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Reports of human infections with influenza A(H5N1) clade 2.3.4.4b viruses associated with outbreaks in dairy cows in the United States underscore the need to assess the potential cross-protection conferred by existing influenza immunity. We serologically evaluated ferrets previously infected with an influenza A(H1N1)pdm09 virus for cross-reactive antibodies and then challenged 3 months later with either highly pathogenic H5N1 clade 2.3.4.4b or low pathogenicity H7N9 virus. Our results showed that prior influenza A(H1N1)pdm09 virus infection more effectively reduced the replication and transmission of the H5N1 virus than did the H7N9 virus, a finding supported by the presence of group 1 hemagglutinin stalk and N1 neuraminidase antibodies in preimmune ferrets. Our findings suggest that prior influenza A(H1N1)pdm09 virus infection may confer some level of protection against influenza A(H5N1) clade 2.3.4.4.b virus.

Abstract Complementary methods toward the selective functionalization of indole and oxindole frameworks employing an alternative strategy in heteroaryl C–H functionalizations are presented herein. This work focuses on a catalyst-controlled, site selective C–H activation/functionalization of 3-acyl indoles, wherein an amide serves as a robust and versatile directing group capable of undergoing concomitant 1,2-acyl translocation/C–H functionalization in the presence of a RhI/AgI co-catalysts to provide the cross-coupled adducts in high yields. In contrast, the use of IrIII/AgI catalysts subverted the 1,2-acyl migration to afford the corresponding C2-functionalized products in good to excellent yields. A notable feature of the catalyst systems was the exceptional level of site selectivity observed in which the corresponding C–H functionalized indoles were obtained exclusively. Mechanistic experiments indicate a concerted 1,2-acyl migration step and indole metallation occurring through an electrophilic aromatic substitution process.

Background: In Nigeria, trauma care faces challenges due to high injury and death rates from road traffic accidents and violence. Improvements are underway, but gaps in service availability, training, and coordination persist, necessitating evidence-based interventions. Purpose: To evaluate trauma care practices in Nigeria, focusing on practitioners' perceptions of training, resources, and care quality to inform policy and practice enhancements. Methods: An exploratory qualitative study was conducted with seven trauma surgeons across Nigeria, using semi-structured interviews and an Interpretive Description analysis approach, adhering to SRQR standards. Results: Analysis of interviews with seven Nigerian trauma surgeons highlighted a trauma care system burdened by high incidences of traffic-related injuries. Despite varying caseloads—from 20 cases per month to 65 weekly—common challenges included delayed care, leading to complications like infection and misaligned wound healing. Surgeons noted strengths in motivated staff and sub-specialization but stressed barriers such as underdeveloped prehospital care, financial constraints, and resource shortages, which hindered effective trauma management and outcomes. Conclusions: Effective trauma care in Nigeria is crucial and achievable through policy reforms, better resource distribution, and enhanced training. Systematic data collection and a national trauma care protocol are recommended to improve patient outcomes and guide future research and policymaking.

We present an interesting case of a 65-year-old female patient who was taking fingolimod for relapsing-remitting multiple sclerosis. She presented with a tongue nodule, oral ulcer, and was found to have CD4 lymphocytopenia. HIV serology was negative. Fingolimod is known to cause lymphocyte redistribution to lymph nodes and was deemed to be the cause of CD4 lymphocytopenia in this patient. Further evaluation with excision biopsy of the tongue nodule confirmed histoplasmosis. Treatment with itraconazole resulted in a complete resolution of her lesions.

Abstract Background The vast majority of genes in the genome are multi-exonic, and are alternatively spliced during transcription, resulting in multiple isoforms for each gene. For some genes, different mRNA isoforms may have differential expression levels or be involved in different pathways. Bulk tissue RNA-seq, as a widely used technology for transcriptome quantification, measures the total expression (TE) levels of each gene across multiple isoforms in multiple cell types for each tissue sample. With recent developments in precise quantification of alternative splicing events for each gene, we propose to study the effects of alternative splicing variation on gene–gene correlation effects. We adopted a variance-component model for testing the TE–TE correlations of one gene with a co-expressed gene, accounting for the effects of splicing variation and splicing-by-TE interaction of one gene on the other. Results We analyzed data from the Genotype-Tissue Expression (GTEx) project (V8). At the 5% FDR level, 38,146 pairs of genes out of ∼10 M examined pairs from GTEx lung tissue showed significant TE-splicing interaction effects, implying isoform-specific and/or sample-specific TE–TE correlations. Additional analysis across 13 GTEx brain tissues revealed strong tissue-specificity of TE-splicing interaction effects. Moreover, we showed that accounting for splicing variation across samples could improve the reproducibility of results and could reduce potential confounding effects in studying co-expressed gene pairs with bulk tissue data. Many of those gene pairs had correlation effects specific to only certain isoforms and would otherwise be undetected. By analyzing gene–gene co-expression variation within functional pathways accounting for splicing, we characterized the patterns of the “hub” genes with isoform-specific regulatory effects on multiple other genes. Conclusions We showed that splicing variation of a gene may interact with TE of the gene and affect the TE of co-expressed genes, resulting in substantial tissue-specific inter-sample variability in gene–gene correlation effects. Accounting for TE-splicing interaction effects could reduce potential confounding effects and improve the robustness of estimation when estimating gene–gene correlations from bulk tissue expression data.

Abstract The neurexin superfamily, consisting of neurexins and Casprs, play important roles in the development, maintenance, function, and plasticity of neuronal circuits. Caspr/CNTNAP genes are linked to alterations in neuronal circuits and associated with neurodevelopmental and neurodegenerative conditions. Casprs are implicated in multiple neuronal signaling pathways, including dopamine; however, the molecular mechanisms by which Casprs differentially alter specific signaling pathways and downstream behaviors are unclear. We find that the C. elegans Caspr nlr-1 functions in neurons to control foraging behaviors, acting in distinct monoamine neurons to modulate locomotor activity in the presence or absence of food. nlr-1 functions in dopamine neurons to reduce activity in the absence of food, similar to the role of dopamine, and regulates dopamine signaling through D2-like receptors. Furthermore, nlr-1 contributes to proper morphology and presynaptic structure of dopamine neurons, dopamine receptor expression and localization, and the behavioral response to dopamine. We find that nlr-1 similarly regulates another dopamine-dependent behavior, the basal slowing response. Therefore, spatial manipulation of a broadly expressed neuronal gene is sufficient to alter neural circuits and behavior and uncovers important functions masked by global manipulation, highlighting the importance of genetic variation and mechanisms that impact spatial expression of genes to behavior.

Abstract We developed and evaluated the Digital Platform for Exercise (DPEx): a decentralized, patient-centric approach designed to enhance all aspects of clinical investigation of exercise therapy. DPEx integrated provision of a treadmill with telemedicine and remote biospecimen collection permitting all study procedures to be conducted in patient’s homes. Linked health biodevices enabled high-resolution monitoring of lifestyle and physiological response. Here we describe the rationale and development of DPEx as well as feasibility evaluation in three different cohorts of patients with cancer: a phase 0a development study among three women with post-treatment primary breast cancer; a phase 0b proof-of-concept trial of neoadjuvant exercise therapy in 13 patients with untreated solid tumors; and a phase 1a level-finding trial of neoadjuvant exercise therapy in 53 men with localized prostate cancer. Collectively, our study demonstrates the utility of a fully digital, decentralized approach to conduct clinical trials of exercise therapy in a clinical population.

Background: Elbow injuries are becoming increasingly prevalent in throwing athletes. Early diagnosis, especially in athletes, can allow for earlier intervention and return to play. It is important for clinicians to have a framework to systemically examine the elbow to accurately diagnose a variety of elbow pathologies in this unique patient population. Indications: The purpose of this video is to educate clinicians on how to diagnose a variety of elbow pathologies in the throwing athlete. Currently, there is no published video describing the evaluation of the elbow in throwing athletes with associated reliability measures for specific examination maneuvers. This video teaches how to perform these examination maneuvers, interpret their findings, and review reliability measures associated with them. Technique Description: This video provides an overview of the physical examination of the elbow in throwing athletes, including evaluation of range of motion, neurologic pathology, and special examination maneuvers depending on the location at the elbow. Results: The discussed tools for evaluation can aid in accurate diagnosis of a variety of elbow pathologies. There is variability among physical maneuvers regarding their reliability measures, with many maneuvers having reliability measures that have not been fully studied. Discussion/Conclusion: Using a detailed history and focused physical examination, a variety of elbow pathologies can be diagnosed. Early and accurate diagnosis is crucial for early intervention for both nonoperative and operative management, allowing for earlier return to competition. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Beta-propeller Protein Associated Neurodegeneration (BPAN) is a devastating neurodevelopmental and neurodegenerative disease linked to variants in WDR45. Currently, there is no cure or disease altering treatment for this disease. This is, in part, due to a lack of insight into early phenotypes of BPAN progression and WDR45’s role in establishing and maintaining neurological function. Here we generated and characterized a mouse model bearing a c52C > T BPAN patient variant in Wdr45. We show this mutation ablates WDR45 protein expression and alters autophagy in the brain. Behavioral analysis of these mice revealed characteristic signs of BPAN including cognitive impairment, hyperactivity, and motor decline. We show these behaviors coincide with widespread glial activation and early development of axonal spheroids in multiple neuron subclasses throughout the brain. Several lines of evidence suggest these spheroids arise from axon terminals. Transcriptomic analysis uncovered multiple disrupted pathways in the cortex including genes associated with synapses, neurites, endosomes, endoplasmic reticulum, and ferroptosis. This is supported by accumulation of the iron regulating transferrin receptor 1 (TFRC) and the endoplasmic reticulum resident calreticulin (CALR) in the cortex as these animals age. CALR forms spheroid structures similar to the axonal spheroids seen in these animals. Taken together, our data suggest that WDR45 is necessary for healthy brain function and maintenance of axon terminals. This model opens the door to therapeutics targeting BPAN and further exploration of the role of WDR45 in neuronal function.

BackgroundPrimary care is the initial contact point for most patients with opioid use disorder (OUD) but lacks tools for guiding treatment. Only a small fraction of patients access evidence-based care. Long-acting injectable buprenorphine has potential to improve medication adherence and program retention in low-barrier primary care treatment settings. We present the first clinical decision support algorithm incorporating long-acting buprenorphine (LAIB) in primary care. We include a protocol for a future evaluation of the algorithm’s implementation process, “Medication for Opioid Use Disorder (MOUD) 2.0,” at a housing and integrated care clinic at a Federally Qualified Health Center.MethodsLiterature review and expert consensus informed creation of the algorithm, which underwent iterative development with feedback from clinicians, staff, and patients. Patients are categorized by adherence to therapy and retention in the program, with recommendations for each category. Adherence is determined by urine screen supplemented by self-report. To ensure all patients in this high morbidity and mortality risk population are treated, we will treat patients as their own controls in the evaluation, with potential for multisite comparisons. We will present descriptive statistics for adherence proportion before and after MOUD 2.0 implementation, testing for differences using McNemar’s test. We will then present pre- and post-implementation unadjusted six-month survival curves for retention.DiscussionLAIB is incorporated as an alternative or adjunctive treatment for patients refractory to sublingual buprenorphine and as an initial treatment for selected patients. We developed an algorithm with 4-, 8-, and 12-week decision points to guide treatment for patients with varying levels of response to sublingual buprenorphine and LAIB. This clinical decision tool incorporates LAIB among treatment options for OUD in primary care settings. The protocol will evaluate the algorithm’s implementation, presenting a replicable method for assessing adherence and retention among high-risk patients in similar settings.

Abstract Importation of malaria infections is a suspected driver of sustained malaria prevalence on areas of Bioko Island, Equatorial Guinea. Quantifying the impact of imported infections is difficult because of the dynamic nature of the disease and complexity of designing a randomized trial. We leverage a six-month travel moratorium in and out of Bioko Island during the initial COVID-19 pandemic response to evaluate the contribution of imported infections to malaria prevalence on Bioko Island. Using a difference in differences design and data from island wide household surveys conducted before (2019) and after (2020) the travel moratorium, we compare the change in prevalence between areas of low historical travel to those with high historical travel. Here, we report that in the absence of a travel moratorium, the prevalence of infection in high travel areas was expected to be 9% higher than observed, highlighting the importance of control measures that target imported infections.

Abstract Background While the association of chronological age with DNA methylation (DNAm) in whole blood has been extensively studied, the tissue-specificity of age-related DNAm changes remains an active area of research. Studies investigating the association of age with DNAm in tissues such as brain, skin, immune cells, fat, and liver have identified tissue-specific and non-specific effects, thus, motivating additional studies of diverse human tissue and cell types. Results Here, we performed an epigenome-wide association study, leveraging DNAm data (Illumina EPIC array) from 961 tissue samples representing 9 tissue types (breast, lung, colon, ovary, prostate, skeletal muscle, testis, whole blood, and kidney) from the Genotype-Tissue Expression (GTEx) project. We identified age-associated CpG sites (false discovery rate

Background Despite the theoretical advantages of treating metastatic bone disease with microwave ablation (MWA), there are few reports characterizing microwave absorption and bioheat transfer in bone. This report describes a computational modeling-based approach to simulate directional microwave ablation (dMWA) in spine, supported by ex vivo and pilot in vivo experiments in porcine vertebral bodies.Materials and methods A 3D computational model of microwave ablation within porcine vertebral bodies was developed. Ex vivo porcine vertebra experiments using a dMWA applicator measured temperatures approximately 10.1 mm radially from the applicator in the direction of MW radiation (T1) and approximately 2.4 mm in the contra-lateral direction (T2). Histologic assessment of ablated ex vivo tissue was conducted and experimental results compared to simulations. Pilot in vivo experiments in porcine vertebral bodies assessed ablation zones histologically and with CT and MRI.Results Experimental T1 and T2 temperatures were within 3–7% and 11–33% of simulated temperature values. Visible ablation zones, as indicated by grayed tissue, were smaller than those typical in other soft tissues. Posthumous MRI images of in vivo ablations showed hyperintensity. In vivo experiments illustrated the technical feasibility of creating directional microwave ablation zones in porcine vertebral body.Conclusion Computational models and experimental studies illustrate the feasibility of controlled dMWA in bone tissue.

This study presents a facile method for assessing the effect of anion functional group substitution on the water affinity of phosphonium-acetate ionic liquids. By combining the same cation with three different α-substituted carboxylate anions, the effect of anion functional group substitution on the IL miscibility with water and hygroscopicity was experimentally evaluated and rationalized using COSMO-RS sigma profile analysis. Lower critical solution temperature (LCST) phase separation experiments and water vapor partial pressure measurements revealed that there is a stark α-substitution dependency on the affinity of water for acetate [AcO], pivalate [PivO], and trifluoroacetate [TFA] derived tributyl(octyl)phosphonium [P4448] ILs. It was found that the IL water affinities varied as: [P4448][AcO] > [P4448][PivO] > [P4448][TFA]. With the lowest water partial pressure and no LCST driven phase separation, [P4448][AcO] exhibited a high affinity for water. On the other hand, [P4448][PivO] and [P4448][TFA] exhibited LCST-driven phase separation and room temperature immiscibility, respectively, with higher water partial pressures, as a result of relatively weak water affinities. COSMO-RS sigma profile analysis revealed that the aliphatic carboxylate anions should incorporate apolar interactions commensurate with or greater than the polar hydrogen bond acceptor interactions for phase immiscibility of the corresponding IL with water. It was found that the relative magnitudes of apolar and polar interactions, assessed using the anion sigma profile peak intensity ratio (Ir), are directly correlated with the IL water affinity, and inversely correlated with the solution water activity coefficient. Therefore, it was concluded that Ir forms a quantitative link between the structural changes at the molecular level and the bulk water affinity exhibited by the ionic liquid as a whole.

The news is an efficient way to share information and plays an important role in shaping and reflecting cultural values and norms. However, research examining news consumption and abortion attitudes is limited. In this exploratory study, we analyzed data from a nationally representative sample of 886 US adults to assess whether self-reported frequency of news consumption—by news format (e.g., television, radio, newspaper, social media), news leaning (i.e., liberal, neutral, conservative), and total sum (i.e., total amount of consumption across leanings)—predicted abortion attitudes and complexity in attitudes. We conducted Poisson and negative binomial regression analyses controlling for demographic variables. We found that gender, political affiliation, Bible literalism, educational attainment, and abortion identity were significant predictors. While we did not observe a relationship between news format and abortion attitudes, we did find that the associations between news leaning and the total sum of news consumed varied across abortion identity. Our findings suggest that attitudes toward abortion may be differentially influenced by partisan news across abortion identity. After Dobbs v. Jackson, there is a need for advocates to tailor strategies to different sub-groups, promote media literacy, and encourage the use of diverse and balanced news sources to foster more informed views on abortion.

Despite having a higher risk of hepatitis C virus (HCV) infections, people who inject drugs (PWID) in sub-Saharan Africa (SSA) have limited access to HCV treatment. There is scarce literature on treatment delivery modalities that overcome logistical and financial barriers. We utilized different service delivery modalities to provide direct-acting antivirals (DAAs) to PWIDs infected with HCV through methadone clinics and needle and syringe program (NSP) sites in Kenya. In collaboration with Kenya’s National AIDS and STI Control Programme (NASCOP), we enrolled individuals with active HCV infection confirmed by HCV RNA detection from methadone and NSP sites in Nairobi, Mombasa, and Kilifi counties. Liver function and hepatitis B virus (HBV) status were assessed at baseline. Those eligible for treatment were offered ledipasvir-sofosbuvir treatment provided by NASCOP through directly observed therapy (DOT). Participants completed a follow-up visit 12 weeks after completing treatment to measure sustained viral response (SVR-12). Challenges faced while delivering HCV treatment at participating sites included the limited availability and reliability of laboratory assays, and financial constraints faced by PWIDs to attend daily DOT. Based on our experience, strategies to deliver HCV treatment for PWID in Kenya should consider improving the availability of laboratory tests and prioritizing treatment through methadone centers to achieve good outcomes.

Despite strong interest in how noise affects marine mammals, little is known for the most abundant and commonly exposed taxa. Social delphinids occur in groups of hundreds of individuals that travel quickly, change behaviour ephemerally and are not amenable to conventional tagging methods, posing challenges in quantifying noise impacts. We integrated drone-based photogrammetry, strategically placed acoustic recorders and broad-scale visual observations to provide complementary measurements of different aspects of behaviour for short- and long-beaked common dolphins. We measured behavioural responses during controlled exposure experiments (CEEs) of military mid-frequency (3–4 kHz) active sonar (MFAS) using simulated and actual Navy sonar sources. We used latent-state Bayesian models to evaluate response probability and persistence in exposure and post-exposure phases. Changes in subgroup movement and aggregation parameters were commonly detected during different phases of MFAS CEEs but not control CEEs. Responses were more evident in short-beaked common dolphins (n = 14 CEEs), and a direct relationship between response probability and received level was observed. Long-beaked common dolphins (n = 20) showed less consistent responses, although contextual differences may have limited which movement responses could be detected. These are the first experimental behavioural response data for these abundant dolphins to directly inform impact assessments for military sonars.

Legume nodules are specialized environments on plant roots that are induced and dominated by nitrogen-fixing bacteria. Bacteriophages (phages) in these nodules could potentially provide top-down controls on the population size and, therefore, the function of nitrogen-fixing symbionts. Here we sought to characterize the diversity and biogeographical patterns of phages that infect nitrogen-fixing Mesorhizobium symbionts isolated from root nodules, leveraging 266 genomes of Mesorhizobium isolated from nodules and 648 nodule metagenomes collected from three species of chickpea plants (Cicer spp.) under different agricultural management practices, spanning eight countries on five continents. We identified 106 phage populations (viral operational taxonomic units [vOTUs]) in Mesorhizobium draft genomes, 37% of which were confirmed as likely prophages. These vOTUs were detected in 64% of the Mesorhizobium-dominated nodule metagenomes and 58% of the Mesorhizobium isolates. Per metagenome, 1 to 16 putative Mesorhizobium vOTUs were detected, with more than half of the nodules containing only one such vOTU. The majority of vOTUs were detected exclusively in Ethiopia, followed by India and Morocco, with the lowest richness of putative Mesorhizobium phages in countries that applied industrial Mesorhizobium inoculants to crops. Two vOTUs were identified in five or more countries and in nodules dominated by different strains of Mesorhizobium, suggesting infection of diverse Mesorhizobium hosts and long-term interactions. Beta-diversity of these Mesorhizobium phage assemblages was significantly correlated with the dominant Mesorhizobium strain, but not with measured environmental parameters. Our findings indicate that nitrogen-fixing nodules in chickpea plants can contain distinct viral assemblages, with potential impacts on the nodule microbiome that bear further exploration.

Upstream of quasi-parallel bow shocks, reflected ions generate ion–ion instabilities. The resulting magnetic fluctuations can advect through the shock and interact with planetary magnetospheres. The amplitude of magnetic fluctuations depends on the strength of the shock, quantified by the Alfvén Mach number ( M _A ), which is the ratio of solar wind velocity to the local Alfvén velocity. With increasing heliocentric distance, the solar wind M _A generally increases, such that Mercury typically experiences a lower M _A ∼ 5 compared to Earth ( M _A ∼ 8), and Mars a slightly higher M _A ∼ 9. Farther out in the solar system, Saturn has even higher M _A (∼10). However, the solar wind flow is highly irregular, and on top of solar cycle variations these values for average M _A at each planet do not capture extreme events. Statistical analysis of OMNIWeb observations from 2015 to 2023 shows that sustained (30 minutes or more) high M _A (30–100) occurs at Earth about once a month. Using a selection of events in the ion foreshock regions of Mercury, Earth, Mars, and Saturn, a linear scaling is calculated for the maximum magnetic fluctuation amplitude as a function of M _A . The resulting slope is ∼0.2. Based on the dominant fluctuation frequency for the largest-amplitude events at each planet, it is found that Mars exists in a special regime where the wave period of the magnetic fluctuations can be similar to or longer than the magnetospheric convection timescale, making Mars more susceptible to space weather effects associated with foreshock fluctuations.

Stripped-envelope supernovae (SESNe) represent a significant fraction of core-collapse supernovae, arising from massive stars that have shed their hydrogen and, in some cases, helium envelopes. The origins and explosion mechanisms of SESNe remain a topic of active investigation. In this work, we employ radiative-transfer simulations to model the light curves and spectra of a set of explosions of single, solar-metallicity, massive Wolf–Rayet stars with ejecta masses ranging from 4 to 11 M _⊙ , which were computed from a turbulence-aided and neutrino-driven explosion mechanism. We analyze these synthetic observables to explore the impact of varying ejecta mass and helium content on observable features. We find that the light curve shape of these progenitors with high ejecta masses is consistent with observed SESNe with broad light curves but not the peak luminosities. The commonly used analytic formula based on rising bolometric light curves overestimates the ejecta mass of these high-initial-mass progenitor explosions by a factor of up to 2.6. In contrast, the calibrated method by Haynie et al., which relies on late-time decay tails, reduces uncertainties to an average of 20% within the calibrated ejecta mass range. Spectroscopically, the He i 1.083 μ m line remains prominent even in models with as little as 0.02 M _⊙ of helium. However, the strength of the optical He i lines is not directly proportional to the helium mass but instead depends on a complex interplay of factors such as the ^56 Ni distribution, composition, and radiation field. Thus, producing realistic helium features requires detailed radiative transfer simulations for each new hydrodynamic model.

Introduction Despite significant progress over past decades, neonatal and infant morbidity and mortality remain unacceptably high in Ethiopia. Simple interventions have been shown to improve the health of children and reduce mortality. These include promotion of exclusive breast feeding for the first 6 months of life, immunisation and utilisation of available newborn healthcare services, which are proven to improve newborn survival. This study aims to determine the impact of a behaviour change intervention that partners Orthodox priests with volunteer community health workers, known in Ethiopia as the Health Development Army and trains them to conduct newborn health outreach to improve care seeking, uptake of key interventions and identification of sick infants.Methods The study designed is a community-randomised trial conducted in the Central Gondar area. The behaviour change intervention pairs trained Orthodox priests with members of the Health Development Army to conduct community health outreach by identifying near-term pregnant women in their communities and educating them on the topics of exclusive breast feeding, immunisation, nutrition and uptake of available child healthcare services. The evaluation of the intervention will enrol up to 150 newborn–mother pairs from communities receiving the behaviour change intervention and another 150 pairs enrolled from control communities. The quantitative analysis will be done by comparing data between the intervention and control groups related to breast feeding, anthropometry, immunisation status and uptake of child health services. The primary outcomes are exclusive breastfeeding through 6 months, mid-upper arm circumference, completion of vaccinations and infant hospitalisation.Ethics and dissemination Ethical approval has been obtained from the University of Washington (STUDY00006942) and the University of Gondar (No.V/P/RCS/05/2523/2019) Institutional Review Boards. Oral consent was obtained for the formative study, whereas written consent (or witnessed thumbprint) will be obtained from all enrolled mothers. Results will be communicated to community members, relevant government agencies and other stakeholders.Trial registration number NCT05111899.

IntroductionCusp ion dispersion signatures reflect properties of remote magnetic reconnection. Since the cusp is easier to observe in situ compared to the reconnection x-line, ion dispersions provide key insight on whether reconnection is variable in space and time. This study is motivated by a specific dispersion signature having two ion populations separated in energy but not space. These are known as overlapping dispersions because when observed by low-Earth orbiting satellites traversing the cusp, they appear as two dispersed ion populations overlapping in magnetic latitudes. Overlapping dispersion signatures have been observed for all interplanetary magnetic field (IMF) orientations and have been associated with multiple reconnection processes, but the three-dimensional magnetic reconnection topology and particle trajectories have not been examined.MethodsForward particle tracing using the GAMERA-CHIMP global magnetohydrodynamic (MHD) with test particle framework is carried out to construct ion dispersion signatures throughout the cusp. Under idealized solar wind driving with steady purely southward IMF, both standard and overlapping dispersions are found.ResultsAnalysis of the test particle trajectories shows that the higher energy population of the overlapping dispersion travels along the axis of a flux rope before heading into the cusp, whereas the lower energy population goes directly into the cusp. Furthermore, the overlapping dispersions observed by the synthetic satellites compare well to Defense Meteorological Satellite Program (DMSP) F16 observations during strongly southward IMF.DiscussionIt is thus concluded that during strongly southward IMF, cusp-entering particles interacting with a magnetopause flux rope (generated by secondary reconnection) is one way to produce an overlapping dispersion. This study lays the groundwork for the forthcoming NASA Tandem Reconnection and Cusp Electrodynamics Reconnaissance Satellites (TRACERS) mission, which will connect the cusp to the magnetosphere—discovering how spatial or temporal variations in magnetic reconnection drive cusp dynamics. The expected launch of TRACERS is in 2025.

Abstract The understanding of how central metabolism and fermentation pathways regulate antimicrobial susceptibility in the anaerobic pathogen Bacteroides fragilis is still incomplete. Our study reveals that B. fragilis encodes two iron‐dependent, redox‐sensitive regulatory pirin protein genes, pir1 and pir2. The mRNA expression of these genes increases when exposed to oxygen and during growth in iron‐limiting conditions. These proteins, Pir1 and Pir2, influence the production of short‐chain fatty acids and modify the susceptibility to metronidazole and amixicile, a new inhibitor of pyruvate: ferredoxin oxidoreductase in anaerobes. We have demonstrated that Pir1 and Pir2 interact directly with this oxidoreductase, as confirmed by two‐hybrid system assays. Furthermore, structural analysis using AlphaFold2 predicts that Pir1 and Pir2 interact stably with several central metabolism enzymes, including the 2‐ketoglutarate:ferredoxin oxidoreductases Kor1AB and Kor2CDAEBG. We used a series of metabolic mutants and electron transport chain inhibitors to demonstrate the extensive impact of bacterial metabolism on metronidazole and amixicile susceptibility. We also show that amixicile is an effective antimicrobial against B. fragilis in an experimental model of intra‐abdominal infection. Our investigation led to the discovery that the kor2AEBG genes are essential for growth and have dual functions, including the formation of 2‐ketoglutarate via the reverse TCA cycle. However, the metabolic activity that bypasses the function of Kor2AEBG following the addition of phospholipids or fatty acids remains undefined. Overall, our study provides new insights into the central metabolism of B. fragilis and its regulation by pirin proteins, which could be exploited for the development of new narrow‐spectrum antimicrobials in the future.

Abstract Hysteretic sorption and desorption of water is observed from 0 to 95% relative humidity and 298–333 K on a glassy polyurethane foam. It is postulated that sorption-induced swelling of the glassy polyurethane increases the concentration of accessible hydrogen-bonding adsorption sites for water. The accessibility of sites is kinetically controlled due to the restricted thermal motions of chains in the glassy polymer, causing a difference in accessible site concentrations during sorption and desorption. This discrepancy leads to hysteresis in the sorbed concentrations of water. A coupled chemo-mechanical model relating volumetric strain, adsorption site concentration, and sorbed water concentration is employed to describe water sorption hysteresis in the glassy polyurethane. This model not only describes the final mass uptake for each relative humidity step, but also captures the dynamics of water uptake, which exhibit diffusion and relaxation rate-controlled regimes.

Abstract Genetic effects on functionally related ‘omic’ traits often co-occur in relevant cellular contexts, such as tissues. Motivated by the multi-tissue methylation quantitative trait loci (mQTLs) and expression QTLs (eQTLs) analysis, we propose X-ING (Cross-INtegrative Genomics) for cross-omics and cross-context integrative analysis. X-ING takes as input multiple matrices of association statistics, each obtained from different omics data types across multiple cellular contexts. It models the latent binary association status of each statistic, captures the major association patterns among omics data types and contexts, and outputs the posterior mean and probability for each input statistic. X-ING enables the integration of effects from different omics data with varying effect distributions. In the multi-tissue cis-association analysis, X-ING shows improved detection and replication of mQTLs by integrating eQTL maps. In the trans-association analysis, X-ING reveals an enrichment of trans-associations in many disease/trait-relevant tissues.

Abstract Objectives Peptidoglycan (PG) is an arthritogenic bacterial cell wall component whose role in human osteoarthritis is poorly understood. The purpose of this study was to determine if PG is present in synovial tissue of osteoarthritis patients at the time of primary total knee arthroplasty (TKA), and if its presence is associated with inflammation and patient reported outcomes. Methods Intraoperative synovial tissue and synovial fluid samples were obtained from 56 patients undergoing primary TKA, none of whom had history of infection. PG in synovial tissue was detected by immunohistochemistry (IHC) and immunofluorescence microscopy (IFM). Synovial tissue inflammation and fibrosis were assessed by histopathology and synovial fluid cytokine quantification. Primary human fibroblasts isolated from arthritis synovial tissue were stimulated with PG to determine inflammatory cytokine response. Results A total of 33/56 (59%) of primary TKA synovial tissue samples were positive for PG by IHC, and PG staining colocalized with markers of synovial macrophages and fibroblasts by IFM. Synovial tissue inflammation and elevated IL-6 in synovial fluid positively correlated with PG positivity. Primary human fibroblasts stimulated with PG secreted high levels of IL-6, consistent with ex vivo findings. Interestingly, we observed a significant inverse correlation between PG and age at time of TKA, indicating younger age at time of TKA was associated with higher PG levels. Conclusion Peptidoglycan is commonly found in synovial tissue from patients undergoing TKA. Our data indicate that PG may play an important role in inflammatory synovitis, particularly in patients who undergo TKA at a relatively younger age.

Abstract Background In Kenya, violence is common among people who inject drugs (PWID) living with HIV and their sexual and injecting partners and may lead to decreased uptake of HIV services, increased HIV risk behaviors, and increased HIV transmission. Violence is defined as any physical harm, threatened harm, or forced sexual acts inflicted on a person in the past year. Understanding the nature of violence and its correlates among PWID and their partners will inform population-specific public health interventions and policy recommendations. Methods This is a cross-sectional study nested in a prospective cohort study conducted in eight public health centers, methadone clinics, and needle syringe programs in Nairobi, Kilifi, and Mombasa counties in Kenya. 3,302 sexual and/or injecting partners of PWID living with HIV were recruited through assisted partner services and participated in the study. Prevalence and correlates of violence were identified using the Wald test and negative binomial regression. Results Out of 3302 study participants, 1439 (44%) had experienced violence within the past year. Physical violence was the most common form of violence experienced (35%), followed by being threatened (23%) or subjected to sexual violence (7%). In an adjusted analysis, female participants reported higher experiences of sexual violence (prevalence ratio [PR] = 2.46; 95% confidence interval [CI] 1.62, 3.74; p

Abstract Neurexins are synaptic adhesion molecules that play diverse roles in synaptic development, function, maintenance, and plasticity. Neurexin genes have been associated with changes in human behavior, where variants in NRXN1 are associated with autism, schizophrenia, and Tourette syndrome. While NRXN1, NRXN2, and NRXN3 all encode major α and β isoforms, NRXN1 uniquely encodes a γ isoform, for which mechanistic roles in behavior have yet to be defined. Here, we show that both α and γ isoforms of neurexin/nrx-1 are required for the C. elegans behavioral response to food deprivation, a sustained period of hyperactivity upon food loss. We find that the γ isoform regulates initiation and the α isoform regulates maintenance of the behavioral response to food deprivation, demonstrating cooperative function of multiple nrx-1 isoforms in regulating a sustained behavior. The γ isoform alters monoamine signaling via octopamine, relies on specific expression of NRX-1 isoforms throughout the relevant circuit, and is independent of neuroligin/nlg-1, the canonical trans-synaptic partner of nrx-1. The α isoform regulates the pre-synaptic structure of the octopamine producing RIC neuron and its maintenance role is conditional on neuroligin/nlg-1. Collectively, these results demonstrate that neurexin isoforms can have separate behavioral roles and act cooperatively across neuronal circuits to modify behavior, highlighting the need to directly analyze and consider all isoforms when defining the contribution of neurexins to behavior.

Phosphonium-derived ionic liquids have emerged as a powerful class of thermoresponsive materials with sought after Lower Critical Solution Temperature (LCST) phase separation with applications across a broad range of fields. Herein, we report the spectroscopic examination of phosphonium salts bearing the general structure [X][P444n] wherein systematic structural variations were designed to gain a fundamental understanding behind the impact of alkyl chain length, anion size, and effective nuclear charge on their temperature-dependent phase separation behavior. Using variable temperature 1H, 31P, and 19F NMR, the bonding changes which drive LCST phase separation for the assembled thermoresponsive ILs were elucidated. For the first time, spectroscopic evidence revealed a delicate balance between the interdependence of alkyl chain length and anion size on phase separation that formed the basis of new LCST design principles.

This study introduces the scaled sigma potential of water (σr), a new metric using the COSMO-RS (Conductor like Screening Model for Real Solvents) framework, as a descriptor of upper and lower critical solution temperature (UCST and LCST) governed phase separation in aqueous ionic liquid (IL) solutions. The maximum and minimum values of σr correspond to the homogenous and phase separated states, at a given composition, for both UCST and LCST cases. Furthermore, the value of σr changes from positive to negative as the temperature increases in LCST exhibiting solutions, while as the temperature increases in UCST exhibiting solutions, the value of σr changes from negative to positive. Therefore, σr provides a less computationally intensive alternate to Gibbs free energy calculations and to the generation of phase diagrams for assessing UCST/LCST behavior in aqueous IL solutions.

IntroductionImpaired cognition is a core feature of schizophrenia that is evident early in the first episode and is frequently accompanied by compromised physical health. Although physical health confers benefits to cognition, it remains unclear whether physical activity, body mass index (BMI) and cardiorespiratory fitness are associated with neurocognition in first episode schizophrenia patients. The purpose of this study was to examine differences in stimulus categorization and motor response selection processes between first-episode schizophrenia patients compared to age-matched controls and explore associations between physical health and these stages of information processing.MethodsFourteen young adult patients receiving care following a first episode of psychosis and a matched sample of nonpsychiatric controls completed a visual oddball task from which the P3 and LRP (lateralized readiness potential) event-related potential (ERP) components were extracted to assess stimulus categorization and response selection processes, respectively. Physical activity, aerobic fitness, and BMI were correlated with ERP measures.ResultsCompared with controls, patients had lower physical activity levels and longer P3 and LRP latencies. Regardless of stimulus probability, patients had reduced accuracy and slower reaction times relative to controls. In patients, marginal associations were found between physical activity and P3 difference waveform amplitude, and BMI was negatively associated with parent P3 waveform amplitude.DiscussionThe present findings suggest that cognitive impairment in first-episode schizophrenia spans both stimulus- and response-related stages of information processing, and may be targeted through physical activity interventions.

Summary: Programmable catalysis—the purposeful oscillation of catalytic potential energy surfaces (PES)—has emerged as a promising method for the acceleration of catalyzed reaction rates. However, theoretical study of programmable catalysis has been limited by onerous computational demands of integrating the stiff differential equations that describe periodic cycling between PESs. This work details methods that reduce the computational cost of finding the limit cycle by ≳108×. These methods produce closed-form analytical solutions for didactic case studies, examination of which provides physical insights of programmable catalysis mechanisms. Generalization of these analyses to more complex reaction networks, including CO oxidation on Pt (111) surfaces, exposes the key catalyst properties required to achieve enhanced rates and conversions via one of two programmable catalysis mechanisms: quasi-static (high frequency) and stepwise (intermediate frequency). Analytical description of each mechanism is critical in understanding the consequences of the Sabatier principle on achievable rate enhancement through programmed catalysis.

Background: There is a growing interest to understand the neurobiological mechanisms that drive the positive associations of physical activity and fitness with measures of cognitive performance. To better understand those mechanisms, several studies have employed eye-based measures (e.g., eye movement measures such as saccades, pupillary measures such as pupil dilation, and vascular measures such as retinal vessel diameter) deemed to be proxies for specific neurobiological mechanisms. However, there is currently no systematic review providing a comprehensive overview of these studies in the field of exercise-cognition science. Thus, this review aimed to address that gap in the literature. Methods: To identify eligible studies, we searched 5 electronic databases on October 23, 2022. Two researchers independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX scale, for interventional studies) and the critical appraisal tool from the Joanna Briggs Institute (for cross-sectional studies). Results: Our systematic review (n = 35 studies) offers the following main findings: (a) there is insufficient evidence available to draw solid conclusions concerning gaze-fixation-based measures; (b) the evidence that pupillometric measures, which are a proxy for the noradrenergic system, can explain the positive effect of acute exercise and cardiorespiratory fitness on cognitive performance is mixed; (c) physical training- or fitness-related changes of the cerebrovascular system (operationalized via changes in retinal vasculature) are, in general, positively associated with cognitive performance improvements; (d) acute and chronic physical exercises show a positive effect based on an oculomotor-based measure of executive function (operationalized via antisaccade tasks); and (e) the positive association between cardiorespiratory fitness and cognitive performance is partly mediated by the dopaminergic system (operationalized via spontaneous eye-blink rate). Conclusion: This systematic review offers confirmation that eye-based measures can provide valuable insight into the neurobiological mechanisms that may drive positive associations between physical activity and fitness and measures of cognitive performance. However, due to the limited number of studies utilizing specific methods for obtaining eye-based measures (e.g., pupillometry, retinal vessel analysis, spontaneous eye blink rate) or investigating a possible dose–response relationship, further research is necessary before more nuanced conclusions can be drawn. Given that eye-based measures are economical and non-invasive, we hope this review will foster the future application of eye-based measures in the field of exercise-cognition science.

Abstract Tryptophan is frequently found on the surface of membrane-associated proteins that interact with the lipid membrane. However, because of their multifaceted interactions, it is difficult to pinpoint the structure-activity relationship of each tryptophan residue. Here, we describe the use of racemic protein crystallography to probe dedicated tryptophan interactions of a model tryptophan-rich bacteriocin aureocin A53 (AucA) by inclusion and/or exclusion of potential ligands. In the presence of tetrahedral anions that are isosteric to the head group of phospholipids, distinct tryptophan H-bond networks were revealed. H-bond donation by W40 was critical for antibacterial activity, as its substitution by 1-methyltryptophan resulted in substantial loss of activity against bacterial clinical isolates. Meanwhile, exclusion of tetrahedral ions revealed that W3 partakes in formation of a dimeric interface, thus suggesting that AucA is dimeric in solution and dissociated to interact with the phosphate head group in the presence of the lipid membrane. Based on these findings, we could predict the tryptophan residue responsible for activity as well as the oligomeric state of a distant homologue lacticin Q (48%).

BackgroundWA Notify was Washington State’s smartphone-based COVID-19 digital exposure notification (EN) tool, which was used to help limit the spread of COVID-19 between November 30, 2020, and May 11, 2023. Following the 2022 Washington State Public Health Association Annual Conference, attendees who had WA Notify activated began receiving ENs alerting them to a possible COVID-19 exposure during the conference. A survey was emailed to all conference attendees to measure WA Notify adoption, mechanisms through which attendees received ENs, and self-reported engagement in protective behaviors postexposure. ObjectiveThis study aimed to learn more about the experiences of WA Notify adopters and nonadopters who may have been exposed to COVID-19 at a large group gathering. MethodsA web-based survey administered through REDCap (Research Electronic Data Capture; Vanderbilt University) was sent to all attendees of the Washington State Public Health Association conference. Self-reported demographic information and characteristics of respondents were summarized. Regression models were used to estimate relative risks to compare WA Notify adoption and testing behaviors between groups. ResultsOf the 464 total registered attendees who were sent the survey, 205 (44%) responses were received; 201 eligible attendees were included in this analysis. Of those, 149 (74%) respondents reported having WA Notify activated on their phones at the time of the conference. Among respondents with WA Notify activated, 54% (n=77) reported learning of their potential exposure from a WA Notify EN. Respondents who reported that they did not have WA Notify activated and learned of their potential exposure via the event-wide email from conference organizers were 39% less likely to test for COVID-19 compared to respondents with WA Notify activated who learned of their potential exposure from the email (relative risk 0.61, 95% CI 0.40-0.93; P=.02), and this gap was even larger when compared to respondents who learned of their exposure from a WA Notify EN. The most commonly cited reason for not having WA Notify activated was privacy concerns (n=17, 35%), followed by not wanting to receive ENs (n=6, 12%) and being unaware of WA Notify (n=5, 10%). ConclusionsDigital EN systems are an important tool to directly and anonymously notify close contacts of potential exposures and provide guidance on the next steps in a timely manner. Given the privacy concerns, there is still a need for increasing transparency surrounding EN technology to increase uptake by the public if this technology were to be used in the future to slow the spread of communicable diseases.

BackgroundAttitudes toward abortion have historically been characterized via dichotomized labels, yet research suggests that these labels do not appropriately encapsulate beliefs on abortion. Rather, contexts, circumstances, and lived experiences often shape views on abortion into more nuanced and complex perspectives. Qualitative data have also been shown to underpin belief systems regarding abortion. Social media, as a form of qualitative data, could reveal how attitudes toward abortion are communicated publicly in web-based spaces. Furthermore, in some cases, social media can also be leveraged to seek health information. ObjectiveThis study applies natural language processing and social media mining to analyze Reddit (Reddit, Inc) forums specific to abortion, including r/Abortion (the largest subreddit about abortion) and r/AbortionDebate (a subreddit designed to discuss and debate worldviews on abortion). Our analytical pipeline intends to identify potential themes within the data and the affect from each post. MethodsWe applied a neural network–based topic modeling pipeline (BERTopic) to uncover themes in the r/Abortion (n=2151) and r/AbortionDebate (n=2815) subreddits. After deriving the optimal number of topics per subreddit using an iterative coherence score calculation, we performed a sentiment analysis using the Valence Aware Dictionary and Sentiment Reasoner to assess positive, neutral, and negative affect and an emotion analysis using the Text2Emotion lexicon to identify potential emotionality per post. Differences in affect and emotion by subreddit were compared. ResultsThe iterative coherence score calculation revealed 10 topics for both r/Abortion (coherence=0.42) and r/AbortionDebate (coherence=0.35). Topics in the r/Abortion subreddit primarily centered on information sharing or offering a source of social support; in contrast, topics in the r/AbortionDebate subreddit centered on contextualizing shifting or evolving views on abortion across various ethical, moral, and legal domains. The average compound Valence Aware Dictionary and Sentiment Reasoner scores for the r/Abortion and r/AbortionDebate subreddits were 0.01 (SD 0.44) and −0.06 (SD 0.41), respectively. Emotionality scores were consistent across the r/Abortion and r/AbortionDebate subreddits; however, r/Abortion had a marginally higher average fear score of 0.36 (SD 0.39). ConclusionsOur findings suggest that people posting on abortion forums on Reddit are willing to share their beliefs, which manifested in diverse ways, such as sharing abortion stories including how their worldview changed, which critiques the value of dichotomized abortion identity labels, and information seeking. Notably, the style of discourse varied significantly by subreddit. r/Abortion was principally leveraged as an information and outreach source; r/AbortionDebate largely centered on debating across various legal, ethical, and moral abortion domains. Collectively, our findings suggest that abortion remains an opaque yet politically charged issue for people and that social media can be leveraged to understand views and circumstances surrounding abortion.

Soil erosion can have a multitude of negative impacts on agroecosystems and society and there remains an urgent need for tools to support its management. Quantitative benchmarks based on holistic understanding of erosion processes, ecosystem function, and land use objectives can be used with monitoring data and models to inform assessments and make objective and actionable decisions about erosion management. However, managers currently lack a framework for establishing benchmarks. Here, we present a framework and evaluation of different approaches to establishing quantitative benchmarks for soil erosion and ecological monitoring and assessment that can inform land management decisions. We use monitoring data collected across Chihuahuan Desert ecosystems in the United States and an aeolian sediment transport model to illustrate how benchmarks can be established. Approaches include establishing benchmarks from relationships between soil erosion indicators, reference states and land potential, including state-and-transition models, and desired conditions from existing monitoring data. We discuss the benefits and caveats of the different approaches and show how combining different benchmarking approaches can help users ensure that benchmarks appropriately reflect thresholds for soil erosion and achievable management outcomes. We finish by identifying future research needs to support establishment and application of erosion benchmarks across agroecosystems and recognize the opportunity to extend the benchmarking approaches to management of other agroecosystem processes and services.

Abstract This letter uses simultaneous observations from Magnetosphere Multiscale (MMS) and Time History of Events and Macroscale Interactions during Substorms (THEMIS) to address the dynamics of the magnetopause and magnetosheath boundary layers during the main phase of a storm during which the interplanetary magnetic field (IMF) reverses from south to north. Near the dawn terminator, MMS observes two boundary layers comprising open and closed field lines and containing energetic electrons and ring current oxygen. Some closed field line regions exhibit sunward convection, presenting an avenue to replenish dayside magnetic flux lost during the storm. Meanwhile, THEMIS observes two boundary layers in the pre‐noon sector which strongly resemble those observed at the flank by MMS. Observations from the three THEMIS spacecraft indicate the boundary layers are still evolving several hours after the IMF has turned northward. These observations advance our knowledge of the dynamic magnetopause and magnetosheath boundary layers under the combined effects of an ongoing storm and changing IMF.

Abstract Disruption of circadian rhythms, such as shift work and jet lag, are associated with negative physiological and behavioral outcomes, including changes in affective state, learning and memory, and cognitive function. The prefrontal cortex (PFC) is heavily involved in all of these processes. Many PFC-associated behaviors are time-of-day dependent, and disruption of daily rhythms negatively impacts these behavioral outputs. Yet how disruption of daily rhythms impacts the fundamental function of PFC neurons, and the mechanism(s) by which this occurs, remains unknown. Using a mouse model, we demonstrate that the activity and action potential dynamics of prelimbic PFC neurons are regulated by time-of-day in a sex specific manner. Further, we show that postsynaptic K+ channels play a central role in physiological rhythms, suggesting an intrinsic gating mechanism mediating physiological activity. Finally, we demonstrate that environmental circadian desynchronization alters the intrinsic functioning of these neurons independent of time-of-day. These key discoveries demonstrate that daily rhythms contribute to the mechanisms underlying the essential physiology of PFC circuits and provide potential mechanisms by which circadian disruption may impact the fundamental properties of neurons.

Abstract High throughput drug screening is an established approach to investigate tumor biology and identify therapeutic leads. Traditional platforms use two-dimensional cultures which do not accurately reflect the biology of human tumors. More clinically relevant model systems such as three-dimensional tumor organoids can be difficult to scale and screen. Manually seeded organoids coupled to destructive endpoint assays allow for the characterization of treatment response, but do not capture transitory changes and intra-sample heterogeneity underlying clinically observed resistance to therapy. We present a pipeline to generate bioprinted tumor organoids linked to label-free, time-resolved imaging via high-speed live cell interferometry (HSLCI) and machine learning-based quantitation of individual organoids. Bioprinting cells gives rise to 3D structures with unaltered tumor histology and gene expression profiles. HSLCI imaging in tandem with machine learning-based segmentation and classification tools enables accurate, label-free parallel mass measurements for thousands of organoids. We demonstrate that this strategy identifies organoids transiently or persistently sensitive or resistant to specific therapies, information that could be used to guide rapid therapy selection.

Abstract Background Animal-borne telemetry instruments (tags) have greatly advanced our understanding of species that are challenging to observe. Recently, non-recoverable instruments attached to cetaceans have increased in use, but these devices have limitations in data transmission bandwidth. We analyze trade-offs in the longevity, resolution, and continuity of data records from non-recoverable satellite-linked tags on deep-diving Ziphius cavirostris in the context of a behavioral response study of acute noise exposure. We present one data collection programming scheme that balances resolution and continuity against longevity to address specific questions about the behavioral responses of animals to noise exposure in experimental contexts. We compare outputs between two programming regimes on a commercially available satellite-linked tag: (1) dive behavior summary defined by conductivity thresholds and (2) depth time-series at various temporal resolutions. Results We found that time-series data vary from the more precisely defined dives from a dive summary record data stream by an acceptable error range for our application. We determined a 5-min time-series data stream collected for 14 days balanced resolution with longevity, achieving complete or nearly complete diving records in 6 out of 8 deployments. We increased our data message reception rate several fold by employing a boat based data capture system. Finally, a tag deployed in a group concurrently with a high-resolution depth recorder showed high depth concordance. Conclusions We present the conceptual framework and iterative process for matching telemetry tag programming to research questions that we used and which should be applicable to a wide range of studies. Although designing new hardware for our specific questions was not feasible at the time, we were able to optimize the sampling regime of a commercially available instrument to meet the needs of our research questions and proposed analyses. Nevertheless, for other study species or designs, the complicated intersection between animal behavior and bandwidth of telemetry systems can often create a severe mismatch among research questions, data collection, and analysis tools. More flexible programming and purpose-built instruments will increase the efficacy of these studies and increase the scientific yield relative to the inherently higher risk of invasive studies.

The association of telomere length with age and mortality across racially diverse pulmonary fibrosis populations is unknown. Here, the authors show that leukocyte telomere length associates with chronologic age and is predictive of mortality in pulmonary fibrosis across racial groups.

Abstract Background In sub-Saharan Africa many people who inject drugs (PWID) are living with undiagnosed or untreated HIV and experience high levels of poverty and conditions that can contribute to worse outcomes from SARS-CoV-2 infection. Identifying the burden of SARS-CoV-2 infection in marginalized populations like PWID may contribute to controlling the pandemic. Methods This is a nested cross-sectional study within an ongoing cohort study that recruits PWID living with HIV and their injecting and/or sexual partners at needle and syringe program sites and methadone clinics in Kenya. Blood samples were collected from consenting participants at enrollment to determine SARS-CoV-2 antibodies using a Platellia BioRad SARS-CoV-2 total antibody enzyme-linked immunosorbent assay. Baseline data were collected on HIV status, antiretroviral therapy and methadone adherence. We used logistic regression to identify factors associated with antibody positivity and descriptive statistics to report SARS-CoV-2 antibody prevalence. Results One thousand participants were enrolled between April and July 2021, of whom 323 (32.3%) were women and 677 (67.7%) were men. Median age of participants was 36 years (interquartile range: 30, 42). SARS-CoV-2 antibody positivity was found in 309 (30.9%) participants. Disruption in obtaining methadone service was reported by 106 (24.3%) of the participants. Men were significantly less likely than women to have SARS-CoV-2 antibodies (adjusted odds ratio [aOR] = 0.68, 95% confidence interval [CI] 0.51, 0.95; p

AbstractAlthough media response to the Dobbs v. Jackson Women’s Health Organization decision was widespread in the United States, the extent to which people were aware of the Mississippi law leading to the decision, the Dobbs v. Jackson case, is unclear, as are the resulting effects of the decision on legal abortion. As such, we examined people’s awareness of abortion legality prior to and after the Dobbs v. Jackson decision announcement, as well as the potential implications associated with the decision (i.e. overturning of Roe v. Wade). We also examined people’s attitudes toward abortion legality, specifically focusing on 15 weeks’ gestation to correspond with the Mississippi law that led to Dobbs v. Jackson. Data were collected across two studies at different times. In Study 1, a 15-minute survey was administered to IPSOS’ KnowledgePanel (N = 1014) prior to the decision announcement. A shorter version of that survey was administered to a second sample using NORC’s AmeriSpeak Omnibus panel (N = 1002). Nearly half of that sample (42.2%) completed the survey prior to the decision announcement. People were generally unaware of the Mississippi law, the Dobbs v. Jackson case, and implications associated with the decision (e.g. overturning Roe v. Wade). People generally endorsed abortion being legal at 15 weeks or later, but this varied by circumstance. We did not find meaningful effects of the decision announcement on people’s knowledge and attitudes. Our findings suggest that the intense response to the decision from the media and people involved in the abortion movement may not represent the general public’s reaction.

Summary: Mutated Ras and Raf kinases are well-known to promote cancer metastasis via flux through the Ras/Raf/MEK/ERK (mitogen-activated protein kinase [MAPK]) pathway. A role for non-mutated Raf in metastasis is also emerging, but the key mechanisms remain unclear. Elevated expression of any of the three wild-type Raf family members (C, A, or B) can drive metastasis. We utilized an in vivo model to show that wild-type C-Raf overexpression can promote metastasis of immortalized prostate cells in a gene dosage-dependent manner. Analysis of the transcriptomic and phosphoproteomic landscape indicated that C-Raf-driven metastasis is accompanied by upregulated MAPK signaling. Use of C-Raf mutants demonstrated that the dimerization domain, but not its kinase activity, is essential for metastasis. Endogenous Raf monomer knockouts revealed that C-Raf’s ability to form dimers with endogenous Raf molecules is important for promoting metastasis. These data identify wild-type C-Raf heterodimer signaling as a potential target for treating metastatic disease.

The effect of active sonars on marine mammal behaviour is a topic of considerable interest and scientific investigation. Some whales, including the largest species (blue whales, Balaenoptera musculus), can be impacted by mid-frequency (1–10 kHz) military sonars. Here we apply complementary experimental methods to provide the first experimentally controlled measurements of behavioural responses to military sonar and similar stimuli for a related endangered species, fin whales (Balaenoptera physalus). Analytical methods include: (i) principal component analysis paired with generalized additive mixed models; (ii) hidden Markov models; and (iii) structured expert elicitation using response severity metrics. These approaches provide complementary perspectives on the nature of potential changes within and across individuals. Behavioural changes were detected in five of 15 whales during controlled exposure experiments using mid-frequency active sonar or pseudorandom noise of similar frequency, duration and source and received level. No changes were detected during six control (no noise) sequences. Overall responses were more limited in occurrence, severity and duration than in blue whales and were less dependent upon contextual aspects of exposure and more contingent upon exposure received level. Quantifying the factors influencing marine mammal responses to sonar is critical in assessing and mitigating future impacts.

Spinal locomotor circuitry is comprised of rhythm generating centers, one for each limb, that are interconnected by local and long-distance propriospinal neurons thought to carry temporal information necessary for interlimb coordination and gait control. We showed previously that conditional silencing of the long ascending propriospinal neurons (LAPNs) that project from the lumbar to the cervical rhythmogenic centers (L1/L2 to C6), disrupts right-left alternation of both the forelimbs and hindlimbs without significantly disrupting other fundamental aspects of interlimb and speed-dependent coordination (Pocratsky et al., 2020). Subsequently, we showed that silencing the LAPNs after a moderate thoracic contusive spinal cord injury (SCI) resulted in better recovered locomotor function (Shepard et al., 2021). In this research advance, we focus on the descending equivalent to the LAPNs, the long descending propriospinal neurons (LDPNs) that have cell bodies at C6 and terminals at L2. We found that conditional silencing of the LDPNs in the intact adult rat resulted in a disrupted alternation of each limb pair (forelimbs and hindlimbs) and after a thoracic contusion SCI significantly improved locomotor function. These observations lead us to speculate that the LAPNs and LDPNs have similar roles in the exchange of temporal information between the cervical and lumbar rhythm generating centers, but that the partial disruption of the pathway after SCI limits the independent function of the lumbar circuitry. Silencing the LAPNs or LDPNs effectively permits or frees-up the lumbar circuitry to function independently.