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Research Square Jun 2024Accurate prediction of the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is crucial for disease management. Machine learning techniques...
Accurate prediction of the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is crucial for disease management. Machine learning techniques have demonstrated success in classifying AD and MCI cases, particularly with the use of resting-state functional magnetic resonance imaging (rs-fMRI) data.This study utilized three years of rs-fMRI data from the ADNI, involving 142 patients with stable MCI (sMCI) and 136 with progressive MCI (pMCI). Graph signal processing was applied to filter rs-fMRI data into low, middle, and high frequency bands. Connectivity-based features were derived from both filtered and unfiltered data, resulting in a comprehensive set of 100 features, including global graph metrics, minimum spanning tree (MST) metrics, triadic interaction metrics, hub tendency metrics, and the number of links. Feature selection was enhanced using particle swarm optimization (PSO) and simulated annealing (SA). A support vector machine (SVM) with a radial basis function (RBF) kernel and a 10-fold cross-validation setup were employed for classification. The proposed approach demonstrated superior performance, achieving optimal accuracy with minimal feature utilization. When PSO selected five features, SVM exhibited accuracy, specificity, and sensitivity rates of 77%, 70%, and 83%, respectively. The identified features were as follows: (Mean of clustering coefficient, Mean of strength)/Radius/(Mean Eccentricity, and Modularity) from low/middle/high frequency bands of graph. The study highlights the efficacy of the proposed framework in identifying individuals at risk of AD development using a parsimonious feature set. This approach holds promise for advancing the precision of MCI to AD progression prediction, aiding in early diagnosis and intervention strategies.
PubMed: 38947050
DOI: 10.21203/rs.3.rs-4549428/v1 -
Research Square Jun 2024Nirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described a clinical...
Nirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described a clinical rebound syndrome whereby individuals experience a relapse of symptoms shortly after completing successful treatment. There is a lack of information on frequency of COVID-19 rebound after NM/r in routine clinical care, contributing factors, and clinical outcomes. : We reviewed electronic medical records to verify COVID-19 diagnosis, symptoms, and treatment with NM/r from January-June 2022. We defined COVID-19 clinical rebound as clear improvement in symptoms followed by recurrence or worsening of symptoms within 30 days of a five-day course of NM/r. We studied 268 adults with median age 57 (IQR 47, 68), 80% White race, 85% non-Hispanic ethnicity, 55% female, 80% vaccinated and boosted against SARS-CoV-2, and 68% with any co-morbidity. Sixteen (6.0%) of studied patients were determined to have COVID-19 clinical rebound. The median time from starting NM/r to rebound was 11 days (IQR 9, 13). Notable demographic and clinical factors with higher proportion (not statistically significant) among COVID-19 rebound patients were female sex (75% rebound vs 54.5% no rebound), Black race (12.5% rebound vs 4.9% no rebound), presence of at least one co-morbidity (81.3% rebound vs 67.5% no rebound), and lack of prior SARS-CoV-2 infection (100% rebound vs 92.9% no rebound). Only one patient (6.25%) was hospitalized after COVID-19 rebound. COVID-19 clinical rebound after treatment with NM/r is mild with favorable outcomes and more common than previously reported from real-world clinical care studies.
PubMed: 38947049
DOI: 10.21203/rs.3.rs-4497916/v1 -
MedRxiv : the Preprint Server For... Jun 2024Understanding COVID-19's impact on children is vital for public health policy, yet age-specific data is scarce, especially in Uganda. This study examines SARS-CoV-2...
BACKGROUND
Understanding COVID-19's impact on children is vital for public health policy, yet age-specific data is scarce, especially in Uganda. This study examines SARS-CoV-2 seroprevalence and risk factors among Ugandan children at two timepoints, along with COVID-19-related knowledge and practices in households, including adult vaccination status.
METHODS
Baseline surveys were conducted in 12 communities from April to May 2021 (post-Alpha wave) and follow-up surveys in 32 communities from November 2021 to March 2022 (Omicron wave). Household questionnaires and blood samples were collected to test for malaria by microscopy and for SARS-CoV-2 using a Luminex assay. Seroprevalence was estimated at both the survey and community level. Mixed-effects logistic regression models assessed the association between individual and household factors and SARS-CoV-2 seropositivity in children, adjusting for household clustering.
RESULTS
More households reported disruptions in daily life at baseline compared to follow-up, though economic impacts lingered. By the follow-up survey, 52.7% of adults had received at least one COVID-19 vaccine dose. Overall seroprevalence in children was higher at follow-up compared to baseline (71.6% versus 19.2%, p < 0.001). Seroprevalence in children ranged across communities from 6-37% at baseline and 50-90% at follow-up. At baseline, children from the poorest households were more likely to be infected. Increasing age remained the only consistent risk factor for SARS-CoV-2 seroconversion at both timepoints.
CONCLUSIONS
Results indicate that a larger number of children were infected by the Delta and Omicron waves of COVID-19 compared to the Alpha wave. This study is the largest seroprevalence survey in children in Uganda, providing evidence that most children were infected with SARS-CoV-2 before the vaccine was widely available to pediatric populations. Pediatric infections were vastly underreported by case counts, highlighting the importance of seroprevalence surveys in assessing disease burden when testing and reporting rates are limited and many cases are mild or asymptomatic.
PubMed: 38947039
DOI: 10.1101/2024.06.09.24308673 -
Research Square Jun 2024Purpose ( )-4-[ F]fluoroglutamine ([ F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent...
Purpose ( )-4-[ F]fluoroglutamine ([ F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent on glutamine metabolism like cancer cells, we explored the potential utility of [ F]FGln as a metabolic imaging marker for inflammation in two rat models: carrageenan-induced paw edema (CIPE) and collagen-induced arthritis (CIA). Procedures: The CIPE model (n = 4) was generated by injecting 200 µL of 3% carrageenan solution into the left hind paw three hours before the PET. The CIA model (n = 4) was generated by injecting 200 µg of collagen emulsion subcutaneously at the tail base 3-4 weeks before the PET. A qualitative scoring system was used to assess the severity of paw inflammation. After a CT scan, 15.7 ± 4.9 MBq of [ F]FGln was injected via the tail vein, followed by a dynamic micro-PET scan for 90 minutes under anesthesia with isoflurane. The standard uptake value of [ F]FGln was measured by placing a volume of interest in each paw. The non-injected right hind paws of the CIPE model rats served as controls for both models. The paws with CIA were pathologically examined after PET. Results In CIPE models, uptake in the injected paw was higher compared to the non-injected paw by 52-83%. In CIA models, uptake in the paws with severe inflammation was higher than the averaged controls by 54-173%, while that with mild and no inflammation was slightly higher (33%) and lower (-7%), respectively. Combined overall, the [ F]FGln uptake in CIA showed a significant positive correlation with inflammation severity ( = 0.88, = 0.009). The pathological findings confirmed profound inflammation in CIA. Conclusions [ F]FGln uptake was increased in both acute and chronic inflammation, and the uptake level was significantly correlated with the severity, suggesting its potential utility as a novel metabolic imaging marker for inflammation.
PubMed: 38947024
DOI: 10.21203/rs.3.rs-4493375/v1 -
MedRxiv : the Preprint Server For... Jun 2024Plasma p-tau217 and Tau-PET are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among...
Plasma p-tau217 and Tau-PET are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In this head-to-head comparison study including 9 cohorts and 1534 individuals, we found that plasma p-tau217 and medial temporal lobe Tau-PET signal showed similar associations with cognitive decline on a global cognitive composite test (R =0.32 vs R =0.32, p =0.812) and with progression to mild cognitive impairment (Hazard ratio[HR] =1.56[1.43-1.70] vs HR =1.63[1.50-1.77], p =0.627). Combined plasma and PET models were superior to the single biomarker models (R =0.36, p<0.01). Furthermore, sequential selection using plasma p-tau217 and then Tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 75% reduction when using plasma p-tau217 alone. We conclude that plasma p-tau217 and Tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use (i.e., plasma p-tau217 followed by Tau-PET in a subset with high plasma p-tau217) is useful for screening in clinical trials in preclinical AD.
PubMed: 38947004
DOI: 10.1101/2024.06.12.24308824 -
Research Square Jun 2024Evaluate the changes in management and outcomes of Californian infants with hypoxic ischemic encephalopathy (HIE).
OBJECTIVE
Evaluate the changes in management and outcomes of Californian infants with hypoxic ischemic encephalopathy (HIE).
STUDY DESIGN
Infants with HIE were identified from a California administrative birth cohort using ICD codes and divided into two epochs, Epoch 1 (2010-2015) and Epoch 2 (2016-2019). Risk ratios (RR) for therapeutic hypothermia (TH) in each epoch and their outcomes were calculated using log-linear regression.
RESULTS
In this cohort, 4779 infants with HIE were identified. Incidence of HIE in California increased yearly from 0.5/1,000 California births to a peak of 1.5/1,000 births in 2018. The use of TH in infants with mild HIE increased in Epoch 2 compared to Epoch 1. There was no significant difference in outcomes between epochs for infants with mild HIE that received TH.
CONCLUSION
Significantly more infants with mild HIE received TH since 2015 in California, but no difference in outcomes was found for these patients.
PubMed: 38946954
DOI: 10.21203/rs.3.rs-4505263/v1 -
MedRxiv : the Preprint Server For... Jun 2024Since the initial description of related hemiplegic migraine (HM), the phenotypic spectrum has expanded from mild episodes in neurotypical individuals to potentially...
INTRODUCTION
Since the initial description of related hemiplegic migraine (HM), the phenotypic spectrum has expanded from mild episodes in neurotypical individuals to potentially life-threatening events frequently seen in individuals with developmental and epileptic encephalopathies. However, the overall longitudinal course throughout childhood remains unknown.
METHODS
We analyzed HM and seizure history in individuals with -related HM, delineating frequency and severity of events in monthly increments through a standardized approach. Combining these data with medication prescription information, we assessed the response of HM to different agents.
RESULTS
Our cohort involved 15 individuals between 3 and 29 years (163 patient years) and included 11 unique and two recurrent variants (p.R1349Q and p.V1393M; both 2). The age of first confirmed HM ranged from 14 months to 13 years (average 3 years). 25% of all HM events were severe (lasting >3 days) and 73% of individuals had at least 1 severe occurrence. Spacing of HM events ranged from 1 month to 14 years and changes in HM severity over time of showed increases or decreases of >2 severity levels in 12/122 events. Eight individuals had epilepsy, but severity of epilepsy did not correlate with frequency and severity of HM events. While levetiracetam ( 6) and acetazolamide ( 5) were the most frequently used medications, they did not show efficacy in HM prevention or HM severity reduction. However, verapamil ( 3) showed efficacy in preventing HM episodes (OR 2.68, CI 1.39-5.67).
SIGNIFICANCE
The longitudinal course of -related HM lacks recognizable patterns for timing and severity of HM events or correlation with seizure patterns. Our data underscores the unpredictability of -related HM, highlighting the need for close surveillance for reoccurring HM events even in individuals with symptom-free periods.
KEY POINTS
24% of hemiplegic migraines (HM) in related disorders are severe, involving cerebral edema and greater than 4 days to recover Timing and severity of HM are unpredictable, with large changes in severity between events, and age of onset ranging from 1-13 yearsEpilepsy occurred in 53% of individuals, with neither the timing nor severity of seizures correlated with HM.
PubMed: 38946946
DOI: 10.1101/2024.06.14.24308953 -
MedRxiv : the Preprint Server For... Jun 2024Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI....
BACKGROUND
Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.
METHODS
161 older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's biomarkers, and brain MRI. Spontaneous CVR was quantified during 5 minutes of rest.
RESULTS
Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for Alzheimer's biomarkers and vascular risk factors.
CONCLUSION
Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, indicating medial temporal microvascular dysfunction's role in cognitive decline.
PubMed: 38946941
DOI: 10.1101/2024.06.18.24309109 -
Arthroplasty Today Jun 2024Mild ligament imbalance is often encountered in the mediolateral plane during complex primary total knee arthroplasty. A constrained (CP) polyethylene insert compatible...
PURPOSE
Mild ligament imbalance is often encountered in the mediolateral plane during complex primary total knee arthroplasty. A constrained (CP) polyethylene insert compatible with the primary femur is useful to manage these cases without the need to fall back on revision implants. The aim of the study was to define the correct indications of the use of a CP insert based on objective data from computer assisted surgery and to compare the early results of a CP insert with a standard posterior stabilized (PS) insert through one-to-one propensity score matching.
METHODS
This is a retrospective case study from a prospectively collected database. One-to-one matching without replacement was used with a caliper width of 0.2 to match the scores between CP (N = 64) and PS groups (N = 1624), resulting in equal covariate matching of PS (N = 64) and CP (N = 64) cohorts. Patients were assessed radiographically and functionally at a minimum follow-up of 3 years.
RESULT
Average coronal and sagittal plane deformities were similar in both the group CP (varus 13.1 ± 5.2 valgus 13 ± 7.9) and the group PS (varus 13.4 ± 4.6 valgus 10.9 ± 8.6). The average residual medial lateral gap difference was significantly higher in group CP (3.8 ± 1.8) in comparison to group PS (1.3 ± 1) ( < .05). A CP insert was chosen where mild ligament imbalance of 3-5 mm persisted after medial soft tissue releases in a varus knee and in cases with residual medial collateral ligament laxity in valgus knees.
CONCLUSIONS
Constrained insert used with the primary femoral component is a valuable option to handle mild ligamentous instability in complex primary total knee arthroplasty after mechanical alignment is achieved with computer navigation.
LEVEL OF EVIDENCE
III.
PubMed: 38946924
DOI: 10.1016/j.artd.2024.101423 -
BME Frontiers 2024: We have developed a baroreceptor-inspired microneedle skin patch for pressure-controlled drug release. : This design is inspired by the skin baroreceptors, which are...
: We have developed a baroreceptor-inspired microneedle skin patch for pressure-controlled drug release. : This design is inspired by the skin baroreceptors, which are mechanosensitive elements of the peripheral nervous system. We adopt the finger touching to trigger the electric stimulation, ensuring a fast-response and user-friendly administration with potentially minimal off-target effects. : Chronic skin diseases bring about large, recurrent skin damage and often require convenient and timely transdermal treatment. Traditional methods lack spatiotemporal controllable dosage, leaving a risk of skin irritation or drug resistance issues. : The patch consists of drug-containing microneedles and stretchable electrode array. The electrode array, integrated with the piezoconductive switch and flexible battery, provides a mild electric current only at the spot that is pressed. Drugs in microneedles will then flow along the current into the skin tissues. The stretchable feature also provides the mechanical robustness and electric stability of the device on large skin area. : This device delivers Cy3 dye in pig skin with spatiotemporally controlled dosage, showing ~8 times higher fluorescence intensity than the passive delivery. We also deliver insulin and observe the reduction of the blood glucose level in the mouse model upon pressing. Compared with passive delivery without pressing, the dosage of drugs released by the simulation is 2.83 times higher. : This baroreceptor-inspired microneedle skin patch acts as a good example of the biomimicking microneedle device in the precise control of the drug release profile at the spatiotemporal resolution.
PubMed: 38946867
DOI: 10.34133/bmef.0044