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Machine learning in the diagnosis, management, and care of patients with low back pain: a scoping review of the literature and future directions.
BACKGROUND CONTEXT: Low back pain (LBP) remains the leading cause of disability globally. In recent years, machine learning (ML) has emerged as a potentially useful tool to aid the diagnosis, management, and prognostication of LBP. PURPOSE: In this review, we assess the scope of ML applications in the LBP literature and outline gaps and opportunities. STUDY DESIGN/SETTING: A scoping review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. METHODS: Articles were extracted from the Web of Science, Scopus, PubMed, and IEEE Xplore databases. Title/abstract and full-text screening was performed by two reviewers. Data on model type, model inputs, predicted outcomes, and ML methods were collected. RESULTS: In total, 223 unique studies published between 1988 and 2023 were identified, with just over 50% focused on low-back-pain detection. Neural networks were used in 106 of these articles. Common inputs included patient history, demographics, and lab values (67% total). Articles published after 2010 were also likely to incorporate imaging data into their models (41.7% of articles). Of the 212 supervised learning articles identified, 168 (79.4%) mentioned use of a training or testing dataset, 116 (54.7%) utilized cross-validation, and 46 (21.7%) implemented hyperparameter optimization. Of all articles, only 8 included external validation and 9 had publicly available code. CONCLUSIONS: Despite the rapid application of ML in LBP research, a majority of articles do not follow standard ML best practices. Furthermore, over 95% of articles cannot be reproduced or authenticated due to lack of code availability. Increased collaboration and code sharing are needed to support future growth and implementation of ML in the care of patients with LBP.
Different effects of cardiomyocyte contractile activity on transverse and axial tubular system luminal content dynamics.
BACKGROUND: Efficient excitation-contraction coupling of mammalian ventricular cardiomyocytes depends on the transverse-axial tubular system (TATS), a network of surface membrane invaginations. TATS enables tight coupling of sarcolemmal and sarcoplasmic reticulum membranes, which is essential for rapid Ca2+-induced Ca2+ release, and uniform contraction upon electrical stimulation. The majority of TATS in healthy ventricular cardiomyocytes is composed of transverse tubules (TT, ∼90 % of TATS in rabbit). The remainder consists of mostly axial tubules (AT), which are less abundant and less well studied. In disease, however, the relative abundance of TT and AT changes. The mechanisms and relevance of this change are not known, and understanding them requires a more targeted effort to study the dynamics of AT structure and function. While TATS content is continuous with the interstitial space, it is contained within a domain of restricted diffusion. We have previously shown that TT are cyclically squeezed during stretch and contraction. This can contribute to TT content mixing and accelerates luminal content exchange with the environment. Here, we explore the effects of cardiomyocyte stretch and contraction on AT. METHODS: TATS structure and diffusion dynamics were studied using 3D electron tomography of rabbit left ventricular cardiomyocytes, preserved at rest or during contraction, and ventricular tissue preserved at rest or during stretch, as well as live-cell TATS content exchange measurements. RESULTS: We show (i) that cardiomyocyte contraction is associated with an increase in the apparent speed of diffusion of TT content that scales with beating rate and degree of cell shortening. In contrast, (ii) AT develop membrane folds and constrictions during contraction, (iii) with no effect of contraction on luminal exchange dynamics, while (iv) cardiomyocyte stretch is associated with AT straightening and AT and TT 'squeezing' that (v) supports an acceleration of the apparent speed of diffusion in AT and TT. Finally, (vi) we present a simple computational model outlining the potential relevance of AT in healthy and diseased cells. CONCLUSIONS: Our results indicate that TT and AT are differently affected by the cardiac contractile cycle, and suggest that AT may play a role in ensuring TATS network content homogeneity in diseased cardiomyocytes. Further research is needed to explore the interplay of structural and functional remodelling of different TATS components in failing myocardium.
Seven Theorems of Joseph G. Gall.
On June 30, 2020, Professor Joseph Grafton Gall announced his retirement at 92. On August 13, 2020, Joe's former trainees and colleagues held a retirement celebration online to celebrate Joe's "Remarkable Career with Astonishing Discoveries", covering Joe's nearly 70 years of education and research. As a representative of Joe's trainees in the 2000s, I gave a speech titled "Seven Theorems of Joe". On September 12, 2024, Joe passed away peacefully, at 96. In memoriam, here I expand and update my previous speech and explain the "Seven Theorems of Joseph G. Gall", a scientists' scientist.
A worldwide study of subcortical shape as a marker for clinical staging in Parkinson's disease.
Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson's disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium. We investigated disease effects using mass univariate and multivariate models on the medial thickness of 27,120 vertices of seven bilateral subcortical structures. Shape differences were observed across all Hoehn and Yahr (HY) stages, as well as correlations with motor and cognitive symptoms. Notably, we observed incrementally thinner putamen from HY1, caudate nucleus and amygdala from HY2, hippocampus, nucleus accumbens, and thalamus from HY3, and globus pallidus from HY4-5. Subregions of the thalami were thicker in HY1 and HY2. Largely congruent patterns were associated with a longer time since diagnosis and worse motor symptoms and cognitive performance. Multivariate regression revealed patterns predictive of disease stage. These cross-sectional findings provide new insights into PD subcortical degeneration by demonstrating patterns of disease stage-specific morphology, largely consistent with ongoing degeneration.
Myocardial iron intake following intravenous iron therapy with ferric carboxymaltose is sustained at 1 year despite recurrence of iron deficiency.
In clinical practice, intravenous (IV) iron therapy is used for the correction of iron deficiency. Patients with chronic causes of iron deficiency, for example, women with abnormal uterine bleeding, patients with inflammatory bowel disease often require repeated dosing with IV iron therapy. After a single standard dose of IV iron therapy (1000 mg) with ferric carboxymaltose, there is a rapid intake of iron into the myocardium, resulting in a sustained increase in myocardial iron content. The increase in myocardial iron content is independent of changes in plasma ferritin levels, and the recurrence of iron deficiency is not accompanied by a normalisation of myocardial iron. The most important implication is that repeated dosing with IV iron (ferric carboxymaltose) can result in cumulative build-up of iron in the myocardium.
Cross-species single-cell RNA sequencing reveals divergent phenotypes and activation states of adaptive immunity in human carotid and experimental murine atherosclerosis.
BACKGROUND AND AIMS: The distinct functions of immune cells in atherosclerosis have been mostly defined by preclinical mouse studies. Contrastingly, the immune cell composition of human atherosclerotic plaques and their contribution to disease progression is only poorly understood. It remains uncertain whether genetic animal models allow for valuable translational approaches. METHODS AND RESULTS: Single cell RNA-sequencing (scRNA-seq) was performed to define the immune cell landscape in human carotid atherosclerotic plaques. The human immune cell repertoire demonstrated an unexpectedly high heterogeneity and was dominated by cells of the T-cell lineage, a finding confirmed by immunohistochemistry. Bioinformatical integration with 7 mouse scRNA-seq data sets from adventitial and atherosclerotic vascular tissue revealed a total of 51 identities of cell types and differentiation states, of which some were only poorly conserved between species and exclusively found in humans. Locations, frequencies, and transcriptional programs of immune cells in mouse models did not resemble the immune cell landscape in human carotid atherosclerosis. In contrast to standard mouse models of atherosclerosis, human plaque leukocytes were dominated by several T-cell phenotypes with transcriptional hallmarks of T-cell activation and memory formation, T-cell receptor-, and pro-inflammatory signaling. Only mice at the age of 22 months partially resembled the activated T-cell phenotype. In a validation cohort of 43 patients undergoing carotid endarterectomy, the abundance of activated immune cell subsets in the plaque defined by multi-color flow cytometry associated with the extend of clinical atherosclerosis. CONCLUSIONS: Integrative scRNA-seq reveals a substantial difference in the immune cell composition of murine and human carotid atherosclerosis - a finding that questions the translational value of standard mouse models for adaptive immune cell studies. Clinical associations suggest a specific role for T-cell driven (auto-) immunity in human plaque formation and -instability.
Dedicated developmental programing for group-supporting behaviors in eusocial honeybees.
The evolutionary changes from solitary to eusocial living in vertebrates and invertebrates are associated with the diversification of social interactions and the development of queen and worker castes. Despite strong innate patterns, our understanding of the mechanisms manifesting these sophisticated behaviors is still rudimentary. Here, we show that doublesex (dsx) manifests group-supporting behaviors in the honeybee (Apis mellifera) worker caste. Computer-based individual behavioral tracking of worker bees with biallelic stop mutations in colonies revealed that the dsx gene is required for the rate and duration of group-supporting behavior that scales the relationship between bees and their work. General sensorimotor functions remained unaffected. Unexpectedly, unlike in other insects, the dsx gene is required for the neuronal wiring of the mushroom body in which the gene is spatially restricted expressed. Together, our study establishes dedicated programming for group-supporting behaviors and provides insight into the connection between development in the neuronal circuitry and behaviors regulating the formation of a eusocial society.
Exploring cardiovascular involvement in IgG4-related disease: a case series approach with cardiovascular magnetic resonance.
BACKGROUND: IgG4-related disease (IgG4-RD) is a relapsing-remitting, fibroinflammatory, multisystem disorder. Cardiovascular involvement from IgG4-RD has not been systematically characterised. In this study, we sought to evaluate consecutive patients with IgG4-RD using a detailed multiparametric cardiovascular magnetic resonance (CMR) imaging protocol. METHODS: We prospectively enrolled 11 patients with histology-confirmed IgG4-RD; with active disease at time of scan. We undertook a detailed multiparametric CMR imaging protocol at 1.5T including cine imaging, native T1 and T2 mapping, stress perfusion imaging with inline quantitation of myocardial blood flow and late gadolinium enhancement (LGE) imaging. RESULTS: All patients exhibited at least one abnormality on CMR imaging. Abnormal elevation of global or segmental left ventricular myocardial T1 and T2 values was present in four patients, suggesting myocardial oedema or inflammation. Abnormal LGE, suggesting myocardial scar fibrosis, was present in nine patients, with eight displaying a non-ischaemic pattern, and one showing an ischaemic pattern. Four patients fulfilled both Lake Louise Criteria for active myocardial inflammation, while a further six fulfilled one criterion. Myocardial perfusion reserve was normal in all evaluable patients. Ten patients had normal ventricular volumes, mass and systolic function. In addition, thoracic aortitis was identified in three patients who underwent 18F-flourodeoxyglucose PET/CT imaging, with resolution following anti-B-cell treatment. CONCLUSIONS: In this cohort of patients with histology-confirmed IgG4-RD, multiparametric CMR revealed no changes in gross cardiac structure and function, but frequent myocardial tissue abnormalities. These data suggest a plausible pathophysiological link between IgG4-RD and cardiovascular involvement.
Optimization of the Operant Silent Gap-in-Noise Detection Paradigm in Humans.
BACKGROUND: In the auditory domain, temporal resolution is the ability to respond to rapid changes in the envelope of a sound over time. Silent gap-in-noise detection tests assess temporal resolution. Whether temporal resolution is impaired in tinnitus and whether those tests are useful for identifying the condition is still debated. We have revisited these questions by assessing the silent gap-in-noise detection performance of human participants. METHODS: Participants were seventy-one young adults with normal hearing, separated into preliminary, tinnitus and matched-control groups. A preliminary group (n = 18) was used to optimise the silent gap-in-noise detection two-alternative forced-choice paradigm by examining the effect of the position and the salience of the gap. Temporal resolution was tested in case-control observational study of tinnitus (n = 20) and matched-control (n = 33) groups using the previously optimized silent gap-in-noise behavioral paradigm. These two groups were also tested using silent gap prepulse inhibition of the auditory startle reflex (GPIAS) and Auditory Brain Responses (ABRs). RESULTS: In the preliminary group, reducing the predictability and saliency of the silent gap increased detection thresholds and reduced gap detection sensitivity (slope of the psychometric function). In the case-control study, tinnitus participants had higher gap detection thresholds than controls for narrowband noise stimuli centred at 2 and 8 kHz, with no differences in GPIAS or ABRs. In addition, ABR data showed latency differences across the different tinnitus subgroups stratified by subject severity. CONCLUSIONS: Operant silent gap-in-noise detection is impaired in tinnitus when the paradigm is optimized to reduce the predictability and saliency of the silent gap and to avoid the ceiling effect. Our behavioral paradigm can distinguish tinnitus and control groups suggesting that temporal resolution is impaired in tinnitus. However, in young adults with normal hearing, the paradigm is unable to objectively identify tinnitus at the individual level. The GPIAS paradigm was unable to differentiate the tinnitus and control groups, suggesting that operant, as opposed to reflexive, silent gap-in-noise detection is a more sensitive measure for objectively identifying tinnitus.