Labeled-to-unlabeled distribution alignment for partially-supervised multi-organ medical image segmentation.

Partially-supervised multi-organ medical image segmentation aims to develop a unified semantic segmentation model by utilizing multiple partially-labeled datasets, with each dataset providing labels for a single class of organs. However, the limited availability of labeled foreground organs and the absence of supervision to distinguish unlabeled foreground organs from the background pose a significant challenge, which leads to a distribution mismatch between labeled and unlabeled pixels. Although existing pseudo-labeling methods can be employed to learn from both labeled and unlabeled pixels, they are prone to performance degradation in this task, as they rely on the assumption that labeled and unlabeled pixels have the same distribution. In this paper, to address the problem of distribution mismatch, we propose a labeled-to-unlabeled distribution alignment (LTUDA) framework that aligns feature distributions and enhances discriminative capability. Specifically, we introduce a cross-set data augmentation strategy, which performs region-level mixing between labeled and unlabeled organs to reduce distribution discrepancy and enrich the training set. Besides, we propose a prototype-based distribution alignment method that implicitly reduces intra-class variation and increases the separation between the unlabeled foreground and background. This can be achieved by encouraging consistency between the outputs of two prototype classifiers and a linear classifier. Extensive experimental results on the AbdomenCT-1K dataset and a union of four benchmark datasets (including LiTS, MSD-Spleen, KiTS, and NIH82) demonstrate that our method outperforms the state-of-the-art partially-supervised methods by a considerable margin, and even surpasses the fully-supervised methods. The source code is publicly available at LTUDA.

Immersive virtual reality-based rehabilitation for subacute stroke: a randomized controlled trial.

OBJECTIVE: Few effective treatments improve upper extremity (UE) function after stroke. Immersive virtual reality (imVR) is a novel and promising strategy for stroke UE recovery. We assessed the extent to which imVR-based UE rehabilitation can augment conventional treatment and explored changes in brain functional connectivity (FC) that were related to the rehabilitation. METHODS: An assessor-blinded, parallel-group randomized controlled trial was performed with 40 subjects randomly assigned to either imVR or Control group (1:1 allocation), each receiving rehabilitation 5 times per week for 3 weeks. Subjects in the imVR received both imVR and conventional rehabilitation, while those in the Control received conventional rehabilitation only. Our primary and secondary outcomes were the Fugl-Meyer assessment's upper extremity subscale (FMA-UE) and the Barthel Index (BI), respectively. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed to assess the effectiveness of the trial. For both the FMA-UE/BI, a one-way analysis of covariance (ANCOVA) model was used, with the FMA-UE/BI at post-intervention or at follow-up, respectively, as the dependent variable, the two groups as the independent variable, baseline FMA-UE/BI, age, sex, site, time since onset, hypertension and diabetes as covariates. RESULTS: Both ITT and PP analyses demonstrated the effectiveness of imVR-based rehabilitation. The FMA-UE score was greater in the imVR compared with the Control at the post-intervention (mean difference: 9.1 (95% CI 1.6, 16.6); P = 0.019) and follow-up (mean difference:11.5 (95% CI 1.9, 21.0); P = 0.020). The results were consistent for BI scores. Moreover, brain FC analysis found that the motor function improvements were associated with a change in degree in ipsilesional premotor cortex and ipsilesional dorsolateral prefrontal cortex immediately following the intervention and in ipsilesional visual region and ipsilesional middle frontal gyrus after the 12-week follow-up. CONCLUSIONS: ImVR-based rehabilitation is an effective tool that can improve the recovery of UE functional capabilities of subacute stroke patients when added to standard care. These improvements were associated with distinctive brain changes at two post-stroke timepoints. The study results will benefit future patients with stroke and provide evidence for a promising new method of stroke rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03086889.

The relationship between family function and the incidence of overweight/obesity in children and adolescents in Chengdu city, Sichuan province of China: based on latent profile analysis.

BACKGROUND: Overweight/obesity in children and adolescents has become a global health problem, and family function may be associated with its occurrence. Studies exploring the association between family function and overweight/obesity in children and adolescents were performed in Western and Taiwan, China. To date, related studies haven't been conducted in Mainland China. OBJECTIVES: To investigate the current status of overweight, obesity, and family function among children and adolescents in Chengdu, China, and to explore their associations. METHODS: Children and adolescents in five primary and middle schools were chosen by cluster sampling. Body Mass Index was used to measure the status of overweight and obesity, and the Chinese family assessment instrument was adopted to assess family function. Latent profile analysis and stepwise logistic regression were applied to identify family classification and explore the relationships between family function and overweight/obesity. RESULTS: A total of 7616 (84.92%) children and adolescents out of 8968 completed the study with qualified-filled questionnaires. Nine hundred and sixty-six (12.68%)participants were overweight and 656 (8.61%) were obese. The family function was categorized into three profiles: mild (63.93%), moderate (12.32%), and severe (23.75%) dysfunction. The prevalence of overweight was 12.16%, 14.71%, and 13.05% for mild, moderate, and severe family dysfunction, respectively. And the prevalence of obesity was 8.19%, 10.77%, and 8.62% respectively. Participants in moderate and severe dysfunction families were more likely to be overweight (moderate: OR = 1.27, 95% CI:1.01 ~ 1.59, P = 0.04; severe: OR = 1.38, 95% CI:1.15 ~ 1.66, P = 0.001) and obese (moderate: OR = 1.35, 95% CI:1.02 ~ 1.79, P = 0.03; severe: OR = 1.55, 95% CI:1.23 ~ 1.96, P < 0.001). Sociodemographic data such as gender, residence, grade, pocket money per week, the number of siblings, and the education level of the mother were all associated with the risk of being overweight/obese in children and adolescents. CONCLUSIONS: The problems of being overweight or obese exist among children and adolescents in Chengdu. And the risk of being overweight or obese increases along with the decrease in family function.

Highly Sensitive Enrichment of Low-Frequency Variants by Hairpin Competition Amplification.

Gene mutations are inevitably accumulated in cells of the human body. It is of great significance to detect mutations at the earliest possible time in physiological and pathological processes. However, genotyping low-copy tumor DNA (ctDNA) in patients is challenging due to abundant wild DNA backgrounds. One novel strategy to enrich rare mutations at low variant allele fractions (VAFs) with quantitative polymerase chain reaction (qPCR) and Sanger sequencing was contrived by introducing artificial hairpins into amplicons to compete with primers, coined as the hairpin competition amplification (HCA) system. The influence imposed by artificial hairpins on primer-binding in a high-temperature PCR system was investigated for the first time in this work, paving the way for the optimization of HCA. HCA differs from the previously reported work in which hairpins are formed to inhibit extension of wild-type DNA using 5-exonuclease-negative polymerase, where the readout is dependent on melting curve analysis after asymmetric PCR. Targeted at six different variants, HCA qPCR and HCA Sanger-enriched mutant DNA at VAFs as low as 0.1 or 0.01% were performed. HCA demonstrated advantages in multiplex reaction and temperature robustness. In profiling gene status from 12 lung cancer ctDNA samples and 16 thyroid cancer FNA DNA samples, HCA demonstrated a 100% concordance rate compared to ddPCR and commercial ARMS kit. HCA qPCR and Sanger sequencing can enrich low-abundance variants with high sensitivity and temperature robustness, presenting a novel and effective tool for precision diagnosis and treatment of rare variant diseases.

Activation of FMS-like tyrosine kinase 3 protects against isoprenaline-induced cardiac hypertrophy by improving autophagy and mitochondrial dynamics.

FMS-like receptor tyrosine kinase 3 (Flt3) expression was reported to increase in the heart in response to pathological stress, but the role of Flt3 activation and its underlying mechanisms remain poorly elucidated. This study was designed to investigate the role of Flt3 activation in sympathetic hyperactivity-induced cardiac hypertrophy and its mechanisms through autophagy and mitochondrial dynamics. In vivo, cardiac hypertrophy was established by subcutaneous injection of isoprenaline (6 mg/kg·day) in C57BL/6 mice for 7 consecutive days. The Flt3-ligand intervention was launched 2 h prior to isoprenaline each day. In vitro, experiments of cardiomyocyte hypertrophy, autophagy, and mitochondrial dynamics were performed in neonatal rat cardiomyocytes (NRCMs). Our results revealed that the expression level of Flt3 protein was significantly increased in the hypertrophic myocardium provoked by isoprenaline administration. Flt3-ligand intervention alleviated isoprenaline-induced cardiac oxidative stress, hypertrophy, fibrosis, and contractile dysfunction. Isoprenaline stimulation impaired autophagic flux in hypertrophic mouse hearts, supported by the accumulation of LC3II and P62 proteins, while Flt3-ligand restored the impairment of autophagic flux. Flt3 activation normalized the imbalance of mitochondrial fission and fusion in the hearts of mice evoked by isoprenaline as evidenced by the neutralization of elevated mitochondrial fission markers and reduced mitochondrial fusion markers. In NRCMs, Flt3-ligand treatment attenuated isoprenaline-stimulated hypertrophy, which was abolished by a Flt3-specific blocker AC220. Activating Flt3 reversed isoprenaline-induced autophagosome accumulation and impairment of autophagic flux probably by enhancing SIRT1 expression and consequently TFEB nuclear translocation. Flt3 activation improved the imbalance of mitochondrial dynamics induced by isoprenaline in NRCMs through the SIRT1/P53 pathway. Activation of Flt3 mitigated ISO-stimulated hypertrophy probably involves the restoration of autophagic flux and balance of mitochondrial dynamics. Therefore, activation of Flt3 attenuates isoprenaline-induced cardiac hypertrophy in vivo and in vitro, the potential mechanism probably attributes to SIRT1/TFEB-mediated autophagy promotion and SIRT1/P53-mediated mitochondrial dynamics balance. These findings suggest that activation of Flt3 may be a novel target for protection against cardiac remodeling and heart failure during sympathetic hyperactivity.

Negative pressure wound therapy compared with conventional wound dressings for closed incisions in orthopaedic trauma surgery: A meta-analysis.

We performed a meta-analysis to evaluate the effect of negative pressure wound therapy compared with conventional wound dressings on closed incisions in orthopaedic trauma surgery. A systematic literature search up to October 2021 was done and 12 studies included 3555 subjects with closed incisions in orthopaedic trauma surgery at the start of the study: 1833 of them were provided with negative pressure wound therapy and 1722 were conventional wound dressings. They were reporting relationships about the effect of negative pressure wound therapy compared with conventional wound dressings on closed incisions in orthopaedic trauma surgery. We calculated the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to assess the effect of negative pressure wound therapy compared with conventional wound dressings on closed incisions in orthopaedic trauma surgery using the dichotomous and continuous methods with a random or fixed-effect model. Negative pressure wound therapy had significantly lower deep surgical site infection (OR, 0.65; 95% CI, 0.48-0.88, P = .005), superficial surgical site infection (OR, 0.23; 95% CI, 0.11-0.49, P = .31), and wound dehiscence (OR, 0.41; 95% CI, 0.21-0.80, P = .009) compared with conventional wound dressings in subjects with closed incisions in orthopaedic trauma surgery. However, negative pressure wound therapy had no significant effect on the length of hospital stay (MD, 0.29; 95% CI, -2.00- 2.58, P = .80) compared with conventional wound dressings in subjects with closed incisions in orthopaedic trauma surgery. Negative pressure wound therapy had significantly lower deep surgical site infection, superficial surgical site infection, and wound dehiscence; however, negative pressure wound therapy had no beneficial effect on the length of hospital stay compared with conventional wound dressings in subjects with closed incisions in orthopaedic trauma surgery. Further studies are required to validate these findings.

Inhibition of the Ras/ERK1/2 pathway contributes to the protective effect of ginsenoside Re against intimal hyperplasia.

Neointimal hyperplasia is the major cause of carotid stenosis after vascular injury, which restricts the long-term efficacy of endovascular treatment and endarterectomy in preventing stenosis. Ginsenoside Re (Re) is a major active ingredient of ginseng having multifaceted pharmacological effects on the cardiovascular system, and is a potential treatment for restenosis. In this study, we demonstrated that Re treatment significantly inhibited vascular injury-induced neointimal thickening, reduced the intimal area and intima/media (I/M) ratio, increased the lumen area, and inhibited pro-inflammatory cytokines. In cultured A7R5 cells, Re inhibited LPS-induced proliferation and migration as evidenced by suppressed colony formation and shortened migration distance, accompanied by the downregulated expression of pro-inflammatory cytokines. Re promoted VSMC apoptosis induced by balloon injury in vivo and LPS challenge in vitro. Moreover, Re inhibited autophagy in VSMCs evoked by balloon injury and LPS as supported by reduced LC3II and increased p62 expressions. Suppression of autophagy with the specific autophagy inhibitor spautin-1 efficiently inhibited LPS-induced cell proliferation and inflammation and promoted caspase-3/7 activities. Mechanistically, we found that Re attenuated Ras/ERK1/2 expression in VSMCs in vivo and in vitro. The MEK1/2 inhibitor PD98059 showed similar effects to Re on cell proliferation, migration, apoptosis, and the levels of autophagy and cytokines. In conclusion, we provided significant evidence that Re inhibited vascular injury-induced neointimal thickening probably by promoting VSMC apoptosis and inhibiting autophagy via suppression of the Ras/MEK/ERK1/2 signaling pathway.

Cognitive control and emotional response in attention-deficit/ hyperactivity disorder comorbidity with disruptive, impulse-control, and conduct disorders.

BACKGROUND: This study investigated cognitive and emotional functioning in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and disruptive, impulse-control, and conduct disorders (DICCD). METHODS: Thirty patients with ADHD, 26 with DICCD, 22 with ADHD+DICCD were recruited from the outpatient department of Shanghai Changning Mental Health Center, plus 20 healthy controls (HC). Differences between the groups in cognitive and emotional functioning were examined using Golden's Stroop and Emotional Stroop tests. For Emotional Stroop Mean reaction time (RT) of positive word (POS) and negative word (NEG) with color congruence (C) or incongruence (I) were recorded as POS-C, POS-I, NEG-C and NEG-I, respectively. RESULTS: For Golden's interference scores (IGs), both errors and RTs in the ADHD group were higher than in the other groups. Longer mean RTs of POS-C, POS-I, NEG-C and neural word (NEU) of the ADHD group, and NEG-I of ADHD+DICCD and DICCD groups were observed compared to HC. After 12 weeks of methylphenidate treatment, differences between ADHD subgroups and HC on Golden's Stroop RT disappeared, but differences in Golden's Stroop errors and Emotional Stroop mean RTs remained. The ADHD+DICCD group showed longer mean RTs in NEG-C, NEG-I and NEU of the Emotional Stroop test than the ADHD group. CONCLUSIONS: Our study shows that regardless of emotional responding, deficit in cognitive control is the core symptom of ADHD. However, emotionally biased stimuli may cause response inhibitory dysfunction among DICCD with callous-unemotional traits, and the comorbidity of ADHD and DICCD tends to account for the negative emotional response characteristic of DICCD. These deficits may be eliminated by medication treatment in ADHD, but not the ADHD with comorbid DICCD. Our results support the notion that ADHD with comorbid DICCD is more closely related to DICCD than to ADHD.

The Relationship of Functional Status of Cortisol, Testosterone, and Parameters of Metabolic Syndrome in Male Schizophrenics.

BACKGROUND: The cross-sectional study is aimed at investigating the relationship between cortisol, testosterone, and metabolic characteristics among male schizophrenics. METHODS: 174 patients were grouped based on their risk of metabolic syndrome (MetS) into the non-MetS, high-risk-MetS (HR-MetS), or MetS groups. Metabolic indices (body mass index (BMI), mean arterial pressure (MAP), cholesterol, triglyceride, and fasting blood glucose (FBG)) were associated with cortisol and testosterone levels using correlation analysis. Multiple linear regression analysis was used to associate the correlations between the WHO Quality of Life-BREF (WHOQOL-BREF) score and the five metabolic indices. RESULTS: The WHOQOL-BREF score for the non-MetS group significantly differed from the scores of the HR-MetS and MetS groups. The triglyceride level was positively correlated with the cortisol level, while all five metabolic indices were negatively correlated with testosterone level. Stepwise regression analysis produced a model predicting WHOQOL-BREF scores with four variables including MAP, intelligence quotient (IQ), FBG, and age. The correlation analysis then showed that there was a weak linear correlation between the testosterone level and all five metabolic indices. CONCLUSIONS: Among the five metabolic indices, the risks of hypertension and hyperglycemia are correlated with the quality of life in male schizophrenics rather than those of obesity or hyperlipidemia.

Activated FMS-like tyrosine kinase 3 ameliorates angiotensin II-induced cardiac remodelling.

AIM: FMS-like receptor tyrosine kinase 3 (Flt3) has been reported to be increased in cardiomyocytes responding to ischaemic stress. This study was to determine whether Flt3 activation could ameliorate pressure overload-induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action. METHODS: In vivo cardiac hypertrophy and remodelling experiments were conducted by infusing angiotensin II (Ang II) chronically in male C57BL/6 mice. Flt3-specific ligand (FL) was administered intraperitoneally every two days (5 µg/mouse). In vitro experiments on hypertrophy, apoptosis and autophagy mechanism were performed in neonatal rat cardiomyocytes (NRCMs) and H9c2 cells with adenovirus vector-mediated overexpression of Flt3. RESULTS: Our results demonstrated that following chronic Ang II infusion for 4 weeks, the mice exhibited heart hypertrophy, fibrosis, apoptosis and contractile dysfunction. Meanwhile, Ang II induced autophagic responses in mouse hearts, as evidenced by increased LC3 II and decreased P62 expression. These pathological alterations in Ang II-treated mice were significantly ameliorated by Flt3 activation with FL administration. In NRCMs and Flt3-overexpressed H9c2 cells, FL attenuated Ang II-induced pathological autophagy and inactivated AMPK/mTORC1/FoxO3a signalling, thereby efficiently mitigating cell hypertrophy and apoptosis. Conversely, the AMPK activator metformin or the mTORC1 inhibitor rapamycin reversed the effects of FL on the alterations of autophagy, hypertrophy and apoptosis in cardiomyocytes induced by Ang II. CONCLUSION: Flt3 activation ameliorates cardiac hypertrophy, fibrosis and contractile dysfunction in the mouse model of chronic pressure overload, most likely via suppressing AMPK/mTORC1/FoxO3a-mediated autophagy. These results provide new evidence supporting Flt3 as a novel therapeutic target in maladaptive cardiac remodelling.