A dynamic brain network decomposition method discovers effective brain hemodynamic sub-networks for Parkinson's disease.

OBJECTIVE: Dopaminergic treatment is effective for Parkinson's disease (PD). Nevertheless, the conventional treatment assessment mainly focuses on human-administered behavior examination while the underlying functional improvements have not been well explored. This paper aims to investigate brain functional variations of PD patients after dopaminergic therapy. Approach. This paper proposed a dynamic brain network decomposition method and discovered brain hemodynamic sub-networks that well characterized the efficacy of dopaminergic treatment in PD. Firstly, a clinical walking procedure with functional near-infrared spectroscopy (fNIRS) was developed, and brain activations during the procedure from fifty PD patients under the OFF and ON states (without and with dopaminergic medication) were captured. Then, dynamic brain networks were constructed with sliding-window analysis of phase lag index and integrated time-varying functional networks across all patients. Afterwards, an aggregated network decomposition algorithm was formulated based on aggregated effectiveness optimization of functional networks in spanning network topology and cross-validation network variations, and utilized to unveil effective brain hemodynamic sub-networks for PD patients. Further, dynamic sub-network features were constructed to characterize the brain flexibility and dynamics according to the temporal switching and activation variations of discovered sub-networks, and their correlations with differential treatment-induced gait alterations were analyzed. Results. The results demonstrated that PD patients exhibited significantly enhanced flexibility after dopaminergic therapy within a sub-network related to the improvement of motor functions. Other sub-networks were significantly correlated with trunk-related axial symptoms and exhibited no significant treatment-induced dynamic interactions. Significance. The proposed method promises a quantified and objective approach for dopaminergic treatment evaluation. Moreover, the findings suggest that the gait of PD patients comprises distinct motor domains, and the corresponding neural controls are selectively responsive to dopaminergic treatment. .

Selective Lattice Doping Enables a Low-cost, High-capacity and Long-lasting Potassium Layered Oxide Cathode for Potassium and Sodium storage.

Layered transition metal oxides are highly promising host materials for K ions, owing to their high theoretical capacities and appropriate operational potentials. To address the intrinsic issues of KxMnO2 cathodes and optimize their electrochemical properties, a novel P3-type oxide doped with carefully chosen cost-effective, electrochemically active and multi-functional elements is proposed, namely K0.57Cu0.1Fe0.1Mn0.8O2. Compared to the pristine K0.56MnO2, its reversible specific is increased from 104 to 135 mAh g-1. In addition, the Cu and Fe co-doping triples the capacity under high current densities, and contributes to long-term stability over 500 cycles with a capacity retention of 68%. Such endeavor holds the potential to make potassium-ion batteries particularly competitive for application in sustainable, low-cost, and large-scale energy storage devices. In addition, the cathode is also extended for sodium storage. Facilitated by the interlayer K ions that protect the layered structure from collapsing and expand the diffusion pathway for sodium ions, the cathode shows a high reversible capacity of 144 mAh g-1, fast kinetics and a long lifespan over 1000 cycles. The findings offer a novel pathway for the development of high-performance and cost-effective sodium-ion batteries.

Effects of right ventricular remodeling in chronic thromboembolic pulmonary hypertension on the outcomes of balloon pulmonary angioplasty: a 2D-speckle tracking echocardiography study.

BACKGROUND: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. METHODS: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. RESULTS: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm-5 to 545.5 ± 383.8 dyn·s·cm-5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%. CONCLUSIONS: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH.

Alcohol and colorectal cancer risk subclassified by mutational signatures of DNA mismatch repair deficiency.

BACKGROUND: We examined whether the association between alcohol consumption and CRC incidence was stronger for tumors with higher contributions of defective MMR (dMMR)-related tumor mutational signatures (TMSs). METHODS: We used data from 227,916 men and women who participated in the Nurses' Health Study (1980-2016), the Nurses' Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2016). Dietary data was collected every 4 years through validated food frequency questionnaires. Relative contributions of two dMMR-related TMSs (c-dMMRa/SBS15 and c-dMMRb/SBS26) were quantified using whole-exome sequencing data in a subset of incident CRC cases. Duplication-method Cox proportional hazards regression models were used to assess the association between alcohol consumption and the risk of CRC subtypes according to different contributions of the TMSs. All statistical tests were 2-sided. RESULTS: We documented 825 incident CRC cases with available TMS data over 26-36 years of follow-up. The association between alcohol consumption and CRC incidence was stronger for tumors with higher contributions of c-dMMRb/SBS26 (P-heterogeneitytrend = 0.02) compared to tumors with lower contributions of this TMS. Compared with nondrinkers, drinkers with ≥15 g/d of alcohol had a high risk of c-dMMRb/SBS26-high CRC [multivariable-adjusted HR: 2.43 (95% CI: 1.55-3.82)], but not c-dMMRb/SBS26-low CRC [0.86 (95% CI: 0.57-1.28)] or c-dMMRb/SBS26-moderate CRC [1.14 (95% CI: 0.76-1.71)]. No significant differential associations were observed for c-dMMRa/SBS15 (P-heterogeneitytrend = 0.41). CONCLUSIONS: High alcohol consumption was associated with an increased incidence of CRC containing higher contributions of c-dMMRb/SBS26, suggesting that alcohol consumption may be involved in colorectal carcinogenesis through the DNA mismatch repair pathway.

A study of the molecular mechanism of action of Jiawei Guizhishaoyaozhimu Decoction during rheumatoid arthritis therapy based on basic of network pharmacology and experimental verification.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which primarily affects the joints. The aim of the present study was to predict the main active ingredients of Jiawei Guizhishaoyaozhimu Decoction (JWGZSYZMD) and potential targets of this treatment during RA therapy by using molecular docking and network pharmacology methods. In addition, another aim was to investigate the therapeutic effects and mechanism of JWGZSYZMD on joint inflammation in rat models of collagen Ⅱ-induced arthritis (CIA). JWGZSYZMD ingredients and targets and genes associated with RA first extracted from traditional Chinese medicine (TCM) Systems Pharmacology Database and Analysis Platform, Bioinformatics Analysis Tool of Molecular Mechanism-TCM and Genecards databases, which were then transferred to the STRING database to set up protein interaction networks. The crystal structures of target proteins were also downloaded from the Protein Data Bank before molecular docking of compounds onto the protein targets was performed using AutoDock Vina software. In addition, a drug compound target visualization network was constructed using Cytoscape 3.7.2 software, which was used to elucidate the main mechanism underlying the anti-RA effect of JWGZSYZMD. A CIA rat model was established and animals were divided into the control, CIA model, JWGZSYZMD treatment (low-, medium- and high-dose) and tripterygium glycoside groups. Compared with the rats in the CIA model group, the joint scores of the rats in the high-dose group of JWGZSYZMD were significantly lower after 21 days of treatment. The expression levels of IL-6, TNF-α, IL-1ß and IL-17A in the synovial supernatant of the model rats were lower compared with those in the CIA group. Also, the expression of the aforementioned cytokines in the high-dose JWGZSYZMD group was significantly lower compared with those in the CIA model group. To conclude, using molecular docking combined with network pharmacology, the material basis and molecular mechanism underlying the effects of JWGZSYZMD during RA therapy were studied, which could potentially provide a reference for future clinical applications.

Light-Sheet Imaging to Reveal Cardiac Structure in Rodent Hearts.

Light-sheet microscopy (LSM) plays a pivotal role in comprehending the intricate three-dimensional (3D) structure of the heart, providing crucial insights into fundamental cardiac physiology and pathologic responses. We hereby delve into the development and implementation of the LSM technique to elucidate the micro-architecture of the heart in mouse models. The methodology integrates a customized LSM system with tissue clearing techniques, mitigating light scattering within cardiac tissues for volumetric imaging. The combination of conventional LSM with image stitching and multiview deconvolution approaches allows for the capture of the entire heart. To address the inherent trade-off between axial resolution and field of view (FOV), we further introduce an axially swept light-sheet microscopy (ASLM) method to minimize out-of-focus light and uniformly illuminate the heart across the propagation direction. In the meanwhile, tissue clearing methods such as iDISCO enhance light penetration, facilitating the visualization of deep structures and ensuring a comprehensive examination of the myocardium throughout the entire heart. The combination of the proposed LSM and tissue clearing methods presents a promising platform for researchers in resolving cardiac structures in rodent hearts, holding great potential for the understanding of cardiac morphogenesis and remodeling.

4'-O-methylbavachalcone alleviates ischemic stroke injury by inhibiting parthanatos and promoting SIRT3.

Cerebral ischemia-reperfusion injury (CIRI) can induce massive death of ischemic penumbra neurons via oxygen burst, exacerbating brain damage. Parthanatos is a form of caspase-independent cell death involving excessive activation of PARP-1, closely associated with intense oxidative stress following CIRI. 4'-O-methylbavachalcone (MeBavaC), an isoprenylated chalcone component in Fructus Psoraleae, has potential neuroprotective effects. This study primarily investigates whether MeBavaC can act on SIRT3 to alleviate parthanatos of ischemic penumbra neurons induced by CIRI. MeBavaC was oral gavaged to the middle cerebral artery occlusion-reperfusion (MCAO/R) rats after occlusion. The effects of MeBavaC on cerebral injury were detected by the neurological deficit score and cerebral infarct volume. In vitro, PC-12 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R), and assessed cell viability and cell injury. Also, the levels of ROS, mitochondrial membrane potential (MMP), and intracellular Ca2+ levels were detected to reflect mitochondrial function. We conducted western blotting analyses of proteins involved in parthanatos and related signaling pathways. Finally, the exact mechanism between the neuroprotection of MeBavaC and parthanatos was explored. Our results indicate that MeBavaC reduces the cerebral infarct volume and neurological deficit scores in MCAO/R rats, and inhibits the decreased viability of PC-12 cells induced by OGD/R. MeBavaC also downregulates the expression of parthanatos-related death proteins PARP-1, PAR, and AIF. However, this inhibitory effect is weakened after the use of a SIRT3 inhibitor. In conclusion, the protective effect of MeBavaC against CIRI may be achieved by inhibiting parthanatos of ischemic penumbra neurons through the SIRT3-PARP-1 axis.

PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure.

Sensory hair cells of the cochlea are essential for hearing, relying on the mechanosensitive stereocilia bundle at their apical pole for their function. Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1) is a stereocilia protein required for normal hearing in mice, and for the formation of the transient stereocilia surface coat, expressed during early postnatal development. While the function of the stereocilia coat remains unclear, growing evidence supports PKHD1L1 as a human deafness gene. In this study we carry out in depth characterization of PKHD1L1 expression in mice during development and adulthood, analyze hair-cell bundle morphology and hearing function in aging PKHD1L1-defficient mouse lines, and assess their susceptibility to noise damage. Our findings reveal that PKHD1L1-deficient mice display no disruption to bundle cohesion or tectorial membrane attachment-crown formation during development. However, starting from 6 weeks of age, PKHD1L1-defficient mice display missing stereocilia and disruptions to bundle coherence. Both conditional and constitutive PKHD1L1 knock-out mice develop high-frequency hearing loss progressing to lower frequencies with age. Furthermore, PKHD1L1-deficient mice are susceptible to permanent hearing loss following moderate acoustic overexposure, which induces only temporary hearing threshold shifts in wild-type mice. These results suggest a role for PKHD1L1 in establishing robust sensory hair bundles during development, necessary for maintaining bundle cohesion and function in response to acoustic trauma and aging.

Blue light protection factor: a method to assess the protective efficacy of cosmetics against blue light-induced skin damage in the Chinese population.

BACKGROUND: Previous studies have shown that visible light (VL), especially blue light (BL), could cause significant skin damage. With the emergence of VL protection products, a harmonization of light protection methods has been proposed, but it has not been widely applied in the Chinese population. OBJECTIVE: Based on this framework, we propose an accurate and simplified method to evaluate the efficacy of BL photoprotection for the Chinese population. METHODS: All subjects (n = 30) were irradiated daily using a blue LED light for four consecutive days. Each irradiation dose was 3/4 MPPD (minimum persistent pigmentation darkening). The skin pigmentation parameters, including L*, M, and ITA°, were recorded. We proposed the blue light protection factor (BPF) metric based on the skin pigmentation parameters to evaluate the anti-blue light efficacies of different products. RESULTS: We found that the level of pigmentation rose progressively and linearly as blue light exposure increased. We proposed a metric, BPF, to reflect the anti-blue light efficacy of products based on the linear changes in skin pigment characteristics following daily BL exposure. Moreover, we discovered that the BPF metric could clearly distinguish the anti-blue light efficacies between two products and the control group, suggesting that BPF is an efficient and simple-to-use metric for anti-blue light evaluation. CONCLUSION: Our study proposed an accurate and simplified method with an easy-to-use metric, BPF, to accurately characterize the anti-blue light efficacies of cosmetic products, providing support for further development of anti-blue light cosmetics.

The Effect of Time Monitoring on the Development of Time-Based Prospective Memory among Children Aged 7-11 Years Old.

Time-based prospective memory (TBPM) refers to the ability of an individual to successfully execute an expected plan in the future at a certain time point or after a definite period of time. This study investigated the potential developmental mechanism of school-age children's TBPM ability from the perspective of time monitoring. Experiment 1 used a between-subjects design of three ages (7, 9, 11) × two TBPM types (time point, time period) to investigate the trends and characteristics of two types of TBPM in children aged 7-11 years old. Experiment 2 used a between-subjects design of three ages (7, 9, 11) × two monitoring conditions (free monitoring, fixed monitoring) to investigate differences in two types of TBPM and monitoring behavior among school-age children under different monitoring conditions. These results showed that the age effect of TBPM was affected by the type of prospective memory (PM) and that time-point PM performance was significantly better than time-period PM performance among school-age children. These findings indicate that clear and definite external cues are helpful for school-age children in performing TBPM tasks. Moreover, there were significant differences found in the TBPM performance of school-age children under different time monitoring conditions. The performance of older children was significantly better than that of younger children. This indicates that older children can better allocate their attentional resources and use time monitoring strategies to improve their performance in PM tasks. Accordingly, this study showed that the TBPM ability of 7- to 11-year-old children is in continuous development and that the time monitoring behavior in the TBPM task is affected by task type and monitoring conditions.

A Comprehensive Evaluation Algorithm of Multi-Point Relay Based on Link-State Awareness for UANETs.

The Multi-Point Relay (MPR) is one of the core technologies for Optimizing Link State Routing (OLSR) protocols, offering significant advantages in reducing network overhead, enhancing throughput, maintaining network scalability, and adaptability. However, due to the restriction that only MPR nodes can forward control messages in the network, the current evaluation criteria for selecting MPR nodes are relatively limited, making it challenging to flexibly choose MPR nodes based on current link states in dynamic networks. Therefore, the selection of MPR nodes is crucial in dynamic networks. To address issues such as unstable links, poor transmission accuracy, and lack of real-time performance caused by mobility in dynamic networks, we propose a comprehensive evaluation algorithm of MPR based on link-state awareness. This algorithm defines five state evaluation parameters from the perspectives of node mobility and load. Subsequently, we use the entropy weight method to determine weight coefficients and employing the method of Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) for comprehensive evaluation to select MPR nodes. Finally, the Comprehensive Evaluation based on Link-state awareness of OLSR (CEL-OLSR) protocol is proposed, and simulated experiments are conducted using NS-3. The results indicate that, compared to PM-OLSR, ML-OLSR, LD-OLSR, and OLSR, CEL-OLSR significantly improves network performance in terms of packet delivery rate, average end-to-end delay, network throughput, and control overhead.

Effect of high NEFA concentration on lipid metabolism disorders in hepatocytes based on lipidomics.

Introduction: High concentrations of nonesterified fatty acids (NEFA) is the key of characteristic of fatty liver in dairy cows. Therefore, the aim of this study was to investigate the effect of high concentration of NEFA on lipid metabolism in hepatocytes through the lipidomic approach and molecular biology techniques. Methods: Stimulate AML-12 cells with different concentrations of NEFA, observe the cellular lipid accumulation, and select 0.6 mM NEFA stimulation concentration for subsequent experiments. Collect cells for lipidomics analysis. Results: High concentration of NEFA (0.6-2.4 mM) significantly reduced the cell viability in a concentration-dependent manner, indicating that high concentrations of NEFA have lipotoxicity on hepatocytes. In addition, NEFA promoted triglycerides (TAG) accumulation, increased the mRNA expression of the lipogenic molecules SREBP1c and FASN, and decreased the mRNA expression of lipolytic molecules CPT1A and HSL in hepatocytes. Mechanistically, high concentration of NEFA induced lipid metabolism disorders in hepatocytes by regulating metabolic pathways such as glycerol phospholipid metabolism, glycosyl phosphatidylinositol anchored biosynthesis, triglyceride metabolism, sphingolipid metabolism, and inositol phosphate metabolism. Discussion: High concentration of NEFA is lipotoxic to cells, promoting lipid accumulation. LPE (18:2), LPE (18:3), LPE (18:1) via glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, glycerolipid metabolism, sphingolipid metabolism, and inositol phosphate metabolism, indicating their potential regulation role in the pathogenesis of fatty liver.

Recent advances in the application of clay-containing hydrogels for hemostasis and wound healing.

INTRODUCTION: Immediate control of bleeding and anti-infection play important roles in wound management. Multiple organ dysfunction syndrome and death may occur if persistent bleeding, hemodynamic instability, and hypoxemia are not addressed. The combination of clay and hydrogel provides a new outlet for wound hemostasis. In this review, the current research progress of hydrogel/clay composite hemostatic agents was reviewed. AREAS COVERED: This paper summarizes the characteristics of several kinds of clay including kaolinite, montmorillonite, laponite, sepiolite, and palygorskite. The advantages and disadvantages of its application in hemostasis were also summarized. Future directions for the application of hydrogel/clay composite hemostatic agents are presented. EXPERT OPINION: Clay can activate the endogenous hemostatic pathway by increasing blood cell concentration and promoting plasma absorption to accelerate the hemostasis. Clay is antimicrobial due to the slow release of metal ions and has a rich surface charge with a high affinity for proteins and cells to promote tissue repair. Hydrogels have some properties such as good biocompatibility, strong adhesion, high stretchability, and good self-healing. Despite promising advances, hydrogel/clay composite hemostasis remains a limitation. Therefore, more evidence is needed to further elucidate the risk factors and therapeutic effects of hydrogel/clay in hemostasis and wound healing.

Remote Epitaxy: Fundamentals, Challenges, and Opportunities.

Advanced heterogeneous integration technologies are pivotal for next-generation electronics. Single-crystalline materials are one of the key building blocks for heterogeneous integration, although it is challenging to produce and integrate these materials. Remote epitaxy is recently introduced as a solution for growing single-crystalline thin films that can be exfoliated from host wafers and then transferred onto foreign platforms. This technology has quickly gained attention, as it can be applied to a wide variety of materials and can realize new functionalities and novel application platforms. Nevertheless, remote epitaxy is a delicate process, and thus, successful execution of remote epitaxy is often challenging. Here, we elucidate the mechanisms of remote epitaxy, summarize recent breakthroughs, and discuss the challenges and solutions in the remote epitaxy of various material systems. We also provide a vision for the future of remote epitaxy for studying fundamental materials science, as well as for functional applications.

Spatial-temporal differentiation of urban eco-efficiency and its driving factors: A comparison of five major urban agglomerations in China.

This paper utilizes an improved undesirable output DEA model to measure the eco-efficiency of cities in five major urban agglomerations in China during 2006-2020. It employs the Theil Index and Geodetector to investigate the spatial-temporal distribution differentiation characteristics and driving factors of urban eco-efficiency. The main findings are as follows. Firstly, the eco-efficiency of all urban agglomerations showed a fluctuating upward trend, but the eco-efficiency performance of different urban agglomerations in China shows a stratification characteristic. Specifically, the Pearl River Delta urban agglomeration consistently ranks first in China, while the mean values of the Yangtze River Delta urban agglomeration, Beijing-Tianjin-Hebei urban agglomeration, and Chengdu-Chongqing urban agglomeration are lower than the national average. Secondly, the overall differences in the urban eco-efficiency of all sample cities show a consistently fluctuating downward trend. The factor that affects the level differences of eco-efficiency in different cities is the intra-regional differences. Last but not least, the top three factors affecting the spatial distribution difference of urban eco-efficiency in the whole sample are environmental pollution control investments, innovation level, and environmental infrastructure investments. In the end, this paper proposes that reducing the intra-regional differences is the primary task to achieve the coordinated improvement of urban eco-efficiency in urban agglomerations, and then puts forward some policy suggestions to improve eco-efficiency for the five major urban agglomerations.

Efficacy of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension patients with pulmonary comorbidity.

Background: Balloon pulmonary angioplasty (BPA) is an established treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but its efficacy in CTEPH patients with a pulmonary comorbidity has not been well-studied. Here, we compared post-BPA outcomes between CTEPH patients with and without chronic pulmonary disease at baseline and analyzed predictors of BPA success. Methods: From August 2017 to October 2022, 62 patients with inoperable CTEPH who underwent BPA were consecutively enrolled and grouped based on the presence of a pulmonary comorbidity at baseline. All patients underwent transthoracic echocardiography, pulmonary function tests, and right heart catheterization. Pre- and post-BPA data were evaluated to identify factors that influence the success of BPA. Results: Among the 62 CTEPH patients, BPA was considered successful in 50 patients and unsuccessful in 12 patients. Responders to BPA had better exercise capacity and right heart function at baseline, but no differences in hemodynamic or respiratory function were detected between the groups. In CTEPH patients with chronic pulmonary disease (n = 14), BPA significantly improved mean pulmonary arterial pressure, pulmonary vascular resistance and right heart function parameters. Only CTEPH patients without chronic pulmonary disease (n = 48) exhibited significant improvement in 6-minute walk distance and respiratory function. Multivariate logistic regression analysis showed that pulmonary comorbidity at baseline was independently associated with the efficacy of BPA. Conclusions: BPA provided significantly improvements in hemodynamics and right heart function in CTEPH patients, independent of pulmonary comorbidity at baseline. However, pulmonary comorbidity can negatively impact post-BPA outcomes.

[Analysis of a child with Microvillus inclusion disease due to variants of MYO5B gene and a literature review].

OBJECTIVE: To explore the clinical and genetic characteristics of a neonate with Microvillus inclusion disease (MVID). METHODS: A neonate with MVID admitted to the First Affiliated Hospital of Zhengzhou University in May 2019 was selected as the study subject. Clinical data were collected. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA). A literature was also carried out to summarize the clinical and genetic characteristics of MVID. RESULTS: The prematurely born neonate had presented with unexplained refractory diarrhea and metabolic acidosis. Active symptomatic treatment was ineffective, and the child had died at 2 months old. WES revealed that he had harbored compound heterozygous variants of the MYO5B gene, namely c.1591C>T (p.R531W) and deletion of exon 9. Sanger sequencing showed that the R531W variant was inherited form his father, and MLPA confirmed that the exon 9 deletion was inherited from his mother. Seven children with MVID were reported in China, of which one was lost during follow-up and six had deceased. One hundred eighty eight patients were reported worldwide and only one was cured. The clinical features of MVID had included refractory diarrhea, metabolic acidosis and poor prognosis. CONCLUSION: The child was diagnosed with MVID due to the compound heterozygous variants of the MYO5B gene, which has provided a basis for genetic counseling and prenatal diagnosis.

A model-based MR parameter mapping network robust to substantial variations in acquisition settings.

Deep learning methods show great potential for the efficient and precise estimation of quantitative parameter maps from multiple magnetic resonance (MR) images. Current deep learning-based MR parameter mapping (MPM) methods are mostly trained and tested using data with specific acquisition settings. However, scan protocols usually vary with centers, scanners, and studies in practice. Thus, deep learning methods applicable to MPM with varying acquisition settings are highly required but still rarely investigated. In this work, we develop a model-based deep network termed MMPM-Net for robust MPM with varying acquisition settings. A deep learning-based denoiser is introduced to construct the regularization term in the nonlinear inversion problem of MPM. The alternating direction method of multipliers is used to solve the optimization problem and then unrolled to construct MMPM-Net. The variation in acquisition parameters can be addressed by the data fidelity component in MMPM-Net. Extensive experiments are performed on R2 mapping and R1 mapping datasets with substantial variations in acquisition settings, and the results demonstrate that the proposed MMPM-Net method outperforms other state-of-the-art MR parameter mapping methods both qualitatively and quantitatively.

Hemoglobin is associated with BMDs and risk of the 10-year probability of fractures in patients with type 2 diabetes mellitus.

Purpose: This study aimed to investigate the associations between hemoglobin (HGB) levels and bone mineral density (BMD) and fracture risk in type 2 diabetes mellitus(T2DM) population of different ages. Method: This cross-sectional study included 641 patients with T2DM (57.9% males). BMD of the femoral neck (FN), total hip (TH), and lumbar spine (LS) were measured using dual-energy X-ray absorptiometry. The 10-year probability of fracture was assessed using a fracture risk assessment tool (FRAX). HGB and other biochemical indices were measured in a certified laboratory at our hospital. Statistical analysis was performed using SPSS 26.0 and R language (R version 4.1.0). Generalized additive models (GAMs) were used to identify the associations between HGB and BMD and fracture risk. Results: Patients with osteoporosis have lower HGB levels than the non-osteoporotic population and lower FN BMD in patients with anemia than in the non-anemic population. In patients with T2DM, there was sex- and age-related variability in the correlation between HGB levels and BMDs and fracture risk. In older men, HGB level was an independent determinant of BMD and was positively correlated with FN and TH BMD. In non-older women, HGB level was an independent determinant of BMD and fracture risk, positively associated with BMDs and negatively associated with 10-year probability of fracture risk. GAMs revealed a positive linear association between HGB level and BMDs in non-older female patients but not in older male patients. Conclusion: Our study provides a new perspective on the association of HGB level and BMDs with fracture risk. Relatively high HGB levels are a protective factor for bone quality in patients with T2DM. However, the bone-protective effect of HGB is influenced by age and sex and persists only in older men and non-older women with T2DM.