1H-nuclear magnetic resonance analysis reveals dynamic changes in the metabolic profile of patients with severe burns.

Background: Severe burn injury causes a hypermetabolic response, resulting in muscle protein catabolism and multiple organ damage syndrome. However, this response has not yet been continuously characterized by metabolomics in patients. This study aims to quantify temporal changes in the metabolic processes of patients with severe burns. Methods: We employed 1H-nuclear magnetic resonance (NMR) spectroscopy to scrutinize metabolic alterations during the initial 35 days following burn injury in a cohort of 17 adult patients with severe burns, with 10 healthy individuals included as controls. Plasma specimens were collected from patients on postburn days 1, 3, 7, 14, 21, 28 and 35. After performing multivariate statistical analysis, repeated-measures analysis of variance and time-series analysis, we quantified changes in metabolite concentrations. Results: Among the 36 metabolites quantified across 119 samples from burn patients, branched-chain amino acids, glutamate, glycine, glucose, pyruvate, lactate, trimethylamine N-oxide and others exhibited obvious temporal variations in concentration. Notably, these metabolites could be categorized into three clusters based on their temporal characteristics. The initial response to injury was characterized by changes in lactate and amino acids, while later changes were driven by an increase in fatty acid catabolism and microbial metabolism, leading to the accumulation of ketone bodies and microbial metabolites. Conclusions: Metabolomics techniques utilizing NMR have the potential to monitor the intricate processes of metabolism in patients with severe burns. This study confirmed that the third day after burn injury serves as the boundary between the ebb phase and the flow phase. Furthermore, identification of three distinct temporal patterns of metabolites revealed the intrinsic temporal relationships between these metabolites, providing clinical data for optimizing therapeutic strategies.

The impact of gut microbiota changes on the intestinal mucus barrier in burned mice: a study using 16S rRNA and metagenomic sequencing.

Background: The gut microbiota is a complex ecosystem that plays a critical role in human health and disease. However, the relationship between gut microbiota and intestinal damage caused by burns is not well understood. The intestinal mucus layer is crucial for maintaining intestinal homeostasis and providing a physiological barrier against bacterial invasion. This study aims to investigate the impact of gut microbiota on the synthesis and degradation of intestinal mucus after burns and explore potential therapeutic targets for burn injury. Methods: A modified histopathological grading system was employed to investigate the effects of burn injury on colon tissue and the intestinal mucus barrier in mice. Subsequently, 16S ribosomal RNA sequencing was used to analyze alterations in the gut microbiota at days 1-10 post-burn. Based on this, metagenomic sequencing was conducted on samples collected at days 1, 5 and 10 to investigate changes in mucus-related microbiota and explore potential underlying mechanisms. Results: Our findings showed that the mucus barrier was disrupted and that bacterial translocation occurred on day 3 following burn injury in mice. Moreover, the gut microbiota in mice was significantly disrupted from days 1 to 3 following burn injury, but gradually recovered to normal as the disease progressed. Specifically, there was a marked increase in the abundance of symbiotic and pathogenic bacteria associated with mucin degradation on day 1 after burns, but the abundance returned to normal on day 5. Conversely, the abundance of probiotic bacteria associated with mucin synthesis changed in the opposite direction. Further analysis revealed that after a burn injury, bacteria capable of degrading mucus may utilize glycoside hydrolases, flagella and internalins to break down the mucus layer, while bacteria that synthesize mucus may help restore the mucus layer by promoting the production of short-chain fatty acids. Conclusions: Burn injury leads to disruption of colonic mucus barrier and dysbiosis of gut microbiota. Some commensal and pathogenic bacteria may participate in mucin degradation via glycoside hydrolases, flagella, internalins, etc. Probiotics may provide short-chain fatty acids (particularly butyrate) as an energy source for stressed intestinal epithelial cells, promote mucin synthesis and accelerate repair of mucus layer.

Glutamine promotes O-GlcNAcylation of G6PD and inhibits AGR2 S-glutathionylation to maintain the intestinal mucus barrier in burned septic mice.

Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. We found that anterior gradient-2 (AGR2) plays a key role in the posttranslational modification of MUC2. Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation.

Effects of enteral nutrition with different energy supplies on metabolic changes and organ damage in burned rats.

Background: Enteral nutrition (EN) is an important treatment for burn patients. However, severe gastrointestinal damage caused by major burns often leads to EN intolerance. Trophic EN solves this problem basically, but how to transition from trophic EN to standard EN smoothly is still a challenge in burn clinical nutrition. The aim of this study is to investigate the effects of EN with different energy supplies on metabolic changes, organ damage and prognosis in burned rats. Methods: Different feeding regimens were designed based on the continuous monitoring of resting energy expenditure in rats. Thirty-two Sprague-Dawley rats were randomly divided into a normal control group, burn +50% REE group, burn +75% REE group and burn +100% REE group. At the end of a nutritional treatment cycle (14th day), nuclear magnetic resonance spectroscopy, blood biochemistry analysis and quantification of subscab bacteria were performed to explore the differences in metabolic changes, degrees of organ damage and prognoses between the groups. Results: Sixteen metabolites involving seven metabolic pathways were identified from the different energy supply groups. After burn injury, resting energy consumption and body weight loss increased obviously. Meanwhile, weight loss was inversely related to energy supply. The greatest changes in the degree of organ damage, the level of plasma proteins, lipids and endotoxins, as well as the quantification of subscab bacteria were observed in the 50% REE group, followed by the 75 and 100% groups. Conclusions: Achieving an early balance between energy supply and expenditure is conducive to mitigating metabolic disorders and improving prognosis after burn injury.

Effects of Different Ratios of Carbohydrate-Fat in Enteral Nutrition on Metabolic Pattern and Organ Damage in Burned Rats.

(1) Background: Nutritional support is one of the most important cornerstones in the management of patients with severe burns, but the carbohydrate-to-fat ratios in burn nutrition therapy remain highly controversial. In this study, we aimed to discuss the effects of different ratios of carbohydrate-fat through enteral nutrition on the metabolic changes and organ damage in burned rats. (2) Methods: Twenty-four burned rats were randomly divided into 5%, 10%, 20% and 30% fat nutritional groups. REE and body weight were measured individually for each rat daily. Then, 75% of REE was given in the first week after burns, and the full dose was given in the second week. Glucose tolerance of the rats was measured on days 1, 3, 7, 10 and 14. Blood biochemistry analysis and organ damage analysis were performed after 7 and 14 days of nutritional therapy, and nuclear magnetic resonance (NMR) and insulin content analysis were performed after 14 days. (3) Results: NMR spectra showed significant differences of glucose, lipid and amino acid metabolic pathways. The energy expenditure increased, and body weight decreased significantly after burn injury, with larger change in the 20%, 5% and 30% fat groups, and minimal change in the 10% fat group. The obvious changes in the level of plasma protein, glucose, lipids and insulin, as well as the organ damage, were in the 30%, 20% and 5% fat groups. In relative terms, the 10% fat group showed the least variation and was closest to normal group. (4) Conclusion: Lower fat intake is beneficial to maintaining metabolic stability and lessening organ damage after burns, but percentage of fat supply should not be less than 10% in burned rats.

Effects of fish oil-containing nutrition supplementation in adult sepsis patients: a systematic review and meta-analysis.

Background: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Although fish oil has been used as an immunonutritional preparations for the treatment of sepsis patients, there is still controversy as to whether it is beneficial to them. We systematically reviewed published clinical trial data to evaluate the effectiveness of fish oil-containing nutrition supplementation in sepsis patients. Methods: A systematic search was undertaken in PubMed, Embase, Chinese Biomedicine Database, the Cochrane Library and the China Knowledge Resource Integrated Database to obtain clinical controlled trails. RCTs on nutrition therapy containing fish oil among adult sepsis patients were selected for analysis in comparison with routine therapy. Results: Twenty-five published trials were included in the meta-analysis. Fish oil-containing nutrition supplementation reduced the mortality compared with the control group (relative risk (RR) 0.74, I 2 = 0%). Fish oil also shortened the ICU stay (MD -3.57 days; 95% CI -4.54, -2.59; p<0.00001; I 2 = 76%), hospital stay (MD -9.92 days; 95% CI -15.37, -4.46; p = 0.0004; I 2 = 91%) and the duration of mechanical ventilation support (MD -2.26; 95% CI -4.27, -0.26; p = 0.03; I 2 = 83%). A subgroup analysis based on the route of administration revealed that parenteral administration of fish oil could reduce mortality in septic patients (RR =0.68, I 2 = 0%), but no significant difference in mortality was observed in the fish oil group administered by enteral route (RR = 0.80, I 2 = 0%). No statistically significant publication biases were detected for the above clinical endpoints (p>0.05). Conclusions: Parenteral nutrition containing fish oil could significantly decrease mortality in sepsis patients while enteral administration could not. Fish oil-containing nutrition supplementation.

Glutamine relieves the hypermetabolic response and reduces organ damage in severe burn patients: A multicenter, randomized controlled clinical trial.

BACKGROUND: Severe burns can cause a hypermetabolic response and organ damage. Glutamine is a conditionally essential amino acid with various pharmacological effects. In this study, whether glutamine could alleviate the hypermetabolic response and maintain organ function after burn injury was analyzed. METHODS: A multicenter, randomized, single-blind, parallel controlled trial was conducted to evaluate the efficacy of glutamine in decreasing hypermetabolism after burn injury. Physiological and biochemical indexes, such as vital signs, metabolic hormones, metabolic rate, and organ damage, were recorded on the 7th and 14th days after treatment. RESULTS: In total, 55 adult burn patients with a total burn surface area (TBSA) of 30-70% were included in this study and randomly divided into the burn control (B, 28 patients) and burn+glutamine (B+G, 27 patients) groups. Except for the glutamine administration, the groups did not differ in the other treatments and nutrition supplements. The levels of diamine oxidase (DAO), lactulose/mannitol (L/M), ß2-microglobulin, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBD) and cardiac troponin l (cTnl) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). The levels of resting energy expenditure (REE), serum catecholamines, glucagon, lactate and Homeostasis model assessment (HOMA) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). No significant difference was found in the length of hospitalization or the mortality rate between the two groups (p > 0.05). CONCLUSIONS: Glutamine moderately alleviates the hypermetabolic response and reduces organ damage after severe burns. Therefore, the early application of glutamine, which is effective and safe, should be used as an active intervention as early as possible.

Roxadustat for the treatment of anemia in patients with chronic kidney diseases: a meta-analysis.

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD). Treating renal anemia with erythropoiesis-stimulating agents (ESAs) or erythropoietin analogs is effective but has side effects. Therefore, we performed a meta-analysis to assess the efficacy and safety of roxadustat in treating CKD-induced anemia. METHODS: We searched publications online and conducted a meta-analysis and calculated relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences (MD) with 95% CIs for continuous data. RESULTS: Of 110 articles, nine were included that contained 12 data sets and 11 randomized control trials on roxadustat. In the non-dialysis-dependent (NDD) high-dose/low-dose subgroups, the change in hemoglobin (Hb) levels was significantly higher in the roxadustat group than in the placebo group (P<0.0001, P=0.001, respectively). The Hb response rate of the roxadustat is higher in the NDD subgroup than in the placebo group (P<0.00001, MD=6.92, 95% CI: 4.03, 11.89). However, in the dialysis-dependent subgroup, there was no significant difference in the change in Hb levels or the Hb response rate between the roxadustat and ESA groups. There was no change in the mortality in the roxadustat group compared to that in the placebo/ESA group. Hyperkalemia may be a side effect of roxadustat. CONCLUSIONS: Roxadustat elevated the serum Hb levels in a manner similar to that observed for ESAs. Roxadustat raised the Hb levels more significantly than the placebo and showed a higher Hb response rate than the placebo group in NDD patients. Roxadustat is a safe and effective drug for anemia in CKD patients.

DyIII single-molecule magnets from ligands incorporating both amine and acylhydrazine Schiff base groups: the centrosymmetric {Dy2} displaying dual magnetic relaxation behaviors.

The novel multidentate chelating ligands N'-(2-pyridylmethylidene)-2-(2-pyridylmethylideneamino)benzohydrazide (Hpphz) and N'-(2-salicylmethylidene)-2-(2-salicylmethylideneamino)benzohydrazide (H3sshz), which incorporate both amine and acylhydrazine Schiff base groups, were synthesized and investigated in DyIII coordination chemistry. The reactions of Hpphz and Dy(OAc)3·4H2O have yielded two {Dy2} featuring double OAc- bridges: [Dy2(H2aphz)2(OAc)4(ROH)2] [R = Me (1) and Et (2)], where the Hpphz ligands were in situ hydrolyzed into 2-amino-(2-pyridylmethylideneamino)benzohydrazide ions (H2aphz-). Besides, the reaction between H3sshz and Dy(NO)3·6H2O afforded a [Dy6(sshz)4(µ3-OH)4(µ4-O)(MeOH)4]2·17.5MeOH·2H2O cluster (3). This cluster contained two discrete {Dy6} cores, each of which consisted of a pair of {Dy3} triangular units. All the complexes displayed a single relaxation process of single-molecule magnet (SMM) behaviors under a zero dc field. Both 1 and 2 showed field-induced dual magnetic-relaxation behaviors. However, their diluted samples (1@Y and 2@Y) only showed one-step relaxation behaviors whether under a zero or applied dc field, indicating that the dual magnetic-relaxation behaviors of 1 and 2 were absent after the dilution. Combined with ab initio calculations, it could be infered that the dual magnetic-relaxation behaviors of 1 and 2 might be ascribled to the joint contributions of the single ion anisotropy and magnetic interactions. Examples of this type are rather rare in previous studies. Ab initio calculations also suggested that the discrepancy between the relaxation processes of 1 and 2 may be caused by the small difference between their magnetic interactions.

Preliminary injury risk estimation for occupants involved in frontal crashes by combining computer simulations and real crashes.

The fatality rate can be dramatically reduced with the help of emergency medical services. The purpose of this study was to establish a computational algorithm to predict the injury severity, so as to improve the timeliness, appropriateness, and efficacy of medical care provided. The computer simulations of full-frontal crashes with rigid wall were carried out using LS-DYNA and MADYMO under different collision speeds, airbag deployment time, and seatbelt wearing condition, in which a total of 84 times simulation was conducted. Then an artificial neural network is adopted to construct relevance between head and chest injuries and the injury risk factors; 37 accident cases with Event Data Recorder data and information on occupant injury were collected to validate the model accuracy through receiver operating characteristic analysis. The results showed that delta-v, seatbelt wearing condition, and airbag deployment time were important factors in the occupant's head and chest injuries. When delta-v increased, the occupant had significantly higher level of severe injury on the head and chest; there is a significant difference of Head Injury Criterion and Combined Thoracic Index whether the occupant wore seatbelt. When the airbag deployment time was less than 20 ms, the severity of head and chest injuries did not significantly vary with the increase of deployment time. However, when the deployment time exceeded 20 ms, the severity of head and chest injuries significantly increased with increase in deployment time. The validation result of the algorithm showed that area under the curve = 0.747, p < 0.05, indicating a medium level of accuracy, nearly to previous model. The computer simulation and artificial neural network have a great potential for developing injury risk estimation algorithms suitable for Advanced Automatic Crash Notification applications, which could assist in medical decision-making and medical care.

Major-Minor Long Short-Term Memory for Word-Level Language Model.

Language model (LM) plays an important role in natural language processing (NLP) systems, such as machine translation, speech recognition, learning token embeddings, natural language generation, and text classification. Recently, the multilayer long short-term memory (LSTM) models have been demonstrated to achieve promising performance on word-level language modeling. For each LSTM layer, larger hidden size usually means more diverse semantic features, which enables the LM to perform better. However, we have observed that when a certain LSTM layer reaches a sufficiently large scale, the promotion of overall effect will slow down, as its hidden size increases. In this article, we analyze that an important factor leading to this phenomenon is the high correlation between the newly extended hidden states and the original hidden states, which hinders diverse feature expression of the LSTM. As a result, when the scale is large enough, simply lengthening the LSTM hidden states will cost tremendous extra parameters but has little effect. We propose a simple yet effective improvement on each LSTM layer consisting of a large-scale Major LSTM and a small-scale Minor LSTM to break the high correlation between the two parts of hidden states, which we call Major-Minor LSTMs (MMLSTMs). In experiments, we demonstrate the LM with MMLSTMs surpasses the existing state-of-the-art model on Penn Treebank (PTB) and WikiText-2 (WT2) data sets and outperforms the baseline by 3.3 points in perplexity on WikiText-103 data set without increasing model parameter counts.

Roles of 12-Lipoxygenase and Its Interaction with Angiotensin II on p21 and p27 Expression in Diabetic Nephropathy.

BACKGROUND: 12-Lipoxygenase (12-LO) and angiotensin II (Ang II) are involved in the development of diabetic renal hypertrophy, in which cyclin-kinase inhibitors, p21 and p27 play pivotal roles. Here, we study the effects of 12-LO and its interaction with Ang II on glomerular p21 and p27 expression in diabetic conditions. METHODS: Models used in the current study include glomerular mesangial cells (MCs); and glomeruli from (1) type 2 diabetic db/db mice; (2) type 2 diabetic rats induced by high-fat diet feeding followed by streptozotocin injection; (3) 12-LO knockout (12-LOKO) mice; and (4) normal rats infused with Ang II or 12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE, arachidonic acid metabolite of 12-LO). RESULTS: The protein expression levels of p21 and p27 were increased in high glucose-stimulated MCs and in glomeruli isolated from db/db mice. In type 2 diabetic rats, cinnamyl-3,4-dihydroxy-α-cynanocinnamate (inhibitor of 12-LO) attenuated the increases in glomerular p21 and p27 protein expression, while in normal rats, 12(S)-HETE injection increased glomerular p21 and p27 expression. 12(S)-HETE and Ang II were mutually stimulated in glomeruli. Glomerular p21 and p27 expression were decreased in 12-LOKO mice compared to levels in control mice, and Ang II stimulation increased the protein expression of p27 in control but not 12-LOKO mice. Ang II stimulation had no effect on p21 protein expression in 12-LOKO mice. CONCLUSION: 12-LO is involved in diabetic renal hypertrophy via the induction of p21 and p27 protein expression and interacts with Ang II to induce p27 upregulation in diabetes. The current results suggest a potential amplifying loop in the pathogenesis of diabetic nephropathy.

A Two-Phase Algorithm for Differentially Private Frequent Subgraph Mining.

Mining frequent subgraphs from a collection of input graphs is an important task for exploratory data analysis on graph data. However, if the input graphs contain sensitive information, releasing discovered frequent subgraphs may pose considerable threats to individual privacy. In this paper, we study the problem of frequent subgraph mining (FSM) under the rigorous differential privacy model. We present a two-phase differentially private FSM algorithm, which is referred to as DFG. In DFG, frequent subgraphs are privately identified in the first phase, and the noisy support of each identified frequent subgraph is calculated in the second phase. In particular, to privately identity frequent subgraphs, we propose a frequent subgraph identification approach, which can improve the accuracy of discovered frequent subgraphs through candidate pruning. Moreover, to compute the noisy support of each identified frequent subgraph, we devise a lattice-based noisy support computation approach, which leverages the inclusion relations between the discovered frequent subgraphs to improve the accuracy of the noisy supports. Through formal privacy analysis, we prove that DFG satisfies ϵ-differential privacy. Extensive experimental results on real datasets show that DFG can privately find frequent subgraphs while achieving high data utility.

Exploration of Pedestrian Head Injuries-Collision Parameter Relationships through a Combination of Retrospective Analysis and Finite Element Method.

There are a very limited number of reports concerning the relationship between pedestrian head injuries and collision parameters through a combination of statistical analysis methods and finite element method (FEM). This study aims to explore the characteristics of pedestrian head injuries in car-pedestrian collisions at different parameters by using the two means above. A retrospective analysis of pedestrian head injuries was performed based on detailed investigation data of 61 car-pedestrian collision cases. The head damage assessment parameters (head injury criterion (HIC), peak stress on the skull, maximal principal strain for the brain) in car-pedestrian simulation experiments with four contact angles and three impact velocities were obtained by FEM. The characteristics of the pedestrian head injuries were discussed by comparing and analyzing the statistical analysis results and finite element analysis results. The statistical analysis results demonstrated a significant difference in skull fractures, contusion and laceration of brain and head injuries on the abbreviated injury scale (AIS)3+ was found at different velocities (p < 0.05) and angles (p < 0.05). The simulation results showed that, in pedestrian head-to-hood impacts, the values of head damage assessment parameters increased with impact velocities. At the same velocity, these values from the impact on the pedestrian's back were successively greater than on the front or the side. Furthermore, head injury reconstruction and prediction results of two selected cases were consistent with the real injuries. Overall, it was further spelled out that, for shorter stature pedestrians, increased head impact velocity results in greater head injury severity in car-pedestrian collision, especially in pedestrian head-to-hood impacts. Under a back impact, the head has also been found to be at greater damage risk for shorter stature pedestrians, which may have implications on automotive design and pedestrian protection research if prevention and treatment of these injuries is to be prioritized over head injuries under a front or side impact.

Differentially Private Frequent Subgraph Mining.

Mining frequent subgraphs from a collection of input graphs is an important topic in data mining research. However, if the input graphs contain sensitive information, releasing frequent subgraphs may pose considerable threats to individual's privacy. In this paper, we study the problem of frequent subgraph mining (FGM) under the rigorous differential privacy model. We introduce a novel differentially private FGM algorithm, which is referred to as DFG. In this algorithm, we first privately identify frequent subgraphs from input graphs, and then compute the noisy support of each identified frequent subgraph. In particular, to privately identify frequent subgraphs, we present a frequent subgraph identification approach which can improve the utility of frequent subgraph identifications through candidates pruning. Moreover, to compute the noisy support of each identified frequent subgraph, we devise a lattice-based noisy support derivation approach, where a series of methods has been proposed to improve the accuracy of the noisy supports. Through formal privacy analysis, we prove that our DFG algorithm satisfies ε-differential privacy. Extensive experimental results on real datasets show that the DFG algorithm can privately find frequent subgraphs with high data utility.

Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods.

In this study, we aimed to explore the molecular mechanisms of and genetic factors influencing diabetic nephropathy (DN). Gene expression profiles associated with DN were obtained from the GEO database (Accession no. GSE20844). The differentially expressed genes (DEGs) between diabetic mice and non-diabetic mice were screened. Subsequently, the DEGs were subjected to functional and pathway analysis. The protein-protein interaction (PPI) network was constructed and the transcription factors (TFs) were screened among the DEGs. A total of 92 upregulated and 118 downregulated genes were screened. Pathway analysis revealed that the p53 signaling pathway, the transforming growth factor (TGF)-ß signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway were significantly enriched by upregulated genes. Serpine1 (also known as plasminogen activator inhibitor-1), early growth response 1 (Egr1) and Mdk were found to be significant nodes in the PPI network by three methods. A total of 12 TFs were found to be differentially expressed, of which nuclear receptor subfamily 4, group A, member 1 (Nr4a1) and peroxisome proliferator-activated receptor gamma (Pparg) were found to have multiple interactions with other DEGs. We demonstrated that the p53 signaling pathway, the TGF-ß signaling pathway and the MAPK signaling pathway were dysregulated in the diabetic mice. The significant nodes (Serpine1, Egr1 and Mdk) and differentially expressed TFs (Nr4a1 and Pparg) may provide a novel avenue for the targeted therapy of DN.

Underbelly injury based identification of the driver in a three-rider motorcycle accident.

This paper presents a three-rider motorcycle accident which took place in a suburb of Chongqing China. In the accident, the motorcycle impacted the terminal of a bridge footpath and led to two riders died and one rider injured. After the accident, one rider received injuries around the groin area including the underbelly area and the perineum area. Another rider suffered from injuries only on the perineum areas. In medico-legal judgments, injuries around the groin area also called groin injuries in victims of motorcycle accidents are usually regarded as "fuel tank injuries" which are commonly found in drivers. But, the injuries around the groin area are sometimes confused with the perineum injuries. Therefore, the perineum injuries are often wrongly reckoned as the "fuel tank injuries" and used to identify the drivers too. Actually, passengers can sometimes suffer from perineum injuries in many head-on impacting motorcycle accidents. It is of vital matters to understand the differences between groin injuries and perineum injuries so that the real driver who should be responsible for the accident can be recognized. In this paper, the three-rider motorcycle accident was presented and the injury information of the three riders was studied in order to distinguish the real driver from the riders. We consider that the groin injury has some differences with the perineum injury and the latter should not always be related to the driver especially in high-speed head-on impacting motorcycle accidents. In addition, the injury on underbelly areas is important to identify the driver.

Differentially Private Frequent Sequence Mining.

In this paper, we study the problem of mining frequent sequences under the rigorous differential privacy model. We explore the possibility of designing a differentially private frequent sequence mining (FSM) algorithm which can achieve both high data utility and a high degree of privacy. We found, in differentially private FSM, the amount of required noise is proportionate to the number of candidate sequences. If we could effectively prune those unpromising candidate sequences, the utility and privacy tradeoff can be significantly improved. To this end, by leveraging a sampling-based candidate pruning technique, we propose PFS2, a novel differentially private FSM algorithm. It is the first algorithm that supports the general gap-constrained FSM in the context of differential privacy. The gap constraints in FSM can be used to limit the mining results to a controlled set of frequent sequences. In our PFS2 algorithm, the core is to utilize sample databases to prune the candidate sequences generated based on the downward closure property. In particular, we use the noisy local support of candidate sequences in the sample databases to estimate which candidate sequences are potentially frequent. To improve the accuracy of such private estimations, a gap-aware sequence shrinking method is proposed to enforce the length constraint on the sample databases. Moreover, to calibrate the amount of noise required by differential privacy, a gap-aware sensitivity computation method is proposed to obtain the sensitivity of the local support computations with different gap constraints. Furthermore, to decrease the probability of misestimating frequent sequences as infrequent, a threshold relaxation method is proposed to relax the user-specified threshold for the sample databases. Through formal privacy analysis, we show that our PFS2 algorithm is ϵ-differentially private. Extensive experiments on real datasets illustrate that our PFS2 algorithm can privately find frequent sequences with high accuracy.

Biomechanical behavior of brain injury caused by sticks using finite element model and Hybrid-III testing.

OBJECTIVE: To study the biomechanical mechanism of head injuries beaten with sticks, which is common in the battery or assaultive cases. METHODS: In this study, the Hybrid-III anthropomorphic test device and finite element model (FEM) of the total human model for safety (THUMS) head were used to determine the biomechanical response of head while being beaten with different sticks. Total eight Hybrid-III tests and four finite element simulations were conducted. The contact force, resultant acceleration of head center of gravity, intracranial pressure and von Mises stress were calculated to determine the different biomechanical behavior of head with beaten by different sticks. RESULTS: In Hybrid-III tests, the stick in each group demonstrated the similar kinematic behavior under the same loading condition. The peak values of the resultant acceleration for thick iron stick group, thin iron stick group, thick wooden stick group and thin wooden stick group were 203.4 g, 221.1 g, 170.5 g and 122.2 g respectively. In finite element simulations, positive intracranial pressure was initially observed in the frontal comparing with negative intracranial pressure in the contra-coup site. Subsequently the intracranial pressure in the coup site was decreasing toward negative value while the contra-coup intracranial pressure increasing toward positive values. CONCLUSIONS: The results illustrated that the stiffer and larger the stick was, the higher the von Mises stress, contact force and intracranial pressure were. We believed that the results in the Hybrid-III tests and THUMS head simulations for brain injury beaten with sticks could be reliable and useful for better understanding the injury mechanism.

Study on pedestrian thorax injury in vehicle-to-pedestrian collisions using finite element analysis.

OBJECTIVE: To explore the relationship between the collision parameters of vehicle and the pedestrian thorax injury by establishing the chest simulation models in car-pedestrian collision at different velocities and angles. METHODS: 87 cases of vehicle-to-pedestrian accidents, with detailed injury information and determined vehicle impact parameters, were included. The severity of injury was scaled in line with the Abbreviated Injury Scale (AIS). The chest biomechanical response parameters and change characteristics were obtained by using Hyperworks and LS-DYNA computing. Simulation analysis was applied to compare the characteristics of injuries. RESULTS: When impact velocities at 25, 40 and 55 km/h, respectively, 1) the maximum values of thorax velocity criterion (VC) were for 0.29, 0.83 and 2.58 m/s; and at the same collision velocity, the thorax VC from the impact on pedestrian's front was successively greater than on his back and on his side; 2) the maximum values of peak stress on ribs were 154, 177 and 209 MPa; and at the same velocity, peak stress values on ribs from the impact on pedestrian's side were greater than on his front and his back. CONCLUSION: There is a positive correlation between the severity and risk of thorax injury and the collision velocity and angle of car-thorax crashes. At the same velocity, it is of greater damage risk when the soft tissue of thorax under a front impact; and there is also a greater risk of ribs fracture under a side impact of the thorax. This result is of vital significance for diagnosis and protection of thorax collision injuries.