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Objectives: To help promote early detection of cognitive impairment in primary care, MyCog Mobile was designed as a cognitive screener that can be self-administered remotely on a personal smartphone. We explore the potential utility of MyCog Mobile in primary care by comparing MyCog Mobile to a commonly used screener, Mini-Cog. Methods: A sample of 200 older adults 65+ years (mean age = 72.56 years), completed the Mini-Cog and MyCog Mobile, which includes 2 memory measures and 2 executive functioning measures. A logistic regression model was conducted to predict failing Mini-Cog scores (≤2) based on MyCog Mobile measures. Results: A total of 20 participants earned a Mini-Cog score ≤2. MyCog Mobile demonstrated an AUC of 0.83 (95% bootstrap CI [0.75, 0.95]), sensitivity of 0.76 (95% bootstrap CI [0.63, 0.97]), and specificity of.88 (95% bootstrap CI [0.63, 0.10]). The subtest Name Matching from MyFaces and MySorting were the only significant predictors of failed Mini-Cogs. Conclusions: MyCog Mobile demonstrated sensitivity and specificity to identify participants who failed the Mini-Cog, and may show promise as a screening tool for cognitive impairment in older adults. Further research is necessary to establish the clinical utility of MyCog Mobile in a larger sample using documented clinical diagnoses. [ABSTRACT FROM AUTHOR]

Background/Objectives: Diagnosing concussions is problematic, in part due to the invisible nature of concussion symptoms, in addition to personal and interpersonal factors that influence symptom reporting. As a result, observable signs of concussion can ensure concussions are identified and appropriately treated. Here, we define a potential novel sign, the spontaneous headshake after a kinematic event (SHAAKE) and evaluate its utility in the diagnosis of concussion. Methods: A cross-sectional survey study of 347 athletes (age 27, IQR: 25–29; 47.6% female; highest level of play: college—46.1%, high school—41.2%) identified whether SHAAKE occurred, the reasons underlying SHAAKEs, and its utility for self-reported concussion. Sensitivity and positive predictive value were calculated across all sports and these parameters, as well as estimates for specificity and negative predictive value leveraging published helmet sensor data, were calculated for football players. Results: The median number of times participants reported SHAAKE was 5 (IQR: 3–10), with 4 (IQR: 2–7) associated with a self-reported concussion. Overall, 84.9% of participants reported concussion symptoms as the most common reason for their SHAAKEs. Across all sports, SHAAKE had a sensitivity of 49.6% and positive predictive value 72.4% for diagnosing concussion. In football players, SHAAKE had a sensitivity of 52.3%, estimated specificity of 99.9%, positive predictive value of 91.9%, and estimated negative predictive value of 99.5% for diagnosing self-reported concussion. Conclusions: These results demonstrate that nearly three-quarters of athletes reported a SHAAKE associated with a self-reported concussion, which supports the potential for SHAAKE to be used as a concussion screening tool. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy more frequently found in deceased former football players. CTE has heterogeneous clinical presentations with multifactorial causes. Previous literature has shown substance use (alcohol/drug) can contribute to Alzheimer's disease and related tauopathies pathologically and clinically. Objective: To examine the association between substance use and clinical and neuropathological endpoints of CTE. Methods: Our sample included 429 deceased male football players. CTE was neuropathologically diagnosed. Informant interviews assessed features of substance use and history of treatment for substance use to define indicators: history of substance use treatment (yes vs no, primary variable), alcohol severity, and drug severity. Outcomes included scales that were completed by informants to assess cognition (Cognitive Difficulties Scale, BRIEF-A Metacognition Index), mood (Geriatric Depression Scale-15), behavioral regulation (BRIEF-A Behavioral Regulation Index, Barratt Impulsiveness Scale-11), functional ability (Functional Activities Questionnaire), as well as CTE status and cumulative p-tau burden. Regression models tested associations between substance use indicators and outcomes. Results: Of the 429 football players (mean age = 62.07), 313 (73%) had autopsy confirmed CTE and 100 (23%) had substance use treatment history. Substance use treatment and alcohol/drug severity were associated with measures of behavioral regulation (FDR-p-values<0.05, ΔR2 = 0.04–0.18) and depression (FDR-p-values<0.05, ΔR2 = 0.02–0.05). Substance use indicators had minimal associations with cognitive scales, whereas p-tau burden was associated with all cognitive scales (p-values <0.05). Substance use treatment had no associations with neuropathological endpoints (FDR-p-values>0.05). Conclusions: Among deceased football players, substance use was common and associated with clinical symptoms. [ABSTRACT FROM AUTHOR]

The presentation of cortical arteries is challenging, as most of their course is hidden in the depth of the sulci. Despite that, demonstrating the arteries on the cortical surface is a standard way of their presentation. To keep advantages of surface presentation while lessening its limitation, we propose a novel context-related method of cerebrovasculature presentation by cortical openings consisting in the removal of a selected region from the cortical mantle and exposing underlying structures. We also introduce a reverse than standard vessel-to-context mapping from a gyrus/lobule to vessels supplying it. The method has the following steps: define a cortical opening, develop a tool to perform them, create cortical openings for gyri and lobules with underlying white matter and intracranial arteries, generate labeled and parcellated images for the created openings, and integrate the cortical opening images with the NOW in BRAIN public repository of 8600 3D neuroimages. The cortical openings are created for 64 gyri and six lobules for the left and right cerebral hemispheres resulting in 210 images arranged in triples as spatially corresponding non-parcellated and unlabeled, parcellated by color and unlabeled, and parcellated and labeled images. The cortical opening approach, generally, increases vessel exposure in a higher number of depicted branches, revealing arteries otherwise hidden deep in sulci, a more complete vessel course, and a lower number of required views. The gyrus/lobule-to-arteries mapping facilitates exploration of a studied region, encapsulates all local arteries, and reduces vascular complexity by decomposing the entire vascular system into smaller sets involved in the studied region. [ABSTRACT FROM AUTHOR]

One of the key challenges in neuroscience is to generate the human nanoscale connectome which requires comprehensive knowledge of synaptome forming the neural microcircuits. The synaptic architecture determines limits of individual mental capacity and provides the framework for understanding neurologic disorders. Here, I address morphology modeling and storage estimation for the human synaptome at the nanoscale. A synapse is defined as a pair of pairs [(presynaptic_neuron),(presynaptic_axonal_terminal);(postsynaptic_neuron),(postsynaptic_dendritic_terminal)]. Center coordinates, radius, and identifier characterize a dendritic or axonal terminal. A synapse comprises topology with the paired neuron and terminal identifiers, location with terminal coordinates, and geometry with terminal radii. The storage required for the synaptome depends on the number of synapses and storage necessary for a single synapse determined by a synaptic model. I introduce three synaptic models: topologic with topology, point with topology and location, and geometric with topology, location, and geometry. To accommodate for a wide range of variations in the numbers of neurons and synapses reported in the literature, four cases of neurons (30;86;100;138 billion) and three cases of synapses per neuron (1,000;10,000;30,000) are considered with three full and simplified (to reduce storage) synaptic models resulting in total 72 cases of storage estimation. The full(simplified) synaptic model of the entire human brain requires from 0.21(0.14) petabytes (PB) to 28.98(18.63) PB for the topologic model, from 0.57(0.32) PB to 78.66(43.47) PB for the point model, and from 0.69(0.38) PB to 95.22(51.75) PB for the geometric model. The full(simplified) synaptic model of the cortex needs from 86.80(55.80) TB to 2.60(1.67) PB for the topologic model, from 235.60(130.02) TB to 7.07(3.91) PB for the point model, and from 285.20(155.00) TB to 8.56(4.65) PB for the geometric model. The topologic model is sufficient to compute the connectome's topology, but it is still too big to be stored on today's top supercomputers related to neuroscience. Frontier, the world's most powerful supercomputer for 86 billion neurons can handle the nanoscale synaptome in the range of 1,000–10,000 synapses per neuron. To my best knowledge, this is the first big data work attempting to provide storage estimation for the human nanoscale synaptome. [ABSTRACT FROM AUTHOR]

Background: Roughly 24–36% of people who are incarcerated in the U.S. are formally diagnosed with opioid use disorder (OUD). Once released, individuals involved with the criminal legal system (CLS) face increased risks of return to use and fatality and are 129 times more likely to die from an overdose within the first two weeks of release compared to those without CLS involvement. People who are CLS-involved and who are seeking a recovery living environment can access temporary stable housing through recovery homes. However, entering a recovery home can be difficult due to fragmentation among recovery housing organizations and their non-uniform application and screening procedures. A navigation pilot program was implemented to provide clients with recovery home placement advice, pre-screening, and referrals in Cook County, IL. Existing research on recovery homes has rarely examined the importance of recovery housing navigation for enhancing service engagement among CLS-involved individuals receiving medications for OUD. Methods: Semi-structured qualitative interviews were conducted with 22 clients and three recovery housing navigators as part of a program evaluation of the navigation program pilot. Qualitative software was used to organize and qualitatively analyze transcripts through several rounds of coding producing emergent themes, which were then triangulated, and expanded using navigator data. Results: Clients seeking recovery home services reported multiple prior challenges securing safe and supportive recovery living environments. Despite low initial expectations, clients described their interactions with housing navigators in favorable terms and felt navigators worked with them effectively to identify and meet their housing and substance use needs in a timely manner. Clients also commented on their partnerships with the navigator throughout the process. Interactions with navigators also calmed fears of rejection many clients had previously experienced and still harbored about the process, which bolstered client-navigator relationships and client motivation to engage with additional services. Conclusion: Evidence from this study suggests recovery home navigation can improve the speed and efficiency with which clients are connected to appropriate services that are tailored to their specific needs as well as increase client motivation to engage with a myriad of recovery services. [ABSTRACT FROM AUTHOR]

Objective We describe the development of a new computer adaptive vocabulary test, Mobile Toolbox (MTB) Word Meaning, and validity evidence from 3 studies. Method Word Meaning was designed to be a multiple-choice synonym test optimized for self-administration on a personal smartphone. The items were first calibrated online in a sample of 7,525 participants to create the computer-adaptive test algorithm for the Word Meaning measure within the MTB app. In Study 1, 92 participants self-administered Word Meaning on study-provided smartphones in the lab and were administered external measures by trained examiners. In Study 2, 1,021 participants completed the external measures in the lab and Word Meaning was self-administered remotely on their personal smartphones. In Study 3, 141 participants self-administered Word Meaning remotely twice with a 2-week delay on personal iPhones. Results The final bank included 1363 items. Internal consistency was adequate to good across samples (ρxx = 0.78 to 0.81, p  < .001). Test–retest reliability was good (ICC = 0.65, p  < .001), and the mean theta score was not significantly different upon the second administration. Correlations were moderate to large with measures of similar constructs (ρ = 0.67–0.75, p  < .001) and non-significant with measures of dissimilar constructs. Scores demonstrated small to moderate correlations with age (ρ = 0.35 to 0.45, p  < .001) and education (ρ = 0.26, p  < .001). Conclusion The MTB Word Meaning measure demonstrated evidence of reliability and validity in three samples. Further validation studies in clinical samples are necessary. [ABSTRACT FROM AUTHOR]

Introduction: Emotional functioning in older adults is influenced by normal aging and cognitive impairment, likely heterogeneous across positive versus negative aspects of emotional functioning. Little is known about positive emotional experiences at the early stages of cognitive impairment. Methods: We assessed different aspects of emotional functioning among 448 participants aged 65+ (Normal Control (NC) = 276, Mild Cognitive Impairment (MCI) = 103, and mild dementia of the Alzheimer type (mild DAT) = 69) and tested moderators. Results: Compared to NC, older adults with MCI and mild DAT have maintained many positive aspects of emotional functioning, despite higher levels of negative affect, sadness, and loneliness. Among the oldest-old, the mild DAT group experienced higher fear and lower self-efficacy. Discussion: Older adults at early stages of cognitive impairment can experience positive aspects of emotional functioning, such as positive affect, purpose, and life satisfaction, all of which are important buildable psychological resources for coping. [ABSTRACT FROM AUTHOR]

Objective: The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties. Method: MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart. Results: All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability. Conclusions: Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the refractive outcome and strabismus at 5 years of age, in children operated for various types of non‐syndromic craniosynostosis, and further analyse the refractive and strabismic development over time. Methods: Eighty‐nine children, who had undergone operations for non‐syndromic craniosynostosis, were examined at 5 years of age. These children also underwent ophthalmological examination preoperatively and up to 1 year after the operation. An age‐matched control group including 32 healthy children was also recruited. Strabismus and eye motility were registered. Refraction was measured in cycloplegia. Results: There was a difference regarding the refractive outcome between the different types of craniosynostosis. Higher values of hypermetropia were found in the metopic craniosynostosis group on both eyes. In the unicoronal craniosynostosis group, high values of hypermetropia and a higher degree of astigmatism were found on the side contralateral to the craniosynostosis. Strabismus was found in 11/88 children of whom 10/11 had unicoronal craniosynostosis. A vertical deviation on the side ipsilateral to the fused suture was highly prevalent (6/10 cases). Ophthalmological dysfunctions were rare in children operated for sagittal craniosynostosis. Conclusion: Ocular manifestations such as strabismus, astigmatism and anisometropia were highly prevalent in children operated for unilateral coronal craniosynostosis. Children operated for metopic craniosynostosis had higher rates of hypermetropia. The screening and follow‐up protocols need to be tailored with regard to the type of craniosynostosis. [ABSTRACT FROM AUTHOR]

Children with autism spectrum disorder (ASD) exhibit significant deficits in social communication and emotion regulation skills. While cognitive behavioral therapy (CBT) applications appear promising, trials to date have largely excluded social communication skill development and have not been designed to include a wider range of emotional challenges. To our knowledge, the present study is the first to pilot a uniquely modified CBT program targeting emotion regulation, including social communication training, and explicitly focusing on the child's areas of circumscribed interest in order to teach skills and promote generalization. Forty participants were randomly assigned to either the CBT group or a waitlist control (WLC) group, resulting in 20 school-aged children in each group. The treatment approach was determined to be feasible and acceptable, and therapy engagement and attendance were reasonably high. Caregivers expressed high satisfaction with the program, qualitatively citing gains in skills such as social problem-solving, emotion identification, and identifying and processing cognitive distortions. The primary outcome of postintervention changes was not significantly different between the groups (CBT vs. WLC). The mean Social Skills Improvement System score decreased by 0.44 points (95% confidence interval [CI]: −5.04, 4.15) in the CBT group and increased by 0.41 points (95% CI: −4.23, 5.04) in the WLC group, and the postintervention changes were not significantly different between the groups (difference: −0.85; 95% CI: −7.29, 5.60; p =.79). The estimated rate of emotional dysregulation episodes decreased by a factor of 0.94 (95% CI: 0.57, 1.56) in the CBT group and increased by a factor of 1.07 (95% CI: 0.51, 2.24) for WLC (p =.74). Among those who reported emotional dysregulation episodes, the mean duration decreased by 1.39 minutes (95% CI: −3.90, 6.67) less for CBT than waitlist (p =.60). Although satisfaction, acceptability, and emotional dysregulation outcome results from this preliminary CBT treatment for ASD are promising, sample size and measurement limitations will be important considerations to inform future trials. [ABSTRACT FROM AUTHOR]

Stroke management employs a variety of diagnostic imaging modalities, image processing and analysis methods, and treatment procedures. This work categorizes methods for stroke imaging, image processing and analysis, and treatment, and provides their taxonomies illustrated by a state-of-the-art review. Imaging plays a critical role in stroke management, and the most frequently employed modalities are computed tomography (CT) and magnetic resonance (MR). CT includes unenhanced non-contrast CT as the first-line diagnosis, CT angiography, and CT perfusion. MR is the most complete method to examine stroke patients. MR angiography is useful to evaluate the severity of artery stenosis, vascular occlusion, and collateral flow. Diffusion-weighted imaging is the gold standard for evaluating ischemia. MR perfusion-weighted imaging assesses the penumbra. The stroke image processing methods are divided into non-atlas/template-based and atlas/template-based. The non-atlas/template-based methods are subdivided into intensity and contrast transformations, local segmentation-related, anatomy-guided, global density-guided, and artificial intelligence/deep learning-based. The atlas/template-based methods are subdivided into intensity templates and atlases with three atlas types: anatomy atlases, vascular atlases, and lesion-derived atlases. The treatment procedures for arterial and venous strokes include intravenous and intraarterial thrombolysis and mechanical thrombectomy. This work captures the state-of-the-art in stroke management summarized in the form of comprehensive and straightforward taxonomy diagrams. All three introduced taxonomies in diagnostic imaging, image processing and analysis, and treatment are widely illustrated and compared against other state-of-the-art classifications. [ABSTRACT FROM AUTHOR]

Arranging Pictures is a new episodic memory test based on the NIH Toolbox (NIHTB) Picture Sequence Memory measure and optimized for self-administration on a personal smartphone within the Mobile Toolbox (MTB). We describe evidence from three distinct validation studies. In Study 1, 92 participants self-administered Arranging Pictures on study-provided smartphones in the lab and were administered external measures of similar and dissimilar constructs by trained examiners to assess validity under controlled circumstances. In Study 2, 1,021 participants completed the external measures in the lab and self-administered Arranging Pictures remotely on their personal smartphones to assess validity in real-world contexts. In Study 3, 141 participants self-administered Arranging Pictures remotely twice with a two-week delay on personal iOS smartphones to assess test-retest reliability and practice effects. Internal consistency was good across samples (ρxx =.80 to.85, p <.001). Test-retest reliability was marginal (ICC =.49, p <.001) and there were significant practice effects after a two-week delay (ΔM = 3.21 (95% CI [2.56, 3.88]). As expected, correlations with convergent measures were significant and moderate to large in magnitude (ρ =.44 to.76, p <.001), while correlations with discriminant measures were small (ρ =.23 to.27, p <.05) or nonsignificant. Scores demonstrated significant negative correlations with age (ρ = -.32 to −.21, p <.001). Mean performance was slightly higher in the iOS compared to the Android group (MiOS = 18.80, NiOS = 635; MAndroid = 17.11, NAndroid = 386; t(757.73) = 4.17, p <.001), but device type did not significantly influence the psychometric properties of the measure. Indicators of potential cheating were mixed; average scores were significantly higher in the remote samples (F(2, 850) = 11.415, p <.001), but there were not significantly more perfect scores. The MTB Arranging Pictures measure demonstrated evidence of reliability and validity when self-administered on personal device. Future research should examine the potential for cheating in remote settings and the properties of the measure in clinical samples. [ABSTRACT FROM AUTHOR]

While cognitive behavioral therapy (CBT) is a first-line treatment for anxiety, it is not typically offered to those with intellectual disability (ID). In this article, we provide a historical perspective on the treatment of mental health concerns in adults with ID, describe an adapted CBT treatment for anxiety in adults with Williams syndrome (WS) and mild to moderate ID, and discuss general modifications to CBT for adults with ID. Strategies used to successfully adapt CBT for adults with WS that may generalize to adults with ID more broadly include (a) using child-based CBT manuals as a framework, (b) involving a caregiver as a therapy partner, (c) incorporating a high level of repetition, (d) simplifying language, (e) slowing the pace of instruction, and (f) incorporating specific examples and adaptations for WS. [ABSTRACT FROM AUTHOR]

Timely detection of cognitive impairment (CI) is critical for the wellbeing of elderly individuals. The MyCog assessment employs two validated iPad-based measures from the NIH Toolbox® for Assessment of Neurological and Behavioral Function (NIH Toolbox). These measures assess pivotal cognitive domains: Picture Sequence Memory (PSM) for episodic memory and Dimensional Change Card Sort Test (DCCS) for cognitive flexibility. The study involved 86 patients and explored diverse machine learning models to enhance CI prediction. This encompassed traditional classifiers and neural-network-based methods. After 100 bootstrap replications, the Random Forest model stood out, delivering compelling results: precision at 0.803, recall at 0.758, accuracy at 0.902, F1 at 0.742, and specificity at 0.951. Notably, the model incorporated a composite score derived from a 2-parameter higher order item response theory (HOIRT) model that integrated DCCS and PSM assessments. The study's pivotal finding underscores the inadequacy of relying solely on a fixed composite score cutoff point. Instead, it advocates for machine learning models that incorporate HOIRT-derived scores and encompass relevant features such as age. Such an approach promises more effective predictive models for CI, thus advancing early detection and intervention among the elderly. [ABSTRACT FROM AUTHOR]

Purpose: To develop the PROMIS Pediatric Stigma (PPS) and Skin (PPS-Skin) by constructing a common metric for measuring stigma in children with various conditions, while capturing the unique features of each condition. Methods: Data from 860 children, ages 8–17, with a diagnosis of epilepsy, pNF (neurofibromatosis type 1 associated neurofibroma plexform), MD (muscular dystrophy), cancer, or skin conditions recruited from three projects were analyzed. Children with epilepsy, pNF and MD (sample-1) completed the original 18-item Neuro-QoL Stigma, while children with cancer and skin conditions (e.g., atopic dermatitis, psoriasis, and genetic skin disorders; sample-2) completed a 16-item version and 6 additional skin related items. Exploratory factor analysis (EFA) and confirmatory analysis (CFA) were used to evaluate unidimensionality of 24 stigma items. Differential item functioning (DIF) was used to evaluate measurement equivalence on group, gender, age, and conditions. Item response theory model (IRT) was used to construct the final measure. Results: Sufficient unidimensionality was supported by both EFA and CFA. No items showed significant DIF indicating stable measurement properties across groups of comparison. All items fit the IRT model and were able to be calibrated together to form the PPS which consists of 18 core items. The PPS-Skin (18 cores items + 6 skin items) was developed by calibrating 6 skin items onto the common metric as the PPS. Conclusions: We used IRT techniques to successfully develop the PPS and the PPS-Skin, which share a common metric and account for unique and common concerns related to chronic conditions. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by hyperphosphorylated tau (p-tau) accumulation. The clinical features associated with CTE pathology are unclear. In brain donors with autopsy-confirmed CTE, we investigated the association of CTE p-tau pathology density and location with cognitive, functional, and neuropsychiatric symptoms. Methods: In 364 brain donors with autopsy confirmed CTE, semi-quantitative p-tau severity (range: 0–3) was assessed in 10 cortical and subcortical regions. We summed ratings across regions to form a p-tau severity global composite (range: 0–30). Informants completed standardized scales of cognition (Cognitive Difficulties Scale, CDS; BRIEF-A Metacognition Index, MI), activities of daily living (Functional Activities Questionnaire), neurobehavioral dysregulation (BRIEF-A Behavioral Regulation Index, BRI; Barratt Impulsiveness Scale, BIS-11), aggression (Brown-Goodwin Aggression Scale), depression (Geriatric Depression Scale-15, GDS-15), and apathy (Apathy Evaluation Scale, AES). Ordinary least squares regression models examined associations between global and regional p-tau severity (separate models for each region) with each clinical scale, adjusting for age at death, racial identity, education level, and history of hypertension, obstructive sleep apnea, and substance use treatment. Ridge regression models that incorporated p-tau severity across all regions in the same model assessed which regions showed independent effects. Results: The sample was predominantly American football players (333; 91.2%); 140 (38.5%) had low CTE and 224 (61.5%) had high CTE. Global p-tau severity was associated with higher (i.e., worse) scores on the cognitive and functional scales: MI (β standardized = 0.02, 95%CI = 0.01–0.04), CDS (β standardized = 0.02, 95%CI = 0.01–0.04), and FAQ (β standardized = 0.03, 95%CI = 0.01–0.04). After false-discovery rate correction, p-tau severity in the frontal, inferior parietal, and superior temporal cortex, and the amygdala was associated with higher CDS (β sstandardized = 0.17–0.29, ps < 0.01) and FAQ (β sstandardized = 0.21–0.26, ps < 0.01); frontal and inferior parietal cortex was associated with higher MI (β sstandardized = 0.21–0.29, ps < 0.05); frontal cortex was associated with higher BRI (β standardized = 0.21, p < 0.01). Regions with effects independent of other regions included frontal cortex (CDS, MI, FAQ, BRI), inferior parietal cortex (CDS) and amygdala (FAQ). P-tau explained 13–49% of variance in cognitive and functional scales and 6–14% of variance in neuropsychiatric scales. Conclusion: Accumulation of p-tau aggregates, especially in the frontal cortex, are associated with cognitive, functional, and certain neurobehavioral symptoms in CTE. [ABSTRACT FROM AUTHOR]

Objective: Exposure to repetitive head impacts (RHI) is associated with later‐life cognitive symptoms and neuropathologies, including chronic traumatic encephalopathy (CTE). Cognitive decline in community cohorts is often due to multiple pathologies; however, the frequency and contributions of these pathologies to cognitive impairment in people exposed to RHI are unknown. Here, we examined the relative contributions of 13 neuropathologies to cognitive symptoms and dementia in RHI‐exposed brain donors. Methods: Neuropathologists examined brain tissue from 571 RHI‐exposed donors and assessed for the presence of 13 neuropathologies, including CTE, Alzheimer disease (AD), Lewy body disease (LBD), and transactive response DNA‐binding protein 43 (TDP‐43) inclusions. Cognitive status was assessed by presence of dementia, Functional Activities Questionnaire, and Cognitive Difficulties Scale. Spearman rho was calculated to assess intercorrelation of pathologies. Additionally, frequencies of pathological co‐occurrence were compared to a simulated distribution assuming no intercorrelation. Logistic and linear regressions tested associations between neuropathologies and dementia status and cognitive scale scores. Results: The sample age range was 18–97 years (median = 65.0, interquartile range = 46.0–76.0). Of the donors, 77.2% had at least one moderate–severe neurodegenerative or cerebrovascular pathology. Stage III–IV CTE was the most common neurodegenerative disease (43.1%), followed by TDP‐43 pathology, AD, and hippocampal sclerosis. Neuropathologies were intercorrelated, and there were fewer unique combinations than expected if pathologies were independent (p < 0.001). The greatest contributors to dementia were AD, neocortical LBD, hippocampal sclerosis, cerebral amyloid angiopathy, and CTE. Interpretation: In this sample of RHI‐exposed brain donors with wide‐ranging ages, multiple neuropathologies were common and correlated. Mixed neuropathologies, including CTE, underlie cognitive impairment in contact sport athletes. ANN NEUROL 2024;95:314–324 [ABSTRACT FROM AUTHOR]

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI) and pathologically defined as neuronal phosphorylated tau aggregates around small blood vessels and concentrated at sulcal depths. Cross-sectional studies suggest that tau inclusions follow a stereotyped pattern that begins in the neocortex in low stage disease, followed by involvement of the medial temporal lobe and subcortical regions with significant neocortical burden in high stage CTE. Here, we define a subset of brain donors with high stage CTE and with a low overall cortical burden of tau inclusions (mean semiquantitative value ≤1) and classify them as cortical-sparing CTE (CSCTE). Of 620 brain donors with pathologically diagnosed CTE, 66 (11%) met criteria for CSCTE. Compared to typical high stage CTE, those with CSCTE had a similar age at death and years of contact sports participation and were less likely to carry apolipoprotein ε4 (p < 0.05). CSCTE had less overall tau pathology severity, but a proportional increase of disease burden in medial temporal lobe and brainstem regions compared to the neocortex (p’s < 0.001). CSCTE also had lower prevalence of comorbid neurodegenerative disease. Clinically, CSCTE participants were less likely to have dementia (p = 0.023) and had less severe cognitive difficulties (as reported by informants using the Functional Activities Questionnaire (FAQ); p < 0.001, meta-cognitional index T score; p = 0.002 and Cognitive Difficulties Scale (CDS); p < 0.001,) but had an earlier onset age of behavioral (p = 0.006) and Parkinsonian motor (p = 0.013) symptoms when compared to typical high stage CTE. Other comorbid tauopathies likely contributed in part to these differences: when cases with concurrent Alzheimer dementia or frontal temporal lobar degeneration with tau pathology were excluded, differences were largely retained, but only remained significant for FAQ (p = 0.042), meta-cognition index T score (p = 0.014) and age of Parkinsonian motor symptom onset (p = 0.046). Overall, CSCTE appears to be a distinct subtype of high stage CTE with relatively greater involvement of subcortical and brainstem regions and less severe cognitive symptoms. [ABSTRACT FROM AUTHOR]

Although no dataset at the nanoscale for the entire human brain has yet been acquired and neither a nanoscale human whole brain atlas has been constructed, tremendous progress in neuroimaging and high-performance computing makes them feasible in the non-distant future. To construct the human whole brain nanoscale atlas, there are several challenges, and here, we address two, i.e., the morphology modeling of the brain at the nanoscale and designing of a nanoscale brain atlas. A new nanoscale neuronal format is introduced to describe data necessary and sufficient to model the entire human brain at the nanoscale, enabling calculations of the synaptome and connectome. The design of the nanoscale brain atlas covers design principles, content, architecture, navigation, functionality, and user interface. Three novel design principles are introduced supporting navigation, exploration, and calculations, namely, a gross neuroanatomy-guided navigation of micro/nanoscale neuroanatomy; a movable and zoomable sampling volume of interest for navigation and exploration; and a nanoscale data processing in a parallel-pipeline mode exploiting parallelism resulting from the decomposition of gross neuroanatomy parcellated into structures and regions as well as nano neuroanatomy decomposed into neurons and synapses, enabling the distributed construction and continual enhancement of the nanoscale atlas. Numerous applications of this atlas can be contemplated ranging from proofreading and continual multi-site extension to exploration, morphometric and network-related analyses, and knowledge discovery. To my best knowledge, this is the first proposed neuronal morphology nanoscale model and the first attempt to design a human whole brain atlas at the nanoscale. [ABSTRACT FROM AUTHOR]

There is concern over late, adverse brain health outcomes associated with contact sports participation, with high neurodegenerative disease risk reported in studies of former American football [[3], [8]], soccer [[9], [16]] and rugby union players [[15]]. Nevertheless, our observation that CTE pathology is present in around two-thirds of former rugby union players examined is in line with experience reporting neuropathological findings in other series of former contact sports athletes, including former American footballers and soccer players [[7], [13]]. In parallel, autopsy studies of former athletes from a range of contact sports describe a frequent finding of chronic traumatic encephalopathy (CTE), a neuropathology uniquely associated with prior history of traumatic brain injury (TBI) and repetitive head impact (RHI) exposure [[7], [12]-[14]]. [Extracted from the article]

The aim of the work was to investigate the effect of non-thermal plasma treatment of an ultra-thin polyethylene terephthalate (PET) film on changes in its physicochemical properties and biodegradability. Plasma treatment using a dielectric barrier discharge plasma reactor was carried out in air at room temperature and atmospheric pressure twice for 5 and 15 min, respectively. It has been shown that pre-treatment of the PET surface with non-thermal atmospheric plasma leads to changes in the physicochemical properties of this polymer. After plasma modification, the films showed a more developed surface compared to the control samples, which may be related to the surface etching and oxidation processes. After a 5-min plasma exposure, PET films were characterized by the highest wettability, i.e., the contact angle decreased by more than twice compared to the untreated samples. The differential scanning calorimetry analysis revealed the influence of plasma pretreatment on crystallinity content and the melt crystallization behavior of PET after soil degradation. The main novelty of the work is the fact that the combined action of two factors (i.e., physical and biological) led to a reduction in the content of the crystalline phase in the tested polymeric material. [ABSTRACT FROM AUTHOR]

The human cerebral cortex is highly convoluted forming patterns of gyri separated by sulci. The cerebral sulci and gyri are fundamental in cortical anatomy as well as neuroimage processing and analysis. Narrow and deep cerebral sulci are not fully discernible either on the cortical or white matter surface. To cope with this limitation, I propose a new sulci presentation method that employs the inner cortical surface for sulci examination from the inside of the cerebrum. The method has four steps, construct the cortical surface, segment and label the sulci, dissect (open) the cortical surface, and explore the fully exposed sulci from the inside. The inside sulcal maps are created for the left and right lateral, left and right medial, and basal hemispheric surfaces with the sulci parcellated by color and labeled. These three‐dimensional sulcal maps presented here are probably the first of this kind created. The proposed method demonstrates the full course and depths of sulci, including narrow, deep, and/or convoluted sulci, which has an educational value and facilitates their quantification. In particular, it provides a straightforward identification of sulcal pits which are valuable markers in studying neurologic disorders. It enhances the visibility of sulci variations by exposing branches, segments, and inter‐sulcal continuity. The inside view also clearly demonstrates the sulcal wall skewness along with its variability and enables its assessment. Lastly, this method exposes the sulcal 3‐hinges introduced here. [ABSTRACT FROM AUTHOR]

Background: At the beginning of the 21st century, international adoptions of children with cleft lip and/or palate increased dramatically in Sweden. Many children arrived partially or totally unoperated, despite being at an age when palatoplasty has usually been performed. To date, the speech development of internationally adopted (IA) children has been described up to age 7–8 years, but later development remains unstudied. Aims: To investigate speech development between ages 5 and 10 years in children born with cleft lip and palate (CLP) adopted from China and to compare them with non‐adopted (NA) children with CLP. A secondary aim was to compare the frequencies of secondary palatal surgery and number of visits to a speech and language pathologist (SLP) between the groups. Methods & Procedures: In a longitudinal study, 23 IA children from China were included and matched with 23 NA children born in Sweden. Experienced SLPs blindly reassessed audio recordings from routine follow‐ups at ages 5 and 10 years. Velopharyngeal function (VPF) was assessed with the composite score for velopharyngeal competence (VPC‐Sum) for single words and rated on a three‐point scale (VPC‐Rate) in sentence repetition. Target sounds in words and sentences were phonetically transcribed. Per cent correct consonants (PCC) were calculated at word and sentence levels. For in‐depth analyses, articulation errors were divided into cleft speech characteristics (CSCs), developmental speech characteristics (DSCs) and s‐errors. Information on secondary palatal surgery and number of visits to an SLP was collected. Outcomes & Results: VPF differed significantly between the groups at both ages when assessed with VPC‐Sum, but not with VPC‐Rate. Regardless of the method for assessing VPF, a similar proportion in both groups had incompetent VPF but fewer IA than NA children had competent VPF at both ages. IA children had lower PCC at both ages at both word and sentence levels. More IA children had CSCs, DSCs and s‐errors at age 5 years, and CSCs and s‐errors at age 10. The development of PCC was significant in both groups between ages 5 and 10 years. The proportion of children receiving secondary palatal surgery did not differ significantly between the groups, nor did number of SLP visits. Conclusions & Implications: CSCs were more persistent in IA children than in NA children at age 10 years. Interventions should target both cleft and DSCs, be comprehensive and continue past the pre‐school years. WHAT THIS PAPER ADDS: What is already known on this subject: At the beginning of the 21st century, IA children with cleft lip and/or palate arrived in Sweden partially or totally unoperated, despite being at an age when palatoplasty has usually been performed. Studies up to age 7–8 years show that adopted children, compared with NA peers, have poorer articulation skills, demonstrate both cleft‐related and developmental articulation errors, and are more likely to have velopharyngeal incompetence. Several studies also report that adopted children more often require secondary palatal surgery due to fistulas, dehiscence or velopharyngeal incompetence compared with NA peers. What this paper adds to existing knowledge: This longitudinal study provides additional knowledge based on longer follow‐ups than previous studies. It shows that the proportion of children assessed to have incompetent VPF was similar among IA and NA children. It was no significant difference between the groups regarding the proportion that received secondary palatal surgery. However, fewer IA children were assessed to have a competent VPF. Developmental articulation errors have ceased in most IA and all NA children at age 10 years, but significantly more adopted children than NA children still have cleft‐related articulation errors. What are the potential or actual clinical implications of this work?: Speech and language therapy should target both cleft‐related and developmental articulation errors. When needed, treatment must be initiated early, comprehensive, and continued past the pre‐school years, not least for adopted children. [ABSTRACT FROM AUTHOR]

The article is a response to a comment made by Willbrand et al. on the author's work on human cerebral sulci. The author's work consists of a novel method for presenting sulci from inside the cerebrum and an illustration of this method using a 3D brain atlas. The author acknowledges the limitations of using a single brain specimen for the cortical model but argues that it still has value and has been validated and recognized by medical and innovation societies. The cortical model has been incorporated into commercial brain atlas products and has received positive reviews from top clinicians and educators. The author concludes by expressing openness to the development of a better cerebral model. [Extracted from the article]

There is conflicting evidence whether single-suture craniosynostosis (SSC), is linked to adversities of cognitive development. To assess the evidence for a link between SSC and cognition, a systematic literature search was conducted and eligible studies assessed for inclusion by two independent readers. Forty-eight studies met inclusion criteria. Small to medium but persistent effects on both general and some specific cognitive functions across age bands were found in higher quality studies for SSC overall. There was limited evidence for effects related to surgical correction. Methodologies varied substantially and there was a lack of longitudinal studies using broad assessment batteries. [ABSTRACT FROM AUTHOR]

The subject of the article is pension insurance as an instrument of social security policy through which the state can influence agricultural activity. The choice of the topic is related to the generational changes in agriculture, as well as the change in legal regulations regarding the cessation of agricultural activity as one of the conditions for obtaining a full pension. The aim of the research was to determine the economic effects of the legal regulation of agricultural pension insurance and to discuss the necessary directions of changes. The work in particular shows the possibilities of implementing the restructuring function aimed at shaping the generational structure of Polish agriculture and the development of the economic base of farmers' social insurance in the future. The introduced solution does not improve the financial situation of the pension fund, both on the expenditure side, due to the increase in the payment of agricultural pensions to farmers conducting agricultural activity, and on the income side, due to the reduction of access of new people to agricultural activity. [ABSTRACT FROM AUTHOR]

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI), but the components of RHI exposure underlying this relationship are unclear. We create a position exposure matrix (PEM), composed of American football helmet sensor data, summarized from literature review by player position and level of play. Using this PEM, we estimate measures of lifetime RHI exposure for a separate cohort of 631 football playing brain donors. Separate models examine the relationship between CTE pathology and players' concussion count, athletic positions, years of football, and PEM-derived measures, including estimated cumulative head impacts, linear accelerations, and rotational accelerations. Only duration of play and PEM-derived measures are significantly associated with CTE pathology. Models incorporating cumulative linear or rotational acceleration have better model fit and are better predictors of CTE pathology than duration of play or cumulative head impacts alone. These findings implicate cumulative head impact intensity in CTE pathogenesis. The relationship between the components of repetitive head impacts and chronic traumatic encephalopathy (CTE) remains unclear. Here, the authors use American football helmet sensor data to show that duration of play, cumulative head impacts and linear and rotational accelerations are significantly associated with CTE pathology. [ABSTRACT FROM AUTHOR]

Cognitive impairment (CI) and dementia can have profound social and emotional effects on older adults. Early detection of CI is imperative both to the identification of potentially treatable conditions and to provide services to minimize the effects of CI in cases of dementia. While primary care settings are ideal for identifying CI, it frequently goes undetected. We tailored a brief, iPad-based, cognitive assessment (MyCog) for primary care settings and piloted it in a sample of older adults. Eighty participants were recruited from an existing cohort study and completed a brief, in-person interview. CI was determined based on a diagnosis of dementia or CI in their medical record or based on a comprehensive cognitive battery performed within the past 18 months. MyCog had a sensitivity of 79% and specificity of 82%, offering a practical, scalable, primary care assessment for the routine case finding of cognitive impairment and dementia. [ABSTRACT FROM AUTHOR]

Background: Malplaced implants in orbital reconstruction may lead to serious complications and necessitate re-intervention. The aim of this study was to describe outcomes, complications and scenarios of re-intervention in a historical case series of orbital fractures treated with free-hand orbital wall reconstruction. The main hypothesis was that early re-interventions are mainly because of malplaced implants in the posterior orbit. Methods: Retrospective review of 90 patients with facial fractures involving the orbit, reconstructed with radiopaque orbital wall implants, from 2011 to 2016. Data were obtained from medical records and computed tomography images. Recorded parameters were fracture type, ocular injury, ocular motility, diplopia, eye position, complications and re-interventions. Secondary reconstructions because of enophthalmos were volumetrically evaluated. Results: Early complications requiring re-intervention within 1 month were seen in 12 (13%) patients, where all except two were because of malplaced implants. The implant incongruence was without exception found in the posterior orbit. Late complications consisted of four (4%) cases of ectropion and five (5%) cases of entropion that needed corrective surgery. The majority of the patients with eye-lid complications had undergone repeated surgeries. Secondary orbital surgeries were performed in nine (10%) patients. Five of these patients had secondary reconstruction for enophthalmos and associated diplopia. None of these patients became completely free from either enophthalmos or diplopia after the secondary surgery. Conclusion: Re-intervention after orbital reconstruction is mainly related to malplaced implants in the posterior orbit. Incomplete results in patients requiring secondary surgery for enophthalmos infer the importance of accurate restoration of the orbit at primary surgery. [ABSTRACT FROM AUTHOR]

Herein, we present a tool called Evident that can be used for deriving effect sizes for a broad spectrum of metadata variables, such as mode of birth, antibiotics, socioeconomics, etc., to provide power calculations for a new study. Evident can be used to mine existing databases of large microbiome studies (such as the American Gut Project, FINRISK, and TEDDY) to analyze the effect sizes for planning future microbiome studies via power analysis. For each metavariable, the Evident software is flexible to compute effect sizes for many commonly used measures of microbiome analyses, including α diversity, β diversity, and log-ratio analysis. In this work, we describe why effect size and power analysis are necessary for computational microbiome analysis and show how Evident can help researchers perform these procedures. Additionally, we describe how Evident is easy for researchers to use and provide an example of efficient analyses using a dataset of thousands of samples and dozens of metadata categories. [ABSTRACT FROM AUTHOR]

Research highlights the increasing overlap of autism spectrum disorder and substance use disorders in young people. However, no behavioral treatments exist addressing this comorbidity despite great need. A team of clinicians developed an integrated behavioral protocol addressing substance use in youth with autism spectrum disorder. The multidisciplinary team developed 12 youth, 7 parent, and 3 joint modules based on established evidence-based therapies shown to have effectiveness separately addressing autism spectrum and substance use. Two cases are discussed to illuminate this integrated intervention. Adaptations to the protocol were made during feedback from patients and their parents. Further research is needed to determine the effectiveness of this preliminary protocol. [ABSTRACT FROM AUTHOR]

Human brain atlases are tools to gather, present, use, and discover knowledge about the human brain. The developments in brain atlases parallel the advances in neuroanatomy. The brain atlas evolution has been from hand-drawn cortical maps to print atlases to digital platforms which, thanks to tremendous advancements in acquisition techniques and computing, has enabled progress in neuroanatomy from gross (macro) to meso-, micro-, and nano-neuroanatomy. Advances in neuroanatomy have been feasible because of introducing new modalities, from the initial cadaveric dissections, morphology, light microscopy imaging and neuroelectrophysiology to non-invasive in vivo imaging, connectivity, electron microscopy imaging, genomics, proteomics, transcriptomics, and epigenomics. Presently, large and long-term brain projects along with big data drive the development in micro- and nano-neuroanatomy. The goal of this work is to address the relationship between neuroanatomy and human brain atlases and, particularly, the impact of these atlases on the understanding, presentation, and advancement of neuroanatomy. To better illustrate this relationship, a brief outline on the evolution of the human brain atlas concept, creation of brain atlases, atlas-based applications, and future brain-related developments is also presented. In conclusion, human brain atlases are excellent means to represent, present, disseminate, and support neuroanatomy. [ABSTRACT FROM AUTHOR]

Oxytocin (OT), the brain's most abundant neuropeptide, plays an important role in social salience and motivation. Clinical trials of the efficacy of OT in autism spectrum disorder (ASD) have reported mixed results due in part to ASD's complex etiology. We investigated whether genetic and epigenetic variation contribute to variable endogenous OT levels that modulate sensitivity to OT therapy. To carry out this analysis, we integrated genome‐wide profiles of DNA‐methylation, transcriptional activity, and genetic variation with plasma OT levels in 290 participants with ASD enrolled in a randomized controlled trial of OT. Our analysis identified genetic variants with novel association with plasma OT, several of which reside in known ASD risk genes. We also show subtle but statistically significant association of plasma OT levels with peripheral transcriptional activity and DNA‐methylation profiles across several annotated gene sets. These findings broaden our understanding of the effects of the peripheral oxytocin system and provide novel genetic candidates for future studies to decode the complex etiology of ASD and its interaction with OT signaling and OT‐based interventions. Lay Summary: Oxytocin (OT) is an abundant chemical produced by neurons that plays an important role in social interaction and motivation. We investigated whether genetic and epigenetic factors contribute to variable OT levels in the blood. To this, we integrated genetic, gene expression, and non‐DNA regulated (epigenetic) signatures with blood OT levels in 290 participants with autism enrolled in an OT clinical trial. We identified genetic association with plasma OT, several of which reside in known autism risk genes. We also show statistically significant association of plasma OT levels with gene expression and epigenetic across several gene pathways. These findings broaden our understanding of the factors that influence OT levels in the blood for future studies to decode the complex presentation of autism and its interaction with OT and OT‐based treatment. [ABSTRACT FROM AUTHOR]