Temporal Connectivity Research Articles

Severe disability and self-reported depression and anxiety among persons living with Type 2 diabetes in Canada

BackgroundThis study aims to estimate the national prevalence of self-reported depression and anxiety disorders among persons living with Type 2 diabetes in Canada, as well as to investigate the potential link between disability severity and these conditions. MethodsWe conducted a cross-sectional analysis of a subsample (N=8,321) of participants living with Type 2 diabetes in the 2017-2018 Canadian Community Health Survey-Annual Component. Modified Poisson regression models were used to examine the association between disability severity and depression and anxiety disorders. Descriptive statistics, prevalence estimates, adjusted relative risk, and 95% confidence intervals are reported. All statistical analyses were conducted using STATA version 18. ResultsThe prevalence of depression and anxiety were 12.4% and 10.1% respectively. Our study found disability severity as a strong risk factor for both psychiatric disorders. We also found (1) dissatisfaction with life, (2) extremely stressful life events, (3) being female (4) single or never married, (5) poor self-rated health, (6) obesity, and (7) current smoker as significant risk factors for both psychiatric disorders. Conversely, increasing age and higher annual personal income status were significant protective factors. LimitationsThe study's limitations include the inability to establish temporal connections between risk factors and psychiatric disorders due to the cross-sectional design and the exclusion of those living in remote parts of the country and others from participation in the survey, which may underestimate the prevalence of Type 2 diabetes and severe disability. ConclusionsThis study's findings point toward a growing demand for tertiary prevention to increase the probability for those living with Type 2 diabetes in Canada of maintaining functional health, improving mental health, and having a better quality of life. Public health prevention efforts targeted at decreasing the prevalence of diabetes and its complications and disability severity are recommended.

Exploring Long Short Term Memory Algorithms for Low Energy Data Aggregation

Long short-term memory methods are employed for data consolidation in intricate low-energy devices. It has enabled accurate and efficient aggregation of statistics in limited electricity settings, facilitating the review and retrieval of data while minimizing electricity wastage. The LSTM rules analyze, organize, and consolidate vast datasets inside weakly connected structures. It has employed a recurrent neural network to handle data processing, particularly nonlinear interactions. The machine's capabilities are subsequently examined and stored utilizing memory blocks. Memory blocks retain extended temporal connections within the data, facilitating adaptive and precise information aggregation. These blocks facilitate the system's ability to shop and utilize relevant capabilities for quick retrieval. The proposed algorithm offers realistic tuning capabilities such as learning rate scheduling and total regularization based on dropout like green information aggregation. These enable systems to reduce over fitting while permitting precise adjustment of the settings. It allows for optimizing the algorithm to provide highly dependable performance within weak structures, enhancing data aggregation techniques' energy efficiency. Standard algorithms provide an efficient, accurate solution for aggregating information in low-power systems. It facilitates evaluating, retrieving, and aggregating accurate and reliable information using memory blocks, adaptive tuning, and efficient learning rate scheduling.

Time use surveys, social practice theory, and activity connections.

Social practice theory (SPT) represents a growing body of research that takes the 'doings and sayings' (social practices) of everyday life as its core unit of enquiry. Time use surveys (TUS) represent a substantial source of micro-data regarding how activities are performed across the 24-h day. Given their apparent complementarities, we ask why TUS have not been utilised more extensively within SPT-inspired research. We advance two contentions: (1) ontological tensions obscure the relevance of TUS data in addressing core SPT research questions, and (2) SPT concepts do not readily translate for application in TUS analysis. In response, we operationalise Schatzki's (2019) concepts of activity events and chains to explore types and forms of temporal activity connection. Using TUS data we examine three activity events: sleeping, reading, and eating. Two types of temporal activity connection (sequence and synchronisation) are identified, together with four forms of connectivity (degrees of uniformity/diversity, sequential directionality, time-varying connections, and symmetrical/asymmetrical relationships). While practices cannot be reduced to activity connections, we argue that this analytical approach offers a systematic basis for examining the ways in which activities combine to underpin the organisation of social practices. Further analysis to compare activity connections across practices, between different groups of practitioners, and over time would offer a valuable resource to empirically examine claims regarding core processes of societal change. We further contend that SPT approaches offer insights for time use research by providing a framework capable of recognising that activities are dynamic and variable rather than homogeneous and stable categories.

Toward a Redefinition of Agricultural Drought Periods—A Case Study in a Mediterranean Semi-Arid Region

Drought is a powerful natural hazard that has significant effects on ecosystems amid the constant threats posed by climate change. This study investigates agricultural drought in a semi-arid Mediterranean basin through the interconnections among four indices: precipitation (meteorological reanalysis), vegetation development, thermal stress, and soil water deficit (remote sensing observations). While drought seems to be a clear concept with effective assessment tools (e.g., SPI and SPEI), the definition of drought periods is blurrier. This article examines the main drivers of agricultural drought, precipitation, soil moisture deficit, incipient vegetation development, and rising soil surface temperature. Their temporal connections in various agrosystems of the basin and the determination of drought periods by revisiting the run theory were investigated. The Pearson correlations at different spatial scales showed a medium to low level of agreement between the indices, which was explained by the geographical heterogeneity and the climatic variability between the agrosystems within the basin. It was also shown that the cascade of impacts expected from lower precipitations was revealed by the cross-correlation analysis. The connection between precipitation deficit and vegetation remains significant for at least one month for most pairs of indices, especially during drought events, suggesting that agricultural drought spells can be connected in time through the three or four selected indices. Short-, mid-, and long-term impacts of precipitation deficiencies on soil moisture, vegetation, and temperature were revealed. As expected, the more instantaneous variables of soil moisture and surface temperature showed no lag with precipitation. Vegetation anomalies at the monthly time step showed a two-month lag with a preceding effect of vegetation to precipitation. Finally, the determination of drought events and stages with varying thresholds on the run theory showed large variability in duration, magnitude, and intensity according to the choice of both normality and dryness thresholds.

Altered resting state hippocampal connectivity associated with amyloid and tau in older adults without dementia from a population‐based cohort study

AbstractBackgroundAlzheimer’s disease (AD) is characterized by amyloid beta plaques and tau‐containing neurofibrillary tangles with disrupted (high and low) resting state hippocampal connectivity. One potential factor that may underlie these differences is that early stages of disease may contribute to greater connectivity and later stages may contribute to lower connectivity (i.e., quadratic associations between amyloid/tau and connectivity). Early stages may be associated with greater recruitment of intranetwork connectivity to compensate, which fails at later stages. Late stages may be associated with greater recruitment of internetwork connectivity, that fails in advanced cognitive impairment. Understanding these dynamics may help us understand resilience to amyloid and tau in cognitively unimpaired individuals.MethodWe recruited 115 adults >65 years old (67‐96, mean 76years) from a population‐based study into a neuroimaging sub‐study. The study area is a formerly heavy manufacturing industrial small‐town area. Participants (106 (92%) CU with CDR = 0) underwent PET imaging for amyloid (PiB) and tau (AV‐1451) and global SUVR measures were computed after appropriate preprocessing. Participants underwent resting state fMRI and hippocampal connectivity was computed for the left/right and anterior/posterior hippocampus. Regression analyses between connectivity and both linear and quadratic terms for amyloid and tau were adjusted for age, sex, race, and education. We adjusted for multiple comparisons using SnPM with FWE correction with α = 0.05 (p‐value threshold of 0.001).ResultWe found a negative quadratic association between left anterior hippocampus with default mode network (DMN) including the posterior cingulate and supramarginal gyrus, where greater amyloid and lower amyloid was associated with low connectivity. Similar effects were found for the right anterior hippocampus. Right anterior hippocampus to cuneus connectivity shows positive U‐shape with amyloid but negative linear relationship with tau. Greater right anterior hippocampus‐inferior parietal and right posterior hippocampus‐inferior temporal connectivity was associated with greater tau. Left posterior hippocampus to left middle temporal showed negative U‐shape with tau.ConclusionAmyloid and tau showed complex inverse U‐shaped associations between heightened intranetwork connectivity and moderate amyloid/tau, but low connectivity with higher severity. Internetwork connectivity was heightened with greater tau. These may reflect altered connectivity due to changes in amyloid and tau in older adults without dementia.

MRI deep learning demonstrates featured neuropathological deteriorations in the AD brain

AbstractBackgroundDeep learning (DL) of non‐invasive brain structural magnetic resonance imaging (sMRI) has shown superb performance in differentiating Alzheimer’s disease (AD) from cognitively healthy participants (HC). Attention is needed to tackle AD pathological progression on sMRI using interpretable DL methods. Here, we studied the feasibility of DL in identifying neurodegenerative progression patterns in AD.MethodData applied to the study were from the multi‐centre Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Open Access Series of Imaging Studies (OASIS) with 2,369 T1‐weighted brain images of 1,005 subjects. An interpretable DL technique named the ensemble 3‐dimensional convolutional neural network (Ensemble 3DCNN) was used to detect the longitudinal trajectory of sMRI changes during AD progression. The model used multiple 3D convolutional neural networks and a meta‐classifier to assess the degree of brain changes through generating an index score, named P‐score. The score was derived as the outcome of training and verifying the Ensemble 3DCNN model for difference in the whole‐brain sMRI between AD and HC. The predictive P‐scores values were used to analyze the sMRI images for mining neurodegenerative brain regions. In addition, dementia stages, and the temporal and spatial connectivity patterns of neurodegeneration progression were also analyzed.ResultBrain regions showing high P‐scores (> 0.73/1.00) included the amygdala, nucleus accumbens, agranular insular cortex, and the hippocampus, matching the isocortex, basal magnocellular complex, and transentorhinal regions identified in Braak staging. The P‐score increased over time in 82% of the degenerative brain regions. The impaired areas were often spatially connected, consistently across multiple time points in the progression of AD. The trajectory of regional brain changes displayed multiple patterns with complex individual variability.ConclusionThe interpretable 3D DL model demonstrated featured deteriorations on the AD sMRI images. The finding confirmed the neuropathological degeneration of AD and captured additional whole‐brain changes, especially, relating to the heterogeneity of AD expression.

Microstructural integrity and structural connectivity of medial temporal lobe subregions is related to Alzheimer’s pathology

AbstractBackgroundThe earliest effects of Alzheimer’s disease pathology on medial temporal lobe (MTL) gray matter microstructure and white matter connectivity are still unknown. Here, we applied ultra‐high‐resolution diffusion MRI to characterize microstructural integrity and structural connectivity of the MTL, and tested associations with Alzheimer’s pathology and memory performance in cognitively normal older adults.Method83 participants (M = 71.7yrs, 66% female) received structural and ultra‐high‐resolution diffusion MRI (0.67×0.67×3mm). Subsamples received [18F]‐florbetapir (FBP) to measure Aß (n = 77; global summary SUVR), [18F]‐MK6240 to measure tau (n = 23; entorhinal SUVR), and performed an object mnemonic discrimination task (n = 74). Structural MRI was processed with ASHS to obtain MTL ROIs (Fig1). Diffusion MRI was processed with FSL DTIfit to calculate mean diffusivity (MD), an index of cellular integrity. Tractography was performed with DSI Studio. ROI‐to‐ROI streamlines were calculated (Fig3A) and used for structural connectivity graph analyses of the MTL network. Analyses controlled for age and sex, with scan interval and education in relevant models.ResultEntorhinal MK6240 SUVR was associated with increased MD in transentorhinal cortex (BA35; r = 0.72, p<0.001), entorhinal cortex (EC; r = 0.61, p = 0.004), and dentate gyrus (DG; r = 0.46, p = 0.04; Fig2A), while global FBP SUVR was associated with higher MD in EC (r = 0.25, p = 0.03). Worse mnemonic discrimination performance was associated with increased MD in DG (r = ‐0.29, p = 0.01), with trends in EC (r = ‐0.23, p = 0.06) and CA3 (r = ‐0.20, p = 0.09; Fig2B). The number of streamlines between EC and DG was not significantly associated with entorhinal MK6240 SUVR (r = ‐0.32, p = 0.17), FBP SUVR, or mnemonic discrimination (ps>0.37). Lower global efficiency of the MTL network was associated with increased entorhinal MK6240 SUVR (r = ‐0.50, p = 0.025) yet better mnemonic discrimination performance (r = ‐0.28, p = 0.02; Fig3B).ConclusionEntorhinal tau pathology and memory performance are closely related to microstructural integrity and structural connectivity of the MTL, suggesting tau‐related MTL neurodegeneration may drive early memory decline.

Increased medial temporal lobe functional connectivity is critical in Alzheimer’s disease: evidences from longitudinal analyses across the whole cognitive continuum

AbstractBackgroundThe medial temporal lobe is extensively connected to the whole brain through two functional networks: the anterior‐temporal (AT) and posterior‐medial (PM) systems. While both increased and decreased functional connectivity (FC) have been reported in Alzheimer’s disease (AD), the specific changes in each network and their clinical relevance throughout AD stages remain to be elucidated. To fill this gap, we aimed to provide a comprehensive overview of AT‐ and PM‐FC changes, and links with AD imaging‐biomarkers, clinical severity and dementia onset, using longitudinal data covering the whole cognitive continuum.MethodLongitudinal data were acquired in 209 cognitively unimpaired (CU) adults aged 19‐85 (n = 56 Aβ‐ over 60), 26 Aβ+ patients with mild cognitive impairment (MCI) (n = 18 AD‐converters), and 26 Aβ+ AD‐demented patients, all followed up to 4 years. All underwent resting‐state (rs)‐fMRI, T1‐w MRI, Florbetapir‐ and FDG‐PET. Connectivity maps were generated from seed‐to‐voxels analyses applied to rs‐fMRI using individual ROIs (AT = perirhinal cortex, PM = parahippocampal cortex). The networks were defined by comparing baseline CU Aβ‐ AT to PM maps (and vice‐versa) using paired permutation t‐tests with FWE correction. Mean FC was then extracted from these masks for each participant. Generalized additive and linear mixed models were run to assess AT‐ and PM‐FC changes across the whole cognitive continuum, and their relationships with i)‐amyloid uptake, ii)‐glucose metabolism, iii)‐hippocampal volume and iv)‐cognitive deficit within participants>60yo, and v)‐AD‐conversion time in MCI patients.ResultResults showed that AT‐FC linearly increased from younger to Aβ+ AD‐demented adults while PM‐FC decreased along the healthy lifespan and then remained stable across the AD continuum (Aβ+ individuals). Higher AT‐FC was associated with i)‐higher amyloid uptake, ii)‐lower glucose metabolism, iii)‐smaller hippocampal volume, iv)‐lower MMSE/Mattis scores and v)‐faster AD‐dementia onset. No such relationships were found with PM‐FC.ConclusionBy encompassing the whole cognitive continuum and assessing longitudinal changes, we highlighted that AT‐ and PM‐FC alterations differ in aging and AD. While reduced PM connectivity seems restricted to age‐related processes (corroborated by no correlation with AD‐signature changes), increased AT connectivity seems to result from specific AD‐related mechanisms. Importantly, we evidenced that AT hyper‐connectivity appears critical in AD and might predict clinical and pathological outcomes.

Microstructural integrity and structural connectivity of medial temporal lobe subregions is related to Alzheimer’s pathology

AbstractBackgroundThe earliest effects of Alzheimer’s disease pathology on medial temporal lobe (MTL) gray matter microstructure and white matter connectivity are still unknown. Here, we applied ultra‐high‐resolution diffusion MRI to characterize microstructural integrity and structural connectivity of the MTL, and tested associations with Alzheimer’s pathology and memory performance in cognitively normal older adults.Method83 participants (M = 71.7yrs, 66% female) received structural and ultra‐high‐resolution diffusion MRI (0.67×0.67×3mm). Subsamples received [18F]‐florbetapir (FBP) to measure Aβ (n = 77; global summary SUVR), [18F]‐MK6240 to measure tau (n = 23; entorhinal SUVR), and performed an object mnemonic discrimination task (n = 74). Structural MRI was processed with ASHS to obtain MTL ROIs (Fig1). Diffusion MRI was processed with FSL DTIfit to calculate mean diffusivity (MD), an index of cellular integrity. Tractography was performed with DSI Studio. ROI‐to‐ROI streamlines were calculated (Fig3A) and used for structural connectivity graph analyses of the MTL network. Analyses controlled for age and sex, with scan interval and education in relevant models.ResultEntorhinal MK6240 SUVR was associated with increased MD in transentorhinal cortex (BA35; r = 0.72, p<0.001), entorhinal cortex (EC; r = 0.61, p = 0.004), and dentate gyrus (DG; r = 0.46, p = 0.04; Fig2A), while global FBP SUVR was associated with higher MD in EC (r = 0.25, p = 0.03). Worse mnemonic discrimination performance was associated with increased MD in DG (r = ‐0.29, p = 0.01), with trends in EC (r = ‐0.23, p = 0.06) and CA3 (r = ‐0.20, p = 0.09; Fig2B). The number of streamlines between EC and DG was not significantly associated with entorhinal MK6240 SUVR (r = ‐0.32, p = 0.17), FBP SUVR, or mnemonic discrimination (ps>0.37). Lower global efficiency of the MTL network was associated with increased entorhinal MK6240 SUVR (r = ‐0.50, p = 0.025) yet better mnemonic discrimination performance (r = ‐0.28, p = 0.02; Fig3B).ConclusionEntorhinal tau pathology and memory performance are closely related to microstructural integrity and structural connectivity of the MTL, suggesting tau‐related MTL neurodegeneration may drive early memory decline.

Braak‐stage II atrophy links lower locus coeruleus – medial temporal lobe connectivity to cognitive decline in preclinical AD

AbstractBackgroundIn preclinical human Alzheimer’s disease (AD), novelty‐related functional connectivity of the locus coeruleus (LC) with the medial temporal lobe (MTL) (ConnLC‐MTL) predicted beta‐amyloid (Aβ)‐related longitudinal cognitive decline. In animals, LC lesions in AD models led to dwindling LC projections to the hippocampus, hippocampal atrophy, and cognitive impairment. Following these observations, we investigated the contribution of cross‐sectional and longitudinal atrophy in early Braak stages as a potential mechanism underlying this relationship.MethodWe included 128 participants of the Harvard Aging Brain Study (HABS) with baseline Pittsburgh Compound‐B Positron Emission Tomography – Distribution Volume Ratio (PiB PET, DVR; 36 Aβ+), as well as baseline functional and longitudinal structural MRI (ntot = 372; ∼ every 3 years; follow‐up 5±3.4 years) and yearly cognitive assessments (PACC5 = Preclinical Alzheimer’s Cognitive Composite; ntot = 874; follow‐up 6.5±3.3 years) (Table 1). ConnLC‐MTL values were derived voxel‐wise and averaged across significant clusters. FreeSurfer‐estimated cortical thickness and hippocampus/amygdala volume (adjusted for intracranial volume) were z‐scored and averaged in two variables (THV2/THV3), encompassing regions associated with Braak stage II and III respectively (Table 1). Baseline associations were evaluated with linear models, longitudinal relationships between ConnLC‐MTL and THV2/THV3 with mixed‐effects models (random intercept and slope). Mediation of ConnLC‐MTL and PACC5 slopes (year 5‐13) by THV2/THV3 slopes (year 0‐5) was calculated (n = 79; bootstrapped n = 1000; Table 1). All models contained age, sex and education as covariates.ResultAt baseline, ConnLC‐MTL positively associated with THV2 (p = 0.005) and with PACC5 (p = 0.045), but not with THV3 (p = 0.26; Figure 1A‐C). Longitudinally, ConnLC‐MTL did not predict changes in THV2 nor THV3. However, we observed faster cortical atrophy with lower ConnLC‐MTL at higher levels of neocortical PiB (THV2: p = 0.02; THV3: p<0.001; Figure 1D‐E). Finally, THV2, but not THV3, mediated the relationship between ConnLC‐MTL and PACC5 decline (p = 0.024) and this effect was stronger in PiB+ individuals compared to PiB‐ (p = 0.026; Figure 2).ConclusionWorse LC‐MTL connectivity was associated with downstream atrophy in the target Braak‐stage II areas, which impacted cognitive performance in preclinical AD. Given that in similar previous animal findings activation of the norepinephrine LC system reversed memory deficits, maintaining optimal ConnLC‐MTL may be a promising intervention target to delay disease progression.

Neuroimaging Correlates of Alzheimer’s Disease biomarkers in a mid‐life, racially diverse high‐risk cohort

AbstractBackgroundClinicians and researchers utilize neuroimaging (NI) biomarkers of Alzheimer’s disease (AD) at an increasing rate. It is crucial that we determine whether these biomarkers generalize to underrepresented populations, particularly Black Americans (BAs), as they are 64% more likely as white individuals to develop AD. BAs may exhibit unique AD biomarker profiles across disease states, including NI biomarkers. Investigating biomarkers in at‐risk individuals may allow for early identification and intervention. Here we analyze comprehensive NI biomarkers including resting state fMRI, white matter lesions, and hippocampal volumes in conjunction with cerebrospinal fluid (CSF) markers in a midlife, racially diverse, cognitively normal cohort with a parental history of AD.MethodData included 57 cognitively normal, middle‐aged individuals, 14 BAs and 43 white. CSF was acquired via lumbar puncture to determine CSF t‐tau and Aβ1‐42 concentrations. Using resting state fMRI data, we analyzed default mode network connectivity between the posterior cingulate & precuneus, parrahippocampal gyrus (PHG), temporal pole, hippocampus, and lateral temporal cortex. We obtained regional WMH data from FLAIR images using an in‐house algorithm, and hippocampal volumes from Freesurfer. In our multivariate model, outcome variables were connectivity values, regional WMH and hippocampal volumes, with race and CSF t‐tau and Aβ1‐42 as our independent variables with a race X CSF interaction term.ResultWe identified a significant race X t‐tau and race X Aβ1‐42 interaction term for temporal and parietal WMH volumes and connectivity between PHG and temporal pole. Higher AD CSF biomarkers negatively correlated with brain connectivity (p = 0.01), and positively with WMH volume (p<0.001) in BAs.ConclusionWe extend our previous work to a middle‐aged cohort to show that DMN connectivity may be a predictor of AD risk in middle‐age, particularly for BAs, and that BAs may exhibit earlier vulnerability to vascular lesions. We support previous work that the temporal lobe is the first region to experience AD‐related connectivity changes, and that WMHs may predispose this region to AD vulnerability. This study emphasizes the need for recruitment of diverse cohorts in NI studies of AD.

Factor V Inhibitor in COVID-19 an Unusual Presentation

Introduction : A huge variety of haematological manifestations and derangements have been frequently published with COVID-19 infections, however Factor V deficiency and COVID-19 infection has not been documented. We are reporting a case of acquired Factor V deficiency due to inhibitor caused by COVID 19 infection . Factor V deficiency is a rare bleeding disorder having either inherited or acquired forms. Acquired factor V deficiency (AFVD) can present at any age, with the manifestations ranging from abnormal deranged PT/PTT to serious bleeding and quite often challenging to diagnose. The risk factors for development of inhibitors include surgical procedures, Hepatitis, antibiotic, Urinary tract infections, blood transfusions, haemodialysis, malignancies like multiple myeloma, amyloidosis and autoimmune disorders. Around 30% of cases of AFVI are found to be idiopathic. Studies suggest that there is a temporal Connection between SARS-CoV-2 infection and the development of coagulopathy. This could be possible since COVID -19 infection is well associated with autoimmune coagulation abnormalities such as lupus anticoagulant, antiphospholipid antibodies, and venous thromboembolism. The precise mechanisms behind the relationship between Covid19 infection and development of Factor V deficiency is not fully understood. SARS-CoV-2 infection induces a proinflammatory state causing endothelial damage, platelet activation and hyperviscosity. We suggest that the factor V inhibitor was formed in the setting of immune dysregulation from the underlying COVID-19 as coagulation profile was normal before admission to hospital. Result and method: A 62 year old gentleman with background of dyslipidemia and IBS was admitted to the hospital with asymptomatic COVID pneumonia. The patient was started on Lopinavir-Ritonivir 500mg BID and enoxaparin 40mg OD. Upon routine testing patient was found to have a deranged coagulation profile (PT: 41.9sec/APTT: 104.7sec/INR: 3.5/Fibrinogen: 3.04gm/L/ D-dimer: <0.30mg/L FEU). Daily results kept showing a steady rise of coagulation parameters (PT: 46.5sec/APTT: 122.0sec/INR: 3.9) however the patient was asymptomatic. Results demonstrated severe factor V deficiency (<5.7%) with mildly reduced Factor VII (53.8%) and a mildly elevated factor VIII (195.4%). PT and APTT mixing studies showed no correction of the prolonged clotting times before and after 2 hours incubation, hence the failure of correction suggested the presence of an inhibitor for which Bethesda test for Inhibitor's titer and autoimmune screening were sent. Considering the Factor V inhibitor deficiency with background of active COVID-19 infection and to prevent bleeding complications, the patient was started on Inhibitor eradication therapy with Dexamethasone 20 mg, and Immune globulin intravenous 45 gm. Inhibitor titers came back positive for an inhibitor level of 9 BU/ml. Autoimmune screen for ANA and anti-B2 glycoprotein came back negative. Malignancy was ruled out. Throughout the hospital stay , we did not encounter any bleeding manisfestions or drop in haemoglobin. Since the patient had a previous record of normal coagulation profile in 2019, a diagnosis of COVID-19 infection-related Factor V deficiency with inhibitor was made. After a four-days course of inhibitors eradication, PT INR and aPTT started coming down with no significant complications, the patient was discharged on oral prednisolone and vitamin K. Follow up in the clinic after 3 weeks showed complete normalization of coagulation profile. Conclusion: A wide range of haematological manifestation have been reported with COVID-19 infection, but the association of Factor V deficiency due to inhibitors and COVID-19 infection have not been reported in the literature earlier. Treatment will be focusing on treating the primary cause and eradication of the inhibitors.

Study on the spatial and temporal correlation and allometric growth mechanism between population aging and carbon emissions in China.

Population aging and carbon emissions are critical issues for China's development. As an enormous complex system, the population and the carbon emission development process have non-negligible differences in time, space, and speed. Therefore, this paper first demonstrates the spatial and temporal correlation between population aging and carbon emissions from 1995 to 2020, then uses the allometric growth analysis model to make a cross-sectional temporal comparison and a vertical spatial comparison of the relationship and development rate of the two, and finally uses the ridge regression model to determine the forces and interaction mechanisms of the factors influencing the relationship between population aging and carbon emissions at allometric rates. The results show that (1) China has a long-term positive temporal correlation effect relationship between population aging and carbon emissions from 1995 to 2020, and the overall correlation is high. The spatial correlation intensity between population aging and carbon emissions varies significantly across Chinese provinces, with a general spatial distribution trend of high in the south, low in the north, and prominent in the center. (2) China's population aging and carbon emissions mainly show a negative allometric growth type of relationship, i.e., a strong trend of population aging expansion and a strengthening trend of carbon emission system shrinking. The number of provinces with negative allometric growth is gradually increasing, mainly in North, East, Central, and Southwest China. (3) From 1995-2010 period to the 2011-2020 period, the influence of the factors of the population, production, and economic dimensions on the population aging index and the carbon emission allometric scalar index gradually weakened, and the influence of the consumption and technology dimensions increased significantly. The factors on the population and consumption side of the dimension mainly contribute to the expansion of carbon emissions and drive positive allometric growth. The production side, the economic structure, and technology dimension factors drive negative allometric growth. The paper fully explores the bidirectional correlation, differential development trend, and interaction mechanism between the two systems of population and carbon emissions and effectively compensates for the lack of research content in terms of elemental correlation, spatial and temporal connection, and speed synergy.

Effects of Cortisol Administration on Resting-State Functional Connectivity in Women with Depression

Previous resting-state functional connectivity (rsFC) research has identified several brain networks impacted by depression and cortisol, including default mode (DMN), frontoparietal (FPN), and salience networks (SN). In the present study, we examined the effects of cortisol administration on rsFC of these networks in individuals varying in depression history and severity. We collected resting-state fMRI scans and self-reported depression symptom severity for 74 women with and without a history of depression after cortisol and placebo administration using a double-blind, crossover design. We conducted seed-based rsFC analyses for DMN, FPN, and SN seeds to examine rsFC changes after cortisol vs. placebo administration in relation to depression history group and severity. Results revealed a main effect of depression group, with lower left amygdala (SN)-middle temporal gyrus connectivity in women with a history of depression. Cortisol administration increased insula (SN)-inferior frontal gyrus and superior temporal gyrus connectivity. We also found that greater depression severity was associated with increased PCC (DMN)-cerebellum connectivity after cortisol. These results did not survive Bonferroni correction for seed ROIs and should be interpreted with caution. Our findings indicate that acute cortisol elevation may normalize aberrant connectivity of DMN and SN regions, which could help inform clinical treatments for depression.

Thalamic connectivity topography in newborns with spina bifida: association with neurological functional level but not developmental outcome at 2years.

Spina bifida affects spinal cord and cerebral development, leading to motor and cognitive delay. We investigated whether there are associations between thalamocortical connectivity topography, neurological function, and developmental outcomes in open spina bifida. Diffusion tensor MRI was used to assess thalamocortical connectivity in 44 newborns with open spina bifida who underwent prenatal surgical repair. We quantified the volume of clusters formed based on the strongest probabilistic connectivity to the frontal, parietal, and temporal cortex. Developmental outcomes were assessed using the Bayley III Scales, while the functional level of the lesion was assessed by neurological examination at 2 years of age. Higher functional level was associated with smaller thalamo-parietal, while lower functional level was associated with smaller thalamo-temporal connectivity clusters (Bonferroni-corrected P < 0.05). Lower functional levels were associated with weaker thalamic temporal connectivity, particularly in the ventrolateral and ventral anterior nuclei. No associations were found between thalamocortical connectivity and developmental outcomes. Our findings suggest that altered thalamocortical circuitry development in open spina bifida may contribute to impaired lower extremity function, impacting motor function and independent ambulation. We hypothesize that the neurologic function might not merely be caused by the spinal cord lesion, but further impacted by the disruption of cerebral neuronal circuitry.

Joint spatio-temporal modeling for visual tracking

Similarity-based approaches have made significant progress in visual object tracking (VOT). Although these methods work well in simple scenes, they ignore the continuous spatio-temporal connection of the object in the video sequence. For this reason, tracking by spatial matching solely can lead to tracking failures because of distractors and occlusion. In this paper, we propose a spatio-temporal joint-modeling tracker named STTrack which implicitly builds continuous connections between the temporal and spatial aspects of the sequence. Specifically, we first design a time-sequence iteration strategy (TSIS) to concentrate on the temporal connection of the object in the video sequence. Then, we propose a novel spatial temporal interaction Transformer network (STIN) to capture the spatio-temporal correlation of the object between frames. The proposed STIN module is robust in object occlusion because it explores the dynamic state change dependencies of the object. Finally, we introduce a spatio-temporal query to suppress distractors by iteratively propagating the target prior. Extensive experiments on six tracking benchmark datasets demonstrate that the proposed STTrack achieves excellent performance while operating in real-time. The code is publicly available at https://github.com/nubsym/STTrack.

Remaining useful life prediction using graph convolutional attention networks with temporal convolution-aware nested residual connections

Degradation of engineered systems can result in poor performance and failure. Graph Convolutional Networks (GCNs) have been used to predict the remaining useful life (RUL) of engineered systems by analyzing condition monitoring data. Conventional GCNs typically stack multiple spectral graph convolutional layers, where each layer aggregates condition monitoring data and then projects the aggregated data into another feature space. However, conventional GCNs suffer from two issues. Firstly, repeated aggregation operations affect the temporal correlation of condition monitoring data. Secondly, repeated aggregation and projection operations may generate less significant features, resulting in poor prediction performance. To address these issues, we introduce a temporal convolutional operation to extract and preserve temporal features prior to repeated aggregation and projection operations. Additionally, we create an internal residual connection to skip some aggregation and projection operations to reduce the negative impact of the less significant features. Finally, we use an attention mechanism to extract the most significant features obtained from previous GCN layers and feed them to next GCN layers. We demonstrate the effectiveness of our method through three case studies. Our numerical results show that the proposed approach outperforms existing data-driven methods.

Rumination-Focused Cognitive Behavioral Therapy Reduces Rumination and Targeted Cross-network Connectivity in Youth With a History of Depression: Replication in a Preregistered Randomized Clinical Trial

BackgroundRumination-focused cognitive behavioral therapy (RF-CBT) is designed to reduce depressive rumination or the habitual tendency to dwell on experiences in a repetitive, negative, passive, and global manner. RF-CBT uses functional analysis, experiential exercises, and repeated practice to identify and change the ruminative habit. This preregistered randomized clinical trial (NCT03859297, R61) is a preregistered replication of initial work. We hypothesized a concurrent reduction of both self-reported rumination and cross-network connectivity between the left posterior cingulate cortex and right inferior frontal and inferior temporal gyri. MethodsSeventy-six youths with a history of depression and elevated rumination were randomized to 10 to 14 sessions of RF-CBT (n = 39; 34 completers) or treatment as usual (n = 37; 28 completers). Intent-to-treat analyses assessed pre-post change in rumination response scale and in functional connectivity assessed using two 5 minute, 12 second runs of resting-state functional magnetic resonance imaging. ResultsWe replicated previous findings: a significant reduction in rumination response scale and a reduction in left posterior cingulate cortex to right inferior frontal gyrus/inferior temporal gyrus connectivity in participants who received RF-CBT compared with those who received treatment as usual. Reductions were large (z change = 0.84; 0.73, respectively [ps < .05]). ConclusionsThis adolescent clinical trial further demonstrates that depressive rumination is a brain-based mechanism that is modifiable via RF-CBT. Here, we replicated that RF-CBT reduces cross-network connectivity, a possible mechanism by which rumination becomes less frequent, intense, and automatic. This National Institute of Mental Health-funded fast-fail study continues to the R33 phase during which treatment-specific effects of RF-CBT will be compared with relaxation therapy.

Does right hemisphere compensate for the left in school-age children with large left middle fossa arachnoid cysts?

BackgroundTo assess the cognitive function changes and brain network neuroplasticity in school-age children having large (diameter > 5 cm) left middle fossa arachnoid cyst (MFACs).MethodsEleven patients and 22 normal controls (NC) between 6 and 14 years of age were included. The CNS Vital Signs (CNS VS) were administered for cognitive assessment. The differences of cognitive data and functional connectivity (FC) in resting-state functional magnetic resonance imaging (rs-fMRI) were compared between the patient group and the NC group. The correlations between the altered FC and cognitive data in the patient group were assessed.ResultsPatient group had significantly poorer attention (including Complex Attention, Sustained Attention, Simple Attention, Cognitive Flexibility, and Executive Function) and memory function (Visual Memory and Working Memory) than the NC group (uncorrected p-value, p-unc < 0.05). Whole-brain local correlation (LCOR) analysis showed an extensively lower LCOR in the patient group (voxel threshold p-unc < 0.001, cluster-size threshold of false discovery rate adjusted p (p-FDR) < 0.001). Functional connectivity (FC) analysis showed that bilateral frontal and temporal lobes connectivity in the patient group was significantly lower than the NC group (p-FDR < 0.05). Seed-based FC analysis indicated that there was altered FC between the right temporal lobe and the left temporal-parietal/temporal-occipital area (p-FDR < 0.05). In the patient group, most of the altered FC had a negative correlation to the cognitive score, while the FC in the right temporal lobe-left temporal-occipital area positively correlated to Verbal/Visual Memory (r = 0.41–0.60, p-FDR < 0.05). In correlation analysis between clinical data and cognitive score, the only significant result was a low correlation between cyst size and Reaction Time (-0.30–-0.36, P-FDR < 0.05).ConclusionsSchool-aged children with large left MFAC showed significantly lower cognitive performance primarily in attention and memory domains. Distinct from neuroplasticity in a unilateral brain lesion, compensation in the healthy hemisphere in MFAC patients was sparse.

22 Cognitive Reserve's Relationship to Brain Burden in Parkinson's Disease Without Dementia

Objective:Individuals with Parkinson's disease (PD) have varying trajectories of cognitive decline. One reason for this heterogeneity may be "cognitive reserve": where higher education/IQ/current mental engagement compensates for increasing brain burden (Stern et al., 2020). With few exceptions, most studies examining cognitive reserve in PD fail to include brain metrics. This study's goal was to examine whether cognitive reserve moderated the relationship between neuroimaging indices of brain burden (diffusion free water fraction and T2-weighted white matter changes) and two commonly impaired domains in PD: executive function and memory. We hypothesized cognitive reserve would mitigate the relationship between higher brain burden and worse cognitive performance.Participants and Methods:Participants included 108 individuals with PD without dementia (age mean=67.9±6.3, education mean=16.6±2.5) who were prospectively recruited for two NIH-funded projects at the University of Florida. All received neuropsychological measures of executive function (Trails B, Stroop, Letter Fluency) and memory (delayed recall: Hopkin's Verbal Learning Test-Revised, WMS-III Logical Memory). Domain specific z-score composites were created using data from age/education matched non-PD peer controls (N=62). For the Cognitive Reserve (CR) proxy, a z-score composite included years of education, WASI-II Vocabulary, and Wechsler Test of Adult Reading. At the time of testing, participants completed multiple MRI scans (T1-weighted, diffusion, Fluid Attenuated Inversion Recovery) from which the following were extracted: 1) whole-brain free water within the white matter (a measure of microstructural integrity and neuroinflammation), 2) white matter hyperintensities/white matter total volume (WMH/WMV), and bilaterally-averaged edge weights of white matter connectivity between 3) dorsolateral prefrontal cortex and caudate and 4) entorhinal cortex and hippocampi. Separate linear regressions for each brain metric used executive function and memory composites as dependent variables; predictors were age, CR proxy, respective brain metric, and a residual centered interaction term (brain metric*CR proxy). Identical models were run in dichotomized short and long disease duration groups (median split=6 years).Results:In all models, a lower CR proxy significantly predicted worse executive function (WMH/WMV: beta=0.49, free water: beta=0.54, frontal edge weight: beta=0.49, p's&lt;0.001) and memory (WMH/WMV: beta=0.42, free water: beta=0.35, temporal edge weight: beta=0.39, p's &lt;0.01). For neuroimaging metrics, higher free water significantly predicted worse executive function (beta=-0.39, p=0.002) but not memory. No other brain metrics were significant predictors of either domain. Accounting for PD duration, higher free water predicted worse executive function for those with both short (beta=-0.49, p=0.04) and long disease duration (beta=-0.48, p=0.02). Specifically in those with long disease duration, higher free water (beta=-0.57 p=0.02) and lower edge weights between entorhinal cortex and hippocampi (beta=0.30, p=0.03) predicted worse memory. Overall, no models contained significant interactions between the CR proxy and any brain metric.Conclusions:Results replicate previous work showing that a cognitive reserve proxy relates to cognition. However, cognitive reserve did not moderate brain burden's relationship to cognition. Across the sample, greater neuroinflammation was associated with worse executive function. For those with longer disease duration, higher neuroinflammation and lower medial temporal white matter connectivity related to worse memory. Future work should examine other brain burden metrics to determine whether/how cognitive reserve influences the cognitive trajectory of PD.