Miracle-dz/UniFAR-FTUs huggingface dataset:
White Matter Imaging Correlates of Early Cognitive Impairment Detected by the Montreal Cognitive Assessment After Transient Ischemic Attack and Minor Stroke

Background and Purpose— Among screening tools for cognitive impairment in large cohorts, the Montreal Cognitive Assessment (MoCA) seems to be more sensitive to early cognitive impairment than the Mini-Mental State Examination (MMSE), particularly after transient ischemic attack or minor stroke. We reasoned that if MoCA-detected early cognitive impairment is pathologically significant, then it should be specifically associated with the presence of white matter hyperintensities (WMHs) and reduced fractional anisotropy (FA) on magnetic resonance imaging. Methods— Consecutive eligible patients with transient ischemic attack or minor stroke (Oxford Vascular Study) underwent magnetic resonance imaging and cognitive assessment. We correlated MoCA and MMSE scores with WMH and FA, then specifically studied patients with low MoCA and normal MMSE. Results— Among 400 patients, MoCA and MMSE scores were significantly correlated (all P<0.001) with WMH volumes (rMoCA=−0.336; rMMSE=−0.297) and FA (rMoCA=0.409; rMMSE=0.369) and—on voxel-wise analyses—with WMH in frontal white matter and reduced FA in almost all white matter tracts. However, only the MoCA was independently correlated with WMH volumes (r=−0.183; P<0.001), average FA values (r=0.218; P<0.001), and voxel-wise reduced FA in anterior tracts after controlling for the MMSE. In addition, patients with low MoCA but normal MMSE (n=57) had higher WMH volumes (t=3.1; P=0.002), lower average FA (t=−4.0; P<0.001), and lower voxel-wise FA in almost all white matter tracts than those with normal MoCA and MMSE (n=238). Conclusions— In patients with transient ischemic attack or minor stroke, early cognitive impairment detected with the MoCA but not with the MMSE was independently associated with white matter damage on magnetic resonance imaging, particularly reduced FA.
Engram cells retain memory under retrograde amnesia

Experimental recovery from retrograde amnesia When memory researchers induce amnesia, they normally assume that the manipulations prevent the memory engram from effective encoding at consolidation. In accordance with this, Ryan et al. found that after the injection of protein synthesis inhibitors, animals could not retrieve a memory. However, to their surprise, the memory could nevertheless be reactivated by light-induced activation of the neurons tagged during conditioning. Increased synaptic strength that is the result of cellular consolidation is thus not a critical requisite for storing a memory. Science, this issue p. 1007 Memory can be retrieved by optogenetic activation of the neurons involved in memory formation when memories would not normally have been stored. Memory consolidation is the process by which a newly formed and unstable memory transforms into a stable long-term memory. It is unknown whether the process of memory consolidation occurs exclusively through the stabilization of memory engrams. By using learning-dependent cell labeling, we identified an increase of synaptic strength and dendritic spine density specifically in consolidated memory engram cells. Although these properties are lacking in engram cells under protein synthesis inhibitor–induced amnesia, direct optogenetic activation of these cells results in memory retrieval, and this correlates with retained engram cell–specific connectivity. We propose that a specific pattern of connectivity of engram cells may be crucial for memory information storage and that strengthened synapses in these cells critically contribute to the memory retrieval process.
Patterns of Change in Hostility from College to Midlife in the UNC Alumni Heart Study Predict High-Risk Status

Objective To examine hostility measured in college and patterns of change in hostility from college to midlife as predictors of high health-related risk later in midlife. Methods Logistic regression models were used to test hostility/risk associations. Results College hostility predicted being a current smoker, consuming more than two drinks of alcohol, low social support, achieving less than expected in career and in relationships, risk for depression, and appraisal of life changing for the worse in terms of family events at midlife. Change in hostility did not predict smoking and drinking; however, it did significantly predict social isolation, lower income (only for women), obesity, avoidance of exercise, high-fat diet, and negative changes in economic life, work life, and physical health events-all risk indicators measured during the next decade. Appraisals of social support, lowered expectations, risk for depression, and reports of family life changing for the worse were predicted at both time periods. When change in hostility was modeled with college hostility, all risk indicators were significantly predicted by college hostility. Conclusions High hostility in college and change in hostility from college to midlife predicts a full range of health risk indicators. When compared with the average population decline in hostility, gains in hostility at midlife are related to increased risk while declines in hostility are related to reduced risk. Higher midlife hostility is associated with increased odds of being in the higher risk group. Future research should focus on developing interventions to reduce hostility.
J-Distance Discord: An Improved Time Series Discord Definition and Discovery Method

A time series discord is a subsequence that is maximally different to all the rest subsequences of a longer time series. Classic discord discovery has been used for detecting anomalous or interesting pattern, which usually represents the most unusual subsequences within a time series. However, an anomalous or interesting pattern may happen twice or more times so that any instance of this pattern is not distinct enough to be a top discord. To mitigate the issue, we propose an improved definition named J-distance discord (JDD), which incorporates the methodologies of KNN (k nearest neighbor) algorithm. JDD measures the similarity between a subsequence and its Jth most similar subsequence and ranks discords according to the similarity. We also propose a JDD discovery method to reduce the extra computational requirements brought by JDD definition. Experiments on synthetic and real world datasets show that JDD captures more de-facto anomalous and interesting patterns compared to the results of the original definition of discord. Besides, the JDD discovery method is as fast as the classic discord discovery method in terms of computational efficiency.
Specific Inhibition of Acyl-CoA Oxidase-1 by an Acetylenic Acid Improves Hepatic Lipid and Reactive Oxygen Species (ROS) Metabolism in Rats Fed a High Fat Diet*

A chronic high fat diet results in hepatic mitochondrial dysfunction and induction of peroxisomal fatty acid oxidation (FAO); whether specific inhibition of peroxisomal FAO benefits mitochondrial FAO and reactive oxygen species (ROS) metabolism remains unclear. In this study a specific inhibitor for the rate-limiting enzyme involved in peroxisomal FAO, acyl-CoA oxidase-1 (ACOX1) was developed and used for the investigation of peroxisomal FAO inhibition upon mitochondrial FAO and ROS metabolism. Specific inhibition of ACOX1 by 10,12-tricosadiynoic acid increased hepatic mitochondrial FAO via activation of the SIRT1-AMPK (adenosine 5′-monophosphate-activated protein kinase) pathway and proliferator activator receptor α and reduced hydrogen peroxide accumulation in high fat diet-fed rats, which significantly decreased hepatic lipid and ROS contents, reduced body weight gain, and decreased serum triglyceride and insulin levels. Inhibition of ACOX1 is a novel and effective approach for the treatment of high fat diet- or obesity-induced metabolic diseases by improving mitochondrial lipid and ROS metabolism.
Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks

Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network. Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling. All moiety conservation relations can be represented as nonnegative integer vectors in the left null space of the stoichiometric matrix corresponding to a biochemical network. Algorithms exist to compute such vectors based only on reaction stoichiometry but their computational complexity has limited their application to relatively small metabolic networks. Moreover, the vectors returned by existing algorithms do not, in general, represent conservation of a specific moiety with a defined atomic structure. Here, we show that identification of conserved moieties requires data on reaction atom mappings in addition to stoichiometry. We present a novel method to identify conserved moieties in metabolic networks by graph theoretical analysis of their underlying atom transition networks. Our method returns the exact group of atoms belonging to each conserved moiety as well as the corresponding vector in the left null space of the stoichiometric matrix. It can be implemented as a pipeline of polynomial time algorithms. Our implementation completes in under five minutes on a metabolic network with more than 4,000 mass balanced reactions. The scalability of the method enables extension of existing applications for moiety conservation relations to genome-scale metabolic networks. We also give examples of new applications made possible by elucidating the atomic structure of conserved moieties.
The origins of the circumventricular organs

The circumventricular organs (CVOs) are specialised neuroepithelial structures found in the midline of the brain, grouped around the third and fourth ventricles. They mediate the communication between the brain and the periphery by performing sensory and secretory roles, facilitated by increased vascularisation and the absence of a blood‐brain barrier. Surprisingly little is known about the origins of the CVOs (both developmental and evolutionary), but their functional and organisational similarities raise the question of the extent of their relationship. Here, I review our current knowledge of the embryonic development of the seven major CVOs (area postrema, median eminence, neurohypophysis, organum vasculosum of the lamina terminalis, pineal organ, subcommissural organ, subfornical organ) in embryos of different vertebrate species. Although there are conspicuous similarities between subsets of CVOs, no unifying feature characteristic of their development has been identified. Cross‐species comparisons suggest that CVOs also display a high degree of evolutionary flexibility. Thus, the term ‘CVO’ is merely a functional definition, and features shared by multiple CVOs may be the result of homoplasy rather than ontogenetic or phylogenetic relationships.
Effects of Mesalamine Treatment on Gut Barrier Integrity After Burn Injury

Gut barrier disruption is often implicated in pathogenesis associated with burn and other traumatic injuries. In this study, the authors examined whether therapeutic intervention with mesalamine (5-aminosalicylic acid [5-ASA]), a common anti-inflammatory treatment for patients with inflammatory bowel disease, reduces intestinal inflammation and maintains normal barrier integrity after burn injury. Male C57BL/6 mice were administered an approximately 20% TBSA dorsal scald burn and resuscitated with either 1 ml normal saline or 100 mg/kg of 5-ASA dissolved in saline. The authors examined intestinal transit and permeability along with the levels of small intestine epithelial cell proinflammatory cytokines and tight junction protein expression 1 day after burn injury in the presence or absence of 5-ASA. A significant decrease in intestinal transit was observed 1 day after burn injury, which accompanied a significant increase in gut permeability. The authors found a substantial increase in the levels of interleukin (IL)-6 (by ~1.5-fold) and IL-18 (by ~2.5-fold) in the small intestine epithelial cells 1 day after injury. Furthermore, burn injury decreases the expression of the tight junction proteins claudin-4, claudin-8, and occludin. Treatment with 5-ASA after burn injury prevented the burn-induced increase in permeability, partially restored normal intestinal transit, normalized the levels of the proinflammatory cytokines IL-6 and IL-18, and restored tight junction protein expression of claudin-4 and occludin compared with that of sham levels. Together these findings suggest that 5-ASA can potentially be used as treatment to decrease intestinal inflammation and normalize intestinal function after burn injury.
Exclusive breastfeeding in hospital predicts longer breastfeeding duration in Canada: Implications for health equity

BACKGROUND Breastfeeding has many established health benefits for women and children. We examined the association between maternal education, newborn feeding in hospital, and long-term breastfeeding duration. METHODS We studied 3195 Canadian mother-infant dyads in the CHILD pregnancy cohort. Newborn feeding was documented from hospital records. Caregivers reported sociodemographic factors and infant feeding at 3, 6, 12, 18, and 24 months. RESULTS Overall, 97% of newborns initiated breastfeeding and 74% were exclusively breastfed in hospital. Exclusively breastfed newborns were ultimately breastfed longer compared with those who received formula supplementation during their hospital stay (median 11.0 vs 7.0 months, P < .001). After controlling for maternal age, ethnicity, birth mode, and gestational age, exclusively breastfed newborns had a 21% reduced risk of breastfeeding cessation (HR = 0.79, 0.71-0.87). This effect was strongest among women without a postsecondary education (HR = 0.65, 0.53-0.79). DISCUSSION Exclusive breastfeeding in hospital is associated with longer breastfeeding duration, particularly among women of lower socioeconomic status. Initiatives that support exclusive breastfeeding of newborns in hospital could improve long-term breastfeeding rates and help reduce health inequities arising in early life.
Low cost shaped beam synthesis for semi-smart base station antennas

The authors present a low cost shaped beam synthesis method for semi-smart base station antennas. Compared with the conventional array synthesis for smart antenna applications, the proposed circular/conformal array shaped beam synthesis for semi-smart antenna has much lower system complexity and instrumentation implementation cost. This is because only few elements are involved and the circular array factor is simplified for coarse granularity beam. Adding to this, a fast quasi-Newton method is used by the linear/conformal array for the beam optimisation. By coding the shaped beam synthesis methodology in C/C++, the shaped beam synthesis for 12-element circular array is implemented for the semi-smart macrocell, showing its advantages of low-consumed time and stable mean square errors. Furthermore, a semi-smart sectored picocell has been designed with 4-element conformal array, which was demonstrated to be superior to the linear one by avoiding the blind angle, exhibiting better accuracy and less consumed processing time.
Molecular Pathways Involved in the Amelioration of Myocardial Injury in Diabetic Rats by Kaempferol

There is growing evidence that chronic hyperglycemia leads to the formation of advanced glycation end products (AGEs) which exerts its effect via interaction with the receptor for advanced glycation end products (RAGE). AGE-RAGE activation results in oxidative stress and inflammation. It is well known that this mechanism is involved in the pathogenesis of cardiovascular disease in diabetes. Kaempferol, a dietary flavonoid, is known to possess antioxidant, anti-apoptotic, and anti-inflammatory activities. However, little is known about the effect of kaempferol on myocardial ischemia-reperfusion (IR) injury in diabetic rats. Diabetes was induced in male albino Wistar rats using streptozotocin (70 mg/kg; i.p.), and rats with glucose level >250 mg/dL were considered as diabetic. Diabetic rats were treated with vehicle (2 mL/kg; i.p.) and kaempferol (20 mg/kg; i.p.) daily for a period of 28 days and on the 28th day, ischemia was produced by one-stage ligation of the left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed and the heart tissue was processed for biochemical, morphological, and molecular studies. Kaempferol pretreatment significantly reduced hyperglycemia, maintained hemodynamic function, suppressed AGE-RAGE axis activation, normalized oxidative stress, and preserved morphological alterations. In addition, there was decreased level of inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and NF-κB), inhibition of active c-Jun N-terminal kinase (JNK) and p38 proteins, and activation of Extracellular signal regulated kinase 1/2 (ERK1/2) a prosurvival kinase. Furthermore, it also attenuated apoptosis by reducing the expression of pro-apoptotic proteins (Bax and Caspase-3), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells, and increasing the level of anti-apoptotic protein (Bcl-2). In conclusion, kaempferol attenuated myocardial ischemia-reperfusion injury in diabetic rats by reducing AGE-RAGE/ mitogen activated protein kinase (MAPK) induced oxidative stress and inflammation.
Autonomous scanning for endomicroscopic mosaicing and 3D fusion

Robot-assisted minimally invasive surgery can benefit from the automation of common, repetitive or well-defined but ergonomically difficult tasks. One such task is the scanning of a pick-up endomicroscopy probe over a complex, undulating tissue surface to enhance the effective field-of-view through video mosaicing. In this paper, the da Vinci® surgical robot, through the dVRK framework, is used for autonomous scanning and 2D mosaicing over a user-defined region of interest. To achieve the level of precision required for high quality mosaic generation, which relies on sufficient overlap between consecutive image frames, visual servoing is performed using a combination of a tracking marker attached to the probe and the endomicroscopy images themselves. The resulting sub-millimetre accuracy of the probe motion allows for the generation of large mosaics with minimal intervention from the surgeon. Images are streamed from the endomicroscope and overlaid live onto the surgeons view, while 2D mosaics are generated in real-time, and fused into a 3D stereo reconstruction of the surgical scene, thus providing intuitive visualisation and fusion of the multi-scale images. The system therefore offers significant potential to enhance surgical procedures, by providing the operator with cellular-scale information over a larger area than could typically be achieved by manual scanning.
CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling

Chemotactic responses in bacteria require large, highly ordered arrays of sensory proteins to mediate the signal transduction that ultimately controls cell motility. A mechanistic understanding of the molecular events underlying signaling, however, has been hampered by the lack of a high-resolution structural description of the extended array. Here, we report a novel reconstitution of the array, involving the receptor signaling domain, histidine kinase CheA, and adaptor protein CheW, as well as a density map of the core-signaling unit at 11.3 Å resolution, obtained by cryo-electron tomography and sub-tomogram averaging. Extracting key structural constraints from our density map, we computationally construct and refine an atomic model of the core array structure, exposing novel interfaces between the component proteins. Using all-atom molecular dynamics simulations, we further reveal a distinctive conformational change in CheA. Mutagenesis and chemical cross-linking experiments confirm the importance of the conformational dynamics of CheA for chemotactic function. DOI: http://dx.doi. org/10.7554/eLife.08419. 001
Stepped-Carrier OFDM-Radar Processing Scheme to Retrieve High-Resolution Range-Velocity Profile at Low Sampling Rate

Recent publications show that the potential of using orthogonal frequency division multiplexing waveforms as radar signals. Since the range resolution is proportional to the RF bandwidth, the major obstacle that obstructs the practical use in automotive and other low-cost radars is the requirement to sample the received signal at sampling rates that span the whole RF signal bandwidth requiring ADCs with sampling rates in the order of GHz. This paper presents a method to achieve the high range resolution induced by a large RF bandwidth, but with a much lower baseband bandwidth, consequently requiring a much slower ADC while at the same time delivering a velocity profile for each subcarrier. In addition, the processing scheme induces a range migration compensation, independent of the number of targets. This is achieved with barely increased computational effort. The scheme is verified with simulations and measurements at 77 GHz.
Dimensions of childhood adversity have distinct associations with neural systems underlying executive functioning

Abstract Childhood adversity is associated with increased risk for psychopathology. Neurodevelopmental pathways underlying this risk remain poorly understood. A recent conceptual model posits that childhood adversity can be deconstructed into at least two underlying dimensions, deprivation and threat, that are associated with distinct neurocognitive consequences. This model argues that deprivation (i.e., a lack of cognitive stimulation and learning opportunities) is associated with poor executive function (EF), whereas threat is not. We examine this hypothesis in two studies measuring EF at multiple levels: performance on EF tasks, neural recruitment during EF, and problems with EF in daily life. In Study 1, deprivation (low parental education and child neglect) was associated with greater parent-reported problems with EF in adolescents (N = 169; 13–17 years) after adjustment for levels of threat (community violence and abuse), which were unrelated to EF. In Study 2, low parental education was associated with poor working memory (WM) performance and inefficient neural recruitment in the parietal and prefrontal cortex during high WM load among adolescents (N = 51, 13–20 years) after adjusting for abuse, which was unrelated to WM task performance and neural recruitment during WM. These findings constitute strong preliminary evidence for a novel model of the neurodevelopmental consequences of childhood adversity.