Background Neurodegeneration due to cerebral folate transport deficiency is a rare autosomal recessive disorder caused by biallelic pathogenic variants in FOLR1 . Onset typically occurs in late infancy and is characterized by psychomotor regression, epilepsy, and a hypomyelinating leukodystrophy on magnetic resonance imaging. If left untreated, progressive neurodegeneration occurs. However, early treatment with folinic acid has been shown to stabilize or reverse neurological features. Approximately thirty patients have been described worldwide. Here, we report the first two cases with genetically proven cerebral folate transport deficiency from South-Eastern Europe, describe the effect of oral folinic acid therapy on clinical and neuroradiological features and review the literature. Results Two siblings presented in childhood with clinical and radiological findings consistent with a hypomyelinating leukodystrophy. Exome sequencing revealed a novel homozygous pathogenic variant in FOLR1 (c.465_466delinsTG; p.W156G), confirming the diagnosis of neurodegeneration due to cerebral folate transport deficiency. Folinic acid treatment was promptly initiated in both patients. The younger sibling was treated early in disease course at 2 years of age, and demonstrated complete recovery in clinical and MRI features. The older sibling, who was 8 years of age at the time of diagnosis and treatment, demonstrated partial but substantial improvements. Conclusion We present the first account in the literature that early treatment initiation with oral folinic acid alone can result in complete neurological recovery of both clinical and radiological abnormalities in neurodegeneration due to cerebral folate deficiency. Moreover, through the report of these patients along with review of the literature, we provide information about the natural history of the disease with comparison of treatment effects at different stages of disease progression. This report also reinforces the importance of universal access to genetic testing to ensure prompt diagnoses for treatable disorders.

This work aimed to describe the synthesis and characterisation of two anionic Ru(III) complexes of the general formula Na[Ru - Cl 2 ( N -4-Cl-Ph-salim) 2 ] and Na[RuCl 2 ( N -3-Br-Ph-salim) 2 , their associated ligands, and determine their antioxidant activity. The ligands N- 4-Cl-phenylsalicylidenimine ( N -4-Cl-Ph-salimH, HL a ) and N- 3-Br-phenylsalicylidenimine ( N -3-Br-Ph-salimH, HL b ), Schiff bases, were synthesised from salicylaldehyde and chloroaniline or bromoaniline. The compounds were characterised us - ing IR spectroscopy and ESI ToF mass spectrometry. The following was confirmed: coordination of ligands on the Ru(III) centre, the molecular formulas, and the corresponding M − ions: [C 26 H 18 N 2 O 2 Cl 4 Ru] − ion, (m/z: 631.9173) and [C 26 H 18 N 2 O 2 Cl 2 Br 2 Ru] − ion, (m/z: 719.8283). The antioxidant activity was determined by the ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays. In contrast to the ligands, both complexes proved to be strong scaven - gers of the ABTS and DPPH radicals with IC 50 (half maximal inhibitory concentration) values comparable to those of Trolox. As such, they present valuable candidates for further research related to their biological properties.

Purpose: The development and evaluation of machine learning models that automatically identify the body part(s) imaged, axis of imaging, and the presence of intravenous contrast material of a CT series of images. Methods: This retrospective study included 6955 series from 1198 studies (501 female, 697 males, mean age 56.5 years) obtained between January 2010 and September 2021. Each series was annotated by a trained board-certified radiologist with labels consisting of 16 body parts, 3 imaging axes, and whether an intravenous contrast agent was used. The studies were randomly assigned to the training, validation and testing sets with a proportion of 70%, 20% and 10%, respectively, to develop a 3D deep neural network for each classification task. External validation was conducted with a total of 35,272 series from 7 publicly available datasets. The classification accuracy for each series was independently assessed for each task to evaluate model performance. Results: The accuracies for identifying the body parts, imaging axes, and the presence of intravenous contrast were 96.0% (95% CI: 94.6%, 97.2%), 99.2% (95% CI: 98.5%, 99.7%), and 97.5% (95% CI: 96.4%, 98.5%) respectively. The generalizability of the models was demonstrated through external validation with accuracies of 89.7 - 97.8%, 98.6 - 100%, and 87.8 - 98.6% for the same tasks. Conclusions: The developed models demonstrated high performance on both internal and external testing in identifying key aspects of a CT series. Graphical Abstract

The contributions of two energetically highest molecular orbitals to the harmonic emission rate are analysed for a two-component laser field. For diatomic molecules exposed to the elliptically polarised field, the emission from the highest-occupied molecular orbital (HOMO) is dominant for various molecular orientations with respect to the laser field. However, the contribution of the lower molecular orbital (HOMO-1) can become significant or even dominant for some molecular orientations. We introduce the ratio of the coherent over the incoherent sum of the HOMO and HOMO-1 contributions as a quantitative measure of the significance of the particular molecular orbital. Also, the gaseous medium response is different for the left and right elliptically polarised light and the molecular characteristics are imprinted into this difference. Moreover, for the orthogonally polarised two-colour (OTC) laser field the relative contributions of HOMO and HOMO-1 depend to a great extent on the relative phase between the field components. The importance of the HOMO-1 can be assessed by the relative error which is made if the harmonic spectra are obtained only with the HOMO contribution. Finally, we investigate the interference of the contributions of two highest molecular orbitals. We show that, for the OTC field, the destructive interference depends linearly on the intensity of the field components. Also, the interference minima shift towards the higher energies with the increase of the component wavelength.

Introduction We evaluated whether 12-week intake of molecular hydrogen (H2) in 5 overweight adults (3 women; age: 50.2 ±11.9 years, body mass index: 29.4 ±2.1 kg/m2) affects brain levels of the glutamate-glutamine-GABA cycle, critical amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation. Methods A 1.5-T single-voxel proton magnetic resonance spectroscopy was used to assess the tissue concentrations of relevant metabolites. Results The mean glutamate and glutamate-plus-glutamine levels at the posterior cingulate gyrus decreased significantly during the study; this was accompanied by a significant drop in GABA levels at left prefrontal white matter, and glutathione levels at anterior cingulate gyrus. No changes in the brain metabolites were found in the comparable group of overweight individuals (n = 4, 2 women; age: 41.0 ±13.9, BMI 26.8 ±1.3 kg/m2) followed-up in the past without this treatment. Conclusions We showed a possible hydrogen-driven upregulation of neurotransmitters involved in appetite stimulation leading to hunger suppression and weight loss. Further studies analyzing appetite-controlling metabolic pathways affected by H2 would require monitoring of additional biomarkers of satiation and satiety during different feeding regimens.

Connectedness is a multidimensional human experience that is essential to successful aging. The aims of this cross-sectional study were to assess connectedness and self-perception of successful aging in older people, to examine whether there are differences in relation to basic characteristics, and to examine whether there is a connection between connectedness and self-perception of successful aging. The respondents were elderly people in the Republic of Croatia. Data were collected using two validated scales: Croatian versions of the Register–Connectedness Scale for Older Adults and the Self-Assessment Scale of Successful Aging. The study included 824 respondents, of which 319 (38.7%) were men and 505 (61.3%) were women. The median age was 72 years. The median connectivity of the respondents was 8.9 (IQR= 7.6–10.2), and the median rating of successful aging was 3.25 (IQR = 1–5). Spearman’s correlation coefficient ρ (p value) was 0.585 (<0.001). Connectivity was rated better by respondents with a higher level of education, who were married, resided in their own homes, used modern technologies, and were active in the community. There is a significant positive association between connectedness and the self-perception of successful aging overall, as well as in all individual connectedness domains.

Conventional co-design methods, such as storyboarding and focus groups, are not always appropriate for people living with dementia (PLwD). In pilot robot co-design workshops in a local memory care facility, we noticed PLwD struggled to understand, express themselves, fully participate, and benefit from the experience. After reflecting on challenges with the facility’s director of program development and education, we redesigned the workshops prioritizing elements of the Eden Alternative’s well-being for PLwD: identity, connectedness, security, and autonomy. We delivered these new workshops over five weeks with 12 PLwD participants. Analysis of resulting video recordings and transcripts shows the new activities allowed participants to see themselves as having knowledge relevant to social robot design; to relate to each other, the robot, and the researchers; to feel comfortable; and to actively contribute to and offer valuable insights for robot design. Participants reported feeling meaning, growth, and joy during the workshops.

Telepresence robots are meant to provide physical access to digital remote spaces. However, they have a range of limitation that make spaces less accessible for remote participants. In this study we reveal, catalogue, and examine telepresence limitations in the context of the classroom. Based on ongoing field study results from participatory observations, surveys and interviews with 22 participants we discuss the extent to which telepresence robots make the classroom accessible and whether the telepresence robots are "disabled."

Background: Covert brain infarction (CBI) is highly prevalent and linked with stroke risk factors, increased mortality, and morbidity. Evidence to guide management is sparse. We sought to gain information on current practice and attitudes toward CBI and to compare differences in management according to CBI phenotype. Methods: We conducted a web-based, structured, international survey from November 2021 to February 2022 among neurologists and neuroradiologists. The survey captured respondents’ baseline characteristics, general approach toward CBI and included two case scenarios designed to evaluate management decisions taken upon incidental detection of an embolic-phenotype and a small-vessel-disease phenotype. Results: Of 627 respondents (38% vascular neurologists, 24% general neurologists, and 26% neuroradiologists), 362 (58%) had a partial, and 305 (49%) a complete response. Most respondents were university hospital senior faculty members experienced in stroke, mostly from Europe and Asia. Only 66 (18%) of respondents had established institutional written protocols to manage CBI. The majority indicated that they were uncertain regarding useful investigations and further management of CBI patients (median 67 on a slider 0–100, 95% CI 35–81). Almost all respondents (97%) indicated that they would assess vascular risk factors. Although most would investigate and treat similarly to ischemic stroke for both phenotypes, including initiating antithrombotic treatment, there was considerable diagnostic and therapeutic heterogeneity. Less than half of respondents (42%) would assess cognitive function or depression. Conclusions: There is a high degree of uncertainty and heterogeneity regarding management of two common types of CBI, even among experienced stroke physicians. Respondents were more proactive regarding the diagnostic and therapeutic management than the minimum recommended by current expert opinions. More data are required to guide management of CBI; meantime, more consistent approaches to identification and consistent application of current knowledge, that also consider cognition and mood, would be promising first steps to improve consistency of care.