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Abstract Type I spiral ganglion neurons are peripheral neurons essential for hearing perception. While they can be subdivided in mice based on characteristic gene expression patterns, detailed examinations of these subtypes in primates and humans are lacking. In this study, we investigated the developmental subtypes of spiral ganglion neurons in the common marmoset (Callithrix jacchus). We confirmed that Type I spiral ganglion can be divided based on the characteristic gene expression patterns of several marker genes. However, some combinations of these genes differ from those in rodents, suggesting common marmoset's suitability for advancing our understanding of human cochlear development. Additionally, identifying the essential time points for subtype specifications and subsequent maturation will aid in studying the primate-specific developmental biology of the inner ear. This could lead to new treatment strategies for hearing loss in humans and be valuable for studying age-related hearing loss, as well as designing regenerative therapies.

Abstract Background Intraoperative use of methylene blue has been shown to reduce postoperative complications and recurrence rates in adults. It has however not been assessed if these beneficial effects would also apply to pediatric pilonidal sinus disease with its high recurrence rates. We, therefore, aimed to assess its effects on complications and recurrences in our retrospective exploratory cohort study. Methods Of 55 consecutive children treated in our centre between January 2009 and December 2020, 48 were retrospectively included. We used logistic regression with a priori chosen predictors of intraoperative use of blue dyes, previous surgery for pilonidal sinus disease, and the presence of comorbidities on the composite outcome of complications and recurrence. Cramér’s V was used to explore associations between the use of blue dyes and the extent of resection. Results The median age in our cohort was 15.3 years. Five patients were below 2 years of age, and 24 (50%) of them were males. Chronic diseases were present in 13 (27%) patients, eight had previously been operated on for pilonidal sinus disease, and blue dyes were used in 34 patients (71%). Their intraoperative use was linked to the composite outcome with an odds ratio of 5.41 (95% confidence interval (CI) 1.52–25.34, P = 0.017) as were comorbidities with an odds ratio of 1.86 (95% CI 1.18–3.25, P = 0.014), but not re-do surgery (odds ratio 2.94 (95% CI 0.37 23.42, P = 0.3)). The use of blue dyes was associated with larger resections (Cramér’s V 0.556 (95% CI 0.329–0.74)). Conclusion The intraoperative use of blue dyes was negatively associated with complications and recurrences in pediatric pilonidal sinus disease. However, if blue dyes were used, the extent of resection was also larger. Larger resections had been shown before to be associated with complications and recurrences, too. This potential interaction requires further elucidation in future studies.

Abstract Introduction Demographics are important prognostic factors in malignant diseases. A nationwide analysis concerning the prognostic impact of demographics in head and neck cancer (HNC) patients (HNCP) has not been performed previously. Methods A retrospective analysis of data from the Center for Cancer Registry Data (ZfKD) and the Federal Statistical Office (Destatis) between 2002 and 2017 was performed. A total of 212′920 HNCP were included. Incidence, tumor stage, age development, sex distribution, age‐, residence‐, and diagnosis‐time‐specific survival were examined. Results Mean age of HNCP increased more rapidly than in the general population (slope coefficient: 0.29 vs. 0.20; p 70 years was found. Furthermore, an OS disadvantage was observed for East Germany compared to West Germany (median 47 vs. 60 months; p

Abstract Highly accurate real-time cochlear nerve monitoring to preserve cochlear nerve function is essential for simultaneous cochlear implantation and ipsilateral vestibular schwannoma resection. In the present study, we developed a novel real-time monitoring system that combines dorsal cochlear nucleus action potential monitoring with intracochlear stimulating electrodes (Auditory Nerve Test System, ANTS). We used this system for a case with vestibular schwannoma resection via the translabyrinthine approach. The monitoring system developed in this study detected highly reliable evoked potentials from the cochlear nerve every two seconds continuously during tumor resection. Near-total tumor resection was achieved, and cochlear implantation was performed successfully after confirming the preservation of cochlear nerve function in a case. The patient’s hearing was well compensated by cochlear implantation after surgery. Our novel method continuously achieved real-time monitoring of the cochlear nerve every two seconds during vestibular schwannoma resection. The usefulness of this monitoring system for simultaneous tumor resection and cochlear implantation was demonstrated in the present case. The system developed in this study is compatible with continuous facial nerve monitoring. This highly accurate and novel monitoring method will broaden the number of candidates for this type of surgery in the future.

Abstract Background Our aim is to evaluate LI-RADS-TR algorithm and its ability to assess the viability of TACE-treated HCC. We prospectively evaluated 100 patients with known HCC, treated with TACE and came for follow-up to assess therapy response and to plan the next step in treatment using triphasic CT study. Imaging response was evaluated according to LI-RADS-TR algorithm and compared to modified Response Evaluation Criteria in Solid Tumors (mRECIST) arterial phase hyperenhancement (APHE) criterion. Reference standard for “viable” tumors in treated observations included presence of strong tumor hyperenhancement in arterial phase and washout in the delayed phase which also shows dense accumulation of iodized oil in the target lesion. Results When equivocal observations were considered as LR-TR viable, LR-TR viable resulted in 92.31% sensitivity, 83.33% specificity and 88% accuracy. On the other side when equivocal observations were considered as LR-TR nonviable, it resulted in 84.62% while the specificity increased to 100% with increased accuracy (92%). The mRECIST criteria for viable tumors (presence of APHE) showed sensitivity of 84.62% and specificity of 75%. mRECIST and LR-TR sensitivities were the same when equivocal lesions were considered as nonviable and lower mRECIST than LR-TR when equivocal lesions were considered as viable, while specificities were higher in LR-TR viable being 100% when equivocal lesions were considered as nonviable, 83.33% when equivocal lesions were considered as viable and 75% in mRECIST-viable. Conclusions LR-TR algorithm showed good diagnostic performance compared to mRECIST, with high specificity and sensitivity when equivocal lesions were considered as nonviable, as well as improved accuracy.

IntroductionMacrophages are essential immune cells in the cochlea that contribute to inflammation, tissue repair, and homeostasis. They also play an important role in local cochlear immunity. The developmental immigration and maturation of macrophages in the cochlea have been investigated and are considered essential for normal hearing acquisition. Most of our current knowledge regarding cochlear development is based on rodent models because of the ethical challenges of using human fetal samples for research. However, inter-species differences between rodents and humans have been reported. In this study, we used a primate animal model to investigate the distributions of macrophages in the developing cochlea. The common marmoset (Callithrix jacchus), a small monkey species that inhabits the New World, was used as the model.MethodsWe investigated the distribution of macrophages in the developing cochlea of the common marmoset by performing immunohistochemical analyses of cochlear tissue from common marmoset embryos at different development stages.ResultsWe revealed detailed distribution changes in the macrophages of a primate animal model cochlea. This observation indicates that most of the changes in the general distribution of macrophages were well preserved between rodents and this primate. The distribution changes observed in the common marmoset were also compatible with observations in the human fetus; although, observations in the human fetus are limited. Our observations in this study also revealed several differences between common marmosets and rodents.ConclusionThe time course of immunological development and maturations established in this study will aid in the study of the primate-specific developmental biology of the inner ear. These observations may eventually lead to new therapeutic strategies for hearing loss in humans. In addition, understanding the immunological steady-state of the cochlea may help in the study of age- and genetic-induced hearing loss and in the design of regenerative therapies.

The wall paintings from the site of Akrotiri, Thera, are often considered to be instrumental to understanding elements of life in the Bronze Age. This is partially due to their high degree of preservation. The large-scale detail present in the scenes allows for a more detailed and nuanced understanding of the imagery that survives in glyptic art that, considered together with the surviving wall paintings, helps to better inform one’s understanding of Aegean life. Many of the iconographic elements and themes, however, remain at least partially enigmatic. This is particularly the case for Xeste 3, a cultic building at Akortiri, where the wall paintings contribute to a larger, programmatic cultic narrative. The current investigation seeks to better understand the monkeys scene from Room 2 of the first floor by deconstructing and examining each visual element via comparative analyses. They are first contextualized within the Aegean, then considered in light of Mesopotamian comparanda. This method allows for possible parallels between the monkeys from Xeste 3 and at least three priestly classes known from contemporary Mesopotamian tradition: the gala, assinnu, and kurgarrû. Each of these priestly classes belonged to the adaptable and widespread cult of Inanna, one of the most powerful and popular deities in Mesopotamia.

Abstract Leucine-rich α-2-glycoprotein 1 (LRG1) is a secreted glycoprotein that under physiological conditions is produced predominantly by the liver. In disease, its local induction promotes pathogenic neovascularisation while its inhibition leads to reduced dysfunctional angiogenesis. Here we examine the role of interleukin-6 (IL-6) in defective angiogenesis mediated by LRG1. IL-6 treatment induced LRG1 expression in endothelial cells and ex vivo angiogenesis cultures and promoted vascular growth with reduced mural cell coverage. In Lrg1 −/− explants, however, IL-6 failed to stimulate angiogenesis and vessels exhibited improved mural cell coverage. IL-6 activated LRG1 transcription through the phosphorylation and binding of STAT3 to a conserved consensus site in the LRG1 promoter, the deletion of which abolished activation. Blocking IL-6 signalling in human lung endothelial cells, using the anti-IL6 receptor antibody Tocilizumab, significantly reduced LRG1 expression. Our data demonstrate that IL-6, through STAT3 phosphorylation, activates LRG1 transcription resulting in vascular destabilisation. This observation is especially timely in light of the potential role of IL-6 in COVID-19 patients with severe pulmonary microvascular complications, where targeting IL-6 has been beneficial. However, our data suggest that a therapy directed towards blocking the downstream angiopathic effector molecule LRG1 may be of greater utility.

Abstract Background Healthcare-associated infections (HAI) are one of the gravest threats to patient safety worldwide. The importance of the hospital environment has recently been revalued in infection prevention and control. Though the literature is evolving rapidly, many institutions still do not consider healthcare environmental hygiene (HEH) very important for patient safety. The evidence for interventions in the healthcare environment on patient colonization and HAI with multidrug-resistant microorganisms (MDROs) or other epidemiologically relevant pathogens was reviewed. Methods We performed a systematic review according to the PRISMA guidelines using the PubMed and Web of Science databases. All original studies were eligible if published before December 31, 2019, and if the effect of an HEH intervention on HAI or patient colonization was measured. Studies were not eligible if they were conducted in vitro, did not include patient colonization or HAI as an outcome, were bundled with hand hygiene interventions, included a complete structural rebuild of the healthcare facility or were implemented during an outbreak. The primary outcome was the comparison of the intervention on patient colonization or HAI compared to baseline or control. Interventions were categorized by mechanical, chemical, human factors, or bundles. Study quality was assessed using a specifically-designed tool that considered study design, sample size, control, confounders, and issues with reporting. The effect of HEH interventions on environmental bioburden was studied as a secondary outcome. Findings After deduplication, 952 records were scrutinized, of which 44 were included for full text assessment. A total of 26 articles were included in the review and analyzed. Most studies demonstrated a reduction of patient colonization or HAI, and all that analyzed bioburden demonstrated a reduction following the HEH intervention. Studies tested mechanical interventions (n = 8), chemical interventions (n = 7), human factors interventions (n = 3), and bundled interventions (n = 8). The majority of studies (21/26, 81%) analyzed either S. aureus, C. difficile, and/or vancomycin-resistant enterococci. Most studies (23/26, 88%) reported a decrease of MDRO-colonization or HAI for at least one of the tested organisms, while 58% reported a significant decrease of MDRO-colonization or HAI for all tested microorganisms. Forty-two percent were of good quality according to the scoring system. The majority (21/26, 81%) of study interventions were recommended for application by the authors. Studies were often not powered adequately to measure statistically significant reductions. Interpretation Improving HEH helps keep patients safe. Most studies demonstrated that interventions in the hospital environment were related with lower HAI and/or patient colonization. Most of the studies were not of high quality; additional adequately-powered, high-quality studies are needed. Systematic registration number: CRD42020204909

Summary: BK polyomavirus (BKPyV) is an opportunistic pathogen that uses the b-series gangliosides GD1b and GT1b as entry receptors. Here, we characterize the impact of naturally occurring VP1 mutations on ganglioside binding, VP1 protein structure, and virus tropism. Infectious entry of single mutants E73Q and E73A and the triple mutant A72V-E73Q-E82Q (VQQ) remains sialic acid dependent, and all three variants acquire binding to a-series gangliosides, including GD1a. However, the E73A and VQQ variants lose the ability to infect ganglioside-complemented cells, and this correlates with a clear shift of the BC2 loop in the crystal structures of E73A and VQQ. On the other hand, the K69N mutation in the K69N-E82Q variant leads to a steric clash that precludes sialic acid binding. Nevertheless, this mutant retains significant infectivity in 293TT cells, which is not dependent on heparan sulfate proteoglycans, implying that an unknown sialic acid-independent entry receptor for BKPyV exists.

Climate change is altering patterns of temporal co-occurrence among species, such as the degree of co-flowering among plant species. Although much is known about how co-flowering affects pollination and plant reproduction, how these interactions are mediated by changes in abiotic conditions is unclear. Using a short-term field experiment based on a long-term flowering phenology dataset, we examine how changes in co-flowering between Linum lewisii and Potentilla pulcherrima affect the pollination and reproductive success of Linum in control and water addition scenarios. Linum is co-flowering less than it used to with Potentilla as the climate changes. We therefore removed Potentilla flowers to alter the degree of co-flowering from 0 to 100%; half of these plots received additional water to relieve drought stress. Linum plants experiencing less overlap with Potentilla had a higher proportion of conspecific pollen on their stigmas in both watered and unwatered plots. Plants experiencing less overlap also produced more seeds per plant, but only in the watering treatment. There was no evidence of pollen limitation of reproduction, but watered plants produced more seeds. These results show that plants that co-flowered to a lesser extent with Potentilla had enhanced reproductive output, probably because they received a higher proportion of Linum pollen, but these biotic effects were only detectable when the plants were less water-limited. This study provides empirical evidence that climate-driven changes in co-flowering can alter reproduction via competition for pollination, and that these biotic effects can be mediated by abiotic conditions.

Tumoral lesions of the temporal bone include benign or malignant tumors and congenital or inflammatory lesions. Temporal bone lesions are difficult to approach. Therefore, making a preoperative diagnosis and considering whether the lesions require treatment are necessary; if they require treatment, then the type of treatment requires consideration. These tumors cannot be observed directly and must be diagnosed based on symptoms and imaging findings. However, the differentiation of temporal bone lesions is difficult because they are rare and large in variety. In this pictorial review, we divided temporal bone lesions by location such as along the facial nerve, along the internal jugular vein, around the endolymphatic sac, in the internal auditory canal/cerebellopontine angle, petrous apex, middle ear, and mastoid, focusing on the imaging findings of temporal bone lesions. Then, we created a diagnostic flowchart that suggested that the systematic separation of imaging findings is useful for differentiation. Although it is necessary to make comprehensive judgments based on the clinical symptoms, patient background, and imaging findings to diagnose temporal bone mass lesions, capturing imaging features can be a useful differentiation method.

Abstract Background Huntington’s disease (HD) is clinically characterized by progressing motor, cognitive and psychiatric symptoms presenting as varying phenotypes within these three major symptom domains. The disease is caused by an expanded CAG repeat tract in the huntingtin gene and the pathomechanism leading to these endophenotypes is assumed to be neurodegenerative. In 2012/2013 we recruited 107 HD gene expansion carriers (HDGECs) and examined the frequency of the three cardinal symptoms and in 2017/2018 we followed up 74 HDGECs from the same cohort to describe the symptom trajectories and individual drift between the endophenotypes as well as potential predictors of progression and remission. Results We found higher age to reduce the probability of improving on psychiatric symptoms; increasing disease burden score ((CAG-35.5) * age) to increase the risk of developing cognitive impairment; increasing disease burden score and shorter education to increase the risk of motor onset while lower disease burden score and higher Mini Mental State Examination increased the probability of remaining asymptomatic. We found 23.5% (N = 8) to improve from their psychiatric symptoms. Conclusions There is no clear pattern in the development of or drift between endophenotypes. In contrast to motor and cognitive symptoms we find that psychiatric symptoms may resolve and thereby not entirely be caused by neurodegeneration. The probability of improving from psychiatric symptoms is higher in younger age and advocates for a potential importance of early treatment.

Abstract Background Inflammatory pseudotumors (IPTs) are rare, idiopathic, and inflammatory lesions that are histopathologically benign. Here, we present three cases of labyrinthine destruction caused by an IPT. Methods The first patient was a 74‐year‐old male with a mass lesion extending from the inner ear to the external ear canal. The second patient was a 62‐year‐old female with a foliated polycystic lesion in the petrous bone on the dorsal side of the left internal auditory canal. The third patient was a 68‐year‐old female with a mass extending from the inner ear to the middle ear, destroying the semicircular canal and cochlea. Results In two cases, we performed surgical resection successfully with no recurrence. In the other case, the lesion showed shrinkage after chemotherapy for colorectal cancer incidentally found during the examination process. Conclusion Surgical technique and indication for IPT should be based on the location and function of the lesion. In addition, there is room to consider pharmacotherapy as a treatment option for IPT of the temporal bone. Level of Evidence 4.

Abstract Population studies point to regional and ethnicity‐specific differences in genetic predisposition for some lysosomal storage disorders (LSDs). The aim of the study was to determine the prevalence of the three treatable forms of lysosomal storage disorders (Gaucher disease [GD], Pompe disease [PD], and Fabry disease [FD]) in a cohort of mostly urban‐dwelling individuals of African ancestry, a previously unknown genetic landscape for LSDs. Large‐scale selective multistep biochemical and genetic screening was performed in patients seeking healthcare for various health concerns. Fluorimetric enzyme assays for GD, PD, and FD were performed on dried blood spots. Targeted gene sequencing was performed on samples that showed significantly lower enzyme activities ( G; p.T158A, (b) c.503G > T; p.R168L, (c) c.1985del. Regarding FD, two subjects had pathogenic GLA mutations, and four had single nucleotide polymorphisms in the 5'UTR, previously implicated in modulating gene expression. The findings highlight a higher incidence of abnormal enzyme levels and pathogenic mutations in the target population reflecting ancestry‐based specific genotype and phenotype variations.

Abstract Background Cryoglobulins (CG) are immunoglobulins which precipitate at low temperature. The analysis of IgG subclass composition of CG is poorly reported. The aim of this study was to determine the subclasses of IgG-containing type I and mixed type II and III CG in relation to clinical manifestations. Methods Out of a previous series of 1675 patients, inclusion criteria were a cryoprecipitate > 1 mL and a total IgG > 300 mg/L. IgG subclasses were quantified by immunoturbidimetry, rheumatoid factor (RF), and C4 by immunonephelometry. Clinical parameters were collected from hospital charts. Results CG samples from 86 patients were included, 10 type I CG and 76 mixed CG. Type I CG subclasses were IgG1 (6/10) and IgG2/IgG3 (4/10), never IgG4. IgG subclass in type II vs. III CG were 73.3 ± 15.2% vs. 52.5 ± 20.7% for IgG1 (p

Cartilage conduction hearing aids (CC-HA), bone anchored hearing aids (Baha), and ADHEAR are good choices to improve hearing in patients who cannot use air conduction hearing aids because of aural atresia or continuous otorrhea. As there are many overlaps in the characteristics of these devices, we conducted a comparative trial of CC-HA, Baha, and ADHEAR. We provided patients with the opportunity to select their devices. The data of 6 patients who underwent comparative trials in our department between October 2021 and August 2022 were retrospectively examined. The gains of Baha and CC-HA outweighed those of ADHEAR. Regarding the sound localization test, there was no significant tendency for any of the hearing devices. Regarding the Glasgow Benefit Inventory, there was no clear tendency among the three devices in the quality of life evaluation. The most satisfactory model was the one subjectively chosen by the patient, regardless of the gain and score of the sound source localization test. Therefore, we believe that it is necessary to provide an opportunity for comparative trials and a consultation with each patient in the process of selecting a device.

Abstract Aim To investigate the meaning of support groups and the features of these groups that African American (AA) women view as improving adherence to high blood pressure (HBP) treatment. The study generated a conceptual model to illuminate features of these groups that influence adherence of AA women to HBP treatment. Design Qualitative research. Methods Used focus groups and open‐ended questions to obtain the views of 26 eligible AA women, recruited from South Los Angeles. Line‐by‐line review and coding of interview transcripts were done. The feedback was used to specify a conceptual model depicting the meaning of support groups. The Consolidated Criteria for the Reporting of Qualitative Research guidelines were used. Results The conceptual model depicts the meaning of support groups as information giving/knowledge sharing, emotional or psychological support, instrumental support and coaching, and facilitators and barriers to joining support groups and factors for consideration in forming these groups.

There are no established indications for facial nerve schwannoma treatment, including surgery, radiation and follow-up observation, and it is difficult to determine treatment policy uniformly. The treatment policy was examined from each treatment course. Data of patients with facial nerve schwannomas at our hospital from 1987 to 2018 were retrospectively examined. Their age, sex, clinical symptoms, tumor localization, treatment policies and outcomes were reviewed. In total, 22 patients underwent surgery and 1 patient underwent radiotherapy; 22 patients were followed up without treatment. After total resection, there were no tumor recurrences, and most patients had grade 3 or 4 postoperative facial paralysis. After subtotal resection, tumor regrowth was observed in four patients and reoperation was required in two patients. Facial nerve function was maintained in four patients and was decreased in two patients. During follow-up, six patients showed tumor growth. Only one patient had worsening facial nerve paralysis; four patients underwent facial nerve decompression owing to facial nerve paralysis during follow-up. If the tumor compresses the brain or it is prone to growth, surgery may be indicated, and when the preoperative facial nerve function is grade ≤ 3, consideration should be given to preserving facial nerve function and subtotal resection should be indicated. If the preoperative facial nerve function is grade ≥ 3, total resection with nerve grafting is an option to prevent regrowth. If there is no brain compression or tumor growth, the follow-up is a good indication, and decompression should be considered in facial nerve paralysis cases.

Cryoglobulins (CGs) are cold precipitating immunoglobulins, and hepatitis C virus (HCV) infection is its most common cause. The purpose of the study was to determine the contribution of HCV in a large cohort of CG. Biological characteristics and specificity of CGs in HCV patients were compared to non-HCV subjects. Cryoglobulin analysis included isotype, clonality, concentration, and rheumatoid factor (RF) in cryoprecipitate and serum complement and RF. This study is an extension of the study carried out on a cohort of 13,439 patients tested for CGs from all medical units, in which 1,675/13,439 (12.5%) patients had a CG, and 680/1,675 (40.6%) had HCV serology or viral load determination (HCV RNA). Among these 680 CG patients tested for HCV, 325 of 680 (47.8%) HCV patients (272 HCV RNA+ and 45 HCV RNA− patients) were compared to 355/680 (52.2%) non-HCV subjects. After a positive detection of CG, HCV status was determined only for 37.7% (256/680) of patients, allowing the diagnosis of a previously unknown HCV infection for 39.8% (102/256). Concentration of HCV RNA+ CGs (median = 80.5 mg/L) was significantly higher than that of HCV RNA− CG (median = 50.5 mg/L, p = 0.001) and HCV− CG (median = 32 mg/L, p < 0.0001). There was no difference of median CG concentration between HCV RNA− patients and non-HCV subjects. Rheumatoid factor titer was significantly higher in type II CG compared to type III CG in HCV RNA+ patients (254 ± 720 vs. 15 ± 21 IU/mL, p < 0.0001) and non-HCV subjects (333 ± 968 vs. 16.8 ± 26 IU/mL, p = 0.0004). Complement functional activity CH50 was lower in HCV RNA+ patients (36 ± 24 U/mL) and in HCV RNA− patients (32 ± 21 U/mL) than in non-HCV subjects (50 ± 25 U/mL, p = 0.001 and p = 0.004). In conclusion, HCV infection and treatment influence CG characteristics. It is essential, and far from always tested, to determine the HCV status of patients with mixed CG, and conversely to search for CG in patients with HCV infection.

Abstract Seismic tomography has revealed the existence of large‐scale velocity heterogeneities in the mantle. The interpretation of seismic velocity anomalies in terms of temperature and chemical composition is nonunique. We use geodynamic observations including gravity, plate motions, dynamic topography, and excess ellipticity of the core‐mantle boundary combined with seismic observations to investigate the thermo‐chemical structure of the mantle through joint inversions. An outstanding issue, however, is the physical connection between mantle density anomalies and the surface geodynamic observations, which requires knowledge of the mantle viscosity structure. Here we perform joint inversions assuming different viscosity profiles and examine the dependence of the results on the viscosity. We first assume that mantle heterogeneity is due to thermal variations, which places a constraint on the relation between seismic velocity and density, and we subsequently relax the constraint to allow for potential nonthermal effects. In all of our joint inversions, a nonthermal origin of density anomalies is required to explain the geodynamic data, though the amount varies with the assumed viscosity structure. A common observation is a high‐density chemical signal in the center of the large low‐shear‐velocity provinces at the base of the mantle resulting in a near neutral or slightly dense overall buoyancy there. Using the derived density models and their corresponding viscosity profiles, we also calculate instantaneous mantle flow fields. The predicted flow fields derived from joint inversions are generally similar but are quite different from flow fields using density models derived from a posteriori scaling of pure seismic tomography models.

Purpose: Our aim was to evaluate the diagnostic potential of diffusion-weighted (DW) and dynamic contrast enhanced MRI (DCE-MR) in the diagnosis and characterization of complex ovarian lesions. Patients and methods: We prospectively evaluated 59 patients with 65 complex ovarian lesions detected at US. MRI examinations were performed using a 1.5 T MRI machine. Masses were classified as benign (n = 30), borderline (n = 7) and malignant (n = 28). Regions of interest were drawn and parameters were calculated such as apparent diffusion coefficient (ADC) values for the diffusion; maximum absolute enhancement (SI-max), maximum relative enhancement (MRE), time to peak (T-max) and wash-in-rate (WIR) for the dynamic parameters. Results: There was a significant difference in ADC values (P

Abstract Background Microorganisms drive high rates of methanogenesis and carbon mineralization in wetland ecosystems. These signals are especially pronounced in the Prairie Pothole Region of North America, the tenth largest wetland ecosystem in the world. Sulfate reduction rates up to 22 μmol cm−3 day−1 have been measured in these wetland sediments, as well as methane fluxes up to 160 mg m−2 h−1—some of the highest emissions ever measured in North American wetlands. While pore waters from PPR wetlands are characterized by high concentrations of sulfur species and dissolved organic carbon, the constraints on microbial activity are poorly understood. Here, we utilized metagenomics to investigate candidate sulfate reducers and methanogens in this ecosystem and identify metabolic and viral controls on microbial activity. Results We recovered 162 dsrA and 206 dsrD sequences from 18 sediment metagenomes and reconstructed 24 candidate sulfate reducer genomes assigned to seven phyla. These genomes encoded the potential for utilizing a wide variety of electron donors, such as methanol and other alcohols, methylamines, and glycine betaine. We also identified 37 mcrA sequences spanning five orders and recovered two putative methanogen genomes representing the most abundant taxa—Methanosaeta and Methanoregulaceae. However, given the abundance of Methanofollis-affiliated mcrA sequences, the detection of F420-dependent alcohol dehydrogenases, and millimolar concentrations of ethanol and 2-propanol in sediment pore fluids, we hypothesize that these alcohols may drive a significant fraction of methanogenesis in this ecosystem. Finally, extensive viral novelty was detected, with approximately 80% of viral populations being unclassified at any known taxonomic levels and absent from publicly available databases. Many of these viral populations were predicted to target dominant sulfate reducers and methanogens. Conclusions Our results indicate that diversity is likely key to extremely high rates of methanogenesis and sulfate reduction observed in these wetlands. The inferred genomic diversity and metabolic versatility could result from dynamic environmental conditions, viral infections, and niche differentiation in the heterogeneous sediment matrix. These processes likely play an important role in modulating carbon and sulfur cycling in this ecosystem.

Summary: Competing models exist in the literature for the relationship between mutant Huntingtin exon 1 (Httex1) inclusion formation and toxicity. In one, inclusions are adaptive by sequestering the proteotoxicity of soluble Httex1. In the other, inclusions compromise cellular activity as a result of proteome co-aggregation. Using a biosensor of Httex1 conformation in mammalian cell models, we discovered a mechanism that reconciles these competing models. Newly formed inclusions were composed of disordered Httex1 and ribonucleoproteins. As inclusions matured, Httex1 reconfigured into amyloid, and other glutamine-rich and prion domain-containing proteins were recruited. Soluble Httex1 caused a hyperpolarized mitochondrial membrane potential, increased reactive oxygen species, and promoted apoptosis. Inclusion formation triggered a collapsed mitochondrial potential, cellular quiescence, and deactivated apoptosis. We propose a revised model where sequestration of soluble Httex1 inclusions can remove the trigger for apoptosis but also co-aggregate other proteins, which curtails cellular metabolism and leads to a slow death by necrosis. : Httex1 aggregation into inclusions has paradoxically been reported as either toxic or beneficial in Huntington’s disease. Ramdzan et al. define a dual mechanism of toxicity that explains this paradox. Soluble Httex1 triggers a fast death by apoptosis, whereas Httex1 inclusions invoke quiescence and redirect death to a slower necrotic pathway. Keywords: Huntington’s disease, flow cytometry, ribosome quality control, stress granule, RNA granule, P bodies, translation

Summary:. Macrodactyly is a rare and debilitating pediatric hand anomaly that has historically been treated with amputation. Recent advances in our understanding of macrodactyly have increasingly implicated the digital nerve as the underlying cause of the condition. In addition, much progress has been made toward digital salvage in treating macrodactyly. Modern techniques often advocate for digital nerve resection to prevent recurrence and treat the underlying etiology. However, little if any emphasis has been given to sensory reconstruction for purposes of protective sensation and acceptable 2-point discrimination at the volar digital pulp. We report 2 cases of macrodactyly treated with digital nerve resection and nerve allograft reconstruction of large sensory nerve gaps which show early promising sensory outcomes. There remain little if any data on the use of nerve allograft in pediatric populations, and its application in the treatment of macrodactyly. This technique permits digit salvage with the potential for improved sensory outcomes without the donor morbidity of autologous nerve harvest.

In this paper, we report a cost-effective and scalable approach to produce highly homogeneous graphene and CNT-based silicone composites with potential applications in diverse fields of research, including biosensors and wearable electronics. This approach includes the fabrication of hybrid fillers based on few-layer graphene and CNTs by water solution blending and manufacturing of graphene/CNT/PDMS composites through calendering in a three-roll mill. The influence of processing parameters, the graphene/CNT ratio, and hybrid filler loading was thoroughly investigated, and the optimal parameters for producing hybrid composites with superior electrical and mechanical properties were found. It was also confirmed that the graphene/CNT hybrid system exhibits a synergistic effect of non-covalent interactions between graphene sheets and CNT sidewalls. This synergistic effect prevents the aggregation of graphene sheets, facilitates the dispersion of graphene and CNTs in the silicone matrix, and contributes to the superior properties of hybrid composites compared to composites with either of these fillers alone.

Viruses are infectious agents that hijack the host cell machinery in order to replicate and generate progeny. Viral infection is initiated by attachment to host cell receptors, and typical viral receptors are cell-surface-borne molecules such as proteins or glycan structures. Sialylated glycans (glycans bearing sialic acids) and glycosaminoglycans (GAGs) represent major classes of carbohydrate receptors and have been implicated in facilitating viral entry for many viruses. As interactions between viruses and sialic acids have been extensively reviewed in the past, this review provides an overview of the current state of structural knowledge about interactions between non-enveloped human viruses and GAGs. We focus here on adeno-associated viruses, human papilloma viruses (HPVs), and polyomaviruses, as at least some structural information about the interactions of these viruses with GAGs is available. We also discuss the multivalent potential for GAG binding, highlighting the importance of charged interactions and positively charged amino acids at the binding sites, and point out challenges that remain in the field.

The Modified Source Multiplication method is used to determine an unknown reactivity level of a reactor from a known one if one has access to the detector counting for both levels when the reactor is fed by a constant neutron source like an Am-Be source. When available, an accelerator driven source, in continuous mode, can be useful as its intensity can be tunable and then adapted to the experimental conditions. However, in that case, the MSM technique must be extended to account for an external source whose intensity, energy and angular distributions can vary from one measurement to another. In this paper, this Modified Multi-Source Multiplication (MMSM) method is applied to measurements done during the FREYA project in the GUINEVERE facility, operated with the GENEPI-3C accelerator providing a mixture of (D,T) and (D,D) neutrons. The monitoring of these sources through the detection of the associated charged particles allows the calculation of the MMSM factors and the estimate of the reactivity values. The results are compared in different configurations with the reactivity obtained with an Am-Be source or in dynamic measurements performed with GENEPI-3C. Their excellent agreement shows the possibility of using such accelerator-based neutron sources for MSM measurements when they are correctly monitored. This is of great interest for deep sub-critical level characterization for which detector count rates per source neutrons might be low.

Three sub-critical (SC) core configurations were investigated in the VENUS-F zero power reactor coupled with the GENEPI-3C accelerator. The SC10 and SC12 were a mock-up of a MYRRHA start-up core and SC11 represented a more complex MYRRHA core loaded with various types of in-pile-sections. The sub-criticality of 11 variants of these VENUS-F cores was changed in several steps from -6$ down to -30$ using the safety and control rods. Their sub-criticalities were determined with the Source Jerk Integral (SJI) method using 11 fission chambers located all over the reactor. For the data analysis, the 8-group delayed neutron parameters from the JEFF-3.1.2 evaluated nuclear data library were used. Reliability and reproducibility of the experimental results were tested by repeating the measurements, swapping the detectors and varying the accelerator beam intensity, thus changing the detector count rates and verifying the validity of the dead time corrections. The obtained results are compared with MCNP calculations.

Many super-resolution imaging techniques use fluorescence emission intensity to obtain precise positional information, but other spectral information is ignored. Here, the authors develop a method that records the spectrum and position of single dye molecules to map the hydrophobicity of a surface.

Glioma can originate from the transformation of neural progenitor cells into glioma initiating cells. Here, the authors demonstrate the use of induced pluripotent stem cells as a suitable model for generating neural progenitor cells, which can be subsequently transformed to glioma initiating cells that are able to the generate human glioma-like tumours in mice.

The pharynx of the child may serve as a reservoir of pathogenic bacteria, including beta-haemolytic group A streptococci (GAS), which can give rise to upper airway infections and post-streptococcal diseases. The objective of this study was to determine the prevalence of beta-haemolytic Streptococcus spp. in pharyngeal samples stemming from children aged 3–14 years in Bouaké, central Côte d’Ivoire. Oropharyngeal throat swabs for microbiological culture and venous blood samples to determine the seroprevalence of antistreptolysin O antibodies (ASO) were obtained from 400 children in March 2017. Identification was carried out using conventional bacteriological methods. Serogrouping was performed with a latex agglutination test, while an immunological agglutination assay was employed for ASO titres. The mean age of participating children was 9 years (standard deviation 2.5 years). In total, we detected 190 bacteria in culture, with 109 beta-haemolytic Streptococcus isolates, resulting in an oropharyngeal carriage rate of 27.2%. Group C streptococci accounted for 82.6% of all isolates, whereas GAS were rarely found (4.6%). The ASO seroprevalence was 17.3%. There was no correlation between serology and prevalence of streptococci (p = 0.722). In conclusion, there is a high pharyngeal carriage rate of non-GAS strains in children from Bouaké, warranting further investigation.

Neutron induced reactions on oxygen have been studied with strong interest because of the uncertainties generated on the helium production in fuel and on the neutron multiplication factor in nuclear reactors [1], [2]. Still large discrepancies exist and new measurements are welcome in order to acquire new data aiming at the uncertainty reduction [3]. SCALP (Scintillating ionization Chamber for ALPha particle production in neutron induced reaction) is a new scintillating ionization chamber [4] used as an active target to measure the cross section of (n, alpha) reactions on various gaseous targets such as 19F or 16O, from the reaction threshold up to 15 MeV. It consists of an ionization chamber filled with CF4 (for fluorine measurements) or CF4+CO2(for oxygen measurements) allowing the detection of the energy deposed by the light charged particles emitted in the (n, alpha) reaction. In addition, four Photo- Multiplier Tubes detect the scintillation light produced by the interaction of the particles in the gas active volume. Taking advantage of the fast response of the scintillation, the neutron kinetic energy can be inferred by time-of-flight measurements. SCALP is then well adapted to mono-energetic neutron beams or to white neutron beams that will be delivered at the NFS Facility [5]. Because of its good resolution, SCALP discriminates different channel outputs, enabling to disentangle the different reactions [6]. We will present the performances of the SCALP detector in terms of temporal and energetic features. We will also present tests made at the GENESIS plate-form at the LPSC Grenoble [7].

Numerous domains, in fundamental research as well as in applications, require the study of reactions induced by neutrons with energies from few MeV up to few tens of MeV. Reliable measurements also are necessary to improve the evaluated databases used by nuclear transport codes. This energy range covers a large number of topics like transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors. A new facility called Neutrons For Science (NFS) is being built for this purpose on the GANIL site at Caen (France). NFS is composed of a pulsed neutron beam for time-of-flight facility as well as irradiation stations for cross-section measurements. Neutrons will be produced by the interaction of deuteron and proton beams, delivered by the SPIRAL-2 linear accelerator, with thick or thin converters made of beryllium or lithium. Continuous and quasi-mono-energetic spectra will be available at NFS up to 40 MeV. In this fast energy region, the neutron flux is expected to be up to 2 orders of magnitude higher than at other existing time-of-flight facilities. In addition, irradiation stations for neutron-, proton- and deuteron-induced reactions will allow performing cross-section measurements by the activation technique. After a description of the facility and its characteristics, the experiments to be performed in the short and medium term will be presented.

Over the past years an experimental programme has been run at the neutron beam of The Svedberg Laboratory with the aim to study light-ion production induced by 96 and 175 MeV neutrons for a wide variety of targets. The measurements have been conducted using the Medley facility which allows measurement of p, d, t, He-3 and alpha production at fixed angles (from 20 to 160 degrees in steps of 20 degrees) over a wide dynamic range. An overview of the results obtained at the now finished campaign at 96 MeV will be given. Since 2007 we have been running at 175 MeV with C, O, Si, Fe, Bi and U as target material. Preliminary results from these measurements will be shown and compared to model calculations with Talys-1.2. We also summarize the Medley measurements of elastic np and nd scattering and of angular distributions of fission fragments.