Multi-Class Deep Learning Model for Detecting Pediatric Distal Forearm Fractures Based on the AO/OTA Classification.

Common pediatric distal forearm fractures necessitate precise detection. To support prompt treatment planning by clinicians, our study aimed to create a multi-class convolutional neural network (CNN) model for pediatric distal forearm fractures, guided by the AO Foundation/Orthopaedic Trauma Association (AO/ATO) classification system for pediatric fractures. The GRAZPEDWRI-DX dataset (2008-2018) of wrist X-ray images was used. We labeled images into four fracture classes (FRM, FUM, FRE, and FUE with F, fracture; R, radius; U, ulna; M, metaphysis; and E, epiphysis) based on the pediatric AO/ATO classification. We performed multi-class classification by training a YOLOv4-based CNN object detection model with 7006 images from 1809 patients (80% for training and 20% for validation). An 88-image test set from 34 patients was used to evaluate the model performance, which was then compared to the diagnosis performances of two readers-an orthopedist and a radiologist. The overall mean average precision levels on the validation set in four classes of the model were 0.97, 0.92, 0.95, and 0.94, respectively. On the test set, the model's performance included sensitivities of 0.86, 0.71, 0.88, and 0.89; specificities of 0.88, 0.94, 0.97, and 0.98; and area under the curve (AUC) values of 0.87, 0.83, 0.93, and 0.94, respectively. The best performance among the three readers belonged to the radiologist, with a mean AUC of 0.922, followed by our model (0.892) and the orthopedist (0.830). Therefore, using the AO/OTA concept, our multi-class fracture detection model excelled in identifying pediatric distal forearm fractures.

Associations Between Brain-Gut Axis and Psychological Distress in Fibromyalgia: A Microbiota and Magnetic Resonance Imaging Study.

An altered brain-gut axis is suspected to be one of the pathomechanisms in fibromyalgia (FM). This cross-sectional study investigated the associations among altered microbiota, psychological distress, and brain functional connectivity (FC) in FM. We recruited 25 FM patients and 25 healthy people in the present study. Psychological distress was measured using standardized questionnaires. Microbiota analysis was performed on the participants' stools. Functional magnetic resonance imaging data were acquired, and seed-based resting-state FC (rs-FC) analysis was conducted with the salience network nodes as seeds. Linear regression and mediation analyses evaluated microbiota, symptoms, and rs-FCs associations. We found altered microbiota diversity in FM, of which Phascolarctobacterium and Lachnoclostridium taxa increased the most and Faecalibacterium taxon decreased the most compared to controls. The Phascolarctobacterium abundance significantly predicted Beck depression inventory (BDI-II) scores in FM (ß = 6.83; P = .033). Rs-FCs from salience network nodes were reduced in FM, of which rs-FCs from the right lateral rostral prefrontal cortex (RPFC) to the lateral occipital cortex, superior division right (RPFC-sLOC) could be predicted by BDI-II scores in patients (ß = -.0064; P = .0054). In addition, the BDI-II score was a mediator in the association between Phascolarctobacterium abundance and rs-FCs of RPFC-sLOC (ab = -.06; 95% CI: -.16 to -9.10-3). In conclusion, microbial dysbiosis might be associated with altered neural networks mediated by psychological distress in FM, emphasizing the critical role of the brain-gut axis in FM's non-pain symptoms and supporting further analysis of mechanism-targeted therapies to reduce FM symptoms. PERSPECTIVE: Our study suggests microbial dysbiosis might be associated with psychological distress and the altered salience network, supporting the role of brain-gut axis dysfunction in fibromyalgia pathomechanisms. Further targeting therapies for microbial dysbiosis should be investigated to manage fibromyalgia patients in the future.

Prediction of posttraumatic functional recovery in middle-aged and older patients through dynamic ensemble selection modeling.

Introduction: Age-specific risk factors may delay posttraumatic functional recovery; complex interactions exist between these factors. In this study, we investigated the prediction ability of machine learning models for posttraumatic (6 months) functional recovery in middle-aged and older patients on the basis of their preexisting health conditions. Methods: Data obtained from injured patients aged ≥45 years were divided into training-validation (n = 368) and test (n = 159) data sets. The input features were the sociodemographic characteristics and baseline health conditions of the patients. The output feature was functional status 6 months after injury; this was assessed using the Barthel Index (BI). On the basis of their BI scores, the patients were categorized into functionally independent (BI >60) and functionally dependent (BI ≤60) groups. The permutation feature importance method was used for feature selection. Six algorithms were validated through cross-validation with hyperparameter optimization. The algorithms exhibiting satisfactory performance were subjected to bagging to construct stacking, voting, and dynamic ensemble selection models. The best model was evaluated on the test data set. Partial dependence (PD) and individual conditional expectation (ICE) plots were created. Results: In total, nineteen of twenty-seven features were selected. Logistic regression, linear discrimination analysis, and Gaussian Naive Bayes algorithms exhibited satisfactory performances and were, therefore, used to construct ensemble models. The k-Nearest Oracle Elimination model outperformed the other models when evaluated on the training-validation data set (sensitivity: 0.732, 95% CI: 0.702-0.761; specificity: 0.813, 95% CI: 0.805-0.822); it exhibited compatible performance on the test data set (sensitivity: 0.779, 95% CI: 0.559-0.950; specificity: 0.859, 95% CI: 0.799-0.912). The PD and ICE plots showed consistent patterns with practical tendencies. Conclusion: Preexisting health conditions can predict long-term functional outcomes in injured middle-aged and older patients, thus predicting prognosis and facilitating clinical decision-making.

Efficacy and safety of add-on anti-CD20 monoclonal antibody to Bruton tyrosine kinase inhibitor treatment for chronic lymphocytic leukemia: a meta-analysis.

The efficacy of Bruton tyrosine kinase inhibitors (BTKi) remains suboptimal in chronic lymphocytic leukemia (CLL) treatment. A systematic review and meta-analysis were conducted to compare the outcomes of combining anti-CD20 monoclonal antibodies (mAb) with BTKi therapy versus BTKi monotherapy for patients with CLL. We searched for relevant studies in the Pubmed, Medline, Embase, and Cochrane databases until December 2022. We estimated the effective results using a hazard ratio (HR) for survival outcomes and relative risk (RR) for response outcomes and safety. Four randomized controlled trials (including 1056 patients) were found until November 2022 and fulfilled the inclusion criteria. Progression-free survival was significantly improved with the addition of anti-CD20 mAb to BTKi over BTKi (HR 0.70, 95% confidence interval (CI) 0.51-0.97), whereas pooled analysis of overall survival did not favor combination therapy compared to BTKi monotherapy (HR 0.72, 95% CI 0.50-1.04). Combination therapy was related to a statistically better complete response (RR, 2.03; 95% CI 1.01 to 4.06) and an undetectable minimal residual disease rate (RR, 6.43; 95% CI 3.54 to 11.67). The risk of grade ≥ 3 adverse events was comparable between the two groups (RR, 1.08; (95% CI 0.80 to 1.45). Overall, adding anti-CD20 mAb to BTKi revealed superior efficacy than BTKi alone in untreated or previously treated CLL patients without affecting the safety of single-agent BTKi. Conducting further randomized studies to confirm our results and determine the optimal therapy for managing patients with CLL is essential.

Functional Connectivity and Structural Signatures of the Visual Cortical System in Fibromyalgia: A Magnetic Resonance Imaging Study.

OBJECTIVE: Abnormal functional connectivity (FC) and structure in the brain are found in patients with fibromyalgia (FM). This study investigated FC and structural alterations of the visual cortical system, the emerging contributor to pain processing, in patients with FM. METHODS: Thirty pain-free participants and 26 patients with FM were enrolled. Clinical characteristics were evaluated using standardized scales. Structural and resting-state functional magnetic resonance imaging were conducted. Seed-based FC analyses, voxel-based morphometry, and surface-based morphometry were performed. The FC and cortical structure of the visual system were compared between the 2 groups. The correlation between functional and structural changes in the visual cortical system with clinical presentation in the FM group was analyzed. RESULTS: The patients with FM showed increased FCs within visual networks, of which the FC between the visual medial network and the right lingual gyrus (LG) was positively correlated with the Fibromyalgia Impact Questionnaire (FIQ) score. However, the FM group showed decreased FCs from the visual occipital network (VON) to several regions, of which the FCs from the VON to the bilateral frontal orbital cortices were negatively correlated with the FIQ and Pittsburgh Sleep Quality Index scores. Cortical thickness of the lateral occipital cortex, LG, and pericalcarine in FM tended to increase. CONCLUSION: Altered FCs and structure in the visual cortical system might be involved in the pathomechanisms and clinical presentation in FM. These findings could potentially support further studies that seek to find diagnostic methods and mechanism-based therapies in patients with FM.

Efficacy and Safety of Bruton Tyrosine Kinase Inhibitor Monotherapy Compared with Combination Therapy for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: A Systematic Review and Meta-Analysis.

The effectiveness and safety of combination treatments such as chemoimmunotherapies in chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) remain controversial. Bruton tyrosine kinase inhibitors (BTKis) are an effective therapy for CLL/SLL patients. This meta-analysis aimed to compare the efficacy and safety of BTKis versus combination therapy in CLL/SLL patients. We searched the PubMed, Cochrane, Medline, and Embase databases through February 2023 for relevant randomized controlled trials (RCTs). Four RCTs (including 1510 patients) were found and met the inclusion criteria. Progression-free survival (PFS) was significantly improved with BTKis when compared to the combination therapy (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.22-0.40), while a pooled analysis of overall survival did not favor single-agent BTKis over the combination therapy (HR, 0.87; 95% CI, 0.67-1.15). We observed consistent benefits for PFS among patients with high-risk disease characteristics. Although there was no difference in complete response between the two arms (risk ratio (RR), 0.54; 95% CI, 0.20-1.46), BTKi use was related to a better overall response rate (RR, 1.10; 95% CI, 1.04-1.16). The risk of grade ≥3 adverse events (AEs) was comparable between the two arms (RR, 0.82; 95% CI, 0.55-1.23). However, the risk of grade ≥3 AEs was significantly lower in the second-generation BTKi group than in the combination therapy group (RR, 0.73; 95% CI, 0.54-0.98). Overall, BTKis have superior efficacy compared to the combination regimens in patients with untreated or treated CLL/SLL without excess toxicity. Further studies are needed to confirm these results and determine the optimal therapy for managing patients with CLL/SLL.

Effect of exercise training on cardiac mitochondrial respiration, biogenesis, dynamics, and mitophagy in ischemic heart disease.

Objective: Cardiac mitochondrial dysfunction was found in ischemic heart disease (IHD). Hence, this study determined the effects of exercise training (ET) on cardiac mitochondrial respiration and cardiac mitochondrial quality control in IHD. Methods: A narrative synthesis was conducted after searching animal studies written in English in three databases (PubMed, Web of Science, and EMBASE) until December 2020. Studies that used aerobic exercise as an intervention for at least 3 weeks and had at least normal, negative (sedentary IHD), and positive (exercise-trained IHD) groups were included. The CAMARADES checklist was used to check the quality of the included studies. Results: The 10 included studies (CAMARADES score: 6-7/10) used swimming or treadmill exercise for 3-8 weeks. Seven studies showed that ET ameliorated cardiac mitochondrial respiratory function as manifested by decreased reactive oxygen species (ROS) production and increased complexes I-V activity, superoxide dismutase 2 (SOD2), respiratory control ratio (RCR), NADH dehydrogenase subunits 1 and 6 (ND1/6), Cytochrome B (CytB), and adenosine triphosphate (ATP) production. Ten studies showed that ET improved cardiac mitochondrial quality control in IHD as manifested by enhanced and/or controlled mitochondrial biogenesis, dynamics, and mitophagy. Four other studies showed that ET resulted in better cardiac mitochondrial physiological characteristics. Conclusion: Exercise training could improve cardiac mitochondrial functions, including respiration, biogenesis, dynamics, and mitophagy in IHD. Systematic review registration: https://www.crd.york.ac.uk/prospero/ display_record.php?RecordID=226817, identifier: CRD42021226817.

Prevalence and Methods for Assessment of Oropharyngeal Dysphagia in Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis aimed to estimate the pooled prevalence of dysphagia in older adults, subgrouping by recruitment settings and varying dysphagia assessment methods. METHODS: Five major databases were systematically searched through January 2022. A random-effects model for meta-analysis was conducted to obtain the pooled prevalence. RESULTS: Prevalence of dysphagia in the community-dwelling elderly screened by water swallow test was 12.14% (95% CI: 6.48% to 19.25%, I2 = 0%), which was significantly lower than the combined prevalence of 30.52% (95% CI: 21.75% to 40.07%, I2 = 68%) assessed by Standardized Swallowing Assessment (SSA) and volume-viscosity swallow test (V-VST). The dysphagia prevalence among elderly nursing home residents evaluated by SSA was 58.69% (95% CI: 47.71% to 69.25%, I2 = 0%) and by the Gugging Swallowing Screen test (GUSS) test was 53.60% (95% CI: 41.20% to 65.79%, I2 = 0%). The prevalence of dysphagia in hospitalized older adults screened by the 10-item Eating Assessment Tool was 24.10% (95% CI: 16.64% to 32.44%, I2 = 0%), which was significantly lower than those assessed by V-VST or GUSS tests of 47.18% (95% CI: 38.30% to 56.14%, I2 = 0%). CONCLUSIONS: Dysphagia is prevalent in the elderly, affecting approximately one in three community-dwelling elderly, almost half of the geriatric patients, and even more than half of elderly nursing home residents. The use of non-validated screening tools to report dysphagia underestimates its actual prevalence.

Cerebral Cortex Apoptosis in Early Aged Hypertension: Effects of Epigallocatechin-3-Gallate.

This study aimed to investigate cerebral cortex apoptosis on the early aged hypertension and the effects of green tea flavonoid epigallocatechin-3-gallate (EGCG). Twenty-four rats were divided into three groups: a control Wistar-Kyoto group (WKY, n = 8), a spontaneously early aged hypertensive group (SHR, n = 8), and an early aged hypertension with EGCG treatment group (SHR-EGCG, n = 8; daily oral EGCG 200 mg/kg-94%, 12 weeks). At 48 weeks old, blood pressures (BPs) were evaluated and cerebral cortexes were isolated for TUNEL assay and Western blotting. Systolic, diastolic, and mean blood pressure levels in the SHR-EGCG were reduced compared to the SHR. The percentage of neural cell deaths, the levels of cytosolic Endonuclease G, cytosolic AIF (Caspase-independent apoptotic pathway), Fas, Fas Ligand, FADD, Caspase-8 (Fas-mediated apoptotic pathway), t-Bid, Bax/Bcl-2, Bak/Bcl-xL, cytosolic Cytochrome C, Apaf-1, Caspase-9 (Mitochondrial-mediated apoptotic pathway), and Caspase-3 (Fas-mediated and Mitochondria-mediated apoptotic pathways) were increased in the SHR relative to WKY and reduced in SHR-EGCG relative to SHR. In contrast, the levels of Bcl-2, Bcl-xL, p-Bad, 14-3-3, Bcl-2/Bax, Bcl-xL/Bak, and p-Bad/Bad (Bcl-2 family-related pro-survival pathway), as well as Sirt1, p-PI3K/PI3K and p-AKT/AKT (Sirt1/PI3K/AKT-related pro-survival pathway), were reduced in SHR relative WKY and enhanced in SHR-EGCG relative to SHR. In conclusion, green tea flavonoid epigallocatechin-3-gallate (EGCG) might prevent neural apoptotic pathways and activate neural survival pathways, providing therapeutic effects on early aged hypertension-induced neural apoptosis.

Effects of Treadmill Exercise on Neural Mitochondrial Functions in Parkinson's Disease: A Systematic Review of Animal Studies.

This systematic review sought to determine the effects of treadmill exercise on the neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson's disease. PubMed, Web of Science, and EMBASE databases were searched through March 2020. The English-published animal studies that mentioned the effects of treadmill exercise on neural mitochondria in Parkinson's disease were included. The CAMARADES checklist was used to assess the methodological quality of the studies. Ten controlled trials were included (median CAMARADES score = 5.7/10) with various treadmill exercise durations (1-18 weeks). Seven studies analyzed the neural mitochondrial respiration, showing that treadmill training attenuated complex I deficits, cytochrome c release, ATP depletion, and complexes II-V abnormalities in Parkinson's disease. Nine studies analyzed the neural mitochondrial quality-control, reporting that treadmill exercise improved mitochondrial biogenesis, mitochondrial fusion, and mitophagy in Parkinson's disease. The review findings supported the hypothesis that treadmill training could attenuate both neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson's disease, suggesting that treadmill training might slow down the progression of Parkinson's disease.

Effects of Mdivi-1 on Neural Mitochondrial Dysfunction and Mitochondria-Mediated Apoptosis in Ischemia-Reperfusion Injury After Stroke: A Systematic Review of Preclinical Studies.

This systematic review sought to determine the effects of Mitochondrial division inhibitor-1 (Mdivi-1) on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in ischemia/reperfusion (I/R) injury after ischemic stroke. Pubmed, Web of Science, and EMBASE databases were searched through July 2021. The studies published in English language that mentioned the effects of Mdivi-1 on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in I/R-induced brain injury were included. The CAMARADES checklist (for in vivo studies) and the TOXRTOOL checklist (for in vitro studies) were used for study quality evaluation. Twelve studies were included (median CAMARADES score = 6; TOXRTOOL scores ranging from 16 to 18). All studies investigated neural mitochondrial functions, providing that Mdivi-1 attenuated the mitochondrial membrane potential dissipation, ATP depletion, and complexes I-V abnormalities; enhanced mitochondrial biogenesis, as well as inactivated mitochondrial fission and mitophagy in I/R-induced brain injury. Ten studies analyzed neural mitochondria-mediated apoptosis, showing that Mdivi-1 decreased the levels of mitochondria-mediated proapoptotic factors (AIF, Bax, cytochrome c, caspase-9, and caspase-3) and enhanced the level of antiapoptotic factor (Bcl-2) against I/R-induced brain injury. The findings suggest that Mdivi-1 can protect neural mitochondrial functions, thereby attenuating neural mitochondria-mediated apoptosis in I/R-induced brain injury. Our review supports Mdivi-1 as a potential therapeutic compound to reduce brain damage in ischemic stroke (PROSPERO protocol registration ID: CRD42020205808). Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020205808].

Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration.

Neural mitochondrial dysfunction, neural oxidative stress, chronic neuroinflammation, toxic protein accumulation, and neural apoptosis are common causes of neurodegeneration. Elamipretide, a small mitochondrially-targeted tetrapeptide, exhibits therapeutic effects and safety in several mitochondria-related diseases. In neurodegeneration, extensive studies have shown that elamipretide enhanced mitochondrial respiration, activated neural mitochondrial biogenesis via mitochondrial biogenesis regulators (PCG-1α and TFAM) and the translocate factors (TOM-20), enhanced mitochondrial fusion (MNF-1, MNF-2, and OPA1), inhibited mitochondrial fission (Fis-1 and Drp-1), as well as increased mitophagy (autophagy of mitochondria). In addition, elamipretide has been shown to attenuate neural oxidative stress (hydrogen peroxide, lipid peroxidation, and ROS), neuroinflammation (TNF, IL-6, COX-2, iNOS, NLRP3, cleaved caspase-1, IL-1ß, and IL-18), and toxic protein accumulation (Aß). Consequently, elamipretide could prevent neural apoptosis (cytochrome c, Bax, caspase 9, and caspase 3) and enhance neural pro-survival (Bcl2, BDNF, and TrkB) in neurodegeneration. These findings suggest that elamipretide may prevent the progressive development of neurodegenerative diseases via enhancing mitochondrial respiration, mitochondrial biogenesis, mitochondrial fusion, and neural pro-survival pathway, as well as inhibiting mitochondrial fission, oxidative stress, neuroinflammation, toxic protein accumulation, and neural apoptosis. Elamipretide or mitochondrially-targeted peptide might be a targeted agent to attenuate neurodegenerative progression.