Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Plantar Pressure Distribution and Posture Balance During Walking in Individuals with Unilateral Chronic Ankle Instability: An Observational Study.

BACKGROUND Patients with chronic ankle instability (CAI) can present with abnormal gait. The purpose of this study was to evaluate plantar pressure distributions and posture balance during walking in unilateral CAI patients. MATERIAL AND METHODS We recruited 24 unilateral CAI patients and 24 healthy individuals; plantar pressure analysis was conducted using the Footscan® 3D pressure system. The following parameters were assessed and recorded: peak force/weight (PF/W), time to peak force (TPF), time to boundary (TTB), and COP velocity. The differences between the affected and unaffected side of the CAI group and control group were determined. Pearson correlation analysis and univariate analysis was used to investigate the correlation between plantar pressure parameters and related factors. RESULTS The comparison of PF/W showed that the plantar pressure of both sides in the CAI group were laterally distributed. The comparison of TPF, TTB, and COP velocity in different groups showed that the posture balance on the affected side of CAI patient was more impaired than the unaffected side and the control group. Male patients with CAI tend to have better posture balance than females, and a low CAIT score is correlated with poor posture balance. CONCLUSIONS The plantar pressure on both sides in unilateral CAI patients was laterally distributed and their balance function was impaired. It is necessary for CAI patients to receive functional training of both sides during rehabilitation, and plantar pressure analysis is promising for diagnosis and evaluation of CAI.

A software program for automated compressive vertebral fracture detection on elderly women's lateral chest radiograph: Ofeye 1.0.

Background: Because osteoporotic vertebral fracture (OVF) on chest radiographs is commonly missed in radiological reports, we aimed to develop a software program which offers automated detection of compressive vertebral fracture (CVF) on lateral chest radiographs, and which emphasizes CVF detection specificity with a low false positivity rate. Methods: For model training, we retrieved 3,991 spine radiograph cases and 1,979 chest radiograph cases from 16 sources, with among them in total 1,404 cases had OVF. For model testing, we retrieved 542 chest radiograph cases and 162 spine radiograph cases from four independent clinics, with among them 215 cases had OVF. All cases were female subjects, and except for 31 training data cases which were spine trauma cases, all the remaining cases were post-menopausal women. Image data included DICOM (Digital Imaging and Communications in Medicine) format, hard film scanned PNG (Portable Network Graphics) format, DICOM exported PNG format, and PACS (Picture Archiving and Communication System) downloaded resolution reduced DICOM format. OVF classification included: minimal and mild grades with <20% or ≥20-25% vertebral height loss respectively, moderate grade with ≥25-40% vertebral height loss, severe grade with ≥40%-2/3 vertebral height loss, and collapsed grade with ≥2/3 vertebral height loss. The CVF detection base model was mainly composed of convolution layers that include convolution kernels of different sizes, pooling layers, up-sampling layers, feature merging layers, and residual modules. When the model loss function could not be further decreased with additional training, the model was considered to be optimal and termed 'base-model 1.0'. A user-friendly interface was also developed, with the synthesized software termed 'Ofeye 1.0'. Results: Counting cases and with minimal and mild OVFs included, base-model 1.0 demonstrated a specificity of 97.1%, a sensitivity of 86%, and an accuracy of 93.9% for the 704 testing cases. In total, 33 OVFs in 30 cases had a false negative reading, which constituted a false negative rate of 14.0% (30/215) by counting all OVF cases. Eighteen OVFs in 15 cases had OVFs of ≥ moderate grades missed, which constituted a false negative rate of 7.0% (15/215, i.e., sensitivity 93%) if only counting cases with ≥ moderate grade OVFs missed. False positive reading was recorded in 13 vertebrae in 13 cases (one vertebra in each case), which constituted a false positivity rate of 2.7% (13/489). These vertebrae with false positivity labeling could be readily differentiated from a true OVF by a human reader. The software Ofeye 1.0 allows 'batch processing', for example, 100 radiographs can be processed in a single operation. This software can be integrated into hospital PACS, or installed in a standalone personal computer. Conclusions: A user-friendly software program was developed for CVF detection on elderly women's lateral chest radiographs. It has an overall low false positivity rate, and for moderate and severe CVFs an acceptably low false negativity rate. The integration of this software into radiological practice is expected to improve osteoporosis management for elderly women.

Chest radiograph prevalence of vertebral deformity among young and middle-aged population of mixed city dwellers and rural residents.

Background: To interpret the importance of minimal and mild vertebral deformities (VDs) among elderly subjects, we need to know their prevalence among mostly non-osteoporotic subjects. Methods: We retrospectively analyzed VDs among 408 female and 374 male patients who had lateral chest radiographs due to mild illness or for routine healthcheck, all with indications other than spine disorders or metabolic disorders. The study subjects were divided into four age groups, i.e., ≤20, 20-34, 35-44, and ≥45 years. For those aged >20 years, 27.2% females had family roots from farming communities, and 26.4% males had the history of being a farmer or physical laborer (this was 36.1% for males aged ≥45 years). Fracture shaped vertebral deformities (FSVDs) were VDs radiographically indistinguishable from vertebral fracture. Acquired short vertebrae were those with decreased vertebral anterior and middle heights, while without anterior wedging or bi-concave changes, and the diagnosis required at least two adjacent short vertebrae in the same subject. Results: Congenital VDs were observed in four cases (three males, one female). In the age group of ≤20, 20-34, 35-44, and ≥45 years, females had any FSVD prevalence of 13.4%, 8.3%, 11.8%, 25.8% respectively, while the prevalence was 29.3%, 26%, 34.3%, 44.8% respectively for males. From the female ≤20 years group to the 21-34 years group, cases involved multiple vertebrae decreased from 53.8% to 16.7%. For cases ≤34 years, no female case had ≥ mild FSVD (which was defined to have ≥20% vertebral height loss), while five male cases had ≥ mild FSVD. For the 35-44 years group, vertebral endplate depression was noted among 2.0% of the females and 2.9% of the males. Among the cases aged ≤44 years, there was only one male and one female had acquired short vertebrae. For the male cases, acquired short vertebrae prevalence was 15.6% in the group of ≥45 years. Conclusions: FSVD is common among young and middle-aged population (≤44 years) assumed with normal bone strength, and with a higher FSVD prevalence among men. FSVD may heal among younger subjects, and physical labor may increase VD prevalence.

[Application of sliding osteotomy in total knee arthroplasty for patients with extra-articular femoral deformity].

OBJECTIVE: In order to observe the clinical effects of sliding osteotomy for patients with severe knee osteoarthritis and varus knee due to complex femoral extra-articular deformity to achieve the medial and lateral soft tissue balancing during total knee arthroplasty. METHODS: From June 2014 to January 2018, a total of 22 patients with severe knee osteoarthritis and complex extra-articular malformation of femurs were treated with total knee arthroplasty. There were 5 males and 17 females in this group, aged 48 to 76 years old, with an average age of (61.3±13.8) years old. All the patients had varus deformities caused by extra-articular deformities of femur. Hip-knee-ankle(HKA) angle was(158.8±9.7) ° before operation, and the average Knee Society Score (KSS) clinical score was 32.6±6.1;KSS function score was 35.8 ±9.6;the average Hospital for Special Surgical (HSS) score was 39.7±4.6;the average range of motion before operation was (80.6±10.7) °. The mechanical alignment method was used in joint replacement. The flexion space was balanced first. The coronal plane vertical sliding osteotomy was performed on the medial femoral condyle for the imbalance of coronal plane. The sliding distance of the osteotomy block was determined by straightening the gap between the inner and outer sides of the space until the space was balanced. After the separated segments were fixed with several screws, the prosthesis was installed as usual. RESULTS: The wounds of all patients healed in the first stage, and no wound complications occurred. All the 22 patients were followed up, and the duration ranged from 18 months to 3 years with an average of (28.2±10.1) months. X-ray showed that the fracture line disappeared for 2 to 5(3.5±1.5) months without nonunion. HKA angle measured at the latest follow up was (178.8±0.7) °, which wassignificantly different from that before operation. The HSS score was 91.3 ±6.0;KSS clinical score 93.7±3.5;KSS functional score 81.2±6.5;and the average range of motion of knee joint was(121.7±11.6) °, which was statistically significant compared with that before operation. CONCLUSION: For severe knee osteoarthritis patients with complex femoral extra-articular deformity, sliding osteotomy is performed. For severe varus deformity, downward sliding the medial femoral condyle is performed. The operation is relatively simple and the damage is small. It is easy to achieve the balance of internal and external soft tissue in flexion extension space. The short-term clinical effect is satisfactory.

Dynamic structural insights into the molecular mechanism of DNA unwinding by the bacteriophage T7 helicase.

The hexametric T7 helicase (gp4) adopts a spiral lock-washer form and encircles a coil-like DNA (tracking) strand with two nucleotides bound to each subunit. However, the chemo-mechanical coupling mechanism in unwinding has yet to be elucidated. Here, we utilized nanotensioner-enhanced Förster resonance energy transfer with one nucleotide precision to investigate gp4-induced unwinding of DNA that contains an abasic lesion. We observed that the DNA unwinding activity of gp4 is hindered but not completely blocked by abasic lesions. Gp4 moves back and forth repeatedly when it encounters an abasic lesion, whereas it steps back only occasionally when it unwinds normal DNA. We further observed that gp4 translocates on the tracking strand in step sizes of one to four nucleotides. We propose that a hypothetical intermediate conformation of the gp4-DNA complex during DNA unwinding can help explain how gp4 molecules pass lesions, providing insights into the unwinding dynamics of gp4.

Detecting Single-Molecule Dynamics on Lipid Membranes with Quenchers-in-a-Liposome FRET.

Tracking membrane-interacting molecules and visualizing their conformational dynamics are key to understanding their functions. It is, however, challenging to accurately probe the positions of a molecule relative to a membrane. Herein, a single-molecule method, termed LipoFRET, is reported to assess interplay between molecules and liposomes. It takes advantage of FRET between a single fluorophore attached to a biomolecule and many quenchers in a liposome. This method was used to characterize interactions between α-synuclein (α-syn) and membranes. These results revealed that the N-terminus of α-syn inserts into the membrane and spontaneously transitions between different depths. In contrast, the C-terminal tail of α-syn is regulated by calcium ions and floats in solution in two conformations. LipoFRET is a powerful tool to investigate membrane-interacting biomolecules with sub-nanometer precision at the single-molecule level.

Identification of Novel Target for Osteosarcoma by Network Analysis.

BACKGROUND Osteosarcoma (OS) is a highly complicated bone cancer involving imbalance of signaling transduction networks in cells. Development of new anti-osteosarcoma drugs is very challenging, mainly due to lack of known key targets. MATERIAL AND METHODS In this study, we attempted to reveal more promising targets for drug design by "Target-Pathway" network analysis, providing the new therapeutic strategy of osteosarcoma. The potential targets used for the treatment of OS were selected from 4 different sources: DrugBank, TCRD database, dbDEMC database, and recent scientific literature papers. Cytoscape was used for the establishment of the "Target-Pathway" network. RESULTS The obtained results suggest that tankyrase 2 (TNKS2) might be a very good potential protein target for the treatment of osteosarcoma. An in vitro MTT assay proved that it is an available option against OS by targeting the TNKS2 protein. Subsequently, cell cycle and apoptosis assay by flow cytometry showed the TNKS2 inhibitor can obviously induce cell cycle arrest, apoptosis, and mitotic cell death. CONCLUSIONS Tankyrase 2 (TNKS2), a member of the multifunctional poly(ADP-ribose) polymerases (PARPs), could be a very useful protein target for the treatment of osteosarcoma.

Asynchrony of Base-Pair Breaking and Nucleotide Releasing of Helicases in DNA Unwinding.

Helicases harness the energy of nucleotide triphosphate hydrolysis to unwind double-stranded DNA (dsDNA) in discrete steps. In spite of intensive studies, the mechanism of stepping is still poorly understood. Here, we applied single-molecule fluorescent resonant energy transfer to characterize the stepping of two nonring helicases, Escherichia coli RecQ ( E. coli RecQ) and Saccharomyces cerevisiae Pif1 (ScPif1). Our data showed that when forked dsDNA with free overhangs are used as substrates, both E. coli RecQ and ScPif1 unwind the dsDNA in nonuniform steps that distribute over broad ranges. When tension is exerted on the overhangs, the overall profile of the step-size distribution of ScPif1 is narrowed, whereas that of E. coli RecQ remains unchanged. Moreover, the measured step sizes of the both helicases concentrate on integral multiples of a half base pair. We propose a universal stepping mechanism, in which a helicase breaks one base pair at a time and sequesters the nascent nucleotides and then releases them after a random number of base-pair breaking events. The mechanism can interpret the observed unwinding patterns quantitatively and provides a general view of the helicase activity.

Hydroxytyrosol inhibits the inflammatory response of osteoarthritis chondrocytes via SIRT6-mediated autophagy.

Osteoarthritis (OA) is a common degenerative joint disease. Inflammation may exaggerate the catabolism and degeneration in the pathogenesis of OA. Hydroxytyrosol (HT) has been used in the management of inflammatory diseases. In addition, reports have revealed that autophagy was a therapeutic target of diseases caused by inflammation. Sirtuin 6 (SIRT6) has also been demonstrated to prevent OA development by reducing both the inflammatory response and chondrocyte senescence. However, the roles of SIRT6 and autophagy in cartilage and its underlying anti­inflammatory mechanism are unknown. Therefore, the present study aimed to determine the effects of HT on autophagy and inflammation in chondrocytes, and clarify whether HT regulates the inflammatory response through SIRT6­mediated autophagy. The expression of protein and mRNA were determined by western blot analysis and reverse transcription­quantitative polymerase chain reaction. The production of cytokines was detected by ELISA. It was demonstrated that HT inhibited the levels of interleukin (IL)­1ß and IL­6 in tumor necrosis factor (TNF)­α­stimulated chondrocytes in a concentration­dependent manner. In addition, HT promoted cell autophagy and increased the mRNA and protein expression levels of SIRT6 in chondrocytes stimulated with TNF-α. Autophagy inhibitor 3-methyladenine or knockdown of SIRT6 decreased the inhibitory effects of HT on the inflammatory response in chondrocytes. In addition, knockdown of SIRT6 attenuated the expression of microtubule-associated protein 1A/1B­light chain 3 and Beclin1 in chondrocytes. Overall, these findings suggested that HT inhibits the inflammatory response of chondrocytes through SIRT6­mediated autophagy. The present study provided a new drug target for the clinical treatment of inflammatory diseases.

Pif1 is a force-regulated helicase.

Pif1 is a prototypical member of the 5' to 3' DNA helicase family conserved from bacteria to human. It has a high binding affinity for DNA, but unwinds double-stranded DNA (dsDNA) with a low processivity. Efficient DNA unwinding has been observed only at high protein concentrations that favor dimerization of Pif1. In this research, we used single-molecule fluorescence resonance energy transfer (smFRET) and magnetic tweezers (MT) to study the DNA unwinding activity of Saccharomyces cerevisiae Pif1 (Pif1) under different forces exerted on the tails of a forked dsDNA. We found that Pif1 can unwind the forked DNA repetitively for many unwinding-rezipping cycles at zero force. However, Pif1 was found to have a very limited processivity in each cycle because it loosened its strong association with the tracking strand readily, which explains why Pif1 cannot be observed to unwind DNA efficiently in bulk assays at low protein concentrations. The force enhanced the unwinding rate and the total unwinding length of Pif1 significantly. With a force of 9 pN, the rate and length were enhanced by more than 3- and 20-fold, respectively. Our results imply that the DNA unwinding activity of Pif1 can be regulated by force. The relevance of this characteristic of Pif1 to its cellular functions is discussed.

No Superiority of High-Flexion vs Standard Total Knee Arthroplasty: An Update Meta-Analysis of Randomized Controlled Trials.

This meta-analysis was performed using a Cochrane systematic review approach to examine published data with an aim to clarify whether standard or high flexion prostheses increase the range of knee motion and clinical outcomes. 1778 patients from 17 randomized controlled trials were identified. No significant differences in the range of motion, weight-bearing flexion and hip functions scores were found between treatment groups. We also found no significant differences in complications with regard to revision, component loosening, deep infection, anterior knee pain, stiffness, post-operative bone fracture and post-operative patella clunk syndrome, but the high flexion prostheses group had a higher incidence of deep venous thrombosis. The results do not support the proposition that high flexion knee prostheses provide substantial clinical advantages over standard knee prostheses.

[A exploration and study of the relationships of hand-foot-mouth disease (HFMD) and the climate].

OBJECTIVE: To explore and study the relationships between the popularity of HFMD and the climate in Qinhuangdao city. METHODS: HFMD cases were collected on a ten-day basis in 2009 in Qinhuangdao city. At the same time, the data about Qinhuangdao's ten-day average temperature and average humidity were provided by the Qinhuangdao Meteorological bureau. Then the collected data were analysed using the great data analysis function in the EXCELE software. RESULTS: The results showed that the disease of HFMD had a positive relationship with seasons. The cases of HFMD began to rise at the last ten days of March and rised dramatically at the middle ten days of April; In July, the cases of HFMD arrived at peak and then decline gradually. The cases of HFMD in October were quite similar to the cases of HFMD in March. Then in November, the cases of HFMD declined rapidly. All these evidences suggested that the peak seasons of HFMD were Spring and Summer. CONCLUSION: The situations of HFMD had a significant positive relationship with the conditions of climate, such as high temperature and high humidity.