Can low-dose intravenous bevacizumab be as effective as high-dose bevacizumab for cerebral radiation necrosis?

Although intravenous bevacizumab (IVBEV) is the most promising treatment for cerebral radiation necrosis (CRN), there is no conclusion on the optimal dosage. Our retrospective study aimed to compare the efficacy and safety of high-dose with low-dose IVBEV in treating CRN associated with radiotherapy for brain metastases (BMs). This paper describes 75 patients who were diagnosed with CRN secondary to radiotherapy for BMs, treated with low-dose or high-dose IVBEV and followed up for a minimum of 6 months. The clinical data collected for this study include changes in brain MRI, clinical symptoms, and corticosteroid usage before, during, and after IVBEV treatment. At the 3-month mark following administration of IVBEV, a comparison of two groups revealed that the median percentage decreases in CRN volume on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium contrast-enhanced image (T1CE), as well as the signal ratio reduction on T1CE, were 65.8% versus 64.8% (p = 0.860), 41.2% versus 51.9% (p = 0.396), and 37.4% versus 35.1% (p = 0.271), respectively. Similarly, at 6 months post-IVBEV, the median percentage reductions of the aforementioned parameters were 59.5% versus 62.0% (p = 0.757), 39.1% versus 31.3% (p = 0.851), and 35.4% versus 28.2% (p = 0.083), respectively. Notably, the incidence of grade ≥3 adverse events was higher in the high-dose group (n = 4, 9.8%) than in the low-dose group (n = 0). Among patients with CRN secondary to radiotherapy for BMs, the administration of high-dose IVBEV did not demonstrate superiority over low-dose IVBEV. Moreover, the use of high-dose IVBEV was associated with a higher incidence of grade ≥3 adverse events compared with low-dose IVBEV.

Aberrant functional connectivity of the globus pallidus in the modulation of the relationship between childhood trauma and major depressive disorder.

BACKGROUND: Childhood trauma plays a crucial role in the dysfunctional reward circuitry in major depressive disorder (MDD). We sought to explore the effect of abnormalities in the globus pallidus (GP)-centric reward circuitry on the relationship between childhood trauma and MDD. METHODS: We conducted seed-based dynamic functional connectivity (dFC) analysis among people with or without MDD and with or without childhood trauma. We explored the relationship between abnormal reward circuitry, childhood trauma, and MDD. RESULTS: We included 48 people with MDD and childhood trauma, 30 people with MDD without childhood trauma, 57 controls with childhood trauma, and 46 controls without childhood trauma. We found that GP subregions exhibited abnormal dFC with several regions, including the inferior parietal lobe, thalamus, superior frontal gyrus (SFG), and precuneus. Abnormal dFC in these GP subregions showed a significant correlation with childhood trauma. Moderation analysis revealed that the dFC between the anterior GP and SFG, as well as between the anterior GP and the precentral gyrus, modulated the relationship between childhood abuse and MDD severity. We observed a negative correlation between childhood trauma and MDD severity among patients with lower dFC between the anterior GP and SFG, as well as higher dFC between the anterior GP and precentral gyrus. This suggests that reduced dFC between the anterior GP and SFG, along with increased dFC between the anterior GP and precentral gyrus, may attenuate the effect of childhood trauma on MDD severity. LIMITATIONS: Cross-sectional designs cannot be used to infer causality. CONCLUSION: Our findings underscore the pivotal role of reward circuitry abnormalities in MDD with childhood trauma. These abnormalities involve various brain regions, including the postcentral gyrus, precentral gyrus, inferior parietal lobe, precuneus, superior frontal gyrus, thalamus, and middle frontal gyrus. CLINICAL TRIAL REGISTRATION: ChiCTR2300078193.

Expression and Function of VEGFRs in Normal Epidermis and Psoriatic Lesional Keratinocytes.

The study aimed to explore the expression and function of VEGFRs in normal epidermis and keratinocytes of psoriatic lesions. In this study, the expression and role of VEGFRs in keratinocytes were examined using examples from psoriatic and healthy individuals. The experiment was completed by immunofluorescence analysis, reverse transcription polymerase chain reaction, Western blot, and real-time quantitative RT-PCR after the skin of nonlesional, adjacent, and lesional skin was excised. Observations indicated that in non-lesional psoriatic areas and adjacent lesional areas of the skin of psoriasis patients, the fluorescent signals of VEGFR-1 and VEGFR-2 were strongly labelled with keratinocytes, and in psoriatic lesions, keratinocytes were present throughout the entire thickness of the epidermis, with the exception of the stratum corneum. The distribution of VEGFR-3 in psoriatic nonlesional and adjacent lesional skin was consistent with that in normal epidermis, whereas all layers of the epidermis of psoriatic lesions expressed VEGFR-3. The mRNA expression levels of VEGFR-1,2,3 steadily increased from the normal epidermis to the psoriatic nonlesional, adjacent lesional, and perilesional areas, with the lesional epidermis' keratinocytes exhibiting the greatest levels of mRNA expression. Ca ions upregulate VEGFR-1,2,3 mRNA and protein expression in keratinocytes of nonlesional areas of psoriasis. VEGFRs protein expression and cortical IOD values of psoriatic and normal population cells showed a positive correlation. Hence, in comparison to normal epidermal keratinocytes, psoriatic lesional regions' keratinocytes considerably enhanced their expression of VEGFR-1,2,3 mRNA and protein. The overexpression of VEGFR-1,2,3 in psoriatic lesions may be encouraged by VEGF and Ca þ ions.

Keyhole morphology monitoring of laser welding based on image processing and principal component analysis.

The keyhole is a specific phenomenon produced by the intense interaction between laser and material. Keyhole morphology can reflect welding stability and welding quality to a certain extent. Nowadays, the keyhole is observed and image processed by a high-speed camera and related algorithms, respectively. However, the binarization threshold is fixed in keyhole extraction, and conventional binarization methods are not adaptive. This will affect the feature extraction of keyhole morphology. In this paper, a dynamic threshold adjustment method is proposed, which can combine the quick positioning of the Otsu method and the weight balance of the average method. Furthermore, seven defined features of the keyhole region are divided into dynamic parameters and shape parameters. The dimension of these parameters is reduced by principal component analysis (PCA). The first three PCs occupy more than 92%, which covers most of the keyhole information. At last, the influence of dynamic parameters and shape parameters on keyhole morphology is presented. This research plays a positive role in monitoring the keyhole morphology of laser welding.

Bipolar Electrochemical Anodization Route for the Fabrication of Porous Anodic Alumina with Nanopore Gradients.

Porous anodic alumina (PAA) films with homogeneous nanopores are achieved by traditional anodization. Here, we present a unique anodization technique based on bipolar electrochemistry to fabricate PAA films with nanopore gradients. In an oxalic acid solution dissolved in ethylene glycol, a stable bipolar anodization process is realized. The PAA film prepared at 280 V exhibits a continuous change in interpore distance from ∼171 to ∼83 nm over a range of only 5 mm on the aluminum sheet. Higher driving voltages lead to larger interpore distances and steeper nanopore gradients. Further, no direct electrical connection is required for this bipolar anodization.

Development of a gRNA-tRNA array of CRISPR/Cas9 in combination with grafting technique to improve gene-editing efficiency of sweet orange.

KEY MESSAGE: Here, we developed a reliable protocol for the fast and efficient gene-edited Anliu sweet orange plants production. The application of in vitro shoot grafting technology significantly reduced the growth cycle of transgenic seedlings, and the survival rate of cleft grafting was more than 90%. In addition, the mutation efficiency of the grafted geneedited sweet orange was significantly improved by short-term heat stress treatments. Thus, the combination strategy of grafting and heat stress treatments provided a reference for the fast and efficient multiplex gene editing of sweet orange.

[The Reliability and Validity of the Chinese Version of the Experienced Level of Existential Emptiness].

BACKGROUND: Psychiatric patients are affected by diseases and mental symptoms that may worsen their ability to adjust emotionally. Being unable to respond to the emptiness, increases the risk of suicidal behaviors. PURPOSE: This study was designed to translate the Experienced Level of Existential Emptiness (ELEE) scale, developed by Hazell in 1984, from the original English into Chinese and then to test its reliability and validity. METHODS: This research adopted a cross-sectional design and collected data using convenience sampling and a structured questionnaire. The subjects of this study were psychiatric outpatients in the acute and chronic wards of a psychiatric hospital in Taiwan. The instruments used in this research included a demographic datasheet; the ELEE; the University of California, Los Angeles Loneliness Scale, version 3; the Beck Depression Inventory-II; the State-Trait Anxiety Inventory Y form; and the Oxford Happiness Inventory. After the data were obtained, the reliability and validity of the Chinese-version scale was tested. RESULTS: Three hundred subjects were surveyed. The content validity index value of the ELEE was between .88 and 1, and the retest reliability and intrinsic consistency were good. From the analysis of criterion-related validity, a higher degree of emptiness was shown to correlate with more-obvious feelings of loneliness, depression, and anxiety. Conversely, a higher sense of happiness was shown to correlate with less-obvious feelings of these three variables. After the construct validity test, which used confirmatory factor analysis and regarded the co-variation coefficient of association and model fit index as the basis of consideration, the scale was reduced to two sub-scales of seven questions each. After the deletion of items, the scale retained good retest reliability and intrinsic consistency, supporting the retention of the 14 questions in the scale. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The findings of this study support using the Chinese version of the ELEE to measure emptiness in patients with mental illness and then providing appropriate medical assistance based on the measured results.

The Glaesserella parasuis phosphoglucomutase is partially required for lipooligosaccharide synthesis.

Lipooligosaccharides (LOSs) are virulence determinants of Glaesserella parasuis, a pathogen of the respiratory tract of pigs. We previously reported that disruption of the galU or galE gene in G. parasuis results in increased sensitivity to porcine serum, indicating that the galactose catabolism pathway is required for polysaccharide formation in G. parasuis. Here, we evaluated the role of the HAPS_0849 gene in LOS synthesis. The G. parasuis SC096 HAPS_0849 mutant produced a highly truncated LOS molecule, although a small fraction of intact LOS was still observed, and this mutant was found to be more sensitive to serum than the parental strain. HAPS_0849 was overexpressed and purified for biochemical assays, and this protein exhibited phosphoglucomutase (PGM) activity. Heterologous expression of a pgm gene from Escherichia coli in the HAPS_0849 mutant led to restoration of the wild-type LOS glycoform, further demonstrating the PGM function of HAPS_0849 in G. parasuis. The autoagglutination and biofilm formation ability of this strain were also investigated. Disruption of HAPS_0849 led to an increased tendency to autoagglutinate and form more biofilms, and these enhanced phenotypes were observed in the absence of glucose. In addition, LOSs from HAPS_0849, galU and lgtB mutants had similar truncated glycoforms, while LOSs from the galE and lex-1 mutants exhibited another type of defective LOS pattern. These findings imply that HAPS_0849 may function upstream of GalU in the generation of glucose 1-phosphate. In conclusion, our results preliminarily described the functions of HAPS_0849 in G. parasuis, and this gene was partially required for LOS synthesis.

[Nursing Experience With Reconstructing Self-Control Using Rational-Emotive Behavior Therapy on a Patient With Schizophrenia and Obsessive-Compulsive Symptoms].

This case report describes a nursing experience caring for a patient with schizophrenia and obsessive-compulsive symptoms. This patient suffered from symptoms of being controlled, obsessive thoughts, and compulsive behaviors. In addition, the patient showed no interest in implementing strategies for dealing with anxiety, no motivation for changing this suffering, and an inability to receive a higher level of rehabilitative job training in daycare. These problems impeded this patient's reintegration into the community. Therefore, the authors employed a five-dimension assessment (physical, emotional, cognitive, social, and spiritual) in order to address the two major nursing problems. The period of nursing care was from October 21, 2016 to January 10, 2017. The two nursing problems addressed included: 1) altered thought processes and 2) ineffective coping. The author provided potentially helpful nursing processes based on the theory of Rational-Emotive Behavior Therapy in order to help the patient cope with symptoms, including being controlled and obsessive-compulsive behaviors. Meanwhile, a relaxation technique was applied to reduce the patient's feelings of discomfort during the nursing processes. As a result, the patient's coping skills to deal with symptoms of being controlled, obsession, and compulsion were improved through refutation of irrational beliefs. In addition to showing rational emotions and appropriate behavior to handle pressures, the patient was also able to apply the relaxation technique to relieve the discomfort from anxiety and pain as needed. This case report suggests that nurses may implement the irrational beliefs refutation training regimen under Rational-Emotive Behavior Therapy for similar cases at the beginning of nursing-patients relationships. Furthermore, providing relaxation techniques in the nursing process may assist patients to deal with stressful life events. The results of this nursing experience are expected to help nursing colleagues apply the above theory and skills with schizophrenia patients with obsessive-compulsive symptoms.

Next-generation sequencing identifies rare variants associated with Noonan syndrome.

Noonan syndrome (NS) is a relatively common genetic disorder, characterized by typical facies, short stature, developmental delay, and cardiac abnormalities. Known causative genes account for 70-80% of clinically diagnosed NS patients, but the genetic basis for the remaining 20-30% of cases is unknown. We performed next-generation sequencing on germ-line DNA from 27 NS patients lacking a mutation in the known NS genes. We identified gain-of-function alleles in Ras-like without CAAX 1 (RIT1) and mitogen-activated protein kinase kinase 1 (MAP2K1) and previously unseen loss-of-function variants in RAS p21 protein activator 2 (RASA2) that are likely to cause NS in these patients. Expression of the mutant RASA2, MAP2K1, or RIT1 alleles in heterologous cells increased RAS-ERK pathway activation, supporting a causative role in NS pathogenesis. Two patients had more than one disease-associated variant. Moreover, the diagnosis of an individual initially thought to have NS was revised to neurofibromatosis type 1 based on an NF1 nonsense mutation detected in this patient. Another patient harbored a missense mutation in NF1 that resulted in decreased protein stability and impaired ability to suppress RAS-ERK activation; however, this patient continues to exhibit a NS-like phenotype. In addition, a nonsense mutation in RPS6KA3 was found in one patient initially diagnosed with NS whose diagnosis was later revised to Coffin-Lowry syndrome. Finally, we identified other potential candidates for new NS genes, as well as potential carrier alleles for unrelated syndromes. Taken together, our data suggest that next-generation sequencing can provide a useful adjunct to RASopathy diagnosis and emphasize that the standard clinical categories for RASopathies might not be adequate to describe all patients.

Transcriptomic analysis of differentially expressed genes in an orange-pericarp mutant and wild type in pummelo (Citrus grandis).

BACKGROUND: The external colour of fruit is a crucial quality feature, and the external coloration of most citrus fruits is due to the accumulation of carotenoids. The molecular regulation of carotenoid biosynthesis and accumulation in pericarp is limited due to the lack of mutant. In this work, an orange-pericarp mutant (MT) which showed altered pigmentation in the pericarp was used to identify genes potentially related to the regulation of carotenoid accumulation in the pericarp. RESULTS: High Performance Liquid Chromatography (HPLC) analysis revealed that the pericarp from MT fruits had a 10.5-fold increase of ß-carotene content over that of the Wild Type (WT). Quantitative real-time PCR (qRT-PCR) analysis showed that the expression of all downstream carotenogenic genes was lower in MT than in WT, suggesting that down-regulation is critical for the ß-carotene increase in the MT pericarp. RNA-seq analysis of the transcriptome revealed extensive changes in the MT gene expression level, with 168 genes down-regulated and 135 genes up-regulated. Gene ontology (GO) and KEGG pathway analyses indicated seven reliable metabolic pathways are altered in the mutant, including carbon metabolism, starch and sucrose metabolism and biosynthesis of amino acids. The transcription factors and genes corresponding to effected metabolic pathways may involved in the carotenoid regulation was confirmed by the qRT-PCR analysis in the MT pericarp. CONCLUSIONS: This study has provided a global picture of the gene expression changes in a novel mutant with distinct color in the fruit pericarp of pummelo. Interpretation of differentially expressed genes (DEGs) revealed new insight into the molecular regulation of ß-carotene accumulation in the MT pericarp.

Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning.

Background: There is a significant imbalance of mitochondrial activity and oxidative stress (OS) status in patients with atopic dermatitis (AD). This study aims to screen skin and peripheral mitochondria-related biomarkers, providing insights into the underlying mechanisms of mitochondrial dysfunction in AD. Methods: Public data were obtained from MitoCarta 3.0 and GEO database. We screened mitochondria-related differentially expressed genes (MitoDEGs) using R language and then performed GO and KEGG pathway analysis on MitoDEGs. PPI and machine learning algorithms were also used to select hub MitoDEGs. Meanwhile, the expression of hub MitoDEGs in clinical samples were verified. Using ROC curve analysis, the diagnostic performance of risk model constructed from these hub MitoDEGs was evaluated in the training and validation sets. Further computer-aided algorithm analyses included gene set enrichment analysis (GSEA), immune infiltration and mitochondrial metabolism, centered on these hub MitoDEGs. We also used real-time PCR and Spearman method to evaluate the relationship between plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels and disease severity in AD patients. Results: MitoDEGs in AD were significantly enriched in pathways involved in mitochondrial respiration, mitochondrial metabolism, and mitochondrial membrane transport. Four hub genes (BAX, IDH3A, MRPS6, and GPT2) were selected to take part in the creation of a novel mitochondrial-based risk model for AD prediction. The risk score demonstrated excellent diagnostic performance in both the training cohort (AUC = 1.000) and the validation cohort (AUC = 0.810). Four hub MitoDEGs were also clearly associated with the innate immune cells' infiltration and the molecular modifications of mitochondrial hypermetabolism in AD. We further discovered that AD patients had considerably greater plasma ccf-mtDNA levels than controls (U = 92.0, p< 0.001). Besides, there was a significant relationship between the up-regulation of plasma mtDNA and the severity of AD symptoms. Conclusions: The study highlights BAX, IDH3A, MRPS6 and GPT2 as crucial MitoDEGs and demonstrates their efficiency in identifying AD. Moderate to severe AD is associated with increased markers of mitochondrial damage and cellular stress (ccf=mtDNA). Our study provides data support for the variation in mitochondria-related functional characteristics of AD patients.

Sono-assembly of ellagic acid into nanostructures significantly enhances aqueous solubility and bioavailability.

INTRODUCTION: Ellagic acid (EA), commonly found in foods, offers significant health benefits in combating chronic diseases. However, its therapeutic potential is hindered by its extremely poor solubility and bioavailability. METHOD: In this study, EA nanoparticles (EA NPs) were produced using a sono-assembly method, without additional agents. RESULTS: EA NPs exhibited stick-like nanoparticle structures with an average size of 147.3 ± 0.73 nm. EA NPs likely adopt a tunnel-type solvate structure, with 4 water participating in disruption of intramolecular hydrogen bonds in EA and establishment of intermolecular hydrogen bonds between EAs. Importantly, EA NPs exhibited remarkable enhancements in water solubility, with 120.7-fold increase in water, and 97.8-fold increase in pH 6.8 buffer. Moreover, ex vivo intestinal permeability studies demonstrated significant improvements (P < 0.5). These findings were further supported by in vivo pharmacokinetic studies, where EA NPs significantly enhanced the relative bioavailability of EA by 4.69 times.

Current Application of Advancing Spectroscopy Techniques in Food Analysis: Data Handling with Chemometric Approaches.

In today's era of increased food consumption, consumers have become more demanding in terms of safety and the quality of products they consume. As a result, food authorities are closely monitoring the food industry to ensure that products meet the required standards of quality. The analysis of food properties encompasses various aspects, including chemical and physical descriptions, sensory assessments, authenticity, traceability, processing, crop production, storage conditions, and microbial and contaminant levels. Traditionally, the analysis of food properties has relied on conventional analytical techniques. However, these methods often involve destructive processes, which are laborious, time-consuming, expensive, and environmentally harmful. In contrast, advanced spectroscopic techniques offer a promising alternative. Spectroscopic methods such as hyperspectral and multispectral imaging, NMR, Raman, IR, UV, visible, fluorescence, and X-ray-based methods provide rapid, non-destructive, cost-effective, and environmentally friendly means of food analysis. Nevertheless, interpreting spectroscopy data, whether in the form of signals (fingerprints) or images, can be complex without the assistance of statistical and innovative chemometric approaches. These approaches involve various steps such as pre-processing, exploratory analysis, variable selection, regression, classification, and data integration. They are essential for extracting relevant information and effectively handling the complexity of spectroscopic data. This review aims to address, discuss, and examine recent studies on advanced spectroscopic techniques and chemometric tools in the context of food product applications and analysis trends. Furthermore, it focuses on the practical aspects of spectral data handling, model construction, data interpretation, and the general utilization of statistical and chemometric methods for both qualitative and quantitative analysis. By exploring the advancements in spectroscopic techniques and their integration with chemometric tools, this review provides valuable insights into the potential applications and future directions of these analytical approaches in the food industry. It emphasizes the importance of efficient data handling, model development, and practical implementation of statistical and chemometric methods in the field of food analysis.

Biomimetic Flexible Sensors and Their Applications in Human Health Detection.

Bionic flexible sensors are a new type of biosensor with high sensitivity, selectivity, stability, and reliability to achieve detection in complex natural and physiological environments. They provide efficient, energy-saving and convenient applications in medical monitoring and diagnosis, environmental monitoring, and detection and identification. Combining sensor devices with flexible substrates to imitate flexible structures in living organisms, thus enabling the detection of various physiological signals, has become a hot topic of interest. In the field of human health detection, the application of bionic flexible sensors is flourishing and will evolve into patient-centric diagnosis and treatment in the future of healthcare. In this review, we provide an up-to-date overview of bionic flexible devices for human health detection applications and a comprehensive summary of the research progress and potential of flexible sensors. First, we evaluate the working mechanisms of different classes of bionic flexible sensors, describing the selection and fabrication of bionic flexible materials and their excellent electrochemical properties; then, we introduce some interesting applications for monitoring physical, electrophysiological, chemical, and biological signals according to more segmented health fields (e.g., medical diagnosis, rehabilitation assistance, and sports monitoring). We conclude with a summary of the advantages of current results and the challenges and possible future developments.

PARASIAS: A new method for analyzing higher-order tensors with shifting profiles.

Higher-order tensor data analysis has been extensively employed to understand complicated data, such as multi-way GC-MS data in untargeted/targeted analysis. However, the analysis can be complicated when one of the modes shifts e.g., the elution profiles of specific compounds often with respect to retention time; something which violates the assumptions of more traditional models. In this paper, we introduce a new analysis method named PARASIAS for analyzing shifted higher-order tensor data by combining spectral transformation and the simple PARAFAC modeling. The proposed method is validated by applications on both simulated and real multi-way datasets. Compared to the state-of-art PARAFAC2 model, the results indicate that fitting of PARASIAS is 13 times faster on simulated datasets and more than eight times faster on average on the real datasets studied. PARASIAS has significant advantages in terms of model simplicity, convergence speed, the robustness to shift changes in the data, the ability to impose non-negativity constraint on the shift mode and the possibility of easily extending to data with multiple shift modes. However, the resolved profiles of PARASIAS model are always a little worse when the number of components in the data are larger than three and without using additional factors in PARASIAS model. In such cases, more components are necessary for PARASIAS to model the data than that would be needed e.g., by PARAFAC2. The reason for this is also discussed in this work.

Tensor methods in data analysis of chromatography/mass spectroscopy-based plant metabolomics.

Plant metabolomics is an important research area in plant science. Chemometrics is a useful tool for plant metabolomic data analysis and processing. Among them, high-order chemometrics represented by tensor modeling provides a new and promising technical method for the analysis of complex multi-way plant metabolomics data. This paper systematically reviews different tensor methods widely applied to the analysis of complex plant metabolomic data. The advantages and disadvantages as well as the latest methodological advances of tensor models are reviewed and summarized. At the same time, application of different tensor methods in solving plant science problems are also reviewed and discussed. The reviewed applications of tensor methods in plant metabolomics cover a wide range of important plant science topics including plant gene mutation and phenotype, plant disease and resistance, plant pharmacology and nutrition analysis, and plant products ingredient characterization and quality evaluation. It is evident from the review that tensor methods significantly promote the automated and intelligent process of plant metabolomics analysis and profoundly affect the paradigm of plant science research. To the best of our knowledge, this is the first review to systematically summarize the tensor analysis methods in plant metabolomic data analysis.

Cortical thickness and curvature abnormalities in patients with major depressive disorder with childhood maltreatment: Neural markers of vulnerability?

BACKGROUND: Childhood maltreatment has been related to various disadvantageous lifetime outcomes. However, the brain structural alterations that occur in major depressive disorder (MDD) patients with childhood maltreatment are incompletely investigated. METHODS: We extensively explored the cortical abnormalities including cortical volume, surface area, thickness, sulcal depth, and curvature in maltreated MDD patients. Twoway ANOVA was performed to distinguish the effects of childhood maltreatment and depression on structural abnormalities. Partial correlation analysis was performed to explore the relationship between childhood maltreatment and cortical abnormalities. Moreover, we plotted the receiver operating characteristic curve to examine whether the observed cortical abnormalities could be used as neuro biomarkers to identify maltreated MDD patients. RESULTS: We reach the following findings: (i) relative to MDD without childhood maltreatment, MDD patients with childhood maltreatment existed increased cortical curvature in inferior frontal gyrus; (ii) compared to HC without childhood maltreatment, decreased cortical thickness was observed in anterior cingulate cortex and medial prefrontal cortex in MDD patients with childhood maltreatment; (iii) we confirmed the inseparable relationship between cortical curvature alterations in inferior frontal gyrus as well as childhood maltreatment; (iv) cortical curvature abnormality in inferior frontal gyrus could be applied as neural biomarker for clinical identification of MDD patients with childhood maltreatment. CONCLUSIONS: Childhood maltreatment have a significant effects on cortical thickness and curvature abnormalities involved in inferior frontal gyrus, anterior cingulate cortex and medial prefrontal cortex, constituting the vulnerability to depression.

Whole-Exome Sequencing Identified Rare Genetic Variants Associated with Undervirilized Genitalia in Taiwanese Pediatric Patients.

Disorders/differences of sex development (DSDs) are a group of rare and phenotypically variable diseases. The underlying genetic causes of most cases of 46XY DSDs remains unknown. Despite the advent of genetic testing, current investigations of the causes of DSDs allow genetic-mechanism identification in about 20-35% of cases. This study aimed primarily to establish a rapid and high-throughput genetic test for undervirilized males with and without additional dysmorphic features. Routine chromosomal and endocrinological investigations were performed as part of DSD evaluation. We applied whole-exome sequencing (WES) complemented with multiplex ligation-dependent probe amplification to seek explainable genetic causes. Integrated computing programs were used to call and predict the functions of genetic variants. We recruited 20 patients and identified the genetic etiologies for 14 (70%) patients. A total of seven of the patients who presented isolated DSD phenotypes were found to have causative variants in the AR, MAP3K1, and FLNA genes. Moreover, the other seven patients presented additional phenotypes beyond undervirilized genitalia. Among them, two patients were compatible with CHARGE syndrome, one with Robinow syndrome, and another three with hypogonadotropic hypogonadism. One patient, who carried a heterozygous FLNA mutation, also harbored a heterozygous PTPN11 mutation and thus presented some phenotypes of Noonan syndrome. We identified several genetic variants (12 nonsense mutations and one microdeletion) that account for syndromic and nonsyndromic DSDs in the Taiwanese population. The identification of these causative genes extended our current understanding of sex development and related congenital disorders.

Porous Structural Microfluidic Device for Biomedical Diagnosis: A Review.

Microfluidics has recently received more and more attention in applications such as biomedical, chemical and medicine. With the development of microelectronics technology as well as material science in recent years, microfluidic devices have made great progress. Porous structures as a discontinuous medium in which the special flow phenomena of fluids lead to their potential and special applications in microfluidics offer a unique way to develop completely new microfluidic chips. In this article, we firstly introduce the fabrication methods for porous structures of different materials. Then, the physical effects of microfluid flow in porous media and their related physical models are discussed. Finally, the state-of-the-art porous microfluidic chips and their applications in biomedicine are summarized, and we present the current problems and future directions in this field.