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Microvascular proliferation is a key feature of glioblastoma and neovascularization has been implicated in tumor progression. Glioblastomas use pro-angiogenic factors such as vascular endothelial growth factor (VEGF) for new blood vessel formation. Yet, anti-VEGF therapy does not prolong overall survival so that alternative angiogenic pathways may need to be explored as drug targets. Both glioma cells and glioma-associated endothelial cells produce TGF-β superfamily ligands which bind TGF-β receptors (TGF-βR). The TGF-βR type III endoglin (CD105), is a marker of proliferating endothelium that has already been studied as a potential therapeutic target. We studied endoglin expression in glioblastoma tissue and in glioma-associated endothelial cells in a cohort of 52 newly diagnosed and 10 recurrent glioblastoma patients by immunohistochemistry and by ex vivo single-cell gene expression profiling of 6 tumors. Endoglin protein levels were similar in tumor stroma and endothelium and correlated within tumors. Similarly, endoglin mRNA determined by ex vivo single-cell gene expression profiling was expressed in both compartments. There was positive correlation between endoglin and proteins of TGF-β superfamily signaling. No prognostic role of endoglin expression in either compartment was identified. Endoglin gene silencing in T98G glioma cells and in human cerebral microvascular endothelial cells (hCMEC) did not affect constitutive or exogenous TGF-β superfamily ligand-dependent signaling, except for a minor facilitation of pSmad1/5 signaling in hCMEC. These observations challenge the notion that endoglin might become a promising therapeutic target in glioblastoma.

The benefits of sport activity on cognition and especially on executive function development are well-known, and in recent years, several kinds of cognitive-motor training (CMT) have been proven effective in adults and older people. Less is known about possible CMT benefits in children. This study aims to confirm the positive influence played by CMTs on specific executive functions (planning abilities and visual search) in young soccer players. Twenty-four 10-year-old athletes were recruited and randomly assigned to the experimental (Exp) and control (Con) groups of 12 players. Both groups were trained for 10 weeks, twice a week (90 min per training), following standard soccer training (technical-tactical exercises). The Exp group, during the first training session of the week, in the last 22 min, performed the experimental treatment, which consisted of a psychokinetic CMT. Both groups were examined before and after the ten-week training using the Tower of London and WISC-IV cancellation tests. Results revealed that the Exp group, following treatment, reported significantly better scores than the Con group in all the cognitive measures. We concluded that the proposed CMT is more effective than motor training alone at improving planning abilities and visual search abilities, even in children.

Organic molecules are a potential source of prebiotic chemistry in the interstellar medium (ISM). Methanol (MetOH) is a very important source of more complex molecules. H 3 O + (aq) and Cl - (aq) are fundamental to living organisms and can be generated in the ISM from the dissociation of HCl with just four water molecules, yielding the (H 3 O) + (H 2 O) 3 Cl - ion-pair. Here, a detailed mechanism, based on density functional theory (DFT) and ab-initio (2 nd order Mϕller-Plesset perturbation theory, MP2) calculations, is suggested for the substitution reactions of these water molecules by MetOH. The time required for formation of an appreciable amount of the product ((H 3 O) + (MetOH) 3 Cl - ) can be only few years. Such reaction can take place in Sagittarius B2, where HCl, H 2 O and MetOH have already been identified and it can be an important source for the formation of more complex prebiotic structures., (© 2022 Wiley-VCH GmbH.)

Pyrene fluorescence after a high-energy electronic excitation exhibits a prominent band shoulder not present after excitation at low energies. The standard assignment of this shoulder as a non-Kasha emission from the second-excited state (S 2 ) has been recently questioned. To elucidate this issue, we simulated the fluorescence of pyrene using two different theoretical approaches based on vertical convolution and nonadiabatic dynamics with nuclear ensembles. To conduct the necessary nonadiabatic dynamics simulations with high-lying electronic states and deal with fluorescence timescales of about 100 ns of this large molecule, we developed new computational protocols. The results from both approaches confirm that the band shoulder is, in fact, due to S 2 emission. We show that the non-Kasha behavior is a dynamic-equilibrium effect not caused by a metastable S 2 minimum. However, it requires considerable vibrational energy, which can only be achieved in collisionless regimes after transitions into highly excited states. This strict condition explains why the S 2 emission was not observed in some experiments.

Importance: Most ocular lesions have been described for children with congenital Zika syndrome. The frequency of finding ocular abnormalities is unknown among children exposed to Zika virus (ZIKV) during pregnancy. This study was conducted on newborns whose mothers were positive for ZIKV, confirmed with reverse-transcription polymerase chain reaction (RT-PCR) testing., Objective: To report ocular fundus manifestations in newborns with congenital ZIKV exposure in French Guiana, Martinique, and Guadeloupe, French West Indies, to assess its prevalence. Risk factors, such as the presence of extraocular fetopathies and the gestational term at infection, were sought., Design, Setting, and Participants: This was a cross-sectional multicentric study, conducted from August 1, 2016, to April 30, 2019, for which data were collected prospectively. The study inception was at the beginning of 2016 from the onset of the ZIKV epidemic in the French West Indies. Newborns whose mothers tested positive (by RT-PCR) for ZIKV during pregnancy were included., Interventions: Fundus examination was performed using widefield retinal imaging after pupil dilation. Infection date, delivery mode, and newborn measurements were collected., Main Outcomes and Measures: Anomalies of the vitreous, choroid, retina, and optic disc., Results: A total of 330 children (mean [SD] age, 68 [IQR, 22-440] days; 170 girls [51.5%]) were included. Eleven children (3.3%) had perivascular retinal hemorrhages, and 3 (0.9%) had lesions compatible with congenital ZIKV infection: 1 child had torpedo maculopathy, 1 child had a chorioretinal scar with iris and lens coloboma, and 1 child had a chorioretinal scar. Retinal hemorrhages were found at childbirth during early screening. Lesions compatible with congenital ZIKV infection were not associated with the presence of extraocular fetopathy. Microcephaly was not associated with lesions compatible with congenital ZIKV infection (odds ratio [OR], 9.1; 95% CI, 0.8-105.3; P = .08), but severe microcephaly was associated with an OR of 81 (95% CI, 5.1-1297.8; P = .002)., Conclusions and Relevance: Results of this cross-sectional study suggest that the ocular anomalies found may be associated with ZIKV in 0.9% of the exposed population. Ocular lesions were rare, affected mostly the choroid and retina, and seemed to be associated with choroiditis-related scarring that developed during fetal growth.

Purpose: CT-guided percutaneous procedures involving the skull base and atlanto-axial cervical spine pose particular challenges due to high density of vital vascular and nervous structures and because the ideal needle trajectory often has a cranio-caudal obliquity different from the axial scan plane. We describe how the variable CT gantry tilt, combined with gantry-needle-target alignment technique, is used to obtain precise and safe needle placement in conventional and non-conventional approaches to the skull base and the atlanto-axial spine., Methods: We retrospectively analyzed consecutive CT-guided needle accesses to the skull base and atlanto-axial spine performed for tissue sampling through fine-needle aspirates and core biopsies, cementoplasty of neoplastic lytic lesions of atlanto-axial spine, pain management injections, and dural puncture for cerebro-spinal fluid sampling. All the accesses were performed with the gantry-needle-target alignment technique. Procedural complications were recorded., Results: Thirty-nine CT-guided procedures were analyzed. Paramaxillary approach was used in 15 cases, postero-lateral in 11, subzygomatic in 3. Nine non-conventional approach were performed: submastoid in 3 cases, suprazygomatic in 2, trans-nasal in 2, trans-mastoid in 1, and trans-auricular in 1. Two peri-procedural complications occurred: one asymptomatic and one resolved within 24 h. All the procedures were successfully completed with successful needle access to the target., Conclusion: The gantry tilt and gantry-needle-target alignment technique allows to obtain double-oblique needle accesses for CT-guided procedures involving the skull base and atlanto-axial cervical spine, minimizing uncertainty of needle trajectory and obtaining safe needle placement in conventional and non-conventional approaches., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Determine whether an association exists between access barriers reported by women aged 15-49 years and the use of essential health services for women and children in Latin America., Methods: Cross-sectional study using multivariate logistic regression models based on the demographic and health surveys of Bolivia, the Dominican Republic, Guatemala, Guyana, Haiti, Honduras, Nicaragua, and Peru., Results: Geographical and financial barriers, the need to obtain permission to visit the doctor, or not wanting to go alone to a health facility significantly reduced the likelihood of completing prenatal checkups and having an assisted delivery. Women who reported difficulties obtaining permission to visit the doctor were less likely to have had a Pap smear in the past two or three years, to complete vaccination of their children, and to seek care for children with acute respiratory infection. Not wanting to go to a health center alone reduced the likelihood of using modern contraceptives., Conclusions: Women who reported barriers to access had a statistically significant lower probability of using essential health services for themselves and their children. Strategies aimed at removing barriers should focus not only on improving the range of services offered, but also address issues related to norms, gender roles, and women's empowerment if sustainable progress toward universal access is to be made.

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The heating of a chromophore due to internal conversion and its cooling down due to energy dissipation to the solvent are crucial phenomena to characterize molecular photoprocesses. In this work, we simulated the ab initio nonadiabatic dynamics of cytosine, a prototypical chromophore undergoing ultrafast internal conversion, in three solvents-argon matrix, benzene, and water-spanning an extensive range of interactions. We implemented an analytical energy-transfer model to analyze these data and extract heating and cooling times. The model accounts for nonadiabatic effects, and excited- and ground-state energy transfer, and can analyze data from any dataset containing kinetic energy as a function of time. Cytosine heats up in the subpicosecond scale and cools down within 25, 4, and 1.3 ps in argon, benzene, and water, respectively. The time constants reveal that a significant fraction of the benzene and water heating occurs while cytosine is still electronically excited.

The Hebbian unlearning algorithm, i.e., an unsupervised local procedure used to improve the retrieval properties in Hopfield-like neural networks, is numerically compared to a supervised algorithm to train a linear symmetric perceptron. We analyze the stability of the stored memories: basins of attraction obtained by the Hebbian unlearning technique are found to be comparable in size to those obtained in the symmetric perceptron, while the two algorithms are found to converge in the same region of Gardner's space of interactions, having followed similar learning paths. A geometric interpretation of Hebbian unlearning is proposed to explain its optimal performances. Because the Hopfield model is also a prototypical model of the disordered magnetic system, it might be possible to translate our results to other models of interest for memory storage in materials.

Background: Progressive familial intrahepatic cholestasis (PFIC) is a spectrum of rare genetic diseases characterized by inadequate bile secretion that requires substantial ongoing care, though little research is published in this area. We report health-related quality of life (HRQoL) and work productivity outcomes from the retrospective, cross-sectional PICTURE study investigating the burden of PFIC on caregivers. Information from caregivers of patients with PFIC 1 or 2 in Germany, the United Kingdom and the United States from September 2020 to March 2021 was included., Results: The PICTURE study sample comprised HRQoL responses from 22 PFIC caregivers. Patients were on average 8.2 years old; most caregivers were 30-49 years old (68%) and mothers (77%). Median CarerQoL-7D score was 67.7/100; mean CarerQoL-VAS score for general happiness was 5.7/10 (SD 2.1). Most caregivers reported fulfilment in their caregiving responsibilities, but problems with mental and physical health, finances, and relationships. When stratified by patient's PFIC type, mean CarerQoL-7D and CarerQoL-VAS scores suggested worse HRQoL outcomes with PFIC2 versus PFIC1 (59.4 vs. 71.2, and 5.3 vs. 6.5, respectively). Additionally, more caregivers reported impact on sleep in the PFIC2 versus PFIC1 subgroup (93% vs. 75%). When stratified by history of PFIC-related surgeries, mean CarerQoL-7D and VAS scores were higher among those whose children had no specified surgeries (67.7 vs. 59.0/100 and 6.2 vs. 5.2/10, respectively). Nearly all caregivers reported an impact of caregiving responsibilities on sleeping (86%) and on personal relationships (82%). No caregivers reported having formal care support. Most caregivers were employed (73%); a third reported mean productivity loss of 12.9 days (SD 19.3) over the last 3 months, and a mean of 2.8 (SD 9.5) missed years of employment during their career. A higher number of workdays were missed by PFIC 2 caregivers compared to PFIC1 over last 3 months (16 days vs. 3 days)., Conclusions: The PICTURE study has demonstrated the prevalent, comprehensive, and meaningful burden that caring for an individual with PFIC has on caregivers. Despite fulfilment from caregiving, the breadth and depth of these responsibilities reduced caregiver reported HRQoL including mental and physical health, productivity, career prospects, sleep, relationships and finances., (© 2022. The Author(s).)

Background: Premature loss of deciduous teeth is the exfoliation or extraction before physiological replacement with < 50% or < 75% of the root of the substitute tooth formed or if there is > 1 mm of alveolar bone covering the permanent successor tooth organ. This study aimed to estimate the prevalence of premature tooth loss in children and identify associated factors in a health center in Acapulco, Guerrero., Methods: We conducted a cross-sectional study in which we collected information from 109 clinical records of children examined from January 2019 to August 2021. Sociodemographic data of the children and parents were collected: socioeconomic level, non-pathological personal history, and the history of premature deciduous tooth loss. Multivariate analysis to identify factors associated with premature deciduous tooth loss was performed with CIETmap statistical software. Odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of the association., Results: The prevalence of premature loss of primary teeth was 40% (43/109). The leading cause was caries (84%, 36/43). The tooth organ with the highest loss occurrence was the lower right second molar (33%, 14/43). Gender was identified as an associated factor, with males having a higher risk of loss (ORa = 2.97; CI95% = 1.33-6.65)., Conclusions: Our results were similar to those reported in other studies. Strategies aimed at health promotion directed at parents and children should be reinforced., (Copyright: © 2022 Permanyer.)

By constructing counterexamples, the authors show that the fixed subgroups are not compressed in direct products of free and surface groups, and hence negate a conjecture in [Zhang, Q., Ventura, E. and J. Wu, Fixed subgroups are compressed in surface groups, Internat. J. Algebra Comput., 25, 2015, 865–887]. [ABSTRACT FROM AUTHOR]

Superionic solid electrolytes have widespread use in energy devices, but the fundamental motivations for fast ion conduction are often elusive. In this Perspective, we draw upon atomistic simulations of a wide range of superionic conductors to illustrate some ways frustration can lower diffusion cation barriers in solids. Based on our studies of halides, oxides, sulfides and hydroborates and a survey of published reports, we classify three types of frustration that create competition between different local atomic preferences, thereby flattening the diffusive energy landscape. These include chemical frustration, which derives from competing factors in the anion-cation interaction; structural frustration, which arises from lattice arrangements that induce site distortion or prevent cation ordering; and dynamical frustration, which is associated with temporary fluctuations in the energy landscape due to anion reorientation or cation reconfiguration. For each class of frustration, we provide detailed simulation analyses of various materials to show how ion mobility is facilitated, resulting in stabilizing factors that are both entropic and enthalpic in origin. We propose the use of these categories as a general construct for classifying frustration in superionic conductors and discuss implications for future development of suitable descriptors and improvement strategies. This article is part of the Theo Murphy meeting issue 'Understanding fast-ion conduction in solid electrolytes'.

Background: Dissociative symptoms are under recognized and scarcely studied by clinicians and researchers in patients with bipolar disorder (BD). We examined the relationship between dissociative symptoms and the psychotic features in patients with BD and assessed clinical and socio-demographic characteristics more frequently associated with dissociative symptoms and treatment response. Methods: Participants were 100 adult outpatients with BD. They were screened with semi-structured interview to collect socio-demographic and clinical characteristics; the Dissociative Experiences Scale-II (DES-II) and the ALDA scale were used to assess dissociative psychopathologies and response to treatment with mood stabilizers, respectively. Results: DES score (mean 31.7 ± 21.7) correlated with clinical variables, BD features, and course of illness. Psychotic symptoms, mixed features, and previous suicide attempts significantly predicted DES score [ F (3, 47) = 39.880, p < 0.001, R 2 corrected = 0.713]. Dissociative symptoms were inversely correlated with poor response to treatment ( r = -0.593; p < 0.001). Limitations: Cross-sectional design with a small sample and backward clinical assessment of psychotic symptoms. Conclusions: Dissociative phenomena are closely related to the presence of psychotic symptoms, mixed features, and previous suicide attempts in BD, especially in BD-I. Given the close association between dissociative and psychotic symptoms, this association could represent a diagnostic indicator of BD-I that may guide the clinician to plan the most appropriate treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Steardo, Carbone, Ventura, de Filippis, Luciano, Segura-Garcia and De Fazio.)

Primary acinic cell carcinoma arising in the nose is exceptionally rare. In this report, we present a unique case of an acinic cell carcinoma of the nasal lateral wall, and it is only the second such case to be reported. We also engage in a systematic review of all 18 cases of acinic cell carcinoma of the nose reported in the literature in English so far., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Dionísio et al.)