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Abstract Background Clear cell renal cell carcinoma (ccRCC) is a type of cancer characterized by a vast intracellular accumulation of lipids that are critical to sustain growth and viability of the cells in the tumour microenvironment. Stearoyl-CoA 9-desaturase 1 (SCD-1) is an essential enzyme for the synthesis of monounsaturated fatty acids and consistently overexpressed in all stages of ccRCC growth. Methods Human clear cell renal cell carcinoma lines were treated with small-molecule inhibitors of protein kinase CK2. Effects on the expression levels of SCD-1 were investigated by RNA-sequencing, RT-qPCR, Western blot, and in vivo studies in mice. Phase-contrast microscopy, fluorescence microscopy, flow cytometry, and MALDI-mass spectrometry analysis were carried out to study the effects on endogenous lipid accumulation, induction of endoplasmic reticulum stress, rescue effects induced by exogenous MUFAs, and the identity of lipid populations. Cell proliferation and survival were investigated in real time employing the Incucyte® live-cell analysis system. Statistical significance was determined by applying the two-tailed Student’s t test when comparing two groups of data whereas the two-way ANOVA, multiple Tukey’s test was employed for multiple comparisons. Results Here, we show that protein kinase CK2 is critical for preserving the expression of SCD-1 in ccRCC lines maintained in culture and heterotransplanted into nude mice. Consistent with this, pharmacological inhibition of CK2 leads to induction of endoplasmic reticulum stress linked to unfolded protein response activation and decreased proliferation of the cells. Both effects could be reversed by supplementing the growth medium with oleic acid indicating that these effects are specifically caused by reduced expression of SCD-1. Analysis of lipid composition by MALDI-mass spectrometry revealed that inhibition of CK2 results in a significant accumulation of the saturated palmitic- and stearic acids. Conclusions Collectively, our results revealed a previously unidentified molecular mechanism regulating the synthesis of monounsaturated fatty acids corroborating the notion that novel therapeutic approaches that include CK2 targeting, may offer a greater synergistic anti-tumour effect for cancers that are highly dependent on fatty acid metabolism.

Abstract Background Medications for opioid use disorder (MOUD) are under-prescribed to adolescents and young adults (AYA). Few published studies have explored challenges to and opportunities to enhance continuous provision of MOUD for AYA. Our report focuses on this emergent theme that was identified as part of a larger qualitative study. Methods We purposively sampled and enrolled medical providers who prescribed MOUD to AYA. Semi-structured individual interviews using chart-stimulated recall explored barriers and facilitators to MOUD retention. We used modified grounded theory in our qualitative analysis, with double coding of interviews. Results Barriers to retention on MOUD included patient-level (i.e., return to substance use) and system-level factors (i.e., cost, delayed receipt, pharmacy challenges, and in-person visit requirements). Facilitators included patient-level (i.e., motivation, support networks) and system-level factors (i.e., telehealth access, availability of certified recovery specialists). Conclusions Our study is the first to look at retention for this key age group, setting it apart from the existing body of literature that looks at medication initiation. Our findings confirm that significant systemic barriers exist to AYA patients’ retention on MOUD. Further research is needed to develop interventions that facilitate continuous delivery of high-quality care among this key population.

Abstract Triple-negative inflammatory breast cancer (TN-IBC) is the most aggressive type of breast cancer, yet its defining genomic, molecular, and immunological features remain largely unknown. In this study, we performed the largest and most comprehensive genomic and transcriptomic analyses of prospectively collected TN-IBC patient samples from a phase II clinical trial (ClinicalTrials.gov, NCT02876107, registered on August 22, 2016) and compared them to similarly analyzed stage III TN-non-IBC patient samples (ClinicalTrials.gov, NCT02276443, registered on October 21, 2014). We found that TN-IBC tumors have distinctive genomic, molecular, and immunological characteristics, including a lower tumor mutation load than TN-non-IBC, and an association of immunosuppressive tumor-infiltrating immune components with an unfavorable response to neoadjuvant chemotherapy. To our knowledge, this is the only study in which TN-IBC and TN-non-IBC samples were collected prospectively. Our analysis improves the understanding of the molecular landscape of the most aggressive subtype of breast cancer. Further studies are needed to discover novel prognostic biomarkers and druggable targets for TN-IBC.

Abstract Ibogaine and its main metabolite noribogaine provide important molecular prototypes for markedly different treatment of substance use disorders and co-morbid mental health illnesses. However, these compounds present a cardiac safety risk and a highly complex molecular mechanism. We introduce a class of iboga alkaloids – termed oxa-iboga – defined as benzofuran-containing iboga analogs and created via structural editing of the iboga skeleton. The oxa-iboga compounds lack the proarrhythmic adverse effects of ibogaine and noribogaine in primary human cardiomyocytes and show superior efficacy in animal models of opioid use disorder in male rats. They act as potent kappa opioid receptor agonists in vitro and in vivo, but exhibit atypical behavioral features compared to standard kappa opioid agonists. Oxa-noribogaine induces long-lasting suppression of morphine, heroin, and fentanyl intake after a single dose or a short treatment regimen, reversal of persistent opioid-induced hyperalgesia, and suppression of opioid drug seeking in rodent relapse models. As such, oxa-iboga compounds represent mechanistically distinct iboga analogs with therapeutic potential.

Summary: Conventional light imaging in living tissues is limited to depths under 100 μm by the significant tissue scattering. Consequently, few commercial imaging devices can image tissue lesions beneath the surface, or measure their invasion depth, critical in dermatology. We present 3D-multisite diffused optical imaging (3D-mDOI) an approach that combines photon migration techniques from diffuse optical tomography, with automated controls and image analysis techniques for estimating lesion’s depth via its optical coefficients. 3D-mDOI is a non-invasive, low-cost, fast, and contact-free instrument capable of estimating subcutaneous tissue structures volumes through multisite-acquisition of re-emitted light diffusion on the sample surface. It offers rapid estimation of Breslow depth, essential for staging melanoma. To standardize the performance, 3D-mDOI employs customized calibrations using physical tissue phantoms, to explore the system’s 3D reconstruction capabilities. We find that 3D-mDOI can reconstruct lesions up to 5 mm below the surface, requiring ∼300 s of computation time.

BackgroundAmerican alligators (Alligator mississippiensis) are maintained in zoos, aquaria, and farms for educational, research, and production purposes. The standard of veterinary medical care and welfare for captive reptiles requires managing pain and discomfort under conditions deemed painful in mammals. While analgesic efficacy and pharmacokinetic data for several reptile species are published, data with respect to analgesic efficacy in crocodilians are clearly lacking.ObjectiveThe objective of this study was to determine the analgesic efficacy of hydromorphone in alligators.MethodsFemale American alligators (N = 9; 57 months of age) were exposed to mechanical noxious stimuli at multiple anatomic sites using von Frey filaments ranging in size from 1.65 to 6.65 grams-force, and their behavioral reactions recorded. In order to evaluate analgesic efficacy, hydromorphone (0.5 mg/kg SC) was administered in the axillary region to the same alligators and the mechanical noxious stimuli were repeated and behaviors recorded.ResultsAdministration of hydromorphone contributed to a range from 62 to 92% reduced avoidance reactions to mechanical noxious stimuli for two anatomic sites (i.e., naris and lateral mandible, respectively).ConclusionAlligators did not appear to experience clinically relevant respiratory depression, hypothermia, or other adverse reactions. Therefore, hydromorphone shows promise as an analgesic option to be administered under painful conditions in American alligators.

BackgroundTexas tortoises (Gopherus berlandieri) are a Texas-state threatened species. Translocation is often suggested as a mitigation option; however, disease status and the potential for spread must be considered prior to such efforts. Mycoplasma infection of the upper respiratory tract is a concern within tortoise populations, which requires monitoring so translocation efforts do not inadvertently spread the disease.ObjectivesWe determined and compared the prevalences of Mycoplasma agassizii in Texas tortoises from donor and recipient sites in southern Texas prior to translocation, treated Mycoplasma agassizii-infected tortoises with danofloxacin, and developed alternate Mycoplasma agassizii treatments for Texas tortoises.MethodsWe collected 171 and 23 Texas tortoises from a 270-ha and a 100-ha donor site and recipient site, respectively. We began a regimen of danofloxacin (6 mg/kg body weight injected subcutaneously every other day for 30 days) for tortoises with clinical signs (N = 20). We noted an additional 10 tortoises began displaying clinical signs of upper respiratory tract disease (URTD) after translocation, so we designed a trial to test tulathromycin (5 mg/kg body weight given intramuscularly once/week for 7 weeks) or oxytetracycline (8 mg/kg body weight given subcutaneously once/day for 14 days) as Mycoplasma treatments for symptomatic tortoises.ResultsWithin the donor and recipient sites, 56 (32.7%) and 8 (34.8%), respectively, had antibody titers suggestive of past exposure. Eighteen tortoises from the donor site (10.5%) and 2 from the recipient site (8.7%) displayed clinical signs (i.e., clear serous nasal discharge, conjunctivitis, and palpebral edema) consistent with Mycoplasmal URTD upon initial collection, even though all polymerase chain reaction (PCR) results were negative for active shedding of Mycoplasma agassizii. We ceased treatment after the first dose of danofloxacin due to adverse reactions, which only began to subside after 72 h from the initial dose. Neither tulathromycin or oxytetracycline caused the clinical signs of URTD to subside after a 50-day treatment period.ConclusionMycoplasma is a persistent issue facing Texas tortoises. Stressors, such as translocation, can cause Mycoplasma-seropositive tortoises to display clinical symptoms of URTD, which can abate without treatment, once the stressor subsides.ImplicationsDanofloxacin, the recommended treatment for Mycoplasma infection in tortoises, is too potent for Texas tortoises.

Aspergillus nidulans is an important model organism for eukaryotic biology and the reference for the section Nidulantes in comparative studies. In this study, we de novo sequenced the genomes of 25 species of this section. Whole-genome phylogeny of 34 Aspergillus species and Penicillium chrysogenum clarifies the position of clades inside section Nidulantes. Comparative genomics reveals a high genetic diversity between species with 684 up to 2433 unique protein families. Furthermore, we categorized 2118 secondary metabolite gene clusters (SMGC) into 603 families across Aspergilli, with at least 40 % of the families shared between Nidulantes species. Genetic dereplication of SMGC and subsequent synteny analysis provides evidence for horizontal gene transfer of a SMGC. Proteins that have been investigated in A. nidulans as well as its SMGC families are generally present in the section Nidulantes, supporting its role as model organism. The set of genes encoding plant biomass-related CAZymes is highly conserved in section Nidulantes, while there is remarkable diversity of organization of MAT-loci both within and between the different clades. This study provides a deeper understanding of the genomic conservation and diversity of this section and supports the position of A. nidulans as a reference species for cell biology.

The mycotoxigenic fungi, Aspergillus flavus and Fusarium verticillioides, commonly co-colonize maize in the field, yet their direct interactions at the chemical communication level have not been well characterized. Here, we examined if and how the two most infamous mycotoxins produced by these species, aflatoxin and fumonisin, respectively, govern interspecies growth and mycotoxin production. We showed that fumonisin producing strains of F. verticillioides suppressed the growth of A. flavus while non-producers did not. Additionally, while aflatoxin did not inhibit F. verticillioides growth, it did suppress fumonisin production. Fumonisin B1 concentration levels plummeted when challenged with a high dose of aflatoxin B1 or with an aflatoxin producing strain. With these findings, expression of the genetic regulators of secondary metabolism was investigated for both fungi. While no strong effect was seen on genes in the aflatoxin biosynthetic gene cluster when exposed to fumonisin B1, the fumonisin repressor FvZBD1, which is adjacent to the cluster, was induced with expression proportionate to concentration when F. verticillioides was challenged with aflatoxin B1. We also assessed the expression of the global regulators of fungal secondary metabolism, veA and laeA, and found that their expression is altered in both A. flavus and F. verticillioides when exposed to their competitor’s mycotoxin. This work gives insight into the ecological roles of mycotoxins and why these fungi may produce them as weapons in the interspecies battle for resource acquisition.

Fusarium verticillioides—a mycotoxigenic fungus and food safety threat—coinhabits maize kernels with Sarocladium zeae. This protective endophyte produces secondary metabolites of interest, pyrrocidines A and B, which inhibit the growth of F. verticillioides and specifically block fumonisin biosynthesis. Previous transcriptomic analyses found FvZBD1 (FVEG_00314), a gene adjacent to the fumonisin biosynthetic gene cluster, to be induced over 4,000-fold in response to pyrrocidine challenge. Deletion of FvZBD1 resulted in dramatic increases in fumonisin production (FB1 >30-fold). Here, using pyrrocidine dose-response assays, we discovered a potent synergy between pyrrocidines A and B, where they functioned powerfully together to inhibit F. verticillioides growth. Further, results provided evidence that FvZBD1 confers partial tolerance to pyrrocidines, particularly pyrrocidine A, and that pyrrocidine functions through FvZBD1 to effectively eliminate fumonisin biosynthesis. Additionally, we showed that the FvABC3 (FVEG_11089) mutant, earlier described as hypersensitive to pyrrocidine, is particularly sensitive to pyrrocidine B. Thus, pyrrocidine A and B show different target specificity (FvZBD1 or FvABC3) and synergistic action. These findings will help inform the optimization of maximally efficacious S. zeae strains for eliminating F. verticillioides colonization and fumonisin contamination in maize cropping systems. This novel study contributes significantly to our knowledge of competitive microorganism relationships and the role of secondary metabolites in antagonistic fungal-fungal interactions.

Background Local angiotensin activity is thought to play a critical role in arterial wall homeostasis and remodeling, and impaired arterial wall integrity contributes to the pathogenesis of subarachnoid hemorrhage (SAH). Here we aimed to assess the association between pharmacologic inhibition of angiotensin‐converting enzyme and subsequent nontraumatic SAH. Methods In a retrospective cohort study based on Optum's Clinformatics Datamart deidentified database records (2000–2021), we included all subjects with a history of hypertension. We collected medication history, and the exposure of interest was the use of an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB). The primary outcome was the subsequent development of nontraumatic SAH. Cox proportional hazard regression models were used to compare the time to SAH by type of antihypertensive treatment. Results A total of 7.5 million patients with hypertension were assessed. Patients on ACEI/ARBs with or without other antihypertensives (n = 4.8 million, follow‐up: 6.3 years) had lower rates of SAH compared with those on alternative antihypertensive regimens (n = 1.3 million, follow‐up: 5.7 years) (hazard ratio [HR]:0.94 [0.91–0.97]; P

Abstract Live capture is an important tool for wildlife research, conservation, and management as it allows for insight into movement, behavior, demographics, diet, and health of wildlife populations. Live capture is also used for conservation translocations or to remove animals from human‐wildlife conflict situations. Improving trapping efficiency is beneficial for ethical considerations of wildlife handling, human safety, and the best use of limited resources. American black bears (Ursus americanus) are often captured using traps. Culvert‐ and box‐style traps are frequently transported using a trailer, and some are affixed to trailers, elevating the trap from the ground. Traps can be set on the ground or on trailers to reduce the set‐up and take‐down times. Although trap elements such as length, height, and visibility can influence trapping efficiency, it is unknown whether trailer presence influences capture success. We assessed the influence of single‐axle trailer presence on capture success of trapping black bears in northeastern Alberta, Canada, during spring 2022 and 2023. We compared capture success between the 2 methods and the influence of trailer presence on age and sex class. Sixty traps were set for a total of 472 trap‐nights resulting in 133 captures of 80 individual bears. Traps set with trailers present required, on average, 1.6 times more trap‐nights per capture (4.9) than those set without trailers (3.1). When only considering new captures, traps with trailers present required 1.9 times more trap‐nights to capture a bear, at 8.5 trap‐nights/capture for traps on trailers and 4.5 trap‐nights/capture when trailers were absent. Trailer presence reduced the success of overall and initial bear captures but did not influence recapture success or the proportion of captured bear age and sex classes. We conclude that wildlife researchers and managers should consider improving trap efficiency of black bears by removing traps from trailers.

ABSTRACT: Mycotoxin contaminated corn poses a risk to poultry production. Although mycotoxin regulatory guidelines are based on the hazards of individual mycotoxin contamination, feed and feed ingredients may be contaminated with multiple mycotoxins. The objective of this study was to assess mycotoxin co-contamination and its impact on the nutrient content of corn grain. Corn samples (n = 328) originating from various regions in the Southeastern U.S. were quantitatively analyzed for fumonisin (FUM), deoxynivalenol (DON), aflatoxin (AFB1) and zearalenone (ZEA) by HPLC-MS/MS. Nutritional content was analyzed by near-infrared spectroscopy, and color data were collected. All 328 samples were found to be contaminated with at least 1 mycotoxin: 100% contained FUM (19-24,680 µg/kg), 69.82% contained DON (0-9,640 µg/kg), 17.07% contained AFB1 (0–939 µg/kg), and 43.60% had detectable levels of ZEA (0-8,093.5 µg/kg). Most of the samples were contaminated with 2 or more mycotoxins, with only 18.29% of the samples containing a single mycotoxin. 38.41% of the samples had 2 mycotoxins present, 36.59 % had 3 mycotoxins, and 4.88% of the samples had all 4 tested mycotoxins present. Samples contaminated with AFB1 had significantly lower fat (P = 0.007) and lightness (P = 0.007); samples contaminated with DON had significantly higher starch (P < 0.001) and lower protein (P < 0.001). Samples contaminated with FUM had significantly higher protein (P = 0.008) and moisture (P = 0.019) and lower starch (P < 0.001). ZEA contaminated samples had significantly lower starch (P = 0.034). A correlation was observed between mycotoxin contamination and altered nutrient content in corn. This study provides further evidence that co-contamination of mycotoxins is the norm in corn, and that mycotoxin contamination correlates with impacts on the nutrient profile of feed corn.

Abstract Maternal antibodies (matAbs) protect against a myriad of pathogens early in life; however, these antibodies can also inhibit de novo immune responses against some vaccine platforms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) matAbs are efficiently transferred during pregnancy and protect infants against subsequent SARS-CoV-2 infections. It is unknown if matAbs inhibit immune responses elicited by different types of SARS-CoV-2 vaccines. Here, we established a mouse model to determine if SARS-CoV-2 spike-specific matAbs inhibit immune responses elicited by recombinant protein and nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccines. We found that SARS-CoV-2 mRNA-LNP vaccines elicited robust de novo antibody responses in mouse pups in the presence of matAbs. Recombinant protein vaccines were also able to circumvent the inhibitory effects of matAbs when adjuvants were co-administered. While additional studies need to be completed in humans, our studies raise the possibility that mRNA-LNP-based and adjuvanted protein-based SARS-CoV-2 vaccines have the potential to be effective when delivered very early in life.

Gait asymmetries are a common problem in clinical populations, such as those with a history of stroke or Parkinson’s disease. The use of a split-belt treadmill is one way to enhance gait symmetry but relies on specialty (and typically expensive) equipment. Alternatively, visual cues have been shown as a method to alter gait mechanics, but their utility in altering gait symmetry has been relatively understudied. Before deploying this method to clinical populations, a proof-of-concept study is needed to explore using visual cues to alter gait symmetry in healthy adults. Therefore, the purpose of this study was to examine the extent to which healthy adults could synchronize to an asymmetric visual cue with a small or large gait asymmetry using wearable sensors to measure gait asymmetries. Seventy-two healthy adults (ages: 23.89 ± 6.08 years) walked on the treadmill for two conditions: with and without the visual cue. Each walking condition lasted 10 min at the participant’s preferred walking speed. Inertial sensors were used to measure gait asymmetries. Some participants did not respond to the visual cue, and groups were separated into responders and non-responders. Participants in the small and large asymmetry-responder groups exhibited statistically significant increased asymmetries in single limb support % (p < 0.01) and step duration (s) (p < 0.05, p < 0.01, respectively). Only the large asymmetry-responder group showed statistically significant (p < 0.01) increased asymmetries in stride length. Overall, asymmetrical walking visual cues can alter gait asymmetries, and inertial sensors were sensitive enough to detect small changes in gait asymmetries.

Background and purpose: Stereotactic ablative body radiotherapy (SABR) is an effective treatment for localized renal cell carcinoma (RCC). However, the role of primary site SABR for locally recurrent or metastatic RCC is unclear. Here, we report outcomes of primary SABR across a diverse cohort of localized, recurrent, and metastatic RCC patients treated at our institution. Materials and methods: RCC patients treated with SABR to lesions of the kidney or nephrectomy bed at our institution with at least 6 months of follow-up were included for analysis. Local control, overall survival, and freedom from distant failure were estimated using the Kaplan-Meier method. Estimated glomerular filtration rate (eGFR) was assessed at baseline and following SABR. Results: Fifty-three patients received primary site SABR. Thirty-seven (70 %) patients had localized RCC, and 16 (30 %) had metastatic RCC. Seven (13 %) had locally recurrent RCC after prior surgery or ablation. The median tumor size was 4.5 cm (IQR 3.7–6.3). At a median follow-up of 23 months (IQR 12–35), 2-year local control was 100 %, and 3-year local control was 94.4 % (95 % CI 84.4 %–100 %). Among patients with initially localized disease, the 2-year freedom from distant failure was 94.6 % (95 % CI 87.6 %–100 %), and the 2-year overall survival was 66.5 % (95 % CI 51.9 %–85.2 %). Twelve (23 %) patients experienced acute grade 1–2 treatment-related toxicity (nausea, vomiting, or small bowel). There were no acute grade 3–4 toxicities. Two (3.8 %) patients developed late grade 3 gastrointestinal toxicity. The median baseline eGFR was 51 mL/min/1.73 m2 (IQR 38–77). At 1-year post-SABR, the median eGFR decline was 5 mL/min/1.73 m2 (IQR −3 to 9). One patient required dialysis following SABR. Conclusion: This analysis demonstrates excellent local control rates across patients with localized, recurrent, and metastatic RCC treated with SABR. Treatment was associated with minimal eGFR decline.

The spot-tailed earless lizards (STEL) are small, phrynosomatid lizards in the Holbrookia genus. Historically, these were considered two subspecies, the Plateau (Holbrookia lacerata lacerata) and Tamaulipan STEL (Holbrookia lacerata subcaudalis); however, each are now recognized as a distinct species (i.e., H. lacerata (plateau STEL) and H. subcaudalis (Tamaulipan STEL)). Recently, the plateau STEL was considered but not awarded federal protection under the Endangered Species Act by the U.S. Fish and Wildlife Service; however, much uncertainty remains about the status of the Tamaulipan STEL and a conclusive policy decision has not been made. In this study, we developed a hybrid theoretic-empirical demographic model and conducted a population viability analysis (PVA) of the Tamaulipan STEL (H. subcaudalis). We evaluated the role of multiple demographic, environmental, and anthropogenic parameters and assessed population-level effects and extinction risks via sensitivity experiments. The baseline simulation demonstrated that Tamaulipan STEL have a relatively low probability of extinction under best case scenario conditions; however, results of elasticity analysis of the baseline simulation and sensitivity analysis of demographic parameters demonstrated that increases in juvenile mortality had the greatest effect on population growth rate and extinction risk. Simulations of anthropogenic impacts showed that small increases in habitat loss (e.g., 2 %) had drastic negative effects on population size and persistence. Results from this study demonstrate the need for conservation and management actions aimed at protecting and increasing populations of young individuals (i.e., decreasing juvenile mortality) and promoting the conservation of available and suitable habitat for STEL throughout their range. These results must be considered in future conservation initiatives focused on this species to achieve successful conservation outcomes.

Spot-tailed Earless Lizards (STEL; Plateau STEL, Holbrookia lacerata; and Tamaulipan STEL, Holbrookia subcaudalis) are lizard species that are in decline both in number and distribution. As a result, this species has been considered for federal threatened status and a 90-day finding by the United States Fish and Wildlife Service stated that federal protection may be warranted. To date, a decision for Endangered Species Act listing for the Plateau STEL has been denied, but a judgement for the Tamaulipan STEL has not yet been decided. The requests to list STEL as a threatened species initiated numerous studies to investigate the status of both species and to add to the knowledge base of STEL. Though many studies have been conducted, much of the resulting information exists in gray literature (e.g., governmental reports, project summaries, etc.) that are not readily available or peer-reviewed. Herein, we consolidate the research results from scientific literature, governmental reports, and petitions to assist future researchers of STEL. We describe the natural history of STEL, their current taxonomy, conservation status, and discuss potential causes for their decline. Our goal is to provide the needed background knowledge for future researchers and policy makers.

ABSTRACT Optimal foraging theory (OFT) and the energy maximization hypothesis (EMH) have long been essential when examining wildlife habitat selection. At high latitudes and altitudes, animals in winter face greater limitations in availability and accessibility of forage. Here we explore the foraging behavior of wood bison (Bison bison athabascae) during winter within the Ronald Lake bison herd in northeastern Alberta, Canada, and examine the trade‐offs they face due to limitations in forage abundance and availability (snow conditions), as well as the need to minimize predation risk. We used Global Positioning System (GPS) location data collected from 70 female wood bison to identify winter foraging sites and craters selected by bison to access forage beneath the snow. Within wetlands used by bison we selected 190 pairs of used (foraged) and random (available) sites to test eight a priori hypotheses explaining how bison traded‐off between forage availability, accessibility, and minimizing predation risk. We found with matched‐paired logistic regression that Carex atherodes was 1.21‐times more likely to be selected per unit increase in ground cover, compared to 1.17‐times per unit ground cover for C. aquatilis and C. utriculata. However, all Carex species showed an increase in selection when cover was > 50% cover within individual craters. While the importance of Carex was clear, forage site selection was still inversely related to snow depth. There is also a neutralizing combined effect of snow depth and Carex species ground cover which suggests that bison maximized their energy return by avoiding areas with deep snow (> 30 cm) that demanded intensive cratering, even when highly selected forage was accessible beneath. Avoidance of forage areas with deep snow demonstrates that wood bison employed a foraging strategy that considers both forage availability and environmental conditions, with snow depth being a limiting factor. We highlight the relationship between optimal foraging based on food availability and the trade‐offs within an energy restrictive winter season, furthering the understanding of how large herbivores forage strategically to maximize energy intake in northern environments.

Background: Over 107,000 people died in the United States (U.S.) from drug overdose in 2022, with over one million overdose deaths since 1999. The U.S. drug market is characterized by a highly toxic, unregulated, and rapidly changing supply. Understanding the extent of exposure to fentanyl among people who use drugs (PWUD) will guide public health interventions aimed to decrease overdose. Methods: We utilized baseline data from the Rhode Island Prescription and Illicit Drug Study, a randomized controlled trial of harm reduction-oriented interventions for PWUD in Rhode Island from 2020 to 2023. We evaluated sociodemographic and drug use-related covariates and examined fentanyl presence in urine drug testing (UDT). We built a classification and regression tree (CART) model to identify subpopulations with the highest likelihood of fentanyl presence in UDT. Results: Among 446 participants, those with fentanyl present in UDT tended to be younger, non-Hispanic white, and had recently injected drugs (p

Abstract In malaria parasites, the regulation of mRNA translation, storage and degradation during development and life-stage transitions remains largely unknown. Here, we functionally characterized the DEAD-box RNA helicase PfDOZI in P. falciparum. Disruption of pfdozi enhanced asexual proliferation but reduced sexual commitment and impaired gametocyte development. By quantitative transcriptomics, we show that PfDOZI is involved in the regulation of invasion-related genes and sexual stage-specific genes during different developmental stages. PfDOZI predominantly participates in processing body-like mRNPs in schizonts but germ cell granule-like mRNPs in gametocytes to impose opposing actions of degradation and protection on different mRNA targets. We further show the formation of stress granule-like mRNPs during nutritional deprivation, highlighting an essential role of PfDOZI-associated mRNPs in stress response. We demonstrate that PfDOZI participates in distinct mRNPs to maintain mRNA homeostasis in response to life-stage transition and environmental changes by differentially executing post-transcriptional regulation on the target mRNAs.

Abstract Global biodiversity gradients are generally expected to reflect greater species replacement closer to the equator. However, empirical validation of global biodiversity gradients largely relies on vertebrates, plants, and other less diverse taxa. Here we assess the temporal and spatial dynamics of global arthropod biodiversity dynamics using a beta-diversity framework. Sampling includes 129 sampling sites whereby malaise traps are deployed to monitor temporal changes in arthropod communities. Overall, we encountered more than 150,000 unique barcode index numbers (BINs) (i.e. species proxies). We assess between site differences in community diversity using beta-diversity and the partitioned components of species replacement and richness difference. Global total beta-diversity (dissimilarity) increases with decreasing latitude, greater spatial distance and greater temporal distance. Species replacement and richness difference patterns vary across biogeographic regions. Our findings support long-standing, general expectations of global biodiversity patterns. However, we also show that the underlying processes driving patterns may be regionally linked.

Abstract mRNA lipid nanoparticle (LNP) vaccines would be useful during an influenza virus pandemic since they can be produced rapidly and do not require the generation of egg-adapted vaccine seed stocks. Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating at unprecedently high levels in wild and domestic birds and have the potential to adapt to humans. Here, we generate an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. The H5 mRNA-LNP vaccine elicits strong T cell and antibody responses in female mice, including neutralizing antibodies and broadly-reactive anti-HA stalk antibodies. The H5 mRNA-LNP vaccine elicits antibodies at similar levels compared to whole inactivated vaccines in female mice with and without prior H1N1 exposures. Finally, we find that the H5 mRNA-LNP vaccine is immunogenic in male ferrets and prevents morbidity and mortality of animals following 2.3.4.4b H5N1 challenge. Together, our data demonstrate that a monovalent mRNA-LNP vaccine expressing 2.3.4.4b H5 is immunogenic and protective in pre-clinical animal models.

ABSTRACT Purpose: CT-guided MWA is a safe and effective tool that should be utilized in the treatment of small renal masses (SRMs). We aim to clarify the utility of CT-guided MWA by examining patient outcomes such as recurrence, treatment success, changes in renal function, and complications. Methods: A retrospective review of consecutive patients with SRMs who underwent same day renal mass biopsy (RMB) and CT-guided MWA between 2015 and 2022 was performed. Treatment safety was assessed by 30-day complications according to the Clavien-Dindo system and change in eGFR >30 days post-procedure. Treatment efficacy was defined by local recurrence and incomplete treatment rates and calculated using the Kaplan-Meier method. Results: A total of 108 renal masses were found in 104 patients. The overall complication rate was 7.4% (8/108), of which 4 were major complications (3.7%). For those with renal function available >30 days post ablation, the median eGFR was 47.2 (IQR: 36.0, 57), compared to 52.3 (IQR: 43.7, 61.5) pre-ablation, p

Abstract In this work, we use a simple multi-agent-based-model (MABM) of a social network, implementing selfish algorithm (SA) agents, to create an adaptive environment and show, using a modified diffusion entropy analysis (DEA), that the mutual-adaptive interaction between the parts of such a network manifests complexity synchronization (CS). CS has been shown to exist by processing simultaneously measured time series from among organ-networks (ONs) of the brain (neurophysiology), lungs (respiration), and heart (cardiovascular reactivity) and to be explained theoretically as a synchronization of the multifractal dimension (MFD) scaling parameters characterizing each time series. Herein, we find the same kind of CS in the emergent intelligence of groups formed in a self-organized social interaction without macroscopic control but with biased self-interest between two groups of agents playing an anti-coordination game. This computational result strongly suggests the existence of the same CS in real-world social phenomena and in human–machine interactions as that found empirically in ONs.

Abstract The expression of genes encompasses their transcription into mRNA followed by translation into protein. In recent years, next-generation sequencing and mass spectrometry methods have profiled DNA, RNA and protein abundance in cells. However, there are currently no reference standards that are compatible across these genomic, transcriptomic and proteomic methods, and provide an integrated measure of gene expression. Here, we use synthetic biology principles to engineer a multi-omics control, termed pREF, that can act as a universal molecular standard for next-generation sequencing and mass spectrometry methods. The pREF sequence encodes 21 synthetic genes that can be in vitro transcribed into spike-in mRNA controls, and in vitro translated to generate matched protein controls. The synthetic genes provide qualitative controls that can measure sensitivity and quantitative accuracy of DNA, RNA and peptide detection. We demonstrate the use of pREF in metagenome DNA sequencing and RNA sequencing experiments and evaluate the quantification of proteins using mass spectrometry. Unlike previous spike-in controls, pREF can be independently propagated and the synthetic mRNA and protein controls can be sustainably prepared by recipient laboratories using common molecular biology techniques. Together, this provides a universal synthetic standard able to integrate genomic, transcriptomic and proteomic methods.

Abstract For generations researchers have been observing the dynamic processes of life through the lens of a microscope. This has offered tremendous insights into biological phenomena that span multiple orders of time- and length-scales ranging from the pure magic of molecular reorganization at the membrane of immune cells, to cell migration and differentiation during development or wound healing. Standard fluorescence microscopy techniques offer glimpses at such processes in vitro, however, when applied in intact systems, they are challenged by reduced signal strengths and signal-to-noise ratios that result from deeper imaging. As a remedy, two-photon excitation (TPE) microscopy takes a special place, because it allows us to investigate processes in vivo, in their natural environment, even in a living animal. Here, we review the fundamental principles underlying TPE aimed at basic and advanced microscopy users interested in adopting TPE for intravital imaging. We focus on applications in neurobiology, present current trends towards faster, wider and deeper imaging, discuss the combination with photon counting technologies for metabolic imaging and spectroscopy, as well as highlight outstanding issues and drawbacks in development and application of these methodologies.

Background Stroke knowledge is critical to treatment adherence and poststroke outcomes. Here, we aimed to quantify the impact of a personalized video‐based educational platform to test the hypothesis that it improves patient satisfaction and stroke knowledge. Methods and Results In a single‐center pilot randomized trial, all patients with stroke and caregivers received standard stroke education during the hospitalization, but half were randomized to receive access to MyStroke, a personalized educational platform that provided brief videos about their stroke, risk factors, medications, and poststroke lifestyle. Satisfaction, stroke knowledge, and quality of life were assessed 7, 30, and 90 days after discharge. A total of 120 subjects (96 patients and 24 caregivers) were randomized to standard education (n=59) or MyStroke. At 90 days post‐stroke, those who received MyStroke were more likely to be satisfied with the stroke education the received (90% versus 73%, P=0.05) and more likely to correctly identify their stroke cause (67% versus 32%, P=0.003). However, MyStroke was not associated with a difference in self‐reported quality of life (EuroQol Visual Analogue Scale: 80 versus 75, P=0.06) or general stroke knowledge (total Stroke Patient Education Retention: 5 versus 5, P=0.47). With respect to secondary end points, MyStroke increased risk factor awareness 7 and 30 days poststroke, but this difference was not significant at 90 days. Conclusions The MyStroke personalized video‐based education platform improved patient and caregiver satisfaction while improving some aspects of personalized stroke knowledge without improving general stroke knowledge. A multicenter trial is needed to confirm these results, clarify generalizability, and target clinically relevant metrics such as stroke recurrence or adherence. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05118503.

Abstract Conspecific and interspecific brood parasitism are alternate reproductive strategies more pervasive in waterfowl than in any other group of birds. While previous research has measured costs incurred by nest hosts incubating parasitized clutches, few studies have focused on the relative success of parasites. Here, we evaluated the success of wood duck (Aix sponsa) and hooded merganser (Lophodytes cucullatus) eggs laid parasitically in Louisiana and Mississippi. We monitored nest boxes, assigned eggs in each nest as host or parasitic, and determined the number of eggs that hatched and failed. Across all study areas (1994–1999 and 2020–2023), we monitored 1750 wood duck and 377 hooded merganser nests; ~13% of wood duck and ~24% of hooded merganser nests were interspecifically parasitized. We modeled egg survival of 2925 host and 691 parasitic eggs from 197 successful nests (≥1 hatched egg, regardless of species). Wood duck eggs laid in hooded merganser nests had lower survival [0.293, CI = 95% credible intervals (after, CI) = 0.176, 0.439] than hooded merganser eggs (0.762, CI = 0.704, 0.810) laid in wood duck nests. Clutch size negatively influenced parasitic wood duck egg survival (β = −.24, CI = −0.39, −0.10) but had a slight positive influence on parasitic hooded merganser eggs (β = .08, CI = 0.04, 0.12). Our results revealed that hooded merganser eggs experience higher success when laid parasitically in wood duck nests, whereas wood duck eggs experience lower success when laid parasitically in hooded merganser nests. Our results reveal new complexity in waterfowl interspecific brood parasitism, where the success of parasitic eggs is species‐, host‐, and context‐specific.

IntroductionThe concept of a sterile uterus was challenged by recent studies that have described the microbiome of the virgin and pregnant uterus for species including humans and cattle. We designed two studies that tested whether the microbiome is introduced into the uterus when the virgin heifer is first inseminated and whether the origin of the microbiome is the vagina/cervix.MethodsThe uterine microbiome was measured immediately before and after an artificial insemination (AI; Study 1; n = 7 AI and n = 6 control) and 14 d after insemination (Study 2; n = 12 AI and n = 12 control) in AI and non-AI (control) Holstein heifers. A third study (Study 3; n = 5 Holstein heifers) that included additional negative controls was subsequently conducted to support the presence of a unique microbiome within the uterus despite the low microbial biomass and regardless of insemination. Traditional bacteriological culture was performed in addition to 16S rRNA gene sequencing on the same samples to determine whether there were viable organisms in addition to those detected based on DNA sequencing (16S rRNA gene sequence).Results and discussionInseminating a heifer did not lead to a large change in the microbiome when assessed by traditional methods of bacterial culture or metataxonomic (16S rRNA gene) sequencing (results of Studies 1 and 2). Very few bacteria were cultured from the body or horn of the uterus regardless of whether an AI was or was not (negative control) performed. The cultured bacterial genera (e.g., Bacillus, Corynebacterium, Cutibacterium, Micrococcus, Staphylococcus, and Streptococcus) were typical of those found in the soil, environment, skin, mucous membranes, and urogenital tract of animals. Metataxonomic sequencing of 16S rRNA gene generated a large number of amplicon sequence variants (ASV), but these larger datasets that were based on DNA sequencing did not consistently demonstrate an effect of AI on the abundance of ASVs across all uterine locations compared with the external surface of the tract (e.g., perimetrium; positive control samples for environment contamination during slaughter and collection). Major genera identified by 16S rRNA gene sequencing overlapped with those identified with bacterial culture and included Cutibacterium, Staphylococcus, and Streptococcus.

Abstract Objective We aim to determine the effect of region of residence (urban vs. rural) on the odds of receiving standard of care treatment for locally advanced BCa in Louisiana and its impact on survival outcomes. Methods Using the Louisiana Tumor Registry, we identified American Joint Committee on Cancer (AJCC) stage II or III, BCa diagnoses in Louisiana residents between 2010 and 2020. Treatment received was classified as standard or non‐standard of care according to American Urological Association (AUA) guidelines and location of residence was determined using Rural Urban Commuting Area‐Tract‐level 2010 (RUCA). Multivariable logistic regression analyses and multivariate cox proportional hazard analyses were performed. Results Of 983 eligible patients, 85.6% (841/983) lived in urban areas. Overall, only 37.5% received standard‐of‐care (SOC) for the definitive management of locally advanced bladder cancer. Individuals living in rural areas (OR 0.53, 95% CI: 0.31–0.91, p = 0.02) were less likely to receive standard of care treatment. Both rural residence and receipt of non‐standard of care therapy were associated with an increased risk of bladder cancer‐specific (adj HR 1.53, 95% CI: 1.09–2.14, p = 0.01 and adj HR: 1.85, 95% CI: 1.43–2.39,

Abstract Background Overdose prevention centers (OPCs) are being implemented in the United States as a strategy to reduce drug-related mortality and morbidity. Previous studies have suggested that people who use drugs (PWUD) with a history of criminal legal system (CLS) involvement (e.g. current probation/parole) are at greater risk of overdose but may also encounter significant barriers to OPC use. The objective of this study was to explore the association between willingness to use an OPC and probation/parole status in a sample of PWUD in Rhode Island. Methods This study utilized data from the Rhode Island Prescription and Illicit Drug Study, which enrolled adult PWUD from August 2020 to February 2023. We used Pearson’s chi-square and Wilcoxon rank-sum tests to assess bivariate associations between willingness to use an OPC and probation/parole status (current/previous/never), as well as other sociodemographic and behavioral characteristics. In multivariable Poisson analyses, we examined the association between willingness to use an OPC and probation/parole status, adjusting for key sociodemographic and behavioral characteristics. Results Among 482 study participants, 67% were male, 56% identified as white, 20% identified as Hispanic/Latine, and the median age was 43 (IQR 35–53). Nearly a quarter (24%) had never been on probation/parole, 44% were not currently on probation/parole but had a lifetime history of probation and parole, and 32% were currently on probation/parole. Most participants (71%) reported willingness to use an OPC, and in both bivariate and multivariable analyses, willingness to use an OPC did not vary by probation/parole status. Crack cocaine use and lifetime non-fatal overdose were associated with greater willingness to use an OPC (all p

Abstract Purpose This study estimated the prevalence of and factors associated with secondhand smoke (SHS) exposure, and assessed attitudes and knowledge about SHS among pregnant women in Cairo, Egypt. Methods Pregnant women in the third trimester were recruited to participate in a survey assessing tobacco smoking and SHS exposure during their current pregnancy. Participants were recruited from three antenatal clinics in Cairo, Egypt, from June 2015 to May 2016. We examined differences in sociodemographic characteristics and SHS exposure, attitudes, and knowledge by smoking/SHS status. We used multivariable ordinary least squares regression to examine the association between husbands’ smoking and pregnant women’s mean daily hours of SHS exposure, adjusting for women’s smoking status, age group, education, and urban (vs. suburban/rural) residence. Results Of two hundred pregnant women aged 16–37 years, about two-thirds (69%) had a husband who smoked tobacco. During their current pregnancy, most women reported being non-smokers (71%), and 38% of non-smokers reported being SHS-exposed. Non-smokers exposed to SHS tended to live in more rural areas and have husbands who smoked in the home. In adjusted analyses, having a husband who smoked was significantly associated with a greater mean number of hours of SHS exposure per day exposed, and this difference was driven by husbands who smoked in the home (p

This paper investigates the use of probabilistic neural networks (PNNs) to model aleatoric uncertainty, which refers to the inherent variability in the input-output relationships of a system, often characterized by unequal variance or heteroscedasticity. Unlike traditional neural networks that produce deterministic outputs, PNNs generate probability distributions for the target variable, allowing the determination of both predicted means and variances in regression scenarios. Contributions of this paper include the development of a probabilistic distance metric to optimize PNN architecture, and the deployment of PNNs in controlled data sets as well as a practical material science case involving fiber-reinforced composites. The findings confirm that PNNs effectively model aleatoric uncertainty, proving to be more appropriate than the commonly employed Gaussian process regression for this purpose. Specifically, in a real-world scientific machine learning context, PNNs yield remarkably accurate output mean estimates with R-squared scores approaching 0.97, and their predicted variances exhibit a high correlation coefficient of nearly 0.77, closely matching observed data variances. Hence, this research contributes to the ongoing exploration of leveraging the sophisticated representational capacity of neural networks to delineate complex input-output relationships in scientific problems.

Abstract Examination of early phases of synucleinopathy when inclusions are present, but long before neurodegeneration occurs, is critical to both understanding disease progression and the development of disease modifying therapies. The rat alpha-synuclein (α-syn) preformed fibril (PFF) model induces synchronized synucleinopathy that recapitulates the pathological features of Parkinson’s disease (PD) and can be used to study synucleinopathy progression. In this model, phosphorylated α-syn (pSyn) inclusion-containing neurons and reactive microglia (major histocompatibility complex-II immunoreactive) peak in the substantia nigra pars compacta (SNpc) months before appreciable neurodegeneration. However, it remains unclear which specific genes are driving these phenotypic changes. To identify transcriptional changes associated with early synucleinopathy, we used laser capture microdissection of the SNpc paired with RNA sequencing (RNASeq). Precision collection of the SNpc allowed for the assessment of differential transcript expression in the nigral dopamine neurons and proximal glia. Transcripts upregulated in early synucleinopathy were mainly associated with an immune response, whereas transcripts downregulated were associated with neurotransmission and the dopamine pathway. A subset of 29 transcripts associated with neurotransmission/vesicular release and the dopamine pathway were verified in a separate cohort of males and females to confirm reproducibility. Within this subset, fluorescent in situ hybridization (FISH) was used to localize decreases in the Syt1 and Slc6a3 transcripts to pSyn inclusion-containing neurons. Identification of transcriptional changes in early synucleinopathy provides insight into the molecular mechanisms driving neurodegeneration.

Abstract Classical fungal mutant strains obtained by mutagenesis have helped to elucidate fundamental metabolic pathways in the past. In the filamentous fungus Neurospora crassa, the gluc-1 strain was isolated long ago and characterized by its low level of β-glucosidase activity, which is essential for the degradation of cellulose, the most abundant biopolymer on Earth and the main polymeric component of the plant cell wall. Based on genomic resequencing, we hypothesized that the causative mutation resides in the β-glucosidase gene gh3-3 (bgl6, NCU08755). In this work, growth patterns, enzymatic activities and sugar utilization rates were analyzed in several mutant and overexpression strains related to gluc-1 and gh3-3. In addition, different mutants affected in the degradation and transport of cellobiose were analyzed. While overexpression of gh3-3 led to the recovery of β-glucosidase activity in the gluc-1 mutant, as well as normal utilization of cellobiose, the full gene deletion strain Δgh3-3 was found to behave differently than gluc-1 with lower secreted β-glucosidase activity, indicating a dominant role of the amino acid substitution in the point mutated gh3-3 gene of gluc-1. Our results furthermore confirm that GH3-3 is the major extracellular β-glucosidase in N. crassa and demonstrate that the two cellodextrin transporters CDT-1 and CDT-2 are essential for growth on cellobiose when the three main N. crassa β-glucosidases are absent. Overall, these findings provide valuable insight into the mechanisms of cellulose utilization in filamentous fungi, being an essential step in the efficient production of biorefinable sugars from agricultural and forestry plant biomass.

The purpose of this study is to investigate the effect of task constraints on the neurobiological systems while maintaining postural control under various sensory feedback manipulations in individuals with and without Chronic Ankle Instability (CAI). Forty-two physically active individuals, with and without CAI, were enrolled in a case-control study conducted at a biomechanics research laboratory. All participants underwent the Sensory Organization Test (SOT), which assesses individuals’ ability to integrate somatosensory, visual, and vestibular feedback to maintain postural control in double-, uninjured-, and injured-limb stances under six different conditions in which variations in the sway-referenced support surface (platform) and visual surroundings, with and without vision, are manipulated to affect somatosensory and visual feedback. Center-of-Pressure (COP) path length was computed from raw data collected during trials of each SOT condition. Sample Entropy (SampEN) values were extracted from the COP path length time series to examine neurobiological systems complexity, with lower SampEN values indicating more predictable and periodic (rigid) neurobiological systems, while higher SampEN values indicate more unpredictable and random systems. The results show that specific task constraints affect the neurobiological systems. Specifically, individuals with CAI demonstrated reduced complexity (decreased SampEN values) in the neurobiological systems during the uninjured-limb stance when all sensory feedback was intact and during both uninjured- and injured-limb stances when they were forced to rely on vestibular feedback. These results highlight the interplay between sensory feedback and task constraints in individuals with CAI and suggest potential adaptations in the neurobiological systems involved in postural control.

Abstract Background Few studies have examined the effectiveness of telephone smoking cessation interventions by severity of behavioral health symptoms. Using data from a telephone counseling study, we examined whether abstinence rates varied by level of behavioral health symptoms. Methods The parent study recruited adults who smoke cigarettes (N = 577) referred by mental health providers at six Veterans Health Administration facilities. Participants were randomized to specialized telephone counseling (intervention) or state Quitline referral (control). Participants completed assessments at baseline and 6 months, including the BASIS-24, a self-report measure of behavioral health symptoms and functioning. We used the BASIS-24 median to dichotomize participants as having high or low scores. The primary outcome was 30-day self-reported abstinence at 6 months. We compared groups on outcomes by logistic regression and performed an interaction effect analysis between treatment assignment and groups. Results At baseline, those with high behavioral health symptoms scores reported heavier nicotine dependence and more sedative and/or antidepressant use, compared to participants with low behavioral health symptoms. At 6 months, participants with low behavioral health symptoms scores in the intervention reported higher rates of 30-day abstinence compared to those in the control arm (26% vs 13%, OR = 2.3, 95% CI = 1.8, 2.9). People with high behavioral health symptoms scores reported no difference in 30-day abstinence between the treatment assignments at 6 months (12% vs. 13%, OR = 1.1, 95% CI = 0.6, 2.0). Conclusions Only participants with low behavioral health symptoms scores reported higher abstinence rates in the intervention compared to the state Quitline. Future research can examine alternative approaches for people with worse mental well-being and functioning. Trial registration The parent study is registered at www.clinicaltrials.gov NCT00724308.

Abstract In sorghum [Sorghum bicolor (L.) Moench] the Maturity (Ma1, Ma2, Ma3, Ma4, Ma5, Ma6) and Dwarf (Dw1, Dw2, Dw3, Dw4) loci, encode genes controlling flowering time and plant height, respectively, which are critical for designing sorghum ideotypes for a maturity timeframe and a harvest method. Publicly available whole-genome resequencing data from 860 sorghum accessions was analyzed in silico to identify genomic variants at 8 of these loci (Ma1, Ma2, Ma3, Ma5, Ma6, Dw1, Dw2, Dw3) to identify novel loss of function alleles and previously characterized ones in sorghum germplasm. From ~ 33 million SNPs and ~ 4.4 million InDels, 1445 gene variants were identified within these 8 genes then evaluated for predicted effect on the corresponding encoded proteins, which included newly identified mutations (4 nonsense, 15 frameshift, 28 missense). Likewise, most accessions analyzed contained predicted loss of function alleles (425 ma1, 22 ma2, 40 ma3, 74 ma5, 414 ma6, 289 dw1, 268 dw2 and 45 dw3) at multiple loci, but 146 and 463 accessions had no predicted ma or dw mutant alleles, respectively. The ma and dw alleles within these sorghum accessions represent a valuable source for manipulating flowering time and plant height to develop the full range of sorghum types: grain, sweet and forage/biomass.

Theory-based transport modeling has been widely successful and is built on the foundations of quasilinear theory. Specifically, the quasilinear expression of the flux can be used in combination with a saturation rule for the toroidal mode amplitude. Most transport models follow this approach. Saturation rules are heuristic and difficult to rigorously derive. We compare three common saturation rules using a fairly accurate quasilinear expression for the fluxes computed using local linear gyrokinetic simulation. We take plasma parameters from experimental H-mode profiles and magnetic equilibrium and include electrons, deuterium, and carbon species. We find that the various saturation rules provide qualitatively similar behavior. This may help to explain why the different theory-based transport models can all predict core tokamak profiles reasonably well. Comparisons with nonlinear local and global gyrokinetic simulations are discussed.

Two new species of Xenolepis are described and illustrated from Papua New Guinea: X. neoguineana Brown & Miller, n. sp., and X. slipihalo Brown & Miller, n. sp. All specimens examined were collected as larvae, most from Syzygium spp. (Myrtaceae), but a few from Garcinia (Clusiaceae), Ziziphus (Rhamnaceae), Amyema (Loranthaceae), and Gomphandra (Stemonuraceae), which represent the first reported food plants for Xenolepis. The new species bring to seven the number of described species in the genus. We also present DNA barcodes, host plants, and an illustration of the male genitalia of an undescribed species from New Guinea, but refrain from naming it owing to the paucity and poor quality of the specimens. Available descriptions and illustrations indicate that Xenolepis, as presently defined, comprises two distinct species groups that are superficially disparate but possess very similar male genitalia.

Abstract Introduction Survivors of SARS‐CoV‐2 pneumonia often develop persistent respiratory symptom and interstitial lung abnormalities (ILAs) after infection. Risk factors for ILA development and duration of ILA persistence after SARS‐CoV‐2 infection are not well described in immunocompromised hosts, such as cancer patients. Methods We conducted a prospective cohort study of 95 patients at a major cancer center and 45 patients at a tertiary referral center. We collected clinical and radiographic data during the index hospitalization for COVID‐19 pneumonia and measured pneumonia severity using a semi‐quantitative radiographic score, the Radiologic Severity Index (RSI). Patients were evaluated in post‐COVID‐19 clinics at 3 and 6 months after discharge and underwent comprehensive pulmonary evaluations (symptom assessment, chest computed tomography, pulmonary function tests, 6‐min walk test). The association of clinical and radiological factors with ILAs at 3 and 6 months post‐discharge was measured using univariable and multivariable logistic regression. Results Sixty‐six (70%) patients of cancer cohort had ILAs at 3 months, of whom 39 had persistent respiratory symptoms. Twenty‐four (26%) patients had persistent ILA at 6 months after hospital discharge. In adjusted models, higher peak RSI at admission was associated with ILAs at 3 (OR 1.5 per 5‐point increase, 95% CI 1.1–1.9) and 6 months (OR 1.3 per 5‐point increase, 95% CI 1.1–1.6) post‐discharge. Fibrotic ILAs (reticulation, traction bronchiectasis, and architectural distortion) were more common at 6 months post‐discharge. Conclusions Post‐COVID‐19 ILAs are common in cancer patients 3 months after hospital discharge, and peak RSI and older age are strong predictors of persistent ILAs.

Abstract Dual-comb interferometry harnesses the interference of two laser frequency combs to provide unprecedented capability in spectroscopy applications. In the past decade, the state-of-the-art systems have reached a point where the signal-to-noise ratio per unit acquisition time is fundamentally limited by shot noise from vacuum fluctuations. To address the issue, we propose an entanglement-enhanced dual-comb spectroscopy protocol that leverages quantum resources to significantly improve the signal-to-noise ratio performance. To analyze the performance of real systems, we develop a quantum model of dual-comb spectroscopy that takes practical noises into consideration. Based on this model, we propose quantum combs with side-band entanglement around each comb lines to suppress the shot noise in heterodyne detection. Our results show significant quantum advantages in the uW to mW power range, making this technique particularly attractive for biological and chemical sensing applications. Furthermore, the quantum comb can be engineered using nonlinear optics and promises near-term experimentation.

IntroductionThe possibility that there is a resident and stable commensal microbiome within the pregnant uterus has been supported and refuted by a series of recent studies. One element of most of the initial studies was that they were based primarily on 16S rRNA gene sequencing from bacteria. To account for this limitation, the current study performed both bacterial culture and 16S rRNA gene sequencing in a side-by-side manner (e.g., same tissues isolated from the same animal).MethodsThe uteruses of 10 mid-pregnant (156 ± 5 d of gestation) Holstein heifers and cows were collected following slaughter. The external surface of the reproductive tract (positive control for contamination during tissue collection) as well as tissues within the pregnant uterus (placentome, inter-cotyledonary placenta, inter-caruncular endometrium, amnionic fluid, allantoic fluid, fetal abomasum content, and fetal meconium) were sampled for bacterial culture and 16S rRNA gene sequencing.ResultsThere were 87 unique bacterial species cultured from the external surface of the pregnant reproductive tract (contamination control) and 12 bacterial species cultured from pregnancy tissues. Six out of 10 cattle (60%) exhibited bacterial growth in at least one location within the pregnant uterus. For the metataxonomic results (16S rRNA gene sequencing), a low targeted microbial biomass was identified. Analyses of the detected amplicon sequence variants (ASV) revealed that there were: (1) genera that were prevalent on both the external surface and within the pregnant uterus; (2) genera that were prevalent on the external surface but either not detected or had very low prevalence within the pregnant uterus; and (3) genera that were either not detected or had low prevalence on the external surface but found with relatively high prevalence within the pregnant uterus.ConclusionThere are a small number of viable bacteria in the pregnant uterus. The 16S rRNA gene sequencing detected a microbial community within the pregnant uterus but with a low biomass. These results are consistent with recent studies of the pregnant bovine uterus and leave open the question of whether there is adequate microbial mass to significantly affect the biology of the normal healthy bovine pregnancy.

BackgroundFirearm-related suicide is the second leading cause of pediatric firearm death. Lethal means counseling (LMC) can improve firearm safe-storage practices for families with youth at risk of suicide.ObjectivesThis study aims to evaluate the feasibility of pediatric emergency department (ED) behavioral mental health (BMH) specialists providing LMC to caregivers of youth presenting with BMH complaints and to test for changes in firearm safety practices, pre-post ED LMC intervention, as measures of preliminary efficacy.MethodsProspective pilot feasibility study of caregivers of youth presenting to a pediatric ED with BMH complaints. Caregivers completed an electronic survey regarding demographics and firearm safe-storage knowledge/practices followed by BMH specialist LMC. Firearm owners were offered a free lockbox and/or trigger lock. One-week follow-up surveys gathered self-reported data on firearm safety practices and intervention acceptability. One-month interviews with randomly sampled firearm owners collected additional firearm safety data. Primary outcomes were feasibility measures, including participant accrual/attrition and LMC intervention acceptability. Secondary outcomes included self-reported firearm safety practice changes. Feasibility benchmarks were manually tabulated, and Likert-scale acceptability responses were dichotomized to strongly agree/agree vs. neutral/disagree/strongly disagree. Descriptive statistics were used for univariate and paired data responses.ResultsIn total, 81 caregivers were approached; of which, 50 (81%) caregivers enrolled. A total of 44% reported having a firearm at home, 80% completed follow-up at one week. More than 80% affirmed that ED firearm safety education was useful and that the ED is an appropriate place for firearm safety discussions. In total, 58% of participants reported not having prior firearm safety education/counseling. Among firearm owners (n = 22), 18% reported rarely/never previously using a safe-storage device, and 59% of firearm owners requested safe storage devices.At 1-week follow-up (n = 40), a greater proportion of caregivers self-reported asking about firearms before their child visited other homes (+28%). Among firearm owners that completed follow-up (n = 19), 100% reported storing all firearms locked at one week (+23% post-intervention). In total, 10 caregivers reported temporarily/permanently removing firearms from the home.ConclusionIt is feasible to provide LMC in the pediatric ED via BMH specialists to families of high-risk youth. Caregivers were receptive to LMC and reported finding this intervention useful, acceptable, and appropriate. Additionally, LMC and device distribution led to reported changes in safe storage practices.

Background The modified Rankin Scale (mRS) is commonly used to measure disability after stroke, traditionally assessed through telephone or in‐person evaluation. Here, we investigated the validity of mRS assessment through an automated text messaging system based on the simplified mRS questionnaire as an alternative method to traditional methods of assessment. Methods and Results A total of 250 patients admitted to 3 hospitals within the University of Pennsylvania Health System with ischemic or hemorrhagic stroke were enrolled. Participants received automated text messages sent 48 hours before their outpatient appointment at about 90 days after stroke. The mRS scores were assigned on the basis of participant responses to 2 to 4 text questions eliciting yes/no responses. The mRS was then evaluated in person or by telephone interview for comparison. Responses were compared with κ. A total of 142 patients (57%) completed the study. The spontaneous response rate to text messages was 46.5% and up to 72% with an additional direct in‐person or phone call reminder. Agreement was substantial (quadratic‐weighted κ=0.87 [95% CI, 0.83–0.89]) between responses derived from the automated text messaging and traditional interviews. Agreement for distinguishing functional independence (mRS 0–1) from dependence (mRS 2–5) was substantial (unweighted κ=0.79 [95% CI, 0.69–0.90]). Conclusions An automated text messaging system is a feasible method for remotely obtaining the mRS after stroke and a potential alternative to traditional in‐person or telephone assessment. Further studies are needed to evaluate the generalizability of text message–based approaches to stroke outcome measurement.