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Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor expressed in several tissues, including the brain, gut, and pancreas. Activation of the BDNF/TrkB/CREB reduces hepatic gluconeogenesis, induces hepatic insulin signal transduction, and protects against pancreatic beta-cell loss in diabetes mellitus (DM). Several studies have investigated the possible association between BDNF and DM and its complications, but the results have been conflicting. In the present study, we aimed at systematically reviewing the literature on the serum and plasma levels of BDNF in DM and its subgroups such as T2DM, DM patients with depression, and patients with retinopathy. A comprehensive search was conducted in PubMed, Scopus, and Web of Science. We identified 28 eligible studies and calculated the standardized mean difference (SMD) of outcomes as an effect measure. The meta-analysis included 2734 patients with DM and 6004 controls. Serum BDNF levels were significantly lower in patients with DM vs. controls (SMD = -1.00, P<0.001). Plasma BDNF levels were not different in patients with DM compared with controls. When conducting subgroup analysis, serum BDNF levels were lower among patients with T2DM (SMD = -1.26, P<0.001), DM and depression (SMD = -1.69, P<0.001), and patients with diabetic retinopathy (DR) vs. controls (SMD = -1.03, P = 0.01). Serum BDNF levels were lower in patients with DM, T2DM, DM with depression, and DM and DR than the controls. Our findings are in line with the hypothesis that decreased BDNF levels might impair glucose metabolism and contribute to the pathogenesis of DM and its complications.

Visual disturbances are a common disease manifestation in multiple sclerosis (MS) due to lesions damaging white matter tracts involved in vision. Vertical occipital fasciculus (VOF), a tract located vertically in the occipital lobe, was neglected for more than a century. We hypothesize that VOF is involved in integrating information between dorsal and ventral visual streams. Thus, its damage in MS, as well as its probable role in visual processing (by using MS as a VOF damage model) needs to be clarified. To study fiber characteristics of VOF in MS, and their clinical and visual learning associations, 57 relapsing–remitting MS (RRMS) and 25 healthy controls (HC) were recruited. We acquired MS Functional Composite, Expanded Disability Status Scale (EDSS), and Brief Visuospatial Memory Test-Revised (BVMT-R), and diffusion MRI scans. Tractography of VOF and optic radiation (OR) was done. VOF’s metrics were statistically tested for between-group differences and clinical and visual tests associations. Along-tract analysis and laterality were also tested. RRMS patients had higher mean, axial, and radial diffusivity (nearly in all fiber points), and lower fractional anisotropy in bilateral VOFs compared to HC. No laterality was noted. These were associated with poor clinical outcomes, poor visual scores in EDSS, and lower total immediate and delayed recall in BVMT-R in RRMS, after adjusting for age, gender, and fiber metrics of OR. VOF damage is present in RRMS and is associated with visual symptoms and visuospatial learning impairments. It seems VOF is involved in integrating information between visual streams.

Previous studies proposed possible applications of spectral-domain optical coherence tomography (SD-OCT) measurements in prognosticating pathologies observed in overweight/obesity, including ocular, vascular, and neurologic consequences. Therefore, we conducted a systematic review and meta-analysis to investigate the changes in the in SD-OCT measurements of the patients with higher body mass index (BMI) compared to normal weight individuals. We conducted a systematic search on PubMed, Scopus, and Embase. The search results underwent two-phase title/abstract and full-text screenings. We then analyzed SD-OCT measurements differences in patients with high BMI and controls, and performed meta-regression, sub-group analysis, quality assessment, and publication bias assessment. The measurements included macular thickness, cup to disc ratio, ganglion cell-inner plexiform layer (GC-IPL) and its sub-sectors, RNFL and peripapillary RNFL (pRNFL) and their sub-layers, and choroidal thickness and its sub-sectors. 19 studies were included in this meta-analysis accounting for 1813 individuals, 989 cases and 824 controls. There was an overall trend towards decreased thickness in high BMI patients, but only two measurements reached statistical significance: temporal retinal nerve fiber layer (RNFL) (Standardized mean difference (SMD): -0.33, 95% confidence interval (CI): -0.53 to -0.14, p<0.01) and the choroidal region 1.0 mm nasal to fovea (SMD: -0.38, 95% CI: -0.60 to -0.16, p<0.01). Some ocular layers are thinner in patients with higher BMI than the controls. These SD-OCT measurements might correlate with adverse events related to increased body weight and have prognostic abilities. As SD-OCT is a robust, rapid and non-invasive tool, future guidelines and studies are needed to evaluate the possibility of their integration into care of the patients with obesity.

The aim was to systematically review the literature and perform a meta-analysis to estimate the performance of artificial intelligence (AI) algorithms in detecting meniscal injuries. A systematic search was performed in the Scopus, PubMed, EBSCO, Cinahl, Web of Science, IEEE Xplore, and Cochrane Central databases on July, 2024. The included studies' reporting quality and risk of bias were evaluated using the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) and the Prediction Model Study Risk of Bias Assessment Tool (PROBAST), respectively. Also, a meta-analysis was done using contingency tables to estimate diagnostic performance metrics (sensitivity and specificity), and a meta-regression analysis was performed to investigate the effect of the following variables on the main outcome: imaging view, data augmentation and transfer learning usage, and presence of meniscal tear in the injury, with a corresponding 95% confidence interval (CI) and a P-value of 0.05 as a threshold for significance. Among 28 included studies, 92 contingency tables were extracted from 15 studies. The reference standard of the studies were mostly expert radiologists, orthopedics, or surgical reports. The pooled sensitivity and specificity for AI algorithms on internal validation were 81% (95% CI: 78, 85), and 78% (95% CI: 72, 83), and for clinicians on internal validation were 85% (95% CI: 76, 91), and 88% (95% CI: 83, 92), respectively. The pooled sensitivity and specificity for studies validating algorithms with an external test set were 82% (95% CI: 74, 88), and 88% (95% CI: 84, 91), respectively. The results of this study imply the lower diagnostic performance of AI-based algorithms in knee meniscal injuries compared with clinicians.

Background and objectives Recent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography–angiography (OCT-A) to discover potential qualitative and quantitative changes in the retina and optic nerve. In this review, we analyze OCT-A studies in patients with MS and examine its utility as a surrogate or precursor to changes in central nervous system tissue. Methods PubMed and EMBASE were systematically searched to identify articles that applied OCT-A to evaluate the retinal microvasculature measurements in patients with MS. Quantitative data synthesis was performed on all measurements which were evaluated in at least two unique studies with the same OCT-A devices, software, and study population compared to controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level. Results The study selection process yielded the inclusion of 18 studies with a total of 1552 evaluated eyes in 673 MS-associated optic neuritis (MSON) eyes, 741 MS without optic neuritis (MSNON eyes), and 138 eyes without specification for the presence of optic neuritis (ON) in addition to 1107 healthy control (HC) eyes. Results indicated that MS cases had significantly decreased whole image superficial capillary plexus (SCP) vessel density when compared to healthy control subjects in the analyses conducted on Optovue and Topcon studies (both P  < 0.0001). Likewise, the whole image vessel densities of deep capillary plexus (DCP) and radial peripapillary capillary (RPC) were significantly lower in MS cases compared to HC (all P  < 0.05). Regarding optic disc area quadrants, MSON eyes had significantly decreased mean RPC vessel density compared to MSNON eyes in all quadrants except for the inferior (all P  < 0.05). Results of the analysis of studies that used prototype Axsun machine revealed that MSON and MSNON eyes both had significantly lower ONH flow index compared to HC (both P  < 0.0001). Conclusions This systematic review and meta-analysis of the studies reporting OCT-A measurements of people with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas, mainly in SCP, DCP, and RPC vessel densities.

A micromechanical study of particle breakage in 2D angular rockfill materials under biaxial compression loading has been conducted using a combined DEM and XFEM approach. In this approach, modeling of the crack propagation is performed on a fixed mesh without the limitations of classic FEM. Each breakage analysis is based on the final crack propagation state in the previous step; therefore, the progressive strength reduction of the particle is incorporated into the breakage analysis during loading. The micromechanics of the non-breakable and breakable assemblies have been studied under different confining pressures. It was found that particle breakage reduced the voids in the assembly, which resulted in a decrease in the final displacement of the particle assembly. Also, the contact forces, particle stresses and anisotropies decreased as a result of particle breakage and a more uniform distribution of contact forces and stresses was created. It was observed, as the confining pressure increased, the particle breakage increased and its effects intensified. Particle breakage was found to be the main cause of the decrease in anisotropies at higher confining pressures which, consequently, led to a reduction in the friction angle of the assembly.

Objectives The detection of renal cell carcinoma (RCC) tumors in the earlier stages is of great importance for more effective treatment. Encouraged by the key role of imaging in the management of RCC, we conducted a systematic review and meta-analysis of the studies that made use of artificial intelligence (AI) for the detection of RCC to quantitatively determine the performance of AI for distinguishing related renal lesions. Materials and methods PubMed, Scopus, CENTRAL, and Embase electronic databases were systematically searched in November 2024 to identify studies that applied AI for the detection or classification of RCC. We conducted a meta-analysis to evaluate the diagnostic performance of utilized algorithms. Moreover, meta-regression was conducted over suspected covariates to evaluate potential sources of inter-study heterogeneity. Publication bias and quality assessment were also done for the included studies. Results Sixty-four studies were included in this systematic review, of which 31 studies were selected for meta-analysis. The studies assessing algorithms’ performance on internal validation showed pooled sensitivity and specificity of 85% (95% confidence interval [CI], 82 to 87) and 76% (95% CI, 70 to 80), respectively. Moreover, externally validated Al algorithms had a pooled sensitivity and specificity of 80% (95% CI, 73 to 84) and 90% (95% CI, 84 to 93), respectively. Studies that performed internal validation for clinician performance had a pooled sensitivity of 79% (95% CI, 72 to 85) and specificity of 60% (95% CI, 49 to 70). Conclusion The findings of the present study validate the acceptable performance of AI algorithms when contrasted with medical professionals in the identification and categorization of RCC. Nevertheless, the presence of heterogeneity between studies and the absence of coherence in the results underscore the necessity for the cautious interpretation of these results and additional prospective studies.

Background Frailty is a chronic condition characterised by the progressive decline of multiple physiological functions. There is a critical need to investigate neuroimaging findings in nondemented frail individuals to better understand the underlying mechanisms and implications of frailty on brain health. This paper is aimed at reviewing neuroimaging studies assessing brain changes in nondemented frail individuals to understand the neuropsychological basis of frailty. Methods A systematic review was conducted on studies focusing on neuroimaging modalities in frailty, including MRI, fMRI, DTI and PET. The review was based on PRISMA instructions and a two‐step screening process. The studies evaluating neuroimaging findings of nondemented frail individuals, regardless of publication time or participant age, were included. Data were extracted from the included studies, and the quality of the studies as well as risk of bias was assessed. Results Out of 1604 studies screened, 22 eligible studies were included. Out of these, 10 studies had good quality, while others had fair quality according to the Newcastle Ottawa scale (NOS). Of these studies, 18 used Fried criteria or a modified version of it to diagnose frailty, while the Edmonton frailty score (EFS), Rockwood and Mitnitski frailty index and frailty index (FI) were implemented by the remaining studies. The MRI findings indicated significant differences in brain structure between nondemented frail and robust individuals, including an increased number and size of white matter hyperintensities, reduced grey matter volume, higher cerebrospinal fluid (CSF) volume and increased number of cerebral microbleeds (CMBs) in frail participants compared to the robust ones. The studies showed no significant difference between at‐risk and robust groups regarding total intracranial volume (TIV). The number of CMBs was associated with prefrailty status and its severity. fMRI studies showed decreased intranetwork mean functional connectivity (FC) in nondemented frail individuals. DTI studies showed lower fractional anisotropy (FA), higher axial diffusivity (AD) and higher radial diffusivity (RD) in the nondemented frail group. The PET scan study showed that mean cortical beta‐amyloid level was not associated with FI, but the accumulation of beta‐amyloid in the anterior and posterior putamen and precuneus region significantly correlated with frailty and its severity. Conclusion The study reveals significant differences in brain structures between nondemented frail and robust individuals, including increased white matter hyperintensities and reduced grey matter volume. These differences suggest that vascular changes and brain atrophy in nondemented frail individuals may contribute to cognitive impairment and dementia in the future.

Background Preclinical rheumatoid arthritis (Pre‐RA) is defined as the early stage before the development of clinical RA. While cachexia is a well‐known and potentially modifiable complication of RA, it is not known if such an association exists also in the Pre‐RA stage. To investigate such issue, we aimed to compare the longitudinal alterations in the muscle composition and adiposity of participants with Pre‐RA with the matched controls. Methods In this observational cohort study, the Osteoarthritis Initiative (OAI) participants were categorized into Pre‐RA and propensity score (PS)‐matched control groups. Pre‐RA was retrospectively defined as the absence of RA from baseline to year‐2, with progression to physician‐diagnosed clinical RA between years 3–8 of the follow‐up period. Using a validated deep learning algorithm, we measured MRI biomarkers of thigh muscles and adiposity at baseline and year‐2 follow‐ups of the cohort. The outcomes were the differences between Pre‐RA and control groups in the 2‐year rate of change for thigh muscle composition [cross‐sectional area (CSA) and intramuscular adipose tissue (Intra‐MAT)] and adiposity [intermuscular adipose tissue (Inter‐MAT) and subcutaneous adipose tissue (SAT)]. Linear mixed‐effect regression models were used for comparison. Results After 1:3 PS‐matching of the groups for confounding variables (demographics, risk factors, co‐morbidities, and knee osteoarthritis status), 408 thighs (102 Pre‐RA and 306 control) of 322 participants were included (age mean ± SD: 61.7 ± 8.9 years; female/male: 1.8). Over a 2‐year period, Pre‐RA was associated with a larger decrease in total thigh muscle CSA [estimate, 95% confidence interval (CI): −180.13 mm2/2‐year, −252.80 to −107.47, P‐value < 0.001]. Further examination of thigh muscle composition showed that the association of the presence of Pre‐RA with a larger decrease in muscle CSA over 2 years was noticeable in the quadriceps, flexors, and sartorius muscle groups (P‐values < 0.05). Comparison of changes in total adipose tissue showed no difference between Pre‐RA and control participants (estimate, 95% CI: 48.48 mm2/2‐year, −213.51 to 310.47, P‐value = 0.691). However, in the detailed analysis of thigh adiposity, Pre‐RA presence was associated with a larger increase in Inter‐MAT (estimate, 95% CI: 150.55 mm2/2‐year, 95.58 to 205.51, P‐value < 0.001). Conclusions Preclinical rheumatoid arthritis is associated with a decrease in muscle cross‐sectional area and an increase in intermuscular adipose tissue, similar to rheumatoid cachexia in clinical rheumatoid arthritis. These findings suggest the presence of cachexia in the preclinical phase of rheumatoid arthritis. Given that cachexia, which can exacerbate health outcomes, is potentially modifiable, this study emphasizes the importance of early identification of patients in their preclinical phase.

INTRODUCTION Obesity is a risk factor for Alzheimer's disease (AD), but its impact on AD blood biomarker (BBM) and amyloid positron emission tomography (PET) trajectories is unknown. METHODS One thousand two hundred twenty‐eight plasma samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assessed using six leading commercial tests (C2N, Fujirebio, Janssen, ALZpath, Roche, and Quanterix). Amyloid PET scans were used to assess amyloid burden in Centiloids (CLs). Spearman partial correlations assessed cross‐sectional associations, while linear mixed‐effects models examined the longitudinal impact of obesity status on BBMs and CLs. RESULTS Higher body mass index at baseline was correlated with lower levels of plasma phosphorylated tau (p‐tau)217, p‐tau217 ratio, neurofilament light chain (NfL), glial fibrillary acidic protein, and CLs. However, baseline obesity predicted higher rate of increase in p‐tau217, p‐tau217 ratio, Roche NfL, and amyloid PET burden over time. DISCUSSION This study provides insights for longitudinal changes in AD pathologies, as measured by BBM levels and CLs, in association with obesity. Highlights Higher body mass index was related to lower baseline plasma tau phosphorylated at threonine 217 (p‐tau217), p‐tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) and amyloid positron emission tomography (PET) burden. Obesity predicts a faster increase in p‐tau217, p‐tau217 ratio, and NfL. Obesity predicts a faster increase in amyloid PET burden. Changes in GFAP over time are not linked with obesity.