Shared genetic links between hypothyroidism and psychiatric disorders: evidence from a comprehensive genetic analysis.

Background: Epidemiologic studies have suggested co-morbidity between hypothyroidism and psychiatric disorders. However, the shared genetic etiology and causal relationship between them remain currently unclear. Methods: We assessed the genetic correlations between hypothyroidism and psychiatric disorders [anxiety disorders (ANX), schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP)] using summary association statistics from genome-wide association studies (GWAS). Two disease-associated pleiotropic risk loci and genes were identified, and pathway enrichment, tissue enrichment, and other analyses were performed to determine their specific functions. Furthermore, we explored the causal relationship between them through Mendelian randomization (MR) analysis. Results: We found significant genetic correlations between hypothyroidism with ANX, SCZ, and MDD, both in the Linkage disequilibrium score regression (LDSC) approach and the high-definition likelihood (HDL) approach. Meanwhile, the strongest correlation was observed between hypothyroidism and MDD (LDSC: rg=0.264, P=7.35×10-12; HDL: rg=0.304, P=4.14×10-17). We also determined a significant genetic correlation between MDD with free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels. A total of 30 pleiotropic risk loci were identified between hypothyroidism and psychiatric disorders, of which the 15q14 locus was identified in both ANX and SCZ (P values are 6.59×10-11 and 2.10×10-12, respectively) and the 6p22.1 locus was identified in both MDD and SCZ (P values are 1.05×10-8 and 5.75×10-14, respectively). Sixteen pleiotropic risk loci were identified between MDD and indicators of thyroid function, of which, four loci associated with MDD (1p32.3, 6p22.1, 10q21.1, 11q13.4) were identified in both FT4 normal level and Hypothyroidism. Further, 79 pleiotropic genes were identified using Magma gene analysis (P<0.05/18776 = 2.66×10-6). Tissue-specific enrichment analysis revealed that these genes were highly enriched into six brain-related tissues. The pathway analysis mainly involved nucleosome assembly and lipoprotein particles. Finally, our two-sample MR analysis showed a significant causal effect of MDD on the increased risk of hypothyroidism, and BIP may reduce TSH normal levels. Conclusions: Our findings not only provided evidence of a shared genetic etiology between hypothyroidism and psychiatric disorders, but also provided insights into the causal relationships and biological mechanisms that underlie their relationship. These findings contribute to a better understanding of the pleiotropy between hypothyroidism and psychiatric disorders, while having important implications for intervention and treatment goals for these disorders.

Evolution and global research trends of immunity in diabetic nephropathy: a bibliometric and visual analysis from 2004 to 2023.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, with an increasing prevalence worldwide, but its pathomechanisms remain incompletely understood. Accumulating evidence suggests that immunity plays an important role in the development of DN. Many papers have been published in the field over the last 20 years, but there has been no bibliometric review of the research hotspots and trends in the field. This study aimed to assess the current research status and future trends of the link between immune and DN using bibliometric analysis. METHODS: Publications on the association between immunity and DN from 2004 to 2023 were retrieved from the Web of Science Core Collection database and screened according to inclusion criteria. VOSviewer and CiteSpace software were employed to visualize research trends and hotspots in the field. Data including author, institution, country, journal, reference, and keyword were analyzed. RESULTS: Ultimately 1246 publications meeting the criteria were included in the bibliometric analysis, involving 838 articles (84.96%) and 408 reviews (15.04%). The literature covered 81 countries and regions, 1751 institutions, and 6584 authors. The top 2 countries in terms of the number of publications were China (435) and the United States (318), and they collaborated most frequently. The United States had the highest number of citations for published papers (18,161), far exceeding the other countries. England had 38 publications but had the highest average number of citations (92.32). The University of California system was the most prolific institution (25 papers, 1062 citations, 42.48 citations per paper). Frontiers in Immunology was the most prolific journal in the field (30 papers). The most cited journal was Kidney International (863 citations). The analysis of keywords and references showed that inflammation, ferroptosis, and lipid metabolism may be future research hotspots in this field. CONCLUSIONS: The number of publications related to immunity and DN has increased annually over the past 20 years, with a significant increase in the last 3 years especially. Our results identified research hotspots and trends in the field. These findings provide valuable perspectives for future research, enhancing our understanding of the immune-related mechanisms of DN and exploring potential therapeutic strategies.

Comprehensive analysis of a novel subtype of immune microenvironment-derived HPV-infected colorectal cancer.

BACKGROUND: The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC. METHODS: We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC. Quantitative polymerase chain reaction, cell proliferation, scratch, and flow cytometry assays were employed to validate the impact of HPV on CRC. RESULTS: The study revealed a high prevalence of HPV infection in CRC, with infection rates ranging from 10% to 31%. There was also a significant increase in tumor proliferation in HPV-infected CRC. The study showed increased immune cell infiltration, including T cells, γδ T cells, cytotoxic cells, and plasmacytoid dendritic cells in HPV-infected CRC (P < 0.05). Furthermore, our findings confirmed that HPV infection promoted M1 polarization. Our results demonstrated that low ISM2 expression was associated with a less advanced clinical stage (P < 0.001) and better survival outcomes (P = 0.039). Low ISM2 expression correlated with a strong tumor immune response, potentially contributing to the improved survival observed in HPV-infected CRC. CONCLUSIONS: These findings provided a novel subtype of HPV-infected CRC. The subtype with a better prognosis showed a "hot" tumor immune microenvironment that may be responsive to immunotherapy.

Association between the triglyceride glucose index and diabetic retinopathy in type 2 diabetes: a meta-analysis.

The triglyceride-glucose (TyG) index is an accessible and reliable surrogate indicator of insulin resistance and is strongly associated with diabetes. However, its relationship with diabetic retinopathy (DR) remains controversial. This meta-analysis aimed to assess the relationship between the TyG index and the prevalence of DR. Initial studies were searched from PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) electronic databases. The retrieval time range was from the establishment of the database to June 2023. Pooled estimates were derived using a random-effects model and reported as odds ratio (OR) with 95% confidence intervals (CIs). Two researchers independently assessed the methodological quality of the included studies. The Newcastle-Ottawa Quality Scale (NOS) was utilized to assess cohort studies or case-control studies. The Agency for Healthcare Research and Quality (AHRQ) methodology checklist was applied to assess cross-sectional studies. Ten observational studies encompassing 13716 patients with type 2 diabetes were included in the meta-analysis. The results showed that a higher TyG index increased the risk of DR compared with a low TyG index (OR: 2.34, 95% CI: 1.31-4.19, P < 0.05). When the index was analyzed as a continuous variable, consistent results were observed (OR: 1.48, 95% CI: 1.12-1.97, P < 0.005). There was no significant effect on the results of the sensitivity analyses excluding one study at a time (P all < 0.05). A higher TyG index may be associated with an increased prevalence of DR in patients with type 2 diabetes. However, high-quality cohort or case-control studies are needed to further substantiate this evidence. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432747.

Comprehensive analysis of HOXC8 associated with tumor microenvironment characteristics in colorectal cancer.

Background: Accumulating evidence have highlighted the essential roles of HOX genes in embryonic development and carcinogenesis. As a member of the HOX gene family, the abnormal expression of HOXC8 gene is associated with the progression and metastasis of various tumors. However, potential roles of HOXC8 in colorectal cancer (CRC) prognosis and tumor microenvironment (TME) remodeling remain unclear. Methods: We conducted an integrated analysis of clinical and molecular characteristics, relevant oncogenic and immune regulation roles and drug sensitivity features of HOXC8 in CRC. Results: HOXC8 expression was markedly high expressed in CRC samples compared to normal samples, and the upregulated expression of HOXC8 was associated with poor prognosis. High HOXC8 expression was significantly associated with invasion-related pathways especially epithelial-mesenchymal transition (EMT). In vitro experiments showed significantly up-regulated HOXC8 expression in some CRC cell lines and its promoting effect on EMT and cell proliferation. TME categorization through transcriptomic analysis of CRC patients with high HOXC8 expression identified two different TME subtypes known as immune-enriched with fibrotic subtype and immune-depleted subtype. Patients with immune-enriched, fibrotic subtype exhibited significantly longer progression-free survival (PFS), upregulated PD-L1 and CTLA4 expression and higher TMB than those with the immune-depleted subtype. Conclusions: HOXC8 overexpression was associated with poor prognosis and specific TME subtypes in CRC. This study provided valuable resource for further exploring the potential mechanisms and therapeutic targets of HOX genes in CRC.

JUND Promotes Tumorigenesis via Specifically Binding on Enhancers of Multiple Oncogenes in Cervical Cancer.

Purpose: Enhancers are genomic regulatory elements located distally from the target gene, which play a critical role in determining cell identity and function. Dysregulation of enhancers has been frequently observed in various types of cancer, including cervical cancer. However, the identity of enhancers and their associated transcriptional regulators that are involved in cervical cancer remains unclear. Methods: With bioinformatics and 3D genomics, we revealed the enhancers in cervical cancer cell line and calculated which transcription factor (TF) is specifically binding on them based on TFs motif database. We knockdowned this TF and studied its function in cervical cancer cell line in vivo and in vitro. Results: We found 14,826 activated enhancers and predicted that JUND (JunD Proto-Oncogene) is relatively enriched in the sequences of these enhancers. Well-known oncogene MYC and JUN were regulated by JUND through enhancers. To further explore the roles of JUND in cervical cancer, we analyzed the gene expression data of clinical cervical cancer samples and knock-downed JUND by CRISPR-Cas9 in Hela cell line. We found JUND is over-expressed in cervical cancer and the expression of JUND increased along with the cervical cancer progresses. Knockdown of JUND decreased the proliferation of Hela cells in vitro and in vivo and blocked cell cycle in G1-phase. Transcriptome sequencing analysis revealed the identification of 2,231 differentially expressed genes in response to the JUND knockdown treatment. This perturbation resulted in the modulation of several biological processes and pathways that have been previously linked to cancer. Conclusion: These findings provide evidence for the significant involvement of JUND in cervical cancer pathogenesis, thereby positioning JUND as a potential therapeutic target for the treatment of this disease.

Leveraging twitter data to understand nurses' emotion dynamics during the COVID-19 pandemic.

The nursing workforce is the largest discipline in healthcare and has been at the forefront of the COVID-19 pandemic response since the outbreak of COVID-19. However, the impact of COVID-19 on the nursing workforce is largely unknown as is the emotional burden experienced by nurses throughout the different waves of the pandemic. Conventional approaches often use survey question-based instruments to learn nurses' emotions, and may not reflect actual everyday emotions but the beliefs specific to survey questions. Social media has been increasingly used to express people's thoughts and feelings. This paper uses Twitter data to describe the emotional dynamics of registered nurse and student nurse groups residing in New South Wales in Australia during the COVID-19 pandemic. A novel analysis framework that considered emotions, talking topics, the unfolding development of COVID-19, as well as government public health actions and significant events was utilised to detect the emotion dynamics of nurses and student nurses. The results found that the emotional dynamics of registered and student nurses were significantly correlated with the development of COVID-19 at different waves. Both groups also showed various emotional changes parallel to the scale of pandemic waves and corresponding public health responses. The results have potential applications such as to adjust the psychological and/or physical support extended to the nursing workforce. However, this study has several limitations that will be considered in the future study such as not validated in a healthcare professional group, small sample size, and possible bias in tweets.

Learning multi-modal brain tumor segmentation from privileged semi-paired MRI images with curriculum disentanglement learning.

Since the brain is the human body's primary command and control center, brain cancer is one of the most dangerous cancers. Automatic segmentation of brain tumors from multi-modal images is important in diagnosis and treatment. Due to the difficulties in obtaining multi-modal paired images in clinical practice, recent studies segment brain tumors solely relying on unpaired images and discarding the available paired images. Although these models solve the dependence on paired images, they cannot fully exploit the complementary information from different modalities, resulting in low unimodal segmentation accuracy. Hence, this work studies the unimodal segmentation with privileged semi-paired images, i.e., limited paired images are introduced to the training phase. Specifically, we present a novel two-step (intra-modality and inter-modality) curriculum disentanglement learning framework. The modality-specific style codes describe the attenuation of tissue features and image contrast, and modality-invariant content codes contain anatomical and functional information extracted from the input images. Besides, we address the problem of unthorough decoupling by introducing constraints on the style and content spaces. Experiments on the BraTS2020 dataset highlight that our model outperforms the competing models on unimodal segmentation, achieving average dice scores of 82.91%, 72.62%, and 54.80% for WT (the whole tumor), TC (the tumor core), and ET (the enhancing tumor), respectively. Finally, we further evaluate our model's variable multi-modal brain tumor segmentation performance by introducing a fusion block (TFusion). The experimental results reveal that our model achieves the best WT segmentation performance for all 15 possible modality combinations with 87.31% average accuracy. In summary, we propose a curriculum disentanglement learning framework for unimodal segmentation with privileged semi-paired images. Moreover, the benefits of the improved unimodal segmentation extend to variable multi-modal segmentation, demonstrating that improving the unimodal segmentation performance is significant for brain tumor segmentation with missing modalities. Our code is available at https://github.com/scut-cszcl/SpBTS.

The N6-methyladenosine METTL3 regulates tumorigenesis and glycolysis by mediating m6A methylation of the tumor suppressor LATS1 in breast cancer.

BACKGROUND: Posttranscriptional modification of tumor-associated factors plays a pivotal role in breast cancer progression. However, the underlying mechanism remains unknown. M6A modifications in cancer cells are dynamic and reversible and have been found to impact tumor initiation and progression through various mechanisms. In this study, we explored the regulatory mechanism of breast cancer cell proliferation and metabolism through m6A methylation in the Hippo pathway.  METHODS: A combination of MeRIP-seq, RNA-seq and metabolomics-seq was utilized to reveal a map of m6A modifications in breast cancer tissues and cells. We conducted RNA pull-down assays, RIP-qPCR, MeRIP-qPCR, and RNA stability analysis to identify the relationship between m6A proteins and LATS1 in m6A regulation in breast cancer cells. The expression and biological functions of m6A proteins were confirmed in breast cancer cells in vitro and in vivo. Furthermore, we investigated the phosphorylation levels and localization of YAP/TAZ to reveal that the activity of the Hippo pathway was affected by m6A regulation of LATS1 in breast cancer cells.  RESULTS: We demonstrated that m6A regulation plays an important role in proliferation and glycolytic metabolism in breast cancer through the Hippo pathway factor, LATS1. METTL3 was identified as the m6A writer, with YTHDF2 as the reader protein of LATS1 mRNA, which plays a positive role in promoting both tumorigenesis and glycolysis in breast cancer. High levels of m6A modification were induced by METTL3 in LATS1 mRNA. YTHDF2 identified m6A sites in LATS1 mRNA and reduced its stability. Knockout of the protein expression of METTL3 or YTHDF2 increased the expression of LATS1 mRNA and suppressed breast cancer tumorigenesis by activating YAP/TAZ in the Hippo pathway. CONCLUSIONS: In summary, we discovered that the METTL3-LATS1-YTHDF2 pathway plays an important role in the progression of breast cancer by activating YAP/TAZ in the Hippo pathway.

Retinoic acid receptor gamma is required for proliferation of pancreatic cancer cells.

Despite the expectation that retinoic acid receptor could be the potential therapeutic targets for pancreatic cancers, there has been the lack of information about the role and the impact of retinoic acid receptor gamma (RARγ, RARG) on pancreatic cancer, unlike other two RARs. Herein, we applied TCGA and GEO database to show that the expression and prognosis of RARG is closely related to pancreatic cancer, which demonstrates that RARG is commonly overexpressed in human pancreatic cancer and is an independent diagnostic marker predicting the poor prognosis of pancreatic cancer patients. In addition, we demonstrated that the reduction in the expression of RARG in human pancreatic cancer cells dramatically suppress their proliferation and tumor growth in vivo, partially attributable to the downregulation of tumor-supporting biological processes such as cell proliferation, antiapoptosis and metabolism and the decreased expression of various oncogenes like MYC and STAT3. Mechanistically, RARG binds on the promoters of MYC, STAT3, and SLC2A1 which is distinguished from well-known conventional Retinotic acid response elements (RAREs) and that the binding is likely to be responsible for the epigenetic activation in the level of chromatin, assessed by the measurement of deposition of the gene activation marker histone H3 K27 acetylation (H3K27ac) using ChIP-qPCR. In this study, we reveal that RARG plays important role in the tumorigenesis of pancreatic cancer and represents new therapeutic targets for human pancreatic cancer.

The efficacy and safety of acupoint catgut embedding therapy for depression: a protocol for systematic review and meta-analysis.

Background: Depression is a common public health problem, characterized by persistent low mood, lack of pleasure and exhaustion. Conventional treatments such as antidepressants and psychotherapy have some limitations, including variable efficacy, adverse side effects and high costs. Acupoint catgut embedding (ACE) therapy, as a subtype of acupuncture, has gained increasing clinical application due to its long-term effects, higher patient compliance, and cost-effectiveness. This study aims to conduct a meta-analysis to evaluate the efficacy and safety of ACE for depression. Methods: Electronic searches will be conducted in 12 databases (both in English and Chinese databases), encompassing from inception to April 2022, without language restrictions. Randomized controlled trials (RCTs) that involve ACE for treating depression will be included. The primary outcome measures will include the response rate, Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI), and Traditional Chinese Medicine Symptom Scale (TCMSSS). The secondary outcome measure will include Quality of Life scale score (QoL) and the incidence of adverse events. Results will be presented as risk ratios for dichotomous data and mean differences for continuous data. Two reviewers will independently conduct study selection, data extraction, and quality assessment. The methodological quality of eligible studies will be evaluated according to the criteria specified by the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0). Meta-analysis will be performed by RevMan 5.3 software. Discussion: Due to the limitations, a safer, high-efficacy and non-pharmacological intervention with minimal side effects is required for treating depression. ACE has the advantages of longer-lasting effects, improved patient compliance, and reduced treatment costs. This protocol represents a meta-analysis and systematic review, aiming to present the current evidence regarding the efficacy and safety of ACE for depression. It seeks to provide clinicians with a theoretical basis and valuable references for complementary and alternative medicine therapies in their treatment approaches. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, Identifier CRD42022325966.

hnRNP A1 in RNA metabolism regulation and as a potential therapeutic target.

Abnormal RNA metabolism, regulated by various RNA binding proteins, can have functional consequences for multiple diseases. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an important RNA binding protein, that regulates various RNA metabolic processes, including transcription, alternative splicing of pre-mRNA, translation, miRNA processing and mRNA stability. As a potent splicing factor, hnRNP A1 can regulate multiple splicing events, including itself, collaborating with other cooperative or antagonistical splicing factors by binding to splicing sites and regulatory elements in exons or introns. hnRNP A1 can modulate gene transcription by directly interacting with promoters or indirectly impacting Pol II activities. Moreover, by interacting with the internal ribosome entry site (IRES) or 3'-UTR of mRNAs, hnRNP A1 can affect mRNA translation. hnRNP A1 can alter the stability of mRNAs by binding to specific locations of 3'-UTR, miRNAs biogenesis and Nonsense-mediated mRNA decay (NMD) pathway. In this review, we conclude the selective sites where hnRNP A1 binds to RNA and DNA, and the co-regulatory factors that interact with hnRNP A1. Given the dysregulation of hnRNP A1 in diverse diseases, especially in cancers and neurodegeneration diseases, targeting hnRNP A1 for therapeutic treatment is extremely promising. Therefore, this review also provides the small-molecule drugs, biomedicines and novel strategies targeting hnRNP A1 for therapeutic purposes.

Imitation Learning: Progress, Taxonomies and Challenges.

Imitation learning (IL) aims to extract knowledge from human experts' demonstrations or artificially created agents to replicate their behaviors. It promotes interdisciplinary communication and real-world automation applications. However, the process of replicating behaviors still exhibits various problems, such as the performance is highly dependent on the demonstration quality, and most trained agents are limited to perform well in task-specific environments. In this survey, we provide an insightful review on IL. We first introduce the background knowledge from development history and preliminaries, followed by presenting different taxonomies within IL and key milestones of the field. We then detail challenges in learning strategies and present research opportunities with learning policy from suboptimal demonstration, voice instructions, and other associated optimization schemes.

The Effectiveness Comparison of Different Acupuncture-Related Therapies on Knee Osteoarthritis: A Meta-Analysis.

Objective: This meta-analysis aims to assess the efficacy of acupuncture-related therapy on knee osteoarthritis (KOA) patients. Method: We searched PubMed, Embase, and CNKI databases to screen eligible trials between 2017 and 2022. All trials that used acupuncture/moxibustion of KOA patients were included. Study selection and data extraction were performed by 2 researchers independently. The statistics was performed by using R 4.1.1. Results: A total of 17 trials were included in our meta-analysis. Meta-analysis results showed the evidence of the relation of several common acupunture/moxibustion treatments by network meta-analysis. In the fixed effect model, acupuncture/moxibustion has superior therapy efficacy than sham treatment (mean difference = -0.34, 95% confidence interval = (-0.52,-0.16), P=0.95). In fixed effect model, specific acupuncture/moxibustion has superior therapy efficacy than usual acupuncture/moxibustion (mean difference = -0.45, 95% confidence interval = (-0.62, -0.29), P < 0.01). Conclusion: Acupuncture/moxibustion has superior therapy efficacy than sham treatment. Specific acupuncture/moxibustion has superior therapy efficacy than usual acupuncture/moxibustion.

Fs-DSM: Few-Shot Diagram-Sentence Matching via Cross-Modal Attention Graph Model.

Diagram-sentence matching is a valuable academic research because it can help learners effectively understand the diagrams with the assisted by sentences. However, there are many uncommon objects, i.e. few-shot contents in diagrams and sentences. The existing methods for image-sentence matching have great limitations when applied to diagrams. Because they focus on the high-frequency objects during training and ignore the uncommon objects. In addition, the specialty leads to the semantic non-intuition of the diagram itself. In this work, we propose a cross-modal attention graph model for the few-shot diagram-sentence matching task named Fs-DSM. Specifically, it is composed of three modules. The graph initialization module regards the region-level diagram features and word-level sentence features as the nodes of Fs-DSM, and edges are represented as similarity between nodes. The information propagation module is a key point of Fs-DSM, in which the few-shot contents are recognized by an uncommon object recognition strategy, and then the nodes are updated by a neighborhood aggregation procedure with cross-modal propagation between all visual and textual nodes, while the edges are recomputed based on the new node features. The global association module integrates the features of regions and words to represent the global diagrams and sentences. By conducting comprehensive experiments in terms of few-shot and conventional image-sentence matching, we demonstrate that Fs-DSM achieves superior performances over the competitors on the AI2D [Formula: see text] diagram dataset and two public benchmark datasets with nature images.

Examination of Community Sentiment Dynamics due to COVID-19 Pandemic: A Case Study from a State in Australia.

The outbreak of the novel Coronavirus Disease 2019 (COVID-19) has caused unprecedented impacts to people's daily life around the world. Various measures and policies such as lockdown and social-distancing are implemented by governments to combat the disease during the pandemic period. These measures and policies as well as virus itself may cause different mental health issues to people such as depression, anxiety, sadness, etc. In this paper, we exploit the massive text data posted by Twitter users to analyse the sentiment dynamics of people living in the state of New South Wales (NSW) in Australia during the pandemic period. Different from the existing work that mostly focuses on the country-level and static sentiment analysis, we analyse the sentiment dynamics at the fine-grained local government areas (LGAs). Based on the analysis of around 94 million tweets that posted by around 183 thousand users located at different LGAs in NSW in 5 months, we found that people in NSW showed an overall positive sentimental polarity and the COVID-19 pandemic decreased the overall positive sentimental polarity during the pandemic period. The fine-grained analysis of sentiment in LGAs found that despite the dominant positive sentiment most of days during the study period, some LGAs experienced significant sentiment changes from positive to negative. This study also analysed the sentimental dynamics delivered by the hot topics in Twitter such as government policies (e.g. the Australia's JobKeeper program, lockdown, social-distancing) as well as the focused social events (e.g. the Ruby Princess Cruise). The results showed that the policies and events did affect people's overall sentiment, and they affected people's overall sentiment differently at different stages.

The miR-1185-2-3p-GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1.

BACKGROUND: Phosphatidylinositol-4-phosphate-binding protein GOLPH3L is overexpressed in human ductal carcinoma of the breast, and its expression levels correlate with the prognosis of breast cancer patients. However, the roles of GOLPH3L in breast tumorigenesis remain unclear. METHODS: We assessed the expression and biological function of GOLPH3L in breast cancer by combining bioinformatic prediction, metabolomics analysis and RNA-seq to determine the GOLPH3L-related pathways involved in tumorigenesis. Dual-luciferase reporter assay and coimmunoprecipitation (Co-IP) were used to explore the expression regulation mechanism of GOLPH3L. RESULTS: We demonstrated that knockdown of GOLPH3L in human breast cancer cells significantly suppressed their proliferation, survival, and migration and suppressed tumor growth in vivo, while overexpression of GOLPH3L promoted aggressive tumorigenic activities. We found that miRNA-1185-2-3p, the expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, is directly involved in suppressing the expression of GOLPH3L. Metabolomics microarray analysis and transcriptome sequencing analysis revealed that GOLPH3L promotes central carbon metabolism in breast cancer by stabilizing the p53 suppressor SERPINE1. CONCLUSIONS: In summary, we discovered a miRNA-GOLPH3L-SERPINE1 pathway that plays important roles in the metabolism of breast cancer and provides new therapeutic targets for human breast cancer.

Detecting Community Depression Dynamics Due to COVID-19 Pandemic in Australia.

The recent Coronavirus Infectious Disease 2019 (COVID-19) pandemic has caused an unprecedented impact across the globe. We have also witnessed millions of people with increased mental health issues, such as depression, stress, worry, fear, disgust, sadness, and anxiety, which have become one of the major public health concerns during this severe health crisis. Depression can cause serious emotional, behavioral, and physical health problems with significant consequences, both personal and social costs included. This article studies community depression dynamics due to the COVID-19 pandemic through user-generated content on Twitter. A new approach based on multimodal features from tweets and term frequency-inverse document frequency (TF-IDF) is proposed to build depression classification models. Multimodal features capture depression cues from emotion, topic, and domain-specific perspectives. We study the problem using recently scraped tweets from Twitter users emanating from the state of New South Wales in Australia. Our novel classification model is capable of extracting depression polarities that may be affected by COVID-19 and related events during the COVID-19 period. The results found that people became more depressed after the outbreak of COVID-19. The measures implemented by the government, such as the state lockdown, also increased depression levels.

The Association Of Serum Cortisol Level With Microalbuminuria In Patients With Type 2 Diabetes And Prediabetes.

Whether cortisol secretion is linked with microalbuminuria remains undefined. We aimed to investigate the relationship between serum cortisol levels and the presence of microalbuminuria in patients with type 2 diabetes (T2DM) and prediabetes. A cross-sectional study was conducted with 211 patients with T2DM or prediabetes. Serum cortisol was measured at 8:00 h, 16:00 h, and 0:00 h. The level and circadian rhythm of ACTH were also evaluated. Urine excretion of albumin was measured. Patients were subdivided into microalbuminuria (MAU) group (n= 120) and normoalbuminuria (NAU) group (n = 91) according to the status of microalbuminuria. Levels of serum cortisol (8:00 h: 426.9 ± 155.0 nmol/; 16:00 h: 303.7 ± 144.7 nmol/L) were significantly higher in MAU group than in NAU group (8:00 h: 370.2 ±130.6 nmol/L, P = 0.004; 16:00 h: 234.7 ± 120.2 nmol/L, P = 0.001). After adjustment for multiple factors, the correlation between cortisol levels (both at 8:00 h (P = 0.005) and at 16:00 h (P = 0.001)) and microalbuminuria remained consistent and significant. Higher levels of cortisol (cut-off value: 390.5 nmol/L at 8:00 h, 203.5 nmol/L at 16:00 h) help to detect the development of microalbuminuria. Serum cortisol secretion is associated with the presence of microalbuminuria in patients with T2DM and patients with prediabetes. Higher levels of cortisol, even in the normal range, may be related with the development of microalbuminuria.