Non-Coding RNAs Extended Omnigenic Module of Cancers.

The emergence of cancers involves numerous coding and non-coding genes. Understanding the contribution of non-coding RNAs (ncRNAs) to the cancer neighborhood is crucial for interpreting the interaction between molecular markers of cancer. However, there is a lack of systematic studies on the involvement of ncRNAs in the cancer neighborhood. In this paper, we construct an interaction network which encompasses multiple genes. We focus on the fundamental topological indicator, namely connectivity, and evaluate its performance when applied to cancer-affected genes using statistical indices. Our findings reveal that ncRNAs significantly enhance the connectivity of affected genes and mediate the inclusion of more genes in the cancer module. To further explore the role of ncRNAs in the network, we propose a connectivity-based method which leverages the bridging function of ncRNAs across cancer-affected genes and reveals the non-coding RNAs extended omnigenic module (NeOModule). Topologically, this module promotes the formation of cancer patterns involving ncRNAs. Biologically, it is enriched with cancer pathways and treatment targets, providing valuable insights into disease relationships.

Critical Role of Tripartite Fusion and LBD Truncation in Certain RARA- and all RARG-Related Atypical APL.

Atypical acute promyelocytic leukemia (aAPL) presents a complex landscape of retinoic acid receptor (RAR) fusion genes beyond the well-known PML::RARA fusion. Among these, 31 individually rare RARA and RARG fusion genes have been documented, often reported in the canonical X::RAR bipartite fusion form. Intriguingly, some artificially mimicked bipartite X::RAR fusions respond well to all-trans retinoic acid (ATRA) in vitro, contrasting with the ATRA resistance observed in patients. To unravel the underlying mechanisms, we conducted a comprehensive molecular investigation into the fusion transcripts in 27 RARA fusion gene-positive aAPL (RARA-aAPL) and 21 RARG-aAPL cases. Our analysis revealed an unexpected novel form of X::RAR::X or X::RAR::Y-type tripartite fusions in certain RARA- and all RARG-aAPL cases, with shared features and notable differences between these two disease subgroups. In RARA-aAPL cases, the occurrence of RARA 3' splices was associated with their 5' fusion partner genes, mapping across the coding region of helix 11_12 (H11_12) within the ligand-binding domain (LBD), resulting in LBD-H12 or H11_12 truncation. In RARG-aAPL cases, RARG 3' splices were consistently localized to the terminus of exon 9, leading to LBD-H11_12 truncation. Significant differences were also observed between RARA and RARG 5' splice patterns. Our analysis also revealed extensive involvement of transposable elements in constructing RARA and RARG 3' fusions, suggesting transposition mechanisms for fusion gene ontogeny. Both protein structural analysis and experimental results highlighted the pivotal role of LBD-H11_12/H12 truncation in driving ATRA unresponsiveness and leukemogenesis in tripartite fusion-positive aAPL, through a protein allosteric dysfunction mechanism.

Synchronization analyze of k-uniform hyper-networks.

Hyper-networks tend to perform better in representing multivariate relationships among nodes. Yet, due to the complexity of the hyper-network structure, research in synchronization dynamics is rarely involved. In this paper, a Kuramoto model more suitable for k-uniform hyper-networks is proposed. And the generalized Laplacian matrix expression of the k-uniform hyper-network is present. We use the eigenvalue ratio of the generalized Laplacian matrix to quantify synchronization. And we studied the effects of some important structure parameters on the synchronization of three types of k-uniform hyper-networks. And obtained different relationships between synchronization and these parameters. The results show the synchronization of the k-uniform hyper-networks is related to both structure and parameters. And as the size of the nodes increases, the synchronization ability gradually increases for ER random hyper-network, while that gradually decreases for NW small-world hyper-network and BA scale-free hyper-network. As the uniformity increases, the synchronization ability of all three types of uniform hyper-networks increases. In addition, when the structure and node size are fixed, the synchronization ability increases with the increase of the hyper-clustering coefficient in BA scale-free hyper-network and ER random hyper-network, while it decreases with the increase of the hyper-clustering coefficient in NW small-world hyper-network.

Discrepancies in breast cancer guideline recommendations despite similar Cochrane systematic review conclusions.

AIM: This study aims to describe the citation patterns of Cochrane systematic reviews (CSR) in guidelines for managing breast cancer. METHODS: We searched for systematic reviews on breast cancer in The Cochrane Library from the date of inception to November 15, 2023, and identified guidelines that cited them. We described how systematic reviews were cited by the guidelines in each database and each year. Additionally, we presented the relationships between the conclusions of the systematic reviews and guideline recommendations and compared the consistency of the recommendations on the same topic across different guidelines. RESULTS: A total of 64 systematic reviews and 228 guidelines were included in this study. The average number of the 64 systematic reviews cited by the guidelines was 5.91. We found that the guideline recommendations were irrelevant or inconsistent with the conclusions of the systematic reviews in 56 (38.36%) cited entries. We grouped recommendations on the same topic across different guidelines into one group, of which only 5 groups (15.15%) had completely consistent recommendations, and the other 28 groups (84.85%) had inconsistent recommendations. CONCLUSION: The average number of citations for CSR on breast cancer in the guidelines was 5.91. There were also situations in which the guideline recommendations were inconsistent with the conclusions of the included systematic reviews, and recommendations on the same topic across different guidelines were inconsistent.

The risk factors of reintubation in intensive care unit patients on mechanical ventilation: A systematic review and meta-analysis.

OBJECTIVE: To assess risk factors of reintubation in intensive care unit patients on mechanical ventilation. METHODOLOGY: We conducted a systematic review of literature (inception to May 2022) and a meta-analysis. Data are reported as pooled odds ratios for categorical variables and mean differences for continuous variables. RESULTS: A total of 2459 studies were retrieved of which 38 studies were included in a meta-analysis involving 22,304 patients. Risk factors identified were: older age, higher APACHE II scores, COPD, pneumonia, shock, low SaO2, low PaO2, low PaO2/FiO2, low hemoglobin, low albumin, high brain natriuretic peptide, low pH, high respiratory rate, low tidal volume, a higher rapid shallow breathing index, a lower vital capacity, a higher number of spontaneous breathing trials, prolonged length of mechanical ventilation, weak cough, a reduced patient's cough peak flow and positive cuff leak test. Subgroup analysis showed that risk factors substantially overlap when reintubation was considered within 48 hours or within 72 hours after extubation. CONCLUSIONS: We identified 21 factors associated with increased risk for reintubation. These allow to recognize the patient at high risk for reintubation at an early stage. Future studies may combine these factors to develop comprehensive predictive algorithms allowing appropriate vigilance.

Conserved Control Path in Multilayer Networks.

The determination of directed control paths in complex networks is important because control paths indicate the structure of the propagation of control signals through edges. A challenging problem is to identify them in complex networked systems characterized by different types of interactions that form multilayer networks. In this study, we describe a graph pattern called the conserved control path, which allows us to model a common control structure among different types of relations. We present a practical conserved control path detection method (CoPath), which is based on a maximum-weighted matching, to determine the paths that play the most consistent roles in controlling signal transmission in multilayer networks. As a pragmatic application, we demonstrate that the control paths detected in a multilayered pan-cancer network are statistically more consistent. Additionally, they lead to the effective identification of drug targets, thereby demonstrating their power in predicting key pathways that influence multiple cancers.

Torque teno mini virus driven childhood acute promyelocytic leukemia: The third case report and sequence analysis.

In this manuscript, we report torque teno mini virus (TTMV) as a cause of acute promyelocytic leukemia (APL) lacking PML::RARA in a 3-year-old boy. Astolfi et al. firstly identified partial integration of the TTMV genome into RARA intron 2, which resulted in in-frame TTMV::RARA fusion in two APL-like pediatric cases without PML::RARA in November 2021. This fascinating report identified an unexpected exogenous genetic cause of APL and could be of great importance for diagnosing and managing APL. Here we report the third childhood APL-like case caused by TTMV integration and investigate the location and structure of the integrated TTMV sequence. These findings suggest TTMV::RARA is a recurrent cause of APL lacking PML::RARA. Considering the widespread prevalence of TTMV in the population, more TTMV::RARA positive APL-like cases might remain to be identified. Establishing a bioinformatic analysis strategy optimized for the highly variable TTMV genome sequence may facilitate the identification of TTMV::RARA by whole transcript sequencing. An effective PCR protocol to identify TTMV::RARA based on a profound analysis of the conservation of TTMV segments in the fusion transcript is also expected. Also, further investigation is needed to elucidate the oncogenic mechanisms of TTMV integration and the clinical features of TTMV::RARA positive patients.

A New Consensus Model Based on Trust Interactive Weights for Intuitionistic Group Decision Making in Social Networks.

A promising feature for group decision making (GDM) lies in the study of the interaction between individuals. In conventional GDM research, experts are independent. This is reflected in the setting of preferences and weights. Nevertheless, each expert's role is played through communication, collaboration, and cooperation with other individuals. The interaction from others may affect the power of an expert as well as his/her opinion. Furthermore, it is noted that a link path with the highest degree of trust is the most efficient information transmission channel. Inspired by these findings, an optimal trust-induced consensus process is designed with the usage of intuitionistic fuzzy preference relation. The comprehensive weight of each expert is decomposed into two portions, namely: 1) the individual weights and 2) interactive weights. Three optimization models are constructed to achieve weight parameters under different decision situations, where the weight parameters are represented through a 2-order additive fuzzy measure and the Shapley value. To reflect the interaction, the Choquet integral is employed for aggregating opinions, and a novel distance measure is adopted for accomplishing a consensus index. An illustrative example and comparison are put in practice to show the effectiveness and improvements of the proposed method.

Protective Effect of Buyang Huanwu Decoction on Cerebral Ischemia Reperfusion Injury by Alleviating Autophagy in the Ischemic Penumbra.

OBJECTIVES: To evaluate the protective effect of Buyang Huanwu Decoction (BHD) against cerebral ischemia reperfusion and investigate whether autophagy is involved in its mechanism of action. METHODS: Adult male Sprague Dawley rats were randomly divided into three groups: the sham, cerebral ischemia reperfusion (I/R), and I/R + BHD groups. A rat model of cerebral I/R injury was established via middle cerebral artery occlusion (MCAO) for 2 h, followed by 1, 3, and 7 d of reperfusion. Neurological scores and regional cerebral blood flow were assessed to determine whether the model was successfully established. Brain infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. The apoptosis rate was detected using TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and neuronal damage was evaluated by Nissl staining. The Beclin-1 and LC3 protein levels in the ischemic core, penumbra, and contralateral area were analysed by Western blotting. The occurrence of autophagy in the penumbra was observed by transmission electron microscopy (TEM). RESULTS: BHD treatment alleviated the cerebral infarct volume, neuronal apoptosis rate, and neuronal damage 3 and 7 d after cerebral I/R injury. Furthermore, 3 d after reperfusion, we observed that the Beclin-1 levels were significantly decreased in the core in the I/R group, whereas transformation of LC3 I to LC3 II exhibited no obvious differences between the sham and I/R groups. In the penumbra, the Beclin-1 levels and transformation of LC3 I to LC3 II in the I/R group were significantly increased compared with that in the sham group. However, no significant difference in the contralateral area was noted between the two groups. BHD significantly inhibited the expression of Beclin-1 and the transformation of LC3 I to LC3 II in the penumbra after cerebral I/R injury but yielded no significant changes in the core and contralateral area. CONCLUSIONS: BHD exerts a neuroprotective effect by inhibiting autophagy in neurons in the penumbra after cerebral I/R injury.

The Influence of Walking Height and Width on the Gait.

Walking stability is an important factor that is related to working accidents at height. The understanding of the relationship between walking stability and walking conditions remains an unmet need. Therefore, this study aimed to investigate the effect of path height, width, and asymmetric conditions on the pressure and time information of the foot-ground interaction during walking. 12 subjects were required to walk at two height, three width, and asymmetric conditions. Plantar pressures during walking were measured with the F-scan insole sensors. The total pressures were normalized with body weight, and the temporal parameters were normalized with stance time. When the walking height increased, the plantar pressure at the "heel strike" phase did not change significantly, while that at "heel rise" and "toe off" phases significantly increased, and the "heel rise" occurred earlier, indicating a greater foot-ground interaction at the forefoot part of the sole. As the path width increased from 0.6 m to 1.2 m, the foot-ground interaction as well as the asymmetric effect approached to that of overground walking. The findings could help improve the risk assessment and footwear design.

Eigenvalue-based entropy in directed complex networks.

Entropy is an important index for describing the structure, function, and evolution of network. The existing research on entropy is primarily applied to undirected networks. Compared with an undirected network, a directed network involves a special asymmetric transfer. The research on the entropy of directed networks is very significant to effectively quantify the structural information of the whole network. Typical complex network models include nearest-neighbour coupling network, small-world network, scale-free network, and random network. These network models are abstracted as undirected graphs without considering the direction of node connection. For complex networks, modeling through the direction of network nodes is extremely challenging. In this paper, based on these typical models of complex network, a directed network model considering node connection in-direction is proposed, and the eigenvalue entropies of three matrices in the directed network is defined and studied, where the three matrices are adjacency matrix, in-degree Laplacian matrix and in-degree signless Laplacian matrix. The eigenvalue-based entropies of three matrices are calculated in directed nearest-neighbor coupling, directed small world, directed scale-free and directed random networks. Through the simulation experiment on the real directed network, the result shows that the eigenvalue entropy of the real directed network is between the eigenvalue entropy of directed scale-free network and directed small-world network.

Acupoint injection combined with pelvic floor rehabilitation in the treatment of postpartum pelvic floor disorders: A protocol of randomized controlled trial.

BACKGROUND: Female pelvic floor dysfunction is one of the common chronic diseases affecting women's physical and mental health. Pregnancy and delivery are one of the main causes. Pelvic floor rehabilitation is a common method for the treatment of postpartum pelvic floor dysfunction, but it has some defects. Acupoint injection has advantages in the treatment of postpartum pelvic floor dysfunction, but there is a lack of standard clinical research to verify it. Therefore, the purpose of this randomized controlled trial is to evaluate the efficacy and safety of acupoint injection combined with pelvic floor rehabilitation in the treatment of postpartum pelvic floor disorders. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of acupoints injection combined with pelvic floor rehabilitation. And it is approved by the Ethics Committee of Clinical Research of our hospital. Patients were randomly divided into observation group (acupoint injection combined with pelvic floor rehabilitation group) or control group (pelvic floor rehabilitation group alone). The patients were followed up for 8 weeks after 12 weeks of treatment. The observation indexes included: pelvic organ prolapse degree, pelvic floor muscle strength, urinary incontinence score, adverse reactions, among others. Data were analyzed using the statistical software package SPSS version 18.0. CONCLUSIONS: This study will evaluate the efficacy and safety of acupoint injection combined with pelvic floor rehabilitation in the treatment of postpartum pelvic floor dysfunction, and provide reliable reference for the clinical application of this project. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/VC65Z.

CBP-JMF: An Improved Joint Matrix Tri-Factorization Method for Characterizing Complex Biological Processes of Diseases.

Multi-omics molecules regulate complex biological processes (CBPs), which reflect the activities of various molecules in living organisms. Meanwhile, the applications to represent disease subtypes and cell types have created an urgent need for sample grouping and associated CBP-inferring tools. In this paper, we present CBP-JMF, a practical tool primarily for discovering CBPs, which underlie sample groups as disease subtypes in applications. Differently from existing methods, CBP-JMF is based on a joint non-negative matrix tri-factorization framework and is implemented in Python. As a pragmatic application, we apply CBP-JMF to identify CBPs for four subtypes of breast cancer. The result shows significant overlapping between genes extracted from CBPs and known subtype pathways. We verify the effectiveness of our tool in detecting CBPs that interpret subtypes of disease.

The peripheral and core regions of virus-host network of COVID-19.

Two thousand nineteen novel coronavirus SARS-CoV-2, the pathogen of COVID-19, has caused a catastrophic pandemic, which has a profound and widespread impact on human lives and social economy globally. However, the molecular perturbations induced by the SARS-CoV-2 infection remain unknown. In this paper, from the perspective of omnigenic, we analyze the properties of the neighborhood perturbed by SARS-CoV-2 in the human interactome and disclose the peripheral and core regions of virus-host network (VHN). We find that the virus-host proteins (VHPs) form a significantly connected VHN, among which highly perturbed proteins aggregate into an observable core region. The non-core region of VHN forms a large scale but relatively low perturbed periphery. We further validate that the periphery is non-negligible and conducive to identifying comorbidities and detecting drug repurposing candidates for COVID-19. We particularly put forward a flower model for COVID-19, SARS and H1N1 based on their peripheral regions, and the flower model shows more correlations between COVID-19 and other two similar diseases in common functional pathways and candidate drugs. Overall, our periphery-core pattern can not only offer insights into interconnectivity of SARS-CoV-2 VHPs but also facilitate the research on therapeutic drugs.

Simple acupuncture combined with fluoxetine in the treatment of poststroke depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Poststroke depression is a common secondary mental disorder after stroke, which increases the recurrence rate and mortality rate after stroke and hinders the recovery of function. As a combination therapy, simple acupuncture combined with fluoxetine has achieved good clinical effect, but there is a lack of evidence-based medicine. The purpose of this study is to evaluate the efficacy and safety of acupuncture combined with fluoxetine in the treatment of poststroke depression by meta-analysis. METHODS: Search Chinese and English databases: China national knowledge infrastructure, VP information Chinese Journal Service Platform, Wanfang, the China Biomedical Database, PubMed, Embase, the Cochrane Library, and web of science. A randomized controlled trial of simple acupuncture combined with fluoxetine in the treatment of poststroke depression will be selected. The retrieval time is of the establishment of the database in January 2021. Selected literature is extracted and deleted by 2 researchers, and the quality of the included literature is evaluated. The included literature is analyzed by Meta with RevMan5.3 software. RESULTS: In this study, the efficacy and safety of acupuncture combined with fluoxetine in the treatment of post-stroke depression are evaluated by Hamilton Depression scale (HAMD) and its reduction rate, Treatment Emergency Symptom Scale, Self-rating Depression Scale, and Activities of Daily living scale. CONCLUSION: This study will provide reliable evidence-based evidence for the clinical application of acupuncture combined with fluoxetine in the treatment of post-stroke depression. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/5J896.

Preparation of sheet-like covalent organic frameworks and their application for efficient preconcentration of 4-(tert-octyl)-phenol and 4-nonylphenol in textiles.

In the design of highly ordered (covalent organic frameworks) COFs with "ordered domains size and orientation" construction in a well-defined arrangement, the molecular monomers are the key factors. Here, the effect of molecular monomers on the construction of COFs has been studied, and two kinds of molecular monomers, i.e., ethanediamine (flexible amine ligand) and 4,4'-diaminobiphenyl (rigid amine ligand) have been used for developing sheet-like COFs-I and sheet-like COFs-II, respectively. Furthermore, they have been evaluated in the dispersive solid phase extraction (dSPE) procedure for textiles prior to the analysis of alkylphenol by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). The results showed that, the optimal usage amount of sheet-like COFs-II used in the dSPE procedure was less than that of sheet-like COFs-I, which may be explained by much higher adsorption capacity of sheet-like COFs via hydrogen-bonding and π-π stacking interactions. Rectilinear calibration graphs were obtained for 4-(tert-octyl)-phenol (4-tOP) and 4-nonylphenol (4-NP) in the range 0.2-20 µg/kg with determination coefficient (r2) higher than 0.9990, and the limits of detection (LODs) of 4-tOP and 4-NP were 0.039 µg/kg and 0.048 µg/kg, respectively. The developed method has been successfully applied to analysis of 50 textile samples, in which 4-tOP and 4-NP were found in six samples with concentrations in the range of 1.6 µg/kg-20.9 µg/kg.

17-DMAG disrupted the autophagy flux leading to the apoptosis of acute lymphoblastic leukemia cells by inducing heat shock cognate protein 70.

AIMS: B-lineage acute lymphoblastic leukemia (B-ALL) is most common in children. We had reported heat shock protein 90 (Hsp90) over-expressed in high risk B-ALL children. 17-DMAG is a water soluble Hsp90 inhibitor, which was proved to be effective for advanced solid tumors and hematological malignancy. However, there is little research on its application in newly diagnosed B-ALL. And the detailed mechanism is seldom discussed. MAIN METHODS: Primary blast cells from 24 newly diagnosed B-ALL pediatric patients and two B-ALL cell lines were used in this study. Cell viability was measured by MTS assay. Apoptosis was evaluated by flow cytometry after annexin V-PI double staining. Protein expression was detected by immunoblotting analysis and immunofluorescence imaging. Cyto-ID autophagy detection assay was performed to show the autophagosomes and LysoTracker labeling to show the lysosomes. Gene knockdown was performed by RNA interference, and mRNA expression was measured by RT-qPCR. KEY FINDINGS: We showed 17-DMAG induced apoptosis in newly diagnosed B-ALL blasts and cell lines effectively. 17-DMAG induced heat shock cognate protein 70 (Hsc70) expression significantly. High expressed Hsc70 inhibited cathepsin D post-transcriptionally to impede the autophagic flux, which lead to the cell death. SIGNIFICANCE: Our work added new information towards understanding the molecular pharmacology of 17-DMAG, and suggested the newly diagnosed B-ALL pediatric patients might be benefited from 17-DMAG. Furthermore, we proved Hsc70 participated in the mechanism of cell death 17-DMAG leading in B-ALL.

HDAC-selective Inhibitor Cay10603 Has Single Anti-tumour Effect in Burkitt's Lymphoma Cells by Impeding the Cell Cycle.

Histone deacetylases (HDACs) inhibitors are novel in cancer therapy nowadays. HDAC6-selective inhibitors exert advantageous effects due to higher selectivity and less toxicity. We explored the anti-tumor effect and the molecular mechanism of cay10603, a potent HDAC6 inhibitor in Burkitt's lymphoma cells. Our study revealed cay10603 inhibited the proliferation of Burkitt's lymphoma cell lines, and induced caspase-dependent apoptosis. Cay10603 inhibited the expression of CDKs and cyclins to impede cell cycle progression in both Burkitt's lymphoma cell lines. Cay10603 also showed the additive effect with vp16 notably. Our data presented the promising anti-tumor effect of cay10603 in the Burkitt's lymphoma therapy.

Is concomitant splenectomy necessary in radical gastric cancer surgery? A systematic review and meta-analysis.

PURPOSE: This study is a systematic review and meta-analysis compare the short- and long-term outcomes of splenectomy (SP) versus splenic preservation (NSP) in radical gastric cancer surgery. METHODS: A comprehensive search of PubMed, Embase, Cochrane Library and Web of Knowledge was performed. Evaluation of short- and long-term outcomes was collected and analyzed by a fixed or random effects model, according to the heterogeneity using RevMan 5.2 software. RESULTS: A total of 5431 gastric cancer patients who underwent radical surgery (1706 with SP and 3725 with NSP) were reviewed in 11 studies included in this study. Compared with NSP, SP was significantly associated with higher rate of overall postoperative complication and increased incidence of pulmonary complications, abdominal abscess and pancreas complications. No statistical difference was observed regarding mortality, wound infection, anastomotic leakage and postoperative 5-year overall survival. CONCLUSION: There was no difference in long-term oncological outcome but remarkably poorer short-term outcomes in SP group than NSP group. Therefore, SP seems unnecessary in radical gastric cancer surgery. However, well-designed, multicenter, prospective, randomized controlled trials are warranted for further validation.