ScalableTrack: Scalable One-Stream Tracking via Alternating Learning.

Transformer-based one-stream trackers are widely used to extract features and interact information for visual object tracking. However, the current one-stream tracker has fixed computational dimensions between different stages, which limits the network's ability to learn context clues and global representations, resulting in a decrease in the ability to distinguish between targets and backgrounds. To address this issue, a new scalable one-stream tracking framework, ScalableTrack, is proposed. It unifies feature extraction and information integration by intrastage mutual guidance, leveraging the scalability of target-oriented features to enhance object sensitivity and obtain discriminative global representations. In addition, we bridge interstage contextual cues by introducing an alternating learning strategy and solve the arrangement problem of the two modules. The alternating learning strategy uses alternate stacks of feature extraction and information interaction to focus on tracked objects and prevent catastrophic forgetting of target information between different stages. Experiments on eight challenging benchmarks (TrackingNet, GOT-10k, VOT2020, UAV123, LaSOT, LaSOT [Formula: see text] , OTB100, and TC128) show that ScalableTrack outperforms state-of-the-art (SOTA) methods with better generalization and global representation ability.

[Cell membrane-coated nanoparticles in disease therapy].

Nanotechnology has attracted increasing attention in the field of medical applications due to its significant potential for development. However, one major challenge that has emerged with nanoparticles is their tendency to activate the host immune clearance system, which hampers the achievement of desired therapeutic outcomes and may lead to harmful side effects. In recent years, membrane-coated nanoparticles have emerged as a promising solution, demonstrating their effectiveness in evading immune system clearance. These innovative nanoparticles inherit essential biological attributes from natural cell membranes, such as anchoring proteins and antigens. Consequently, membrane-coated nanoparticles exhibit unique capabilities such as immune evasion, prolonged circulation, targeted drug release, and immune modulation, substantially enhancing their versatility and prospects within the realm of biomedical applications. This review provides a comprehensive overview of the current applications of cell membrane-coated nanoparticles in disease therapy, highlighting their immense potential in this rapidly evolving platform. Additionally, the review outlines the promising prospects of this technology in disease therapy.

The impact of maternal occupation on children's health: A mediation analysis using the parametric G-formula.

BACKGROUND: Previous studies have found that maternal occupational choice can directly impact fetal health and mothers' energy and time available for childcare. Moreover, reduced caregiving time is associated with poorer child health. However, how maternal occupational factors (work nature/income/stress) affect child health has not been fully explored. METHODS: Data were extracted from China Family Panel Studies (CFPS) from 2014 to 2020. A parametric G-formula Model was constructed to simulate the direct impact of maternal occupational factors (work nature, income, and stress) on child health. Furthermore, we explored their indirect effects mediated by maternal physical health, mental health, or occupational factors for the overall sample and by different age groups of the children. RESULTS: Maternal work nature and income had positive direct impacts on child health, especially for children whose mothers were employers of budgeted positions. Maternal work stress had a negative direct impact on children's health. Maternal work stress mediated the positive impact of maternal work income (9%). Maternal work stress affected children's health directly for children aged under 6, while for children aged 7-15, it had an indirect impact mediated by maternal physical health (43%), mental health (44%), and income (47%). CONCLUSION: Attention should be paid to maternal occupational factors (especially to work stress) and to the varying care needs of children from their mothers at different ages to improve children's health and prevent the transmission of maternal occupation to children's health.

The efficacy and safety of continuous blood purification in neonates with septic shock and acute kidney injury: a two-center retrospective study.

To investigate the efficacy and safety of continuous blood purification (CBP) in neonates with septic shock and acute kidney injury (AKI). This retrospective study was conducted at two tertiary care children's hospitals between January 2015 and May 2022. A total of 26 neonates with septic shock and AKI were included in this study, with a mortality rate of 50%. Fourteen neonates (53.8%) received continuous veno-venous hemodiafiltration, and 12 (46.2%) received continuous veno-venous hemofiltration. Compared with the indices before CBP, urine output increased 12 h after CBP initiation (P = 0.003) and serum creatinine decreased (P = 0.019). After 24 h of CBP, blood urea nitrogen had decreased (P = 0.006) and mean arterial pressure had increased (P = 0.007). At the end of CBP, the vasoactive-inotropic score and blood lactate were decreased (P = 0.035 and 0.038, respectively) and PH was increased (P = 0.015). Thrombocytopenia was the most common complication of CBP.  Conclusion: CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. However, the mortality rate remains high, and whether CBP improves the prognosis of neonates with septic shock and AKI remains unclear. What is Known: • Over 50% of children with septic shock have severe AKI, of which 21.6% required CBP. • The clinical application of CBP in septic shock has attracted increasing attention. What is New: • CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. • The mortality rate in neonates with septic shock and AKI receiving CBP remains high.

The Effects of IL-23/IL-18-Polarized Neutrophils on Renal Ischemia-Reperfusion Injury and Allogeneic-Skin-Graft Rejection in Mice.

Neutrophils display heterogeneity and plasticity with different subgroups and immune-regulatory functions under various surrounding conditions. Neutrophils induced by IL-23/IL-18 (referred to N(IL-23+IL-18) neutrophils) have a unique gene-expression profile, with highly expressing IL-17, MHC-II, and costimulatory molecules. The adoptive transfer of N(IL-23+IL-18) neutrophils significantly increased the pathogenesis in a renal ischemia-reperfusion injury mouse model. N(IL-23+IL-18) neutrophils directly and efficiently induced allogeneic T cell proliferation in vitro. N(IL-23+IL-18) neutrophils enhanced the syngeneic T cell response to allogeneic antigens in mixed-lymphocyte reaction assays. The adoptive transfer of the donor or host N(IL-23+IL-18) neutrophils significantly enhanced the antidonor antibody production in an allogeneic-skin-transplanted mouse model, accompanied by increased Tfh cells in the spleens. Therefore, the neutrophil subset induced by IL-23/IL-18 promotes tissue injury and antidonor humoral response in the allogeneic transplantation mouse model.

High efficiency double light-emitting layer sky blue phosphor organic light-emitting diode with slow emission efficiency attenuation.

In this study, by doping the iridium (III) double ((4,6-difluorobenzene) -pyridine-N, C2'Pyridinformate (FIrpic) into 4,4', 4″ three (carbazole) trioxilamine (TcTa) and 9 (4 tert-butyl-benzene) -3,6 double (triphenylsilyl) -9H carbazole (CzSi) layers as light emitting layers (EMLs) to achieve sky blue phosphor organic electroluminescence (EL) devices with very low efficiency roll-off. The dependence of the EL performance on the doping concentration of the light-emitting molecules and the different EML thicknesses are studied in detail. Experimental data show that the thin-film-doped TcTa layer is very important for the efficiency of the device. Finally, the optimal device achieves extremely high power efficiency, current efficiency, and external quantum efficiency (EQE), reaching 74.82 lm/W, 66.68 cd/A, and 31.9 %, respectively. At a certain luminance of 2000 cd/m2 (3.4 V), the same device retained power efficiency with current efficiency and external quantum efficiency of 57.71 lm/W, 62.46 cd/A and 29.3 %, respectively, based on theoretical discussion, the improved EL efficiency was attributed to the energy levels of the host and luminescent molecules, which helps to balance the charge carrier in the emitter molecule distribution and expand the recombination region.

[Diagnosis and treatment of a child with alveolar capillary dysplasia with misalignment of pulmonary veins due to variant of FOXF1 gene].

OBJECTIVE: To explore the diagnosis, treatment and genetic characteristics of a neonate with severe pulmonary hypertension and respiratory failure. METHODS: Perinatal history, clinical manifestations, laboratory finding and diagnosis and treatment data of the child were collected. Whole exome sequencing was carried out for the child, and Sanger sequencing was used to verify the candidate variants. RESULTS: The female neonate has developed progressive respiratory failure and refractory pulmonary hypertension shortly after birth. Conventional treatment such as mechanical ventilation, vasoactive drugs, and inhaled nitric oxide were ineffective. She has developed sustained pulmonary hypertension after weaning from extracorporeal membrane oxygenation therapy, and had died after the treatment had ceased. Whole exome sequencing revealed that she has harbored a heterozygous de novo variant of c.682_683insGCGGCGGC (p.G234Rfs*148) of the FOXF1 gene, which was predicted as pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG), with evidence items of PVS1_Strong+PM2_Supporting+PS2. Based on her clinical manifestations and result of genetic testing, the child was diagnosed with alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV). CONCLUSION: Discovery of the c.682_683insGCGGCGGC (p.G234 Rfs*148) variant of the FOXF1 gene has expanded the mutational spectrum of the FOXF1 gene, which has facilitated implementation of specific treatment and provided a basis for clinical diagnosis and genetic counseling.

The Potency of Serum Omentin-1 Quantification in Predicting Major Adverse Cardiac and Cerebrovascular Events Risk in Patients Receiving Hemodialysis.

Omentin-1 regulates inflammation, lipid accumulation, endothelial dysfunction, and atherosclerosis; the latter factors contribute to the occurrence of major adverse cardiac and cerebrovascular events (MACCE). This study aimed to explore the predictive implication of serum omentin-1 for MACCE risk in patients receiving hemodialysis. A total of 319 patients receiving hemodialysis and 160 healthy controls were prospectively enrolled in this study. Omentin-1 from serum was detected by enzyme-linked immunosorbent assay. MACCE was recorded during follow-up (median 18.9 months; range 1.9-62.9 months) in patients receiving hemodialysis. Omentin-1 was reduced in patients receiving hemodialysis versus healthy controls (P < 0.001). In patients receiving hemodialysis, omentin-1 was negatively related to C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol (all P < 0.05); whereas omentin-1 was not related to other clinical characteristics. Notably, the 1-year, 2-year, 3-year, 4-year, and 5-year accumulating MACCE rates in patients receiving hemodialysis were 7.9%, 18.3%, 25.9%, 36.1%, and 41.4%, respectively. Interestingly, high omentin-1 related to decreased accumulating MACCE rate (P = 0.003), which was further validated by multivariate Cox regression analysis (hazard ratio = 0.458, P = 0.006). Additionally, by direct comparison, omentin-1 was reduced in hemodialysis patients who experienced MACCE compared to those who did not (P < 0.001); meanwhile, the receiver operator characteristic curve displayed that omentin-1 had an acceptable ability to estimate MACCE risk with an area under the curve (95% confidence interval) of 0.703 (0.628-0.777). Serum omentin-1 reflects reduced inflammation and lipid accumulation, as well as predicts decreased MACCE risk in patients receiving hemodialysis.

Systematic evaluation of membrane-camouflaged nanoparticles in neutralizing Clostridium perfringens ε-toxin.

Clostridium perfringens ε-toxin (ETX) is the main toxin leading to enterotoxemia of sheep and goats and is classified as a potential biological weapon. In addition, no effective treatment drug is currently available in clinical practice for this toxin. We developed membrane-camouflaged nanoparticles (MNPs) with different membrane origins to neutralize ETX and protect the host from fatal ETX intoxication. We evaluated the safety and therapeutic efficacy of these MNPs in vitro and in vivo. Compared with membranes from karyocytes, such as Madin-Darby canine kidney (MDCK) cells and mouse neuroblastoma N2a cells (N2a cells), membrane from erythrocytes, which do not induce any immune response, are superior in safety. The protective ability of MNPs was evaluated by intravenous injection and lung delivery. We demonstrate that nebulized inhalation is as safe as intravenous injection and that both modalities can effectively protect mice against ETX. In particular, pulmonary delivery of nanoparticles more effectively treated the challenge of inhaled toxins than intravenously injected nanoparticles. Moreover, MNPs can alter the biological distribution of ETX among different organs in the body, and ETX was captured, neutralized and slowly delivered to the liver and spleen, where nanoparticles with ETX could be phagocytized and metabolized. This demonstrates how MNPs treat toxin infections in vivo. Finally, we injected the MNPs into mice in advance to find out whether MNPs can provide preventive protection, and the results showed that the long-cycle MNPs could provide at least a 3-day protection in mice. These findings demonstrate that MNPs provide safe and effective protection against ETX intoxication, provide new insights into membrane choices and delivery routes of nanoparticles, and new evidence of the ability of nanoparticles to provide preventive protection against infections.

Real-life effects, complications, and outcomes in 39 critically ill neonates receiving continuous kidney replacement therapy.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has been expanded from simple kidney replacement therapy to the field of critical illness in children. However, CKRT is rarely used in critically ill neonates in the neonatal intensive care unit (NICU). This study aimed to describe patients' clinical characteristics at admission and CKRT initiation, CKRT effects, short-term outcomes, and predictors of death in critically ill neonates. METHODS: A 7-year single-center retrospective study in a tertiary NICU. RESULTS: Thirty-nine critically ill neonates received CKRT between May 2015 and April 2022 with a mortality rate of 35.9%. The most common primary diagnosis was neonatal sepsis in 15 cases (38.5%). Continuous veno-venous hemodiafiltration and continuous veno-venous hemofiltration were applied in 43.6% and 56.4% of neonates, respectively. The duration of CKRT was 44 (18, 72) h. Thirty-one patients (79.5%) had complications due to CKRT-related adverse events, and the most common complication was thrombocytopenia. Approximately 12 h after the CKRT initiation, urine volume, mean arterial pressure, and pH were increased, and serum creatinine, blood urea nitrogen, and blood lactate were decreased. In the multivariate logistic regression analysis, neonatal critical illness score [odds ratio 0.886 (0.786 ~ 0.998), P = 0.046] was an independent risk factor for death in critically ill neonates who received CKRT. CONCLUSIONS: CKRT can be an effective and feasible technique in critically ill neonates, but the overall mortality and CKRT-related complications are relatively high. Furthermore, the probability of death is greater among neonates with greater severity of illness at CKRT initiation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Analysis of risk factors for death in 59 cases of critically ill neonates receiving continuous renal replacement therapy: a two-centered retrospective study.

To investigate the risk factors for death in critically ill neonates receiving continuous renal replacement therapy (CRRT). This retrospective study analyzed the clinical data of critically ill neonates receiving CRRT at two tertiary hospitals from January 2015 to December 2021. A multi-factor logistic regression analysis was performed, and the predictive value of relevant risk factors on death was verified by receiver operating characteristic (ROC) curve. A total of 59 cases of critically ill neonates were included in this study, with a mortality of 37.3%. The most common primary disease in these cases was neonatal sepsis, followed by neonatal asphyxia, and inborn errors of metabolism (IEM). Univariate analysis showed that the risk factors related to death included primary diseases; the number of organs involved in multiple organ dysfunction syndrome (MODS), neonatal critical illness scores (NCIS), and indications of CRRT; the blood lactate, blood glucose, hemoglobin, and platelet before CRRT initiation; and the incidence of bleeding or thrombosis during CRRT. Multi-factor logistic regression analysis showed that risk factors for death in critically ill neonates receiving CRRT included the occurrence of neonatal sepsis, the number of organs involved in MODS, and the NCIS. ROC curve analysis showed that the number of organs involved in MODS and NCIS had a good predictive value for death in critically ill neonates receiving CRRT, with the areas under the curve (AUC) being 0.700 and 0.810, respectively. CONCLUSION: Neonatal sepsis, the number of organs involved in MODS, and NCIS were independent risk factors for death in critically ill neonates receiving CRRT. Moreover, the number of organs involved in MODS and NCIS could effectively predict death in critically ill neonates receiving CRRT. WHAT IS KNOWN: • The population to which CRRT is applicable is gradually expanding from critically ill children to critically ill neonates. • The mortality of critically ill neonates receiving CRRT remains high. WHAT IS NEW: • The most common primary disease in critically ill neonates receiving CRRT was neonatal sepsis, followed by neonatal asphyxia and inborn errors of metabolism (IEM). • The number of organs involved in MODS and NCIS could effectively predict death in critically ill neonates receiving CRRT.

Efficacy of Respiratory Training in Relieving Postoperative Pain in Patients with Spinal Nerve Root Entrapment Syndrome.

Background: Breathing exercise can help patients with dyspnea to change the wrong breathing pattern, improve the degree of freedom of respiratory muscles, increase alveolar ventilation, promote breathing, and relieve the symptoms of dyspnea patients. Therefore, this study is aimed at investigating the role of breathing training in alleviating postoperative pain in patients with spinal nerve root entrapment syndrome. Objective: To explore the effect of respiratory training in relieving postoperative pain in patients with spinal nerve root entrapment syndrome. Methods: Fifty-eight patients with spinal nerve root entrapment syndrome treated in our hospital from May 2020 to May 2021 were analyzed retrospectively. The patients were randomly divided into a control group (n = 29) and an observation group (n = 29). The control group was given routine postoperative pain nursing, and the observation group was given respiratory training on the basis of the control group. The scores of visual analogue scale (VAS), self-rating anxiety scale (SAS), Oswestry dysfunction index questionnaire (ODI), the dosage of postoperative analgesics, and the time of first out-of-bed activity were recorded before pain nursing intervention and 3 days and 7 days after intervention. Results: The VAS, SAS, and ODI scores of the observation group after 3 d and 7 d of intervention were lower than those of the control group. Compared with the same group, the scores of VAS, SAS, and ODI after 3 d and 7 d of intervention were lower than those before intervention, and those after 7 d of intervention were lower than those after 3 d of intervention (P < 0.05). The dosage of postoperative analgesics and the time of first out-of-bed activity in the observation group were lower than those in the control group (P < 0.05). Conclusion: Respiratory training can effectively relieve postoperative pain, reduce anxiety, and improve spinal function in patients with spinal nerve root entrapment syndrome, which is beneficial to the prognosis of patients and is worthy of promotion.

PVBase: A MALDI-TOF MS Database for Fast Identification and Characterization of Potentially Pathogenic Vibrio Species From Multiple Regions of China.

The potentially pathogenic species of the genus Vibrio pose a threat to both humans and animals, creating medical burdens and economic losses to the mariculture industry. Improvements in surveillance and diagnosis are needed to successfully manage vibriosis outbreaks. Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) can provide rapid diagnosis and has been widely used in the identification of Vibrio spp. The main weakness of this technology is the limited number of strains and species of Vibrio in the existing commercial database. Here, we develop a new in-house database named PVBase containing 790 main spectra projections (MSP) of ten Vibrio species that come from various regions of China and include abundant clinical and environmental strains. PVBase was validated through a blind test of 65 Vibrio strains. The identification accuracy and scoring of Vibrio strains was greatly improved through the addition of PVBase. Identification accuracy increased from 73.4 to 100%. The number of strains with identification scores above 2.2 increased from 53.1% to 96.9% and 53.1% of strains had an identification score above 2.59. Moreover, perfect discrimination was obtained when using all of the MSPs created for the Vibrio species, even for very closely related species such as V. cholerae, V. albensis, and V. mimicus or V. alginolyticus, V. parahaemolyticus, and V. harveyi. In addition, we used phyloproteomic analysis to study whether there are differences in protein fingerprints of different regions or pathogenic strains. We found that MSP characteristics of Vibrio species were not related to their region or source. With the construction of PVBase, the identification efficiency of potentially pathogenic Vibrio species has been greatly improved, which is an important advance for epidemic prevention and control, and aquaculture disease detection.

Unintentional Action Localization via Counterfactual Examples.

How do humans localize unintentional action like " A boy falls down while playing skateboard "? Cognitive science shows that an 18-month-old baby understands the intention by observing the actions and comparing the feedback. Motivated by this evidence, we propose a causal inference approach that constructs a video pool containing intentional knowledge, conducts the counterfactual intervention to observe intentional action, and compares the unintentional action with intentional action to achieve localization. Specifically, we first build a video pool, where each video contains the same action content as an original unintentional action video. Then we conduct the counterfactual intervention to generate counterfactual examples. We further maximize the difference between the predictions of factual unintentional action and counterfactual intentional action to train the model. By disentangling the effects of different clues on the model prediction, we encourage the model to highlight the intention clue and alleviate the negative effect brought by the training bias of the action content clue. We evaluate our approach on a public unintentional action dataset and achieve consistent improvements on both unintentional action recognition and localization tasks.

Probabilistic Temporal Modeling for Unintentional Action Localization.

Humans have the inherent advantage of understanding action intention, while it is an enormous challenge to train the machine to localize unintentional action in videos due to the lack of reliable annotations for stable training. The annotations of unintentional action are unreliable since different annotators are affected by their subjective appraisals and intrinsic ambiguity, which brings heavy difficulties for the training. To address this issue, we propose a probabilistic framework for unintentional action localization by modeling the uncertainty of annotations. Our framework consists of two main components, including Temporal Label Aggregation (TLA) and Dense Probabilistic Localization (DPL). We first formulate each annotated failure moment as a temporal label distribution. Then we propose a TLA component to aggregate temporal label distributions of different failure moments in an online manner and generate dense probabilistic supervision. Based on TLA, We further develop a DPL component to jointly train three heads (i.e., probabilistic dense classification, probabilistic temporal detection, and probabilistic regression) with different supervision granularities and make them highly collaborative. We evaluate our approach on the largest unintentional action dataset OOPS and demonstrate that our approach can achieve significant improvement over the baseline and state-of-the-art methods.

Case Report: Transient antenatal bartter syndrome in an extremely preterm infant with a novel MAGED2 variant.

Variants in the MAGED2 may cause antenatal transient Bartter syndrome, which is characterised by polyhydramnios, preterm labour, postnatal polyuria, hypokalaemia and metabolic alkalosis. Transient gross hematuria and acute kidney injury in such cases have not been reported previously. The patient, a boy, was born at a gestational age of 27 + 5 weeks. Polyhydramnios has been detected at 24 weeks of gestation. Polyuria, hyponatraemia, hypokalaemia, weight loss, transient hematuria and acute kidney injury occur after birth. The urinary ultrasonography showed no abnormality, and after a month of treatment with liquid electrolytes and nutritional management, the clinical symptoms improved. Whole-exome sequencing revealed a variant in MAGED2: c.1426C > T, p.Arg476X, inherited from the mother, who was healthy. During the 1-year follow-up, the child grew and developed with normal renal function and electrolyte levels. This is the first report of transient antenatal Bartter syndrome caused by a MAGED2 variant in China in an extremely preterm infant who exhibited previously unreported symptoms: transient hematuria and acute kidney injury. This newly found variant expands the spectrum of genetic variants associated with antenatal Bartter syndrome; it can be detected by early genetic testing and overmedication, thereby avoided.

Longitudinal change in microRNA-130a expression and its correlation with the risk of developing major adverse cardiovascular and cerebral events in patients undergoing continuous ambulatory peritoneal dialysis.

BACKGROUND: MicroRNA-130a (miR-130a) regulates angio-cellular dysregulation, atherosclerosis, and cardiocerebral injuries, serving as a biomarker for major adverse cardiovascular and cerebral events (MACCE) in several chronic diseases. However, its clinical application in patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD), who are at a high risk of developing MACCE, has not been reported. Therefore, this study aimed to explore this aspect. METHODS: miR-130a expression in peripheral blood mononuclear cells obtained from 50 healthy controls (HCs) at recruitment and 257 ESRD patients undergoing CAPD at month (M)0, M12, M24, and M36 was determined by reverse transcription-quantitative polymerase chain reaction. ESRD patients undergoing CAPD were followed up until MACCE occurred or M36. Then, MACCE were recorded, and MACCE-free survival was calculated. RESULTS: miR-130a expression was significantly lower in ESRD patients undergoing CAPD than in HCs (p < 0.001). In addition, miR-130a expression significantly decreased from M0 to M36 in ESRD patients undergoing CAPD (p < 0.001). Moreover, miR-130a expression at M0, M12, and M24 was significantly lower in patients with MACCE than in those without MACCE (all p < 0.05). Furthermore, high miR-130a expression at M0, M12, and M36 was significantly correlated with prolonged MACCE-free survival in ESRD patients undergoing CAPD (all p < 0.05), and high miR-130a expression at M0 was an independent factor for improved MACCE-free survival (p = 0.015; hazard ratio (HR) (95% confidential interval): 0.456 (0.243-0.857)). CONCLUSION: miR-130a expression decreases continuously with disease progression in patients with ESRD undergoing CAPD. Additionally, this expression is negatively correlated with MACCE risk in these patients.

A novel synonymous ABCA3 variant identified in a Chinese family with lethal neonatal respiratory failure.

BACKGROUND: Lethal respiratory failure is primarily caused by a deficiency of pulmonary surfactant, and is the main cause of neonatal death among preterm infants. Pulmonary surfactant metabolism dysfunction caused by variants in the ABCA3 gene is a rare disease with very poor prognosis. Currently, the mechanisms associated with some ABCA3 variants have been determined, including protein mistrafficking and impaired phospholipid transport. However, some novel variants and their underlying pathogenesis has not been fully elucidated yet. In this study we aimed to identify the genetic features in a family with lethal respiratory failure. METHODS: We studied members of two generations of a Chinese family, including a female proband, her parents, her monozygotic twin sister, and her older sister. Trio whole exome sequencing (WES) were used on the proband and her parents to identify the ABCA3 variants. Sanger sequencing and real-time quantitative polymerase chain reaction (PCR) were used on the monozygotic twin sister of proband to validate the ABCA3 synonymous variant and exon deletion, respectively. The potential pathogenicity of the identified synonymous variant was predicted using the splice site algorithms dbscSNV11_AdaBoost, dbscSNV11_RandomForest, and Human Splicing Finder (HSF). RESULTS: All patients showed severe respiratory distress, which could not be relieved by mechanical ventilation, supplementation of surfactant, or steroid therapy, and died at an early age. WES analysis revealed that the proband had compound heterozygous ABCA3 variants, including a novel synonymous variant c.G873A (p.Lys291Lys) in exon 8 inherited from the mother, and a heterozygous deletion of exons 4-7 inherited from the father. The synonymous variant was consistently predicted to be a cryptic splice donor site that may lead to aberrant splicing of the pre-mRNA by three different splice site algorithms. The deletion of exons 4-7 of the ABCA3 gene was determined to be a likely pathogenic variant. The variants were confirmed in the monozygotic twin sister of proband by Sanger sequencing and qPCR respectively. The older sister of proband was not available to determine if she also carried both ABCA3 variants, but it is highly likely based on her clinical course. CONCLUSIONS: We identified a novel synonymous variant and a deletion in the ABCA3 gene that may be responsible for the pathogenesis in patients in this family. These results add to the known mutational spectrum of the ABCA3 gene. The study of ABCA3 variants may be helpful for the implementation of patient-specific therapies.

Effects of sleep disorders and sedative-hypnotic medications on health-related quality of life in dialysis patients.

PURPOSE: Sleep disorders are very common among dialysis patients, leading patients to frequently take sedative-hypnotic medications; however, the effects of sleep disorders and the use of such drugs on health-related quality of life (HRQOL) have rarely been investigated. METHODS: The Pittsburgh Sleep Quality Index and Short Form-12 were used to assess sleep quality and patient health situations, respectively. Logistic regression was employed to identify factors associated with deterioration of the mental component summary (MCS) score and the physical component summary (PCS) score. RESULTS: A total of 461 patients undergoing dialysis were recruited. The prevalence of sleep disorders was 67.0%. Among the study population, 30.4% of patients took sedative-hypnotic medications to improve their sleep quality. Both the PCS (81.25 vs. 71.88, p < 0.001) and MCS scores (78.63 vs. 74.63, p < 0.001), which indicate HRQOL, were decreased among patients with sleep disorders compared with good sleepers. However, neither the PCS nor MCS scores showed any significant difference between patients with sleep disorders who used sedative-hypnotic medications and those who did not. CONCLUSION: Sleep disorders were closely associated with deterioration of both mental HRQOL and physical HRQOL. Sedative-hypnotic medication use did not affect HRQOL among patients with sleep disorders undergoing dialysis.

Re-weighted Discriminatively Embedded K-Means for Multi-view Clustering.

Recent years, more and more multi-view data are widely used in many real world applications. This kind of data (such as image data) are high dimensional and obtained from different feature extractors, which represents distinct perspectives of the data. How to cluster such data efficiently is a challenge. In this paper, we propose a novel multi-view clustering framework, called Re-weighted Discriminatively Embedded KMeans (RDEKM), for this task. The proposed method is a multiview least-absolute residual model which induces robustness to efficiently mitigates the influence of outliers and realizes dimension reduction during multi-view clustering. Specifically, the proposed model is an unsupervised optimization scheme which utilizes Iterative Re-weighted Least Squares to solve leastabsolute residual and adaptively controls the distribution of multiple weights in a re-weighted manner only based on its own low-dimensional subspaces and a common clustering indicator matrix. Furthermore, theoretical analysis (including optimality and convergence analysis) and the optimization algorithm are also presented. Compared to several state-of-the-art multi-view clustering methods, the proposed method substantially improves the accuracy of the clustering results on widely used benchmark datasets, which demonstrates the superiority of the proposed work.