Residential mobility and persistently depressed voting among disadvantaged adults in a large housing experiment.

This study examines the impact of residential mobility on electoral participation among the poor by matching data from Moving to Opportunity, a US-based multicity housing-mobility experiment, with nationwide individual voter data. Nearly all participants in the experiment were Black and Hispanic families who originally lived in high-poverty public housing developments. Notably, the study finds that receiving a housing voucher to move to a low-poverty neighborhood decreased adult participants' voter participation for nearly two decades-a negative impact equal to or outpacing that of the most effective get-out-the-vote campaigns in absolute magnitude. This finding has important implications for understanding residential mobility as a long-run depressant of voter turnout among extremely low-income adults.

Rapid Access to 2-Substituted Bicyclo[1.1.1]pentanes.

The replacement of aryl rings with saturated carbocyclic structures has garnered significant interest in drug discovery due to the potential for improved pharmacokinetic properties upon substitution. In particular, 1,3-difunctionalized bicyclo[1.1.1]pentanes (BCPs) have been widely adopted as bioisosteres for parasubstituted arene rings, appearing in a number of lead pharmaceutical candidates. However, despite the pharmaceutical value of 2-substituted BCPs as replacements for ortho- or meta-substituted arene rings, general and rapid syntheses of these scaffolds remain elusive. Current approaches to 2-substituted BCPs rely on installation of the bridge substituent prior to BCP core construction, leading to lengthy step counts and often nonmodular sequences. While challenging, direct functionalization of the strong bridge BCP C-H bonds would offer a more streamlined pathway to diverse 2-substituted BCPs. Here, we report a generalizable synthetic linchpin strategy for bridge functionalization via radical C-H abstraction of the BCP core. Through mild generation of a strong hydrogen atom abstractor, we rapidly synthesize novel 2-substituted BCP synthetic linchpins in one pot. These synthetic linchpins then serve as common precursors to complex 2-substituted BCPs, allowing one-step access to a number of previously inaccessible electrophile and nucleophile fragments at the 2-position via two new metallaphotoredox protocols. Altogether, this platform enables the expedient synthesis of four pharmaceutical analogues, all of which show similar or improved properties compared to their aryl-containing equivalents, demonstrating the potential of these 2-substituted BCPs in drug development.

Salvage surgery for local recurrences after stereotactic ablative radiotherapy of colorectal pulmonary metastases.

INTRODUCTION: Local control following stereotactic ablative radiotherapy (SABR) for patients with colorectal pulmonary metastases is reportedly lower than for metastases from other tumors. Such recurrences may still be amenable to salvage therapy. We describe our experience with salvage surgery in 17 patients. METHODS: Patients who underwent salvage metastasectomy for a local recurrence following SABR for colorectal pulmonary metastases were identified from the surgical institutional databases of three Dutch major referral hospitals. Kaplan-Meier survival analysis was performed to determine survival. RESULTS: Seventeen patients underwent 20 salvage resections for local recurrence of colorectal pulmonary metastases. All patients had a progressive lesion on consecutive CT scans, with local uptake on 18 fluorodeoxyglucose-positron emission tomography computed tomography (FDG-PET CT), and were discussed in a thoracic oncology tumor board. Median time to local recurrence following SABR was 20 months (interquartile range [IQR]: 13-29). Fourteen procedures were performed minimally invasively. Extensive adhesions were observed during three procedures. A Clavien-Dindo grade III-IV complication occurred after four resections (20%). The 90-day mortality was 0%. The estimated median overall survival and progression-free survival following salvage resection were 71 months (confidence intervals [CI]: 50-92) and 39 months (CI: 19-58), respectively. Salvage resections were significantly more extensive, compared to the potential resection assessed on pre-SABR imaging. CONCLUSIONS: Our experience with 20 salvage pulmonary metastasectomy procedures for local recurrences following SABR in colorectal cancer patients demonstrates that salvage resection is a feasible option with acceptable morbidity and good oncological outcome in a highly selected cohort.

An OMICs-based meta-analysis to support infection state stratification.

MOTIVATION: A fundamental problem for disease treatment is that while antibiotics are a powerful counter to bacteria, they are ineffective against viruses. Often, bacterial and viral infections are confused due to their similar symptoms and lack of rapid diagnostics. With many clinicians relying primarily on symptoms for diagnosis, overuse and misuse of modern antibiotics are rife, contributing to the growing pool of antibiotic resistance. To ensure an individual receives optimal treatment given their disease state and to reduce over-prescription of antibiotics, the host response can in theory be measured quickly to distinguish between the two states. To establish a predictive biomarker panel of disease state (viral/bacterial/no-infection), we conducted a meta-analysis of human blood infection studies using machine learning. RESULTS: We focused on publicly available gene expression data from two widely used platforms, Affymetrix and Illumina microarrays as they represented a significant proportion of the available data. We were able to develop multi-class models with high accuracies with our best model predicting 93% of bacterial and 89% viral samples correctly. To compare the selected features in each of the different technologies, we reverse-engineered the underlying molecular regulatory network and explored the neighbourhood of the selected features. The networks highlighted that although on the gene-level the models differed, they contained genes from the same areas of the network. Specifically, this convergence was to pathways including the Type I interferon Signalling Pathway, Chemotaxis, Apoptotic Processes and Inflammatory/Innate Response. AVAILABILITY: Data and code are available on the Gene Expression Omnibus and github. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The influence of antineoplastic agents on the peri-implant bone around osseointegrated titanium implants: an in vivo histomorphometric and immunohistochemical study.

BACKGROUND AND OBJECTIVE: The interaction between antineoplastic drugs used for treating cancer and non-affected tissues remains poorly assessed and may be critical for maintaining the quality of life for patients during and after treatment. This pre-clinical study evaluated the effects of cisplatin (CIS) and 5-fluorouracil (5-FU) on the peri-implant repair process around osseointegrated titanium implants installed in the tibiae of rats. MATERIAL AND METHODS: Were used 90 male rats, randomly divided into three groups (n = 30): physiological saline solution (PSS), CIS, and 5-FU. Titanium implants (4.0 × 2.2 mm) were inserted in both tibiae of all animals at day 0. The animals received either PSS, CIS, or 5-FU at 35 and 37 days. Euthanasia was performed at 50, 65, and 95 days after surgery. Histometric (bone/implant contact [BIC]) and bone area fraction occupancy (% BAFO), histological, and immunohistochemical (for bone morphogenetic protein 2/4 [BMP2/4], Runt-related transcription factor 2 [RUNX2], osteocalcin [OCN], and tartrate-resistant acid phosphatase [TRAP]) analyses were performed. Data were statistically analyzed. RESULTS: Groups CIS and 5-FU presented lower BIC and lower BAFO as compared with PSS in all time points. The imbalance in bone turnover was observed by the lower number of BMP2/4-, RUNX2-, and OCN-positive cells/mm2 and the higher number of TRAP-positive cells/mm in groups CIS and 5-FU as compared with PSS in all time points. Persistent and exacerbated inflammation was observed in groups CIS and 5-FU. CONCLUSIONS: Both antineoplastic agents interfered negatively in the bone turnover around osseointegrated titanium implants. CLINICAL RELEVANCE: Closer and more careful follow-up of patients with osseointegrated implants that will undergo chemotherapy with either CIS or 5-FU shall be performed.

Antineoplastic agents aggravate the damages caused by nicotine on the peri-implant bone: an in vivo histomorphometric and immunohistochemical study in rats.

OBJECTIVE: To assess the interaction between chemotherapy and normal tissues is critical to assure quality of life during and after the treatment of cancer. This study evaluated the influence of cisplatin (CIS) and 5-fluorouracil (5-FU) over the peri-implant tissues around osseointegrated titanium implants in animals previously exposed to nicotine. Materials and methods One hundred twenty male rats were divided into two groups, receiving via subcutaneous injection, either physiological saline solution (PSS) (n = 30) or nicotine hemissulfate (NIC) (n = 90) for 30 days prior to implants' placement. One titanium implant (4.0 × 2.2 mm) was installed in each tibia of all animals. PSS and NIC were continued for 30 days after surgery. Five days after cessation, rats were subdivided into three subgroups in accordance with systemic treatments with either PSS, CIS, or 5-FU. Euthanasia was performed at 50, 65, and 95 days post-surgery. Histometric, histopathological, and immunohistochemical analyses were performed. RESULTS: NIC-CIS and NIC-5FU presented lower BIC (50, 65, and 95 days) and bone area fraction occupancy (BAFO) (65 and 95 days) than group NIC. Intense inflammatory infiltration, severe tissue breakdown, reduced expression of bone formation biomarkers, and upregulation of TRAP were observed in NIC-CIS and NIC-5FU when compared with group NIC. TRAP expression was significantly higher in NIC-5FU as compared with NIC-CIS at 50 and 95 days. Groups NIC, NIC-CIS, and NIC-5FU presented statistically significant negative impact in all outcome parameters than group PSS. CONCLUSION: CIS and 5-FU severely disrupted the peri-implant tissues around osseointegrated implants in animals previously exposed to nicotine. CLINICAL RELEVANCE: Assessing the interaction between chemotherapy and normal tissues is critical to assure quality of life during and after the cancer treatment.

A critical review of cognitive behavioural therapy for hoarding disorder: How can we improve outcomes?

Psychological treatment for hoarding problems has historically been associated with poor outcomes. When treated as a subgroup of obsessive-compulsive disorder, individuals with hoarding beliefs were less likely to respond to treatment than individuals exhibiting other obsessive-compulsive beliefs and behaviours. When treated as its own disorder using cognitive behavioural therapy, individuals report approximately 25% improvement in symptoms on average. However, less than a third of people experience clinically meaningful change. Further, changes in functioning and quality of life are not routinely assessed. In this paper, we review the current conceptualization and treatment of hoarding problems to shed light on how treatment for hoarding disorder may be improved. Utilizing a harm reduction approach before administering treatment may be important to ensure the safety of individuals. Research should test whether treatment outcomes improve by including strategies that enhance a client's interpersonal functioning and ability to regulate emotions (i.e., based on dialectal behaviour therapy and mentalization-based treatments), especially while discarding and organizing belongings. We should also use modern learning theory to improve the delivery of exposure activities.

Depression, perceived disability and unemployment are associated with reduced life satisfaction in anorexia nervosa.

Life satisfaction is a core aspect of an individual's wellbeing and describes the subjective assessment of their quality of life. Reduced life satisfaction is frequently reported in anorexia nervosa (AN),  but the factors contributing to this are still unclear. This study sought to extend previous work by examining 12 potential correlates of AN life satisfaction. One hundred and five female AN patients were administered questionnaires assessing life satisfaction, depression, anxiety, stress, employment status, marital status, body mass index, eating disorder symptomatology, perceived disability and readiness for change. A stepwise linear regression revealed that only depression, perceived disability and employment status were significantly associated with AN life satisfaction. The findings thus highlight prevailing mood and personal functioning as critical foci for clinical management strategies in people with AN. Addressing depressive symptoms and perceived disability while bettering employment prospects could facilitate improved AN life satisfaction.

SAR towards indoline and 3-azaindoline classes of IDO1 inhibitors.

A novel series of IDO1 inhibitors have been identified with good IDO1 Hela cell and human whole blood activity. These inhibitors contain an indoline or a 3-azaindoline scaffold. Their structure-activity-relationship studies have been explored. Compounds 37 and 41 stood out as leads due to their good potency in IDO1 Hela assay, good IDO1 unbound hWB IC50s, reasonable unbound clearance, and good MRT in rat and dog PK studies.

Neural reactivity parameters of awareness predetermine one-year survival in patients with disorders of consciousness.

Objective: The current investigation evaluated the sensitivity of neural-reactivity markers of awareness versus standard clinical assessments in predicting 1-year survival in nonresponsive-awake patients with disorders of consciousness (DOC).Methods: Pre-attentive auditory mismatch-negativity (MMN) event-related potentials (ERP's), globally induced electroencephalography (EEG) spectral power following verbal command, and clinical parameters were assessed. The study included 10 patients with DOC with mixed etiology and 10 healthy controls (HC) at baseline. The clinical status of patients with DOC was reassessed after 1 year.Results: Unlike baseline clinical assessment scores, baseline MMN amplitudes of non-survivors and induced theta-power following verbal-command clearly distinguished the non-surviving patients versus surviving patients. Baseline MMN peak-amplitude latencies in survivors with DOC were significantly related to clinical outcome over a 1-year period.Conclusion: Current findings underscore the increased sensitivity of EEG-reactivity markers of awareness versus standard clinical scores in predicting 1-year clinical outcome and survival in patients with DOC. Further longitudinal research in larger DOC samples is needed to confirm the prognostic-reliability, and validity of neural reactivity parameters of awareness in patients with DOC. Current finding may have implications for clinical care and medical-legal decisions in unresponsive-awake patients, and could assist clinicians to predict their survival up to 1 year from admission.

How good is your metalens? Experimental verification of metalens performance criterion.

A metric for evaluation of overall metalens performance is presented. It is applied to determination of optimal operating spectral range of a metalens, both theoretically and experimentally. This metric is quite general and can be applied to the design and evaluation of future metalenses, particularly achromatic metalenses.

Nonlinear Diffraction in Asymmetric Dielectric Metasurfaces.

Metasurfaces provide new and promising mechanisms with which to control and manipulate light at the nanoscale. While most metasurfaces are designed to operate in the linear regime, it was recently shown that such metasurfaces may also generate nonlinear signals by manipulation of the higher-order susceptibility terms. As such, metasurfaces can generate additional harmonics without the need for light propagation, as typically occurs in nonlinear crystals. While such demonstrations typically rely on the nonlinear properties of metals, we hereby report the design, fabrication, and experimental characterization of a resonant dielectric metasurface made of amorphous silicon to create and manipulate second harmonic light and control its diffraction patterns. As shown in the paper, the second harmonic generation of light follows selection rules that rely on the asymmetry of the meta-atom. Given the fact that silicon crystals are centrosymmetric, the generation of the second harmonic signal in amorphous silicon is intriguing. In fact, the second harmonic signal is generated mostly from the surface of the meta-atom. It is the use of nanostructures that increases the surface-to-volume ratio and enables second harmonic generation. Additionally, the meta-atom is designed to exploit its spectral resonances in the principal and the second harmonic frequencies for providing electromagnetic field enhancement, which assists in boosting the generation of second harmonic signals.

Mechanistic Chromatographic Column Characterization for the Analysis of Flavonoids Using Quantitative Structure-Retention Relationships Based on Density Functional Theory.

This work aimed to unravel the retention mechanisms of 30 structurally different flavonoids separated on three chromatographic columns: conventional Kinetex C18 (K-C18), Kinetex F5 (K-F5), and IAM.PC.DD2. Interactions between analytes and chromatographic phases governing the retention were analyzed and mechanistically interpreted via quantum chemical descriptors as compared to the typical 'black box' approach. Statistically significant consensus genetic algorithm-partial least squares (GA-PLS) quantitative structure retention relationship (QSRR) models were built and comprehensively validated. Results showed that for the K-C18 column, hydrophobicity and solvent effects were dominating, whereas electrostatic interactions were less pronounced. Similarly, for the K-F5 column, hydrophobicity, dispersion effects, and electrostatic interactions were found to be governing the retention of flavonoids. Conversely, besides hydrophobic forces and dispersion effects, electrostatic interactions were found to be dominating the IAM.PC.DD2 retention mechanism. As such, the developed approach has a great potential for gaining insights into biological activity upon analysis of interactions between analytes and stationary phases imitating molecular targets, giving rise to an exceptional alternative to existing methods lacking exhaustive interpretations.

The global decline of freshwater megafauna.

Freshwater ecosystems are among the most diverse and dynamic ecosystems on Earth. At the same time, they are among the most threatened ecosystems but remain underrepresented in biodiversity research and conservation efforts. The rate of decline of vertebrate populations is much higher in freshwaters than in terrestrial or marine realms. Freshwater megafauna (i.e., freshwater animals that can reach a body mass ≥30 kg) are intrinsically prone to extinction due to their large body size, complex habitat requirements and slow life-history strategies such as long life span and late maturity. However, population trends and distribution changes of freshwater megafauna, at continental or global scales, remain unclear. In the present study, we compiled population data of 126 freshwater megafauna species globally from the Living Planet Database and available literature, and distribution data of 44 species inhabiting Europe and the United States from literature and databases of the International Union for Conservation of Nature and NatureServe. We quantified changes in population abundance and distribution range of freshwater megafauna species. Globally, freshwater megafauna populations declined by 88% from 1970 to 2012, with the highest declines in the Indomalaya and Palearctic realms (-99% and -97%, respectively). Among taxonomic groups, mega-fishes exhibited the greatest global decline (-94%). In addition, freshwater megafauna experienced major range contractions. For example, distribution ranges of 42% of all freshwater megafauna species in Europe contracted by more than 40% of historical areas. We highlight the various sources of uncertainty in tracking changes in populations and distributions of freshwater megafauna, such as the lack of monitoring data and taxonomic and spatial biases. The detected trends emphasize the critical plight of freshwater megafauna globally and highlight the broader need for concerted, targeted and timely conservation of freshwater biodiversity.

Antineoplastic agents exacerbate periodontal inflammation and aggravate experimental periodontitis.

AIM: This study evaluated the effects of 5-fluorouracil (5-FU) and cisplatin (CIS) in healthy periodontal tissues and in the early stages of experimental periodontitis (EP) in rats. METHODS: One hundred and eighty male rats were divided into three groups, which were submitted to the following systemic treatments: physiological saline solution (PSS); CIS and 5FU. Each group was subdivided into two subgroups: without (NEP) and with (EP) induction of EP. Animals were euthanized at 3, 5 and 7 days post-treatment. Histological, histometric (percentage of bone in the furcation [PBF]) and immunohistochemical (for tumour necrosis factor-α, interleukin-1ß and receptor activator of nuclear factor-κB ligand) analyses were performed. Data were statistically analysed. RESULTS: CIS-NEP and 5FU-NEP showed more inflammation than PSS-NEP at 3, 5 and 7 days. CIS-EP and 5FU-EP showed more inflammation and lower PBF than PSS-EP at all periods of evaluation. 5FU-EP showed lower PBF than CIS-EP at 5 and 7 days. CONCLUSION: 5-FU and CIS exacerbated periodontal inflammation and aggravated the progression of EP in its early stages.

Non-Linear Quantitative Structure⁻Activity Relationships Modelling, Mechanistic Study and In-Silico Design of Flavonoids as Potent Antioxidants.

In this work, we developed quantitative structure-activity relationships (QSAR) models for prediction of oxygen radical absorbance capacity (ORAC) of flavonoids. Both linear (partial least squares-PLS) and non-linear models (artificial neural networks-ANNs) were built using parameters of two well-established antioxidant activity mechanisms, namely, the hydrogen atom transfer (HAT) mechanism defined with the minimum bond dissociation enthalpy, and the sequential proton-loss electron transfer (SPLET) mechanism defined with proton affinity and electron transfer enthalpy. Due to pronounced solvent effects within the ORAC assay, the hydration energy was also considered. The four-parameter PLS-QSAR model yielded relatively high root mean square errors (RMSECV = 0.783, RMSEE = 0.668, RMSEP = 0.900). Conversely, the ANN-QSAR model yielded considerably lower errors (RMSEE = 0.180 ± 0.059, RMSEP1 = 0.164 ± 0.128, and RMSEP2 = 0.151 ± 0.114) due to the inherent non-linear relationships between molecular structures of flavonoids and ORAC values. Five-fold cross-validation was found to be unsuitable for the internal validation of the ANN-QSAR model with a high RMSECV of 0.999 ± 0.253; which is due to limited sample size where resampling with replacement is a considerably better alternative. Chemical domains of applicability were defined for both models confirming their reliability and robustness. Based on the PLS coefficients and partial derivatives, both models were interpreted in terms of the HAT and SPLET mechanisms. Theoretical computations based on density functional theory at ωb97XD/6-311++G(d,p) level of theory were also carried out to further shed light on the plausible mechanism of anti-peroxy radical activity. Calculated energetics for simplified models (genistein and quercetin) with peroxyl radical derived from 2,2'-azobis (2-amidino-propane) dihydrochloride suggested that both SPLET and single electron transfer followed by proton loss (SETPL) mechanisms are competitive and more favorable than HAT in aqueous medium. The finding is in good accord with the ANN-based QSAR modelling results. Finally, the strongly predictive ANN-QSAR model was used to predict antioxidant activities for a series of 115 flavonoids designed combinatorially with flavone as a template. Structural trends were analyzed, and general guidelines for synthesis of new flavonoid derivatives with potentially potent antioxidant activities were given.

Differences in regional grey matter volumes in currently ill patients with anorexia nervosa.

Neurobiological findings in anorexia nervosa (AN) are inconsistent, including differences in regional grey matter volumes. Methodological limitations often contribute to the inconsistencies reported. The aim of this study was to improve on these methodologies by utilising voxel-based morphometry (VBM) analysis with the use of diffeomorphic anatomic registration through an exponentiated lie algebra algorithm (DARTEL), in a relatively large group of individuals with AN. Twenty-six individuals with AN and 27 healthy controls underwent a T1-weighted magnetic resonance imaging (MRI) scan. AN participants were found to have reduced grey matter volumes in a number of areas including regions of the basal ganglia (including the ventral striatum), and parietal and temporal cortices. Body mass index (BMI) and global scores on the Eating Disorder Examination Questionnaire (EDE-Q) were also found to correlate with grey matter volumes in a region of the brainstem (including the substantia nigra and ventral tegmental area) in AN, and predicted 56% of the variance in grey matter volumes in this area. The brain regions associated with grey matter reductions in AN are consistent with regions responsible for cognitive deficits associated with the illness including anhedonia, deficits in affect perception and saccadic eye movement abnormalities. Overall, the findings suggest reduced grey matter volumes in AN that are associated with eating disorder symptomatology.

Interpretation of ANN-based QSAR models for prediction of antioxidant activity of flavonoids.

Quantitative structure-activity relationships (QSARs) built using machine learning methods, such as artificial neural networks (ANNs) are powerful in prediction of (antioxidant) activity from quantum mechanical (QM) parameters describing the molecular structure, but are usually not interpretable. This obvious difficulty is one of the most common obstacles in application of ANN-based QSAR models for design of potent antioxidants or elucidating the underlying mechanism. Interpreting the resulting models is often omitted or performed erroneously altogether. In this work, a comprehensive comparative study of six methods (PaD, PaD2 , weights, stepwise, perturbation and profile) for exploration and interpretation of ANN models built for prediction of Trolox-equivalent antioxidant capacity (TEAC) QM descriptors, is presented. Sum of ranking differences (SRD) was used for ranking of the six methods with respect to the contributions of the calculated QM molecular descriptors toward TEAC. The results show that the PaD, PaD2 and profile methods are the most stable and give rise to realistic interpretation of the observed correlations. Therefore, they are safely applicable for future interpretations without the opinion of an experienced chemist or bio-analyst. © 2018 Wiley Periodicals, Inc.

Target-based drug discovery through inversion of quantitative structure-drug-property relationships and molecular simulation: CA IX-sulphonamide complexes.

In this work, a target-based drug screening method is proposed exploiting the synergy effect of ligand-based and structure-based computer-assisted drug design. The new method provides great flexibility in drug design and drug candidates with considerably lower risk in an efficient manner. As a model system, 45 sulphonamides (33 training, 12 testing ligands) in complex with carbonic anhydrase IX were used for development of quantitative structure-activity-lipophilicity (property)-relationships (QSPRs). For each ligand, nearly 5,000 molecular descriptors were calculated, while lipophilicity (logkw) and inhibitory activity (logKi) were used as drug properties. Genetic algorithm-partial least squares (GA-PLS) provided a QSPR model with high prediction capability employing only seven molecular descriptors. As a proof-of-concept, optimal drug structure was obtained by inverting the model with respect to reference drug properties. 3509 ligands were ranked accordingly. Top 10 ligands were further validated through molecular docking. Large-scale MD simulations were performed to test the stability of structures of selected ligands obtained through docking complemented with biophysical experiments.

High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

PRIMARY OBJECTIVE: Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. DESIGN AND METHODS: HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. RESULTS: There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. CONCLUSIONS: These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.