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Mites in the family Halarachnidae are common endoparasites infesting the nasal tissues of a variety of marine mammals. These mites are easily transmissible and compromise the health of their hosts, especially in captive environments. While these mites are noted by marine mammal caretakers, they may easily be misidentified due to repeated revisions to halarachnid mite taxonomy and reclassification of misidentified specimens. Species identification currently requires multiple taxonomic keys, knowledge of revisions to species classifications through time, and training in acarology, which is impractical for marine mammal clinicians. Therefore, to summarize the known taxonomy and aid in future identification of halarachnid mites, we present a pictorial key composed of illustrations based on existing literature and images obtained by scanning electron microscopy (SEM) and high-resolution light microscopy (LM). Illustrations are organized into flow charts for the identification of both adult and larval stages. Dorsal shield silhouettes are also provided to facilitate the identification of adults. We hope that this key be used to simplify future taxonomic research, provide a standard for species identification, and aid in the diagnosis of halarachnid infestations in captive and rehabilitated marine mammal populations.

Abstract Representatives of Schizomida, known as short-tailed whip scorpions, are an understudied group within Megoperculata. They are found subterraneanly in tropical and sub-tropical regions. They lack eyes, have superior mobility, and possess a flagellum which is relevant to their mating, but in general little is known about their general biology. Fossil representatives of Schizomida from a variety of time periods are available for study. Using 23 fossil specimens (14 of which are described here for the first time) and 86 extant individuals from the literature, changes in both body size and flagella shape in Schizomida were compared over time. Measurements of prosoma length and leg length were used as a proxy for body size, and a comparative size analysis was carried out. Individuals from the Cretaceous period were found to be significantly smaller than extant individuals, contrary to our expectations. For flagellum shape, images were used to create reconstructions, which were then analysed using an elliptic Fourier analysis followed by a principal component analysis. The morphological diversity of the male flagellum shape was found to have decreased between the Cretaceous and modern fauna. We discuss potential explanations for our findings, although a greater understanding of the general biology of Schizomida is required to properly interpret our results.

ABSTRACT Background Approximately one‐third of US adults have a tattoo, and the prevalence is increasing. Tattooing can result in long‐term exposure to carcinogens and inflammatory and immune responses. Methods We examined tattooing and risk of hematologic cancers in a population‐based case–control study with 820 cases diagnosed 2019–2021 and 8200 frequency‐matched controls, ages 18–79 years. We calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariable‐adjusted logistic regression models. Results The prevalence of tattooing was 22% among Hodgkin lymphoma (HL) cases, 11% among non‐Hodgkin lymphoma (NHL) cases, 16% among myeloid neoplasm cases, and 15% among controls. Though there were no clear patterns of associations between ever receiving a tattoo and risk of HL, NHL, or myeloid neoplasms overall, in analyses restricted to ages 20–60 years, ever receiving a tattoo (OR 2.06 [95% CI 1.01, 4.20]) and receiving a tattoo 10+ years prior (OR 2.64 [95% CI 1.23, 5.68]) were associated with an aggregated group of rarer mature B‐cell NHLs. We also observed elevated risks for a 10+ year latency for myelodysplastic syndromes and chronic myeloid leukemia (OR 1.48 [95% CI 0.40, 5.41], and OR 1.24 [95% CI 0.45, 3.43], respectively). Conclusions Though estimates were imprecise, we found some suggestive evidence that tattooing may be associated with an increased risk of certain hematologic cancer subtypes. With an estimated 46% prevalence of tattooing in US individuals ages 30–49, additional studies are needed to understand the degree to which these exposures may be associated with hematologic cancer risk.

Background: Limited knowledge is currently available on the effects of modified atmospheric packaging (MAP) on the metabolite profiles of cooked beef. The objective was to evaluate the impact of packaging on the cooked color and cooked metabolite profile of normal-pH (normal bright-red color) and atypical-dark-cutting beef (inherently slightly dark-colored) longissimus lumborum muscle. Methods: Normal-pH (pH 5.56) and atypical dark-cutting (pH 5.63) loins (n = 6) were procured from a commercial meat processor. Steaks were randomly assigned to one of three different packaging methods: vacuum packaging, carbon monoxide (CO-MAP), and high oxygen (HiOx-MAP). Following 5 d of retail display, steaks were cooked to 71 °C on a clamshell-style grill, and samples were collected for untargeted metabolites using gas-chromatography mass spectrometry. Results: Raw atypical dark-cutting steaks were less red (p < 0.05) than raw normal-pH steaks. However, there were no differences in internal cooked color between normal-pH and atypical dark-cutting steaks. Steaks packaged in HiOx-MAP steaks had a lower (p < 0.05) cooked redness than vacuum and CO-MAP steaks. A total of 129 metabolite features were identified in the study. Serine and tryptophan were over-abundant in cooked atypical dark-cutting beef compared to raw atypical samples. Citric acid levels were greater in HiOx-MAP packaged beef compared with VP both in normal and atypical dark-cutting beef after cooking, while no differentially abundant metabolites were shared between vacuum and CO-MAP steaks after cooking. Discussion: A slight increase in pH did not influence metabolite profiles in different packaging. However, there were packaging effects within normal and atypical dark-cutting beef. Conclusions: This study suggests that packaging conditions change metabolite profiles, which can influence cooked metabolites. Therefore, the metabolomics approach can be used to better understand cooked color defects such as premature browning.

A growing number of inexpensive, publicly available, validated air quality monitors are currently generating granular and longitudinal data on air quality. The expansion of interconnected networks of these monitors providing open access to longitudinal data represents a valuable data source for health researchers, citizen scientists, and community members; however, the distribution of these data collection systems will determine the groups that will benefit from them. Expansion of these and other exposure measurement networks represents a unique opportunity to address persistent inequities across racial, ethnic, and class lines, if the distribution of these devices is equitable. We present a lean template for local implementation, centered on groups known to experience excess burden of pulmonary disease, leveraging five resources, (a) publicly available, inexpensive air quality monitors connected via Wi-Fi to a centralized system, (b) discharge data from a state hospital repository (c) the U.S. Census, (d) monitoring locations generously donated by community organizations and (e) NIH grant funds. We describe our novel approach to targeting air-quality mediated pulmonary health disparities, review logistical and analytic challenges encountered, and present preliminary data that aligns with a growing body of research: in a high-burden zip code in Durham North Carolina, the census tract with the highest proportions of African Americans experienced worse air quality than a majority European-American census tract in the same zip code. These results, while not appropriate for use in causal inference, demonstrate the potential of equitably distributed, interconnected air quality sensors.

Exposure-based cognitive behavioral therapy (CBT) is a gold standard treatment for Social Anxiety Disorder (SAD), but many patients do not gain complete symptom relief. Since fear extinction is central to the effectiveness of exposure within CBT, adjunctive treatments that target neurocognitive systems underlying fear extinction could increase the effectiveness of CBT. Successful fear extinction and cognitive tasks like working memory share neurocognitive substrates. The present study evaluates the neural impact of working memory training (WMT) as an adjunctive CBT treatment by exploring changes in intrinsic network connectivity associated with combining WMT with exposure exercises. The sample included twenty-four adults (Mean Age = 27.42(9.75), 62.5% female) with elevated social anxiety symptoms. Participants completed either a WMT or sham training (ST) condition, followed by a speech-based massed exposure session (WMT+Exp versus ST+Exp). Compared to ST+Exp, WMT+Exp participants exhibited lower connectivity between the default and visual networks and visual and dorsal networks. Lower connectivity between these networks was associated with lower subjective distress at the end of the massed exposure across the whole sample. WMT+Exp completers exhibited unique functional connectivity between the frontoparietal and dorsal attention networks. WM+Exp was associated with a neural connectivity profile involving networks critical to working memory, fear learning, and emotion regulation, as well as emotional and sensory processing functions. Data provisionally point to combined working memory training and exposure facilitating improvement in neural connections useful for benefitting from CBT for SAD.

BackgroundLong-acting injectable (LAI) HIV antiretroviral therapy (ART) presents a major opportunity to facilitate and sustain HIV viral suppression, thus improving health and survival among people living with HIV and reducing the risk of onward transmission. However, realizing the public health potential of LAI ART requires reaching patients who face barriers to daily oral ART adherence and thus can clinically benefit from alternative treatment modalities. Ryan White HIV/AIDS Program Part A medical case management (MCM) programs provide an array of services to address barriers to HIV care and treatment among economically and socially marginalized people living with HIV. These programs have demonstrated effectiveness in improving engagement along the continuum of care, but findings of limited program impact on durable viral suppression highlight the need to further innovate and hone strategies to support long-term ART adherence. ObjectiveThis study aims to adapt and expand Ryan White MCM service strategies to integrate LAI ART regimen options, with the larger goal of improving health outcomes in the populations that could most benefit from alternatives to daily oral ART regimens. MethodsIn 3 phases of work involving patient and provider participants, this study uses role-specific focus groups to elicit perceptions of LAI versus daily oral ART; discrete choice experiment (DCE) surveys to quantify preferences for different ART delivery options and related supports; and a nonrandomized trial to assess the implementation and utility of newly developed tools at 6 partnering Ryan White HIV/AIDS Program Part A MCM programs based in urban, suburban, and semirural areas of New York. Findings from the focus groups and DCEs, as well as feedback from advisory board meetings, informed the design and selection of the tools: a patient-facing, 2-page fact sheet, including frequently asked questions and a side-by-side comparison of LAI with daily oral ART; a patient-facing informational video available on YouTube (Google Inc); and a patient-provider decision aid. Implementation outcomes, measured through provider interviews, surveys, and service reporting, will guide further specification of strategies to integrate LAI ART options into MCM program workflows. ResultsThe study was funded in late April 2021 and received approval from the institutional review board in May 2021 under protocol 20-096. Focus groups were conducted in late 2021 (n=21), DCEs ran from June 2022 to January 2023 (n=378), and tools for piloting were developed by May 2023. The trial (May 2023 through January 2024) has enrolled >200 patients. ConclusionsThis study is designed to provide evidence regarding the acceptability, feasibility, appropriateness, and utility of a package of patient-oriented tools for comparing and deciding between LAI ART and daily oral ART options. Study strengths include formative work to guide tool development, a mixed methods approach, and the testing of tools in real-world safety-net service settings. Trial RegistrationClinicaltrials.gov NCT05833542; https://clinicaltrials.gov/study/NCT05833542 International Registered Report Identifier (IRRID)DERR1-10.2196/56892

Improving social functioning deficits—a core characteristic of schizophrenia-spectrum disorders—is often listed by patients as a key recovery goal. Evidence suggests that social deficits also extend to people with schizotypy, a group at heightened risk for psychotic and other psychopathological disorders. One challenge of social functioning research in schizotypy is understanding whether social deficits arise from receiving less pleasure from social activities or from participating less in high-pleasure activities. However, limited information exists on what constitutes highly pleasurable, common social activities. In this study, 357 college students rated the frequency and enjoyment of 38 social activities. Our aims were to categorize activities based on their frequency and enjoyment, and whether these correlated with validated social functioning and schizotypy measures. We found that social activities could be characterized based on their frequency and enjoyment and created a frequency–enjoyment matrix that could be useful for future studies. Activities were correlated with social functioning, generally reaching a small effect size level, with increasing frequency and enjoyment showing associations with greater social functioning. Further, negative and disorganized—but not positive—traits were associated with less engagement and pleasure. Although follow-up studies in community samples are needed, our findings have the potential to help researchers and clinicians better understand which activities participants are more likely to engage in and derive pleasure from. The findings may also illustrate the extent to which social deficits may be due to less engagement or less pleasure from social activities, as well as which aspects of schizophrenia-spectrum disorders are associated with these facets of social functioning.

In this survey of 31 hospitals, large metropolitan facilities had a 9.5-fold odds of reporting preparedness for special pathogens; hospitals with special pathogens teams had a 14.3-fold odds of reporting preparedness for special pathogens. In the postpandemic world, healthcare institutions must invest in special pathogen responses to maximize patient safety.

Abstract Objective: The objective of this study was to determine factors associated with testing positive for SARS-CoV-2 among healthcare personnel. Secondary objectives were to assess representativeness of recruited participants and the effectiveness of a multiple-contact protocol for recruiting healthcare personnel in this COVID-19 study. Design: Survey study, conducted as part of an observational test-negative study of COVID-19 vaccine effectiveness. Setting: University of Utah Health system, including both inpatient and outpatient facilities. Participants: Clinical and non-clinical healthcare personnel at University of Utah Health. 1456 were contacted and 503 (34.5%) completed the survey. Cases were all eligible employees testing positive for COVID-19, with 3:1 randomly selected, matched controls (test negative) selected weekly. Methods: Online survey. Results: Significant differences in the demographics of participants and the source population were observed; e.g., nursing staff comprised 31.6% of participants but only 23.3% of the source population. The multiple-contact recruitment protocol increased participation by ten percentage points and ensured equal representation of controls. Potential exposure to illness outside of work was strongly predictive of testing positive for SARS-CoV-2 (OR = 3.74; 95% CI: 2.29, 6.11) whereas potential exposure at work was protective against testing positive (OR: 0.51, 95% CI: 0.29, 0.88). Conclusions: Carefully designed recruitment protocols increase participation and representation of controls, but bias in participant demographics still exists. The negative association between potential workplace exposure and positive test suggests testing bias in the test-negative design. Healthcare personnel’s potential exposures to COVID-19 outside of the workplace are important predictors of SARS-CoV-2 seropositivity.

Lipoproteins of the opportunistic pathogen Staphylococcus aureus play a crucial role in various cellular processes and host interactions. Consisting of a protein and a lipid moiety, they support nutrient acquisition and anchor the protein to the bacterial membrane. Recently, we identified several processed and secreted small linear peptides that derive from the secretion signal sequence of S. aureus lipoproteins. Here, we show, for the first time, that the protein moiety of the S. aureus lipoprotein CamS has a biological role that is distinct from its associated linear peptide staph-cAM373. The small peptide was shown to be involved in interspecies horizontal gene transfer, the primary mechanism for the dissemination of antibiotic resistance among bacteria. We provide evidence that the CamS protein moiety is a potent repressor of cytotoxins, such as α-toxin and leukocidins. The CamS-mediated suppression of toxin transcription was reflected by altered disease severity in in vivo infection models involving skin and soft tissue, as well as bloodstream infections. Collectively, we have uncovered the role of the protein moiety of the staphylococcal lipoprotein CamS as a previously uncharacterized repressor of S. aureus toxin production, which consequently regulates virulence and disease outcomes. Notably, the camS gene is conserved in S. aureus, and we also demonstrated the muted transcriptional response of cytotoxins in 2 different S. aureus lineages. Our findings provide the first evidence of distinct biological functions of the protein moiety and its associated linear peptide for a specific lipoprotein. Therefore, lipoproteins in S. aureus consist of 3 functional components: a lipid moiety, a protein moiety, and a small linear peptide, with putative different biological roles that might not only determine the outcome of host-pathogen interactions but also drive the acquisition of antibiotic resistance determinants.

AbstractTechnology, digital advances, and social media are increasingly used to facilitate and influence online consumer purchasing behavior. Growth at the intersection of e-commerce, social networking usage, and functionality has given rise to the social commerce phenomenon. Social commerce sites allow consumers and sellers to engage in two concurrent types of interaction during the buying process. Consumers engage in marketing content from sellers and user-generated content from other consumers. This study investigates how social commerce sites’ combined e-commerce and social networking functionality may impact consumer purchasing behavior. It focuses on seller-generated and user-generated social cues communicated through profile pictures, logos, and other social networking practices (e.g. “follows,” “likes”) and their correlation to retail shop performance indicators on a social commerce site. Using a sample of social and commercial performance indicators from retail shops on “Etsy.com” and a negative binomial regression analysis, we evaluate the effect of social signals on consumer purchasing behavior with a classical Stimulus-Response framework. Findings suggest consumers are more likely to purchase from shops with seller-generated social cues and show greater engagement in the volume of reviews and follows. More importantly, these features also appear to lower the negative impact of the age of an online shop. This finding may be advantageous to new entrants to social commerce or online retail outlets.

Summary: Streptococcus pyogenes is an obligate human pathobiont associated with many disease states. Here, we present a model of S. pyogenes infection using intact murine epithelium. We were able to perform RNA sequencing to evaluate genetic changes undertaken by both the bacterium and host at 5 and 24 h post-infection. Analysis of these genomic data demonstrate that S. pyogenes undergoes genetic adaptation to successfully infect the murine epithelium, including changes to metabolism and activation of the Rgg2/Rgg3 quorum-sensing (QS) system. Subsequent experiments demonstrate that an intact Rgg2/Rgg3 QS cascade is necessary to establish a stable superficial skin infection. QS cascade activation results in increased murine morbidity and bacterial burden on the skin. This phenotype is associated with gross changes to the murine skin and with evidence of inflammation. These experiments offer a method to investigate S. pyogenes-epithelial interactions and demonstrate that a well-studied QS pathway is critical to a persistent infection.

Abstract The development of fully solution-processed, biodegradable piezoelectrics is a critical step in the development of green electronics towards the worldwide reduction of harmful electronic waste. However, recent printing processes for piezoelectrics are hindered by the high sintering temperatures required for conventional perovskite fabrication techniques. Thus, a process was developed to manufacture lead-free printed piezoelectric devices at low temperatures to enable integration with eco-friendly substrates and electrodes. A printable ink was developed for screen printing potassium niobate (KNbO3) piezoelectric layers in microns of thickness at a maximum processing temperature of 120 °C with high reproducibility. Characteristic parallel plate capacitor and cantilever devices were designed and manufactured to assess the quality of this ink and evaluate its physical, dielectric, and piezoelectric characteristics; including a comparison of behaviour between conventional silicon and biodegradable paper substrates. The printed layers were 10.7–11.2 μm thick, with acceptable surface roughness values in the range of 0.4–1.1 μm. The relative permittivity of the piezoelectric layer was 29.3. The poling parameters were optimised for the piezoelectric response, with an average longitudinal piezoelectric coefficient for samples printed on paper substrates measured as d 33, eff, paper = 13.57 ± 2.84 pC/N; the largest measured value was 18.37 pC/N on paper substrates. This approach to printable biodegradable piezoelectrics opens the way forward for fully solution-processed green piezoelectric devices.

Abstract Background Adherence to cancer screening is important for cancer survivors because they are at high risk of subsequent cancer diagnoses or recurrence. We assessed adherence to breast, cervical, and colorectal cancer‐(CRC)‐screening guidelines and evaluated demographic disparities among a population‐based sample of survivors. Methods A representative sample of Utah survivors diagnosed from 2012–2018 with any reportable invasive cancer was selected from central cancer registry records for a survey about survivorship needs. We estimated the proportion of eligible survivors adhering to U.S. Preventive Services Task Force screening guidelines and calculated risk ratios and 95% confidence intervals. Analyses were age‐adjusted and weighted to account for sample design and nonresponse. Results And 1421 survivors completed the survey (57.2% response rate). Screening adherence was 74.4% for breast, 69.4% for cervical, and 79.7% for CRC. Rural residents were more likely to adhere to breast cancer screening than urban residents (86.1% vs. 72.7%; adjusted RR = 1.19, CI = 1.05, 1.36). Higher educational attainment was associated with increased adherence to cervical and colorectal cancer screening. Younger age was associated with greater adherence to cervical cancer screening (p = 0.006) but lower adherence to CRC screening (p = 0.003). CRC screening adherence was lower among the uninsured and those without a primary care provider (45.6%) compared to those with a regular provider (83.0%; adjusted RR = 0.57, CI = 0.42, 0.79). Conclusions Surveys based on samples from central cancer registries can provide population estimates to inform cancer control. Findings demonstrate work is needed to ensure all Utah cancer survivors obtain recommended cancer screenings. Efforts should focus particularly on increasing uptake of breast and cervical cancer screening and reducing demographic disparities in CRC screening. Precis Despite high risk for subsequent cancer diagnosis, Utah cancer survivors are not all obtaining recommended breast, cervical, and colorectal cancer screenings. This presents a significant healthcare gap.

Abstract Background Recruitment of sufficient participants for clinical trials remains challenging. Primary care is an important avenue for patient recruitment but is underutilized. We developed and pilot tested a questionnaire to measure relevant barriers and facilitators to primary care providers’ involvement in recruiting patients for clinical trials. Methods Prior research informed the development of the questionnaire. The initial instrument was revised using feedback obtained from cognitive interviews. We invited all primary care providers practicing within the University of Utah Health system to complete the revised questionnaire. We used a mixed-mode design to collect paper responses via in-person recruitment and email contacts to collect responses online. Descriptive statistics, exploratory factor analysis, Cronbach’s alpha, and multivariable regression analyses were conducted. Results Sixty-seven primary care providers participated in the survey. Exploratory factor analysis suggested retaining five factors, representing the importance of clinical trial recruitment in providers’ professional identity, clinic-level interventions to facilitate referral, patient-related barriers, concerns about patient health management, and knowledge gaps. The five factors exhibited good or high internal consistency reliability. Professional identity and clinic-level intervention factors were significant predictors of providers’ intention to participate in clinical trial recruitment activities. Conclusions Results of this exploratory analysis provide preliminary evidence of the internal structure, internal consistency reliability, and predictive validity of the questionnaire to measure factors relevant to primary care providers’ involvement in clinical trial recruitment.

Abstract Background: The use of cognitive-enhancing medications and supplements among healthy adults continues to rise. Limited data exists on their use among resident physicians. Given their highly competitive and stressful lifestyle, we sought to evaluate the prevalence, motivations, and side effects of using cognitive-enhancing supplements and medications among resident physicians at a large United States academic institution. Methods: An anonymous web-based survey was circulated to resident physicians inquiring about using cognitive-enhancing supplements and medications, as well as personal characteristics such as gender, marital and parental status, medical diagnoses, and medical specialty. Before circulation, we performed a pilot study. Weighted logistic regression analyses estimated the impact of personal characteristics on the probability of using both supplements and medications. Results: Survey response rate was 46.4%. Of respondents, 48.6% were female, 45.9% were married, 70.9% were without children, and 67.2% were in a non-surgical medical specialty. Few respondents had a related medical diagnosis, with attention deficit hyperactivity disorder being the most common (7.1%). Male, non-married, surgical residents were more likely to take supplements (odds ratio (OR) = 1.06, 1.05, and 1.05). Males, without children, and those who felt pressure to perform well, were afraid of being left behind, felt pressure because colleagues take them, or felt they could not reach their current level of training without medications were more likely to take medications (OR = 1.11, 1.04, 1.05, and 1.08). Adverse effects with medications were common. Conclusion: Supplement and medication use for cognitive enhancement was high among resident physicians at a single institution despite few having a related medical diagnosis. This study raises awareness of the growing pressure in competitive residency environments to use cognitive enhancement regardless of the potential side effects.

Genetic regulatory networks (GRNs) regulate the flow of genetic information from the genome to expressed messenger RNAs (mRNAs) and thus are critical to controlling the phenotypic characteristics of cells. Numerous methods exist for profiling mRNA transcript levels and identifying protein-DNA binding interactions at the genome-wide scale. These enable researchers to determine the structure and output of transcriptional regulatory networks, but uncovering the complete structure and regulatory logic of GRNs remains a challenge. The field of GRN inference aims to meet this challenge using computational modeling to derive the structure and logic of GRNs from experimental data and to encode this knowledge in Boolean networks, Bayesian networks, ordinary differential equation (ODE) models, or other modeling frameworks. However, most existing models do not incorporate dynamic transcriptional data since it has historically been less widely available in comparison to "static" transcriptional data. We report the development of an evolutionary algorithm-based ODE modeling approach (named EA) that integrates kinetic transcription data and the theory of attractor matching to infer GRN architecture and regulatory logic. Our method outperformed six leading GRN inference methods, none of which incorporate kinetic transcriptional data, in predicting regulatory connections among TFs when applied to a small-scale engineered synthetic GRN in Saccharomyces cerevisiae. Moreover, we demonstrate the potential of our method to predict unknown transcriptional profiles that would be produced upon genetic perturbation of the GRN governing a two-state cellular phenotypic switch in Candida albicans. We established an iterative refinement strategy to facilitate candidate selection for experimentation; the experimental results in turn provide validation or improvement for the model. In this way, our GRN inference approach can expedite the development of a sophisticated mathematical model that can accurately describe the structure and dynamics of the in vivo GRN.

Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain and psychological distress. Research suggests people with FM experience increased somatosensory sensitization which generalizes to other sensory modalities and may indicate neural hyperexcitability. However, the available evidence is limited, and studies including measures of neural responsivity across sensory domains and both central and peripheral aspects of the neuraxis are lacking. Thirty-nine participants (51.5 ± 13.6 years of age) with no history of neurological disorders, psychosis, visual, auditory, or learning deficits, were recruited for this study. People with FM (N = 19) and control participants (CNT, N = 20) did not differ on demographic variables and cognitive capacity. Participants completed a task that combined innocuous auditory stimuli with electrocutaneous stimulation (ECS), delivered at individually-selected levels that were uncomfortable but not painful. Event-related potentials (ERPs) and electrodermal activity were analyzed to examine the central and sympathetic indices of neural responsivity. FM participants reported greater sensitivity to ECS and auditory stimulation, as well as higher levels of depression, anxiety, ADHD, and an array of pain-related experiences than CNT. In response to ECS, the P50 deflection was greater in FM than CNT participants, reflecting early somatosensory hyperexcitability. The P50 amplitude was positively correlated with the FM profile factor obtained with a principal component analysis. The N100 to innocuous tones and sympathetic reactivity to ECS were greater in FM participants, except in the subgroup treated with gabapentinoids, which aligns with previous evidence of symptomatic improvement with GABA-mimetic medications. These results support the principal tenet of generalized neural hyperexcitability in FM and provide preliminary mechanistic insight into the impact of GABA-mimetic pharmacological therapy on ameliorating the neural excitation dominance.

The dorsal striatum (DS) mediates the selection of actions for reward acquisition necessary for survival. Striatal pathology contributes to several neuropsychiatric conditions, including aberrant selection of actions for specific rewards in addiction. A major source of glutamate driving striatal activity is the rostral intralaminar nuclei (rILN) of the thalamus. Yet, the information that is relayed to the striatum to support action selection is unknown. Here, we discovered that rILN neurons projecting to the DS are innervated by a range of cortical and subcortical afferents and that rILN→DS neurons stably signaled at two time points in mice performing an action sequence task reinforced by sucrose reward: action initiation and reward acquisition. In vivo activation of this pathway increased the number of successful trials, whereas inhibition decreased the number of successful trials. These findings illuminate a role for the rostral intralaminar nuclear complex in reinforcing actions.

Abstract The end-Permian extinction (EPE) has been considered to be contemporaneous on land and in the oceans. However, re-examined floristic records and new radiometric ages from Gondwana indicate a nuanced terrestrial ecosystem response to EPE global change. Paleosol geochemistry and climate simulations indicate paleoclimate change likely caused the demise of the widespread glossopterid ecosystems in Gondwana. Here, we evaluate the climate response of plants to the EPE via dendrochronology snapshots to produce annual-resolution records of tree-ring growth for a succession of late Permian and early Middle Triassic fossil forests from Antarctica. Paleosol geochemistry indicates a shift in paleoclimate towards more humid conditions in the Early and early Middle Triassic relative to the late Permian. Paleosol morphology, however, supports inferences of a lack of forested ecosystems in the Early Triassic. The plant responses to this paleoclimate change were accompanied by enhanced stress during the latest Permian as determined by high-resolution paleoclimate analysis of wood growth intervals. These results suggest that paleoclimate change during the late Permian exerted significant stress on high-latitude forests, consistent with the hypothesis that climate change was likely the primary driver of the extinction of the glossopterid ecosystems.

Quantum channel correction could provide a remedy to unavoidable losses in long-distance quantum communication, but the break-even point has escaped demonstration so far. Here, the authors fill this gap using distillation by heralded amplification, followed by teleportation of entanglement.

Abstract Abdominal aortic aneurysm (AAA) formation and expansion is highly complex and multifactorial, and the improvement of animal models is an important step to enhance our understanding of AAA pathophysiology. In this study, we explore our ability to influence aneurysm growth in a topical elastase plus β-Aminopropionitrile (BAPN) mouse model by varying elastase concentration and by altering the cross-linking capability of the tissue. To do so, we assess both chronic and acute effects of elastase concentration using volumetric ultrasound. Our results suggest that the applied elastase concentration affects initial elastin degradation, as well as long-term vessel expansion. Additionally, we assessed the effects of BAPN by (1) removing it to restore the cross-linking capability of tissue after aneurysm formation and (2) adding it to animals with stable aneurysms to interrupt cross-linking. These results demonstrate that, even after aneurysm formation, lysyl oxidase inhibition remains necessary for continued expansion. Removing BAPN reduces the aneurysm growth rate to near zero, resulting in a stable aneurysm. In contrast, adding BAPN causes a stable aneurysm to expand. Altogether, these results demonstrate the ability of elastase concentration and BAPN to modulate aneurysm growth rate and severity. The findings open several new areas of investigation in a murine model that mimics many aspects of human AAA.

Background and Aims: Fecal microbiota transplant (FMT) via colonoscopy is highly effective treatment for Clostridioides difficile infection (CDI). We aimed to determine baseline patient characteristics that predict failure to respond to colonoscopy-based FMT. Methods: We evaluated adult patients who received FMT for CDI not responding to standard therapies at a single tertiary center between 2014 and 2018 in this retrospective cohort study. We defined clinical success as formed stool or C difficile–negative diarrhea at 2 months after FMT. If patients required a second FMT, follow-up was extended 2 months after repeat infusion. We performed multivariate logistic regression and a random forest model to identify variables predictive of response to FMT. Results: Clinical success was attained in 87.3% of 103 patients who underwent FMT for CDI. In the multivariate model, the odds of FMT failure for family donation compared with stool bank were odds ratio 4.13 (1.00–7.01 P = .049). Diarrhea while taking anti-CDI antibiotics was common (37.8% of patients) and did not predict failure (odds ratio 0.64, 0.19–2.11 P = .46) in the univariate model. A machine learning model to predict response using clinical factors only achieved a sensitivity of 70%, specificity of 77%, and negative predictive value of 96%. Conclusion: Colonoscopy-based FMT was highly effective for CDI, even in a population where immunosuppression and proton pump inhibitor use were common. Family stool donation was associated with FMT failure, compared with the use of a stool bank. The study suggests that the use of a stool bank may not only improve access to FMT but also its efficacy.

ABSTRACT Transposable elements (TEs) are mobile genomic sequences that encompass roughly 50% of the human genome. Class 1 TEs, or “retrotransposons,” mobilize through the production of an RNA intermediate that is then reverse transcribed to form complementary DNA (cDNA) molecules capable of genomic reinsertion. While TEs are traditionally silenced to maintain genomic integrity, the recognition of immunostimulatory cues, such as those provided by microorganisms, drastically alters host transcription to induce the differential expression of TEs. Emerging evidence demonstrates that the inducible production of TE cDNA is not an inert phenomenon but instead has been coopted by host immunity to facilitate cross talk between host and constituents of the microbiota by agonizing intrinsic antiviral receptors. Here, we demonstrate that immunostimulation of toll-like receptor 4 (TLR4) with lipopolysaccharide (LPS) and TLR5 with bacterial flagella (FLA) alters the expression of retrotransposons, such as human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs). Next, we demonstrate that reverse transcriptase inhibitor (RTi) delivery ameliorates the acute production of the proinflammatory cytokine “tumor necrosis factor alpha” (TNF-α) in response to FLA in a monocytic cell line (THP-1). Collectively, our findings demonstrate that TLR5-mediated cross talk between the host and microbiota is partially dependent on the reverse transcription (RT) of retrotransposons. IMPORTANCE The microbiota is a potent reservoir of immunostimulatory and immunosuppressive motifs that fundamentally shape host immunity. Despite broad associations between microbial composition and host immunity, the mechanisms underlying host microbiota-induced immunoregulation remain poorly defined. Here, we demonstrate a novel mechanism by which motifs overabundant during dysbiotic conditions influence host immunity through the upregulation of endogenous RT to produce motifs that agonize antiviral receptors.

AimThis systematic review aims to estimate the relationship between prenatal exposure to opioids and neurodevelopmental outcomes and examines potential sources of heterogeneity between the studies.MethodsWe searched four databases through May 21st, 2022: PubMed, Embase, PsycInfo and the Web of Science according to a specified search strings. Study inclusion criteria include: (1) cohort and case-control peer-reviewed studies published in English; (2) studies comparing neurodevelopmental outcomes among children with prenatal opioid-exposure (prescribed or used non-medically) vs. an unexposed group. Studies investigating fetal alcohol syndrome or a different primary prenatal exposure other than opioids were excluded. Two main performed data extraction using “Covidence” systematic review platform. This systematic review was conducted in accordance with PRISMA guidelines. The Newcastle-Ottawa-Scale was used for quality assessment of the studies. Studies were synthesized based on the type of neurodevelopmental outcome and the instrument used to assess neurodevelopment.ResultsData were extracted from 79 studies. We found significant heterogeneity between studies due to their use of different instruments to explore cognitive skills, motor, and behavioral outcomes among children of different ages. The other sources of heterogeneity included: procedures to assess prenatal exposure to opioids; period of pregnancy in which exposure was assessed; type of opioids assessed (non-medical, medication used for opioid use dis-order, prescribed by health professional), types of co-exposure; source of selection of prenatally exposed study participants and comparison groups; and methods to address lack of comparability between exposed and unexposed groups. Cognitive and motor skills as well as behavior were generally negatively affected by prenatal opioid exposure, but the significant heterogeneity precluded a meta-analysis.ConclusionWe explored sources of heterogeneity in the studies assessing the association between prenatal exposure to opioids and neurodevelopmental outcomes. Sources of heterogeneity included different approaches to participant recruitment as well as exposure and outcome ascertainment methods. Nonetheless, overall negative trends were observed between prenatal opioid exposure and neuro-developmental outcomes.

Abstract The primary dystonia DYT6 is caused by mutations in the transcription factor Thanatos‐associated protein 1 (THAP1). To understand THAP1’s functions, we generated mice lacking THAP1 in the nervous system. THAP1 loss causes locomotor deficits associated with transcriptional changes. Since many of the genes misregulated involve dopaminergic signaling, we pharmacologically challenged the two striatal canonical dopamine pathways: the direct, regulated by the D1 receptor, and the indirect, regulated by the D2 receptor. We discovered that depleting THAP1 specifically interferes with the D2 receptor responses, pointing to a selective misregulation of the indirect pathway in DYT6 with implications for pathogenesis and treatment.

Abstract Bio-inspired Topographically Mediated Surfaces (TMSs) based on high aspect ratio nanostructures have recently been attracting significant attention due to their pronounced antimicrobial properties by mechanically disrupting cellular processes. However, scalability of such surfaces is often greatly limited, as most of them rely on micro/nanoscale fabrication techniques. In this report, a cost-effective, scalable, and versatile approach of utilizing diamond nanotechnology for producing TMSs, and using them for limiting the spread of emerging infectious diseases, is introduced. Specifically, diamond-based nanostructured coatings are synthesized in a single-step fabrication process with a densely packed, needle- or spike-like morphology. The antimicrobial proprieties of the diamond nanospike surface are qualitatively and quantitatively analyzed and compared to other surfaces including copper, silicon, and even other diamond surfaces without the nanostructuring. This surface is found to have superior biocidal activity, which is confirmed via scanning electron microscopy images showing definite and widespread destruction of E. coli cells on the diamond nanospike surface. Consistent antimicrobial behavior is also observed on a sample prepared seven years prior to testing date. Graphical Abstract

Here we describe a publicly available environmental DNA (eDNA) sequence dataset, consisting of samples collected from a National Oceanic and Atmospheric Administration (NOAA) Great Lakes Environmental Research Laboratory (GLERL) on Lake Erie. We sequenced samples drawn from before, during, and after a 2019 Microcystis harmful algal bloom (HAB) using 3rd generation sequencing with the Oxford Nanopore MinION device. We classified the eDNA reads taxonomically, and estimated the abundances of all taxa in each sample. While the taxonomic data showed evidence of significant human and E. coli contamination, we found abundant Mycrocystis, especially in the samples drawn from bloom environments. The raw sequence data are available in the Sequence Read Archive (SRA) under accession number PRJNA812770. HABs pose a significant and increasing risk, both to human health and to the Blue Economy, and genomic approaches to early detection promise to help mitigate these risks. As such, this dataset could be of interest to freshwater ecology research teams, or any stakeholders interested in the detection and mitigation of HABs.

Abstract Background Retaining participants over time is a frequent challenge in research studies evaluating long-term health outcomes. This study’s objective was to compare the impact of prepaid and postpaid incentives on response to a six-month follow-up survey. Methods We conducted an experiment to compare response between participants randomized to receive either prepaid or postpaid cash card incentives within a multisite study of children under 15 years in age who were hospitalized for a serious, severe, or critical injury. Participants were parents or guardians of enrolled children. The primary outcome was survey response. We also examined whether demographic characteristics were associated with response and if incentive timing influenced the relationship between demographic characteristics and response. We evaluated whether incentive timing was associated with the number of calls needed for contact. Results The study enrolled 427 children, and parents of 420 children were included in this analysis. Follow-up survey response did not differ according to the assigned treatment arm, with the percentage of parents responding to the survey being 68.1% for the prepaid incentive and 66.7% with the postpaid incentive. Likelihood of response varied by demographics. Spanish-speaking parents and parents with lower income and lower educational attainment were less likely to respond. Parents of Hispanic/Latino children and children with Medicaid insurance were also less likely to respond. We found no relationship between the assigned incentive treatment and the demographics of respondents compared to non-respondents. Conclusions Prepaid and postpaid incentives can obtain similar participation in longitudinal pediatric critical care outcomes research. Incentives alone do not ensure retention of all demographic subgroups. Strategies for improving representation of hard-to-reach populations are needed to address health disparities and ensure the generalizability of studies using these results.

BackgroundMany women with HIV (WWH) have suboptimal adherence to oral antiretroviral therapy (ART) due to multilevel barriers to HIV care access and retention. A long-acting injectable (LAI) version of ART was approved by the US Food and Drug Administration in January 2021 and has the potential to overcome many of these barriers by eliminating the need for daily pill taking. However, it may not be optimal for all WWH. It is critical to develop tools that facilitate patient-provider shared decision making about oral versus LAI ART modalities to promote women’s adherence and long-term HIV outcomes. ObjectiveThis study will develop and pilot test a web-based patient decision aid called i.ART+support (i.ARTs). This decision aid aims to support shared decision making between WWH and their providers, and help women choose between oral and LAI HIV treatment. MethodsThe study will occur in 3 phases. In phase 1, we will utilize a mixed methods approach to collect data from WWH and medical and social service providers to inform i.ARTs content. During phase 2, we will conduct focus groups with WWH and providers to refine i.ARTs content and develop the web-based decision aid. In phase 3, i.ARTs will be tested in a randomized controlled trial with 180 women in Miami, Florida, and assessed for feasibility, usability, and acceptability, as well as to evaluate the associations between receiving i.ARTs and viral suppression, ART pharmacy refills, and clinic attendance. ResultsThis study was funded in March 2021. Columbia University’s IRB approved the study protocols (approval number IRB-AAAT5314). Protocols for phase 1 interviews have been developed and interviews with service providers started in September 2021. We will apply for Clinicaltrials.gov registration prior to phase 3, which is when our first participant will be enrolled in the randomized controlled trial. This is anticipated to occur in April 2023. ConclusionsThis study is the first to develop a web-based patient decision aid to support WWH choices between oral and LAI ART. Its strengths include the incorporation of both patient and provider perspectives, a mixed methods design, and implementation in a real-world clinical setting. International Registered Report Identifier (IRRID)DERR1-10.2196/35646

Differences in cannabis use patterns among racial, ethnic and sexual minoritized identity subgroups have been attributed to marginalized identity stressors. However, associations at the intersection of these minoritized identities remain underexplored in a changing medical cannabis law (MCL) context. We estimated medical cannabis and daily cannabis use, and cannabis use disorder (CUD) by intersecting racial, ethnic and sexual minoritized identity subgroups. We included 189,800 adults in the 2015–2019 National Survey on Drug Use and Health identifying as non-Hispanic white, non-Hispanic Black, or Hispanic and self-reported heterosexual, gay/lesbian, or bisexual sexual identity. We estimated the adjusted odds of past-year: (a) any medical cannabis, (b) daily cannabis use (i.e., 300 + days/year), and (c) DSM-5-proxy CUD by sexual identity, stratified by race and ethnicity. Cannabis measures were higher among sexual minoritized groups than heterosexual adults across racial and ethnic subgroups. Bisexual adults had higher odds of any medical cannabis use than their heterosexual counterparts: non-Hispanic white (6.4% vs. 1.8%; aOR = 2.6, 95% CI = [2.5–3.5]), non-Hispanic Black (4.1% vs. 1.7%; aOR = 2.7, 95% CI = [1.6–4.5]), and Hispanic adults (5.3% vs. 1.8 %; aOR = 2.6, 95% CI = [1.9–3.3]). We found heterogeneous associations with state MCL status across subgroups stratified by race and ethnicity. Bisexual adults in MCL states had higher odds of any medical cannabis use among non-Hispanic white (aOR = 2.0, 95% CI = [1.4–2.9]) and Hispanic (aOR = 3.6, 95% CI = [1.2–10.2]) adults compared to their non-MCL counterparts, but this was marginal among non-Hispanic Black bisexual adults (aOR = 1.6, 95% CI = [1.0–2.6]). Studies should assess intended and unintended cannabis policy effects among racial, ethnic, and sexual identity subgroups.

ABSTRACT Staphylococcus hominis is frequently isolated from human skin, and we hypothesize that it may protect the cutaneous barrier from opportunistic pathogens. We determined that S. hominis makes six unique autoinducing peptide (AIP) signals that inhibit the major virulence factor accessory gene regulator (agr) quorum sensing system of Staphylococcus aureus. We solved and confirmed the structures of three novel AIP signals in conditioned medium by mass spectrometry and then validated synthetic AIP activity against all S. aureus agr classes. Synthetic AIPs also inhibited the conserved agr system in a related species, Staphylococcus epidermidis. We determined the distribution of S. hominis agr types on healthy human skin and found S. hominis agr-I and agr-II were highly represented across subjects. Further, synthetic AIP-II was protective in vivo against S. aureus-associated dermonecrotic or epicutaneous injury. Together, these findings demonstrate that a ubiquitous colonizer of human skin has a fundamentally protective role against opportunistic damage. IMPORTANCE Human skin is home to a variety of commensal bacteria, including many species of coagulase-negative staphylococci (CoNS). While it is well established that the microbiota as a whole maintains skin homeostasis and excludes pathogens (i.e., colonization resistance), relatively little is known about the unique contributions of individual CoNS species to these interactions. Staphylococcus hominis is the second most frequently isolated CoNS from healthy skin, and there is emerging evidence to suggest that it may play an important role in excluding pathogens, including Staphylococcus aureus, from colonizing or infecting the skin. Here, we identified that S. hominis makes 6 unique peptide inhibitors of the S. aureus global virulence factor regulation system (agr). Additionally, we found that one of these peptides can prevent topical or necrotic S. aureus skin injury in a mouse model. Our results demonstrate a specific and broadly protective role for this ubiquitous, yet underappreciated skin commensal.

CD13, an ectoenzyme on myeloid and stromal cells, also circulates as a shed, soluble protein (sCD13) with powerful chemoattractant, angiogenic, and arthritogenic properties, which require engagement of a G protein–coupled receptor (GPCR). Here we identify the GPCR that mediates sCD13 arthritogenic actions as the bradykinin receptor B1 (B1R). Immunofluorescence and immunoblotting verified high expression of B1R in rheumatoid arthritis (RA) synovial tissue and fibroblast-like synoviocytes (FLSs), and demonstrated binding of sCD13 to B1R. Chemotaxis, and phosphorylation of Erk1/2, induced by sCD13, were inhibited by B1R antagonists. In ex vivo RA synovial tissue organ cultures, a B1R antagonist reduced secretion of inflammatory cytokines. Several mouse arthritis models, including serum transfer, antigen-induced, and local innate immune stimulation arthritis models, were attenuated in Cd13–/– and B1R–/– mice and were alleviated by B1R antagonism. These results establish a CD13/B1R axis in the pathogenesis of inflammatory arthritis and identify B1R as a compelling therapeutic target in RA and potentially other inflammatory diseases.

Abstract The resistance of pest species to chemical controls has vast ecological, economic, and societal costs. In most cases, resistance is only detected after spreading throughout an entire population. Detecting resistance in its incipient stages, by comparison, provides time to implement preventative strategies. Incipient resistance can be detected by coupling standard toxicology assays with large‐scale gene expression experiments. We apply this approach to a system where an invasive parasite, sea lamprey (Petromyzon marinus), has been treated with the highly effective pesticide 3‐trifluoromethyl‐4‐nitrophenol (TFM) for 60 years. Toxicological experiments revealed that lamprey from treated populations did not have higher survival to TFM exposure than lamprey from untreated populations, demonstrating that full‐fledged resistance has not yet evolved. In contrast, we find hundreds of genes differentially expressed in response to TFM in the population with the longest history of exposure, many of which relate to TFM’s primary mode of action, the uncoupling of oxidative phosphorylation, and subsequent depletion of ATP. Three genes critical to oxidative phosphorylation, ATP5PB, PLCB1, and NDUFA9, were nearly fixed for alternative alleles in comparisons of SNPs between treated and untreated populations (FST > 5 SD from the mean). ATP5PB encodes subunit b of ATP synthase and an additional subunit, ATP5F1B, was canalized for high expression in treated populations, but remained plastic in response to TFM treatment in individuals from the untreated population. These combined genomic and transcriptomic results demonstrate that an adaptive, genetic response to TFM is likely driving incipient resistance in a damaging pest species.

Researchers from the National Institute for Occupational Safety and Health (NIOSH) are developing a coal pillar rib rating (CPRR) technique to measure the integrity of coal ribs. The CPRR characterizes the rib composition and evaluates its impact on the inherent stability of the coal ribs. The CPRR utilizes four parameters: rib homogeneity, bedding condition, face cleat orientation with respect to entry direction, and rib height. All these parameters are measurable in the field. A rib data collecting procedure and a simple sheet to calculate the CPRR were developed. The developed CPRR can be used as a rib quality mapping tool in underground coal mines and to determine the potential of local rib instabilities and support requirements associated with overburden depth. CPRR calculations were conducted for 22 surveyed solid coal ribs, mainly composed of coal units. Based on this study, the rib performance was classified into four categories. A preliminary minimum primary rib support density (PRSD) line was obtained from these surveyed cases. Two sample cases are presented that illustrate the data collection form and CPRR calculations.

Background: Focal Electrically-Administered Seizure Therapy (FEAST) is a form of electroconvulsive therapy (ECT) that spatially focuses the electrical stimulus to initiate seizure activity in right prefrontal cortex. Two open-label non-comparative studies suggested that FEAST has reduced cognitive side effects when compared to historical data from other forms of ECT. In two different ECT clinics, we compared the efficacy and cognitive side effects of FEAST and Right Unilateral Ultrabrief Pulse (RUL-UBP) ECT. Methods: Using a non-randomized, open-label design, 39 depressed adults were recruited after referral for ECT. Twenty patients received FEAST (14 women; age 45.2 ± 12.7), and 19 received RUL-UBP ECT (16 women; age 43.2 ± 16.4). Key cognitive outcome measures were the postictal time to reorientation and the Columbia University Autobiographical Memory Interview: Short-Form (CUAMI-SF). Antidepressant effects were assessed using the Hamilton Rating Scale for Depression (HRSD24). Results: In the Intent-to-treat sample, a repeated measures mixed model suggested no between group difference in HRSD24 score over time (F1,35 = 0.82, p = 0.37), while the response rate favored FEAST (FEAST: 65%; RUL-UBP ECT: 57.9%), and the remission rate favored RUL-UBP ECT (FEAST: 35%; RUL-UBP ECT: 47.4%). The FEAST group had numeric superiority in average time to reorientation (FEAST: 6.6 ± 5.0 min; RUL-UBP ECT: 8.8 ± 5.8 min; Cohens d = 0.41), and CUAMI-SF consistency score (FEAST: 69.2 ± 14.2%; RUL-UBP ECT: 63.9 ± 9.9%; Cohens d = 0.43); findings that failed to meet statistical significance. Conclusions: FEAST exerts similar efficacy relative to an optimal form of conventional ECT and may have milder cognitive side effects. A blinded, randomized, non-inferiority trial is needed.

Abstract Patients undergoing head and neck free flap reconstruction should be evaluated for radiation‐induced venous stenosis and presence of central venous port as a potential risk for flap failure.

Background: There is a growing body of literature showing that gender discrimination impacts physicians' work and life experiences. Impact on income, promotion, and parenthood has been documented. Based on these findings, we hypothesized that the experiences of academic physicians who identify as women or gender nonconforming would be different from their counterparts who are men. This survey study explores the influences of gender on academic physicians' experiences with discrimination in life and at work. Materials and Methods: In the spring of 2017, academic physicians (n?=?752) at a medical school in the West were invited to participate in a survey that measured experiences with discrimination using the Everyday Discrimination Scale and additional items. We used a mixed-methods approach to analyze the data, employing chi square and t-tests to analyze quantitative data and modified content analysis to code open-ended responses. Results: The response rate was 24% (180/752). There was no significant difference between women and men in reported frequency of discrimination in everyday life (p?=?0.474). However, women were significantly more likely than men to select gender as a reason for being treated differently in everyday life (p?=?0.000) and report discrimination in the workplace (p?0.000). Open-ended responses describing experiences of discrimination differed based on gender: women were twice as likely than men to report receiving negative treatment owing to gender. Finally, men discussed having gender privilege, whereas women discussed experiencing gender discrimination. Conclusions: This study contributes to the growing body of literature about how gender influences the experience of practicing medicine.

Abstract Objectives To determine whether functional and anatomical outcomes following suture neurorrhaphy are improved by the addition of electrical stimulation with or without the addition of polyethylene glycol (PEG). Methods In a rat model of facial nerve injury, complete facial nerve transection and repair was performed via (a) suture neurorrhaphy alone, (b) neurorrhaphy with the addition of brief (30 minutes) intraoperative electrical stimulation, or (c) neurorrhaphy with the addition electrical stimulation and PEG. Functional recovery was assessed weekly for 16 weeks. At 16 weeks postoperatively, motoneuron survival, amount of regrowth, and specificity of regrowth were assessed by branch labeling and tissue analysis. Results The addition of brief intraoperative electrical stimulation improved all functional outcomes compared to suturing alone. The addition of PEG to electrical stimulation impaired this benefit. Motoneuron survival, amount of regrowth, and specificity of regrowth were unaltered at 16 weeks postoperative in all treatment groups. Conclusion The addition of brief intraoperative electrical stimulation to neurorrhaphy in this rodent model shows promising neurological benefit in the surgical repair of facial nerve injury. Level of Evidence Animal study.

Abstract Germline variants in tumor suppressor genes (TSGs) can result in RNA mis-splicing and predisposition to cancer. However, identification of variants that impact splicing remains a challenge, contributing to a substantial proportion of patients with suspected hereditary cancer syndromes remaining without a molecular diagnosis. To address this, we used capture RNA-sequencing (RNA-seq) to generate a splicing profile of 18 TSGs (APC, ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, and TP53) in 345 whole-blood samples from healthy donors. We subsequently demonstrated that this approach can detect mis-splicing by comparing splicing profiles from the control dataset to profiles generated from whole blood of individuals previously identified with pathogenic germline splicing variants in these genes. To assess the utility of our TSG splicing profile to prospectively identify pathogenic splicing variants, we performed concurrent capture DNA and RNA-seq in a cohort of 1000 patients with suspected hereditary cancer syndromes. This approach improved the diagnostic yield in this cohort, resulting in a 9.1% relative increase in the detection of pathogenic variants, demonstrating the utility of performing simultaneous DNA and RNA genetic testing in a clinical context.

Glycoprotein nonmetastatic melanoma protein B (GPNMB) is involved in various cell functions such as cell adhesion, migration, proliferation, and differentiation. In this study, we set forth to determine the role of GPNMB in systemic sclerosis (SSc) fibroblasts. Dermal fibroblasts were isolated from skin biopsies from healthy subjects and patients with diffuse cutaneous (dc)SSc. GPNMB was upregulated in dcSSc fibroblasts compared to normal fibroblasts, and correlated negatively with the modified Rodnan skin score. In addition, dcSSc fibroblasts secreted higher levels of soluble (s)GPNMB (147.4 ± 50.2 pg/ml vs. 84.8 ± 14.8 pg/ml, p

Background Ectopic deciduosis is a benign presence of endometrial tissue outside of the uterus during pregnancy that rarely presents with pleuropulmonary manifestations and recurrent pneumothorax. Case Description We report a 35-year-old woman at 15 weeks' gestation with a history of recurrent intrapartum right pneumothorax found to have pleural, pulmonary, and diaphragmatic lesions and a middle lobe air leak. Wedge resection of the middle lobe and mechanical pleurodesis was performed. Histopathological analysis was progesterone receptor and PAX8 positive consistent with ectopic deciduosis. Conclusion Ectopic deciduosis is a rare cause of recurrent pneumothorax in pregnancy and should be considered when evaluating these patients.

Monitoring the environment for pollution, pesticides, and pathogens is crucial for protecting human, agriculture, and overall ecosystem health. Diverse strategies ranging from physical sensors to sentinel species have been used for environmental monitoring. The European honey bee, Apis mellifera, is a globally managed pollinator that can serve as a continuous biomonitoring species. During foraging, honey bees are exposed to contaminants and pathogens and carry them to their hives where they can be detected and quantified. Although individual bees are vulnerable to environmental stressors, the honey bee colony as a whole is more resilient and can accumulate contaminants or respond to them without collapsing. This allows for long-term monitoring of the colony to map contaminants in a geographical area and study ecotoxicology gradients over space and time. In this paper, we review demonstrated and proposed uses of honey bees for environmental monitoring. We focus our discussion on heavy metals, air pollutants, pesticides, and plant pathogens that can be detected in bees and their hive materials including honey, wax, and stored pollen. We present the use of gene expression, microbiome profiling, and other high-throughput methodologies to study dose-dependent exposure and increase detection sensitivity; for example, stored pollen analysis with next generation sequencing can reveal the presence of plant viruses, fungi, and invasive species earlier than traditional detection methods. Finally, we discuss opportunities for using honey bees to monitor emerging threats such as climate change and antimicrobial resistance. This narrative review highlights the versatility and potential utility of the European honey bee as a biomonitoring species for ecosystem health.

Tumor mutation burden (TMB) is often used as a biomarker for immunogenicity and prerequisite for immune checkpoint inhibitor (ICI) therapy. However, it is becoming increasingly evident that not all tumors with high TMB respond to ICIs as expected. It has been shown that the ability of T-cells to infiltrate the tumor microenvironment and elicit a specific immune response is dependent not only on the TMB, but also on intra-tumor heterogeneity and the fraction of low-frequency subclonal mutations that make up the tumor. High intra-tumor heterogeneity leads to inefficient recognition of tumor neoantigens by T-cells due to their diluted frequency and spatial heterogeneity. Clinical studies have shown that tumors with a high degree of intra-tumor heterogeneity respond poorly to ICI therapy, and previous cytotoxic treatment may increase the intra-tumor heterogeneity and render second-line ICI therapy less effective. This paper reviews the role of ICI therapy when following chemotherapy or radiation to determine if they may be better suited as first-line therapy in patients with high TMB, low intra-tumor heterogeneity, and high PD-1, PD-L1, or CTLA-4 expression.

[This corrects the article DOI: 10.1371/journal.pone.0246298.].

Dietary protein is required to support recovery and adaptation following exercise training. While prior research demonstrates that many athletes meet total daily protein needs, intake seems to be predominantly skewed toward the evening meal. An even distribution of protein doses of ≥0.24 g/kg BW consumed throughout the course of a day is theorized to confer greater skeletal muscle anabolism outcomes compared to a skewed pattern of intake. Protein quality is also an important dietary consideration for athletes, with the amino acid leucine seemingly serving as the primary driver of the postprandial anabolic response. The present study investigates protein consumption characteristics among a cohort of NCAA D1 soccer players and evaluates differences between male and female athletes. Athletes were instructed to complete 3-day food diaries, which were subsequently analyzed and compared to UEFA expert group-issued nutrition guidelines for soccer players. Breakfast, lunch, and dinner accounted for 81.4% of the total daily dietary protein intake. Most athletes (77.8%) ingested optimum amounts of protein at dinner but not at breakfast (11.1%) or lunch (47.2%). In addition, statistically significant sex-based differences in daily dietary protein intake, meal-specific protein amounts, and protein quality measures were detected. Findings indicate suboptimal dietary protein intake practices among the collegiate soccer athletes.

The complex chemistry that occurs in star-forming regions can provide insight into the formation of prebiotic molecules at various evolutionary stages of star formation. To study this process, we present millimeter-wave interferometric observations of the neighboring hot cores W3(H _2 O) and W3(OH) carried out using the NOEMA interferometer. We have analyzed distributions of six molecules that account for most observed lines across both cores and have constructed physical parameter maps for rotational temperature, column density, and velocity field with corresponding uncertainties. We discuss the derived spatial distributions of these parameters in the context of the physical structure of the source. We propose the use of HCOOCH _3 as a new temperature tracer in W3(H _2 O) and W3(OH) in addition to the more commonly used ${\mathrm{CH}}_{3}\mathrm{CN}$ . By analyzing the physically derived parameters for each molecule across both W3(H _2 O) and W3(OH), the work presented herein further demonstrates the impact of physical environment on hot cores at different evolutionary stages.