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Among marsupials, the endangered numbat (Myrmecobius fasciatus) is the only obligate myrmecophage with a diet comprised strictly of termites. Like many other specialised myrmecophagous mammals, numbats have a gracile and highly specialised skull morphology with an elongated rostrum and small braincase. Myrmecobiidae is one of four taxonomic families within the Australasian marsupial order Dasyuromorphia, and to date, the muscular anatomy of any member of this group is relatively poorly known. We utilised microdissection and contrast-enhanced microcomputed tomography scanning to provide the first comprehensive qualitative and quantitative descriptions of jaw muscle anatomy in numbats and quolls (Dasuyrus species). The arrangement of the jaw muscles across these species was conservative, both in gross anatomy and muscle proportions, corresponding to a 'generalised' mammalian pattern. In contrast to Dasyurus, the jaw muscles of the numbat were greatly reduced. Many aspects of the muscle anatomy of the numbat were similar to patterns reported in other myrmecophagous species, particularly a greatly reduced temporalis muscle. Unusually, the digastric muscle in the numbat was comprised of a single, large anterior belly while the posterior belly was absent. We propose that the enlarged anterior belly of the digastric may be linked to jaw stabilisation and coordination of tongue movements during feeding. The lateral insertion and fascial connection of the digastric to the tongue in numbats may also aid in distributing stress evenly across the jaw and minimise muscle fatigue. The muscle descriptions and three-dimensional models provided in this study will facilitate further analysis of musculoskeletal adaptation and evolution within the Dasyuromorphia.

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BACKGROUND: Bacteria and fungi are dynamically interconnected, leading to beneficial or antagonistic relationships with plants. Within this interkingdom interaction, the microbial community directly associated with the pathogen make up the pathobiome. While the overall soil bacterial community associated with Fusarium wilt diseases has been widely examined, the specific bacterial populations that directly interact with the Fusarium wilt pathogens are yet to be discovered. In this study, we define the bacterial community associated with the hyphae of Fusarium oxysporum f. sp. niveum race 2 (FON2). Using the 16S rRNA gene metabarcoding, we describe the hyphosphere pathobiome of three isolates of FON2. RESULTS: Our results show a core microbiome that is shared among the three tested hyphospheres. The core hyphosphere community was made up of 15 OTUs (Operational Taxonomic Units) that were associated with all three FON2 isolates. This core consisted of bacterial members of the families, Oxalobacteraceae, Propionibacteriaceae, Burkholderiaceae, Micrococcaceae, Bacillaceae, Comamonadaceae, Pseudomonadaceae and unclassified bacteria. The hyphosphere of FON2 was dominated by order Burkholderiales. While all three isolate hyphospheres were dominated by these taxa, the specific OTU differed. We also note that while the dominant OTU of one hyphosphere might not be the largest OTU for other hyphospheres, they were still present across all the three isolate hyphospheres. Additionally, in the correlation and co-occurrence analysis the most abundant OTU was negatively correlated with most of the other OTU populations within the hyphosphere. CONCLUSIONS: The study indicates a core microbiota associated with FON2. These results provide insights into the microbe-microbe dynamic of the pathogen's success and its ability to recruit a core pathobiome. Our research promotes the concept of pathogens not being lone invaders but recruits from the established host microbiome to form a pathobiome.

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People attract infants' and adults' gaze when presented on a computer screen. However, in live social situations, adults inhibit their gaze at strangers to avoid sending inappropriate social signals. Such inhibition of gaze has never been directly investigated in infants. The current preregistered study measured gaze and neural responses (EEG alpha power) to a confederate in a live social situation compared to a video of this confederate. Adults looked less at the live confederate than at the video of the confederate, although their neural responses suggest that they were overall equally attentive in both situations. Infants also looked less at the live confederate than at the video of the confederate, with similar neural response patterns. The gaze difference between live social and video situations increased with age. The study shows that young infants are already sensitive to social context and show decreased gaze to strangers in social situations. RESEARCH HIGHLIGHTS: This study shows that infants and adults look more at a video of a stranger than at a stranger that is present live in a social situation. Neural responses suggest that adults are equally attentive in both live and video situations but inhibit their gaze at the stranger in live social situations. Infants show a similar pattern of shorter gaze at a stranger who is present in person than at a video of this stranger. The study shows that gaze in infants and adults may diverge from cognitive processes measured through EEG, highlighting the importance of combining behavioural and neural measures in natural interactions.

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PURPOSE: The Oncotype DX Genomic Prostate Score (GPS) assay has been validated as a strong prognostic indicator of adverse pathology, biochemical recurrence, distant metastasis (DM), and prostate cancer (PCa)-related death (PCD) in men with localized PCa after radical prostatectomy. However, it has yet to be tested in men undergoing external beam radiation therapy (EBRT), for whom assessing PCa progression risk could inform decisions on treatment intensity. We analyzed whether GPS results are associated with time to biochemical failure (BCF), DM, and PCD after EBRT in men with localized PCa and whether the association is modified by race. METHODS AND MATERIALS: We conducted a retrospective study of men with localized PCa treated with EBRT at the VA Health Care System in Durham, NC from 2000 to 2016. Study endpoints were time to BCF per the Phoenix criteria, DM, and PCD. The association of GPS results, per 20-unit increase or dichotomous variable (0-40 vs 41-100), was evaluated with each endpoint using univariable and multivariable Cox proportional hazards models. Results were then stratified by race. RESULTS: A total of 238 patients (69% Black) met the eligibility criteria. Median follow-up for patients who did not experience BCF was 7.6 years. GPS results per 20-unit increase were significantly associated with BCF (hazard ratio [HR], 3.62; 95% confidence interval [CI], 2.59-5.02), DM (HR, 4.48; 95% CI, 2.75-7.38), and PCD (HR, 5.36; 95% CI, 3.06-9.76) in univariable analysis. GPS results remained significant in multivariable models adjusted for baseline clinical and pathological factors, with HRs being similar to the univariable analysis. There was no significant interaction between the GPS assay and race (P = .923). HRs for BCF were similar in Black men (HR, 3.88; 95% CI, 2.40-6.24) versus non-Black men (HR, 4.01; 95% CI, 2.42-6.45). CONCLUSIONS: Among men treated with EBRT, the GPS assay is a strong, independent prognostic indicator of time to BCF, DM, and PCD, and performs similarly in Black and non-Black men.

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PURPOSE: Exercise is a powerful adjunct therapy for patients diagnosed with cancer which can alleviate treatment side-effects and improve a range of outcomes including fatigue and health-related quality of life. Recently, preclinical evidence has suggested that if exercise is performed during chemotherapy infusion, there is enhanced perfusion that may improve drug delivery and attenuate the hypoxic microenvironment. This study aimed to determine the safety and feasibility of delivering an aerobic exercise intervention to cancer patients during chemotherapy infusion. METHODS: A randomised crossover trial was conducted for adults (18-60) undergoing chemotherapy treatment with non-vesicant agents for cancer. In randomised order, during two consecutive chemotherapy infusions, participants either received usual care or performed 20 min of supervised low-intensity cycling. RESULTS: Sixty-five percent of patients approached agreed to participate, and exercise was safely delivered with neither adverse events nor interference to treatment reported for all participants with a mixed cancer diagnosis (N = 10, 90% female, 51.2 ± 7.4 years). There were no significant differences between exercise and usual care in participant-reported difficulty or comfort levels, but exercise significantly reduced boredom (p = 0.01). No significant differences were detected in the symptoms experienced following either intervention. CONCLUSIONS: Exercise during chemotherapy infusion appears to be safe and feasible. Further research is required with a larger sample size to evaluate the impact on tumour perfusion, symptom experience, and opportunity for physical activity increase.

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OBJECTIVE: The aim of this study was to perform a needs assessment of pediatric (PEM) and general emergency medicine (EM) provider knowledge, comfort, and current practice patterns in the evaluation of pediatric tropical infectious diseases. METHODS: An online survey was developed based on educational priorities identified by an expert panel via modified Delphi methodology. The survey included assessment of providers' typical evaluation, diagnosis, and treatment of tropical diseases and was distributed to PEM and EM providers in 2 large professional organizations. RESULTS: A total of 333 physicians (285 PEM, 32 EM, 8 combined PEM/EM, and 8 general pediatricians in emergency department) participated. Fifty-five percent of vignettes were answered correctly. Those who trained outside the United States or Canada (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-3.0) and PEM-trained providers (OR, 2.6; 95% CI, 1.2-5.9) were more likely to answer questions correctly. Providers answered more questions correctly about dengue (76%) and tuberculosis (77%) than typhoid (53%) and malaria (39%) (OR, 3.8; 95% CI, 3.0-4.9). Diagnostic evaluation for tropical diseases was variable with greater than 75% agreement for only 2 tests: blood smears in febrile patients from Africa (86%) and bacterial stool cultures in patients with bloody stools from Africa, Asia, or Latin America (94%). Providers had low (62%) or medium (35%) comfort level with pediatric tropical diseases, and 93% were interested in accessing emergency department-specific resources. CONCLUSIONS: Pediatric EM and EM providers' knowledge and evaluation for pediatric tropical diseases are variable. Providers recognized their knowledge gaps and expressed interest in gaining access to resources and guidelines to standardize and improve evaluation and treatment of these diseases.

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Extracellular vesicles (EVs) are shed by many different cell types. Their nucleic acids content offers new opportunities for biomarker research in different solid tumors. The role of EV RNA in prostate cancer (PCa) is still largely unknown. EVs were isolated from different benign and malignant prostate cell lines and blood plasma from patients with PCa (n = 18) and controls with benign prostatic hyperplasia (BPH) (n = 7). Nanoparticle tracking analysis (NTA), Western blot, electron microscopy, and flow cytometry analysis were used for the characterization of EVs. Non-coding RNA expression profiling of PC3 metastatic PCa cells and their EVs was performed by next generation sequencing (NGS). miRNAs differentially expressed in PC3 EVs were validated with qRT-PCR in EVs derived from additional cell lines and patient plasma and from matched tissue samples. 92 miRNAs were enriched and 48 miRNAs were depleted in PC3 EVs compared to PC3 cells, which could be confirmed by qRT-PCR. miR-99b-5p was significantly higher expressed in malignant compared to benign EVs. Furthermore, expression profiling showed miR-10a-5p (p = 0.018) and miR-29b-3p (p = 0.002), but not miR-99b-5p, to be overexpressed in plasma-derived EVs from patients with PCa compared with controls. In the corresponding tissue samples, no significant differences in the miRNA expression could be observed. We thus propose that EV-associated miR-10a-5p and miR-29b-3p could serve as potential new PCa detection markers.

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Introdução. Pacientes com insuficiência cardíaca (IC) portadores de apneia obstrutiva do sono (AOS) tem taxas de morbi mortalidade elevados e o tratamento com a pressão positiva contínua nas vias aéreas (CPAP) pode reduzir estes riscos. Objetivo geral. Realizar uma revisão sistemática de ensaios clínicos randomizados sobre os efeitos da terapia por CPAP em pacientes com IC portadores de AOS. Fontes de informação. Pesquisamos as bases de dados eletrônicas PubMed, Embase, Web of Science e Lilacs nos últimos 10 anos, sem limites de linguagem. Critérios de elegibilidade. Ensaios clínicos randomizados, estudos de pacientes com IC apresentando fração de ejeção do ventrículo esquerdo (FEVE) reduzida (<50%) portadores de apneia obstrutiva do sono e que fossem tratados com CPAP. Resultados. A FEVE aumentou consideravelmente nos grupos que receberam a terapia por CPAP (média basal: 30,6%; média pós CPAP: 36,7%), assim como a saturação de oxigênio (SaO2) (média basal: 94%; média pós CPAP: 95,3%) e houve redução no índice de apneia/hipopneia (média basal: 39,6; média pós CPAP: 12,3). Conclusões. Nossa revisão sistemática de ensaios clínicos randomizados confirma que a terapia por CPAP em pacientes com IC portadores de AOS melhora variáveis preditoras de morbi mortalidade.

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Chikungunya is a mosquito-transmitted virus found primarily in Africa and Asia. In late 2013, chikungunya virus emerged in the Western hemisphere, spreading from the Caribbean to South, Central, and North America (MMWR Morb Mortal Wkly Rep. 2014;63:1121-1128). Symptoms can be similar to nonspecific viral presentations including fever, joint pain, joint swelling, and rash. The diagnosis of infectious tropical diseases in the emergency department often requires a high index of suspicion, given the nonspecific early findings that characterize many of these tropical diseases. This report presents a case of chikungunya in a pediatric patient traveling from Guatemala to the United States. Proper recognition of infection and diagnosis are vital from a public health perspective. Considering patients will remain viremic for up to a week and potentially expose local mosquitoes to infection, it is important to educate the patient on mosquito bite prevention in geographic areas of the United States where competent mosquito vectors exist as a means of avoiding further spread.

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BACKGROUND: Populus natural variants have been shown to realize a broad range of sugar yields during saccharification, however, the structural features responsible for higher sugar release from natural variants are not clear. In addition, the sugar release patterns resulting from digestion with two distinct biological systems, fungal enzymes and Clostridium thermocellum, have yet to be evaluated and compared. This study evaluates the effect of structural features of three natural variant Populus lines, which includes the line BESC standard, with respect to the overall process of sugar release for two different biological systems. RESULTS: Populus natural variants, SKWE 24-2 and BESC 876, showed higher sugar release from hydrothermal pretreatment combined with either enzymatic hydrolysis or Clostridium thermocellum fermentation compared to the Populus natural variant, BESC standard. However, C. thermocellum outperformed the fungal cellulases yielding 96.0, 95.5, and 85.9% glucan plus xylan release from SKWE 24-2, BESC 876, and BESC standard, respectively. Among the feedstock properties evaluated, cellulose accessibility and glycome profiling provided insights into factors that govern differences in sugar release between the low recalcitrant lines and the BESC standard line. However, because this distinction was more apparent in the solids after pretreatment than in the untreated biomass, pretreatment was necessary to differentiate recalcitrance among Populus lines. Glycome profiling analysis showed that SKWE 24-2 contained the most loosely bound cell wall glycans, followed by BESC 876, and BESC standard. Additionally, lower molecular weight lignin may be favorable for effective hydrolysis, since C. thermocellum reduced lignin molecular weight more than fungal enzymes across all Populus lines. CONCLUSIONS: Low recalcitrant Populus natural variants, SKWE 24-2 and BESC 876, showed higher sugar yields than BESC standard when hydrothermal pretreatment was combined with biological digestion. However, C. thermocellum was determined to be a more robust and effective biological catalyst than a commercial fungal cellulase cocktail. As anticipated, recalcitrance was not readily predicted through analytical methods that determined structural properties alone. However, combining structural analysis with pretreatment enabled the identification of attributes that govern recalcitrance, namely cellulose accessibility, xylan content in the pretreated solids, and non-cellulosic glycan extractability.

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BACKGROUND: Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium thermocellum, which combine enzyme production, hydrolysis, and fermentation are promising alternatives to historical economic challenges of using fungal enzymes for biological conversion of lignocellulosic biomass. However, limited research has integrated CBP with real pretreated biomass, and understanding how pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can provide valuable insights into CBP and suggest other novel biomass deconstruction strategies. This study focused on determining the effect of pretreatment by dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co-solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn stover and Populus with much different recalcitrance by C. thermocellum vs. fungal enzymes and changes in pretreated biomass related to these differences. RESULTS: Coupling CELF fractionation of corn stover and Populus with subsequent CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left in the pretreated solids within only 48 h without adding enzymes. These results were better than those from the conventional DA followed by either CBP or fungal enzymes or CELF followed by fungal enzyme hydrolysis, especially at viable enzyme loadings. Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated Populus solids were virtually equal, while DA improved the enzyme accessibility for corn stover more than Populus. Confocal scanning light microscopy (CSLM), transmission electron microscopy (TEM), and NMR characterization of solids from both pretreatments revealed differences in cell wall structure and lignin composition, location, coalescence, and migration-enhanced digestibility of CELF-pretreated solids. CONCLUSIONS: Adding THF to DA pretreatment (CELF) greatly enhanced deconstruction of corn stover and Populus by fungal enzymes and C. thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock recalcitrance. Composition measurements, material balances, cellulase adsorption, and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility, cell wall fractures, and cellular dislocation and cell wall delamination. Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C. thermocellum could be related to lignin removal and alteration, thereby pointing to these factors being key contributors to biomass recalcitrance as a barrier to low-cost biological conversion to sustainable fuels.

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