BCSLinker: automatic method for constructing a knowledge graph of venous thromboembolism based on joint learning.

Background: Venous thromboembolism (VTE) is characterized by high morbidity, mortality, and complex treatment. A VTE knowledge graph (VTEKG) can effectively integrate VTE-related medical knowledge and offer an intuitive description and analysis of the relations between medical entities. However, current methods for constructing knowledge graphs typically suffer from error propagation and redundant information. Methods: In this study, we propose a deep learning-based joint extraction model, Biaffine Common-Sequence Self-Attention Linker (BCSLinker), for Chinese electronic medical records to address the issues mentioned above, which often occur when constructing a VTEKG. First, the Biaffine Common-Sequence Self-Attention (BCsSa) module is employed to create global matrices and extract entities and relations simultaneously, mitigating error propagation. Second, the multi-label cross-entropy loss is utilized to diminish the impact of redundant information and enhance information extraction. Results: We used the electronic medical record data of VTE patients from a tertiary hospital, achieving an F1 score of 86.9% on BCSLinker. It outperforms the other joint entity and relation extraction models discussed in this study. In addition, we developed a question-answering system based on the VTEKG as a structured data source. Conclusion: This study has constructed a more accurate and comprehensive VTEKG that can provide reference for diagnosing, evaluating, and treating VTE as well as supporting patient self-care, which is of considerable clinical value.

Fusion with ARRDC1 or CD63: A Strategy to Enhance p53 Loading into Extracellular Vesicles for Tumor Suppression.

Small extracellular vesicles (sEVs) have emerged as promising therapeutic agents and drug delivery vehicles. Targeted modification of sEVs and their contents using genetic modification strategies is one of the most popular methods. This study investigated the effects of p53 fusion with arrestin domain-containing protein 1 (ARRDC1) and CD63 on the generation of sEVs, p53 loading efficiency, and therapeutic efficacy. Overexpression of either ARRDC1-p53 (ARP) or CD63-p53 (CDP) significantly elevated p53 mRNA and protein levels. The incorporation of ARRDC1 and CD63 significantly enhanced HEK293T-sEV biogenesis, evidenced by significant increases in sEV-associated proteins TSG101 and LAMP1, resulting in a boost in sEV production. Importantly, fusion with ARRDC1 or CD63 substantially increased the efficiency of loading both p53 fusion proteins and its mRNA into sEVs. sEVs equipped with ARP or CDP significantly enhanced the enrichment of p53 fusion proteins and mRNA in p53-null H1299 cells, resulting in a marked increase in apoptosis and a reduction in cell proliferation, with ARP-sEVs demonstrating greater effectiveness than CDP-sEVs. These findings underscore the enhanced functionality of ARRDC1- and CD63-modified sEVs, emphasizing the potential of genetic modifications in sEV-based therapies for targeted cancer treatment.

Risk factors and outcomes for refeeding syndrome in acute ischaemic stroke patients.

AIM: Patients with acute ischaemic stroke are more likely to develop refeeding syndrome due to increased need for nutritional support when suffering alterations of consciousness and impairment of swallowing. This study aimed to evaluate the incidence, risk factors and outcomes of refeeding syndrome in stroke patients. METHODS: This was a retrospective observational study, using the prospective stroke database from hospital, included all consecutive acute ischaemic stroke patients who received enteral nutrition for more than 72 h from 1 January 2020 and 31 December 2022. Refeeding syndrome was defined as occurrence of new-onset hypophosphataemia within 72 h after enteral feeding. Multiple logistic regression analysis was conducted to evaluate risk factors and relationships between refeeding syndrome and stroke outcomes. RESULTS: 338 patients were included in the study. 50 patients (14.8%) developed refeeding syndrome. Higher scores on National Institutes of Health Stroke Scale and Nutritional Risk Screening 2002, albumin <30 g/L and BMI <18.5 kg/m2 were risk factors for refeeding syndrome. Moreover, refeeding syndrome was independently associated with a 3-month modified Rankin Scale score of >2 and 6-month mortality. CONCLUSIONS: Refeeding syndrome was common in stroke patients and higher baseline National Institutes of Health Stroke Scale, higher Nutritional Risk Screening 2002, albumin <30 g/L and BMI <18.5 kg/m2 were independent risk factors of refeeding syndrome. Occurrence of refeeding syndrome was significantly associated with higher 3-month modified Rankin Scale and 6-month mortality.

N-acetylcysteine Protects Against Myocardial Ischemia-Reperfusion Injury Through Anti-ferroptosis in Type 1 Diabetic Mice.

The hearts of subjects with diabetes are vulnerable to ischemia-reperfusion injury (IRI). In contrast, experimentally rodent hearts have been shown to be more resistant to IRI at the very early stages of diabetes induction than the heart of the non-diabetic control mice, and the mechanism is largely unclear. Ferroptosis has recently been shown to play an important role in myocardial IRI including that in diabetes, while the specific mechanisms are still unclear. Non-diabetic control (NC) and streptozotocin-induced diabetic (DM) mice were treated with the antioxidant N-acetylcysteine (NAC) in drinking water for 4 week starting at 1 week after diabetes induction. Mice were subjected to myocardial IRI induced by occluding the coronary artery for 30 min followed by 2 h of reperfusion, subsequently at 1, 2, and 5 week of diabetes induction. The post-ischemic myocardial infarct size in the DM mice was smaller than that in NC mice at 1 week of diabetes but greater than that in the NC mice at 2 and 5 week of diabetes, which were associated with a significant increase of ferroptosis at 2 and 5 week but a significant reduction of ferroptosis at 1 week of diabetes. NAC significantly attenuated post-ischemic ferroptosis as well as oxidative stress and reduced infarct size at 2 and 5 week of diabetes. Application of erastin, a ferroptosis inducer, reversed the cardioprotective effects of NAC. It is concluded that increased oxidative stress and ferroptosis are the major factors attributable to the increased vulnerability to myocardial IRI in diabetes and that attenuation of ferroptosis represents a major mechanism whereby NAC confers cardioprotection against myocardial IRI in diabetes.

Characterizing Infections in Two Epidemic Waves of SARS-CoV-2 Omicron Variants: A Cohort Study in Guangzhou, China.

BACKGROUND: After the adjustment of COVID-19 epidemic policy, mainland China experienced two consecutive waves of Omicron variants within a seven-month period. In Guangzhou city, as one of the most populous regions, the viral infection characteristics, molecular epidemiology, and the dynamic of population immunity are still elusive. METHODS: We launched a prospective cohort study in the Guangdong Provincial CDC from December 2022 to July 2023. Fifty participants who received the same vaccination regimen and had no previous infection were recruited. RESULTS: 90% of individuals were infected with Omicron BA.5* variants within three weeks in the first wave. Thirteen cases (28.26%) experienced infection with XBB.1* variants, occurring from 14 weeks to 21 weeks after the first wave. BA.5* infections exhibited higher viral loads in nasopharyngeal sites compared to oropharyngeal sites. Compared to BA.5* infections, the XBB.1* infections had significantly milder clinical symptoms, lower viral loads, and shorter durations of virus positivity. The infection with the BA.5* variant elicited varying levels of neutralizing antibodies against XBB.1* among different individuals, even with similar levels of BA.5* antibodies. The level of neutralizing antibodies specific to XBB.1* determined the risk of reinfection. CONCLUSIONS: The rapid large-scale infections of the Omicron variants have quickly established herd immunity among the population in mainland China. In the future of the COVID-19 epidemic, a lower infection rate but a longer duration can be expected. Given the large population size and ongoing diversified herd immunity, it remains crucial to closely monitor the molecular epidemiology of SARS-CoV-2 for the emergence of new variants of concern in this region. Additionally, the timely evaluation of the immune status across different age groups is essential for informing future vaccination strategies and intervention policies.

Feasibility of implant placement in healed mandibular molar sites: A retrospective cone beam computed tomography study.

STATEMENT OF PROBLEM: Implant placement in the mandibular molar sites plays a crucial role in the restoration of edentulous mandibles. However, the evaluation of bone quantity before implant surgery using cone beam computed tomography (CBCT) is lacking. PURPOSE: The purpose of this clinical study was to evaluate CBCT images of edentulous patients to analyze the feasibility of implant placement in healed mandibular molar sites. MATERIAL AND METHODS: The CBCT data of 138 patients were analyzed in the sagittal plane for measurements of mandibular bone height (MBH), superior bone height (SBH), inferior bone height (IBH), buccal bone width (BBW), lingual bone width (LBW), and alveolar bone widths (ABWs). The edentulous sites were categorized according to the bone quantity and complexity of the implant surgery. Multivariate analysis of variance (MANOVA) was used to analyze the site, sex, and age-related variations. An independent t test was used to compare the difference of bone dimension in different sites and between sexes. One-way ANOVA followed by post hoc tests were used to analyze the difference between different age groups. Categorical variables were presented as number of events and percentages. The chi-squared test was used to compare categorical variables (α=.05). RESULTS: A total of 534 sites of interest were recorded, including 274 hemimandibles. A significant difference in BBW was found between the first and second molar sites. Men had higher MBH, SBH, IBH, and BBW than women. The distribution of implant surgical complexity in the conventional group was 63.5%, while the buccolingual tilted implant group accounted for 17.0%, and the complicated group accounted for 19.5%. Of the 274 hemimandibles, an implant could be placed directly at molar sites in 88% of situations. CONCLUSIONS: The BBW at the mandibular second molar site was greater than that at the first molar site. The amount of available bone in the SBH and BBW was greater in men than in women at the healed molar sites. Age did not significantly affect the complexity of the implant surgery. Implants can be placed directly in healed mandibular molar sites in most patients who require a complete arch mandibular implant-supported restoration.

Incorporating mesopelagic fish into the evaluation of conservation areas for marine living resources under climate change scenarios.

Mesopelagic fish (meso-fish) are central species within the Southern Ocean (SO). However, their ecosystem role and adaptive capacity to climate change are rarely integrated into protected areas assessments. This is a pity given their importance as crucial prey and predators in food webs, coupled with the impacts of climate change. Here, we estimate the habitat distribution of nine meso-fish using an ensemble model approach (MAXENT, random forest, and boosted regression tree). Four climate model simulations were used to project their distribution under two representative concentration pathways (RCP4.5 and RCP8.5) for short-term (2006-2055) and long-term (2050-2099) periods. In addition, we assess the ecological representativeness of protected areas under climate change scenarios using meso-fish as indicator species. Our models show that all species shift poleward in the future. Lanternfishes (family Myctophidae) are predicted to migrate poleward more than other families (Paralepididae, Nototheniidae, Bathylagidae, and Gonostomatidae). In comparison, lanternfishes were projected to increase habitat area in the eastern SO but lose area in the western SO; the opposite was projected for species in other families. Important areas (IAs) of meso-fish are mainly distributed near the Antarctic Peninsula and East Antarctica. Negotiated protected area cover 23% of IAs at present and 38% of IAs in the future (RCP8.5, long-term future). Many IAs of meso-fish still need to be included in protected areas, such as the Prydz Bay and the seas around the Antarctic Peninsula. Our results provide a framework for evaluating protected areas incorporating climate change adaptation strategies for protected areas management. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00188-9.

Research on Ocular Artifacts Removal from Single-Channel Electroencephalogram Signals in Obstructive Sleep Apnea Patients Based on Support Vector Machine, Improved Variational Mode Decomposition, and Second-Order Blind Identification.

The electroencephalogram (EEG) has recently emerged as a pivotal tool in brain imaging analysis, playing a crucial role in accurately interpreting brain functions and states. To address the problem that the presence of ocular artifacts in the EEG signals of patients with obstructive sleep apnea syndrome (OSAS) severely affects the accuracy of sleep staging recognition, we propose a method that integrates a support vector machine (SVM) with genetic algorithm (GA)-optimized variational mode decomposition (VMD) and second-order blind identification (SOBI) for the removal of ocular artifacts from single-channel EEG signals. The SVM is utilized to identify artifact-contaminated segments within preprocessed single-channel EEG signals. Subsequently, these signals are decomposed into variational modal components across different frequency bands using the GA-optimized VMD algorithm. These components undergo further decomposition via the SOBI algorithm, followed by the computation of their approximate entropy. An approximate entropy threshold is set to identify and remove components laden with ocular artifacts. Finally, the signal is reconstructed using the inverse SOBI and VMD algorithms. To validate the efficacy of our proposed method, we conducted experiments utilizing both simulated data and real OSAS sleep EEG data. The experimental results demonstrate that our algorithm not only effectively mitigates the presence of ocular artifacts but also minimizes EEG signal distortion, thereby enhancing the precision of sleep staging recognition based on the EEG signals of OSAS patients.

Application of LightGBM hybrid model based on TPE algorithm optimization in sleep apnea detection.

Introduction: Sleep apnoea syndrome (SAS) is a serious sleep disorder and early detection of sleep apnoea not only reduces treatment costs but also saves lives. Conventional polysomnography (PSG) is widely regarded as the gold standard diagnostic tool for sleep apnoea. However, this method is expensive, time-consuming and inherently disruptive to sleep. Recent studies have pointed out that ECG analysis is a simple and effective diagnostic method for sleep apnea, which can effectively provide physicians with an aid to diagnosis and reduce patients' suffering. Methods: To this end, in this paper proposes a LightGBM hybrid model based on ECG signals for efficient detection of sleep apnea. Firstly, the improved Isolated Forest algorithm is introduced to remove abnormal data and solve the data sample imbalance problem. Secondly, the parameters of LightGBM algorithm are optimised by the improved TPE (Tree-structured Parzen Estimator) algorithm to determine the best parameter configuration of the model. Finally, the fusion model TPE_OptGBM is used to detect sleep apnoea. In the experimental phase, we validated the model based on the sleep apnoea ECG database provided by Phillips-University of Marburg, Germany. Results: The experimental results show that the model proposed in this paper achieves an accuracy of 95.08%, a precision of 94.80%, a recall of 97.51%, and an F1 value of 96.14%. Discussion: All of these evaluation indicators are better than the current mainstream models, which is expected to assist the doctor's diagnostic process and provide a better medical experience for patients.

SMMF: a self-attention-based multi-parametric MRI feature fusion framework for the diagnosis of bladder cancer grading.

Background: Multi-parametric magnetic resonance imaging (MP-MRI) may provide comprehensive information for graded diagnosis of bladder cancer (BCa). Nevertheless, existing methods ignore the complex correlation between these MRI sequences, failing to provide adequate information. Therefore, the main objective of this study is to enhance feature fusion and extract comprehensive features from MP-MRI using deep learning methods to achieve an accurate diagnosis of BCa grading. Methods: In this study, a self-attention-based MP-MRI feature fusion framework (SMMF) is proposed to enhance the performance of the model by extracting and fusing features of both T2-weighted imaging (T2WI) and dynamic contrast-enhanced imaging (DCE) sequences. A new multiscale attention (MA) model is designed to embed into the neural network (CNN) end to further extract rich features from T2WI and DCE. Finally, a self-attention feature fusion strategy (SAFF) was used to effectively capture and fuse the common and complementary features of patients' MP-MRIs. Results: In a clinically collected sample of 138 BCa patients, the SMMF network demonstrated superior performance compared to the existing deep learning-based bladder cancer grading model, with accuracy, F1 value, and AUC values of 0.9488, 0.9426, and 0.9459, respectively. Conclusion: Our proposed SMMF framework combined with MP-MRI information can accurately predict the pathological grading of BCa and can better assist physicians in diagnosing BCa.

Kinetic 18F-FDG PET/CT imaging of hepatocellular carcinoma: a dual input four-compartment model.

BACKGROUND: The endoplasmic reticulum plays an important role in glucose metabolism and has not been explored in the kinetic estimation of hepatocellular carcinoma (HCC) via 18F-fluoro-2-deoxy-D-glucose PET/CT. METHODS: A dual-input four-compartment (4C) model, regarding endoplasmic reticulum was preliminarily used for kinetic estimation to differentiate 28 tumours from background liver tissue from 24 patients with HCC. Moreover, parameter images of the 4C model were generated from one patient with negative findings on conventional metabolic PET/CT. RESULTS: Compared to the dual-input three-compartment (3C) model, the 4C model has better fitting quality, a close transport rate constant (K1) and a dephosphorylation rate constant (k6/k4), and a different removal rate constant (k2) and phosphorylation rate constant (k3) in HCC and background liver tissue. The K1, k2, k3, and hepatic arterial perfusion index (HPI) from the 4C model and k3, HPI, and volume fraction of blood (Vb) from the 3C model were significantly different between HCC and background liver tissues (all P < 0.05). Meanwhile, the 4C model yielded additional kinetic parameters for differentiating HCC. The diagnostic performance of the top ten genes from the most to least common was HPI(4C), Vb(3C), HPI(3C), SUVmax, k5(4C), k3(3C), k2(4C), v(4C), K1(4C) and Vb(4C). Moreover, a patient who showed negative findings on conventional metabolic PET/CT had positive parameter images in the 4C model. CONCLUSIONS: The 4C model with the endoplasmic reticulum performed better than the 3C model and produced additional useful parameters in kinetic estimation for differentiating HCC from background liver tissue.

Effect of brominated flame retardants exposure on liver function and the risk of non-alcoholic fatty liver disease in the US population.

BACKGROUND: The relationship between brominated flame retardants (BFRs) exposure and the human liver was still not well understood. METHODS: A total of 3108 participants (age > 12) from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016 were included as the study population, with nine BFRs exhibiting a detection rate of over 70% serving as the exposure factor. The singular effects and combined effects of BFRs exposure on liver injury, non-alcoholic fatty liver disease (NAFLD), and advanced hepatic fibrosis (AHF) were evaluated separately. Finally, COX regression was employed to explore the hazard ratios associated with individual BFRs. RESULTS: In our analysis of individual exposures, we found significant positive association of PBB153 with alanine aminotransferase (ALT), PBB153 with aspartate aminotransferase (AST), PBDE47, PBDE85, PBDE99, PBDE100, and PBDE154 with alkaline phosphatase (ALP), PBDE28 and PBB153 with gamma-glutamyl transaminase (GGT), PBB153 with the risk of NAFLD and AHF; and significant negative association of PBB153 with ALP, PBDE28, PBDE47, PBDE99, PBDE100, PBDE85, PBDE209, and PBDE154 with albumin (ALB), PBB153 with AST/ALT. The nonlinear analysis results from Restricted Cubic Spline (RCS) further validated these associations (all P<0.05). In the mixed analysis combining Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analysis, BFRs were positively associated with ALT (ß>0, P<0.001), GGT (ß>0, P<0.001), and the risk of NAFLD (OR>1, P=0.007). Conversely, BFRs exhibited significant negative correlations with ALP (ß<0, P<0.001), ALB (ß<0, P<0.001), and AST/ALT (ß<0, P<0.001). Furthermore, the COX regression analysis revealed that PBB153 had the highest hazard ratio among the BFRs. CONCLUSIONS: BFR exposure may increase the risk of liver injury and NAFLD, with no significant association with AHF risk. The impact of BFR exposure on liver health should not be overlooked, especially in individuals residing in impoverished areas.

Resolving the In Situ Three-Dimensional Structure of Fly Mechanosensory Organelles Using Serial Section Electron Tomography.

Mechanosensory organelles (MOs) are specialized subcellular entities where force-sensitive channels and supporting structures (e.g., microtubule cytoskeleton) are organized in an orderly manner. The delicate structure of MOs needs to be resolved to understand the mechanisms by which they detect forces and how they are formed. Here, we describe a protocol that allows obtaining detailed information about the nanoscopic ultrastructure of fly MOs by using serial section electron tomography (SS-ET). To preserve fine structural details, the tissues are cryo-immobilized using a high-pressure freezer followed by freeze-substitution at low temperature and embedding in resin at room temperature. Then, sample sections are prepared and used to acquire the dual-axis tilt series images, which are further processed for tomographic reconstruction. Finally, tomograms of consecutive sections are combined into a single larger volume using microtubules as fiducial markers. Using this protocol, we managed to reconstruct the sensory organelles, which provide novel molecular insights as to how fly mechanosensory organelles work and are formed. Based on our experience, we think that, with minimal modifications, this protocol can be adapted to a wide range of applications using different cell and tissue samples. Key features • Resolving the high-resolution 3D ultrastructure of subcellular organelles using serial section electron tomography (SS-ET). • Compared with single-axis tilt series, dual-axis tilt series provides a much wider coverage of Fourier space, improving resolution and features in the reconstructed tomograms. • The use of high-pressure freezing and freeze-substitution maximally preserves the fine structural details.

Enhanced immunity against SARS-CoV-2 in returning Chinese individuals.

Global COVID-19 vaccination programs effectively contained the fast spread of SARS-CoV-2. Characterizing the immunity status of returned populations will favor understanding the achievement of herd immunity and long-term management of COVID-19 in China. Individuals were recruited from 7 quarantine stations in Guangzhou, China. Blood and throat swab specimens were collected from participants, and their immunity status was determined through competitive ELISA, microneutralization assay and enzyme-linked FluoroSpot assay. A total of 272 subjects were involved in the questionnaire survey, of whom 235 (86.4%) were returning Chinese individuals and 37 (13.6%) were foreigners. Blood and throat swab specimens were collected from 108 returning Chinese individuals. Neutralizing antibodies against SARS-CoV-2 were detected in ~90% of returning Chinese individuals, either in the primary or the homologous and heterologous booster vaccination group. The serum NAb titers were significantly decreased against SARS-CoV-2 Omicron BA.5, BF.7, BQ.1 and XBB.1 compared with the prototype virus. However, memory T-cell responses, including specific IFN-γ and IL-2 responses, were not different in either group. Smoking, alcohol consumption, SARS-CoV-2 infection, COVID-19 vaccination, and the time interval between last vaccination and sampling were independent influencing factors for NAb titers against prototype SARS-CoV-2 and variants of concern. The vaccine dose was the unique common influencing factor for Omicron subvariants. Enhanced immunity against SARS-CoV-2 was established in returning Chinese individuals who were exposed to reinfection and vaccination. Domestic residents will benefit from booster homologous or heterologous COVID-19 vaccination after reopening of China, which is also useful against breakthrough infection.

EI-MVSNet: Epipolar-Guided Multi-View Stereo Network With Interval-Aware Label.

Recent learning-based methods demonstrate their strong ability to estimate depth for multi-view stereo reconstruction. However, most of these methods directly extract features via regular or deformable convolutions, and few works consider the alignment of the receptive fields between views while constructing the cost volume. Through analyzing the constraint and inference of previous MVS networks, we find that there are still some shortcomings that hinder the performance. To deal with the above issues, we propose an Epipolar-Guided Multi-View Stereo Network with Interval-Aware Label (EI-MVSNet), which includes an epipolar-guided volume construction module and an interval-aware depth estimation module in a unified architecture for MVS. The proposed EI-MVSNet enjoys several merits. First, in the epipolar-guided volume construction module, we construct cost volume with features from aligned receptive fields between different pairs of reference and source images via epipolar-guided convolutions, which take rotation and scale changes into account. Second, in the interval-aware depth estimation module, we attempt to supervise the cost volume directly and make depth estimation independent of extraneous values by perceiving the upper and lower boundaries, which can achieve fine-grained predictions and enhance the reasoning ability of the network. Extensive experimental results on two standard benchmarks demonstrate that our EI-MVSNet performs favorably against state-of-the-art MVS methods. Specifically, our EI-MVSNet ranks 1st on both intermediate and advanced subsets of the Tanks and Temples benchmark, which verifies the high precision and strong robustness of our model.

Magnetic resonance-guided focused ultrasound for essential tremor: a prospective, single center, single-arm study.

JOURNAL/nrgr/04.03/01300535-202409000-00041/figure1/v/2024-01-16T170235Z/r/image-tiff The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor. In 2018, the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital. This prospective, single center, open-label, single-arm study was part of a worldwide prospective multicenter clinical trial (ClinicalTrials.gov Identifier: NCT03253991) conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population. From 2019 to 2020, 10 patients with medication refractory essential tremor were recruited into this open-label, single arm study. The treatment efficacy was determined using the Clinical Rating Scale for Tremor. Safety was evaluated according to the incidence and severity of adverse events. All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus. At the baseline assessment, the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3 ± 3.6, and this improved after treatment to 23.1 ± 6.4 at a 12-month follow-up assessment. A total of 50 adverse events were recorded, and 2 were defined as serious. The most common intraoperative adverse events were nausea and headache. The most frequent postoperative adverse events were paresthesia and equilibrium disorder. Most of the adverse events were mild and usually disappeared within a few days. Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective, with a good safety profile, for patients in Chinese mainland.

PTEN-mediated dephosphorylation of 53BP1 confers cellular resistance to DNA damage in cancer cells.

Homologous recombination (HR) repair for DNA double-strand breaks (DSBs) is critical for maintaining genome stability and conferring the resistance of tumor cells to chemotherapy. Nuclear PTEN which contains both phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and protein phosphatase plays a key role in HR repair, but the underlying mechanism remains largely elusive. We find that SUMOylated PTEN promotes HR repair but represses nonhomologous end joining (NHEJ) repair by directly dephosphorylating TP53-binding protein 1 (53BP1). During DNA damage responses (DDR), tumor suppressor ARF (p14ARF) was phosphorylated and then interacted efficiently with PTEN, thus promoting PTEN SUMOylation as an atypical SUMO E3 ligase. Interestingly, SUMOylated PTEN was subsequently recruited to the chromatin at DSB sites. This was because SUMO1 that was conjugated to PTEN was recognized and bound by the SUMO-interacting motif (SIM) of breast cancer type 1 susceptibility protein (BRCA1), which has been located to the core of 53BP1 foci on chromatin during S/G2 stage. Furthermore, these chromatin-loaded PTEN directly and specifically dephosphorylated phosphothreonine-543 (pT543) of 53BP1, resulting in the dissociation of the 53BP1 complex, which facilitated DNA end resection and ongoing HR repair. SUMOylation-site-mutated PTENK254R mice also showed decreased DNA damage repair in vivo. Blocking the PTEN SUMOylation pathway with either a SUMOylation inhibitor or a p14ARF(2-13) peptide sensitized tumor cells to chemotherapy. Our study therefore provides a new mechanistic understanding of PTEN in HR repair and clinical intervention of chemoresistant tumors.

Efficient Dynamic Correspondence Network.

We tackle the problem of establishing dense correspondences between a pair of images in an efficient way. Most existing dense matching methods use 4D convolutions to filter incorrect matches, but 4D convolutions are highly inefficient due to their quadratic complexity. Besides, these methods learn features with fixed convolutions which cannot make learnt features robust to different challenge scenarios. To deal with these issues, we propose an Efficient Dynamic Correspondence Network (EDCNet) by jointly equipping pre-separate convolution (Psconv) and dynamic convolution (Dyconv) to establish dense correspondences in a coarse-to-fine manner. The proposed EDCNet enjoys several merits. First, two well-designed modules including a neighbourhood aggregation (NA) module and a dynamic feature learning (DFL) module are combined elegantly in the coarse-to-fine architecture, which is efficient and effective to establish both reliable and accurate correspondences. Second, the proposed NA module maintains linear complexity, showing its high efficiency. And our proposed DFL module has better flexibility to learn features robust to different challenges. Extensive experimental results show that our algorithm performs favorably against state-of-the-art methods on three challenging datasets including HPatches, Aachen Day-Night and InLoc.

USP7 reduces the level of nuclear DICER, impairing DNA damage response and promoting cancer progression.

Endoribonuclease DICER is an RNase III enzyme that mainly processes microRNAs in the cytoplasm but also participates in nuclear functions such as chromatin remodelling, epigenetic modification and DNA damage repair. The expression of nuclear DICER is low in most human cancers, suggesting a tight regulation mechanism that is not well understood. Here, we found that ubiquitin carboxyl-terminal hydrolase 7 (USP7), a deubiquitinase, bounded to DICER and reduced its nuclear protein level by promoting its ubiquitination and degradation through MDM2, a newly identified E3 ubiquitin-protein ligase for DICER. This USP7-MDM2-DICER axis impaired histone γ-H2AX signalling and the recruitment of DNA damage response (DDR) factors, possibly by influencing the processing of small DDR noncoding RNAs. We also showed that this negative regulation of DICER by USP7 via MDM2 was relevant to human tumours using cellular and clinical data. Our findings revealed a new way to understand the role of DICER in malignant tumour development and may offer new insights into the diagnosis, treatment and prognosis of cancers.

Introduction and preliminary application report for a novel 3D printed perforator navigator for fibular flap surgery.

The aim of this study was to introduce and report on a 3D-printed perforator navigator and its clinical application. Integrated imaging and 3D printing techniques were employed for the design and manufacture of a perforator navigator. Key techniques included establishing a digital image coordinate system, localizing perforator fascia piercing points, creating a reference plane for the perforator course, and projecting the perforator course onto the body surface. All cases of maxillofacial defect repaired with free fibular myocutaneous flaps, from January 2019 to January 2022, were reinvestigated. Patients treated using traditional perforator localization methods were assigned into group Ⅰ, while those who had a navigator used during treatment were allocated to group Ⅱ. Outcome measurements included perforator positioning accuracy, perforator preparation time (PT), and flap growth score. Capillary refilling time and degree of flap swelling were recorded on the 1st, 3rd, and 7th days after surgery. On the 10th day after surgery, the flap survival situation was graded. In total, 25 patients were included in the study. Perforator preparation time for group Ⅱ was significantly less (p ＝ 0.04) than for group Ⅰ (1038.6 ± 195.4 s versus 1271.4 ± 295.1 s. In group Ⅱ, the mean positioning deviation for the perforator navigator was 2.12 cm less than that for the high-frequency color Doppler (p ＝ 0.001). Group Ⅱ also had a higher score than group Ⅰ for overall flap growth evaluation (nonparametric rank sum test, p ＝ 0.04). Within the scale of the study, it seems that perforator localization and navigation using a 3D-printed navigator is technically feasible, and helps to improve the clinical outcome of free fibular flaps. The perforator navigator will play a useful role in displaying the perforator course, improving the accuracy of perforator localization, reducing surgical injury, and ultimately enhancing flap success rate.