Comprehensive evaluation of computational methods for predicting cancer driver genes.

Optimal methods could effectively improve the accuracy of predicting and identifying candidate driver genes. Various computational methods based on mutational frequency, network and function approaches have been developed to identify mutation driver genes in cancer genomes. However, a comprehensive evaluation of the performance levels of network-, function- and frequency-based methods is lacking. In the present study, we assessed and compared eight performance criteria for eight network-based, one function-based and three frequency-based algorithms using eight benchmark datasets. Under different conditions, the performance of approaches varied in terms of network, measurement and sample size. The frequency-based driverMAPS and network-based HotNet2 methods showed the best overall performance. Network-based algorithms using protein-protein interaction networks outperformed the function- and the frequency-based approaches. Precision, F1 score and Matthews correlation coefficient were low for most approaches. Thus, most of these algorithms require stringent cutoffs to correctly distinguish driver and non-driver genes. We constructed a website named Cancer Driver Catalog (http://159.226.67.237/sun/cancer_driver/), wherein we integrated the gene scores predicted by the foregoing software programs. This resource provides valuable guidance for cancer researchers and clinical oncologists prioritizing cancer driver gene candidates by using an optimal tool.

Magnetoelectricity-Mediated Tunable Absorption and Release of Peroxide Dianions.

Peroxide dianion (O22-) has strong oxidizing activity and ease of proton abstraction and is extremely unstable. Direct and controllable adsorption and release of O22- has large application implication and is a large challenge so far. Here, we use a unique metal (Ni)-organic (diphenylalanine, DPA) framework (MOF), Ni(DPA)2, as adsorbents for absorption and release of O22-. This MOF structure has room-temperature magnetoelectricity via distortion of the Ni-centered octahedron {NiN2O4} and thus possesses a tunable ferroelectric polarization under applied electric/magnetic fields. Controllable adsorption and release of O22- are realized in such a MOF system via electrochemical redox measurements. Structural/spectroscopic characterization and calculations reveal that a number of NH active sites in the nanopores of MOF can effectively adsorb O22- by hydrogen bonds and then tunable ferroelectric polarization induces controllable release of O22- under applied magnetic fields. This work presents a constructive way for controllable adsorption and release of reactive oxygen species.

Target Density Effects on Charge Transfer of Laser-Accelerated Carbon Ions in Dense Plasma.

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft x-ray regime. We use the tricellulose acetate (C_{9}H_{16}O_{8}) foam of 2 mg/cm^{3} density and 1 mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. We diagnose the plasma parameters to be T_{e}=17 eV and n_{e}=4×10^{20} cm^{-3}. We observe the average charge states passing through the plasma to be higher than those predicted by the commonly used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects, which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. The underlying physics is actually the balancing of the lifetime of excited states versus the collisional frequency. In previous measurement with partially ionized plasma from gas discharge and z pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we are able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-glass laser radiation. The finding is important for heavy ion beam driven high-energy-density physics and fast ignitions. The method provides a new approach to precisely address the beam-plasma interaction issues with high-intensity short-pulse lasers in dense plasma regimes.

Determination of the coefficient of thermal expansion of ultra-low-expansion glass using an ultrasonic immersion testing method.

The coefficient of thermal expansion (CTE) of ultra-low-expansion (ULE) glass is critical to the development of precision optical systems. Herein, an ultrasonic immersion pulse-reflection method is proposed to characterize the CTE of ULE glass. The ultrasonic longitudinal wave velocity of ULE-glass samples with significantly different CTE values was measured using a correlation algorithm combined with moving-average filtering, which can achieve 0.2 m/s precision with a contribution to the ultrasonic CTE measurement uncertainty of 0.47 ppb/°C. Furthermore, the established ultrasonic CTE measurement model predicted the 5°C-35°C mean CTE with a root-mean-square error of 0.9 ppb/°C. Notably, a complete uncertainty analysis methodology was established in this paper, which can provide directional guidance for the subsequent development of higher-performance measurement devices and the improvement of relevant signal processing procedures.

Lead exposure disturbs ATP7B-mediated copper export from brain barrier cells by inhibiting XIAP-regulated COMMD1 protein degradation.

The brain barrier is an important structure for metal ion homeostasis. According to studies, lead (Pb) exposure disrupts the transportation of copper (Cu) through the brain barrier, which may cause impairment of the nervous system; however, the specific mechanism is unknown. The previous studies suggested the X-linked inhibitor of apoptosis (XIAP) is a sensor for cellular Cu level which mediate the degradation of the MURR1 domain-containing 1 (COMMD1) protein. XIAP/COMMD1 axis was thought to be an important regulator in Cu metabolism maintenance. In this study, the role of XIAP-regulated COMMD1 protein degradation in Pb-induced Cu disorders in brain barrier cells was investigated. Pb exposure significantly increased Cu levels in both cell types, according to atomic absorption technology testing. Western blotting and reverse transcription PCR (RT-PCR) showed that COMMD1 protein levels were significantly increased, whereas XIAP, ATP7A, and ATP7B protein levels were significantly decreased. However, there were no significant effects at the messenger RNA (mRNA) level (XIAP, ATP7A, and ATP7B). Pb-induced Cu accumulation and ATP7B expression were reduced when COMMD1 was knocked down by transient small interfering RNA (siRNA) transfection. In addition, transient plasmid transfection of XIAP before Pb exposure reduced Pb-induced Cu accumulation, increased COMMD1 protein levels, and decreased ATP7B levels. In conclusion, Pb exposure can reduce XIAP protein expression, increase COMMD1 protein levels, and specifically decrease ATP7B protein levels, resulting in Cu accumulation in brain barrier cells.

Prevalence and architecture of posttranscriptionally impaired synonymous mutations in 8,320 genomes across 22 cancer types.

Somatic synonymous mutations are one of the most frequent genetic variants occurring in the coding region of cancer genomes, while their contributions to cancer development remain largely unknown. To assess whether synonymous mutations involved in post-transcriptional regulation contribute to the genetic etiology of cancers, we collected whole exome data from 8,320 patients across 22 cancer types. By employing our developed algorithm, PIVar, we identified a total of 22,948 posttranscriptionally impaired synonymous SNVs (pisSNVs) spanning 2,042 genes. In addition, 35 RNA binding proteins impacted by these identified pisSNVs were significantly enriched. Remarkably, we discovered markedly elevated ratio of somatic pisSNVs across all 22 cancer types, and a high pisSNV ratio was associated with worse patient survival in five cancer types. Intriguing, several well-established cancer genes, including PTEN, RB1 and PIK3CA, appeared to contribute to tumorigenesis at both protein function and posttranscriptional regulation levels, whereas some pisSNV-hosted genes, including UBR4, EP400 and INTS1, exerted their function during carcinogenesis mainly via posttranscriptional mechanisms. Moreover, we predicted three drugs associated with two pisSNVs, and numerous compounds associated with expression signature of pisSNV-hosted genes. Our study reveals the prevalence and clinical relevance of pisSNVs in cancers, and emphasizes the importance of considering posttranscriptional impaired synonymous mutations in cancer biology.

CirGRDB: a database for the genome-wide deciphering circadian genes and regulators.

Circadian rhythms govern various kinds of physiological and behavioral functions of the living organisms, and disruptions of the rhythms are highly detrimental to health. Although several databases have been built for circadian genes, a resource for comprehensive post-transcriptional regulatory information of circadian RNAs and expression patterns of disease-related circadian RNAs is still lacking. Here, we developed CirGRDB (http://cirgrdb.biols.ac.cn) by integrating more than 4936 genome-wide assays, with the aim of fulfilling the growing need to understand the rhythms of life. CirGRDB presents a friendly web interface that allows users to search and browse temporal expression patterns of interested genes in 37 human/mouse tissues or cell lines, and three clinical disorders including sleep disorder, aging and tumor. More importantly, eight kinds of potential transcriptional and post-transcriptional regulators involved in the rhythmic expression of the specific genes, including transcription factors, histone modifications, chromatin accessibility, enhancer RNAs, miRNAs, RNA-binding proteins, RNA editing and RNA methylation, can also be retrieved. Furthermore, a regulatory network could be generated based on the regulatory information. In summary, CirGRDB offers a useful repository for exploring disease-related circadian RNAs, and deciphering the transcriptional and post-transcriptional regulation of circadian rhythms.

Demonstration of Coherent Terahertz Transition Radiation from Relativistic Laser-Solid Interactions.

Coherent transition radiation in the terahertz (THz) region with energies of sub-mJ/pulse has been demonstrated by relativistic laser-driven electron beams crossing the solid-vacuum boundary. Targets including mass-limited foils and layered metal-plastic targets are used to verify the radiation mechanism and characterize the radiation properties. Observations of THz emissions as a function of target parameters agree well with the formation-zone and diffraction model of transition radiation. Particle-in-cell simulations also well reproduce the observed characteristics of THz emissions. The present THz transition radiation enables not only a potential tabletop brilliant THz source, but also a novel noninvasive diagnostic for fast electron generation and transport in laser-plasma interactions.

Absorption, distribution and pathological injury in mice due to ricin poisoning via the alimentary pathway.

The aim of this work was to investigate the potential interactions between intestinal absorbance and ricin poisoning. The Caco-2 cell monolayer and everted intestinal sac (VEIS) models were used. The distribution of ricin in CD-1 mice intoxicated with 0.1 mg/kg of ricin intragastrically was determined by immunohistochemistry. The results showed that ricin could not transfer across the healthy Caco-2 cell monolayer within three hours after poisoning. However, it could pass through the everted rat intestinal wall after 0.5 h of incubation. The toxin in the liver, spleen, lungs and kidneys of mice could be detected as early as 1 h after intoxication. The pathological results were in accordance with the cytotoxicities of ricin in Caco-2, HepG 2, H1299 and MDCK cells, indicating that though no significant symptom in mice could be observed within 3 h after ricin intoxication, important tissues, especially the kidneys, were being injured by the toxin and that the injuries were progressing.

Nanoclay Hydrogel Microspheres with a Sandwich-Like Structure for Complex Tissue Infection Treatment.

Addressing complex tissue infections remains a challenging task because of the lack of effective means, and the limitations of traditional bioantimicrobial materials in single-application scenarios hinder their utility for complex infection sites. Hence, the development of a bioantimicrobial material with broad applicability and potent bactericidal activity is necessary to treat such infections. In this study, a layered lithium magnesium silicate nanoclay (LMS) is used to construct a nanobactericidal platform. This platform exhibits a sandwich-like structure, which is achieved through copper ion modification using a dopamine-mediated metallophenolic network. Moreover, the nanoclay is encapsulated within gelatin methacryloyl (GelMA) hydrogel microspheres for the treatment of complex tissue infections. The results demonstrate that the sandwich-like micro- and nanobactericidal hydrogel microspheres effectively eradicated Staphylococcus aureus (S. aureus) while exhibiting excellent biocompatibility with bone marrow-derived mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs). Furthermore, the hydrogel microspheres upregulated the expression levels of osteogenic differentiation and angiogenesis-related genes in these cells. In vivo experiments validated the efficacy of sandwich-like micro- and nanobactericidal hydrogel microspheres when injected into deep infected tissues, effectively eliminating bacteria and promoting robust vascular regeneration and tissue repair. Therefore, these innovative sandwich-like micro- and nanobacteriostatic hydrogel microspheres show great potential for treating complex tissue infections.

Enhancer demethylation-regulated gene score identified molecular subtypes, inspiring immunotherapy or CDK4/6 inhibitor therapy in oesophageal squamous cell carcinoma.

BACKGROUND: The 5-year survival rate of oesophageal squamous cell carcinoma (ESCC) is approximately 20%. The prognosis and drug response exhibit substantial heterogeneity in ESCC, impeding progress in survival outcomes. Our goal is to identify a signature for tumour subtype classification, enabling precise clinical treatments. METHODS: Utilising pre-treatment multi-omics data from an ESCC dataset (n = 310), an enhancer methylation-eRNA-target gene regulation network was constructed and validated by in vitro experiments. Four machine learning methods collectively identified core target genes, establishing an Enhancer Demethylation-Regulated Gene Score (EDRGS) model for classification. The molecular function of EDRGS subtyping was explored in scRNA-seq (n = 60) and bulk-seq (n = 310), and the EDRGS's potential to predict treatment response was assessed in datasets of various cancer types. FINDINGS: EDRGS stratified ESCCs into EDRGS-high/low subtypes, with EDRGS-high signifying a less favourable prognosis in ESCC and nine additional cancer types. EDRGS-high exhibited an immune-hot but immune-suppressive phenotype with elevated immune checkpoint expression, increased T cell infiltration, and IFNγ signalling in ESCC, suggesting a better response to immunotherapy. Notably, EDRGS outperformed PD-L1 in predicting anti-PD-1/L1 therapy effectiveness in ESCC (n = 42), kidney renal clear cell carcinoma (KIRC, n = 181), and bladder urothelial carcinoma (BLCA, n = 348) cohorts. EDRGS-low showed a cell cycle-activated phenotype with higher CDK4 and/or CDK6 expression, demonstrating a superior response to the CDK4/6 inhibitor palbociclib, validated in ESCC (n = 26), melanoma (n = 18), prostate cancer (n = 15) cells, and PDX models derived from patients with pancreatic cancer (n = 30). INTERPRETATION: Identification of EDRGS subtypes enlightens ESCC categorisation, offering clinical insights for patient management in immunotherapy (anti-PD-1/L1) and CDK4/6 inhibitor therapy across cancer types. FUNDING: This study was supported by funding from the National Key R&D Program of China (2021YFC2501000, 2020YFA0803300), the National Natural Science Foundation of China (82030089, 82188102), the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-018, 2022-I2M-2-001, 2021-I2M-1-067), the Fundamental Research Funds for the Central Universities (3332021091).

High-brightness betatron emission from the interaction of a sub picosecond laser pulse with pre-ionized low-density polymer foam for ICF research.

Direct laser acceleration (DLA) of electrons in plasmas of near-critical density (NCD) is a very advancing platform for high-energy PW-class lasers of moderate relativistic intensity supporting Inertial Confinement Fusion research. Experiments conducted at the PHELIX sub-PW Nd:glass laser demonstrated application-promising characteristics of DLA-based radiation and particle sources, such as ultra-high number, high directionality and high conversion efficiency. In this context, the bright synchrotron-like (betatron) radiation of DLA electrons, which arises from the interaction of a sub-ps PHELIX laser pulse with an intensity of 1019 W/cm2 with pre-ionized low-density polymer foam, was studied. The experimental results show that the betatron radiation produced by DLA electrons in NCD plasma is well directed with a half-angle of 100-200 mrad, yielding (3.4 ± 0.4)·1010 photons/keV/sr at 10 keV photon energy. The experimental photon fluence and the brilliance agree well with the particle-in-cell simulations. These results pave the way for innovative applications of the DLA regime using low-density pre-ionized foams in high energy density research.

Material sensitivity of patient-specific finite element models in the brace treatment of scoliosis.

Objectives: To study the mechanical sensitivity of different intervertebral disc and bone material parameters and ligaments under different force configurations and magnitudes in the scoliosis model. Methods: The finite element model of a 21-year-old female is built using computed tomography. Local range of motion testing and global bending simulations are performed for the model verification. Subsequently, Five force of different directions and configurations were applied to the finite element model applying the brace pad position. The material parameters of the model were related to different spinal flexibilities and included different material parameters of cortical bone, cancellous bone, nucleus and annulus. The virtual X-ray technique measured Cobb angle, thoracic Lordosis, and lumbar Kyphosis. Results: The difference in peak displacement is 9.28 mm, 19.99 mm, 27.06 mm, 43.99 mm, and 50.1 mm under five force configurations. The maximum Cobb angle difference due to material parameters are 4.7° and 6.2°, which are converted to thoracic and lumbar in-brace correction difference of 18% and 15.5%. The maximum difference in Kyphosis and Lordosis angle is 4.4° and 5.8°. The average thoracic and lumbar Cobb angle variation difference in intervertebral disc control group is larger than that in bone control group, while the average Kyphosis and Lordosis angle is inverse. The displacement distribution of models with or without ligaments is similar, with a peak displacement difference of 1.3 mm in C5. The peak stress occurred at the junction of the cortical bone and ribs. Conclusion: Spinal flexibility largely influences the treatment effect of the brace. The intervertebral disc has a greater effect on the Cobb angle, the bone has a greater effect on the Kyphosis and Lordosis angles, and the rotation is affected by both. Patient-specific material is the key to increasing accuracy in the personalized finite element model. This study provides a scientific basis for using controllable brace treatment for scoliosis.

High-density electron transfer in Ni-metal-organic framework@FeNi-layered double hydroxide for efficient electrocatalytic oxygen evolution.

The electrochemical oxygen evolution reaction is a bottleneck reaction in hydrolysis and electrolysis because the four-step electron transfer leads to slow reaction kinetics and large overpotentials. This situation can be improved by fast charge transfer by optimizing the interfacial electronic structure and enhancing polarization. Herein, a unique metal (Ni) organic (diphenylalanine, DPA) framework Ni(DPA)2 (Ni-MOF) with tunable polarization is designed to bond with FeNi-LDH (layered double hydroxides) nanoflakes. The Ni-MOF@FeNi-LDH heterostructure delivers excellent oxygen evolution performance exemplified by an ultralow overpotential of 198 mV at 100 mA cm-2 compared to other (FeNi-LDH)-based catalysts. Experiments and theoretical calculations show that FeNi-LDH exists in an electron-rich state in Ni-MOF@FeNi-LDH due to polarization enhancement caused by interfacial bonding with Ni-MOF. This effectively changes the local electronic structure of the metal Fe/Ni active sites and optimizes adsorption of the oxygen-containing intermediates. Polarization and electron transfer of Ni-MOF are further enhanced by magnetoelectric coupling consequently giving rise to better electrocatalytic properties as a result of high-density electron transfer to active sites. These findings reveal a promising interface and polarization modulation strategy to improve electrocatalysis.

Intensive bracing management combined with physiotherapeutic scoliosis-specific exercises for adolescent idiopathic scoliosis patients with a major curve ranging from 40-60° who refused surgery: a prospective cohort study.

BACKGROUND: Current guidelines for brace management of adolescent idiopathic scoliosis (AIS) are mostly recommended for curves between 25° to 40°. For AIS patients with curves >40°, surgery is often considered since bracing may be less effective; however, there are still some patients and families who refuse operation. Therefore, further research is necessary to determine optimal bracing management in this group. To date, few protocols for such have been reported in literature. AIM: The aim of this study was to introduce and evaluate the effectiveness of the treatment protocol comprising of intensive bracing management and physiotherapeutic scoliosis-specific exercises (PSSE) in AIS patients with a major curve of 40-60° who refuse surgery. DESIGN: This is a prospective cohort study. SETTING: The study was carried out in an outpatient clinic. POPULATION: 10-18-year-old AIS patients having 40-60°curves and a Risser grade of 0-3, but firmly refusing surgery were eligible. Patients who had a proximal thoracic curve or had undergone any other form of treatment previously were excluded from the study. METHODS: A total of 82 patients were recruited and received the treatment. The primary outcome was defined as "success" when the main curve was below 50° upon reaching skeletal maturity, and "failure" if otherwise. The secondary outcome was defined as improved (>5° reduction), unchanged (≤5° change) or progressed (>5° increase) based on the evolution of the main curve. The per protocol (PP) and intent to treat (ITT) analyses were performed to quantify success rates, while the dropouts were considered as failures. Risk factors associated with bracing failure were identified and a receiver operating characteristic (ROC) curve was used to determine the cut-off value. RESULTS: A total of 77 patients completed the treatment, while 5 dropped out. The average main curve was 47.40±5.93° at baseline and 38.56±11.85° at last follow-up (P<0.001). Our management was successful in 83% and 78% of patients based on the PP and ITT analyses, respectively. When compared with the curve magnitude at baseline, 65% patients improved, 30% remained unchanged, and 5% progressed when using a 5° threshold. Univariate comparison and logistic regression analysis demonstrated that patients with successful outcomes had a significantly smaller baseline curve, larger Risser Stage, and larger in-brace correction (IBC) rate. CONCLUSIONS: For AIS patients with 40-60° curves who refused surgery, our intensive bracing management along with PSSE was practical and effective, achieving success in 78% of patients based on an ITT analysis. A larger baseline curve, smaller Risser Stage, and smaller IBC rate were associated with treatment failure. CLINICAL REHABILITATION IMPACT: Our intensive management provides new insights into improving the effectiveness of bracing in patients with AIS who refuse surgery. This is a promising option for patients with 40-60° curves, since their scoliosis may be treated using a non-surgical technique instead of surgery in the future.

Autistic clinical profiles, age at first concern, and diagnosis among children with autism spectrum disorder.

Background: To explore the relationship between autistic clinical profiles and age at first concern and diagnosis among children with autism spectrum disorder. The clinical profiles included the severity of autism, cognition, adaptability, language development, and regression. Methods: The multivariate linear regression model was used to examine the association of diagnostic age and first-concern age with autistic clinical profiles and with further stratification analysis. Results: A total of 801 autistic children were included. Language delay and regression were associated with earlier diagnostic age (language delay: crudeß: -0.80, 95%CI%: -0.92--0.68; regression: crudeß: -0.21, 95%CI%: -0.43--0.00) and the age of first concern of autistic children (language delay: crudeß: -0.55, 95%CI%: -0.65--0.45; regression: crudeß: -0.17, 95%CI%: -0.34--0.00). After stratification by sex, language delay tended to be more associated with the earlier diagnostic age among boys (crudeß: -0.85, 95%CI%: -0.98--0.72) than among girls (crudeß: -0.46, 95%CI%: -0.77--0.16). After stratification by maternal education level or family income level, language delay was most associated with the earlier diagnostic age in autistic children from families with higher socioeconomic levels. Conclusion: Language delay, rather than other symptoms, promoted an earlier diagnostic age. Among male autistic children or children from families with higher socioeconomic levels, language delay was most significantly associated with an earlier age of diagnosis. Cognitive delay, or adaptive delay, was associated with a later age at diagnosis and presented only in autistic children from families with lower socioeconomic levels. There may be sex or socioeconomic inequality in the diagnostic age for autistic children. More publicity and public education about the diversity of autistic symptoms are urgently needed in the future, especially for low-socioeconomic families.

Integrated multi-omics profiling yields a clinically relevant molecular classification for esophageal squamous cell carcinoma.

Integrated molecular analysis of human cancer has yielded molecular classification for precise management of cancer patients. Here, we analyzed the whole genomic, epigenomic, transcriptomic, and proteomic data of 155 esophageal squamous cell carcinomas (ESCCs). Multi-omics analysis led to the classification of ESCCs into four subtypes: cell cycle pathway activation, NRF2 oncogenic activation, immune suppression (IS), and immune modulation (IM). IS and IM cases were highly immune infiltrated but differed in the type and distribution of immune cells. IM cases showed better response to immune checkpoint blockade therapy than other subtypes in a clinical trial. We further developed a classifier with 28 features to identify the IM subtype, which predicted anti-PD-1 therapy response with 85.7% sensitivity and 90% specificity. These results emphasize the clinical value of unbiased molecular classification based on multi-omics data and have the potential to further improve the understanding and treatment of ESCC.

Finite element analysis in brace treatment on adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a musculoskeletal disorder characterized as three-dimensional (3D) deformity, and bracing is a common conservative treatment for AIS. Finite element analysis (FEA) is a technique for numerically solving the differential equations arising in engineering and mathematical modeling and has been widely used in biomechanical studies. Recently, FEA has been under intensive focus to improve the clinical outcomes of brace treatment. This review focuses on using FEA to assist brace treatment for AIS and technique choices that may be encountered during the construction of the finite element model (FEM). The construction of geometric models, the mechanical property, element type, the boundary condition, and the observation items of FEA have been summarized while establishing FEM. In each technical aspect, different fields and limitations of FEA are discussed. The observation items based on FEA are collected in addition to the biomechanical value in clinical research. We also summarized the technical aspects of brace treatment by FEA and observation items and provided guidance and directions to improve the brace treatment.

Finite element analysis of fixation effect for femoral neck fracture under different fixation configurations.

In this study, the biomechanical differences among three internal fixation configurations for treatment of Pauwels type II and III femoral neck fractures were analyzed. Using finite element analysis, the femur displacement and stress distributions of the internal fixation device and fracture section were obtained for different patients and movement conditions. The results show that patients with osteoporosis are more prone to femoral varus and femoral neck shortening, and the fracture probability of the device for these patients is higher than that for patients with normal bone. The treatment effect of the inverted-triangle screw (ITS) fixation and proximal femoral nail anti-rotation (PFNA) fixation is better than that of dynamic hip screw (DHS) fixation. The ITS fixation is more suitable for the treatment of the normal bone patients with Pauwels II femur neck fracture. However, the PFNA fixation has better biomechanical advantages and better capability for anti-femoral neck shortening. Therefore, it is suitable for the treatment of femoral neck fracture patients with osteoporosis.

Comprehensive characterization of posttranscriptional impairment-related 3'-UTR mutations in 2413 whole genomes of cancer patients.

The 3' untranslated region (3'-UTR) is the vital element regulating gene expression, but most studies have focused on variations in RNA-binding proteins (RBPs), miRNAs, alternative polyadenylation (APA) and RNA modifications. To explore the posttranscriptional function of 3'-UTR somatic mutations in tumorigenesis, we collected whole-genome data from 2413 patients across 18 cancer types. Our updated algorithm, PIVar, revealed 25,216 3'-UTR posttranscriptional impairment-related SNVs (3'-UTR piSNVs) spanning 2930 genes; 24 related RBPs were significantly enriched. The somatic 3'-UTR piSNV ratio was markedly increased across all 18 cancer types, which was associated with worse survival for four cancer types. Several cancer-related genes appeared to facilitate tumorigenesis at the protein and posttranscriptional regulation levels, whereas some 3'-UTR piSNV-affected genes functioned mainly via posttranscriptional mechanisms. Moreover, we assessed immune cell and checkpoint characteristics between the high/low 3'-UTR piSNV ratio groups and predicted 80 compounds associated with the 3'-UTR piSNV-affected gene expression signature. In summary, our study revealed the prevalence and clinical relevance of 3'-UTR piSNVs in cancers, and also demonstrates that in addition to affecting miRNAs, 3'-UTR piSNVs perturb RBPs binding, APA and m6A RNA modification, which emphasized the importance of considering 3'-UTR piSNVs in cancer biology.