Communications medicine最新文献

Background: To assess the integrity of the developing nervous system, the Prechtl general movement assessment (GMA) is recognized for its clinical value in diagnosing neurological impairments in early infancy. GMA has been increasingly augmented through machine learning approaches intending to scale-up its application, circumvent costs in the training of human assessors and further standardize classification of spontaneous motor patterns. Available deep learning tools, all of which are based on single sensor modalities, are however still considerably inferior to that of well-trained human assessors. These approaches are hardly comparable as all models are designed, trained and evaluated on proprietary/silo-data sets.

Methods: With this study we propose a sensor fusion approach for assessing fidgety movements (FMs). FMs were recorded from 51 typically developing participants. We compared three different sensor modalities (pressure, inertial, and visual sensors). Various combinations and two sensor fusion approaches (late and early fusion) for infant movement classification were tested to evaluate whether a multi-sensor system outperforms single modality assessments. Convolutional neural network (CNN) architectures were used to classify movement patterns.

Results: The performance of the three-sensor fusion (classification accuracy of 94.5%) is significantly higher than that of any single modality evaluated.

Conclusions: We show that the sensor fusion approach is a promising avenue for automated classification of infant motor patterns. The development of a robust sensor fusion system may significantly enhance AI-based early recognition of neurofunctions, ultimately facilitating automated early detection of neurodevelopmental conditions.

Background: The optimal timing for initiating dialysis and prognostic markers in chronic kidney disease (CKD) patients are under debate, with mortality and cardiovascular risks varying among patients. This study investigates whether the apoptosis inhibitor of macrophage (AIM), which is mostly bound to pentameric IgM, could serve as an effective indicator.

Methods: We prospectively followed 423 patients at dialysis initiation and 563 at various CKD stages. AIM dissociation from IgM and other serum components were measured in their serum samples. In vitro treatment of IgM-AIM complexes with their serum was conducted to assess AIM release from IgM. Survival analysis determined the associations of each variable with mortality and cardiovascular risk, and a cutoff value was calculated and validated using cross-validation.

Results: AIM dissociation from IgM increases with CKD progression and correlates with the serum uremic state, as shown by enhanced AIM release from IgM in vitro with sera from patients starting dialysis, but not those at earlier CKD stages. Patients at dialysis initiation with high proportion of serum IgM-free AIM (fAIM%) show elevated uremic toxins and other toxic metabolites, higher mortality, and increased cardiovascular risk compared to those with low fAIM%. This prognostic association is not seen with other CKD biomarkers, such as eGFR, creatinine, or inositol-phosphate. We determined the fAIM% cutoff of 46.27%, which predicts mortality two years post-dialysis initiation.

Conclusions: These findings suggest that the serum fAIM% could function as a prognostic marker at dialysis initiation and may have potential as a criterion for determining dialysis timing.

Background: People living with dementia often experience changes in independence and daily living, affecting their well-being and quality of life. Behavioural changes correlate with cognitive decline, functional impairment, caregiver distress, and care availability.

Methods: We use data from a 3-year prospective observational study of 141 people with dementia at home, using the Bristol Activities of Daily Living Scale, Neuropsychiatric Inventory and cognitive assessments, alongside self-reported and healthcare-related data.

Results: Here we show, psychiatric behavioural symptoms and difficulties in activities of daily living, fluctuate alongside cognitive decline. 677 activities of daily living and 632 psychiatric behaviour questionnaires are available at intervals of 3 months. Clustering shows three severity-based groups. Mild cognitive decline associates with higher caregiver anxiety, while the most severe group interacts more with community services, but less with hospitals.

Conclusions: We characterise behavioural symptoms and difficulties in activities of daily living in dementia, offering clinically relevant insights not commonly considered in current practice. We provide a holistic overview of participants' health during their progression of dementia.

Background: The Supporting Harm Reduction through Peer Support (SHARPS) study involved designing and implementing a peer-delivered, harm reduction intervention for people experiencing homelessness and problem substance use. Normalisation Process Theory (NPT) provided a framework for the study.

Methods: Four Peer Navigators (individuals with personal experience of problem substance use and/or homelessness) were recruited and hosted in six third sector (not-for-profit) homelessness services in Scotland and England (United Kingdom). Each worked with participants to provide practical and emotional support, with the aim of reducing harms, and improving well-being, social functioning and quality of life. NPT guided the development of the intervention and, the process evaluation, which assessed the acceptability and feasibility of the intervention for this cohort who experience distinct, and often unmet, health challenges. While mixed-methods data collection was undertaken, this paper draws only on the qualitative data.

Results: The study found that, overall, the intervention is feasible, and acceptable to, the intervention participants, the Peer Navigators and staff in host settings. Some challenges were encountered but these were outweighed by benefits. NPT is particularly useful in encouraging our team to focus on the relationship between different aspects of the intervention and context(s) and identify ways of maximising 'fit'.

Conclusions: To our knowledge, this is the first application of NPT to this cohort, and specifically by non-clinicians (peers) in non-healthcare settings (homelessness services). Our application of NPT helped us to identify ways in which the intervention could be enhanced, with the key aim of improving the health/well-being of this underserved group.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

Results: Here we identified substantial changes in response to MMKD intervention, aside from metabolic changes associated with a ketogenic diet, we identified a a global elevation across all plasmanyl and plasmenyl ether lipid species, with many changes linked to clinical and biochemical markers of AD. We further validated our findings by leveraging our prior clinical studies into lipid related changeswith AD (n = 1912), and found that the lipidomic signature with MMKD was inversely associated with the lipidomic signature of prevalent and incident AD.

Conclusions: Intervention with a MMKD was able to alter the plasma lipidome in ways that contrast with AD-associated patterns. Given its low risk and cost, MMKD could be a promising approach for prevention or early symptomatic treatment of AD.

Background: Multiple sulfatase deficiency (MSD) is an exceptionally rare neurodegenerative disorder due to the absence or deficiency of 17 known cellular sulfatases. The activation of all these cellular sulfatases is dependent on the presence of the formylglycine-generating enzyme, which is encoded by the SUMF1 gene. Disease-causing homozygous or compound heterozygous variants in SUMF1 result in MSD. Other than symptomatic treatment, no curative therapy exists as of yet for MSD. Eight out of these 17 sulfatases are primarily localized in the lysosome.

Methods: Two siblings with attenuated MSD underwent hematopoietic cell transplantation (HCT), evaluating the possibility of lysosomal enzymatic cross-correction from the donor cells.

Results: There is evidence of correction of currently available biomarkers within 3 months post-HCT. Untargeted metabolomics also shows continued correction of multiple biochemical abnormalities in the post-HCT period. Furthermore, this article also presents the neuropsychological outcomes of these children as well as the results of untargeted metabolomics analysis in this condition.

Conclusions: These data suggest biochemical benefits post-transplant along with slowing of disease progression. Long-term follow-up is necessary to fully evaluate the therapeutic benefit of HCT in MSD.

Background: Cochlear implants (CIs) are neuroprosthetic devices which restore hearing in severe-to-profound hearing loss through electrical stimulation of the auditory nerve. Current CIs use an externally worn audio processor. A long-term goal in the field has been to develop a device in which all components are contained within a single implant. Here, we present initial clinical results with the totally implantable cochlear implant (TICI). The primary objective of this study was to assess the safety of the device in adults who suffer from bilateral severe-to-profound sensorineural hearing loss.

Methods: This study used a design with non-randomized single group assignment (trial registration: NCT04571333). Six implantations took place beginning in September 2020. Data collection took place at the two participating CI centers. Adverse events (the primary outcome), speech perception, patient reported outcomes, and device usage statistics were collected over the subsequent 52 weeks. A within-subjects comparison was used in which each participant was evaluated both with the TICI and with an external SONNET audio processor.

Results: One anticipated serious adverse device effect (ASADE) occurred. After treatment the event resolved without sequelae. No unanticipated serious adverse device effects (USADE) occurred. Speech perception in quiet and in noise scores were comparable between the TICI and the SONNET audio processor. Scores on the validated patient reported outcome instruments HUI3, SSQ-12, and HISQUI-19 all increased over the duration of the study. User satisfaction scores as reported in their daily diary also increased over the duration of the study. Based on device usage metrics, all but one user used the TICI without an external processor the majority of the time.

Conclusions: The primary outcome of assessing the safety of the device was achieved. The TICI provides high levels of hearing performance, comparable to those of a conventional CI. The development of the TICI expands the range of options for treatment of hearing loss.

Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.

Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes. This integrative approach involved germline genotype and tumor RNA-seq data from 1165 metastatic CRC patients. The patients were enrolled in a randomized clinical trial receiving either cetuximab or bevacizumab in combination with chemotherapy. An external cohort of paired CRC normal and tumor samples, along with protein-protein interaction databases, was used for replication.

Results: We identify promising predictive and prognostic gene signatures from pre-treatment gene expression profiles. Our study discerns sets of genes, each forming a signature that collectively contribute to define patient subgroups with different prognosis and response to the therapies. Using an external cohort, we show that the genes influencing OS within the signatures, such as FANCI and PRC1, are upregulated in CRC tumor vs. normal tissue. These signatures are highly associated with immune features, including macrophages, cytotoxicity, and wound healing. Furthermore, the corresponding proteins encoded by the genes within the signatures interact with each other and are functionally related.

Conclusions: This study underscores the utility of gene signatures derived from transcriptomic-causal networks in patient stratification for effective therapies. The interpretability of the findings, supported by replication, highlights the potential of these signatures to identify patients likely to benefit from cetuximab or bevacizumab.

Background: Improvement in gene modifications of donor pigs has led to the prevention of early cardiac xenograft rejection and significantly prolonged cardiac xenograft survival in both heterotopic and orthotopic preclinical non-human primate (NHP) models. This progress formed the basis for FDA approval for compassionate use transplants in two patients.

Methods: Based on our earlier report of 9-month survival of seven gene-edited (7-GE) hearts transplanted (life-supporting orthotopic) in baboons, we transplanted 10 gene-edited pig hearts into baboons (n = 4) using non-ischemic continuous perfusion preservation (NICP) and immunosuppression regimen based on co-stimulation blockade by anti-CD40 monoclonal antibody. This pivotal study expands on the 7-GE backbone, with 3 additional gene edits, using 10-GE pigs as donors to baboon recipients.

Results: 10 GE cardiac xenografts provide life-supporting function up to 225 days (mean 128 ± 36 days) in a non-human primate model. Undetectable or latent porcine cytomegalovirus (PCMV) does not influence cardiac xenograft survival in this study but still needs more exploration with a larger cohort. Xenograft histology demonstrates adipose (Fat) deposition (n = 1), chronic vasculopathy (n = 1), micro and macro thrombosis, and acute cellular rejection (n = 1).

Conclusions: These data demonstrate that 10 GE cardiac xenografts have variable cardiac xenograft survival in NHP due to perhaps presence of 4th antigen and require further study. However, these 10GE organs may be suitable for clinical cardiac xenotransplantation and have already been utilized in two human cases.

Background: Digital data sources such as mobile phone call detail records (CDRs) are increasingly being used to estimate population mobility fluxes and to predict the spatiotemporal dynamics of infectious disease outbreaks. Differences in mobile phone operators' geographic coverage, however, may result in biased mobility estimates.

Methods: We leverage a unique dataset consisting of CDRs from three mobile phone operators in Bangladesh and digital trace data from Meta's Data for Good program to compare mobility patterns across these sources. We use a metapopulation model to compare the sources' effects on simulated outbreak trajectories, and compare results with a benchmark model with data from all three operators, representing around 100 million subscribers across the country.

Results: We show that mobility sources can vary significantly in their coverage of travel routes and geographic mobility patterns. Differences in projected outbreak dynamics are more pronounced at finer spatial scales, especially if the outbreak is seeded in smaller and/or geographically isolated regions. In some instances, a simple diffusion (gravity) model was better able to capture the timing and spatial spread of the outbreak compared to the sparser mobility sources.

Conclusions: Our results highlight the potential biases in predicted outbreak dynamics from a metapopulation model parameterized with non-population representative data, and the limits to the generalizability of models built on these types of novel human behavioral data.