Miracle-dz/UniFAR-FTUs huggingface dataset:
Diet modulates brain network stability, a biomarker for brain aging, in young adults

Significance To better understand how diet influences brain aging, we focus here on the presymptomatic period during which prevention may be most effective. Large-scale life span neuroimaging datasets show functional communication between brain regions destabilizes with age, typically starting in the late 40s, and that destabilization correlates with poorer cognition and accelerates with insulin resistance. Targeted experiments show that this biomarker for brain aging is reliably modulated with consumption of different fuel sources: Glucose decreases, and ketones increase the stability of brain networks. This effect replicated across both changes to total diet as well as fuel-specific calorie-matched bolus, producing changes in overall brain activity that suggest that network “switching” may reflect the brain’s adaptive response to conserve energy under resource constraint. Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones. We first established network stability as a biomarker for brain aging using two large-scale (n = 292, ages 20 to 85 y; n = 636, ages 18 to 88 y) 3 T functional MRI (fMRI) datasets. To determine whether diet can influence brain network stability, we additionally scanned 42 adults, age < 50 y, using ultrahigh-field (7 T) ultrafast (802 ms) fMRI optimized for single-participant-level detection sensitivity. One cohort was scanned under standard diet, overnight fasting, and ketogenic diet conditions. To isolate the impact of fuel type, an independent overnight fasted cohort was scanned before and after administration of a calorie-matched glucose and exogenous ketone ester (d-β-hydroxybutyrate) bolus. Across the life span, brain network destabilization correlated with decreased brain activity and cognitive acuity. Effects emerged at 47 y, with the most rapid degeneration occurring at 60 y. Networks were destabilized by glucose and stabilized by ketones, irrespective of whether ketosis was achieved with a ketogenic diet or exogenous ketone ester. Together, our results suggest that brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain.
Extracellular voltage thresholds for maximizing information extraction in primate auditory cortex: implications for a brain computer interface

Objective. Research by Oby (2016 J. Neural. Eng. 13 036009) demonstrated that the optimal threshold for extracting information from visual and motor cortices may differ from the optimal threshold for identifying single neurons via spike sorting methods. The optimal threshold for extracting information from auditory cortex has yet to be identified, nor has the optimal temporal scale for representing auditory cortical activity. Here, we describe a procedure to jointly optimize the extracellular threshold and bin size with respect to the decoding accuracy achieved by a linear classifier for a diverse set of auditory stimuli. Approach. We used linear multichannel arrays to record extracellular neural activity from the auditory cortex of awake squirrel monkeys passively listening to both simple and complex sounds. We executed a grid search of the coordinate space defined by the voltage threshold (in units of standard deviation) and the bin size (in units of milliseconds), and computed decoding accuracy at each point. Main results. The optimal threshold for information extraction was consistently near two standard deviations below the voltage trace mean, which falls significantly below the range of three to five standard deviations typically used as inputs to spike sorting algorithms in basic research and in brain-computer interface (BCI) applications. The optimal binwidth was minimized at the optimal voltage threshold, particularly for acoustic stimuli dominated by temporally dynamic features, indicating that permissive thresholding permits readout of cortical responses with temporal precision on the order of a few milliseconds. Significance. The improvements in decoding accuracy we observed for optimal readout parameters suggest that standard thresholding methods substantially underestimate the information present in auditory cortical spiking patterns. The fact that optimal thresholds were relatively low indicates that local populations of cortical neurons exhibit high temporal coherence that could be leveraged in service of future auditory BCI applications.
MKL1 deficiency results in a severe neutrophil motility defect due to impaired actin polymerization.

Megakaryoblastic leukemia 1 (MKL1) promotes the regulation of essential cell processes, including actin cytoskeletal dynamics by co-activating serum response factor. Recently, the first human case with MKL1 deficiency, leading to a novel primary immunodeficiency, was identified. We report a second family with two siblings with a homozygous frameshift mutation in MKL1. The index case deceased as an infant from progressive and severe pneumonia by Pseudomonas aeruginosa and poor wound healing. The younger sib was preemptively transplanted shortly after birth. The immunodeficiency was marked by a pronounced actin polymerization defect and a strongly reduced motility and chemotactic response by MKL1-deficient neutrophils. Apart from the lack of MKL1, subsequent proteomic and transcriptomic analyses of patient neutrophils revealed actin and several actin-related proteins to be downregulated, confirming a role for MKL1 as transcriptional co-regulator. Degranulation was enhanced upon suboptimal neutrophil activation, while production of reactive oxygen species was normal. Neutrophil adhesion was intact but without proper spreading. The latter could explain the observed failure in firm adherence and transendothelial migration under flow conditions. No apparent defect in phagocytosis and bacterial killing was found. Also monocyte-derived macrophages showed intact phagocytosis; lymphocyte counts and proliferative capacity were normal. Non-hematopoietic primary patient fibroblasts demonstrated defective differentiation into myofibroblasts but normal migration and filamentous actin (F-actin) content, most probably due to compensatory mechanisms of MKL2, which is not expressed in neutrophils. Our findings extend current insight into the severe immune dysfunction in MKL1 deficiency, with cytoskeletal dysfunction and defective extravasation of neutrophils as most prominent features.
Are single item mood scales (SIMS) valid for people with traumatic brain injury?

ABSTRACT Objectives: Single-item mood scales (SIMS) are used in clinical practice and research as simple and convenient measures to track mood and response to interventions but have rarely been formally evaluated in neurological samples. The current study sought to evaluate the psychometric properties of SIMS in verbal and visual formats. Participants: Sixty-one people living in community settings in metropolitan and regional Australia, with a history of traumatic brain injury. Methods: SIMS were compared with measures of related constructs (depressed mood and satisfaction with life) on two occasions between one and three weeks apart. Results: The study met COSMIN method quality criteria for evaluation of validity. The SIMS showed evidence of construct validity, having moderate magnitude correlation coefficients with measures of similar constructs, and conversely low and non-significant correlation with dissimilar constructs. There was also evidence of discriminant validity, with significant differences based on diagnostic status (participants with depression rated SIMS lower). Correlation coefficients on the SIMS between Times 1 and 2 were of moderate magnitude, with a small but statistically significant increase in mean ratings. Conclusions: the data support the SIMS as a valid measure that can be administered to track changes in mood in clinical practice and research.
Characteristics associated with elevated 1‐h plasma glucose levels during a 75‐g oral glucose tolerance test in non‐obese Japanese men

Elevated 1‐h plasma glucose (1h‐PG; ≥155 mg/dL) during an oral glucose tolerance test is a risk factor for type 2 diabetes. However, the metabolic characteristics of non‐obese Asians with elevated 1h‐PG are unknown. Thus, we studied 59 non‐obese Japanese men with normal glucose tolerance. We divided study participants into the Low 1h‐PG group (<155 mg/dL) and the High 1h‐PG group (≥155 mg/dL). We compared the metabolic characteristics of the groups, including tissue‐specific insulin sensitivity measured using a two‐step hyperinsulinemic‐euglycemic clamp. Insulinogenic index and adiponectin levels were significantly lower in the High 1h‐PG group than in the Low 1h‐PG group. Other characteristics, including insulin sensitivity, adiposity and ectopic fat accumulation, were similar between the groups. In conclusion, non‐obese Japanese men with high 1h‐PG have impaired early‐phase insulin secretion and lower adiponectin levels. Insulin resistance and abnormal fat distribution were not evident in this population.
Genome-wide, integrative analysis of circular RNA dysregulation and the corresponding circular RNA-microRNA-mRNA regulatory axes in autism

Circular RNAs (circRNAs), a class of long noncoding RNAs, are known to be enriched in mammalian neural tissues. Although a wide range of dysregulation of gene expression in autism spectrum disorder (ASD) have been reported, the role of circRNAs in ASD remains largely unknown. Here, we performed genome-wide circRNA expression profiling in postmortem brains from individuals with ASD and controls and identified 60 circRNAs and three coregulated modules that were perturbed in ASD. By integrating circRNA, microRNA, and mRNA dysregulation data derived from the same cortex samples, we identified 8170 ASD-associated circRNA-microRNA-mRNA interactions. Putative targets of the axes were enriched for ASD risk genes and genes encoding inhibitory postsynaptic density (PSD) proteins, but not for genes implicated in monogenetic forms of other brain disorders or genes encoding excitatory PSD proteins. This reflects the previous observation that ASD-derived organoids show overproduction of inhibitory neurons. We further confirmed that some ASD risk genes (NLGN1, STAG1, HSD11B1, VIP, and UBA6) were regulated by an up-regulated circRNA (circARID1A) via sponging a down-regulated microRNA (miR-204-3p) in human neuronal cells. Particularly, alteration of NLGN1 expression is known to affect the dynamic processes of memory consolidation and strengthening. To the best of our knowledge, this is the first systems-level view of circRNA regulatory networks in ASD cortex samples. We provided a rich set of ASD-associated circRNA candidates and the corresponding circRNA-microRNA-mRNA axes, particularly those involving ASD risk genes. Our findings thus support a role for circRNA dysregulation and the corresponding circRNA-microRNA-mRNA axes in ASD pathophysiology.
Prediagnostic Circulating Levels of Sex Steroid Hormones and SHBG in Relation to Risk of Ductal Carcinoma In Situ of the Breast among UK Women

Background: Sex steroid hormones and sex hormone–binding globulin (SHBG) have been implicated in the etiology of invasive breast cancer, but their associations with risk of the precursor lesion, ductal carcinoma in situ (DCIS) of the breast, remain unclear. Methods: We used Cox proportional hazards regression models to estimate the associations of serum levels of estradiol (premenopausal women only), testosterone, and/or SHBG with DCIS risk among 182,935 women. After a median follow-up of 7.1 years, 186 and 531 DCIS cases were ascertained in premenopausal and postmenopausal women, respectively. Results: Total and free estradiol were positively associated with risk of DCIS among premenopausal women. The HRs for the highest versus the lowest tertiles were 1.54 (1.06–2.23) and 1.72 [95% confidence interval (CI), 1.15–2.57], respectively. Among postmenopausal women, elevated levels of free testosterone (FT), and to a lesser extent, total testosterone, were positively associated with DCIS risk. The HRs for the highest versus the lowest quartiles were 1.42 (95% CI, 1.09–1.85) and 1.16 (95% CI, 0.91–1.48), respectively. Serum SHBG levels were inversely associated with risk of DCIS among postmenopausal women (HRq4 vs. q1: 0.75; 95% CI, 0.56–0.99). Conclusions: This study suggests that elevated levels of estradiol are associated with increased risk of DCIS among premenopausal women, and that among postmenopausal women, elevated levels of testosterone, and particularly those of FT, are associated with increased DCIS risk, while elevated levels of SHBG are associated with reduced risk. Impact: These findings may be helpful in developing prevention strategies aimed at reducing breast cancer risk among premenopausal and postmenopausal women.
Risk Assessment Tool for Adverse Outcomes of Occupational Stress: Development and Investigation of its Psychometric Properties

Introduction While psychosocial factors at work have been widely mentioned as important contributors to occupational stress, only recent research suggests that some non-work factors (e.g. some socioeconomic, personality and health risks) could also contribute to the adverse outcomes of work-related stress. Objective The aim of our study was to develop a comprehensive instrument that would include a broad spectrum of work and non-work risks related to adverse negative outcomes of occupational stress. Methods A preliminary version of the instrument was obtained through three consecutive rounds of a Delphi study. Seven qualified experts in the workplace stress field, who participated in the first round, proposed and evaluated risk factors for adverse outcomes of occupational stress. The proposed most prominent risk factors were later reassessed in two online surveys by an expanded group of 20 experts. The final version of the instrument consisted of 130 risk factors, which were classified into 17 categories based on substantive considerations. Results After the questionnaire had been completed by 349 Slovenian employees in different occupations a principal component analysis (PCA) was conducted. A four component solution (Direct Oblimin rotation, 68% explained variance) showed minimal crossloading and reduced the used variables into the following components, i.e. (i) organizational context, (ii) socio-economic characteristics of the employee, (iii) job characteristics and (iv) individual characteristics of the employee. Conclusion The study represents an important step toward the development of a comprehensive instrument for identifying potential risk factors associated with harmful work-related outcomes. Further validation of the tool in different work settings and samples is needed.
Cross-Corpus Speech Emotion Recognition Based on Deep Domain-Adaptive Convolutional Neural Network

In this letter, we propose a novel deep domain-adaptive convolutional neural network (DDACNN) model to handle the challenging cross-corpus speech emotion recognition (SER) problem. The framework of the DDACNN model consists of two components: a feature extraction model based on a deep convolutional neural network (DCNN) and a domain-adaptive (DA) layer added in the DCNN utilizing the maximum mean discrepancy (MMD) criterion. We use labeled spectrograms from source speech corpus combined with unlabeled spectrograms from target speech corpus as the input of two classic DCNNs to extract the emotional features of speech, and train the model with a special mixed loss combined with a cross-entrophy loss and an MMD loss. Compared to other classic cross-corpus SER methods, the major advantage of the DDACNN model is that it can extract robust speech features which are time-frequency related by spectrograms and narrow the discrepancies between feature distribution of source corpus and target corpus to get better cross-corpus performance. Through several cross-corpus SER experiments, our DDACNN achieved the state-of-the-art performance on three public emotion speech corpora and is proved to handle the cross-corpus SER problem efficiently. key words: cross-corpus speech emotion recognition, deep convolutional neural network, domain adaptation
Direct 3D Printing of Highly Anisotropic, Flexible, Constriction-Resistive Sensors for Multidirectional Proprioception in Soft Robots.

A key missing technology for the emerging field of soft robotics is the provision of highly selective multidirectional tactile sensing that can be easily integrated into a robot using simple fabrication techniques. Conventional strain sensors, such as strain gauges, are typically designed to respond to strain in a single direction and are mounted on the external surface of a structure. Herein, we present a technique to 3D print multidirectional, anisotropic and constriction-resistive strain sensors, which can be directly integrated into the interior of soft robots. Using a carbon nanotube reinforced polylactic acid (PLA-CNT), both the sensing element and the conductive interconnect of the sensor system are 3D printed. The sensor's sensitivity and anisotropy can be adjusted by controlling the air gap between printed adjacent tracks, infill density, and build orientation relative to the main loading direction. In particular, sensors printed with a near-zero air gap, i.e., adjacent tracks form a kissing bond, can achieve a gauge factor of ~1342 perpendicular to the raster orientation and a gauge factor of ~1 parallel to the raster orientation. The maximum directional selectivity of this ultra-sensitive sensor is 31.4, which is approximately nine times greater than the highest value reported for multidirectional sensors so far. The high sensitivity stems from the progressive opening and closing of the kissing-bond between adjacent tracks. The potential of this type of sensors and the simple manufacturing process is demonstrated by integrating the sensor with a soft robotic actuator. The sensors are able to identify and quantify the bending deformation and angle in different directions. The ability to fabricate sensors with customizable footprints and directional selectivity during 3D printing of soft robotic systems paves the way towards highly customizable, highly integrated multifunctional soft robots that are better able to sense both themselves and their environments.
Evaluating quality and impact of acute paediatric inpatient care: Defining the domains for a Person Centred Outcome Measure (PCOM) in children and young people admitted with self-harm or eating disorders

Background and purpose: In the United Kingdom, the prevalence of children and young people (CYP), up to the age of 18 years, accessing acute paediatric inpatient care with mental health problems is increasing, with self-harm and eating disorders particularly prevalent. This initial period of acute inpatient care can involve multiple assessments and interventions in order to meet physical, psychological and social needs. However, there is a distinct paucity of published literature reporting CYP service users’ experiences and outcomes of being in receipt of non-specialist inpatient care. Therefore this project aimed to undertake the preliminary work in developing a Person Centred Outcome Measure (PCOM) for this patient group by identifying the domains for a PCOM and establishing how such a measure could be implemented. Methods: A two phase sequential design was adopted which involved: (1) a rapid review of the literature and (2) an evaluation of experiences and outcomes through stakeholder engagement events with children and young people admitted with self-harm or eating disorders, their parents and carers, and professionals from health, social care and education. Findings: Rapid review of the literature • There is a lack of reported outcomes relating to CYP admitted to inpatient care with self-harm within the literature. • Outcomes reported by CYP appear to relate to aspects of care delivery, communication and the inpatient environment; • CYP reports predominantly relate to deficits in service provision which is recognised to negatively impact on experience and inhibit recovery and outcome. Findings: Stakeholder workshops • In total 96 CYP, parents and carers, and professionals participated in the stakeholder event. • Disparities in experiences and the implied quality of being in receipt of care were identified. • Synthesis of findings identified five domains that could be used to develop a PCOM that included: Privacy and surveillance; Receiving holistic care; Making choices and being understood through timely, relevant and appropriate communication; Working together to plan and achieve care goals; and Respect and empowerment • Variation was evident between CYP stakeholders as to the acceptability of when and how outcomes are measured. Conclusion: Findings from this project provide the foundations for a PCOM for CYP admitted to acute paediatric care with self harm or eating disorders to be developed, tested, implemented and evaluated. The domains identified have the potential to be further developed and validated as an instrument with a larger and more diverse sample of CYP.
Integrated Hydrologic Modeling to Untangle the Impacts of Water Management During Drought

Over the past century, groundwater levels in California's San Joaquin Valley have dropped by more than 30 m in some areas mostly due to excessive groundwater extraction used to irrigate agricultural lands and sustain a growing population. Between 2012 and 2015, California experienced the worst drought in its recorded history, depleting surface water supplies and further exacerbating groundwater depletion in the region. Due to a lack of groundwater regulation, exact quantities of extracted groundwater in California are unknown and hard to quantify. Recent adoption of the Sustainable Groundwater Management Act has intensified efforts to identify sustainable groundwater use. However, understanding sustainable use in a highly productive agricultural system with an extremely complex surface water allocation system, variable groundwater use, and spatially extensive and diverse irrigation practices is no easy task. Using an integrated hydrologic model coupled with a land surface model, we evaluated how water management activities, specifically a suite of irrigation and groundwater pumping scenarios, impact surface water–groundwater fluxes and storage components and how those activities and the relationships between them change during drought. Results showed that groundwater pumping volume had the most significant impact on long‐term water storage changes. A comparison with total water storage anomaly (TWSA) estimates from NASA's Gravity Recover and Climate Experiment (GRACE) provided some insight regarding which combinations of pumping and irrigation matched the GRACE TWSA estimates, lending credibility to these scenarios. In addition, the majority of long‐term water storage changes during the recent drought occurred in groundwater storage in the deeper subsurface.