Active immunization with recombinant GnRH6-CRM197 inhibits reproductive function of male rats.

Gonadotropin-releasing hormone (GnRH) vaccines have been successfully used for the inhibition of gonadal development and function, but current GnRH-based vaccines often present variability in the response. Cross-reactive material 197 (CRM197) has been used as carrier molecules to enhance an immune response to associated antigens. So, the synthetic mammalian tandem-repeated GnRH hexamer (GnRH6) gene was integrated into the expression plasmid pET-21a. Recombinant GnRH6-CRM197 protein was subsequently overexpressed in Escherichia coli strain BL21 and purified through Nickel column affinity chromatography and the antigenicity and biological effects of GnRH6-CRM197 were evaluated in rats. Sixteen 4-month-old adult male rats were randomly divided into two groups: the GnRH6-CRM197 group (n = 8) and the control group (n = 8). The GnRH6-CRM197 group rats were subcutaneously immunized with 100 µg of GnRH6-CRM197, administered thrice at 2-week intervals with GnRH6-CRM197.The control group received only a white oil adjuvant. Following the initial immunization, the weights of animals were recorded, and blood samples were collected from the orbital sinus at 4, 4.5, 5, 5.5, 6, 6.5, and 7 months. Serum antibody titers and testosterone concentrations were quantified using ELISA and CLIA, respectively. Additionally, testicular tissues were collected for morphological examination. The results revealed a significant increase in serum GnRH antibody titers (p < 0.05), but a significant decrease in serum testosterone concentrations (p < 0.05), and the weight, length, width, and girth of the testis, and the number of spermatogonia cells, spermatocytes, and sperm cells in the immunized rats. Furthermore, seminiferous tubules revealed significant atrophy and no sperm were observed in the immunized animals. Thus, GnRH6-CRM197 may be an effective antigen and a potential immunocastration vaccine.

Regulation of mesenchymal stem cell differentiation by autophagy.

Autophagy, a process that isolates intracellular components and fuses them with lysosomes for degradation, plays an important cytoprotective role by eliminating harmful intracellular substances and maintaining cellular homeostasis. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity for self-renewal that can give rise to a subset of tissues and therefore have potential in regenerative medicine. However, a variety of variables influence the biological activity of MSCs following their proliferation and transplantation in vitro. The regulation of autophagy in MSCs represents a possible mechanism that influences MSC differentiation properties under the right microenvironment, affecting their regenerative and therapeutic potential. However, a deeper understanding of exactly how autophagy is mobilized to function as well as clarifying the mechanisms by which autophagy promotes MSCs differentiation is still needed. Here, we review the current literature on the complex link between MSCs differentiation and autophagy induced by various extracellular or intracellular stimuli and the molecular targets that influence MSCs lineage determination, which may highlight the potential regulation of autophagy on MSCs' therapeutic capacity, and provide a broader perspective on the clinical application of MSCs in the treatment of a wide range of diseases.

Integrative proteomic and transcriptomic analysis in the female goat ovary to explore the onset of puberty.

Puberty is considered a prerequisite for affecting reproductive performance and productivity. Little was known about molecular changes in pubertal goat ovaries. Therefore, we measured and performed a correlation analysis of the mRNA and proteins changes in the pre-pubertal and pubertal goat ovaries. The results showed that only six differentially expressed genes and differentially abundant proteins out of 18,139 genes and 7550 proteins quantified had significant correlations. CNTN2 and THBS1, discovered in the mRNA-mRNA interaction network, probably participated in pubertal and reproductive regulation by influencing GnRH receptor signals, follicular development, and ovulation. The predicted core transcription factors may either promote or inhibit the expression of reproductive genes and act synergistically to maintain normal reproductive function in animals. The interaction between PKM and TIMP3 with other proteins may impact animal puberty through energy metabolism and ovarian hormone secretion. Pathway enrichment analyses revealed that the co-associated key pathways between ovarian genes and proteins at puberty included calcium signalling pathway and olfactory transduction. These pathways were associated with gonadotropin-releasing hormone synthesis and secretion, signal transmission, and cell proliferation. In summary, these results enriched the potential molecules and signalling pathways that affect puberty and provided new insights for regulating and promoting the onset of puberty. SIGNIFICANCE: This study conducted the first transcriptomic and proteomic correlation analysis of pre-pubertal and pubertal goat ovaries and identified six significantly correlated molecules at both the gene and protein levels. Meanwhile, we were drawn to several molecules and signalling pathways that may play a regulatory role in the onset of puberty and reproduction by influencing reproductive-related gene expression, GnRH receptor signals, energy metabolism, ovarian hormone secretion, follicular development, and ovulation. This information contributed to identify potential biomarkers in pubertal goat ovaries, which was vital for predicting the onset of puberty and improving livestock performance.

Grid1 regulates the onset of puberty in female rats.

The study aimed to investigate the effect of Grid1, encoding the glutamate ionotropic receptor delta type subunit 1 (GluD1), on puberty onset in female rats. Grid1 mRNA and protein expression was detected in the hypothalamus of female rats at prepuberty and puberty. The levels of Grid1 mRNA in the hypothalamus, the fluorescence intensity in the arcuate nucleus and paraventricular nucleus of the prepubertal rats was significantly lower than pubertal. Additionally, the expression of Grid1 was suppressed in primary hypothalamus cells and prepubertal rat. Finally, investigated the effect of Grid1 knockdown on puberty onset and reproductive performance. Treatment of hypothalamic neurons with LV-Grid1 decreased the level of Grid1 and Rfrp-3 (encoding RFamide-related peptide 3) mRNA expression, but increased the Gnrh (encoding gonadotropin-releasing hormone) mRNA levels. After an ICV injection, the time for the rat vaginal opening occurred earlier. Moreover, Gnrh mRNA expression was increased, whereas Rfrp-3 mRNA expression was decreased in the hypothalamus. The concentration of progesterone (P4) in the serum was significantly decreased compare with control group. Ovary hematoxylin-eosin staining revealed that the LV-Grid1 group mainly contained primary and secondary follicles. The reproductive performance of the rats was not affected by the Grid1 knockdown. Therefore, Grid1 may affect the onset of puberty in female rats by regulating the levels of Gnrh, and Rfrp-3 in the hypothalamus, as well as the concentrations of P4, but not reproduction performance.

The application of mesenchymal stem cells in the treatment of traumatic brain injury: mechanisms, results, and problems.

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be derived from a wide variety of human tissues and organs. They can differentiate into a variety of cell types, including osteoblasts, adipocytes, and chondrocytes, and thus show great potential in regenerative medicine. Traumatic brain injury (TBI) is an organic injury to brain tissue with a high rate of disability and death caused by an external impact or concussive force acting directly or indirectly on the head. The current treatment of TBI mainly includes symptomatic, pharmacological, and rehabilitation treatment. Although some efficacy has been achieved, the definitive recovery effect on neural tissue is still limited. Recent studies have shown that MSC therapies are more effective than traditional treatment strategies due to their strong multi-directional differentiation potential, self-renewal capacity, and low immunogenicity and homing properties, thus MSCs are considered to play an important role and are an ideal cell for the treatment of injurious diseases, including TBI. In this paper, we systematically reviewed the role and mechanisms of MSCs and MSC-derived exosomes in the treatment of TBI, thereby providing new insights into the clinical applications of MSCs and MSC-derived exosomes in the treatment of central nervous system disorders.

Base-Assisted Polymerizations of Elemental Sulfur and Alkynones for Temperature-Controlled Synthesis of Polythiophenes or Poly(1,4-dithiin)s.

With the increasing demand for functional polythiophenes in extensive applications such as organic solar cells, electronic skins, thermoelectric materials, and field effect transistors, efficient and economic synthetic approaches for polythiophenes are urgently required. In this work, KOH-assisted polymerizations of elemental sulfur and alkynones were developed to directly afford polythiophenes with various backbones, regioselective structures, and high molecular weights (Mns up to 20700 g/mol) in high yields (up to 97%) at 80 °C in 30 min. When the same polymerization was conducted at room temperature, stable and unique poly(1,4-dithiin)s (Mns up to 21800 g/mol) could be rapidly obtained in high yields (up to 87%) in 10 min. The temperature-controlled KOH-assisted polymerizations of sulfur and alkynones possessed high efficiency, mild conditions, and simple operation, which had provided an economic, efficient, and convenient approach for the direct conversion from elemental sulfur to functional polythiophenes and poly(1,4-dithiin)s with the in situ constructed aromatic or nonaromatic heterocycles embedded in the polymer backbones, demonstrating great synthetic simplicity, high efficiency, good selectivity, and robustness. It is anticipated to accelerate the development of semiconducting polymer materials and their applications.

Integrative proteomic and phosphoproteomic analysis in the female goat hypothalamus to study the onset of puberty.

BACKGROUND: Puberty marks the end of childhood and achieve sexual maturation and fertility. The role of hypothalamic proteins in regulating puberty onset is unclear. We performed a comprehensive differential proteomics and phosphoproteomics analysis in prepubertal and pubertal goats to determine the roles of hypothalamic proteins and phosphoproteins during the onset of puberty. RESULTS: We used peptide and posttranslational modifications peptide quantification and statistical analyses, and identified 69 differentially expressed proteins from 5,057 proteins and 576 differentially expressed phosphopeptides from 1574 phosphorylated proteins. Combined proteomic and phosphoproteomics, 759 correlated proteins were identified, of which 5 were differentially expressed only at the protein level, and 201 were only differentially expressed at the phosphoprotein level. Pathway enrichment analyses revealed that the majority of correlated proteins were associated with glycolysis/gluconeogenesis, Fc gamma R-mediated phagocytosis, focal adhesion, GABAergic synapse, and Rap1 signaling pathway. These pathways are related to cell proliferation, neurocyte migration, and promoting the release of gonadotropin-releasing hormone in the hypothalamus. CTNNB1 occupied important locations in the protein-protein interaction network and is involved in focal adhesion. CONCLUSION: The results demonstrate that the proteins differentially expression only at the protein level or only differentially expressed at the phosphoprotein level and their related signalling pathways are crucial in regulating puberty in goats. These differentially expressed proteins and phosphorylated proteins may constitute the proteomic backgrounds between the two different stages.

BG2: Bayesian variable selection in generalized linear mixed models with nonlocal priors for non-Gaussian GWAS data.

BACKGROUND: Genome-wide association studies (GWASes) aim to identify single nucleotide polymorphisms (SNPs) associated with a given phenotype. A common approach for the analysis of GWAS is single marker analysis (SMA) based on linear mixed models (LMMs). However, LMM-based SMA usually yields a large number of false discoveries and cannot be directly applied to non-Gaussian phenotypes such as count data. RESULTS: We present a novel Bayesian method to find SNPs associated with non-Gaussian phenotypes. To that end, we use generalized linear mixed models (GLMMs) and, thus, call our method Bayesian GLMMs for GWAS (BG2). To deal with the high dimensionality of GWAS analysis, we propose novel nonlocal priors specifically tailored for GLMMs. In addition, we develop related fast approximate Bayesian computations. BG2 uses a two-step procedure: first, BG2 screens for candidate SNPs; second, BG2 performs model selection that considers all screened candidate SNPs as possible regressors. A simulation study shows favorable performance of BG2 when compared to GLMM-based SMA. We illustrate the usefulness and flexibility of BG2 with three case studies on cocaine dependence (binary data), alcohol consumption (count data), and number of root-like structures in a model plant (count data).

Altered Proteomic Profile of Exosomes Secreted from Vero Cells Infected with Porcine Epidemic Diarrhea Virus.

Porcine epidemic diarrhea virus (PEDV) infection causes severe diarrhea in pigs and can be fatal in newborn piglets. Exosomes are extracellular vesicles secreted by cells that transfer biologically active proteins, lipids, and RNA to neighboring or distant cells. Herein, the morphology, particle size, and secretion of exosomes derived from a control and PEDV-infected group are examined, followed by a proteomic analysis of the exosomes. The results show that the exosomes secreted from the Vero cells had a typical cup-shaped structure. The average particle size of the exosomes from the PEDV-infected group was 112.4 nm, whereas that from the control group was 150.8 nm. The exosome density analysis and characteristic protein determination revealed that the content of exosomes in the PEDV-infected group was significantly higher than that in the control group. The quantitative proteomics assays revealed 544 differentially expressed proteins (DEPs) in the PEDV-infected group's exosomes compared with those in the controls, with 236 upregulated and 308 downregulated proteins. The DEPs were closely associated with cellular regulatory pathways, such as the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, extracellular matrix-receptor interaction, focal adhesion, and cytoskeletal regulation. These findings provide the basis for further investigation of the pathogenic mechanisms of PEDV and the discovery of novel antiviral targets.

Evaluation on coupling coordinated development of population economy and eco-geological environment in the twin-city economic circle of Chengdu-Chongqing region.

Using the CRITIC method, comprehensive index evaluation method, VAR model, coupling coordination model and other methods, this paper evaluates the comprehensive development of the population economy and eco-geological environment composite system in the twin-city economic circle of Chengdu-Chongqing region from 2000 to 2020, verifies the dynamic coupling relationship between subsystems and measures the coupling coordination degree of complex system. Meanwhile, the differences in the development process of each subsystem are discussed and the spatial-temporal evolution characteristics and laws of coupling coordination of the composite system during the research period are analyzed. The results reveal the following: (1) There is a long-term coordinated relationship between population, economy and eco-geological environment in Chengdu-Chongqing region, which have the conditions for emergence and generation. (2) The subsystems of population, economy and eco-geological environment in Chengdu-Chongqing region show an overall upward trend, among which the Sichuan part obviously outperforms the Chongqing part. Besides, the growth rate of the economy subsystem is significantly higher than that of the population, eco-geological environment subsystem. (3) The coupling coordinated development of the composite system has shown a benign upward development trend, gradually changing from "composite spiral structure" to "two cores outstanding, peripheral collapse, the west superior to the east", while the main coordination state has developed from "Basic synergy-Economic lag" in 2000 to "Basic synergy-Population lag" in 2022. In addition, Cheng-De-Mian and Yuzhong districts with the better level of economic development have shown "Advanced synergy-Ecological lag".

Comparison of CT-guided thoracic sympathetic nerve block and radiofrequency in the treatment of primary palmar hyperhidrosis.

Background: Primary palmar hyperhidrosis (PPH) is a condition marked by an overactive secretion of the hand's exocrine glands and is frequently hereditary. The profuse sweating associated with this condition can significantly impair the patient's daily activities and quality of life. Objective: The objective of this study was to compared the benefits and drawbacks of thoracic sympathetic block and thoracic sympathetic radiofrequency in the treatment of PPH. Methods: A retrospective analysis was conducted on 69 patients. They were divided into groups A and B according to their treatment. Group A (34 cases) received CT-guided percutaneous thoracic sympathetic nerve chain anhydrous alcohol chemical damage block, and group B (35 cases) received CT-guided percutaneous thoracic sympathetic nerve chain radiofrequency thermocoagulation. Results: Palmar sweating disappeared immediately after the operation. The recurrence rates at 1, 3, 6, 12, 24, and 36 months were 5.88% vs. 2.86% (P > 0.05), 20.59% vs. 5.71% (P > 0.05), 32.35% vs. 11.43% (P < 0.05),32.35% vs. 11.43% (P < 0.05), 25% vs. 14.71% (P < 0.05), and 68.75% vs. 20.59% (P < 0.05), respectively. The incidence of intercostal neuralgia and compensatory hyperhidrosis was higher in group A compared with of group B (52.94% vs. 22.86%, P < 0.05; 55.88% vs. 22.86%, P < 0.05). Conclusion: Both methods were found to be effective in treating PPH, but thoracic sympathetic radiofrequency had a longer-term effect, a lower recurrence rate, and a lower incidence of intercostal neuralgia and compensatory hyperhidrosis than a thoracic sympathetic block.

A facile bioorthogonal chemistry-based reversible to irreversible strategy to surmount the dilemma between injectability and stability of hyaluronic acid hydrogels.

Injectable and stable hydrogels have great promise for clinical applications. Fine-tuning the injectability and the stability of the hydrogels at different stages has been challenging due to the limited number of coupling reactions. A distinct "reversible to irreversible" concept using a thiazolidine-based bioorthogonal reaction between 1,2-aminothiols and aldehydes in physiological conditions to surmount the dilemma between injectability and stability is presented for the first time. Upon mixing aqueous solutions of aldehyde-functionalized hyaluronic acid (SA-HA) and cysteine-capped ethylenediamine (DI-Cys), SA-HA/DI-Cys hydrogels formed through reversible hemithioacetal crosslinking within 2 min. The reversible kinetic intermediate facilitated thiol-triggered gel-to-sol transition, shear-thinning and injectability of the SA-HA/DI-Cys hydrogel but then converted to the irreversible thermodynamic network after injection, thereby permitting the resulting gel with improved stability. As compared to the Schiff base hydrogels, the hydrogels generated from this simple, yet effective concept awarded improved protection to the embedded mesenchymal stem cells and fibroblast during injection, retained the cells homogeneously within the gel, and allowed them further proliferation in vitro and in vivo. There is potential for the proposed approach of "reversible to irreversible" based on thiazolidine chemistry to be applied as a general coupling technique for developing injectable and stable hydrogels for biomedical applications.

Bayesian model selection for generalized linear mixed models.

We propose a Bayesian model selection approach for generalized linear mixed models (GLMMs). We consider covariance structures for the random effects that are widely used in areas such as longitudinal studies, genome-wide association studies, and spatial statistics. Since the random effects cannot be integrated out of GLMMs analytically, we approximate the integrated likelihood function using a pseudo-likelihood approach. Our Bayesian approach assumes a flat prior for the fixed effects and includes both approximate reference prior and half-Cauchy prior choices for the variances of random effects. Since the flat prior on the fixed effects is improper, we develop a fractional Bayes factor approach to obtain posterior probabilities of the several competing models. Simulation studies with Poisson GLMMs with spatial random effects and overdispersion random effects show that our approach performs favorably when compared to widely used competing Bayesian methods including deviance information criterion and Watanabe-Akaike information criterion. We illustrate the usefulness and flexibility of our approach with three case studies including a Poisson longitudinal model, a Poisson spatial model, and a logistic mixed model. Our proposed approach is implemented in the R package GLMMselect that is available on CRAN.

Knockdown of lncRNA Meg3 delays the onset of puberty in female rats.

This study investigated how lncRNA Meg3 affects the onset of puberty in female rats. We determined Meg3 expression in the hypothalamus-pituitary-ovary axis of female rats at the infancy, prepubertal, pubertal, and adult life stages, using quantitative reverse transcription polymerase chain reaction (qRT-PCR). We also assessed the effects of Meg3 knockdown on the expression levels of puberty-related genes and Wnt/ß-catenin proteins in the hypothalamus, time of puberty onset, levels of reproductive genes and hormones, and ovarian morphology in female rats. Meg3 expression in the ovary varied significantly between prepuberty and puberty (P < 0.01). Meg3 knockdown decreased the expression of Gnrh, and Kiss1 mRNA (P < 0.05) and increased the expression of Wnt (P < 0.01) and ß-catenin proteins (P < 0.05) in the hypothalamic cells. Onset of puberty in Meg3 knockdown rats was delayed compared to the control group (P < 0.05). Meg3 knockdown decreased Gnrh mRNA levels (P < 0.05) and increased Rfrp-3 mRNA levels (P < 0.05) in the hypothalamus. The serum concentrations of progesterone (P4) and estradiol (E2) of Meg3 knockdown rats were lower than those in the control animals (P < 0.05). Higher longitudinal diameter and ovary weight were found in Meg3 knockdown rats (P < 0.05). These findings suggest that Meg3 regulates the expression of Gnrh, Kiss-1 mRNA and Wnt/ß-catenin proteins in the hypothalamic cells, and Gnrh, Rfrp-3 mRNA of the hypothalamus and the serum concentration of P4 and E2, and its knockdown delays the onset of puberty in female rats.

BGWAS: Bayesian variable selection in linear mixed models with nonlocal priors for genome-wide association studies.

BACKGROUND: Genome-wide association studies (GWAS) seek to identify single nucleotide polymorphisms (SNPs) that cause observed phenotypes. However, with highly correlated SNPs, correlated observations, and the number of SNPs being two orders of magnitude larger than the number of observations, GWAS procedures often suffer from high false positive rates. RESULTS: We propose BGWAS, a novel Bayesian variable selection method based on nonlocal priors for linear mixed models specifically tailored for genome-wide association studies. Our proposed method BGWAS uses a novel nonlocal prior for linear mixed models (LMMs). BGWAS has two steps: screening and model selection. The screening step scans through all the SNPs fitting one LMM for each SNP and then uses Bayesian false discovery control to select a set of candidate SNPs. After that, a model selection step searches through the space of LMMs that may have any number of SNPs from the candidate set. A simulation study shows that, when compared to popular GWAS procedures, BGWAS greatly reduces false positives while maintaining the same ability to detect true positive SNPs. We show the utility and flexibility of BGWAS with two case studies: a case study on salt stress in plants, and a case study on alcohol use disorder. CONCLUSIONS: BGWAS maintains and in some cases increases the recall of true SNPs while drastically lowering the number of false positives compared to popular SMA procedures.

The Role of BTBD7 in Normal Development and Tumor Progression.

BTB/POZ domain-containing protein 7 (BTBD7) has a relative molecular weight of 126KD and contains two conserved BTB/POZ protein sequences. BTBD7 has been shown to play an essential role in normal human development, precancerous lesions, heat-stress response, and tumor progression. BTBD7 promotes branching morphogenesis during development and participates in the salivary gland, lung, and tooth formation. Furthermore, many studies have shown that aberrant expression of BTBD7 promotes heat stress response and the progression of precancerous lesions. BTBD7 has also been found to play an important role in cancer. High expression of BTBD7 affects tumor progression by regulating multiple pathways. Therefore, a complete understanding of BTBD7 is crucial for exploring human development and tumor progression. This paper reviews the research progress of BTBD7, which lays a foundation for the application of BTBD7 in regenerative medicine and as a biomarker for tumor prediction or potential therapeutic target.

Construction of Urban Environmental Performance Evaluation System Based on Multivariate System Theory and Comparative Analysis: A Case Study of Chengdu-Chongqing Twin Cities, China.

Based on the related environmental data of Chengdu and Chongqing from 2011 to 2020, this paper constructs a multivariate environment performance evaluation system, combines the self-built indicator system determination criteria and rules, evaluates and compares the environmental performance of Chengdu and Chongqing, and also discusses the impact of COVID-19 on urban environmental performance. The research results show that the overall environmental performance increased from 2011 to 2020, but there are differences between different subsystems, mainly manifested in the best water environment performance, followed by air environment and solid waste; moreover, the noise environment maintains a relatively stable level. By comparing the average levels of various subsystems of the Chengdu-Chongqing dual cities from 2011 to 2020, it can be seen that Chengdu City has better environmental performance in air environment and solid waste, while Chongqing City has better environmental performance in the water environment and noise environment. In addition, this paper also found that the impact of the epidemic on urban environmental performance mainly comes from the impact on the air environment. At present, the overall environmental performance of the two places has shown a trend of environmentally coordinated development. In the future, Chengdu and Chongqing should further optimize and improve their relatively weak environmental subsystems, deepen the joint action mechanism between the two places, and build a green and high-quality development economic circle for the Chengdu-Chongqing twin cities.

An Analysis of BMP1 Associated with m6A Modification and Immune Infiltration in Pancancer.

Background: This research explores the underlying link between diagnosis and therapy between bone morphogenetic protein 1 (BMP1) and various cancers. Methods: Three immunotherapeutic cohorts, by the composition of IMvigor210, GSE35640, and GSE78220 were obtained from previously published articles and the Gene Expression Omnibus database. The different expressions of BMP1 in various clinical parameters were conducted, and prognostic analysis was executed utilizing Cox proportional hazard regression and Gene Expression Profiling Interactive Analysis. Moreover, the correlation between BMP1 and tumor microenvironment was analyzed using ESTIMATE and CIBERSORT algorithms. Tumor mutational burden and microsatellite instability were also included. The correlation between m6A modification and the gene expression level was analyzed using Tumor IMmune Estimation Resource, the University of Alabama at Birmingham Cancer data analysis portal. Gene Set Cancer Analysis analyzed the correlation of BMP1 expression level with copy number variations and methylation. Furthermore, the correlation between BMP1 and therapeutic response after antineoplastic drug use was illustrated for further discussion. Results: BMP1 expression had significant differences in 14 cancers. It presented an intimate relationship with immune-relevant biomarkers. A variation analysis indicated that BMP1 had a significant association with immunotherapeutic response. The expression level of BMP1 was closely associated with insulin-like growth factor binding protein 3, an m6A modification relative gene. Except for a few cancer types, methylation negatively correlated with BMP1, and copy number variations positively correlated with BMP1. Notably, low BMP1 expression was connected with immunotherapeutic response in the cohorts, and its expression was related to increased sectional sensitivity of drugs. Conclusion: BMP1 may serve as a potential biomarker for prognostic prediction and immunologic infiltration in diversified cancers, providing a new thought approach for oncotherapy.

Characterizing Sampling Variability for Item Response Theory Scale Scores in a Fixed-Parameter Calibrated Projection Design.

A common practice of linking uses estimated item parameters to calculate projected scores. This procedure fails to account for the carry-over sampling variability. Neglecting sampling variability could consequently lead to understated uncertainty for Item Response Theory (IRT) scale scores. To address the issue, we apply a Multiple Imputation (MI) approach to adjust the Posterior Standard Deviations of IRT scale scores. The MI procedure involves drawing multiple sets of plausible values from an approximate sampling distribution of the estimated item parameters. When two scales to be linked were previously calibrated, item parameters can be fixed at their original published scales, and the latent variable means and covariances of the two scales can then be estimated conditional on the fixed item parameters. The conditional estimation procedure is a special case of Restricted Recalibration (RR), in which the asymptotic sampling distribution of estimated parameters follows from the general theory of pseudo Maximum Likelihood (ML) estimation. We evaluate the combination of RR and MI by a simulation study to examine the impact of carry-over sampling variability under various simulation conditions. We also illustrate how to apply the proposed method to real data by revisiting Thissen et al. (2015).

CT-Guided Thermocoagulation of the Pterygopalatine Ganglion for Refractory Trigeminal Autonomic Cephalalgia.

INTRODUCTION: Trigeminal autonomic cephalalgia (TAC) is a type of one-sided cerebral painful headache, with attacks regularly accompanied by autonomic responses, such as tearing, runny nose, panic, nausea and vomiting on the affected side. Currently, the most common treatment strategies are drugs, nerve grafts and surgery. Clinical understanding of TACs is limited. Here, we report the case of thermocoagulation treatment of the pterygopalatine ganglion in an uncommon TAC under local anesthesia. CASE PRESENTATION: A rare case of TAC was treated with computed tomography (CT)-guided thermocoagulation within the pterygopalatine ganglion. Pain and autonomic signs were relieved immediately after surgery, with the patent retaining only slight numbness on the left side of the face. This numbness completely resolved at 6 months of follow-up and there was no recurrence. DISCUSSION: Trigeminal autonomic cephalalgia seriously affects the patient's quality of life, but clinical understanding is limited. In the case reported here, we performed CT-guided thermocoagulation of the pterygopalatine ganglion at 90 °C for 180 s for treatment of a trigeminal autonomic headache. To our knowledge, this is the first report of using thermocoagulation at 90 °C to treat the pterygopalatine ganglion. We found that this strategy results in fewer side effects and is a more cost-effective treatment for such patients than other options. CONCLUSION: Computed tomography-guided thermocoagulation of the pterygopalatine ganglion at 90 °C for 180 s for treatment of trigeminal autonomic headache is a safe and economical treatment option.