where the gas is subject to convective overstability, generating a persistent giant vortex. We find that the vortex produces objects of Moon and Mars mass, with a mass function of power-law $d\mathrm{ln}N/d\mathrm{ln}M=-1.6\pm 0.3$ . The protoplanets grow rapidly, doubling in mass in about five orbits, following pebble accretion rates. The mass range and mass doubling rate are in broad agreement with previous low-resolution global models. We conclude that Mars-mass planetary embryos are the natural outcome of planet formation inside the disk vortices seen in millimeter and radio images of protoplanetary disks.

The Yamuna River in India and the Mississippi River in the United States hold significant commercial, cultural, and ecological importance. This preliminary survey compares the bacterial communities sampled in surface waters at 11 sites (Yamuna headwaters, Mississippi headwaters, Yamuna River Yamunotri Town, Mississippi River at Winona, Tons River, Yamuna River at Paonta Sahib, Yamuna River Delhi-1, Yamuna River Delhi-2, Yamuna River before Sangam, Sangam, Ganga River before Sangam). Bacterial 16S rDNA analyses demonstrate dominance of Proteobacteria and Bacteroidetes phyla. Actinobacteria were also dominant at sites near Sangam in India and sites in Minnesota. A dominance of Epsilonbacteraeota were found in Delhi, India. Principal component analysis (PCA) using unique operational taxonomic units (OTUs) resulted in the identification of 3 groups that included the Yamuna River locations in Delhi (Delhi locations), Yamuna headwaters and Yamuna River at Yamunotri (Yamuna River locations below the Glacier) and Mississippi, Ganga, Tons, and other Yamuna River locations. Diversity indices were significantly higher at the Yamuna River locations below the Glacier (Simpson D = 0.986 and Shannon H = 5.06) as compared (p value

BackgroundEmulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients.MethodsWe used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000-2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance.ResultsWe identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29-1.44).ConclusionIn this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation.

Abstract The TRPM4 gene codes for a membrane ion channel subunit related to inflammation in the central nervous system. Recent investigation has identified an association between TRPM4 single nucleotide polymorphisms (SNPs) rs8104571 and rs150391806 and increased intracranial (ICP) pressure following traumatic brain injury (TBI). We assessed the influence of these genotypes on clinical outcomes and ICP in TBI patients. We included 292 trauma patients with TBI. DNA extraction and real-time PCR were used for TRPM4 rs8104571 and rs150391806 allele discrimination. Five participants were determined to have the rs8104571 homozygous variant genotype, and 20 participants were identified as heterozygotes; 24 of these 25 participants were African American. No participants had rs150391806 variant alleles, preventing further analysis of this SNP. Genotypes containing the rs8104571 variant allele were associated with decreased Glasgow outcome scale-extended (GOSE) score (P = 0.0231), which was also consistent within our African-American subpopulation (P = 0.0324). Regression analysis identified an association between rs8104571 variant homozygotes and mortality within our overall population (P = 0.0230) and among African Americans (P = 0.0244). Participants with rs8104571 variant genotypes exhibited an overall increase in ICP (P = 0.0077), although a greater frequency of ICP measurements > 25 mmHg was observed in wild-type participants (P =

Sea-level projections depend sensitively on the parameterization used for basal slip in glacier flow models. During slip over rock-beds, ice-bed separation increases with slip velocity and basal water pressure. We present a method for using these variables and measured bed topography to estimate the average bed slope in contact with ice, ${\bar m}$. Three-dimensional numerical modeling of slip over small areas of former beds has shown that changes in ${\bar m}$ with increasing slip velocity and water pressure mimic changes in basal drag. Computed values of ${\bar m}$ can thus provide the form of the slip law that relates drag to velocity and water pressure, avoiding computationally expensive numerical modeling. The method is applied to 618 sections from four former glacier beds. Results generally show an increase in ${\bar m}$, and hence inferred basal drag, with slip velocity up to a limiting value, consistent with a regularized Coulomb slip law.

Single-limb balance training is integral to preventing and rehabilitating lower extremity injuries. Previous investigations have shown that when using instability devices, differences may or may not exist in the postural sway parameters during use, depending on the specific devices being assessed. Thus, this investigation sought to examine the differences between a commonly used foam pad and a novel instability device (block) in postural sway measures. Twenty-two healthy individuals with no history of lower extremity injury or neurological disorders participated in this investigation. The participants performed three single-limb static balance exercises on a force platform sampling at 120 Hz. Each condition contained three 10-s trials separated by thirty seconds. The mean CoP values of the three trials in each condition were then compared using a within-subjects repeated-measures analysis of variance. Statistically significant differences were seen in the sway area between conditions (p = 0.009), the CoP path length (p = 0.007), the peak medial–lateral CoP displacement (p = 0.004), and the average sway velocity (p = 0.007). All variables displayed similar trends whereby the control condition showed significantly lower values than both instability devices, with no differences between devices. This investigation provides supporting evidence that different instability devices may deliver similar changes to postural sway parameters compared to control conditions. The novel block instability device used in this investigation may be used similarly to the traditional foam pad in prevention and rehabilitation settings based on the absence of differences between the two devices.

Utah Lake is unusual due to its large surface area, shallow depth, phosphorus-rich sediments, and well-mixed, unstratified waters. This creates conditions where water column phosphorous concentrations tend toward equilibrium, with lake sediments containing high concentrations of geologic phosphorus. To help understand the potential impact of phosphorous load reductions, we computed a time history of phosphorus mass in the lake using state and federal records of lake volume, dissolved phosphorus concentrations, and outflow. We show that historically, Utah Lake phosphorus concentrations have remained stable over time, in the range of 0.02 to 0.04 mg/L, despite large changes in lake volume and internal phosphorus mass. We performed sorption calculations using data from the literature, demonstrating that it would take unrealistically large load changes to alter water column phosphorus concentrations under sorption processes. The sorption model produces results consistent with historical data that show relatively constant phosphorous concentrations despite large lake volume changes. We show, through several lines of evidence, that water column phosphorus concentrations are insensitive to external loads. Phosphorous load reduction is unlikely to have a significant effect on phosphorus concentrations in Utah Lake and, by extension, in other sorption-dominated shallow lakes with phosphorus-rich sediment.

The study area is composed of mainly basement rocks, with problems of low yield of groundwater in most of the boreholes drilled. Therefore, this study was carried out to evaluate the hydraulic parameters of the basement aquifers using the vertical electrical sounding (VES), constant rate pumping test, and borehole logs. The mean value of aquifer resistivity and thickness are 408.4 Ωm and 20.2 m. The depth ranges from 20.9-88.0 m with a mean value of 55.5 m; showing appreciable groundwater potential mostly within the southern part. The value of transmissivity and hydraulic conductivity from the resistivity data ranges from 2.058-1761.033 m2/day and 0.205-138.664 m/day with a mean value of 152.251 m2/day and 8.841 m/day, respectively, indicating porous and permeable zones within the southern and northwestern part of the study area. The value of longitudinal conductance and transverse unit resistance ranges from 0.0034-4.2333 m-hom and 38.1-146439 Ωm2 with a mean value of 0.3250 m-hom and 9704.1 Ωm2; indicating poor to moderate protective capacity in almost the entire area except for the small portion within the southern part. The mean value of fracture contrast and the reflection coefficient are 0.743 and -0.333, showing that the southern part has more water-filled fractures. Conclusively, this study reveals, that the aquifer depth ranges from 60-90 m, the transmissivity and hydraulic conductivity demonstrate high porosity and permeability within the southern parts of the study area, and serve as a baseline for groundwater resource management policy in Nigeria.

IntroductionMetastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint inhibitors (ICIs). Oncolytic viruses (OV) represent a novel approach to immunotherapy for patients with MUM.MethodsWe developed an OV with a Vesicular Stomatitis Virus (VSV) vector modified to express interferon-beta (IFN-β) and Tyrosinase Related Protein 1 (TYRP1) (VSV-IFNβ-TYRP1), and conducted a Phase 1 clinical trial with a 3 + 3 design in patients with MUM. VSV-IFNβ-TYRP1 was injected into a liver metastasis, then administered on the same day as a single intravenous (IV) infusion. The primary objective was safety. Efficacy was a secondary objective.Results12 patients with previously treated MUM were enrolled. Median follow up was 19.1 months. 4 dose levels (DLs) were evaluated. One patient at DL4 experienced dose limiting toxicities (DLTs), including decreased platelet count (grade 3), increased aspartate aminotransferase (AST), and cytokine release syndrome (CRS). 4 patients had stable disease (SD) and 8 patients had progressive disease (PD). Interferon gamma (IFNγ) ELIspot data showed that more patients developed a T cell response to virus encoded TYRP1 at higher DLs, and a subset of patients also had a response to other melanoma antigens, including gp100, suggesting epitope spreading. 3 of the patients who responded to additional melanoma antigens were next treated with ICIs, and 2 of these patients experienced durable responses.DiscussionOur study found that VSV-IFNβ -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM. Although there were no clear objective radiographic responses to VSV-IFNβ-TYRP1, dose-dependent immunogenicity to TYRP1 and other melanoma antigens was seen.

BackgroundTo end the HIV epidemic by 2030, we must double down on efforts to tailor prevention interventions to both young men who have sex with men and transgender and nonbinary youth. There is an urgent need for interventions that specifically focus on pre-exposure prophylaxis (PrEP) uptake in sexual and gender minority youth (SGMY) populations. There are several factors that impact the ability of SGMY to successfully engage in the HIV prevention continuum, including uptake of PrEP. Patient activation, having the knowledge, skills, and self-efficacy to manage one’s health, is an important indicator of willingness and ability to manage one’s own health and care autonomously. Patient navigation also plays an important role in helping SGMY access PrEP and PrEP care, as navigators help guide patients through the health care system, set up medical appointments, and get financial, legal, and social support. ObjectiveThis study aims to evaluate the feasibility and acceptability of a digital PrEP navigation and activation intervention among a racially and ethnically diverse sample of SGMY living in the Los Angeles area. MethodsIn phase 1, we will conduct formative research to inform the development of PrEPresent using qualitative data from key informant interviews involving PrEP care providers and navigators and working groups with SGMY. In phase 2, we will complete 2 rounds of usability testing of PrEPresent with 8-10 SGMY assessing both the intervention content and mobile health delivery platform to ensure features are usable and content is understood. In phase 3, we will conduct a pilot randomized controlled trial to evaluate the feasibility and acceptability of PrEPresent. We will randomize, 1:1, a racially and ethnically diverse sample of 150 SGMY aged 16-26 years living in the Los Angeles area and follow participants for 6 months. ResultsPhase 1 (formative work) was completed in April 2021. Usability testing was completed in December 2021. As of June 2023, 148 participants have been enrolled into the PrEPresent pilot randomized controlled trial (phase 3). Enrollment is expected to be completed in July 2023, with final results anticipated in December 2023. ConclusionsThe PrEPresent intervention aims to bridge the gaps in PrEP eligibility and PrEP uptake among racially and ethnically diverse SGMY. By facilitating the delivery of PrEP navigation and focusing on improving patient activation, the PrEPresent intervention has the potential to positively impact the PrEP uptake cascade in the HIV care continuum as well as serve as a model for the tailoring of PrEP interventions based on behavior-based qualifications for PrEP instead of generalized gender-based eligibility. Trial RegistrationClinicalTrials.gov NCT05281393; https://clinicaltrials.gov/ct2/show/NCT05281393 International Registered Report Identifier (IRRID)DERR1-10.2196/50866

Abstract It is well established that an elevated potassium level (hyperkalemia) is associated with a risk of adverse events including morbidity, mortality and healthcare system cost. Hyperkalemia is commonly encountered in many chronic conditions including kidney disease, diabetes and heart failure. Furthermore, hyperkalemia may result from the use of renin-angiotensin-aldosterone system inhibitors (RAASi), which are disease-modifying treatments for these conditions. Therefore, balancing the benefits of optimizing treatment with RAASi while mitigating hyperkalemia is crucial to ensure patients are optimally treated. In this review, we will briefly discuss the definition, causes, epidemiology and consequences of hyperkalemia. The majority of the review will be focused on management of hyperkalemia in the acute and chronic setting, emphasizing contemporary approaches and evolving data on the relevance of dietary restriction and the use of novel potassium binders.

Abstract A machine-learned spin-lattice interatomic potential (MSLP) for magnetic iron is developed and applied to mesoscopic scale defects. It is achieved by augmenting a spin-lattice Hamiltonian with a neural network term trained to descriptors representing a mix of local atomic configuration and magnetic environments. It reproduces the cohesive energy of BCC and FCC phases with various magnetic states. It predicts the formation energy and complex magnetic structure of point defects in quantitative agreement with density functional theory (DFT) including the reversal and quenching of magnetic moments near the core of defects. The Curie temperature is calculated through spin-lattice dynamics showing good computational stability at high temperature. The potential is applied to study magnetic fluctuations near sizable dislocation loops. The MSLP transcends current treatments using DFT and molecular dynamics, and surpasses other spin-lattice potentials that only treat near-perfect crystal cases.

Abstract Background Suicide is the tenth leading cause of death in the United States, with over half of cases involving firearms. Despite research indicating negative effects of exposure to suicide, there is little research on who typically finds the body of the suicide decedent. Understanding who finds the body of the suicide decedent may be important to understand trauma and mental health effects. Findings Of the 332 people who died by suicide in El Paso County, Colorado, 182 (55%) used firearms. Those who died by firearm suicide were more likely to be male (83.5% vs. 67.3%) have military affiliation (39.0% vs. 19.3%) and were less likely to have a known mental health diagnosis (47.3% vs. 64.7%) compared to those who died from other means. Most suicide decedents were found by a family member or friend (60.2%). The remaining decedents were found by a stranger/acquaintance (21.0%) or a first responder (22.4%) One-fifth of suicides involved forced witnessing (19%) and the majority were already deceased when the body was discovered (73.2%). Conclusions While most suicide decedents are discovered by a family member or a friend, it is unknown what the bereavement and trauma-related outcomes are among people who discover a suicide decedent who has died by violent means, especially by firearms. Further studies exploring who discovers suicide decedents and targeted postvention strategies for supporting impacted family, friends, first responders, and strangers are needed.

Pseudomonas putida has been engineered to produce medium chain length oleochemicals, including medium chain length free fatty acids and their ester forms, compounds which may be useful as biodiesel blending agents.

Abstract Objective To understand the patterns of temporal bone fracture and facial nerve injury from ballistic trauma. Study Design Retrospective case series. Methods Retrospective review of 42 patients evaluated following temporal bone ballistic injury at a single institution, university‐based level‐one trauma center between 2012 and 2021. Demographics, facial nerve status, CT images, interventions, complications, and outcomes were reviewed. Results Mean age 30.3 years (range 5–58 years); 79% male. Racial demographics reflected the surrounding community. Seven mortalities occurred. Nineteen patients (54%) demonstrated facial nerve injury. Of those, 13/19 displayed immediate paralysis, 1 delayed, 5 unknown (due to altered mental status). On consultation, House‐Brackmann grade 6 paralysis was common (13/19). Fracture was otic capsule‐sparing in 17/19 (90%), universally comminuted, with significant disruption along the mastoid tip (16/19), external auditory canal (EAC) (15/19), and periauricular soft tissues (13/19). Nine patients underwent surgical intervention: Transmastoid facial nerve decompression to remove compressive bony spicules (n = 5); eye protection surgery (n = 3); and peripheral facial nerve exploration (n = 1), noting transection at the pes. One required middle cranial fossa and transmastoid repair of cerebrospinal fistulae in setting of severe meningitis. House‐Brackmann scores improved in 80% following transmastoid nerve decompression despite CT evidence of likely additional injury in its extratemporal course. Conclusions Common patterns of temporal bone fracture seen in blunt trauma (longitudinal/transverse, otic capsule‐sparing/disrupting) were not found in patients with ballistic facial nerve injury. Rather, injury was commonly apparent in the EAC, mastoid tip, and periauricular soft tissues. Clinicians should have high suspicion for extratemporal facial nerve injury following ballistic trauma.

Abstract In pollen‐limited plant communities, the foraging behavior of pollinators might mediate coexistence and competitive exclusion of plant species by determining which plants receive conspecific pollen. A key question is whether realistic pollinator foraging behavior promotes coexistence or exclusion of plant species. We use a simulation model to understand how pollinator foraging behavior impacts the coexistence dynamics of pollen‐limited plants. To determine whether pollinators are likely to provide a biologically important coexistence mechanism, we compare our results to bee foraging data from the literature and from a novel experimental analysis. Model results indicate that strong specialization at the level of individual foraging paths is required to promote coexistence. However, few empirical studies have robustly quantified within‐bout specialization. Species‐level data suggest that foraging behavior is sufficient to permit pollinator‐mediated coexistence in species‐poor plant communities and possibly in diverse communities where congeneric plants co‐occur. Our experiments using bumblebees show that individual‐level specialization does exist, but not at levels sufficient to substantially impact coexistence dynamics. The literature on specialization within natural foraging paths suffers from key limitations, but overall suggests that pollinator‐mediated coexistence should be rare in diverse plant communities.

Background:. There is limited research on the impact of revisional surgery after breast reconstruction on patient experience and postoperative quality of life (QoL). Methods:. Patients undergoing mastectomy with immediate implant-based or autologous free-flap breast reconstruction from 2008 to 2020 were reviewed. These patients were categorized by revisions (0–1, 2–3, and 4+) and surveyed on QoL metrics using BREAST-Q and Was It Worth It? (WIWI) questionnaires. BREAST-Q QoL, satisfaction, and WIWI metrics between revision groups were evaluated. Results:. Among 252 patients, a total of 150 patients (60%) underwent zero to one revisions, 72 patients (28%) underwent two to three revisions, and 30 patients (12%) underwent four or more revisions. Median follow-up was 6 years (range, 1–11 years). BREAST-Q satisfaction among patients with four or more revisions was significantly lower (P = 0.03), while core QoL domains (chest physical, psychosocial, and sexual well-being) did not significantly differ. Analysis of unplanned reoperations due to complications and breast satisfaction showed no significant difference in QoL scores between groups (P = 0.08). Regarding WIWI QoL metrics, four or more revisions were associated with a higher rate of worse QoL (P = 0.035) and worse overall experience (P = 0.001). Most patients in all revision groups felt it was worthwhile to undergo breast reconstruction (86%), would choose breast reconstruction again (83%), and would recommend breast reconstruction to others (79%). Conclusions:. Overall, a majority of patients undergoing revisions after breast reconstruction still have a worthwhile experience. Although reoperations after breast reconstruction do not significantly impact long-term BREAST-Q QoL domains, patients undergoing four or more revisions have significantly lower breast satisfaction, worse QoL, and a postoperative experience worse than expected.

OBJECTIVES:. This narrative review article seeks to highlight the effects of citrate on physiology during massive transfusion of the bleeding patient. DATA SOURCES:. A limited library of curated articles was created using search terms including “citrate intoxication,” “citrate massive transfusion,” “citrate pharmacokinetics,” “hypocalcemia of trauma,” “citrate phosphate dextrose,” and “hypocalcemia in massive transfusion.” Review articles, as well as prospective and retrospective studies were selected based on their relevance for inclusion in this review. STUDY SELECTION:. Given the limited number of relevant studies, studies were reviewed and included if they were written in English. This is not a systematic review nor a meta-analysis. DATA EXTRACTION AND SYNTHESIS:. As this is not a meta-analysis, new statistical analyses were not performed. Relevant data were summarized in the body of the text. CONCLUSIONS:. The physiologic effects of citrate independent of hypocalcemia are poorly understood. While a healthy individual can rapidly clear the citrate in a unit of blood (either through the citric acid cycle or direct excretion in urine), the physiology of hemorrhagic shock can lead to decreased clearance and prolonged circulation of citrate. The so-called “Diamond of Death” of bleeding—coagulopathy, acidemia, hypothermia, and hypocalcemia—has a dynamic interaction with citrate that can lead to a death spiral. Hypothermia and acidemia both decrease citrate clearance while circulating citrate decreases thrombin generation and platelet function, leading to ionized hypocalcemia, coagulopathy, and need for further transfusion resulting in a new citrate load. Whole blood transfusion typically requires lower volumes of transfused product than component therapy alone, resulting in a lower citrate burden. Efforts should be made to limit the amount of citrate infused into a patient in hemorrhagic shock while simultaneously addressing the induced hypocalcemia.

Changing climates are causing agricultural water shortages at unprecedented scales and magnitudes, especially in regions historically reliant on irrigation. Identifying and understanding systems of farming that allow continuity in agricultural operations in times of water scarcity are increasingly urgent needs. Vegetable dry farming relies on winter rains stored in soils to reduce irrigation to 0–2 events per season and has become prevalent on California’s Central Coast in recent decades. Until now, this system has been unexplored in scientific literature beyond extension publications, despite its promise as a model for low-water agriculture in arid regions. Dry farm management presents a unique challenge given that low water content restricts nutrient access in surface soils, which farmers typically target for fertility management. Managing soil nutrients at depth, as well as microorganisms that help plants access nutrients and alleviate water stress (e.g. arbuscular mycorrhizal fungi, or AMF) could be crucial to dry farm success. We engaged in a collaborative research design process with farmers managing seven commercial dry farm tomato fields to identify and answer three key management questions: 1. What are the depths at which nutrients influence harvest outcomes given low water content in surface soils?, 2. Are commercially available AMF inoculants effective at improving harvest outcomes?, and 3. How does the broader fungal community change in dry farm soils, and are those changes associated with harvest outcomes? Only soil nutrients below 60 cm depth were correlated with tomato yield and fruit quality. We identified a fungal class, Sordariomycetes, as a ‘signature’ fungal group in dry farm soils that distinguished them from irrigated management and correlated with positive fruit quality, while commercial AMF inoculation showed little benefit. These findings can inform management practices that optimize fruit yield and quality, and can guide farmers and policymakers alike in efforts to minimize agricultural water use.

Given the important role turbulence plays in the settling and growth of dust grains in protoplanetary disks, it is crucial that we determine whether these disks are turbulent and to what extent. Protoplanetary disks are weakly ionized near the midplane, which has led to a paradigm in which largely laminar magnetic field structures prevail deeper in the disk, with angular momentum being transported via magnetically launched winds. Yet, there has been little exploration of the precise behavior of the gas within the bulk of the disk. We carry out 3D, local shearing box simulations that include all three low-ionization effects (ohmic diffusion, ambipolar diffusion, and the Hall effect) to probe the nature of magnetically driven gas dynamics 1–30 au from the central star. We find that gas turbulence can persist with a generous yet physically motivated ionization prescription (order unity Elsässer numbers). The gas velocity fluctuations range from 0.03 to 0.09 of the sound speed c _s at the disk midplane to ∼ c _s near the disk surface, and are dependent on the initial magnetic field strength. However, the turbulent velocities do not appear to be strongly dependent on the field polarity, and thus appear to be insensitive to the Hall effect. The midplane turbulence has the potential to drive dust grains to collision velocities exceeding their fragmentation limit, and likely reduces the efficacy of particle clumping in the midplane, though it remains to be seen if this level of turbulence persists in disks with lower ionization levels.

Ionization drives important chemical and dynamical processes within protoplanetary disks, including the formation of organics and water in the cold midplane and the transportation of material via accretion and magnetohydrodynamic flows. Understanding these ionization-driven processes is crucial for understanding disk evolution and planet formation. We use new and archival Atacama Large Millimeter/submillimeter Array observations of HCO ^+ , H ^13 CO ^+ , and N _2 H ^+ to produce the first forward-modeled 2D ionization constraints for the DM Tau protoplanetary disk. We include ionization from multiple sources and explore the disk chemistry under a range of ionizing conditions. Abundances from our 2D chemical models are postprocessed using non-LTE radiative transfer, visibility sampling, and imaging, and are compared directly to the observed radial emission profiles. The observations are best fit by a modestly reduced cosmic-ray ionization rate ( ζ _CR ∼10 ^−18 s ^−1 ) and a hard X-ray spectrum (hardness ratio = 0.3), which we associate with stellar flaring conditions. Our best-fit model underproduces emission in the inner disk, suggesting that there may be an additional mechanism enhancing ionization in DM Tau’s inner disk. Overall, our findings highlight the complexity of ionization in protoplanetary disks and the need for high-resolution multiline studies.

The streaming instability (SI) is a leading candidate for planetesimal formation, which can concentrate solids through two-way aerodynamic interactions with the gas. The resulting concentrations can become sufficiently dense to collapse under particle self-gravity, forming planetesimals. Previous studies have carried out large parameter surveys to establish the critical particle to gas surface density ratio ( Z ), above which SI-induced concentration triggers planetesimal formation. The threshold Z depends on the dimensionless stopping time ( τ _s , a proxy for dust size). However, these studies neglected both particle self-gravity and external turbulence. Here, we perform 3D stratified shearing box simulations with both particle self-gravity and turbulent forcing, which we characterize via a turbulent diffusion parameter, α _D . We find that forced turbulence, at amplitudes plausibly present in some protoplanetary disks, can increase the threshold Z by up to an order of magnitude. For example, for τ _s = 0.01, planetesimal formation occurs when Z ≳ 0.06, ≳0.1, and ≳0.2 at α _D = 10 ^−4 , 10 ^−3.5 , and 10 ^−3 , respectively. We provide a single fit to the critical Z required for the SI to work as a function of α _D and τ _s (although limited to the range τ _s = 0.01–0.1). Our simulations also show that planetesimal formation requires a mid-plane particle-to-gas density ratio that exceeds unity, with the critical value being largely insensitive to α _D . Finally, we provide an estimation of particle scale height that accounts for both particle feedback and external turbulence.

It is generally accepted that the Moon accreted from the disk formed by an impact between the proto-Earth and impactor, but its details are highly debated. Some models suggest that a Mars-sized impactor formed a silicate melt-rich (vapor-poor) disk around Earth, whereas other models suggest that a highly energetic impact produced a silicate vapor-rich disk. Such a vapor-rich disk, however, may not be suitable for the Moon formation, because moonlets, building blocks of the Moon, of 100 m–100 km in radius may experience strong gas drag and fall onto Earth on a short timescale, failing to grow further. This problem may be avoided if large moonlets (≫100 km) form very quickly by streaming instability, which is a process to concentrate particles enough to cause gravitational collapse and rapid formation of planetesimals or moonlets. Here, we investigate the effect of the streaming instability in the Moon-forming disk for the first time and find that this instability can quickly form ∼100 km-sized moonlets. However, these moonlets are not large enough to avoid strong drag, and they still fall onto Earth quickly. This suggests that the vapor-rich disks may not form the large Moon, and therefore the models that produce vapor-poor disks are supported. This result is applicable to general impact-induced moon-forming disks, supporting the previous suggestion that small planets (

Kuiper Belt objects (KBOs) show an unexpected trend, whereby large bodies have increasingly higher densities, up to five times greater than their smaller counterparts. Current explanations for this trend assume formation at constant composition, with the increasing density resulting from gravitational compaction. However, this scenario poses a timing problem to avoid early melting by decay of ^26 Al. We aim to explain the density trend in the context of streaming instability and pebble accretion. Small pebbles experience lofting into the atmosphere of the disk, being exposed to UV and partially losing their ice via desorption. Conversely, larger pebbles are shielded and remain icier. We use a shearing box model including gas and solids, the latter split into ices and silicate pebbles. Self-gravity is included, allowing dense clumps to collapse into planetesimals. We find that the streaming instability leads to the formation of mostly icy planetesimals, albeit with an unexpected trend that the lighter ones are more silicate-rich than the heavier ones. We feed the resulting planetesimals into a pebble accretion integrator with a continuous size distribution, finding that they undergo drastic changes in composition as they preferentially accrete silicate pebbles. The density and masses of large KBOs are best reproduced if they form between 15 and 22 au. Our solution avoids the timing problem because the first planetesimals are primarily icy and ^26 Al is mostly incorporated in the slow phase of silicate pebble accretion. Our results lend further credibility to the streaming instability and pebble accretion as formation and growth mechanisms.

β-Adrenergic signaling is a core regulator of brown adipocyte function. Here, the authors provide unbiased insight into the transcriptional network controlled by lipolysis in brown adipocytes, showing that lipolysis is required for much of the thermogenic gene program activated by β-adrenergic signals.

Abstract Background If not accounted for, genotype x environment (G×E) interactions can decrease the accuracy of genetic evaluations and the efficiency of breeding schemes. These interactions are reflected by genetic correlations between countries lower than 1. In countries that are characterized by a heterogeneity of production systems, they are also likely to exist within country, especially when production systems are diverse, as is the case in South Africa. We illustrate several alternative approaches to assess the existence of G×E interactions for production traits and age at first calving in Holsteins in South Africa. Data from 257,836 first lactation cows were used. First, phenotypes that were collected in different regions were considered as separate traits and various multivariate animal models were fitted to calculate the estimates of heritability for each region and the genetic correlations between them. Second, a random regression approach using long-term averages of climatic variables at the herd level in a reaction norm model, was used as an alternative way to account for G×E interactions. Genetic parameter estimates and goodness-of-fit measures were compared. Results Genetic correlations between regions as low as 0.80 or even lower were found for production traits, which reflect strong G×E interactions within South Africa that can be linked to the production systems (pasture vs total mixed ration). A random regression model including average rainfall during several decades in the herd surroundings gave the best goodness-of-fit for production traits. This can be related to a preference for total mixed ration on farms with limited rainfall. For age at first calving, the best model was based on a random regression on maximum relative humidity and maximum temperature in summer. Conclusions Our results indicate that G×E interactions can be accounted for when genetic evaluations of production traits are performed in South Africa, by either considering production records in different regions as different correlated traits or using a reaction norm model based on herd management characteristics. From a statistical point of view, climatic variables such as average rainfall over a long period can be included in a random regression model as proxies of herd production systems and climate.

Abstract Premise We present approaches used to generate long‐read Nanopore sequencing reads for the Liliales and demonstrate how modifications to standard protocols directly impact read length and total output. The goal is to help those interested in generating long‐read sequencing data determine which steps may be necessary for optimizing output and results. Methods Four species of Calochortus (Liliaceae) were sequenced. Modifications made to sodium dodecyl sulfate (SDS) extractions and cleanup protocols included grinding with a mortar and pestle, using cut or wide‐bore tips, chloroform cleaning, bead cleaning, eliminating short fragments, and using highly purified DNA. Results Steps taken to maximize read length can decrease overall output. Notably, the number of pores in a flow cell is correlated with the overall output, yet we did not see an association between the pore number and the read length or the number of reads produced. Discussion Many factors contribute to the overall success of a Nanopore sequencing run. We showed the direct impact that several modifications to the DNA extraction and cleaning steps have on the total sequencing output, read size, and number of reads generated. We show a tradeoff between read length and the number of reads and, to a lesser extent, the total sequencing output, all of which are important factors for successful de novo genome assembly.

Background: Post-exertional malaise (PEM) is considered a characteristic feature of chronic multi-symptom illnesses (CMI) like Gulf War illness (GWI); however, its pathophysiology remains understudied. Previous investigations in other CMI populations (i.e., Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) have reported associations between PEM and expression of genes coding for adrenergic, metabolic, and immune function. Objectives: To investigate whether PEM is meditated by gene expression in Veterans with GWI. Methods: Veterans with GWI (n = 37) and healthy control Gulf War Veterans (n = 25) provided blood samples before and after 30-min of cycling at 70% of age-predicted heart rate reserve. Relative quantification of gene expression, symptom measurements, and select cardiopulmonary parameters were compared between groups at pre-, 30 minpost-, and 24 hpost-exercise using a doubly multivariate repeated measures analysis of variance (RM-MANOVA). Mediation analyses were used to test indirect effects of changes in gene expression on symptom responses (i.e., PEM) to the standardized exercise challenge. Results: Veterans with GWI experienced large symptom exacerbations following exercise compared to controls (Cohen's d: 1.65; p

Stimuli responsive self‐folding structures with 2D layered materials (2DLMs) are important for flexible electronics, wearables, biosensors, bioelectronics, and photonics. Previously, strategies have been developed to self‐fold 2D materials to form various robots, sensors, and actuators. Still, there are limitations with scalability and a lack of design tools to obtain complex structures for reversible actuation, high integration, and reliable function. Herein, a mass‐producible strategy for creating monolayer graphene‐based reversible self‐folding structures using either gradient or differentially cross‐linked films of a negative epoxy photoresist widely used in microfluidics and micromechanical systems, namely, SU8 is demonstrated. Wafer‐scale patterning and integration of complex and functional devices in the form of rings, polyhedra, flowers, and bidirectionally folded origami birds are achieved. Also, gold (Au) electrodes to realize functional graphene–Au Schottky interfaces with enhanced photoresponse and 3D angle sensitive detection are integrated. The experiments are guided and rationalized by theoretical methods including coarse‐grained models, specifically developed for the tunable mechanics of this photoresist that simulate the folding dynamics, and finite element method (FEM) electromagnetic simulations. This work suggests a comprehensive framework for the rational design and scalable fabrication of complex 3D self‐actuating optical and electronic devices through the folding of 2D monolayer graphene.

IntroductionProposals for embodied metaphor and embodied cognition have suggested abstract concepts are understood indirectly through the simulation of previous sensory experiences in a different domain. While exceptions have been observed for sensory deficits and impairments that are common, such as vision and audition, it is commonly assumed that somatosensation (proprioception, haptic touch, pain, pressure, temperature, etc.) is fundamental for the comprehension of production of sensory metaphors and much abstract thought in general. In this way, our past sensory experiences are critical to our understanding not just of the world around us but also of our sense of selves. This would suggest that Kim, who was born without somatosensation, would have difficulty understanding, using, or even thinking about many abstract concepts typically linked to different sensory experiences through metaphor, including a creation of a sense of self.MethodsTo examine her comprehension of sensory metaphors, Kim was asked to select the best sensory idiomatic expression given its context. Her friends and family as well as a representative sample of individuals online were recruited to complete the survey as controls. Additionally, we transcribed and analyzed six hours of unprompted speech to determine if Kim spontaneously uses somatosensory metaphors appropriately.ResultsResults from the idiomatic expression survey indicate that Kim performs as well as controls despite lacking any previous direct sensory experiences of these concepts. Analysis of the spontaneous speech highlights that Kim appropriately uses tactile expressions in both their concrete sensory and abstract metaphorical meanings.DiscussionTaken together, these two studies demonstrate that what is lost in sensory experiences can be made up in linguistic experiences, as Kim's understanding of tactile words was acquired in the complete absence of somatosensory experiences. This study demonstrates that individuals can comprehend and use tactile language and metaphor without recruiting past somatosensory experiences, and thus challenges a strong definition of embodied cognition which requires sensory simulations in language comprehension and abstract thought.

In this research, we explore the preliminary effects of processing conditions using a novel additive manufacturing (AM) process, known as additive friction stir deposition (AFSD), on resulting build direction (BD) mechanical performance. Using the AFSD process, a feasibility study of three AM builds of identical size are created using differentiating processing parameters. A relationship referred to as the deposition pitch, exhibiting similarities to weld pitch, is determined to be a simple but effective predictor of the interlayer bonding in AFSD processing of AA7020. The deposition pitch directly correlates the necessary temperature, time, and pressure required for effective solid-state bonding. Using this correlation, increased mechanical performance in the BD is achieved through an increase in deposition pitch. A reduction in the deposition pitch from 4.46 rev/mm to 1.08 rev/mm resulted in a significant decrease in failure strain from 24.4% to 0.82%, with the failure mechanism shifting from a ductile failure to brittle failure. The inverse relationship between grain refinement and BD failure strain at high deposition pitches suggests deposition pitch and heat input are the dominant factors in the resulting BD mechanical properties.

Abstract Background Refugia is considered to be critical for maintaining biodiversity; while discerning the type and pattern of refugia is pivotal for our understanding of evolutionary processes in the context of conservation. Interglacial and glacial refugia have been studied throughout subtropical China. However, studies on refugia along the oceanic–continental gradient have largely been ignored. We used a liana Actinidia eriantha, which occurs across the eastern moist evergreen broad-leaved forests of subtropical China, as a case study to test hypotheses of refugia along the oceanic–continental gradient and ‘oceanic’ adaptation. Results The phylogeographic pattern of A. eriantha was explored using a combination of three cpDNA markers and 38 nuclear microsatellite loci, Species distribution modelling and dispersal corridors analysis. Our data showed intermediate levels of genetic diversity [haplotype diversity (h T) = 0.498; unbiased expected heterozygosity (UH E) = 0.510] both at the species and population level. Microsatellite loci revealed five clusters largely corresponding to geographic regions. Coalescent time of cpDNA lineages was dated to the middle Pliocene (ca. 4.03 Ma). Both geographic distance and climate difference have important roles for intraspecific divergence of the species. The Zhejiang-Fujian Hilly Region was demonstrated to be a refugium along the oceanic–continental gradient of the species and fit the ‘refugia in refugia’ pattern. Species distribution modelling analysis indicated that Precipitation of Coldest Quarter (importance of 44%), Temperature Seasonality (29%) and Mean Temperature of Wettest Quarter (25%) contributed the most to model development. By checking the isolines in the three climate layers, we found that A. eriantha prefer higher precipitation during the coldest quarter, lower seasonal temperature difference and lower mean temperature during the wettest quarter, which correspond to ‘oceanic’ adaptation. Actinidia eriantha expanded to its western distribution range along the dispersal corridor repeatedly during the glacial periods. Conclusions Overall, our results provide integrated evidence demonstrating that the Zhejiang-Fujian Hilly Region is a refugium along the oceanic–continental gradient of Actinidia eriantha in subtropical China and that speciation is attributed to ‘oceanic’ adaptation. This study gives a deeper understanding of the refugia in subtropical China and will contribute to the conservation and utilization of kiwifruit wild resources in the context of climate change.