Search

In sub-Saharan Africa, little is known about pulmonary hypertension in left heart disease (PH-LHD). We used multivariate logistic and cox-hazard proportional regression models to examine factors associated with increased right ventricular systolic pressure (RVSP) and the effect of real-world HIV status scenarios on 6-month survival rate in the Pan African Pulmonary Hypertension Cohort (PAPUCO) study, a prospective cohort from four African countries. Exposure to biomass fuel smoke (aOR, 95%CI 3.07, 1.02–9.28), moderate to severe NYHA/FC III/IV (aOR, 95%CI 4.18, 1.01–17.38), and unknown HIV status (aOR, 95%CI 2.73, 0.96–7.73) predicted moderate to severe RVSP at the time of presentation. Six months later, HIV infection, moderate-to-severe NYHA/FC, and alcohol consumption were associated with decreased survival probabilities. Upon adjusting for HIV infection, it was observed that an incremental rise in RVSP (1 mmHg) and inter-ventricular septal thickness (1 mm) resulted in an 8% (aHR, 95%CI 1.08, 1.02–1.13) and 20% (aHR, 95%CI 1.2, 1.00–1.43) increase in the probability of mortality due to PH-LHD. In contrast, the risk of death from PH-LHD was reduced by 23% for each additional unit of BMI. (aHR, 95%CI 0.77, 0.59–1.00). In conclusion, the present study offers insights into the determinants that are notably linked to unfavorable survival outcomes in patients with pulmonary hypertension due to left heart disease. Certain factors identified in this study are readily evaluable and amenable to modification, even in settings with limited resources. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) has ten genotypes (A–J) and over 40 sub-genotypes based on the divergence of ≥ 8% and 4 to < 8% in the complete genome respectively. These genotypes and sub-genotypes influence the disease prognosis, response to therapy and route of viral transmission. Besides, infection with mixed genotypes and recombinant genotypes has also been reported. This study aimed at mapping the de novo genotypes and correlate them with the immigration trends in order to inform future research on the underlying reasons for the relative distribution of HBV genotypes from a large sample size pooled from many primary studies. Data was extracted from 59 full research articles obtained from Scopus, PubMed, EMBASE, Willy library, African Journal Online (AJOL) and Google Scholar. Studies that investigated the genotypes, sub-genotypes, mixed genotypes and recombinant were included. The Z-test and regression were used for the analysis. The study protocol is registered with PROSPERO under the registration number CRD42022300220. Overall, genotype E had the highest pooled prevalence significantly higher than all the other genotypes (P < 0.001). By region, genotype A posted the highest pooled prevalence in eastern and southern Africa, E in west Africa and D in north Africa (P < 0.0001). Regarding the emerging genotypes B and C on the African continent, genotype B was significantly higher in south Africa than C (P < 0.001). In contrast, genotype C was significantly higher in east Africa than west Africa (P < 0.0001). The A1 and D/E were the most diverse sub-genotypes and genotype mixtures respectively. Finally, we observed a general progressive decrease in the prevalence of predominant genotypes but a progressive increase in the less dominant by region. Historical and recent continental and intercontinental migrations can provide a plausible explanation for the HBV genotype distribution pattern on the African continent. [ABSTRACT FROM AUTHOR]

The Hepatitis B virus (HBV) is a highly infectious virus and is endemic in Uganda. It is one of the major etiological agents for liver diseases including liver cancer. In this work, we evaluated the prevalence of the HBV serological markers and the associated socio-demographic factors among hepatitis B surface antigen (HBsAg) seronegative persons screened during routine immunization against the virus in eastern Uganda. Data on the socio-demographic characteristics were collected using a structured questionnaire, while that on the serological markers were obtained from serum samples and evaluated by using the 5-panel HBV One Step Hepatitis B Virus Combo Test Device (FastepR, HBV-P43M). The following markers were evaluated by the panel: HBsAg, HBsAb, HBcAb, and HBeAb. Data were analyzed using SPSS (version 26), and multinomial logistic regression was used to elicit the adjusted odds ratio. All the analysis were performed at a 95% confidence limit, and a P value ≤ 0.05 was considered significant. The 424 participants included in this study were mainly female (62.3%), married (55.4%) and aged 30 years and above (54.2%). The seropositivity of the HBsAb, HBeAb, HBcAb marker prevalence rates was 48(11.3%), 73(17.2%) and 45(10.6%) respectively. The majority of the participants (327, 77.1%) did not present with any marker. Married paricipants were significantly associated with reduced HBsAb seropositvity rate, whereas young people aged 18–29 years were associated the with increased odds of HBsAb seropositivity (p < 0.05). Male participants were significantly associated with the HBeAb and HBcAb seropositivity (p < 0.05). Similarly, contact with an HBV infected person was significantly associated with HBeAb and HBcAb seropositivity (p < 0.05). Further still, blood transfusion was significantly associated with the increased risk of HBcAb seropositivity (P < 0.05). This study has revealed a prevalence of HBV serological markers among the HBsAg seronegative persons in this community and an increased risk of transmission of the virus in the community. Our findings have key consequences pertaining the interventions that are pertinent in the control and prevention of the spread of the virus among apparently health persons. [ABSTRACT FROM AUTHOR]

The most important potato viruses in Uganda are Potato virus Y (PVY), Potato leafroll virus (PLRV), Potato virus X (PVX), Potato virus S (PVS), Potato virus A (PVA) and Potato virus M (PVM). Utilization of R genes in breeding for resistance to viruses has not been explored in Uganda due to limited information on the prevalence of R genes in the available genotypes. This study aimed at identifying potato genotypes with R genes for resistance to potato viruses important in Uganda. The study screened 71 potato accessions from the National Potato Breeding Programme at Kachwekano Zonal Agricultural Research and Development Institute for the presence of resistance genes to viruses using diagnostic molecular markers. The results indicated that 21 out of 71 genotypes had resistance markers, of which nine genotypes, NKRN59.58, Derby, Markies, Sifra, 395017.229, Nakpot 5, 20108.5, Royal and 393220.54, had Ryadg gene for PVY resistance and two genotypes, Kimuri and 319919.3, had Rysto gene for resistance to PVY and PVA. Nine genotypes, 395011.2, Markies, Nakpot 5, 20108.5, Sifra, 20157.6, Royal, 2015.8 and Ambition, had the Nbtbr gene for resistance to PVX. In addition, 14 genotypes, 395011.2, Markies, Nakpot 5, Sarpouna, 393220.54, 391046.14, Sarpomira, 395077.12, Sifra, 20157.6, Royal, Ambition, Kimuri and Caruso, had the Nsadg gene conferring resistance to PVS. Four genotypes, Markies, Sifra, Nakpot 5 and Royal, had the Ryadg, Nbtbr and Nsadg genes for combined resistance to PVY, PVX and PVS. The resistant genotypes could be used as parents to introgress resistance genes into susceptible cultivars. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that tumor-driving alterations are often different among gliomas that originated from different brain regions and have underscored the importance of analyzing molecular characteristics of gliomas stratified by brain region. Therefore, to elucidate molecular characteristics of diffuse cerebellar gliomas (DCGs), 27 adult, mostly glioblastoma cases were analyzed. Comprehensive analysis using whole-exome sequencing, RNA sequencing, and Infinium methylation array ( n = 17) demonstrated their distinct molecular profile compared to gliomas in other brain regions. Frequent mutations in chromatin-modifier genes were identified including, noticeably, a truncating mutation in SETD2 ( n = 4), which resulted in loss of H3K36 trimethylation and was mutually exclusive with H3F3A K27M mutation ( n = 3), suggesting that epigenetic dysregulation may lead to DCG tumorigenesis. Alterations that cause loss of p53 function including TP53 mutation ( n = 9), PPM1D mutation ( n = 2), and a novel type of PPM1D fusion ( n = 1), were also frequent. On the other hand, mutations and copy number changes commonly observed in cerebral gliomas were infrequent. DNA methylation profile analysis demonstrated that all DCGs except for those with H3F3A mutations were categorized in the 'RTK I (PDGFRA)' group, and those DCGs had a gene expression signature that was highly associated with PDGFRA. Furthermore, compared with the data of 315 gliomas derived from different brain regions, promoter methylation of transcription factors genes associated with glial development showed a characteristic pattern presumably reflecting their tumor origin. Notably, SOX10, a key transcription factor associated with oligodendroglial differentiation and PDGFRA regulation, was up-regulated in both DCG and H3 K27M-mutant diffuse midline glioma, suggesting their developmental and biological commonality. In contrast, SOX10 was silenced by promoter methylation in most cerebral gliomas. These findings may suggest potential tailored targeted therapy for gliomas according to their brain region, in addition to providing molecular clues to identify the region-related cellular origin of DCGs. [ABSTRACT FROM AUTHOR]

Euwallacea spp. (Coleoptera: Scolytidae) are polyphagous globally distributed invasive ambrosia beetles. One of the species was recently detected attacking Ricinus communis growing in Coffea canephora gardens in Uganda. This study was undertaken to: (a) determine the distribution, incidence, and relative abundance of Euwallacea sp. on R. communis in Uganda; (b) determine the influence of the presence of C. canephora on the incidence and abundance of Euwallacea sp. on R. communis; and (c) identify ambrosia fungus of Euwallacea sp. on R. communis. Five C. canephora farms with R. communis and five others with R. communis but without C. canephora were sampled in each of the six districts surveyed. Incidence of Euwallacea sp. on R. communis was measured, by inspecting the host trees in each farm for the presence or absence of the pest. Abundance of Euwallacea sp. on R. communis was estimated, by counting holes of Euwallacea sp. at the lower 1.7 m of R. communis stems. A fungus was isolated from galleries of Euwallacea sp. on R. communis and identified. Results show that Euwallacea sp. was present on R. communis in all districts surveyed, with 30–70% of the farms infested in each district and 5–28 holes of Euwallacea sp. found on each sampled stem of R. communis. Coffea canephora appeared to facilitate the infestation of R. communis by Euwallacea sp., although it did not seem to influence the multiplication of the insect inside the host. Cunninghamella echinulata appeared to be the ambrosia fungus associated with Euwallacea sp. Therefore, Euwallacea sp. is a threat to many economically important plants in Uganda that are known to be hosts of this pest. [ABSTRACT FROM AUTHOR]

Major oxide, trace element and volatile (HO, CO, S, F, and Cl) compositions have been analyzed for olivine-hosted melt inclusions in eight basalt samples from Yellowstone National Park and the Snake River Plain (SRP) to identify the least differentiated melt compositions and assess the volatile budget of the Yellowstone hotspot. Melt-inclusion chemistry was evaluated to understand potential overprinting effects in the shallow mantle and crust of magmas derived from deeper levels. Maximum water concentrations of 3.3 wt% and CO up to 1,677 ppm have been observed in olivine-hosted melt inclusions from the Gerritt Basalts at Mesa Falls, Idaho (SRP region), which is significantly higher than the maximum concentrations measured in lavas from other hotspots such as Hawaii (~0.8-0.9 wt%). Maximum water concentrations were generally observed in the least differentiated melt inclusions in terms of incompatible major oxide concentrations, indicating that high water concentrations are characteristic of the mantle or perhaps lower crust rather than resulting from differentiation enhancement within the shallow crust, even taking into account the fact that water behaves as an incompatible element during crystal fractionation. Enrichment in Ba coupled with depletion in Th in many of the melt inclusions and their host rocks is a characteristic of many arc lavas and may indicate that volatiles in Yellowstone-Snake River Plain basalts could have a subduction zone origin. [ABSTRACT FROM AUTHOR]

We propose an alternative breeding methodology for common buckwheat ( Fagopyrum esculentum Moench), involving the use of the self-compatibility ( S h) gene derived from F. homotropicum Ohnishi. This methodology involves inbred development of homostyle ( S h S h) and pin ( ss) lines by using the self-compatibility gene ( S h). Further, single-cross hybrid seeds are produced using these inbred homostyle and pin lines as pollen and seed parents, respectively. This strategy successfully produced self-compatible homostyle hybrids ( S h s); the percentage of hybrid plants among the progeny was more than 90%. In a greenhouse trial, the heterosis (best parent) in top dry weight, including stem and leaves, was 29.1–48.1% during the early growth stage. The seed yield of the progeny obtained in single-cross experiments was superior to that of an open-pollinated standard variety “Kitawasesoba” by 10% on average. These results suggest that heterosis breeding can be used to increase seed yield in common buckwheat. [ABSTRACT FROM AUTHOR]

Hot water treatment was applied to Tartary buckwheat (var. ‘Hokkai T8’) for emasculation. Apical clusters of flower buds were soaked in a constant temperature water bath (42–44°C) in the afternoon and then the flowers which opened in the next morning were used for the investigation of self-fertilization and the artificial pollination. Hand pollination was carried out by rubbing the anthers taken from the male parent (var. ‘Hokkai T10’) to the stigma of the flowers treated by hot water. The seed set by self-fertilization was almost 0% when treated at 42°C for 8 min or more, at 43°C for 5 min or more and at 44°C for 3 min or more. With artificial pollination, the best performance was obtained when treated at 44°C for 3 min, in which the seed set was 55.1% and the matured seed was obtained 37.7% of the hand-pollinated flowers. Nine out of 26 progeny seedlings emerged and the cotyledonal color of them were all reddish green, probably indicating the hybrid of ‘Hokkai T8’ and ‘Hokkai T10’. The hybridization was reconfirmed by the segregation in F2. The hot water treatment at 44°C for 3 min was available to other seven varieties. From 24.5% to 100% of the hand-pollinated flowers set mature seeds though only one self-fertilized seed remained without artificial pollinations. This hot water treatment must be practically useful in hybridization breeding of Tartary buckwheat. [ABSTRACT FROM AUTHOR]

An origin of the Tinaquillo Peridotite Complex in northern Venezuela, and a model for the tectonic framework of the boundary zone between the southern Caribbean Plate margin and the South American Plate (SAP) during Late Jurassic to Mid-Cretaceous time are developed using newly measured Sr, Nd, Pb and Hf isotopic compositions as well as major and trace element geochemistry for some hornblendite veins and their spinel peridotite host rocks. Depleted geochemical characteristics, principally major element concentrations, and Nd and Hf isotopes (e.g., εNd = + 27; εHf = +50; ca. 3.4 Ga-Nd model age) of the Tinaquillo peridotites suggest a genetic link between this complex and the Guiana Shield farther to the south within Venezuela. Scattered zones within the Tinaquillo peridotite were overprinted by what we interpret as channelized hydrous fluids (<∼3%) derived from the eastward-dipping subduction of the Farallon Plate beneath the SAP in the Late Jurassic, leading to modification of the original Sr, Nd and Hf isotopic compositions as well as the incompatible element concentrations. The hornblendite veins have Sr, Nd, Pb and Hf isotopic compositions, falling within the range of present-day Pacific/Atlantic MORB, but trace element abundance patterns with combinations of arc- and MORB-like characteristics. These results rule out the possibility of local melting of the host peridotites to produce magmas from which the hornblendite veins formed. We suggest that during inception of the westward-dipping subduction of the Protocaribbean Plate immediately following polarity reversal in the Mid-Cretaceous, melts infiltrated the mantle lithosphere and produced the veins. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the thermal characteristics of Mg1− XCaXFe2O4 ferrite powder by applying AC magnetic field and to predict the effect of thermal coagulation in vivo. We found that heating characteristics of the ferrite powder became greater as the frequency through the 400 kHz to 700 kHz range. The highest heat generation was attained using 7–15 nm ferrite powder. We also carried out a heat transfer simulation in which we were able to demonstrate that this material has sufficient heat generating characteristics to thermally coagulate a tumor cell and that it is possible to predict the range of the coagulation from the present simulation. [ABSTRACT FROM AUTHOR]

Provides information on a study which examined comprehensive gene expression profiles of oligodendroglial tumors using the oligonucleotide microarray. Composition of oligodendrogliomas; Discovery in neuro-oncology; Marker separating oligodendrogliomas into subgroups; Keys to investigate the molecular biologic features of tumor cells.

Purpose: We aimed to evaluate the effect of deep learning-based reconstruction (DLR) on high-spatial-resolution three-dimensional T2-weighted fast asymmetric spin-echo (HR-3D T2-FASE) imaging in the preoperative evaluation of cerebellopontine angle (CPA) tumors. Methods: This study included 13 consecutive patients who underwent preoperative HR-3D T2-FASE imaging using a 3 T MRI scanner. The reconstruction voxel size of HR-3D T2-FASE imaging was 0.23 × 0.23 × 0.5 mm. The contrast-to-noise ratios (CNRs) of the structures were compared between HR-3D T2-FASE images with and without DLR. The observers' preferences based on four categories on the tumor side on HR-3D T2-FASE images were evaluated. The facial nerve in relation to the tumor on HR-3D T2-FASE images was assessed with reference to intraoperative findings. Results: The mean CNR between the tumor and trigeminal nerve and between the cerebrospinal fluid and trigeminal nerve was significantly higher for DLR images than non-DLR-based images (14.3 ± 8.9 vs. 12.0 ± 7.6, and 66.4 ± 12.0 vs. 53.9 ± 8.5, P < 0.001, respectively). The observer's preference for the depiction and delineation of the tumor, cranial nerves, vessels, and location relation on DLR HR-3D T2FASE images was superior to that on non-DLR HR-3D T2FASE images in 7 (54%), 6 (46%), 6 (46%), and 6 (46%) of 13 cases, respectively. The facial nerves around the tumor on HR-3D T2-FASE images were visualized accurately in five (38%) cases with DLR and in four (31%) without DLR. Conclusion: DLR HR-3D T2-FASE imaging is useful for the preoperative assessment of CPA tumors. [ABSTRACT FROM AUTHOR]

Examines the findings of a study on the isotopic characteristics of the upper mantle xenolith from Wikieup in Arizona, including abundant composite xenoliths, bearing evidence of magmatic modification. Description of the xenoliths; What did mineral and whole rock composition show; Methodology used to conduct the study.

Purpose: Leptomeningeal enhancement (LME) suggests leptomeningeal dissemination (LMD) of tumor cells, which is a complication of end-stage glioblastoma, and is associated with a poor prognosis. However, magnetic resonance imaging (MRI) occasionally indicates the disappearance of peri-brainstem LME after surgical resection of glioblastoma. Since preoperative LMD may affect treatment indications, we aimed to analyze the clinical significance of preoperative LME of the brainstem in glioblastoma. Methods: We retrospectively collected clinical and radiological data from consecutive patients with glioblastoma and preoperative LME of the brainstem, who were treated at our hospital between 2017 and 2020. Results: Among 112 patients with glioblastoma, nine (8%) showed preoperative LME of the brainstem. In comparison with tumors without LME, tumor size was significantly associated with the preoperative LME of the brainstem (p = 0.016). In addition, there was a trend toward significance for a relationship between deep tumor location and preoperative LME of the brainstem (p = 0.058). Notably, among six patients who underwent surgical resection for glioblastoma with LME of the brainstem, four showed significant radiological disappearance of the LME on postoperative MRI. This suggests that the LME did not result from LMD in these cases. Moreover, these four patients lived longer than would be expected from the presence of LMD. However, this LME disappearance was not observed after biopsy or chemoradiotherapy. Conclusions: These findings suggest that preoperative LME does not necessarily indicate the presence of untreatable LMD; moreover, LME may disappear after surgical tumor resection. Thus, transient preoperative LME could be attributed to other mechanisms, including impaired venous flow due to intratumoral arteriovenous shunts, which can be resolved by reducing the tumor burden. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to assess the effect of super-resolution deep learning-based reconstruction (SR-DLR), which uses k-space properties, on image quality of intracranial time-of-flight (TOF) magnetic resonance angiography (MRA) at 3 T. Methods: This retrospective study involved 35 patients who underwent intracranial TOF-MRA using a 3-T MRI system with SR-DLR based on k-space properties in October and November 2022. We reconstructed MRA with SR-DLR (matrix = 1008 × 1008) and MRA without SR-DLR (matrix = 336 × 336). We measured the signal-to-noise ratio (SNR), contrast, and contrast-to-noise ratio (CNR) in the basilar artery (BA) and the anterior cerebral artery (ACA) and the sharpness of the posterior cerebral artery (PCA) using the slope of the signal intensity profile curve at the half-peak points. Two radiologists evaluated image noise, artifacts, contrast, sharpness, and overall image quality of the two image types using a 4-point scale. We compared quantitative and qualitative scores between images with and without SR-DLR using the Wilcoxon signed-rank test. Results: The SNRs, contrasts, and CNRs were all significantly higher in images with SR-DLR than those without SR-DLR (p < 0.001). The slope was significantly greater in images with SR-DLR than those without SR-DLR (p < 0.001). The qualitative scores in MRAs with SR-DLR were all significantly higher than MRAs without SR-DLR (p < 0.001). Conclusion: SR-DLR with k-space properties can offer the benefits of increased spatial resolution without the associated drawbacks of longer scan times and reduced SNR and CNR in intracranial MRA. [ABSTRACT FROM AUTHOR]

Childhood HBV immunization remains globally fundamental to the elimination of hepatitis B virus (HBV). However, monitoring proportions of HBV vaccine seroprotection and their determinants among African Pediatric recipients is crucial. This study sought to verify extent of immune protection accorded by the HBV vaccine in African children of up to 17 years of age by pooling the prevalence of seroprotection reported by primary studies conducted in the Northern, Western, and Southern African regions. We included 19 eligible articles out of the 197 initially downloaded, published from 1999 to 2021 from African Journals Online (AJOL), EMBASE, Scopus, and PubMed. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO), University of York Centre for Reviews and Dissemination, under the registration number CRD42022361277. Significantly higher (p < 0.0001) proportion of HBV vaccine seroprotection (69.07%) was found among children under 15 years of age than children 15–17 years (32.368%), 95% CI [34.2454–39.0847%]. Whereas successful integration of the HBV vaccine on the extended programs on immunizations (EPI) has been a major achievement in the reduction of HBV infection in Africa, markedly reduced HBV vaccine seroprotection is persistently demonstrated among adolescent children 15–17 years of age. Future studies are required to clarify the need for booster dose vaccination in most at risk populations and age groups. [ABSTRACT FROM AUTHOR]

The physical and chemical structure of activated carbon (AC) varies with the carbonization temperature, activation process and time. The texture and toughness of the starting raw material also determine the morphology of AC produced. The Brunauer-Emmet-Teller surface area (SBET) is small for AC produced at low temperatures but increases from 500 to 700 °C, and generally drops in activated carbons synthesized > 700 °C. Mild chemical activators and low activator concentrations tend to generate AC with high SBET compared to strong and concentrated oxidizing chemicals, acids and bases. Activated carbon from soft starting materials such as cereals and mushrooms have larger SBET approximately twice that of tough materials such as stem berks, shells and bones. The residual functional groups observed in AC vary widely with the starting material and tend to reduce under extreme carbonization temperatures and the use of highly concentrated chemical activators. Further, the adsorption capacity of AC shows dependency on the size of the adsorbate where large organic molecules such as methylene blue are highly adsorbed compared to relatively small adsorbates such as phenol and metal ions. Adsorption also varies with adsorbate concentration, temperature and other matrix parameters. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the influence of super-resolution deep learning-based reconstruction (SR-DLR), which utilizes k-space data, on the quality of images and the quantitation of the apparent diffusion coefficient (ADC) for diffusion-weighted images (DWI) in brain magnetic resonance imaging (MRI). Methods: A retrospective analysis was performed on 34 patients who had undergone DWI using a 3 T MRI system with SR-DLR reconstruction based on k-space data in August 2022. DWI was reconstructed with SR-DLR (Matrix = 684 × 684) and without SR-DLR (Matrix = 228 × 228). Measurements were made of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) in white matter (WM) and grey matter (GM), and the full width at half maximum (FWHM) of the septum pellucidum. Two radiologists assessed image noise, contrast, artifacts, blur, and the overall quality of three image types using a four-point scale. Quantitative and qualitative scores between images with and without SR-DLR were compared using the Wilcoxon signed-rank test. Results: Images with SR-DLR showed significantly higher SNRs and CNRs than those without SR-DLR (p < 0.001). No statistically significant variances were found in the apparent diffusion coefficients (ADCs) in WM and GM between images with and without SR-DLR (ADC in WM, p = 0.945; ADC in GM, p = 0.235). Moreover, the FWHM without SR-DLR was notably lower compared to that with SR-DLR (p < 0.001). Conclusion: SR-DLR has the potential to augment the quality of DWI in DL MRI scans without significantly impacting ADC quantitation. [ABSTRACT FROM AUTHOR]

Objectives: As a novel follow-up method for intracranial aneurysms treated with stent-assisted coil embolization (SACE), we developed four-dimensional magnetic resonance angiography (MRA) with minimized acoustic noise utilizing ultrashort-echo time (4D mUTE-MRA). We aimed to assess whether 4D mUTE-MRA is useful for the evaluation of intracranial aneurysms treated with SACE. Methods: This study included 31 consecutive patients with intracranial aneurysm treated with SACE who underwent 4D mUTE-MRA at 3 T and digital subtraction angiography (DSA). For 4D mUTE-MRA, five dynamic MRA images with a spatial resolution of 0.5 × 0.5 × 0.5 mm3 were obtained every 200 ms. Two readers independently reviewed the 4D mUTE-MRA images to evaluate the aneurysm occlusion status (total occlusion, residual neck, and residual aneurysm) and the flow in the stent using a 4-point scale (from 1 [not visible] to 4 [excellent]). The interobserver and intermodality agreement was assessed using κ statistics. Results: On DSA images, 10 aneurysms were classified as total occlusion, 14 as residual neck, and 7 as residual aneurysm. In terms of aneurysm occlusion status, the intermodality and interobserver agreement was excellent (κ = 0.92 and κ = 0.96, respectively). For the flow in the stents on 4D mUTE-MRA, the mean score was significantly higher for single stents than multiple stents (p <.001) and for open-cell type stents than closed-cell type (p <.01). Conclusions: 4D mUTE-MRA is a useful tool with a high spatial and temporal resolution for the evaluation of intracranial aneurysms treated with SACE. Key Points: • In the evaluation of intracranial aneurysms treated with SACE on 4D mUTE-MRA and DSA, the intermodality and interobserver agreement in aneurysm occlusion status was excellent. • 4D mUTE-MRA shows good to excellent visualization of flow in the stents, especially for cases treated with a single or open-cell stent. • 4D mUTE-MRA can provide hemodynamic information related to embolized aneurysms and the distal arteries to stented parent arteries. [ABSTRACT FROM AUTHOR]

Introduction: Perinatal depression is common among women living with HIV, but depression care is limited in low-resource settings. We examined (1) characteristics of women receiving Problem Solving Therapy (PST) versus antidepressant therapy (ADT), (2) treatment response by modality, and (3) correlates of treatment response. Methods: This analysis used data from 191 Ugandan women in the intervention arm of a cluster randomized controlled trial of task-shifted, stepped-care depression treatment for pregnant women living with HIV (PWLWH). Treatment response was defined as scoring < 5 on the nine-item Patient Health Questionnaire (PHQ-9). Bivariate analysis and multivariable logistic regression were used to examine characteristics of women by treatment group and correlates of treatment response. Results: Of 134 participants with depression, 129 (96%) were treated: 84 (65%) received PST and 45 (35%) received ADT. Severe depression at treatment initiation was more common in those receiving ADT (28.9% versus 4.8%, Fischer's Exact Test < 0.001). Treatment response was higher for PST (70/84; 83.3%) than ADT (30/45; 66.7%; p =.03). ADT side effects were rare and minor; no infants had serious congenital defects. Of 22 participants (19%) who did not respond to treatment, only five received intensified management. Social support and interpersonal violence were associated with treatment response (adjusted odds ratio, [aOR] = 3.06, 95% CI = 1.08–8.66 and aOR = 0.64, 95% CI = 0.44–0.93). Discussion: Both depression treatment modalities yielded high response rates in Ugandan PWLWH; ADT was well-tolerated. Our results highlight a need to build capacity to implement the stepped-care protocol for non-responders and screen for social support and interpersonal violence. Significance: What is Already Known on this Subject?Prior research has demonstrated the feasibility and effectiveness of delivering collaborative care for depression in low-resource settings including Uganda. What this Study adds?Both Problem-Solving Therapy and antidepressant therapy yielded high treatment response rates among pregnant women living with HIV in Uganda who met criteria for depression, and antidepressant therapy was well tolerated. This study highlights a need to build capacity to implement the task-shifted stepped-care protocol for women whose depression does not respond to initial treatment, and to screen for social support and interpersonal violence. [ABSTRACT FROM AUTHOR]

We have previously reported that 12p gain may predict the presence of malignant components and poor prognosis for CNS germ cell tumor (GCT). Recently, 3p25.3 gain was identified as an independent predictor of poor prognosis for testicular GCT. Eighty-one CNS GCTs were analyzed. Copy number was calculated using methylation arrays. Five cases (6.2%) showed 3p25.3 gain, but only among the 40 non-germinomatous GCTs (NGGCTs) (5/40, 12.5%; p = 0.03). Among NGGCTs, those with a yolk sac tumor component showed a significantly higher frequency of 3p25.3 gain (18.2%) than those without (1.5%; p = 0.048). NGGCTs with gain showed significantly shorter progression-free survival (PFS) than those without (p = 0.047). The 3p25.3 gain and 12p gain were independent from each other. The combination of 3p25.3 gain and/or 12p gain was more frequent among NGGCTs with malignant components (69%) than among those without (29%; p = 0.02). Germinomas containing a higher number of copy number alterations showed shorter PFS than those with fewer (p = 0.03). Taken together, a finding of 3p25.3 gain may be a copy number alteration specific to NGGCTs and in combination with 12p gain could serve as a marker of negative prognosis or treatment resistance. Germinoma with frequent chromosomal instability may constitute an unfavorable subgroup. [ABSTRACT FROM AUTHOR]

Background: Brain perivascular macrophages (PVMs) are potential treatment targets for subarachnoid hemorrhage (SAH), and previous studies revealed that their depletion by clodronate (CLD) improved outcomes after experimental SAH. However, the underlying mechanisms are not well understood. Therefore, we investigated whether reducing PVMs by CLD pretreatment improves SAH prognosis by inhibiting posthemorrhagic impairment of cerebral blood flow (CBF). Methods: In total, 80 male Sprague–Dawley rats received an intracerebroventricular injection of the vehicle (liposomes) or CLD. Subsequently, the rats were categorized into the prechiasmatic saline injection (sham) and blood injection (SAH) groups after 72 h. We assessed its effects on weak and severe SAH, which were induced by 200- and 300-µL arterial blood injections, respectively. In addition, neurological function at 72 h and CBF changes from before the intervention to 5 min after were assessed in rats after sham/SAH induction as the primary and secondary end points, respectively. Results: CLD significantly reduced PVMs before SAH induction. Although pretreatment with CLD in the weak SAH group provided no additive effects on the primary end point, rats in the severe SAH group showed significant improvement in the rotarod test. In the severe SAH group, CLD inhibited acute reduction of CBF and tended to decrease hypoxia-inducible factor 1α expression. Furthermore, CLD reduced the number of PVMs in rats subjected to sham and SAH surgery, although no effects were observed in oxidative stress and inflammation. Conclusions: Our study proposes that pretreatment with CLD-targeting PVMs can improve the prognosis of severe SAH through a candidate mechanism of inhibition of posthemorrhagic CBF reduction. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the image quality of deep learning–based reconstruction (DLR), model-based (MBIR), and hybrid iterative reconstruction (HIR) algorithms for lower-dose (LD) unenhanced head CT and compare it with those of standard-dose (STD) HIR images. Methods: This retrospective study included 114 patients who underwent unenhanced head CT using the STD (n = 57) or LD (n = 57) protocol on a 320-row CT. STD images were reconstructed with HIR; LD images were reconstructed with HIR (LD-HIR), MBIR (LD-MBIR), and DLR (LD-DLR). The image noise, gray and white matter (GM-WM) contrast, and contrast-to-noise ratio (CNR) at the basal ganglia and posterior fossa levels were quantified. The noise magnitude, noise texture, GM-WM contrast, image sharpness, streak artifact, and subjective acceptability were independently scored by three radiologists (1 = worst, 5 = best). The lesion conspicuity of LD-HIR, LD-MBIR, and LD-DLR was ranked through side-by-side assessments (1 = worst, 3 = best). Reconstruction times of three algorithms were measured. Results: The effective dose of LD was 25% lower than that of STD. Lower image noise, higher GM-WM contrast, and higher CNR were observed in LD-DLR and LD-MBIR than those in STD (all, p ≤ 0.035). Compared with STD, the noise texture, image sharpness, and subjective acceptability were inferior for LD-MBIR and superior for LD-DLR (all, p < 0.001). The lesion conspicuity of LD-DLR (2.9 ± 0.2) was higher than that of HIR (1.2 ± 0.3) and MBIR (1.8 ± 0.4) (all, p < 0.001). Reconstruction times of HIR, MBIR, and DLR were 11 ± 1, 319 ± 17, and 24 ± 1 s, respectively. Conclusion: DLR can enhance the image quality of head CT while preserving low radiation dose level and short reconstruction time. Key Points: • For unenhanced head CT, DLR reduced the image noise and improved the GM-WM contrast and lesion delineation without sacrificing the natural noise texture and image sharpness relative to HIR. • The subjective and objective image quality of DLR was better than that of HIR even at 25% reduced dose without considerably increasing the image reconstruction times (24 s vs. 11 s). • Despite the strong noise reduction and improved GM-WM contrast performance, MBIR degraded the noise texture, sharpness, and subjective acceptance with prolonged reconstruction times relative to HIR, potentially hampering its feasibility. [ABSTRACT FROM AUTHOR]

Background: The preservation of the anterior choroidal artery (AChA) is essential for avoiding neurological sequelae after mesial temporal lobe epilepsy (mTLE) surgery. The purpose of this study is to reveal the anatomical variation in which the perforating branches arise from the plexal segment of the AChA by using a modern neuroimaging modality. Methods: This study analyzed 3D rotational angiography (3DRA) images from 56 subjects. The AChA and perforating branches were visualized using slab MIP. We analyzed branching patterns, courses of the perforating arteries arising from the plexal segment of the AChA, and the anastomosis of the AChA with other cerebral arteries. Results: The slab MIP applied to 3DRA visualized one or more perforating branches from the AChA in 92.9% of cases. The presence of perforating branches arising from the AChA plexal segment was 17.3%. Most of the branching points of plexal perforators were likely located in the operative field during hippocampal resection. The course of the AChA plexal perforators included the posterior limb of the internal capsule. Anastomosis with other cerebral arteries was visualized in 25% of the AChA with plexal perforators. Conclusions: 3DRA slab MIP was useful for visualizing the perforating branches of the AChA. Our results showed the possibility that surgical manipulation of the choroid plexus may cause infarction in the AChA territory. We suggest that the existence of the AChA plexal perforators should be recognized to further enhance the safety of hippocampal resection for mTLE. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the efficacy of a combined wavelet and deep-learning reconstruction (DLR) method for under-sampled pituitary MRI. Methods: This retrospective study included 28 consecutive patients who underwent under-sampled pituitary T2-weighted images (T2WI). Images were reconstructed using either the conventional wavelet denoising method (wavelet method) or the wavelet and DLR methods combined (hybrid DLR method) at five denoising levels. The signal-to-noise ratio (SNR) of the CSF, hypothalamic, and pituitary images and the contrast between structures were compared between the two image types. Noise quality, contrast, sharpness, artifacts, and overall image quality were evaluated by two board-certified radiologists. The quantitative and the qualitative analyses were performed with robust two-way repeated analyses of variance. Results: Using the hybrid DLR method, the SNR of the CSF progressively increased as denoising levels increased. By contrast, with the wavelet method, the SNR of the CSF, hypothalamus, and pituitary did not increase at higher denoising levels. There was a significant main effect of denoising methods (p < 0.001) and denoising levels (p < 0.001), and an interaction between denoising methods and denoising levels (p < 0.001). For all five qualitative scores, there was a significant main effect of denoising methods (p < 0.001) and an interaction between denoising methods and denoising levels (p < 0.001). Conclusions: The hybrid DLR method can provide higher image quality for T2WI of the pituitary with compressed sensing (CS) than the wavelet method alone, especially at higher denoising levels. Key Points: •The signal-to-noise ratios of cerebrospinal fluid progressively increased with the hybrid DLR method, with an increase in the denoising level for cerebrospinal fluid in pituitary T2WI with CS. •The signal-to-noise ratios of cerebrospinal fluid using the conventional wavelet method did not increase at higher denoising levels. •All qualitative scores of hybrid deep-learning reconstructions at all denoising levels were higher than those for the wavelet denoising method. [ABSTRACT FROM AUTHOR]

Zinc nanoparticles applied in the production of zinc–air batteries provide the highest specific energy among various metal–air combinations used in batteries in practice. Recent technical advances provide an opportunity to successfully solve the problems experienced during the early development of batteries of this type. For example, there is a major limitation in recharging cycles due to the massive formation of zinc oxide. In the present work, a reduction process is proposed on the basis of the use of alcohol solvent by applying microwave in-liquid plasma. The occurrence of reduction was confirmed by calculating the chemical potential of ethanol and methanol as well as spectra of plasma emission in the temperature range 1500–2000 K. Characterization of synthesized nanoparticles was carried out by energy-dispersive X-ray spectrometry and transmission electron microscopy. [ABSTRACT FROM AUTHOR]

Despite the exposures of Precambrian and Paleozoic rocks and the accretionary tectonic history of the northern Pacific (northeastern Asia, Alaska, and Kamchatka), it is likely that a considerable portion of the lower crust of the continental margins is much younger and was generated by Cretaceous postaccretion magmatic events. Data on xenoliths suggest that Late Cretaceous and Paleocene mafic intrusions and cumulates of calc-alkaline magmas may become more important with increasing depth. This conclusion is based on the petrological and geochronological investigation of lower-middle crustal xenoliths borne by mantlederived alkali basalt lavas and U-Pb dating of zircon cores from the igneous rocks of the region. We studied deep mafic xenoliths of granulites and gabbroids (accounting for <2% of the general xenolith population) from the Late Neogene alkali basalt lavas of the Enmelen and Viliga volcanic fields (Russia) and the Imuruk volcanic field in the Seward Peninsula, St. Lawrence Island, and Nunivak Island (Alaska). Depleted MORB-like varieties and relatively enriched in radiogenic isotopes and LREE rocks were distinguished among plagioclase-bearing xenoliths. The most representative collection of Enmelen xenoliths was subdivided into three groups: LREE enriched charnockitoids and mafic melts, pyroxene-plagioclase cumulates with a positive Eu anomaly, and LREE depleted garnet gabbroids. Mineral thermobarometry and calculated seismic velocities ( P = 5-12 kbar, T = 740-1100°C, and V = 7.1 ± 0.3 km/s) suggest that the xenoliths were transported from the lower and middle crust, and the rocks show evidence for their formation through the magmatic fractionation of calc-alkaline magmas and subsequent granulite-facies metamorphism. The U-Pb age of zircon from the xenoliths ranges from the Cretaceous to Paleocene, clustering mainly within 107-56 Ma (147 crystals from 17 samples were dated). The zircon dates were interpreted as reflecting the magmatic and metamorphic stages of the growth and modification of the regional crust. The distribution of the obtained age estimates corresponds to the main magmatic pulses in two largest magmatic belts of the region, Okhotsk-Chukchi and Anadyr-Bristol. The absence of older inherited domains in zircons from both the xenoliths and igneous rocks of the regions is a strong argument in favor of the idea on the injection of juvenile material and underplating of calc-alkaline magmas in the lower crust during that time interval. This conclusion is supported by isotope geochemical data: the Sr, Nd, and Pb isotope ratios of the rocks and xenolith minerals show mantle signatures (Sr/Sr = 0.7040-0.70463, Nd/Nd = 0.51252-0.51289, Pb/Pb = 18.32-18.69) corresponding to an OIB source and are in general similar to those of the Cretaceous calc-alkaline basalts and andesites from continental-margin suprasubduction volcanoplutonic belts. Xenoliths from Nunivak Island and Cape Navarin show more depleted (MORB-like) geochemical and isotopic characteristics, which indicates variations in the composition of the lower crust near the southern boundary of the Bering Sea shelf. [ABSTRACT FROM AUTHOR]

The Coast Range ophiolite (CRO) of California is one of the most extensive tracts of oceanic crust preserved in the North American Cordillera, but its origin has long remained controversial. We present here new data on mineral compositions in mantle peridotites that underlie crustal sections of the ophiolite, and show that these are dominantly refractory harzburgites related to high apparent melting in a supra-subduction zone (SSZ) setting. Abyssal peridotite (characterized by high-Al spinels and relatively high Ti, Na, Nd, Sm, Lu, and Hf in pyroxene) occurs at one location where it is associated with SSZ mantle peridotite and volcanic rocks with both oceanic and arc-like geochemistry. SSZ mantle peridotites (characterized by intermediate-Cr/Al or high-Cr spinels, and by extremely low Ti, Na, Nd, Sm, Lu, and Hf in pyroxenes) are associated with crustal sections containing arc-related volcanic rocks, including boninites. This convergence between conclusions based on crustal lithologies and their underlying mantle sections confirms previous proposals that link the CRO to SSZ processes, and seriously undermines hypotheses that invoke formation of the ophiolite at a mid-ocean ridge spreading center. [ABSTRACT FROM AUTHOR]

We conducted a feasibility study to predict malignant glioma grades via radiomic analysis using contrast-enhanced T1-weighted magnetic resonance images (CE-T1WIs) and T2-weighted magnetic resonance images (T2WIs). We proposed a framework and applied it to CE-T1WIs and T2WIs (with tumor region data) acquired preoperatively from 157 patients with malignant glioma (grade III: 55, grade IV: 102) as the primary dataset and 67 patients with malignant glioma (grade III: 22, grade IV: 45) as the validation dataset. Radiomic features such as size/shape, intensity, histogram, and texture features were extracted from the tumor regions on the CE-T1WIs and T2WIs. The Wilcoxon–Mann–Whitney (WMW) test and least absolute shrinkage and selection operator logistic regression (LASSO-LR) were employed to select the radiomic features. Various machine learning (ML) algorithms were used to construct prediction models for the malignant glioma grades using the selected radiomic features. Leave-one-out cross-validation (LOOCV) was implemented to evaluate the performance of the prediction models in the primary dataset. The selected radiomic features for all folds in the LOOCV of the primary dataset were used to perform an independent validation. As evaluation indices, accuracies, sensitivities, specificities, and values for the area under receiver operating characteristic curve (or simply the area under the curve (AUC)) for all prediction models were calculated. The mean AUC value for all prediction models constructed by the ML algorithms in the LOOCV of the primary dataset was 0.902 ± 0.024 (95% CI (confidence interval), 0.873–0.932). In the independent validation, the mean AUC value for all prediction models was 0.747 ± 0.034 (95% CI, 0.705–0.790). The results of this study suggest that the malignant glioma grades could be sufficiently and easily predicted by preparing the CE-T1WIs, T2WIs, and tumor delineations for each patient. Our proposed framework may be an effective tool for preoperatively grading malignant gliomas. [ABSTRACT FROM AUTHOR]

Radiation therapy is associated with the subsequent development of cerebral aneurysms; however, stereotactic radiosurgery (SRS)-associated aneurysm cases have not been well documented, with only 18 cases reported to date. We present a case of intracranial aneurysms with the rupture occurring 20 years after SRS for a growth hormone-producing pituitary adenoma. This is the first report of aneurysms diagnosed following transsphenoidal surgery and SRS for pituitary adenoma. We believe that the aneurysm reported here is a consequence of the SRS treatment, and thus this may be a very rare long-term complication following radiation treatments. [ABSTRACT FROM AUTHOR]

Background: Some childhood cancer survivors experience employment difficulties. This study aimed to describe pediatric brain-tumor survivors’ employment status.Methods: A cross-sectional, observational study was conducted, with questionnaires distributed to 101 pediatric brain-tumor survivors (aged 15 years or older) and their attending physicians from nine institutions in Japan. We compared category and time-series histories for participants’ first-time employment using national census information. Factors related to delayed employment or early employment termination were examined using survival-time analyses.Results: Excluding students and homemakers, 38 brain-tumor survivors (median age 27 years, with 15 years since diagnosis) were of working age. Of these, 12 (32%) were unemployed and 9 (24%) had never been employed. First-time employment occurred later for brain-tumor survivors than the general population, particularly in those with lower educational levels. The number of brain-tumor survivors whose first job was terminated within the first year was higher than that for the general population, particularly in male survivors and germ cell-tumor survivors. Brain-tumor survivors described their working patterns (irregular), job types (specialist or professional), reasons for early termination (unsuitable job), and thoughts about working (they wished to serve their communities but lacked confidence).Conclusion: Brain-tumor survivors are associated with high unemployment rates and multiple unemployment-related factors. Education and welfare systems should identify individual methods of social participation for this group. [ABSTRACT FROM AUTHOR]

Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling. We showed that pure germinomas are characterized by global low DNA methylation, a unique epigenetic feature making them distinct from all other iGCTs subtypes. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, possibly indicating the cell of origin for these tumors. Unlike PGC, however, hypomethylation extends to long interspersed nuclear element retrotransposons. Histologically and epigenetically distinct microdissected components of mixed-GCTs shared identical somatic mutations in the MAPK or PI3K pathways, indicating that they developed from a common ancestral cell. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a rare malignancy confined to the central nervous system (CNS), and majority of PCNSL is pathologically classified as diffuse large B-cell lymphoma (DLBCL). We have now performed whole-exome sequencing for 41 tumor tissues of DLBCL-type PCNSL and paired normal specimens and also RNA-sequencing for 30 tumors, revealing a very high frequency of nonsynonymous somatic mutations in PIM1 (100 %), BTG2 (92.7 %), and MYD88 (85.4 %). Many genes in the NF-κB pathway are concurrently mutated within the same tumors. Further, focal deletion or somatic mutations in the HLA genes are associated with poor prognosis. Copy number amplification and overexpression of genes at chromosome 7q35 were both found to predict short progression-free survival as well. Oncogenic mutations in GRB2 were also detected, the effects of which in cultured cells were attenuated by inhibitors of the downstream kinases MAP2K1 and MAP2K2. Individuals with tumors positive for MYD88 mutations also harbored the same mutations at a low frequency in peripheral blood mononuclear cells, suggesting that MYD88 mutation-positive precancerous cells originate outside of the CNS and develop into lymphoma after additional genetic hits that confer adaptation to the CNS environment. [ABSTRACT FROM AUTHOR]

Germ cell tumors constitute a heterogeneous group that displays a broad spectrum of morphology. They often arise in testes; however, extragonadal occurrence, in particular brain, is not uncommon, and whether they share a common pathogenesis is unknown. We performed whole exome sequencing in 41 pairs of central nervous system germ cell tumors (CNS GCTs) of various histology and their matched normal tissues. We then performed targeted sequencing of 41 selected genes in a total of 124 CNS GCTs, 65 testicular germ cell tumors (tGCTs) and 8 metastatic GCTs to the CNS. The results showed that mutually exclusive mutations of genes involved in the MAPK pathway were most common (48.4 %), typically in KIT (27.4 %), followed by those in the PI3K pathway (12.9 %), particularly in MTOR (6.5 %), among the 124 CNS GCTs. Pure germinomas and non-germinomatous germ cell tumors (NGGCTs), as well as CNS and testicular GCTs, showed similar mutational profiles, suggesting that GCTs share a common molecular pathogenesis. Mutated MTOR identified in CNS GCTs upregulated phosphorylation of the AKT pathway proteins including AKT and 4EBP1 in nutrient-deprived conditions and enhanced soft-agar colony formation; both events were suppressed in a dose-dependent manner by addition of the MTOR inhibitor pp242. Our findings indicate that the dominant genetic drivers of GCTs regardless of the site of origin are activation of the MAPK and/or PI3K pathways by somatic point mutations. Mutated MTOR represents a potential target for novel targeted therapies for refractory GCTs. [ABSTRACT FROM AUTHOR]

Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O- methylguanine- DNA methyltransferase ( MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-naïve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency. [ABSTRACT FROM AUTHOR]

Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 15 in Japan. The pathogenesis of iGCTs is largely unexplored. Although a subset of iGCTs is known to have KIT mutation, its impact on the biology and patients' survival has not been established. In this study, we investigated genes involved in the KIT signaling pathway. 65 iGCTs (30 pure germinomas, 14 teratomas, 18 mixed GCTs, 2 yolk sac tumors, 1 choriocarcinoma) were screened for mutation of KIT, KRAS, NRAS, HRAS, BRAF, PDGFRA, and IDH1 by direct sequencing. KIT expression was examined by immunohistochemistry and quantitative PCR. Chromosomal status was analyzed by array-comparative genomic hybridization (aCGH). Somatic mutations were detected only in KIT and RAS, which were frequently observed in pure germinomas (60.0 %), but rare in non-germinomatous GCTs (NGGCTs) (8.6 %). All KIT/ RAS mutations were mutually exclusive. Regardless of the mutation status or mRNA expression, the KIT protein was expressed in all germinomas, while only in 54.3 % of NGGCTs. Amplification of KIT was found in one pure germinoma by aCGH. In pure germinomas, high expression of KIT mRNA was associated with the presence of KIT/ RAS alterations and severe chromosomal instability. Our results indicate that alterations of the KIT signaling pathway play an important role in the development of germinomas. Pure germinomas may develop through two distinct pathogeneses: one with KIT/ RAS alterations, elevated KIT mRNA expression and severe chromosomal instability, and the other through yet an unidentified mechanism without any of the above abnormalities. [ABSTRACT FROM AUTHOR]

Purpose: To understand the influence of disease and treatment on the health-related quality of life (HRQOL) of children with brain tumors, compared to the HRQOL of children with other cancers, from the viewpoints of children and parents. Methods: A total of 133 children aged 5-18 years and 165 parents of children aged 2-18 completed questionnaires of the Pediatric Quality of Life Inventory Cancer Module (Pain and Hurt, Nausea, Procedural Anxiety, Treatment Anxiety, Worry, Cognitive Problems, Perceived Physical Appearance, and Communication scales); higher scores indicate a better HRQOL. The Cancer Module scores, weighted by age and treatment status, were compared to those obtained in a previous study of children with other cancers (mostly leukemia). Results: The weighted mean scores for Pain and Hurt (effect size d = 0.26) and Nausea ( d = 0.23) from child reports and the scores for Nausea ( d = 0.28) from parent reports were higher for children with brain tumors than scores for children with other cancers. The scores for Procedural Anxiety ( d = −0.22) and Treatment Anxiety ( d = −0.32) from parent reports were lower for parents of children with brain tumors than the scores for parents of children with other cancers. The child-reported Pain and Hurt score of the Cancer Module was higher ( d = 0.29) and in less agreement ( intraclass correlation coefficient = 0.43) with scores from the Brain Tumor Module, indicating that assessments completed with the Cancer Module misesteem pain and hurt problems in children with brain tumors. Conclusions: The profiles of cancer-specific HRQOL in children with brain tumors differ from those of children with other cancers; we therefore suggest that these children receive specific psychological support. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that brain tumors arise from the transformation of neural stem/precursor/progenitor cells. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma. Here we show that anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for the self-renewal and tumorigenicity of glioblastoma stem cells (GSCs). Furthermore, we demonstrate that pleiotrophin is transactivated directly by SOX2, a transcription factor essential for the maintenance of both neural stem cells and GSCs. We speculate that the pleiotrophin-ALK axis may be a promising target for the therapy of glioblastoma. [ABSTRACT FROM AUTHOR]

Purpose: Health-related quality of life (HRQOL) is not only a degree of health but also reflects patient perceptions and expectations of health. For children with brain tumors, better understanding of HRQOL requires the use of complementary reports from parents and interviewer-administered reports for children. Here, we aimed to test whether or not the trait anxiety of children and the psychological distress of their parents influence children's and parents' responses to HRQOL questionnaires, and whether or not the report-administration method for children influences children's responses to HRQOL questionnaires. Methods: One hundred and thirty-four children aged 5-18 with brain tumors and one of their parents completed the Pediatric Quality of Life Inventory (PedsQL) Brain Tumor Module questionnaires. In addition, the children also completed the State-Trait Anxiety Inventory for Children (STAIC), and the parents also completed the Kessler-10 (K10) and health and sociodemographic characteristics questionnaires. The child questionnaires were administered either by the child (self-administered) or an interviewer. Rater-dependent perceptions about HRQOL were derived from the subscales scores of the PedsQL Brain Tumor Module using structural equation modeling based on a multitrait-multimethod model. The STAIC trait-anxiety score, K10 score, report-administration method, and other health and sociodemographic factors related to each child's or parent's perceptions were identified through multiple linear regression analyses of the questionnaire responses. We used a path analysis to estimate the change in a PedsQL child-reported score that occurs when interviewer-administration changes the child's perception about HRQOL. Results: Surveys for 89 children were self-administered while those for 45 were interviewer-administered. The perceptions of the children and parents were calculated by fitting data to the model (chi-squared P = 0.087, normed fit index = 0.932, comparative fit index = 0.978, standardized root mean squared residual = 0.053, and root mean square error of approximation = 0.054). The children's perception of HRQOL was affected by their STAIC trait-anxiety score ( b = −0.43, 95% CI [−0.60, −0.25]). The parent's perception was affected by their child's treatment status ( b = 0.26, 95% CI [0.09, 0.43]), the parent's K10 score ( b = −0.21, 95% CI [−0.37, −0.04]), and by education level ( b = 0.17, 95% CI [0.00, 0.34]). The change in the child-reported PedsQL score in relation to the method of administration ranged from −1.1 (95% CI: −3.5, 1.3) on the procedural anxiety subscale to −2.5 (95% CI: −7.6, 2.6) on the movement and balance subscale. Conclusion: Child-reporting of HRQOL is little influenced by the method of administration. Children's perception about HRQOL tended to be influenced by their trait anxiety, while parents' perception was influenced by their psychological distress, academic background, and their child's treatment status. [ABSTRACT FROM AUTHOR]

The Marie Byrd Land province includes 18 large (up to 1,800 km) central volcanoes distributed across an active volcano-tectonic dome. The typical volcano structure consists of a basal 1,000-5,000 m of basanite surmounted by trachyte and subordinate intermediate rocks, plus phonolite, or pantellerite, or comendite. The volumes of felsic sections are large (~30-700 km), but these rocks probably make up <10% of volcanic rock in the province. This paper describes pantellerite volcanoes in the Ames and Flood Ranges, which include a large and varied suite of these iron-rich, silica-poor rhyolites. Isotopic and trace element data, maintenance of isotopic equilibrium throughout the basalt-felsic range, and the results of modeling, all exclude significant crustal contamination and point to fractional crystallization as the process that controls magmatic evolution. The most unusual feature of these volcanoes is the apparent need to derive pantellerites from basanite, the long interval of fractionation at the base of the lithosphere and crust, involving kaersutite as the key phase in developing pantellerite, and a plumbing system that permitted coeval eruption of pantellerite and phonolite from the same edifice. Peralkalinity most likely developed in upper crustal reservoirs during the final 4-5% of magmatic history, by fractionating a high proportion of plagioclase under low pHO. Mantle plume activity appears to drive doming and volcanism. This, a stationary plate, and continental lithospheric structure seem to provide an optimal environment for the evolution of a diverse, large volume suite of felsic rocks by fractional crystallization. [ABSTRACT FROM AUTHOR]

The present study investigated the role of O-linked β- N-acetylglucosamine ( O-GlcNAc) glycosylation ( O-GlcNAcylation) in AMPA receptor trafficking. Alloxan, an inhibitor of O-GlcNAc transferase, potentiated responses of AMPA receptors composed of the GluR1 subunit expressed in Xenopus oocytes. No potentiating effect of alloxan was obtained with mutant GluR1 (S831A) receptor lacking CaMKII phosphorylation site. Alloxan facilitated basal synaptic transmission to approximately 120% of basal levels and enhanced Schaffer collateral-CA1 long-term potentiation (LTP) in rat hippocampal slices, especially in the late phase of the LTP. Alloxan stimulated translocation of the GluR1 and GluR2 subunit from the cytosol towards the plasma membrane in rat hippocampal slices with the LTP, although it had no effect on subcellular distribution of the NR1 subunit. Taken together, the results of the present study show that alloxan regulates AMPA receptor trafficking by inhibiting O-GlcNAcylation, to modulate hippocampal synaptic transmission and synaptic plasticity. [ABSTRACT FROM AUTHOR]

The middle Jurassic Coast Range Ophiolite (CRO) is one of the most important tectonic elements in western California, cropping out as tectonically dismembered elements that extend 700 km from south to north. The volcanic and plutonic sections are commonly interpreted to represent a supra-subduction zone (SSZ) ophiolite, but models specifying a mid-ocean ridge origin have also been proposed. These contrasting interpretations have distinctly different implications for the tectonic evolution of the western Cordillera in the Jurassic. If an SSZ origin is confirmed, we can use the underlying mantle peridotites to elucidate melt processes in the mantle wedge above the subduction zone. This study uses laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) to study pyroxenes in peridotites from four mantle sections in the CRO. Trace element signatures of these pyroxenes record magmatic processes characteristic of both mid-ocean ridge and supra-subduction zone settings. Group A clinopyroxene display enriched REE concentrations [e.g., Gd (0.938–1.663 ppm), Dy (1.79–3.24 ppm), Yb (1.216–2.047 ppm), and Lu (0.168–0.290 ppm)], compared to Group B and C clinopyroxenes [e.g., Gd (0.048–0.055 ppm), Dy (0.114–0.225 ppm), Yb (0.128–0.340 ppm), and Lu (0.022–0.05 ppm)]. These patterns are also evident in orthopyroxene. The differences between these geochemical signatures could be a result of a heterogeneous upper mantle or different degrees of partial melting of the upper mantle. It will be shown that CRO peridotites were generated through fractional melting. The shapes of REE patterns are consistent with variable degrees of melting initiated within the garnet stability field. Models call for 3% dry partial melting of MORB-source asthenosphere in the garnet lherzolite field for abyssal peridotites and 15–20% further partial melting in the spinel lherzolite field, possibly by hydrous melting for SSZ peridotites. These geochemical variations and occurrence of both styles of melting regimes within close spatial and temporal association suggest that certain segments of the CRO may represent oceanic lithosphere, attached to a large-offset transform fault and that east-dipping, proto-Franciscan subduction may have been initiated along this transform. [ABSTRACT FROM AUTHOR]

Activator protein 1 (AP-1, also known as JUN) transcription factors are dimers of JUN, FOS, MAF and activating transcription factor (ATF) family proteins characterized by basic region and leucine zipper domains. Many AP-1 proteins contain defined transcriptional activation domains, but BATF and the closely related BATF3 (refs 2, 3) contain only a basic region and leucine zipper, and are considered to be inhibitors of AP-1 activity. Here we show that Batf is required for the differentiation of IL17-producing T helper (TH17) cells. TH17 cells comprise a CD4+ T-cell subset that coordinates inflammatory responses in host defence but is pathogenic in autoimmunity. Batf-/- mice have normal TH1 and TH2 differentiation, but show a defect in TH17 differentiation, and are resistant to experimental autoimmune encephalomyelitis. Batf-/- T cells fail to induce known factors required for TH17 differentiation, such as RORγt (encoded by Rorc) and the cytokine IL21 (refs 14–17). Neither the addition of IL21 nor the overexpression of RORγt fully restores IL17 production in Batf-/- T cells. The Il17 promoter is BATF-responsive, and after TH17 differentiation, BATF binds conserved intergenic elements in the Il17a–Il17f locus and to the Il17, Il21 and Il22 (ref. 18) promoters. These results demonstrate that the AP-1 protein BATF has a critical role in TH17 differentiation. [ABSTRACT FROM AUTHOR]

Six isolates of Cassava brown streak virus (CBSV, genus Ipomovirus; Potyviridae) from the Lake Victoria basin in Uganda and Tanzania were characterized. Virus particles were 650 nm long. The complete coat protein (CP)-encoding sequences (1,101 nucleotides, nt) were 90.7–99.5 and 93.7–99.5% identical at the nt and amino acid (aa) levels, respectively. The 3′ untranslated region was 225, 226 or 227 nt long. These eight isolates were only 75.8–77.5% (nt) and 87.0–89.9% (aa) identical when compared to the partial CP sequences (714 nt) of six CBSV isolates characterized previously from the costal lowlands of Tanzania and Mozambique. Hence, two genetically different and geographically separated populations of CSBV exist in East Africa. [ABSTRACT FROM AUTHOR]

Quantitative thermobarometry of inclusions in zoned garnet from a Franciscan eclogite block record a counter-clockwise P– T path from blueschist to eclogite and back. Garnet retains prograde zoning from inclusion-rich Alm52Grs30Pyp6Sps12 cores to inclusion-poor Alm62Grs25Pyp12Sps1 mantles, with overgrowths of highly variable composition. Barometry using the Waters–Martin version of the garnet–phengite–omphacite thermobarometer yields conditions of 7–15 kbar, 400–500°C (garnet cores), 18–22 kbar, ∼550°C (mantles), and 10–14 kbar, 350–450°C (overgrowths), in agreement with clinozoisite–sphene–rutile–garnet–quartz barometry. These pressures are ∼10–15 kbar less than those obtained using more recent, fully thermodynamic calibrations of the phengite–omphacite–garnet thermobarometer. Low early temperatures suggest that the block was subducted in a thermally mature subduction zone and not at the inception of subduction when prograde temperature is expected to be higher. Franciscan high-grade blocks likely represent crust subducted throughout the history of this convergent margin, rather than only at the inception of the subduction zone. [ABSTRACT FROM AUTHOR]

Summary. Sweet potato feathery mottle virus (SPFMV, genus Potyvirus, family Potyviridae), Sweet potato chlorotic stunt virus (SPCSV, genus Crinivirus, family Closteroviridae) and sweet potato virus G (SPVG) were detected in naturally infected sweet potato plants grown in the Delta region in Egypt. Before this study, SPVG was reported only from China. Two isolates of SPFMV and one isolate of SPVG were characterized for the 3′-proximal genomic sequences. Phylogenetic analyses indicated that the SPFMV isolates belong to the ‘russet crack’ strain group (RC). Serological tests using monoclonal antibodies, and phylogenetic analysis of a partial sequence of the Hsp70 gene, indicated that the Egyptian SPCSV belongs to the so-called non-East African strain group of SPCSV. [ABSTRACT FROM AUTHOR]

Abstract. We have observed a cleaved NiO(100) surface by means of non-contact atomic force microscopy (NC-AFM) using a Fe-coated tip. The shape and magnetic properties of the Fe-coated tip are confirmed by ex situ scanning electron microscopy (SEM) and magnetic force microscopy (MFM) imaging. Also, in situ change f-v measurement shows that the contact-potential difference (CPD) is different between noncoated Si and Fe-coated tips. The Fe-coated tip can produce atomically resolved NC-AFM images of a cleaved NiO(100) surface at room temperature. [ABSTRACT FROM AUTHOR]