Examining the causal relationship between circulating immune cells and the susceptibility to osteomyelitis: A Mendelian randomization study.

BACKGROUND: Osteomyelitis is considered as a deleterious inflammatory condition affecting the bone, primarily attributed to pathogenic infection. However, the underlying factors predisposing individuals to osteomyelitis remain incompletely elucidated. The immune system plays a multifaceted role in the progression of this condition, yet previous observational studies and randomized controlled trials investigating the association between circulating immune cell counts and osteomyelitis have been constrained. In order to address this knowledge gap, we conducted a Mendelian randomization (MR) analysis to evaluate the impact of diverse immune cell counts on the risk of developing osteomyelitis. METHODS: In our study, we utilized single nucleotide polymorphisms (SNPs) that have been strongly linked to circulating immune cells or specific lymphocyte subtypes, as identified in large-scale genome-wide association studies (GWAS). These SNPs served as instrumental variables (IVs) for our MR analysis. We employed a more relaxed clumping threshold to conduct MR analysis on several related lymphocyte subtypes. To estimate causal effects, we utilized the Wald ratio, as well as the random-effects inverse variance weighted (IVW) and weighted median (WM) methods. To enhance the credibility of our results, we performed F-statistic calculations and a series of sensitivity analyses. RESULTS: Our findings revealed a significant correlation between the absolute count of circulating lymphocytes and the risk of osteomyelitis [odds ratio(OR) 1.20；95 % confidence interval (CI), 1.08-1.32；P = 0.0005]. Furthermore, we identified a causal relationship between the absolute count of CD8+ T cells and susceptibility to osteomyelitis (OR 1.16; 95 % CI, 1.04-1.30; P = 0.0098). Importantly, these findings remained robust across a wide range of sensitivity analyses. CONCLUSION: Through our MR analysis, we have provided evidence supporting a causal relationship between genetic predisposition to higher circulating immune cell counts and an increased risk of osteomyelitis. Specifically, our findings highlight the association between elevated CD8+ T cell counts and a heightened susceptibility to osteomyelitis. These results offer valuable insights for the future exploration of immunotherapy approaches in the management of osteomyelitis.

Verbal-Person Nets: Pose-Guided Multi-Granularity Language-to-Person Generation.

Person image generation conditioned on natural language allows us to personalize image editing in a user-friendly manner. This fashion, however, involves different granularities of semantic relevance between texts and visual content. Given a sentence describing an unknown person, we propose a novel pose-guided multi-granularity attention architecture to synthesize the person image in an end-to-end manner. To determine what content to draw at a global outline, the sentence-level description and pose feature maps are incorporated into a U-Net architecture to generate a coarse person image. To further enhance the fine-grained details, we propose to draw the human body parts with highly correlated textual nouns and determine the spatial positions with respect to target pose points. Our model is premised on a conditional generative adversarial network (GAN) that translates language description into a realistic person image. The proposed model is coupled with two-stream discriminators: 1) text-relevant local discriminators to improve the fine-grained appearance by identifying the region-text correspondences at the finer manipulation and 2) a global full-body discriminator to regulate the generation via a pose-weighting feature selection. Extensive experiments conducted on benchmarks validate the superiority of our method for person image generation.

N6-methyladenosine reader YTHDF3 contributes to the aerobic glycolysis of osteosarcoma through stabilizing PGK1 stability.

PURPOSE: N6-methyladenosine (m6A) modification is a pivotal transcript chemical modification of eukaryotics, which has been identified to play critical roles on tumor metabolic reprogramming. However, the functions of m6A-reading protein YTH N6-methyladenosine RNA-binding protein 3 (YTHDF3) in osteosarcoma is still unclear. This research planned to investigate the bio-functions and mechanism in osteosarcoma tumorigenesis. METHODS: The aerobic glycolysis of osteosarcoma cells were calculated by glucose uptake, lactate production analysis, ATP analysis and metabolic flux analysis for extracellular acidification rate (ECAR). Molecular binding was identified by RIP-qPCR, RNA decay analysis. RESULTS: Results indicated that YTHDF3 is upregulated in the osteosarcoma tissue samples and cells, and closely correlated to the poor prognosis of osteosarcoma patients. Functionally, gain and loss-of-functional assays illustrated that YTHDF3 promoted the proliferation and aerobic glycolysis of osteosarcoma cells in vitro, and accelerated the tumor growth in vivo. Mechanistically, a m6A-modified PGK1 mRNA functioned as the target of YTHDF3, and YTHDF3 enhanced the PGK1 mRNA stability via m6A-dependent manner. CONCLUSIONS: In conclusion, these findings indicated that YTHDF3 functioned as an oncogene in osteosarcoma tumorigenesis through m6A/PGK1 manner, providing a therapeutic strategy for human osteosarcoma.

Pseudo-Pair Based Self-Similarity Learning for Unsupervised Person Re-Identification.

Person re-identification (re-ID) is of great importance to video surveillance systems by estimating the similarity between a pair of cross-camera person shorts. Current methods for estimating such similarity require a large number of labeled samples for supervised training. In this paper, we present a pseudo-pair based self-similarity learning approach for unsupervised person re-ID without human annotations. Unlike conventional unsupervised re-ID methods that use pseudo labels based on global clustering, we construct patch surrogate classes as initial supervision, and propose to assign pseudo labels to images through the pairwise gradient-guided similarity separation. This can cluster images in pseudo pairs, and the pseudos can be updated during training. Based on pseudo pairs, we propose to improve the generalization of similarity function via a novel self-similarity learning:it learns local discriminative features from individual images via intra-similarity, and discovers the patch correspondence across images via inter-similarity. The intra-similarity learning is based on channel attention to detect diverse local features from an image. The inter-similarity learning employs a deformable convolution with a non-local block to align patches for cross-image similarity. Experimental results on several re-ID benchmark datasets demonstrate the superiority of the proposed method over the state-of-the-arts.

[Clinical characteristics and cost-effectiveness of intramedullary nail and plate for the treatment of open tibial fractures].

OBJECTIVE: To analyze clinical characteristics and cost-effectiveness of different final surgical options for treating patients with open tibial fractures. METHODS: A retrospective analysis was conducted by enrolling 55 surgically treated patients with open tibial fractures from January 2018 to June 2019. All the patients were categorized in intramedullary nailing (IMN) group and locking compression plate(LCP) group according to the final fixation option. There were 35 cases in group IMN including 27 males and 8 females, aged from 25 to 69 years old with an average of (49.0±10.6) years old. Based on Gustilo-Anderson classification, there were 1 case of typeⅠ, 19 cases of typeⅡand 15 cases of type Ⅲ. There were 20 cases in group LCP including 15 males and 5 females, aged from 46 to 72 years old with an average age of (53.4±14.7) years old. Based on Gustilo-Anderson classification, there were 2 cases of typeⅠ, 11 cases of typeⅡand 7 cases of type Ⅲ. Preoperative waiting time, surgical debridement times, intraoperative bleeding loss, blood and albumin transfusion, operation time, bacterial cultures and complications, bone union time, Johner-Wruhs criteria at 1 year after operation and total cost within 1 year after surgery between two groups were compared. The variables recorded between two groups were statistically analyzed and compared respectively, then the factors affecting hospital costs were evaluated by univariate and multiple linear regression analysis respectively, finally the cost-effectiveness analysis was performed. RESULTS: Total 55 patients were enrolled with an average follow-up time of(16.4±7.1) months ranged from 14 to 27 months postoperatively. There were no significantly statistical differences of the demographic materials between the two groups. The intraoperative bleeding loss were(243.18±118.82) ml and (467.86±490.53) ml respectively in group IMN and LCP, the significantly statistical difference was discovered(P<0.05). The surgical duration were(247.50±57.94) min and(350.00±178.77) min respectively in group IMN and LCP, the significantly statistical difference was discovered(P<0.05). There were no significantly statistical differences of the average days before operation, surgical debridement times, received blood and albumin transfusion, wound cultures, complications and bone union time between the two groups(P>0.05). The univariate analysis of the factors affecting the hospital costs indicated that patients with smoke or alcohol (P=0.042), high energy damage (P=0.012), patients with comorbidity diseases(P=0.045), surgical debridement over 2 times (P=0.001), intraoperative bleeding loss over 400 ml (P<0.001), blood and albumin transfusion (P=0.027), wound cultures (P=0.000) and complications (P=0.035) were the factors. The multiple linear regression analysis demonstrated the smoke or alcohol using[ß=-0.256, t=-2.628, 95%CI(-29 667.09, -4 997.47), P=0.014] was the only factor affecting the total cost. The excellent and good rate were 80% and 85% respectively based on the Johner-Wruhs criteria. The average total cost within 1 year after surgery was (136 435.90±39 093.98) CNY in group IMN and (140 034.62±56 821.12) CNY in group LCP. The total surgical duration and total intraoperative bleeding loss were significant lower in group IMN than in group LCP. The average total costs of was significantly higher. The average cost for every 1% of excellent and good rate was 1 705.45 CNY in group IMN and 1 647.46 CNY in group LCP. Each 1% increasing of excellent and good rate cost 719.74 CNY more in group LCP compared with group IMN. CONCLUSION: Both IMN and LCP could provide a satisfactory outcome for open tibial fractures. Meanwhile considering the total cost, patients with smoke or alcohol history, traffic accident, comorbidity diseases, surgical debridement over 2 times, intraoperative bleeding loss over 400 ml, and complications should not be ignored.

Circular RNA circNRIP1 plays oncogenic roles in the progression of osteosarcoma.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Increasing evidence suggests that aberrant expression of circRNAs is associated with the occurrence and progression of many cancers. Here, we investigated the role of circNRIP1 in osteosarcoma and explored its possible underlying mechanisms. Three pairs of osteosarcoma tissues and adjacent normal tissues were applied to the detection of altered expression of circRNAs through circRNAs microarray. And the level of circNRIP1 expression was elevated in osteosarcoma tissues. Compared with that in adjacent normal tissue, circNRIP1 expression level was obviously elevated in 100 osteosarcoma tissues. Besides, circNRIP1 knockdown inhibited proliferation and migration, promoted apoptosis of osteosarcoma cells. Bioinformatic analysis demonstrated circNRIP1 contributed to FOXC2 expression by sponging miR-199a. Furthermore, METTL3 elevated circNRIP1 expression level via m6A modification. In short, METTL3-induced circNRIP1 exerted an oncogenic role in osteosarcoma by sponging miR-199a, which may provide new ideas for the treatment of osteosarcoma.

Clinical Efficacy of Vertical or Parallel Technique of a Micro-Locking Plate for Treatment of Dubberley B-Type Capitellar Fractures.

OBJECTIVE: To evaluate the clinical efficacy of micro-locking plate through vertical or parallel technique for treatment of Dubberley B-type capitellar fractures. METHODS: A retrospective analysis was performed in 24 patients (17 males and seven females, with an average age of 44.9 years, range from 19 to 75 years) with capitellar fractures that were treated with micro-locking plate using vertical or parallel technique between January 2016 to January 2019. The inclusion criteria include closed capitellar fracture, normal anterior elbow joint movement before injury, and recent capitellar fracture with injury within past 3 weeks. Fractures classified according to Dubberley included four cases of type IB, eight cases of type IIB, and 12 cases of type IIIB. Radiographic evaluation was performed. Surgery time, blood loss, range of motion of the elbow, forearm rotation, and complications were recorded. Elbow joint function was evaluated by Mayo Elbow Performance Score (MEPS). RESULTS: The mean follow-up period was 19.6 months (range, 12-36 months). The average clinical healing time for fractures was 11.2 ± 3.2 weeks (range, 8-20 weeks). Fracture united in all patients. Two patients showed slight delayed union, but union was achieved eventually. The mean time from injury to surgery was 6.3 ± 3.1 days (range, 2-15 days). The average surgical time was 68.1 ± 11.5 min (range, 50-90 min), and the mean blood loss was 75.2 ± 26.5 mL (range, 40-120 mL). The mean range of flexion was 122.5° ± 10.5°(range, 95°-140°). The mean range of extension was 8.5° ± 5.8°(range, 0°-20°). The mean range of pronation was 79.7° ± 8.0°(range, 65°-90°). The mean range of supination was 80.5° ± 7.1°(range, 60°-90°). The mean MEPS at final follow-up was 89.8 ± 9.0 (range, 60-100). Based on the MEPS, 18 (75%) patients had excellent, five (20.8%) patients had good, and one (4.2%) patient had fair. None of the 24 patients suffered vascular or nerve injury. One patient showed superficial infection, which was treated with surgical dressing. CONCLUSIONS: The vertical or parallel technique of the micro-locking plate is an excellent method for treating Dubberley B-type capitellar fractures.

Medi-Care AI: Predicting medications from billing codes via robust recurrent neural networks.

In this paper, we present an effective deep prediction framework based on robust recurrent neural networks (RNNs) to predict the likely therapeutic classes of medications a patient is taking, given a sequence of diagnostic billing codes in their record. Accurately capturing the list of medications currently taken by a given patient is extremely challenging due to undefined errors and omissions. We present a general robust framework that explicitly models the possible contamination through overtime decay mechanism on the input billing codes and noise injection into the recurrent hidden states, respectively. By doing this, billing codes are reformulated into its temporal patterns with decay rates on each medical variable, and the hidden states of RNNs are regularized by random noises which serve as dropout to improved RNNs robustness towards data variability in terms of missing values and multiple errors. The proposed method is extensively evaluated on real health care data to demonstrate its effectiveness in suggesting medication orders from contaminated values.

Positive feedback loop SP1/MIR17HG/miR-130a-3p promotes osteosarcoma proliferation and cisplatin resistance.

Long noncoding RNAs (lncRNAs) have been identified to be critical regulator in the osteosarcoma (OS) tumorigenesis. However, the role of lncRNA MIR17HG in the OS proliferation and chemotherapy resistance is still unclear. Here, this research aims to investigate the function of lncRNA MIR17HG in the OS proliferation and cisplatin resistance. Clinically, results revealed that higher MIR17HG expression was associated with shorter overall survival. Functional investigations indicated that MIR17HG promoted the proliferation, invasion and cisplatin resistance of OS cells in vitro, and the MIR17HG knockdown inhibited the growth in vivo. Mechanistically, MIR17HG targeted the miR-130a-3p/SP1 axis, moreover, transcription factor SP1 bind with the MIR17HG promoter region to promote its expression. Taken together, MIR17HG displays the tumor-promotive role in the progression of OS through SP1/MIR17HG/miR-130a-3p/SP1 feedback loop. Our findings might help us to offer novel therapeutic strategies for OS.

Exploring Inter-Instance Relationships within the Query Set for Robust Image Set Matching.

Image set matching (ISM) has attracted increasing attention in the field of computer vision and pattern recognition. Some studies attempt to model query and gallery sets under a joint or collaborative representation framework, achieving impressive performance. However, existing models consider only the competition and collaboration among gallery sets, neglecting the inter-instance relationships within the query set which are also regarded as one important clue for ISM. In this paper, inter-instance relationships within the query set are explored for robust image set matching. Specifically, we propose to represent the query set instances jointly via a combined dictionary learned from the gallery sets. To explore the commonality and variations within the query set simultaneously to benefit the matching, both low rank and class-level sparsity constraints are imposed on the representation coefficients. Then, to deal with nonlinear data in real scenarios, the'kernelized version is also proposed. Moreover, to tackle the gross corruptions mixed in the query set, the proposed model is extended for robust ISM. The optimization problems are solved efficiently by employing singular value thresholding and block soft thresholding operators in an alternating direction manner. Experiments on five public datasets demonstrate the effectiveness of the proposed method, comparing favorably with state-of-the-art methods.

Application of transforaminal-lumbar interbody fusion technology combined with lesion clearance and chemotherapy via catheter for the treatment of spinal tuberculosis.

The aim of the present study was to analyze the clinical and radiological outcomes of active thoracolumbar spinal tuberculosis (TB) treated by application of transforaminal-lumbar interbody fusion technology combined with lesion clearance and chemotherapy via catheter (TCLC). Posterior debridement and indwelling catheterization in the lesion area were performed for direct injection of anti-TB drugs, so as to reduce the recurrence rate. The present prospective study comprised 26 patients with active thoracolumbar spinal TB who underwent TCLC at Hong Hui Hospital affiliated to Xi'an Jiaotong University (Xi'an, China). The kyphotic Cobb angle at presentation, after surgery and at the final follow-up were 22.7±9.8, 9.8±7.3 and 10.3±8.8°, respectively, with an average correction of 13.1±5.4° after surgery, and a loss of correction of 1.8±1.0° at the final follow-up. The rate of correction and loss of correction were 56.6 and 8.3%, respectively. At six months after the surgery, all abnormal erythrocyte sedimentation rates and C-reactive protein levels had returned to normal. The average time to union was ~5 months. All patients had bony union and improved neurological function, with their daily activity returning to normal. In conclusion, in the present study, application of TCLC for the treatment of spinal TB achieved satisfactory healing of lesions. The surgical treatment for spinal TB comprised the removal of the disease as far as possible, and the local administration of anti-TB chemotherapy to the lesion is key to successful treatment.

Vector semirational rogue waves and modulation instability for the coupled higher-order nonlinear Schrödinger equations in the birefringent optical fibers.

We report the existence and properties of vector breather and semirational rogue-wave solutions for the coupled higher-order nonlinear Schrödinger equations, which describe the propagation of ultrashort optical pulses in birefringent optical fibers. Analytic vector breather and semirational rogue-wave solutions are obtained with Darboux dressing transformation. We observe that the superposition of the dark and bright contributions in each of the two wave components can give rise to complicated breather and semirational rogue-wave dynamics. We show that the bright-dark type vector solitons (or breather-like vector solitons) with nonconstant speed interplay with Akhmediev breathers, Kuznetsov-Ma solitons, and rogue waves. By adjusting parameters, we note that the rogue wave and bright-dark soliton merge, generating the boomeron-type bright-dark solitons. We prove that the rogue wave can be excited in the baseband modulation instability regime. These results may provide evidence of the collision between the mixed ultrashort soliton and rogue wave.