Improving prognostic accuracy in lung transplantation using unique features of isolated human lung radiographs.

Ex vivo lung perfusion (EVLP) enables advanced assessment of human lungs for transplant suitability. We developed a convolutional neural network (CNN)-based approach to analyze the largest cohort of isolated lung radiographs to date. CNNs were trained to process 1300 longitudinal radiographs from n = 650 clinical EVLP cases. Latent features were transformed into principal components (PC) and correlated with known radiographic findings. PCs were combined with physiological data to classify clinical outcomes: (1) recipient time to extubation of <72 h, (2) ≥ 72 h, and (3) lungs unsuitable for transplantation. The top PC was significantly correlated with infiltration (Spearman R: 0·72, p < 0·0001), and adding radiographic PCs significantly improved the discrimination for clinical outcomes (Accuracy: 73 vs 78%, p = 0·014). CNN-derived radiographic lung features therefore add substantial value to the current assessments. This approach can be adopted by EVLP centers worldwide to harness radiographic information without requiring real-time radiological expertise.

Dynamic development of microglia and macrophages after spinal cord injury.

Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response, with resident microglia and infiltrating macrophages playing pivotal roles. While previous studies have grouped these two cell types together based on similarities in structure and function, an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes. In this study, we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury. Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury, gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed. Regarding macrophages, our findings highlighted abundant communication with other cells, including fibroblasts and neurons. Both pro-inflammatory and neuroprotective effects of macrophages were also identified; the pro-inflammatory effect may be related to integrin ß2 (Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway. These findings were validated by in vivo experiments. This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury, and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.

Airway pepsinogen A4 identifies lung transplant recipients with microaspiration and predicts chronic lung allograft dysfunction.

BACKGROUND: Aspiration is a known risk factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration; however, they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs, while others, such as pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant. METHODS: Expression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to preexisting markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after antireflux surgery were assessed in a third cohort of LTRs. RESULTS: PGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Antireflux surgery was associated with reduced airway PGA4. CONCLUSIONS: Airway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.

Clinical characteristics and associated factors of posttraumatic epilepsy after traumatic brain injury in children: A retrospective case-control study.

BACKGROUND: Traumatic brain injury (TBI) affects approximately 69 million individuals annually, often resulting in well-documented complications such as epilepsy. Although numerous studies have been performed on posttraumatic epilepsy (PTE) in adults over the past decade, research on chronic consequences of TBI in children remains limited. Herein, we retrospectively assessed children who had experienced moderate to severe TBI to determine their clinical characteristics and identify associated factors associated with the development of PTE in the pediatric population. METHODS: The study population comprised children aged 0-18 years who had experienced moderate to severe TBI and underwent treatment at the Children's Hospital of Chongqing Medical University between 2011 and 2021. They were categorized into two groups: the PTE group, comprising individuals diagnosed with PTE within a one-year follow-up period, and the nPTE group, consisting of those who did not develop PTE during the same timeframe. The primary objective was to investigate the clinical characteristics and identify related associated factors. The relationship between various clinical factors and the incidence of PTE was assessed through univariate and multivariate logistic regression. RESULTS: A total of 132 patients were assessed. Most participants were male (65%) and the age distribution skewed towards younger children, with a median age of 41.0 months (interquartile range: 45.3). Upon their last clinical visit, 64 children (49%) were diagnosed with PTE. Notably, the first posttraumatic seizure predominantly occurred within the first week following the traumatic event. Further analyses revealed that increasing injury severity, as indicated by a lower Glasgow Coma Scale (GCS) score (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.54-1.12, p= 0.018), a contusion load ≥3 (OR: 8.1, 95% CI: 2.3-28.9, p= 0.001), immediate posttraumatic seizures (IPTS) (OR: 8.9, 95% CI: 2.5-31.2, p < 0.001), and early posttraumatic seizures (EPTS) (OR: 54, 95% CI: 11-276, p < 0.001), were all significantly associated with a higher risk of developing PTE. CONCLUSION: This study highlights that the onset of PTE was associated with the markers of injury severity or PTS and identified GCS scores, contusion loads of ≥3, IPTS, and EPTS as independent associated factors significantly associated with the development of PTE.

Efficacy of Noninvasive Brain Stimulation in Treating General Psychopathology Symptoms in Schizophrenia: A Meta-Analysis.

OBJECTIVES: Noninvasive brain stimulation (NIBS) has been shown to effectively alleviate negative and positive symptoms in patients with schizophrenia. However, its impact on depressive symptoms and general psychopathology symptoms (GPSs), which are crucial for functional outcomes, remains uncertain. We aimed to compare the efficacy of various NIBS interventions in treating depressive symptoms and GPSs. METHODS: We conducted a comprehensive search of multiple databases and performed a meta-analysis to evaluate the efficacy of NIBS in treating depressive symptoms and GPSs in schizophrenia. The effect sizes of NIBS for depression symptoms and GPSs were estimated using standard mean differences (SMDs) with 95% confidence intervals (CIs). Subgroup analyses were employed to examine potential influencing factors on the pooled SMD of NIBS for GPSs. RESULTS: Our search yielded 35 randomized controlled trials involving 1715 individuals diagnosed with schizophrenia. The protocol of this systematic review was registered with INPLASY (protocol ID: INPLASY202320082). Neither repetitive transcranial magnetic stimulation (rTMS) nor transcranial direct current stimulation (tDCS) demonstrated significant improvements in depressive symptoms compared to sham controls. NIBS exhibited a small-to-moderate effect size for GPSs, with a pooled SMD of -0.2956 (95% CI: -0.459 to -0.132) and a heterogeneity (I2) of 58.9% (95% CI: 41.5% to 71.1%; p < 0.01) based on a random-effects model. Subgroup analyses of different types of NIBS, different frequencies of rTMS, and different stimulation sites of rTMS revealed no significant differences. Only sex had a significant influence on the effect size of NIBS for general psychopathology symptoms (p < 0.05). However, rTMS might be superior to tDCS, and high-frequency rTMS outperformed low-frequency rTMS in treating GPSs. CONCLUSIONS: We found a small-to-moderate effect size of NIBS in alleviating GPSs in patients with schizophrenia. Both rTMS and tDCS were more effective than sham stimulation in reducing GPSs in schizophrenia. The frequency used was associated with rTMS efficacy for GPSs.

Effects of Repetitive Transcranial Magnetic Stimulation on Pallidum GABAergic Neurons and Motor Function in Rat Models of Kernicterus.

Kernicterus is a serious complication of hyperbilirubinemia, caused by neuronal injury due to excessive unconjugated bilirubin (UCB) in specific brain areas. This injury induced by this accumulation in the globus pallidus can induce severe motor dysfunction. Repetitive transcranial magnetic stimulation (rTMS) has shown neuroprotective effects in various neurological diseases. This study aimed to investigate the effects of rTMS on pallidal nerve damage and motor dysfunction in a rat model of kernicterus. Rats were divided into a sham group (n = 16), a model group (bilirubin with sham rTMS; n = 16) and an rTMS group (bilirubin with rTMS; n = 16). High-frequency rTMS (10 Hz) was applied starting from 24 h postmodeling for 7 days. The rotarod test, western blotting and immunohistochemical staining were performed to measure motor function and protein expression levels. The rTMS mitigated the negative effects of UCB on the general health of kernicterus-model rats and improved their growth and development. Furthermore, the rTMS alleviated UCB-induced motor dysfunction and increased the expression of GABAergic neuronal marker GAD67 in the globus pallidus. Notably, it also inhibited apoptosis-related protein caspase-3 activation. In conclusion, rTMS could alleviate motor dysfunction by inhibiting apoptosis and increasing globus pallidus GAD67 in kernicterus rat models, indicating that it may be a promising treatment for kernicterus.

The mediating role of negative symptoms in "secondary factors" determining social functioning in chronic schizophrenia.

Background: Chronic schizophrenia is significantly influenced by negative symptoms, with several known contributors to secondary negative symptoms. However, the impact of these factors and negative symptoms on social functioning warrants further exploration. Methods: We assessed the clinical symptoms, antipsychotic adverse reactions, and social functioning of 283 hospitalized patients with chronic schizophrenia using various standardized interviews and scales. We conducted multiple regression and mediation analyses to elucidate the impact of secondary factors on negative symptoms, and the relationship among these "secondary factors," negative symptoms, and social functioning. Results: Our findings identified depressive symptoms, extrapyramidal symptoms, and positive symptoms as significant contributors to secondary negative symptoms. We found that negative symptoms play a notable mediating role in the effect of depressive and positive symptoms on social functioning. However, the relationship between positive symptoms, negative symptoms, and social functioning proved to be intricate. Conclusion: Our findings propose that negative symptoms act as pivotal mediators in the correlation between "secondary factors" (including the depressive symptoms and positive symptoms) and social functioning. The treatment of chronic schizophrenia necessitates focusing on key factors such as depressive and positive symptoms, which might significantly contribute to the development of secondary negative symptoms. Further research is essential to clarify the complex relationship among positive symptoms, negative symptoms, and social functioning in schizophrenia.

A machine-learning approach to human ex vivo lung perfusion predicts transplantation outcomes and promotes organ utilization.

Ex vivo lung perfusion (EVLP) is a data-intensive platform used for the assessment of isolated lungs outside the body for transplantation; however, the integration of artificial intelligence to rapidly interpret the large constellation of clinical data generated during ex vivo assessment remains an unmet need. We developed a machine-learning model, termed InsighTx, to predict post-transplant outcomes using n = 725 EVLP cases. InsighTx model AUROC (area under the receiver operating characteristic curve) was 79 ± 3%, 75 ± 4%, and 85 ± 3% in training and independent test datasets, respectively. Excellent performance was observed in predicting unsuitable lungs for transplantation (AUROC: 90 ± 4%) and transplants with good outcomes (AUROC: 80 ± 4%). In a retrospective and blinded implementation study by EVLP specialists at our institution, InsighTx increased the likelihood of transplanting suitable donor lungs [odds ratio=13; 95% CI:4-45] and decreased the likelihood of transplanting unsuitable donor lungs [odds ratio=0.4; 95%CI:0.16-0.98]. Herein, we provide strong rationale for the adoption of machine-learning algorithms to optimize EVLP assessments and show that InsighTx could potentially lead to a safe increase in transplantation rates.

Influence of Tiapride and Topiramate on Tic Severity and Behavioral/Emotional Problems in Children with Tourette Syndrome: A Retrospective Study.

OBJECTIVES: To investigate the effect of tiapride and topiramate on patients with Tourette syndrome (TS). METHODS: This retrospective analysis included 126 children diagnosed with TS at Children's Hospital of Chongqing Medical University from 2019 to 2021, with treatment including tiapride (n = 60) and topiramate (n = 66). Their tic severity values were assessed with the Yale Global Tic Severity Scale (YGTSS). Furthermore, behavioral and emotional problems were assessed with the Conner's Parent Rating Scale (CPRS) and the Children Behavior Checklist (CBCL). RESULTS: Compared with premedication, the scores of tic severity were significantly decreased in both tiapride and topiramate groups after treatment, especially topiramate. Moreover, it was noted that five subscores of CPRS were significantly reduced in TS patients thanks to medication. However, there was no significant difference in CBCL after treatment, in both tiapride and topiramate groups. CONCLUSIONS: Tiapride and topiramate were proven to be effective on tics and some behavioral/emotional problems in TS patients, and topiramate may provide better treatment.

Effects of group mindfulness-based cognitive therapy and group cognitive behavioural therapy on symptomatic generalized anxiety disorder: a randomized controlled noninferiority trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. METHODS: This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. RESULTS: ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: - 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. CONCLUSIONS: Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. TRIAL REGISTRATION: Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018).

Activation of the AKT/GSK-3ß/ß-catenin pathway via photobiomodulation therapy promotes neural stem cell proliferation in neonatal rat models of hypoxic-ischemic brain damage.

Background: Hypoxic-ischemic brain damage (HIBD) significantly affects neurodevelopment in infants and is a leading cause of severe neurological morbidity and mortality in neonates. Our previous study found that photobiomodulation therapy (PBMT) improves the impaired spatial learning and memory of HIBD rat models. However, the neuroprotective mechanism conferred by PBMT in HIBD is unclear. Methods: In the present study, HIBD model rats were treated with PBMT at 5 mW/cm2 per day in the dark for 14 days (10 min each day), and primary neural stem cells (NSCs) after oxygen-glucose deprivation (OGD) were treated with PBMT for 10 min at 1, 5, 10, and 20 mW/cm2 in the dark. PBMT promoted hippocampal neural stem cell (NSC) proliferation in vivo and in vitro. Results: Mechanistically, PBMT upregulated phosphatidylinositol 3 kinase (PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3 beta (p-GSK-3ß), ß-catenin, and cyclin D1 expression in vivo and in vitro, promoting NSC proliferation. Furthermore, both LY294002 (a PI3K inhibitor) and IWR-1 (a Wnt/ß-catenin inhibitor) inhibited the PBMT promotion of NSC proliferation after OGD and suppressed ß-catenin and cyclin D1 expression in vitro. Conclusions: PBMT improved the spatial learning and memory of HIBD rats and promoted hippocampal NSC proliferation through the AKT/GSK-3ß/ß-catenin pathway.