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Viral infections have already been implicated with otitis media and sudden sensorineural hearing loss. However, the pathophysiology of COVID-19 as it relates to otologic disorders is not well-defined. With the spread of SARS-CoV-2, it is important to evaluate its colonization of middle ear mucosa. Middle ear and nasal tissue samples for quantitative RT-PCR and histologic evaluations were obtained from post-mortem COVID-19 patients and non-diseased control patients. Here we present evidence that SARS-CoV-2 colonizes the middle ear epithelium and co-localizes with the primary viral receptor, angiotensin-converting enzyme 2 (ACE2). Both middle ear and nasal epithelial cells show relatively high expression of ACE2, required for SARS-CoV-2 entry. The epithelial cell adhesion molecule (EpCAM) was use as a biomarker of epithelia. Furthermore, we found that the viral load in the middle ear is lower than that present in the nasal cavity.

Background: data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. Methods: in this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18–55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (0·05 for all analyses). Interpretation: in this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Genes, sex, age, diet, lifestyle, gut microbiome, and multiple other factors affect human metabolomic profiles. Understanding metabolomic variation is critical in human nutrition research as metabolites that are sensitive to change versus those that are more stable might be more informative for a particular study design. This study aims to identify stable metabolomic regions and determine the genetic and environmental contributions to stability. Using a classic twin design, 1H nuclear magnetic resonance (NMR) urinary metabolomic profiles were measured in 128 twins at baseline, 1 month, and 2 months. Multivariate mixed models identified stable urinary metabolites with intraclass correlation coefficients ≥0.51. Longitudinal twin modeling measured the contribution of genetic and environmental influences to variation in the stable urinary NMR metabolome, comprising stable metabolites. The conservation of an individual’s stable urinary NMR metabolome over time was assessed by calculating conservation indices. In this study, 20% of the urinary NMR metabolome is stable over 2 months (intraclass correlation (ICC) 0.51–0.65). Common genetic and shared environmental factors contributed to variance in the stable urinary NMR metabolome over time. Using the stable metabolome, 91% of individuals had good metabolomic conservation indices ≥0.70. To conclude, this research identifies 20% of the urinary NMR metabolome as stable, improves our knowledge of the sources of metabolomic variation over time, and demonstrates the conservation of an individual’s urinary NMR metabolome.

To assess the speed and accuracy of a checklist user interface for the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD).A diagnostic tool formatted as a checklist was developed and compared to an existing diagnostic tool, the DC/TMD diagnsostic decision trees. Both types of tools use the DC/TMD and were tested by dental students, interns, and residents in the USA and Japan for diagnosis of hypothetical patients. The comparisons were done in a randomized, crossover, controlled, double-blinded trial.Overall, subjects using the experimental tool answered 25% more correct diagnoses (P.001) and missed 27% fewer diagnoses (P.01). They were also able to finalize their diagnoses faster than those using the control tool, in 16% less time (P.05). The difference in accuracy was more pronounced in complex cases, while the difference in speed was more pronounced in simple cases.This checklist is an alternative user interface for the DC/TMD.

Six-state amino acid recoding strategies are commonly applied to combat the effects of compositional heterogeneity and substitution saturation in phylogenetic analyses. While these methods have been endorsed from a theoretical perspective, their performance has never been extensively tested. Here, we test the effectiveness of six-state recoding approaches by comparing the performance of analyses on recoded and non-recoded data sets that have been simulated under gradients of compositional heterogeneity or saturation. In our simulation analyses, non-recoding approaches consistently outperform six-state recoding approaches. Our results suggest that six-state recoding strategies are not effective in the face of high saturation. Furthermore, while recoding strategies do buffer the effects of compositional heterogeneity, the loss of information that accompanies six-state recoding outweighs its benefits. In addition, we evaluate recoding schemes with 9, 12, 15, and 18 states and show that these consistently outperform six-state recoding. Our analyses of other recoding schemes suggest that under conditions of very high compositional heterogeneity, it may be advantageous to apply recoding using more than six states, but we caution that applying any recoding should include sufficient justification. Our results have important implications for the more than 90 published papers that have incorporated six-state recoding, many of which have significant bearing on relationships across the tree of life. [Compositional heterogeneity; Dayhoff 6-state recoding; S&R 6-state recoding; six-state amino acid recoding; substitution saturation.]

Echinometra is the most widespread genus of sea urchin and has been the focus of a wide range of studies in ecology, speciation, and reproduction. However, available genetic data for this genus are generally limited to a few select loci. Here, we present a chromosome-level genome assembly based on 10x Genomics, PacBio, and Hi-C sequencing for Echinometra sp. EZ from the Persian/Arabian Gulf. The genome is assembled into 210 scaffolds totaling 817.8 Mb with an N50 of 39.5 Mb. From this assembly, we determined that the E. sp. EZ genome consists of 2n = 42 chromosomes. BUSCO analysis showed that 95.3% of BUSCO genes were complete. Ab initio and transcript-informed gene modeling and annotation identified 29,405 genes, including a conserved Hox cluster. E. sp. EZ can be found in high-temperature and high-salinity environments, and we therefore compared E. sp. EZ gene families and transcription factors associated with environmental stress response (“defensome”) with other echinoid species with similar high-quality genomic resources. While the number of defensome genes was broadly similar for all species, we identified strong signatures of positive selection in E. sp. EZ noncoding elements near genes involved in environmental response pathways as well as losses of transcription factors important for environmental response. These data provide key insights into the biology of E. sp. EZ as well as the diversification of Echinometra more widely and will serve as a useful tool for the community to explore questions in this taxonomic group and beyond.

The late Miocene Messinian salinity crisis was an evaporitic episode that occurred throughout the Mediterranean; it concluded with a transition from hypersaline to fresher-water “lake sea” (Lago Mare) conditions prior to the Pliocene. Whereas numerous researchers propose that Lago Mare sediments accumulated in a Mediterranean-wide lake filled with Paratethyan waters, other workers reject this hypothesis. Here, to test this Paratethyan-overflow model, we develop a novel time-probabilistic approach to evaluate the distribution of precession-related deposits. We apply our methodology to 24 circum-Mediterranean sites, focusing on two previously untested parameters: the probability of preserving intrabasin precession cycles; and the similarities in interbasin preservation. Our results, which show an increase in preservation and similarity in successively younger cycles, display a trend opposite to what is expected from a flooded Mediterranean. Consequently, we conclude that Lago Mare accumulations were deposited in disconnected, shallow lacustrine environments, thereby casting doubt on the widely accepted Paratethyan-supply hypothesis.

Intracellular nucleotide binding and oligomerization domain (NOD) and Toll-like (TLR) receptors have emerged as pivotal sensors of infection. Both Nod1 and Nod2 contain a caspase activation and recruitment domain (CARD) that interacts with the adaptor protein RIP2 (receptor-interaction protein-2). This leads to ubiquitination of RIP2 and in turn to the activation of NFκB and MAPK transcription factors, to command the host defensive response against pathogenic infections. RIP2 is also activated by TLRs 2 and 4, although the mechanism of this activation is less. The role of RIP2 in otitis media (OM) pathogenesis has yet to be examined. Herein, we used in vivo animal models including C57BL/6 wild-type (WT) and RIP2−/− knockout mice inoculated in the middle ear (ME) with non-typeable Haemophilus influenzae (NTHi), a common human OM pathogen, to evaluate the expression of RIP2 and its signaling genes at the cellular level to determine the role of RIP2 in OM pathogenesis and recovery. The Nod1, Nod2, and Ripk2 genes are minimally expressed in the normal ME. However, they are strongly upregulated during acute OM, as are many genes related to RIP2 signaling. However, while signaling genes were expressed by various ME cell types, only mucosal epithelial and stromal cells expressed the NODs, RIP2, and signaling genes required for the activation of the host defensive response. Whereas WT mice clear ME bacteria and recover from OM within 5 days after infection, RIP2-deficient mice show persistent ME bacterial carriage and inflammation to at least 15 days. This includes significantly prolonged mucosal hyperplasia and ME leukocytic infiltration. Recruitment of macrophages is also delayed in comparison to WT mice. Thus, RIP2 is required to elicit a robust innate immune response that promotes bacterial clearance and increases host innate resistance. The results also identify the structural cells of the ME mucosa, as opposed to leukocytes, as the primary sites of NOD/RIP2 activity in the infected ME.

Metastatic melanoma may be included in the differential diagnosis of hyoid masses in patients with a history of melanoma. Hyoid resection is well tolerated and of diagnostic and therapeutic benefit in patients with tumors metastatic to the hyoid bone., Metastatic melanoma may be included in the differential diagnosis of hyoid massess in patients with a history of melanoma. Hyoid resection is well tolerated and of diagnostic and therapeutic benefit in patients with tumors metastatic to the hyoid bone.

Graphical abstract, Resistant starches (RS) are dietary compounds processed by the gut microbiota into metabolites, such as butyrate, that are beneficial to the host. The production of butyrate by the microbiome appears to be affected by the plant source and type of RS as well as the individual’s microbiota. In this study, we used in vitro culture and metaproteomic methods to explore individual microbiome's functional responses to RS2 (enzymatically-resistant starch), RS3 (retrograded starch) and RS4 (chemically-modified starch). Results showed that RS2 and RS3 significantly altered the protein expressions in the individual gut microbiomes, while RS4 did not result in significant protein changes. Significantly elevated protein groups were enriched in carbohydrate metabolism and transport functions of families Eubacteriaceae, Lachnospiraceae and Ruminococcaceae. In addition, Bifidobacteriaceae was significantly increased in response to RS3. We also observed taxon-specific enrichments of starch metabolism and pentose phosphate pathways corresponding to this family. Functions related to starch utilization, ABC transporters and pyruvate metabolism pathways were consistently increased in the individual microbiomes in response to RS2 and RS3. Given that these taxon-specific responses depended on the type of carbohydrate sources, we constructed a functional ecological network to gain a system-level insight of functional organization. Our results suggest that while some microbes tend to be functionally independent, there are subsets of microbes that are functionally co-regulated by environmental changes, potentially by alterations of trophic interactions.

Background There is a known significant risk of negative mental health consequences following traumatic injury, yet no standard approach to prevent psychiatric illness in trauma patients currently exists. Mindfulness-based psychotherapies have been shown to reduce symptoms of post-traumatic stress disorder, depression and anxiety and improve resiliency, however it is unknown whether a mindfulness intervention immediately following traumatic injury would lead to diminished mental health consequences. Methods Multi-system trauma patients at the University of Alberta Hospital (N = 63) and the Foothills Hospital (N = 60) were assigned to the experimental and control groups respectively. Patients in the experimental group were asked to use the guided mindfulness application “Stop, Breathe & Think” for 28 consecutive days. All patients completed the Depression Anxiety Stress Scale (DASS-21) and Connor-Davidson Resilience Scale (CD-RISC) 48 hours and 28 days following admission. An exit interview was conducted for patients in the experimental group. Results There was no significant difference in mean enrollment DASS-21 scores, mean enrollment CD-RISC scores, mean follow-up DASS-21 scores and mean follow-up CD-RISC scores between experimental and control groups. Paired t-tests of mean admission and mean follow-up DASS-21 and CD-RISC scores were not significantly different in the experimental group. Paired t-tests of mean admission and follow-up CD-RISC scores were not significantly different in the control group whereas mean followup DASS-21 scores were decreased in the control group relative to enrolment DASS-21 scores (p = 0.014). Patients reported improved mood after use of mindfulness, and most planned to continue using the therapy and would recommend it to others. Conclusion Our study did not demonstrate an objective benefit of mindfulness intervention immediately following traumatic injury. Exit interview data suggests that a web-based mindfulness intervention may be beneficial for certain trauma patients however further research is required to identify those most likely to realize substantial gains.

BackgroundOtitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility.MethodsWe performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues.ResultsA large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma.ConclusionSPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.

Extreme environmental gradients represent excellent study systems to better understand the variables that mediate patterns of genomic variation between populations. They also allow for more accurate predictions of how future environmental change might affect marine species. The Persian/Arabian Gulf is extreme in both temperature and salinity, whereas the adjacent Gulf of Oman has conditions more typical of tropical oceans. The sea urchin Echinometra sp. EZ inhabits both of these seas and plays a critical role in coral reef health as a grazer and bioeroder, but, to date, there have been no population genomic studies on this or any urchin species in this unique region. E sp. EZ’s life history traits (e.g., large population sizes, large reproductive clutches, and long life spans), in theory, should homogenize populations unless nonneutral processes are occurring. Here, we generated a draft genome and a restriction site-associated DNA sequencing data set from seven populations along an environmental gradient across the Persian/Arabian Gulf and the Gulf of Oman. The estimated genome size of E. sp. EZ was 609 Mb and the heterozygosity was among the highest recorded for an echinoderm at 4.5%. We recovered 918 high-quality SNPs from 85 individuals which we then used in downstream analyses. Population structure analyses revealed a high degree of admixture between all sites, although there was population differentiation and significant pairwise FST values between the two seas. Preliminary results suggest migration is bidirectional between the seas and nine candidate loci were identified as being under putative natural selection, including one collagen gene. This study is the first to investigate the population genomics of a sea urchin from this extreme environmental gradient and is an important contribution to our understanding of the complex spatial patterns that drive genomic divergence.

Background Otitis media (OM) is a common and potentially serious disease of childhood. Although OM is multifactorial on origin, bacterial infection is a unifying component. Many studies have established a critical role for innate immunity in bacterial clearance and OM resolution. A key component of innate immunity is the recruitment of immune and inflammatory cells, including macrophages. Methods To explore the role of macrophages in OM, we evaluated the expression of genes related to macrophage function during a complete episode of acute OM in the mouse caused by middle ear (ME) inoculation with Haemophilus influenzae. We also combined CCR2 deficiency with chlodronate liposome toxicity to deplete macrophages during OM. Results Macrophage genes were robustly regulated during OM. Moreover, macrophage depletion enhanced and prolonged the infiltration of neutrophils into the infected ME and increased the persistence of bacterial infection. Conclusions The results illustrate the critical role played by macrophages in OM resolution.

To date, genomic analyses in amoebozoans have been mostly limited to model organisms or medically important lineages. Consequently, the vast diversity of Amoebozoa genomes remain unexplored. A draft genome of Cochliopodium minus, an amoeba characterized by extensive cellular and nuclear fusions, is presented. C. minus has been a subject of recent investigation for its unusual sexual behavior. Cochliopodium’s sexual activity occurs during vegetative stage making it an ideal model for studying sexual development, which is sorely lacking in the group. Here we generate a C. minus draft genome assembly. From this genome, we detect a substantial number of lateral gene transfer (LGT) instances from bacteria (15%), archaea (0.9%) and viruses (0.7%) the majority of which are detected in our transcriptome data. We identify the complete meiosis toolkit genes in the C. minus genome, as well as the absence of several key genes involved in plasmogamy and karyogamy. Comparative genomics of amoebozoans reveals variation in sexual mechanism exist in the group. Similar to complex eukaryotes, C. minus (some amoebae) possesses Tyrosine kinases and duplicate copies of SPO11. We report a first example of alternative splicing in a key meiosis gene and draw important insights on molecular mechanism of sex in C. minus using genomic and transcriptomic data.

In the post-natal mouse cochlea, type II spiral ganglion neurons (SGNs) innervating the electromotile outer hair cells (OHCs) of the ‘cochlear amplifier' selectively express the type III intermediate filament peripherin gene (Prph). Immunolabeling showed that Prph knockout (KO) mice exhibited disruption of this (outer spiral bundle) afferent innervation, while the radial fiber (type I SGN) innervation of the inner hair cells (~95% of the SGN population) was retained. Functionality of the medial olivocochlear (MOC) efferent innervation of the OHCs was confirmed in the PrphKO, based on suppression of distortion product otoacoustic emissions (DPOAEs) via direct electrical stimulation. However, “contralateral suppression” of the MOC reflex neural circuit, evident as a rapid reduction in cubic DPOAE when noise is presented to the opposite ear in wildtype mice, was substantially disrupted in the PrphKO. Auditory brainstem response (ABR) measurements demonstrated that hearing sensitivity (thresholds and growth-functions) were indistinguishable between wildtype and PrphKO mice. Despite this comparability in sound transduction and strength of the afferent signal to the central auditory pathways, high-intensity, broadband noise exposure (108 dB SPL, 1 h) produced permanent high frequency hearing loss (24–32 kHz) in PrphKO mice but not the wildtype mice, consistent with the attenuated contralateral suppression of the PrphKO. These data support the postulate that auditory neurons expressing Prph contribute to the sensory arm of the otoprotective MOC feedback circuit.

Tinnitus has been the No. 1 disability at the Veteran Administration for the last 15 years, yet its interaction with hearing loss secondary to etiologies such as age, noise trauma, and traumatic brain injuries remains poorly characterized. Our objective was to analyze hearing loss and tinnitus, including audiogram data, of the Million Veteran Program within the context of military exposures in an aging population.Health records, questionnaires, audiograms, and military data were aggregated for 758,005 Veteran participants in the Million Veteran Program 2011 to 2020, with relative risks (RR) calculated for ancestries, sex, hearing loss and military exposures such as combat, blast, and military era served. A multivariate model with significant demographic measures and exposures was then analyzed. Next, audiogram data stratified by sex were compared for those with and without tinnitus by two methods: first, mean thresholds at standard frequencies were compared to thresholds adjusted per ISO 7029:2000E age and sex formulae. Second, levels for those ≤40 years of age were compared with those 41 and older. Finally, a proportional hazards model was examined to ascertain the timing between the onset of tinnitus and hearing loss, calculated separately for electronic health record diagnoses (ICD) and self-report.Tinnitus was either self-reported, diagnosed, or both in 37.5% (95% CI, 37.4 to 37.6), mean age 61.5 (95% CI, 61.4 to 61.5), range 18 to 112 years. Those with hearing loss were 4.15 times (95% CI, 4.12 to 4.15) as likely to have tinnitus. Americans of African descent were less likely to manifest tinnitus (RR 0.61, 95% CI, 0.60 to 0.61), as were women (RR 0.65, 95% CI, 0.64 to 0.65). A multivariate model indicated a higher RR of 1.73 for traumatic brain injury (95% CI, 1.71 to 1.73) and daily combat noise exposure (1.17, 95% CI, 1.14 to 1.17) than age (0.998, 95% CI, 0.997 to 0.998). Subjects ≤40 years of age had small but significantly elevated hearing thresholds through all standard frequencies compared to Veterans without tinnitus, and the effect of tinnitus on hearing thresholds diminished with age. In the hazard model, those40 with new onset of tinnitus were at risk for hearing loss sooner and with greater incidence than those who were younger. The rate of hearing loss following tinnitus approached 100%. In contrast, only approximately 50% of those who self-reported hearing loss initially were at risk for later hearing loss, in contrast to ICD comparison, where those with ICD of hearing loss were more likely to sustain an ICD of tinnitus subsequently.Evidence suggests that the occurrence of tinnitus in the military is more closely related to environmental exposures than to aging. The finding that tinnitus affects hearing frequencies across the audiogram spectrum suggests an acoustic injury independent of tonotopicity. Particularly for males40, tinnitus may be a harbinger of audiologic damage predictive of later hearing loss.

The Spectrometer/Telescope for Imaging X-rays (STIX) is one of six remote sensing instruments on-board Solar Orbiter. The telescope applies an indirect imaging technique that uses the measurement of 30 visibilities, i.e., angular Fourier components of the solar flare X-ray source. Hence, the imaging problem for STIX consists of the Fourier inversion of the data measured by the instrument. In this work, we show that the visibility amplitude and phase calibration of 24 out of 30 STIX sub-collimators has reached a satisfactory level for scientific data exploitation and that a set of imaging methods is able to provide the first hard X-ray images of solar flares from Solar Orbiter. Four visibility-based image reconstruction methods and one count-based are applied to calibrated STIX observations of six events with GOES class between C4 and M4 that occurred in May 2021. The resulting reconstructions are compared to those provided by an optimization algorithm used for fitting the amplitudes of STIX visibilities. We show that the five imaging methods produce results morphologically consistent with the ones provided by the Atmospheric Imaging Assembly on board the Solar Dynamic Observatory (SDO/AIA) in UV wavelengths. The χ2 values and the parameters of the reconstructed sources are comparable between methods, thus confirming their robustness., Solar Physics, 297 (7), ISSN:0038-0938, ISSN:1573-093X

Collagen X biomarker (CXM) is suggested to be a biomarker of linear growth velocity. However, early childhood data are limited. This study examines the relationship of CXM to the linear growth rate and bone development, including the possible modifying effects of vitamin D supplementation. We analyzed a cohort of 276 term-born children participating in the Vitamin D Intervention in Infants (VIDI) study. Infants received 10 μg/d (group-10) or 30 μg/d (group-30) vitamin D3 supplementation for the first 2 years of life. CXM and length were measured at 12 and 24 months of age. Tibial bone mineral content (BMC), volumetric bone mineral density (vBMD), cross-sectional area (CSA), polar moment of inertia (PMI), and periosteal circumference (PsC) were measured using peripheral quantitative computed tomography (pQCT) at 12 and 24 months. We calculated linear growth as length velocity (cm/year) and the growth rate in length (SD unit). The mean (SD) CXM values were 40.2 (17.4) ng/mL at 12 months and 38.1 (12.0) ng/mL at 24 months of age (p = 0.12). CXM associated with linear growth during the 2-year follow-up (p = 0.041) but not with bone (p = 0.53). Infants in group-30 in the highest tertile of CXM exhibited an accelerated mean growth rate in length compared with the intermediate tertile (mean difference [95% CI] −0.50 [−0.98, −0.01] SD unit, p = 0.044) but not in the group-10 (p = 0.062) at 12 months. Linear association of CXM and growth rate until 12 months was weak, but at 24 months CXM associated with both length velocity (B for 1 increment of √CXM [95% CI] 0.32 [0.12, 0.52] cm/yr, p = 0.002) and growth rate in length (0.20 [0.08, 0.32] SD unit, p = 0.002). To conclude, CXM may not reliably reflect linear growth from birth to 12 months of age, but its correlation with growth velocity improves during the second year of life.

Medusozoa is a widely distributed ancient lineage that harbors one-third of Cnidaria diversity divided into 4 classes. This clade is characterized by the succession of stages and modes of reproduction during metagenic lifecycles, and includes some of the most plastic body plans and life cycles among animals. The characterization of traditional genomic features, such as chromosome numbers and genome sizes, was rather overlooked in Medusozoa and many evolutionary questions still remain unanswered. Modern genomic DNA sequencing in this group started in 2010 with the publication of the Hydra vulgaris genome and has experienced an exponential increase in the past 3 years. Therefore, an update of the state of Medusozoa genomics is warranted. We reviewed different sources of evidence, including cytogenetic records and high-throughput sequencing projects. We focused on 4 main topics that would be relevant for the broad Cnidaria research community: (i) taxonomic coverage of genomic information; (ii) continuity, quality, and completeness of high-throughput sequencing datasets; (iii) overview of the Medusozoa specific research questions approached with genomics; and (iv) the accessibility of data and metadata. We highlight a lack of standardization in genomic projects and their reports, and reinforce a series of recommendations to enhance future collaborative research.

Defects resulting from open resection of anterior skull base neoplasms are difficult to reconstruct. Our objective was to review the literature and describe an evidence-based algorithm that can guide surgeons reconstructing anterior skull base defects.A research librarian designed database search strategies. Two investigators independently reviewed the resulting abstracts and full text articles. Studies on reconstruction after open anterior skull base resection were included. Studies of lateral and posterior skull base reconstruction, endoscopic endonasal surgery, traumatic and congenital reconstruction were excluded. Based on the review, a reconstructive algorithm was proposed.The search strategy identified 603 unique abstracts. 53 articles were included. Adjacent subsites resected, defect size, radiotherapy history, and contraindications to free tissue transfer were identified as key factors influencing decision making and were used to develop the algorithm. Discussion of the reconstructive ladder as it applies to skull base reconstruction and consideration of patient specific factors are reviewed. Patients with a prior history of radiotherapy or with simultaneous resection of multiple anatomic subsites adjacent to the anterior skull base will likely benefit from free tissue transfer.Reconstruction of anterior skull base defects requires knowledge of the available reconstructive techniques and consideration of defect-specific and patient-specific factors.

To date, genomic analyses in amoebozoans have been mostly limited to model organisms or medically important lineages. Consequently, the vast diversity of Amoebozoa genomes remain unexplored. A draft genome of Cochliopodium minus, an amoeba characterized by extensive cellular and nuclear fusions, is presented. C. minus has been a subject of recent investigation for its unusual sexual behavior. Cochliopodium’s sexual activity occurs during vegetative stage making it an ideal model for studying sexual development, which is sorely lacking in the group. Here we generate a C. minus draft genome assembly. From this genome, we detect a substantial number of lateral gene transfer (LGT) instances from bacteria (15%), archaea (0.9%) and viruses (0.7%) the majority of which are detected in our transcriptome data. We identify the complete meiosis toolkit genes in the C. minus genome, as well as the absence of several key genes involved in plasmogamy and karyogamy. Comparative genomics of amoebozoans reveals variation in sexual mechanism exist in the group. Similar to complex eukaryotes, C. minus (some amoebae) possesses Tyrosine kinases and duplicate copies of SPO11. We report a first example of alternative splicing in a key meiosis gene and draw important insights on molecular mechanism of sex in C. minus using genomic and transcriptomic data.

Purpose: Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice. Methods: We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications. We assessed PM5 at 5 stringencies with incorporation of 8 in silico tools. For each analysis, we quantified a positive likelihood ratio (pLR, true positive rate/false positive rate), the predictive value of PM5-lookup in ClinVar compared with the functional truthset. Results: pLR was 16.3 (10.6-24.9) for variants for which there was exactly 1 additional colocated deleterious variant on ClinVar, and the variant under examination was equally or more damaging when analyzed using BLOSUM62. pLR was 71.5 (37.8-135.3) for variants for which there were 2 or more colocated deleterious ClinVar variants, and the variant under examination was equally or more damaging than at least 1 colocated variant when analyzed using BLOSUM62. Conclusion: These analyses support the graded use of PM5, with potential to use it at higher evidence weighting where more stringent criteria are met.

The medial olivocochlear (MOC) efferent feedback circuit projecting to the cochlear outer hair cells (OHCs) confers protection from noise-induced hearing loss and is generally thought to be driven by inner hair cell (IHC) - type I spiral ganglion afferent (SGN) input. Knockout of the Prph gene (PrphKO) encoding the peripherin type III intermediate filament disrupted the OHC - type II SGN innervation and virtually eliminated MOC – mediated contralateral suppression from noise delivered to the opposite ear, measured as a reduction in cubic distortion product otoacoustic emissions. Electrical stimulation of the MOC pathway elicited contralateral suppression indistinguishable between wildtype (WT) and PrphKO mice, indicating that the loss of contralateral suppression was not due to disruption of the efferent arm of the circuit; IHC – type I SGN input was also normal, based on auditory brainstem responses. High-intensity, broadband noise (108 dB SPL, 1 hour) produced permanent hearing loss in PrphKO mice, but not in WT littermates. These findings associate OHC-type II input with MOC efferent - based otoprotection at loud sound levels.

Cnidocytes are the explosive stinging cells found only in cnidarians (corals, jellyfish, etc). Specialized for prey capture and defense, cnidocytes are morphologically complex and vary widely in form and function across taxa; how such diversity evolved is unknown. Using CRISPR/Cas9-mediated genome editing in the burrowing sea anemoneNematostella vectensis, we show that a single transcription factor (NvSox2) acts as a binary switch between two alternative cnidocyte fates. Knockout ofNvSox2caused a complete transformation of nematocytes (piercing cells) into spirocytes (ensnaring cells). The type of spirocyte induced byNvSox2knockout (robust spirocyte) is not normally found inN. vectensisbut is common in sea anemones from other habitats. Homeotic control of cell fate provides a mechanistic explanation for the discontinuous distribution of cnidocyte types across cnidarians and demonstrates how simple counts of cell types can underestimate biodiversity.

Objectives: This study is an evaluation of the emergency department (ED) satisfaction with the current radiologic reporting system used at a major Northeastern academic medical center. The radiology reports are the main form of communication and usually the final product of any radiological investigation delivered to clinicians. The aim of this study was to improve current radiology reporting practices and to better tailor reports to match the needs and expectations of ED clinicians. Methods: A 9-question online survey was sent to ED residents, fellows, faculty, and nurse practitioners/advanced practice providers at a major Northeastern academic medical center in the United States. For the open-ended section, coding and emergent theme categorization was conducted for quantification of responses. The survey was designed to evaluate the attitudes toward the structure, style, form, and wording used in reports. Results: The response rate was 48.6% (68/140). The ED respondents were generally satisfied with radiology reports, their language, vocabulary, and clarity. They preferred the impression section to be before the findings in simple examinations and to stratify the reports according to emergency status for complex examinations. They did not like extended differential, hedge terms, and delayed reporting. Additionally, ED respondents recommended focused, fast reporting with considerable changes toward a more standardized report. Conclusions: This evaluation delivered a list of actionable recommendations. The top recommendation is to standardize reporting structure, style, and lexicon, in addition to being focused, timely, and brief.