A defective viral genome strategy elicits broad protective immunity against respiratory viruses.

RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short- and long-term protection against SARS-CoV-2 and other respiratory infections in animal models.

Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection.

Mycobacterium tuberculosis (Mtb) infects lung myeloid cells, but the specific Mtb-permissive cells and host mechanisms supporting Mtb persistence during chronic infection are incompletely characterized. We report that after the development of T cell responses, CD11clo monocyte-derived cells harbor more live Mtb than alveolar macrophages (AM), neutrophils, and CD11chi monocyte-derived cells. Transcriptomic and functional studies revealed that the lysosome pathway is underexpressed in this highly permissive subset, characterized by less lysosome content, acidification, and proteolytic activity than AM, along with less nuclear TFEB, a regulator of lysosome biogenesis. Mtb infection does not drive lysosome deficiency in CD11clo monocyte-derived cells but promotes recruitment of monocytes that develop into permissive lung cells, mediated by the Mtb ESX-1 secretion system. The c-Abl tyrosine kinase inhibitor nilotinib activates TFEB and enhances lysosome functions of macrophages in vitro and in vivo, improving control of Mtb infection. Our results suggest that Mtb exploits lysosome-poor lung cells for persistence and targeting lysosome biogenesis is a potential host-directed therapy for tuberculosis.

Spatiotemporal Developmental Gradient of Thalamic Morphology, Microstructure, and Connectivity fromthe Third Trimester to Early Infancy.

Thalamus is a critical component of the limbic system that is extensively involved in both basic and high-order brain functions. However, how the thalamic structure and function develops at macroscopic and microscopic scales during the perinatal period development is not yet well characterized. Here, we used multishell high-angular resolution diffusion MRI of 144 preterm-born and full-term infants in both sexes scanned at 32-44 postmenstrual weeks (PMWs) from the Developing Human Connectome Project database to investigate the thalamic development in morphology, microstructure, associated connectivity, and subnucleus division. We found evident anatomic expansion and linear increases of fiber integrity in the lateral side of thalamus compared with the medial part. The tractography results indicated that thalamic connection to the frontal cortex developed later than the other thalamocortical connections (parieto-occipital, motor, somatosensory, and temporal). Using a connectivity-based segmentation strategy, we revealed that functional partitions of thalamic subdivisions were formed at 32 PMWs or earlier, and the partition developed toward the adult pattern in a lateral-to-medial pattern. Collectively, these findings revealed faster development of the lateral thalamus than the central part as well as a posterior-to-anterior developmental gradient of thalamocortical connectivity from the third trimester to early infancy.SIGNIFICANCE STATEMENT This is the first study that characterizes the spatiotemporal developmental pattern of thalamus during the third trimester to early infancy. We found that thalamus develops in a lateral-to-medial pattern for both thalamic microstructures and subdivisions; and thalamocortical connectivity develops in a posterior-to-anterior gradient that thalamofrontal connectivity appears later than the other thalamocortical connections. These findings may enrich our understanding of the developmental principles of thalamus and provide references for the atypical brain growth in neurodevelopmental disorders.

Profiling cortical morphometric similarity in perinatal brains: Insights from development, sex difference, and inter-individual variation.

The topological organization of the macroscopic cortical networks important for the development of complex brain functions. However, how the cortical morphometric organization develops during the third trimester and whether it demonstrates sexual and individual differences at this particular stage remain unclear. Here, we constructed the morphometric similarity network (MSN) based on morphological and microstructural features derived from multimodal MRI of two independent cohorts (cross-sectional and longitudinal) scanned at 30-44 postmenstrual weeks (PMW). Sex difference and inter-individual variations of the MSN were also examined on these cohorts. The cross-sectional analysis revealed that both network integration and segregation changed in a nonlinear biphasic trajectory, which was supported by the results obtained from longitudinal analysis. The community structure showed remarkable consistency between bilateral hemispheres and maintained stability across PMWs. Connectivity within the primary cortex strengthened faster than that within high-order communities. Compared to females, male neonates showed a significant reduction in the participation coefficient within prefrontal and parietal cortices, while their overall network organization and community architecture remained comparable. Furthermore, by using the morphometric similarity as features, we achieved over 65 % accuracy in identifying an individual at term-equivalent age from images acquired after birth, and vice versa. These findings provide comprehensive insights into the development of morphometric similarity throughout the perinatal cortex, enhancing our understanding of the establishment of neuroanatomical organization during early life.

Rich Club Reorganization in Nurses Before and After the Onset of Occupational Burnout: A Longitudinal MRI Study.

BACKGROUND: Studies on potential disruptions in rich club structure in nursing staff with occupational burnout are lacking. Moreover, existing studies on nurses with burnout are limited by their cross-sectional design. PURPOSE: To investigate rich club reorganization in nursing staff before and after the onset of burnout and the underlying impact of anatomical distance on such reconfiguration. STUDY TYPE: Prospective, longitudinal. POPULATION: Thirty-nine hospital nurses ( 23.67 ± 1.03 $$ 23.67\pm 1.03 $$ years old at baseline, 24.67 ± 1.03 $$ 24.67\pm 1.03 $$ years old at a follow-up within 1.5 years, 38 female). FIELD STRENGTH/SEQUENCE: Magnetization-prepared rapid gradient-echo and gradient-echo echo-planar imaging sequences at 3.0 T. ASSESSMENT: The Maslach Burnout Inventory and Symptom Check-List 90 testing were acquired at each MRI scan. Rich club structure was assessed at baseline and follow-up to determine whether longitudinal changes were related to burnout and to changes in connectivities with different anatomical distances (short-, mid-, and long range). STATISTICAL TESTS: Chi-square, paired-samples t, two-sample t, Mann-Whitney U tests, network-based statistic, Spearman correlation analysis, and partial least squares regression analysis. Significance level: Bonferroni-corrected P < 0.05 $$ P<0.05 $$ . RESULTS: In nurses who developed burnout: 1) Strengths of rich club, feeder, local, short-, mid-, and long-range connectivities were significantly decreased at follow-up compared with baseline. 2) At follow-up, strengths of above connectivities and that between A5m.R and dlPu.L were significantly correlated with emotional exhaustion (r ranges from -0.57 to -0.73) and anxiety scores (r = -0.56), respectively. 3) Longitudinal change (follow-up minus baseline) in connectivity strength between A5m.R and dlPu.L reflected change in emotional exhaustion score (r = 0.87). Longitudinal changes in strength of connectivities mainly involving parietal lobe were significantly decreased in nurses who developed burnout compared with those who did not. DATA CONCLUSION: In nurses after the onset of burnout, rich club reorganization corresponded to significant reductions in strength of connectivities with different anatomical distances. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Highly Anisotropic Second-Order Nonlinear Optical Effects in the Chiral Lead-Free Perovskite Spiral Microplates.

Chiral metal halide perovskites with intrinsic asymmetric structures have drawn increased research interest for the application of second-order nonlinear optics (NLO). However, designing chiral perovskites with the features of a large NLO coefficient, high laser-induced damage thresholds (LDT), and environmental friendliness remains a major challenge. Herein, we have synthesized two chiral hybrid bismuth halides: (R/S-MBA)4Bi2Br10 spiral structure microplates, templated by chiral (R/S)-methylbenzylamine (R/S-MBA). The as-grown chiral lead-free perovskite spiral microplates exhibit a recorded second harmonic generation (SHG) effect with a large effective second-order NLO coefficient (deff) of 11.9 pm V-1 and a high LDT of up to 59.2 mJ cm-2. More importantly, the twisted screw structures show competitive circular polarization sensitivity at 1200 nm with an anisotropy factor (gSHG-CD) of 0.58, which is about 3 times higher than that of reported Pb-based chiral perovskites. These findings provide a new platform to design multifunctional lead-free chiral perovskites for nonlinear photonic applications.

Preterm-birth alters the development of nodal clustering and neural connection pattern in brain structural network at term-equivalent age.

Preterm-born neonates are prone to impaired neurodevelopment that may be associated with disrupted whole-brain structural connectivity. The present study aimed to investigate the longitudinal developmental pattern of the structural network from preterm birth to term-equivalent age (TEA), and identify how prematurity influences the network topological organization and properties of local brain regions. Multi-shell diffusion-weighted MRI of 28 preterm-born scanned a short time after birth (PB-AB) and at TEA (PB-TEA), and 28 matched term-born (TB) neonates in the Developing Human Connectome Project (dHCP) were used to construct structural networks through constrained spherical deconvolution tractography. Structural network development from preterm birth to TEA showed reduced shortest path length, clustering coefficient, and modularity, and more "connector" hubs linking disparate communities. Furthermore, compared with TB newborns, premature birth significantly altered the nodal properties (i.e., clustering coefficient, within-module degree, and participation coefficient) in the limbic/paralimbic, default-mode, and subcortical systems but not global topology at TEA, and we were able to distinguish the PB from TB neonates at TEA based on the nodal properties with 96.43% accuracy. Our findings demonstrated a topological reorganization of the structural network occurs during the perinatal period that may prioritize the optimization of global network organization to form a more efficient architecture; and local topology was more vulnerable to premature birth-related factors than global organization of the structural network, which may underlie the impaired cognition and behavior in PB infants.

Age-Related Differences of Cortical Topology Across the Adult Lifespan: Evidence From a Multisite MRI Study With 1427 Individuals.

BACKGROUND: Healthy aging is usually accompanied by alterations in brain network architecture, influencing information processing and cognitive performance. However, age-associated coordination patterns of morphological networks and cognitive variation are not well understood. PURPOSE: To investigate the age-related differences of cortical topology in morphological brain networks from multiple perspectives. STUDY TYPE: Prospective, observational multisite study. POPULATION: A total of 1427 healthy participants (59.1% female, 51.75 ± 19.82 years old) from public datasets. FIELD STRENGTH/SEQUENCE: 1.5 T/3 T, T1-weighted magnetization prepared rapid gradient echo (MP-RAGE) sequence. ASSESSMENT: The multimodal parcellation atlas was used to define regions of interest (ROIs). The Jensen-Shannon divergence-based individual morphological networks were constructed by estimating the interregional similarity of cortical thickness distribution. Graph-theory based global network properties were then calculated, followed by ROI analysis (including global/nodal topological analysis and hub analysis) with statistical tests. STATISTICAL TESTS: Chi-square test, Jensen-Shannon divergence-based similarity measurement, general linear model with false discovery rate correction. Significance was set at P < 0.05. RESULTS: The clustering coefficient (q = 0.016), global efficiency (q = 0.007), and small-worldness (q = 0.006) were significantly negatively quadratic correlated with age. The group-level hubs of seven age groups were found mainly distributed in default mode network, visual network, salient network, and somatosensory motor network (the sum of these hubs' distribution in each group exceeds 55%). Further ROI-wise analysis showed significant nodal trajectories of intramodular connectivities. DATA CONCLUSION: These results demonstrated the age-associated reconfiguration of morphological networks. Specifically, network segregation/integration had an inverted U-shaped relationship with age, which indicated age-related differences in transmission efficiency. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Skeletal Transformation of Oxindoles into Quinolinones Enabled by Synergistic Copper/Iminium Catalysis.

We describe a synergistic Cu/secondary amine catalysis for skeletal transformation of an oxindole core into a quinolinone skeleton, which generates several structurally new pyridine-fused quinolinones. The synergistic reactions allow expansion of a five-membered lactam ring by radical cation-triggered C-C bond cleavage and enable a further intramolecular cyclization with the aim to construct totally distinct core skeletons.

Photoluminescence Lightening: Extraordinary Oxygen Modulated Dynamics in WS2 Monolayers.

Transition metal dichalcogenide monolayers exhibit ultrahigh surface sensitivity since they expose all atoms to the surface and thereby influence their optoelectronic properties. Here, we report an intriguing lightening of the photoluminescence (PL) from the edge to the interior over time in the WS2 monolayers grown by physical vapor deposition method, with the whole monolayer brightened eventually. Comprehensive optical studies reveal that the PL enhancement arises from the p doping induced by oxygen adsorption. First-principles calculations unveil that the dissociation of chemisorbed oxygen molecule plays a significant role; i.e., the dissociation at one site can largely promote the dissociation at a nearby site, facilitating the photoluminescence lightening. In addition, we further manipulate such PL brightening rate by controlling the oxygen concentration and the temperature. The presented results uncover the extraordinary surface chemistry and related mechanism in WS2 monolayers, which deepens our insight into their unique PL evolution behavior.

Solidification of municipal solid waste incineration fly ash with alkali-activated technology.

Alkali-activation is effective municipal solid waste incineration fly ash (MSWIFA) solidification/stabilization (S/S) technology. Percolation and migration of heavy metals in MSWIFA S/S matrix is a complicated and slow process. Here, several alkali-activated MSWIFA samples are selected to comparatively investigate the long-term leaching behavior and environmental availability of Pb, Zn and Cd when exposed in different erosion environment. Acid environment posed the more serious destroy to MSWIFA S/S matrices. RAC demonstrated that potential risk level of heavy metals is higher in acid rain environment, and Cd, Zn showed the prominent risk. When soaked in acid rain solution, the surface of alkali-activated MSWIFA S/S matrices was cracked seriously and a large number of hardened slurry peeled off. However, more stable structural properties and lower heavy metal leachability can be found in alkali-activated MSWIFA/aluminosilicate. The immobilization efficiency of Pb, Zn and Cd were all above 99.0%. Microstructure and morphology results indicated that there is new phase Friedel's salts generated and much more amorphous substance such as C-(A)-S-H gel with incorporation of aluminosilicate, which all contributed much to the formation of compact and stable microstructure, then significantly facilitated the encapsulation of heavy metal. These findings will provide theoretical basis and new insight for resource utilization and security landfill of MSWIFA.

Aberrant dynamic structure-function relationship of rich-club organization in treatment-naïve newly diagnosed juvenile myoclonic epilepsy.

Neuroimaging studies have shown that juvenile myoclonic epilepsy (JME) is characterized by impaired brain networks. However, few studies have investigated the potential disruptions in rich-club organization-a core feature of the brain networks. Moreover, it is unclear how structure-function relationships dynamically change over time in JME. Here, we quantify the anatomical rich-club organization and dynamic structural and functional connectivity (SC-FC) coupling in 47 treatment-naïve newly diagnosed patients with JME and 40 matched healthy controls. Dynamic functional network efficiency and its association with SC-FC coupling were also calculated to examine the supporting of structure-function relationship to brain information transfer. The results showed that the anatomical rich-club organization was disrupted in the patient group, along with decreased connectivity strength among rich-club hub nodes. Furthermore, reduced SC-FC coupling in rich-club organization of the patients was found in two functionally independent dynamic states, that is the functional segregation state (State 1) and the strong somatomotor-cognitive control interaction state (State 5); and the latter was significantly associated with disease severity. In addition, the relationships between SC-FC coupling of hub nodes connections and functional network efficiency in State 1 were found to be absent in patients. The aberrant dynamic SC-FC coupling of rich-club organization suggests a selective influence of densely interconnected network core in patients with JME at the early phase of the disease, offering new insights and potential biomarkers into the underlying neurodevelopmental basis of behavioral and cognitive impairments observed in JME.

Altered dynamic functional connectivity in rectal cancer patients with and without chemotherapy: a resting-state fMRI study.

Purpose: Understanding the mechanism of brain functional alterations in rectal cancer (RC) patients is of great significance to improve the prognosis and quality of life of patients. Additionally, the influence of chemotherapy on brain function in RC patients is still unclear. In this study, we aimed to investigate the alterations of brain functional network dynamics in RC patients and explore the effects of chemotherapy on temporal dynamics of dynamic functional connectivity (DFC).Methods: The group independent component analysis (GICA) and sliding window method were applied to investigate abnormalities of DFC based on resting-state functional magnetic resonance imaging (rs-fMRI) of 18 RC patients without chemotherapy (RC_NC), 21 RC patients with chemotherapy (RC_C) and 33 healthy controls (HC). Then, the Spearman correlation between aberrant properties and clinical measures was calculated.Results: Two discrete states were identified. Compared to HC, RC_NC exhibited increased mean dwell time (MDT) and fractional windows (FW) in state 2 and decreased transition numbers between the two states. Notably, three temporal properties in RC_C showed an intermediate trend in comparison with RC_NC and HC. Furthermore, RC_C also demonstrated abnormal intra- and inter-network connections, involving the visual (VIS), default mode (DM), and cognitive control (CC) networks, and most connections related to VIS were correlated with the severity of anxiety and depression.Conclusions: Our study suggested that abnormal DFC patterns could be manifested in RC patients and chemotherapy would further correct abnormalities of network dynamics, which may provide new insights into the brain functional alterations in patients with RC from the time-varying connectivity perspective.

The effect of beta-amyloid and tau protein aggregations on magnetic susceptibility of anterior hippocampal laminae in Alzheimer's diseases.

Previous studies have reported the changes of magnetic susceptibility induced by iron deposition in hippocampus of Alzheimer's disease (AD) brains. It is well-known that hippocampus is divided into well-defined laminar architecture, which, however, is difficult to be resolved with in-vivo MRI due to the limited imaging resolution. The present study aims to investigate layer-specific magnetic susceptibility in the hippocampus of AD patients using high-resolution ex-vivo MRI, and elucidate its relationship with beta amyloid (Aß) and tau protein histology. We performed quantitative susceptibility mapping (QSM) and T2* mapping on postmortem anterior hippocampus samples from four AD, four Primary Age-Related Tauopathy (PART), and three control brains. We manually segmented each sample into seven layers, including four layers in the cornu ammonis1 (CA1) and three layers in the dentate gyrus (DG), and then evaluated AD-related alterations of susceptibility and T2* values and their correlations with Aß and tau in each hippocampal layer. Specifically, we found (1) layer-specific variations of susceptibility and T2* measurements in all samples; (2) the heterogeneity of susceptibility were higher in all layers of AD patients compared with the age- and gender-matched PART cases while the heterogeneity of T2* values were lower in four layers of CA1; and (3) voxel-wise MRI-histological correlation revealed both susceptibility and T2* values in the stratum molecular (SM) and stratum lacunosum (SL) layers were correlated with the Aß content in AD, while the T2* values in the stratum radiatum (SR) layer were correlated with the tau content in the PART but not AD. These findings suggest a selective effect of the Aß- and tau-pathology on the susceptibility and T2* values in the different layers of anterior hippocampus. Particularly, the alterations of magnetic susceptibility in the SM and SL layers may be associated with Aß aggregation, while those in the SR layermay reflect the age-related tau protein aggregation.

Diffusion MRI of the infant brain reveals unique asymmetry patterns during the first-half-year of development.

The human brain demonstrates anatomical and functional lateralization/asymmetry between the left and right hemispheres, and such asymmetry is known to start from the early age of life. However, how the asymmetry changes with brain development during infancy remained unknown. In this study, we aimed to systematically investigate the spatiotemporal pattern of brain asymmetry in healthy preterm-born infants during the first-half-year of development, using high angular resolution diffusion MRI. Sixty-five healthy preterm-born infants (gestational age between 25.3-36.6 weeks) were scanned with postmenstrual age (PMA) ranging from term-equivalent age (TEA) to 6-months. At the regional level, we performed a region-of-interest-based analysis by segmenting the brain into 63 symmetrical pairs of regions, based on which the laterality index was assessed and correlated with PMA. At the voxel level, we performed a fixel-based analysis of each fiber component between the native and left-right flipped data, separately in TEA-1 month, 1-3 months, and 3-6 months groups. The infant brains demonstrated extensive regions with structural asymmetry during their first half-of-year of life. A distinct central-peripheral asymmetry pattern was observed in mean diffusivity, namely, leftward lateralization in the neocortex and rightward asymmetry in the deep brain regions. Besides, the posterior brain demonstrated a higher lateralization index compared with the anterior brain in all metrics, which is congruent with the brain developmental pattern from caudal to rostral. Regionally, language processing regions showed a rightward asymmetry, while visuospatial processing regions exhibited leftward lateralization in fractional anisotropy, fibre density, and fibre cross-section measurements, and most white matter regions were lateralized to the left in these measurements. The laterality index of several regions (12 out 63) demonstrated significant developmental changes in mean diffusivity. At the fixel level, the fiber cross-section of inferior fronto-occipital fasciculus showed significant leftward asymmetry and the extent of asymmetry increased with PMA. In summary, the results revealed unique spatiotemporal patterns of macro- and micro-structural asymmetry in early life, which dynamically changed with age. These findings may contribute to the understanding of brain development during infancy.

Developmental pattern of the cortical topology in high-functioning individuals with autism spectrum disorder.

A number of studies have indicated alterations of brain morphology in individuals with autism spectrum disorder (ASD); however, how ASD influences the topological organization of the brain cortex at different developmental stages is not yet well characterized. In this study, we used structural images of 492 high-functioning participants in the Autism Brain Imaging Data Exchange database acquired from 17 international imaging centers, including 75 autistic children (age 7-11 years), 91 adolescents with ASD (age 12-17 years), and 80 young adults with ASD (age 18-29 years), and 246 typically developing controls (TDCs) that were age, gender, handedness, and full-scale IQ matched. Cortical thickness (CT) and surface area (SA) were extracted and the covariance between cortical regions across participants were treated as a network to examine developmental patterns of the cortical topological organization at different stages. A center-paired resampling strategy was developed to control the center bias during the permutation test. Compared with the TDCs, network of SA (but not CT) of individuals with ASD showed reduced small-worldness in childhood, and the network hubs were reorganized in the adulthood such that hubs inclined to connect with nonhub nodes and demonstrated more dispersed spatial distribution. Furthermore, the SA network of the ASD cohort exhibited increased segregation of the inferior parietal lobule and prefrontal cortex, and insular-opercular cortex in all three age groups, resulting in the emergence of two unique modules in the autistic brain. Our findings suggested that individuals with ASD may undergo remarkable remodeling of the cortical topology from childhood to adulthood, which may be associated with the altered social and cognitive functions in ASD.

Microstructural profiles of thalamus and thalamocortical connectivity in patients with disorder of consciousness.

Thalamus and thalamocortical connectivity are crucial for consciousness; however, their microstructural changes in patients with a disorder of consciousness (DOC) have not yet been thoroughly characterized. In the present study, we applied the novel fixel-based analysis to comprehensively investigate the thalamus-related microstructural abnormalities in 10 patients with DOC using 7-T diffusion-weighted imaging data. We found that compared to healthy controls, patients with DOC showed reduced fiber density (FD) and fiber density and cross-section (FDC) in the mediodorsal, anterior, and ventral anterior thalamic nuclei, while fiber-bundle cross-section (FC) was not significantly altered in the thalamus. Impaired thalamocortical connectivity in the DOC cohort was mainly connected to the middle frontal gyrus, anterior cingulate gyrus, fusiform gyrus, and sensorimotor cortices, including the precentral gyrus and postcentral gyrus, with predominant microstructural abnormalities in FD and FDC. Correlation analysis showed that FC of the right mediodorsal thalamus was negatively correlated with the level of consciousness. Our results suggest that microstructural abnormalities of thalamus and thalamocortical connectivity in DOC were mainly attributed to axonal injury. In particular, the microstructural integrity of the thalamus is a vital factor in consciousness generation.

Altered Functional Connectivity of Hippocampal Subfields in Poststroke Dementia.

BACKGROUND: The hippocampus (HP) plays a critical role in memory and orientational functions and is functionally heterogeneous along the longitudinal anterior-posterior axis. Although the previous study has reported volumetric atrophy in hippocampal subfields of patients with poststroke dementia (PSD), how the functional connectivity (FC) is altered in these subfields remains unclear. PURPOSE: To examine the FC changes of the HP subfields in patients with PSD. STUDY TYPE: Prospective. POPULATION: Seventeen normal controls, 20 PSD, and 24 nondemented poststroke (PSND) patients. FIELD STRENGTH/SEQUENCE: A 3.0 T/ T1-weighted imaging, resting-state functional and diffusion tensor imaging. ASSESSMENT: We first segmented the HP using independent component analysis, and then used granger causality analysis to calculate the directed FCs (dFCs) between the subfields and the whole brain, and compared the dFCs among PSD, PSND, and controls. STATISTICAL TESTS: Student's t-test, chi-square test, one-way ANCOVA, multiple regression, support vector machine, multiple comparison correction, and reproducibility analysis. A P value < 0.05 was considered statistically significant. RESULTS: Our results showed HP was functionally divided into HPhead , HPbody , and HPtail bilaterally along the longitudinal axis. PSD patients showed significant dementia-specific decreases in the inward information flow and increases in the outward information flow associated with the bilateral entire HP/HPhead and left HPbody (P < 0.05). Moreover, we observed significant correlations (P < 0.05) between the cognition score and the dFCs related to the bilateral entire HP and left HPhead in the PSD group. Furthermore, dFCs of the HP and its subfields improved the classification between the PSD and PSND patients (accuracy/sensitivity/specificity: 94%/95%/93%) compared to the clinical and demographic parameters alone. DATA CONCLUSION: These findings suggest that altered transmission and reception of information in the HP. These alternations were specific to individual subfields in PSD patients and may offer insight into the neurophysiological mechanisms underlying PSD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Pain-Evoked Reorganization in Functional Brain Networks.

Recent studies indicate that a significant reorganization of cerebral networks may occur in patients with chronic pain, but how immediate pain experience influences the organization of large-scale functional networks is not yet well characterized. To investigate this question, we used functional magnetic resonance imaging in 106 participants experiencing both noxious and innocuous heat. Painful stimulation caused network-level reorganization of cerebral connectivity that differed substantially from organization during innocuous stimulation and standard resting-state networks. Noxious stimuli increased somatosensory network connectivity with (a) frontoparietal networks involved in context representation, (b) "ventral attention network" regions involved in motivated action selection, and (c) basal ganglia and brainstem regions. This resulted in reduced "small-worldness," modularity (fewer networks), and global network efficiency and in the emergence of an integrated "pain supersystem" (PS) whose activity predicted individual differences in pain sensitivity across 5 participant cohorts. Network hubs were reorganized ("hub disruption") so that more hubs were localized in PS, and there was a shift from "connector" hubs linking disparate networks to "provincial" hubs connecting regions within PS. Our findings suggest that pain reorganizes the network structure of large-scale brain systems. These changes may prioritize responses to painful events and provide nociceptive systems privileged access to central control of cognition and action during pain.

Detecting neonatal acute bilirubin encephalopathy based on T1-weighted MRI images and learning-based approaches.

BACKGROUND: Neonatal hyperbilirubinemia is a common clinical condition that requires medical attention in newborns, which may develop into acute bilirubin encephalopathy with a significant risk of long-term neurological deficits. The current clinical challenge lies in the separation of acute bilirubin encephalopathy and non-acute bilirubin encephalopathy neonates both with hyperbilirubinemia condition since both of them demonstrated similar T1 hyperintensity and lead to difficulties in clinical diagnosis based on the conventional radiological reading. This study aims to investigate the utility of T1-weighted MRI images for differentiating acute bilirubin encephalopathy and non-acute bilirubin encephalopathy neonates with hyperbilirubinemia. METHODS: 3 diagnostic approaches, including a visual inspection, a semi-quantitative method based on normalized the T1-weighted intensities of the globus pallidus and subthalamic nuclei, and a deep learning method with ResNet18 framework were applied to classify 47 acute bilirubin encephalopathy neonates and 32 non-acute bilirubin encephalopathy neonates with hyperbilirubinemia based on T1-weighted images. Chi-squared test and t-test were used to test the significant difference of clinical features between the 2 groups. RESULTS: The visual inspection got a poor diagnostic accuracy of 53.58 ± 5.71% indicating the difficulty of the challenge in real clinical practice. However, the semi-quantitative approach and ResNet18 achieved a classification accuracy of 62.11 ± 8.03% and 72.15%, respectively, which outperformed visual inspection significantly. CONCLUSION: Our study indicates that it is not sufficient to only use T1-weighted MRI images to detect neonates with acute bilirubin encephalopathy. Other more MRI multimodal images combined with T1-weighted MRI images are expected to use to improve the accuracy in future work. However, this study demonstrates that the semi-quantitative measurement based on T1-weighted MRI images is a simple and compromised way to discriminate acute bilirubin encephalopathy and non-acute bilirubin encephalopathy neonates with hyperbilirubinemia, which may be helpful in improving the current manual diagnosis.