Functional connectivity between the habenula and posterior default mode network contributes to the response of the duloxetine effect in major depressive disorder.

This study aims to investigate the functional connectivity (FC) changes of the habenula (Hb) among patients with major depressive disorder (MDD) after 12 weeks of duloxetine treatment (MDD12). Patients who were diagnosed with MDD for the first time and were drug-naïve were recruited at baseline as cases. Healthy controls (HCs) matched for sex, age, and education level were also recruited at the same time. At baseline, all participants underwent resting-state functional MRI. FC analyses were performed using the Hb seed region of interest, and three groups including HCs, MDD group and MDD12 group were compared using whole-brain voxel-wise comparisons. Compared to the HCs, the MDD group had decreased FC between the Hb and the right anterior cingulate cortex at baseline. Compared to the HCs, the FC between the Hb and the left medial superior frontal gyrus decreased in the MDD12 group. Additionally, the FC between the left precuneus, bilateral cuneus and Hb increased in the MDD12 group than that in the MDD group. No significant correlation was found between HDRS-17 and the FC between the Hb, bilateral cuneus, and the left precuneus in the MDD12 group. Our study suggests that the FC between the post-default mode network and Hb may be the treatment mechanism of duloxetine and the treatment mechanisms and the pathogenesis of depression may be independent of each other.

Every Problem, Every Step, All In Focus: Learning to Solve Vision-Language Problems with Integrated Attention.

Integrating information from vision and language modalities has sparked interesting applications in the fields of computer vision and natural language processing. Existing methods, though promising in tasks like image captioning and visual question answering, face challenges in understanding real-life issues and offering step-by-step solutions. In particular, they typically limit their scope to solutions with a sequential structure, thus ignoring complex inter-step dependencies. To bridge this gap, we propose a graph-based approach to vision-language problem solving. It leverages a novel integrated attention mechanism that jointly considers the importance of features within each step as well as across multiple steps. Together with a graph neural network method, this attention mechanism can be progressively learned to predict sequential and non-sequential solution graphs depending on the characterization of the problem-solving process. To tightly couple attention with the problem-solving procedure, we further design new learning objectives with attention metrics that quantify this integrated attention, which better aligns visual and language information within steps, and more accurately captures information flow between steps. Experimental results on VisualHow, a comprehensive dataset of varying solution structures, show significant improvements in predicting steps and dependencies, demonstrating the effectiveness of our approach in tackling various vision-language problems.

A case of comorbidity of schizophrenic catatonia and chronic intestinal pseudo-obstruction Successfully managed with lorazepam.

It is challenging to manage schizophrenic catatonia and comorbid chronic intestinal pseudo-obstruction (CIPO). The pathology of catatonia is unclear. There are few reports or research on this issue. In this case, we present a middle-aged woman diagnosed with schizophrenia with catatonic features and comorbid CIPO. In the treatment process, modified electroconvulsive therapy (mECT) improved her stupor and CIPO partially. Lorazepam alleviated her stupor and CIPO completely. It is the first report describing complete remission with lorazepam in patient suffering from comorbid schizophrenic catatonia and CIPO, which may benefit the exploration of pathophysiology and treatment of comorbidity of schizophrenia with catatonia and CIPO.

From imaging to clinical outcome: dual-region CT radiomics predicting FOXM1 expression and prognosis in hepatocellular carcinoma.

Background: Liver cancer, especially hepatocellular carcinoma (HCC), remains a significant global health challenge. Traditional prognostic indicators for HCC often fall short in providing comprehensive insights for individualized treatment. The integration of genomics and radiomics offers a promising avenue for enhancing the precision of HCC diagnosis and prognosis. Methods: From the Cancer Genome Atlas (TCGA) database, we categorized mRNA of HCC patients by Forkhead Box M1 (FOXM1) expression and performed univariate and multivariate studies to pinpoint autonomous HCC risk factors. We deployed subgroup, correlation, and interaction analyses to probe FOXM1's link with clinicopathological elements. The connection between FOXM1 and immune cells was evaluated using the CIBERSORTx database. The functions of FOXM1 were investigated through analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). After filtering through TCGA and the Cancer Imaging Archive (TCIA) database, we employed dual-region computed tomography (CT) radiomics technology to noninvasively predict the mRNA expression of FOXM1 in HCC tissues. Radiomic features were extracted from both tumoral and peritumoral regions, and a radiomics score (RS) was derived. The performance and robustness of the constructed models were evaluated using 10-fold cross-validation. A radiomics nomogram was developed by incorporating RS and clinical variables from the TCGA database. The models' discriminative abilities were assessed using metrics such as the area under the curve (AUC) of the receiver operating characteristic curves (ROC) and precision-recall (PR) curves. Results: Our findings emphasized the overexpression of FOXM1 as a determinant of poor prognosis in HCC and illustrated its impact on immune cell infiltration. After selecting arterial phase CT, we chose 7 whole-tumor features and 3 features covering both the tumor and its surroundings to create WT and WP models for FOXM1 prediction. The WT model showed strong predictive capabilities for FOXM1 expression by PR curve. Conversely, the WP model did not demonstrate the good predictive ability. In our study, the radiomics score (RS) was derived from whole-tumor regions on CT images. The RS was significantly associated with FOXM1 expression, with an AUC of 0.918 in the training cohort and 0.837 in the validation cohort. Furthermore, the RS was correlated with oxidative stress genes and was integrated with clinical variables to develop a nomogram, which demonstrated good calibration and discrimination in predicting 12-, 36-, and 60-month survival probabilities. Additionally, bioinformatics analysis revealed FOXM1's potential role in shaping the immune microenvironment, with its expression linked to immune cell infiltration. Conclusion: This study highlights the potential of integrating FOXM1 expression and radiomics in understanding HCC's complexity. Our approach offers a new perspective in utilizing radiomics for non-invasive tumor characterization and suggests its potential in providing insights into molecular profiles. Further research is needed to validate these findings and explore their clinical implications in HCC management.

Case Report: Primary hepatic neuroendocrine tumor: two cases report with literature review.

Background & Aims: Primary hepatic neuroendocrine tumors (PHNETs) are rare malignant liver tumors that present diagnostic challenges owing to their rarity and absence of specific clinical features. This study aimed to investigate the characteristics of this rare liver tumor to enhance our understanding of the disease, improve diagnostic accuracy, and explore standardized diagnostic and treatment approaches. Case description: During physical examination, two elderly women, aged 64 and 74 years, were found to have liver masses. 18F-FDG Positron Emission Tomography-Computed Tomography (18F-FDG PET-CT) and Ga68-DOTATATE PET-CT scans of both individuals revealed multiple liver masses that were initially suspected to be hepatic neuroendocrine tumors. Subsequent puncture pathology confirmed the diagnosis of neuroendocrine tumors. Furthermore, in Case 1, the tumor was also detected by 18F-FDG PET-CT in the lung, suggesting a metastatic tumor, in conjunction with liver immunohistochemistry and imaging findings. Laboratory tests revealed no significant abnormalities in liver function or autoimmune liver disease indicators, and there was no evidence of viral hepatitis infection. However, partial hepatectomy was not indicated for cases with distant metastasis or multiple space-occupying lesions. Individualized treatment approaches have been developed for such situations. A large portion of the tumor underwent Transarterial Embolization (TAE), and targeted combination chemotherapy or endocrine therapy was administered based on the pathological results. During regular follow-ups a 13 and 12 months, the tumor remained stable. The patients' quality of life was good, and their psychological well-being was healthy. They led active lifestyles, demonstrated a thorough understanding of their disease and its progression, and actively cooperated during the follow-up process. Conclusion: Our findings suggest that a combination of serological, radiological, and immunohistochemical examinations can aid in the diagnosis of PHNET. In addition, we determined that TAE combined with drug therapy could be an effective method for controlling PHNET progression. Regular postoperative follow-ups are important for monitoring the prognosis and tumor progression status of patients with PHNET.

Changes of cortical thickness in the first episode, drug-naive depression patients with and without melancholic features.

Melancholic depression (MD) is a more severe type of major depressive disorder (MDD) with a core feature of anhedonia. However, its pathophysiology remains unclear. The current study aims to investigate whether there is a significant difference in cortical thickness (CT) that can be used to differentiate MD patients from non-melancholic depression (NMD) patients. We recruited 137 first-episode drug-naive MDD patients and 75 healthy controls (HCs) for structural magnetic resonance imaging, analyzed using the Surface-based morphometry approach. Meanwhile, the MDD patients were divided into the MD and NMD subgroups according to their scores on the Montgomery-Asberg Depression Rating Scale and Hamilton Depression Rating Scale. No significant CT differences among the three groups were found. We also did not find significant CT changes between the NMD and the HCs groups or between the MD and NMD groups. However, the CT of the left postcentral gyrus and right precuneus among MD patients were larger than HCs. Moreover, the CT of the left postcentral gyrus and right precuneus were not correlated with the severity of the disease and illness duration. The findings suggest that the CT alterations of the left postcentral gyrus and the right precuneus are distinct pathological mechanisms for MD.

CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4.

BACKGROUND: Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear. METHODS: Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings. RESULTS: CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo. CONCLUSION: Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer.

Suppressing circIDE/miR-19b-3p/RBMS1 axis exhibits promoting-tumour activity through upregulating GPX4 to diminish ferroptosis in hepatocellular carcinoma.

Ferroptosis is a newly characterized form of iron-dependent non-apoptotic cell death, which is closely associated with cancer progression. However, the functions and mechanisms in regulation of escaping from ferroptosis during hepatocellular carcinoma (HCC) progression remain unknown. In this study, we reported that the RNA binding motif single stranded interacting protein 1 (RBMS1) participated in HCC development，and functioned as a regulator of ferroptosis. Clinically, the downregulation of RBMS1 occurred in HCC tissues, and low RBMS1 expression was associated with worse HCC patients survival. Mechanistically, RBMS1 overexpression inhibited HCC cell growth by attenuating the expression of glutathione peroxidase 4 (GPX4)and further facilitated ferroptosis in vitro and in vivo. More importantly, a novel circIDE (hsa_circ_0000251) was identified to elevate RBMS1 expression via sponging miR-19b-3p in HCC cells. Collectively, our findings established circIDE/miR-19b-3p/RBMS1 axis as a regulator of ferroptosis, which could be a promising therapeutic target and prognostic factor.

Realizing the Heteromorphic Superlattice: Repeated Heterolayers of Amorphous Insulator and Polycrystalline Semiconductor with Minimal Interface Defects.

An unconventional "heteromorphic" superlattice (HSL) is realized, comprised of repeated layers of different materials with differing morphologies: semiconducting pc-In2 O3 layers interleaved with insulating a-MoO3 layers. Originally proposed by Tsu in 1989, yet never fully realized, the high quality of the HSL heterostructure demonstrated here validates the intuition of Tsu, whereby the flexibility of the bond angle in the amorphous phase and the passivation effect of the oxide at interfacial bonds serve to create smooth, high-mobility interfaces. The alternating amorphous layers prevent strain accumulation in the polycrystalline layers while suppressing defect propagation across the HSL. For the HSL with 7:7 nm layer thickness, the observed electron mobility of 71 cm2  Vs-1 , matches that of the highest quality In2 O3 thin films. The atomic structure and electronic properties of crystalline In2 O3 /amorphous MoO3 interfaces are verified using ab-initio molecular dynamics simulations and hybrid functional calculations. This work generalizes the superlattice concept to an entirely new paradigm of morphological combinations.

HDAC3 increases HMGB3 expression to facilitate the immune escape of breast cancer cells via down-regulating microRNA-130a-3p.

OBJECTIVE: Histone deacetylase 3 (HDAC3) has been reported to repress the expression of various genes by eliminating acetyl group from histone. The objective of this study was to discuss the effect of HDAC3/microRNA-130a-3p (miR-130a-3p)/high-mobility group box 3 (HMGB3) on immune escape of breast cancer. METHODS: HDAC3, miR-130a-3p and HMGB3 expression in breast cancer tissues and cells were tested, and the correlation between HDAC3, miR-130a-3p and HMGB3 was analyzed. CD8, CD69 and programmed cell death protein 1 (PD-1) expression was detected. MDA-MB-231 cells were treated with relative plasmid of HDAC3 or miR-130a-3p to test cell viability, migration, epithelial-mesenchymal transition (EMT) and apoptosis in MDA-MB-231 cells. The cytotoxicity of CD8+/CD69+/PD-1+T cells in MDA-MB-231 cells was tested, and CD8+/CD69+/PD-1+T cell proliferation and apoptosis before and after co-culture with MDA-MB-231 cells were detected. RESULTS: HDAC3 and HMGB3 expression were raised and miR-130a-3p expression was diminished in breast cancer tissues and cells. HDAC3 was negatively correlated with miR-130a-3p while miR-130a-3p was negatively correlated with HMGB3. Down-regulating HDAC3 or up-regulating miR-130a-3p restrained cell viability, migration, EMT and anti-CD8+/CD69+/PD-1+T cytotoxicity and facilitated apoptosis of breast cancer cells. HDAC3 regulated HMGB3 by mediating miR-130a-3p expression. Down-regulating miR-130a-3p reversed the role of HDAC3 reduction on breast cancer cells. HDAC3 regulated CD8+/CD69+/PD-1+T cell proliferation and apoptosis by mediating miR-130a-3p. CONCLUSION: This study provides evidence that HDAC3 increases HMGB3 expression to promote the immune escape of breast cancer cells via down-regulating miR-130a-3p.

microRNA-6785-5p-loaded human umbilical cord mesenchymal stem cells-derived exosomes suppress angiogenesis and metastasis in gastric cancer via INHBA.

OBJECTIVE: Exosomes (Exos) are known to transfer microRNAs (miRNAs) to participate in human diseases. We aim to identify the role of human umbilical cord mesenchymal stem cells (HUCMSCs)-derived Exos (HUCMSC-Exos) conveying miR-6785-5p in gastric cancer (GC). METHODS: MiR-6785-5p and inhibin subunit beta A (INHBA) expression in GC tissues and cells were determined. GC cells were transfected with the vectors that altered miR-6785-5p or INHBA expression. HUCMSCs were transfected with altered miR-6785-5p or INHBA vectors, and the HUCMSC-Exos were extracted. Then, HUCMSC-Exos were co-cultured with GC cells. The proliferation, migration, invasion, apoptosis and angiogenesis of GC cells were assessed. The binding relationship between miR-6785-5p and INHBA was verified. RESULTS: MiR-6785-5p was down-regulated and INHBA was up-regulated in GC tissues and cells. Elevation of miR-6785-5p or inhibition of INHBA restricted the malignant development of GC cells. HUCMSC-Exos suppressed malignant episodes of GC cells, which could be further enhanced by up-regulated miR-6785-5p or down-regulated INHBA. Elevated INHBA abolished the impacts of up-regulated miR-6785-5p in HUCMSC-Exos on GC cells. INHBA was confirmed as a target gene of miR-6785-5p. CONCLUSION: HUCMSC-Exos containing elevated miR-6785-5p suppress angiogenesis and metastasis in GC via inhibiting INHBA. This study may further the understanding on molecular mechanisms of GC.

Timely Reliability Analysis of Virtual Machines Considering Migration and Recovery in an Edge Server.

For the edge computing network, whether the end-to-end delay satisfies the delay constraint of the task is critical, especially for delay-sensitive tasks. Virtual machine (VM) migration improves the robustness of the network, whereas it also causes service downtime and increases the end-to-end delay. To study the influence of failure, migration, and recovery of VMs, we define three states for the VMs in an edge server and build a continuous-time Markov chain (CTMC). Then, we develop a matrix-geometric method and a first passage time method to obtain the VMs timely reliability (VTR) and the end-to-end timely reliability (ETR). The numerical results are verified by simulation based on OMNeT++. Results show that VTR is a monotonic function of the migration rate and the number of VMs. However, in some cases, the increase in task VMs (TVMs) may conversely decrease VTR, since more TVMs also brings about more failures in a given time. Moreover, we find that there is a trade-off between TVMs and backup VMs (BVMs) when the total number of VMs is limited. Our findings may shed light on understanding the impact of VM migration on end-to-end delay and designing a more reliable edge computing network for delay-sensitive applications.

TP73-AS1 promotes breast cancer cell proliferation through miR-200a-mediated TFAM inhibition.

P73 antisense RNA 1T (TP73-AS1 or PDAM) is a long non-coding RNA, which can regulate apoptosis through regulation of p53 signaling-related anti-apoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in breast cancer (BC) growth and the underlying mechanism remain unclear so far. In the present study, the effect of TP73-AS1 in BC cell lines and clinical tumor samples was detected so as to reveal its role and function. In the present study, TP73-AS1 was specifically upregulated in BC tissues and BC cell lines and was correlated to a poorer prognosis in patients with BC. TP73-AS1 knocking down suppressed human BC cell proliferation in vitro through regulation of TFAM. In our previous study, we demonstrated that miR-200a inhibits BC cell proliferation through targeting TFAM; here we revealed that TP73-AS1 could regulate miR-200a through direct targeting. Moreover, TP73-AS1 might compete with TFAM for miR-200a binding thus to promote TFAM expression. Data from the present study revealed that TP73-AS1 promoted BC cell proliferation through acting as a competing endogenous RNA (ceRNA) by sponging miR-200a. In conclusion, we regarded TP73-AS1 as an oncogenic lncRNA promoting BC cell proliferation and a potential target for human BC treatment.

The predictive value of Ki-67 before neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis.

AIM: To review the predictive values of Ki-67 before neoadjuvant chemotherapy (NAC) for breast cancer patients. METHODS: PubMed and EMBASE were searched. Random-effect model meta-analysis was conducted using Revman software. RESULTS: High Ki-67 was associated with more pathological complete responses (pCRs) events (odds ratio: 3.10; 95% CI: 2.52-3.81; 53 studies, 10,848 patients) regardless of HR+, HER2+ and triple-negative breast cancer types, the definitions of pCR and cut-off points for Ki-67. Ki-67 could predict pCR in those who received anthracyclines plus taxanes, and anthracyclines only, and those from Asia and Europe. CONCLUSION: High Ki-67 before NAC was a predictor for pCR in neoadjuvant setting for breast cancer patients.

Current Treatments for Breast Cancer-Related Lymphoedema: A Systematic Review

Background and objective: Breast cancer-related lymphoedema (BCRL) is a disabling complication with long term impact on quality on life after breast cancer treatment. Its management remains a major challenge for patients and health care professionals; the goal of this overview was to summarize effects of different treatment strategies for patients with BCRL. Methods: A thorough search was undertaken to allow a systematic review or meta-analysis of treatments for BCRL. Two investigators independently selected studies and abstracted the data. Results: Combined physical therapy (CPT) with different combinations of surgery, oral pharmaceuticals, low-level laser therapy, weight reduction, mesenchymal stem cell therapy, kinesio tex taping, and acupuncture might be effective in reducing lymphoedema, but exercise demonstrated no obvious benefit. The results of direct comparisons showed CPT might be more effective than standard physiotherapy (ST). Manual lymphatic drainage (MLD) may not offer additional benefits to ST for swelling reduction, but could facilitate compression bandaging. MLD seemed to have similar effects with self-administered simple lymphatic drainage (SLD) or using an intermittent pneumatic compression pump (IPC). IPC might also not be associated with additional effectiveness for CPT. Efficacy of stem cell therapy vs. compression sleeve or CPT, as well as the effects of daflon and coumarin could not be established. Conclusion: Although many treatments for BCRL might reduce lymphoedema volume, their effects were not well established. The quality of many of the original studies in the included reviews was not optimal, so that in future randomized control trials are a high priority.

Altered resting-state regional homogeneity after 13 weeks of paliperidone injection treatment in schizophrenia patients.

This study aimed to explore the effects of the long-acting antipsychotic drug palmitate paliperidone in resting-state brain activity of schizophrenia patients. Seventeen schizophrenia outpatients were included and received palmitate paliperidone injection (PAL) treatment for 13 weeks. These patients were compared to seventeen matched healthy controls. All subjects underwent two scan sessions of resting-state magnetic resonance imaging (baseline and the 13th week) and regional homogeneity (ReHo) at resting-state where compared. After 13 weeks of treatment, PAL increased ReHo of the prefrontal cortex, anterior cingulate gyrus and orbital frontal gyrus, while PAL decreased ReHo of the thalamus, parahippocampal gyrus and superior temporal gyrus. Furthermore, improvement of psychiatric symptoms correlated with changing amplitude of ReHo: positively correlated with postcentral gyrus and negatively correlated with the occipital cortex. Baseline ReHo values of the middle occipital gyrus were positively correlated with the rate of reduction of psychiatric symptoms and improvement of social function. These results suggested that PAL might achieve its clinical effect in schizophrenia by influencing the resting-state function of the occipital cortex, lateral prefrontal cortex and temporal lobe. Baseline function of the inferior occipital gyrus might potentially predict the short-term effect of PAL in schizophrenia.

Biological Matrix Effects in Quantitative Tandem Mass Spectrometry-Based Analytical Methods: Advancing Biomonitoring.

The ability to quantify levels of target analytes in biological samples accurately and precisely in biomonitoring involves the use of highly sensitive and selective instrumentation such as tandem mass spectrometers and a thorough understanding of highly variable matrix effects. Typically, matrix effects are caused by co-eluting matrix components that alter the ionization of target analytes as well as the chromatographic response of target analytes, leading to reduced or increased sensitivity of the analysis. Thus, before the desired accuracy and precision standards of laboratory data are achieved, these effects must be characterized and controlled. Here we present our review and observations of matrix effects encountered during the validation and implementation of tandem mass spectrometry-based analytical methods. We also provide systematic, comprehensive laboratory strategies needed to control challenges posed by matrix effects in order to ensure delivery of the most accurate data for biomonitoring studies assessing exposure to environmental toxicants.

Multiple facial basal cell carcinomas in xeroderma pigmentosum treated with topical imiquimod 5% cream.

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by solar sensitivity, photophobia, early onset of freckling, and solar-induced cutaneous neoplastic changes. Management of patients with XP is a therapeutic challenge as they usually develop multiple cutaneous malignancies, making surgical therapy difficult, and continue to form skin malignancies at a high rate. We describe a 30-year-old Chinese man with XP who had been previously treated with excision and dermatoplasty. Upon recurrence of multiple superficial, ulcerative, and pigmented lesions, imiquimod 5% cream was recommended for 4 months. His multiple facial lesions demonstrated an excellent response to topical imiquimod 5% cream with minor side effects. This favorable response indicates that topical application of imiquimod 5% cream is an effective means of treating multiple basal cell carcinomas in XP.