Quantitative morphological analysis framework of infant cranial sutures and fontanelles based on CT images.

Characterizing the suture morphological variation is a crucial step to investigate the influence of sutures on infant head biomechanics. This study aimed to establish a comprehensive quantitative framework for accurately capturing the cranial suture and fontanelle morphologies in infants. A total of 69 CT scans of 2-4 month-old infant heads were segmented to identify semilandmarks at the borders of cranial sutures and fontanelles. Morphological characteristics, including length, width, sinuosity index (SI), and surface area, were measured. For this, an automatic method was developed to determine the junction points between sutures and fontanelles, and thin-plate-spline (TPS) was utilized for area calculation. Different dimensionality reduction methods were compared, including nonlinear and linear principal component analysis (PCA), as well as deep-learning-based variational autoencoder (VAE). Finally, the significance of various covariates was analyzed, and regression analysis was performed to establish a statistical model relating morphological parameters with global parameters. This study successfully developed a quantitative morphological framework and demonstrate its application in quantifying morphologies of infant sutures and fontanelles, which were shown to significantly relate to global parameters of cranial size, suture SI, and surface area for infants aged 2-4 months. The developed framework proved to be reliable and applicable in extracting infant suture morphology features from CT scans. The demonstrated application highlighted its potential to provide valuable insights into the morphologies of infant cranial sutures and fontanelles, aiding in the diagnosis of suture-related skull fractures. Infant suture, Infant fontanelle, Morphological variation, Morphology analysis framework, Statistical model.

Subject-specific finite element head models for skull fracture evaluation-a new tool in forensic pathology.

Post-mortem computed tomography (PMCT) enables the creation of subject-specific 3D head models suitable for quantitative analysis such as finite element analysis (FEA). FEA of proposed traumatic events is an objective and repeatable numerical method for assessing whether an event could cause a skull fracture such as seen at autopsy. FEA of blunt force skull fracture in adults with subject-specific 3D models in forensic pathology remains uninvestigated. This study aimed to assess the feasibility of FEA for skull fracture analysis in routine forensic pathology. Five cases with blunt force skull fracture and sufficient information on the kinematics of the traumatic event to enable numerical reconstruction were chosen. Subject-specific finite element (FE) head models were constructed by mesh morphing based on PMCT 3D models and A Detailed and Personalizable Head Model with Axons for Injury Prediction (ADAPT) FE model. Morphing was successful in maintaining subject-specific 3D geometry and quality of the FE mesh in all cases. In three cases, the simulated fracture patterns were comparable in location and pattern to the fractures seen at autopsy/PMCT. In one case, the simulated fracture was in the parietal bone whereas the fracture seen at autopsy/PMCT was in the occipital bone. In another case, the simulated fracture was a spider-web fracture in the frontal bone, whereas a much smaller fracture was seen at autopsy/PMCT; however, the fracture in the early time steps of the simulation was comparable to autopsy/PMCT. FEA might be feasible in forensic pathology in cases with a single blunt force impact and well-described event circumstances.

Characterization of linezolid- and methicillin-resistant coagulase-negative staphylococci in a tertiary hospital in China.

BACKGROUND: Recently, linezolid-resistant staphylococci have become an emerging problem worldwide. Understanding the mechanisms of resistance, molecular epidemiology and transmission of linezolid-resistant CoNS in hospitals is very important. METHODS: The antimicrobial susceptibilities of all isolates were determined by the microdilution method. The resistance mechanisms and molecular characteristics of the strains were determined using whole-genome sequencing and PCR. RESULTS: All the strains were resistant to oxacillin and carried the mecA gene; 13 patients (36.1%) had prior linezolid exposure. Most S. epidermidis and S. hominis isolates were ST22 and ST1, respectively. MLST typing and evolutionary analysis indicated most linezolid-resistant CoNS strains were genetically related. In this study, we revealed that distinct CoNS strains have different mechanisms of linezolid resistance. Among ST22-type S. epidermidis, acquisition of the T2504A and C2534T mutations in the V domain of the 23 S rRNA gene, as well as mutations in the ribosomal proteins L3 (L101V, G152D, and D159Y) and L4 (N158S), were linked to the development of linezolid resistance. In S. cohnii isolates, cfr, S158Y and D159Y mutations in the ribosomal protein L3 were detected. Additionally, emergence of the G2576T mutation and the cfr gene were major causes of linezolid resistance in S. hominis isolates. The cfr gene, G2576T and C2104T mutations, M156T change in L3 protein, and I188S change in L4 protein were found in S. capitis isolates. CONCLUSION: The emergence of linezolid-resistant CoNS in the environment is concerning because it involves clonal dissemination and frequently coexists with various drug resistance mechanisms.

Designing electrode configuration of electroosmosis based edema treatment as a complement to hyperosmotic therapy.

BACKGROUND: Hyperosmotic therapy is a mainstay treatment for cerebral edema. Although often effective, its disadvantages include mainly acting on the normal brain region with limited effectiveness in eliminating excess fluid in the edema region. This study investigates how to configure our previously proposed novel electroosmosis based edema treatment as a complement to hyperosmotic therapy. METHODS: Three electrode configurations are designed to drive the excess fluid out of the edema region, including 2-electrode, 3-electrode, and 5-electrode designs. The focality and directionality of the induced electroosmotic flow (EOF) are then investigated using the same patient-specific head model with localized edema. RESULTS: The 5-electrode design shows improved EOF focality with reduced effect on the normal brain region than the other two designs. Importantly, this design also achieves better directionality driving excess edema tissue fluid to a larger region of surrounding normal brain where hyperosmotic therapy functions better. Thus, the 5-electrode design is suggested to treat edema more efficiently via a synergic effect: the excess fluid is first driven out from the edema to surrounding normal brain via EOF, where it can then be treated with hyperosmotic therapy. Meanwhile, the 5-electrode design drives 2.22 mL excess fluid from the edema region in an hour comparable to the other designs, indicating a similar efficiency of EOF. CONCLUSIONS: The results show that the promise of our previously proposed novel electroosmosis based edema treatment can be designed to achieve better focality and directionality towards a complement to hyperosmotic therapy.

CD24 is a Potential Biomarker for Prognosis in Human Breast Carcinoma.

BACKGROUND/AIMS: CD24 is a highly glycosylated mucin-like antigen on the cell surface, which has recently emerged as a novel oncogene and metastasis promoter. We performed bioinformatics analysis to investigate whether CD24 can serve as a prognostic indicator in breast cancer. METHODS: CD24 expression was assessed using SAGE Genie tools and Oncomine analysis. The PrognoScan database, Kaplan-Meier Plotter, and bc-GenExMiner were used to identify the prognostic roles of CD24 in breast cancer. RESULTS: We found that CD24 was more frequently overexpressed in breast cancer than in normal breast tissue and correlated with worse prognosis. Meanwhile, high CD24 expression was associated with increased risk of HER2, basal-like, triple-negative breast cancer, and higher Scarff-Bloom-Richardson grade. Data mining in multiple big databases confirmed a positive correlation between CD24 mRNA expression and SDC1 mRNA expression in breast cancer tissue. CONCLUSIONS: Our findings suggest that CD24 overexpression is more common in breast cancer than in corresponding normal tissue. In addition, CD24 and SDC1 can serve as prognostic indicators for breast cancer. However, large-scale and comprehensive research is needed to further confirm these results.

Higher impact energy in traumatic brain injury interferes with noncovalent and covalent bonds resulting in cytotoxic brain tissue edema as measured with computational simulation.

BACKGROUND: Cytotoxic brain tissue edema is a complicated secondary consequence of ischemic injury following cerebral diseases such as traumatic brain injury and stroke. To some extent the pathophysiological mechanisms are known, but far from completely. In this study, a hypothesis is proposed in which protein unfolding and perturbation of nucleotide structures participate in the development of cytotoxic edema following traumatic brain injury (TBI). METHODS: An advanced computational simulation model of the human head was used to simulate TBI. The consequences of kinetic energy transfer following an external dynamic impact were analyzed including the intracranial pressure (ICP), strain level, and their potential influences on the noncovalent and covalent bonds in folded protein structures. RESULTS: The result shows that although most of the transferred kinetic energy is absorbed in the skin and three bone layers, there is a substantial amount of energy reaching the gray and white matter. The kinetic energy from an external dynamic impact has the theoretical potential to interfere not only with noncovalent but also covalent bonds when high enough. The induced mechanical strain and pressure may further interfere with the proteins, which accumulate water molecules into the interior of the hydrophobic structures of unfolded proteins. Simultaneously, the noncovalent energy-rich bonds in nucleotide adenosine-triphosphates may be perturbed as well. CONCLUSIONS: Based on the analysis of the numerical simulation data, the kinetic energy from an external dynamic impact has the theoretical potential to interfere not only with noncovalent, but also with covalent bonds when high enough. The subsequent attraction of increased water molecules into the unfolded protein structures and disruption of adenosine-triphosphate bonds could to some extent explain the etiology to cytotoxic edema.

Decompressive craniectomy (DC) at the non-injured side of the brain has the potential to improve patient outcome as measured with computational simulation.

OBJECTIVE: Decompressive craniectomy (DC) is efficient in reducing the intracranial pressure in several complicated disorders such as traumatic brain injury (TBI) and stroke. The neurosurgical procedure has indeed reduced the number of deaths. However, parallel with the reduced fatal cases, the number of vegetative patients has increased significantly. Mechanical stretching in axonal fibers has been suggested to contribute to the unfavorable outcome. Thus, there is a need for improving treatment procedures that allow both reduced fatal and vegetative outcomes. The hypothesis is that by performing the DC at the non-injured side of the head, stretching of axonal fibers at the injured brain tissue can be reduced, thereby having the potential to improve patient outcome. METHODS: Six patients, one with TBI and five with stroke, were treated with DC and where each patient's pre- and postoperative computerized tomography (CT) were analyzed and transferred to a finite element (FE) model of the human head and brain to simulate DC both at the injured and non-injured sides of the head. Poroelastic material was used to simulate brain tissue. RESULTS: The computational simulation showed slightly to substantially increased axonal strain levels over 40 % on the injured side where the actual DC had been performed in the six patients. However, when the simulation DC was performed on the opposite, non-injured side, there was a substantial reduction in axonal strain levels at the injured side of brain tissue. Also, at the opposite, non-injured side, the axonal strain level was substantially lower in the brain tissue. The reduced axonal strain level could be verified by analyzing a number of coronal sections in each patient. Further analysis of axial slices showed that falx may tentatively explain part of the different axonal strain levels between the DC performances at injured and opposite, non-injured sides of the head. CONCLUSIONS: By using a FE method it is possible to optimize the DC procedure to a non-injured area of the head thereby having the potential to reduce axonal stretching at the injured brain tissue. The postoperative DC stretching of axonal fibers may be influenced by different anatomical structures including falx. It is suggested that including computational FE simulation images may offer guidance to reduce axonal strain level tailoring the anatomical location of DC performance in each patient.

Evaluating child helmet protection and testing standards: A study using PIPER child head models aged 1.5, 3, 6, and 18 years.

The anatomy of children's heads is unique and distinct from adults, with smaller and softer skulls and unfused fontanels and sutures. Despite this, most current helmet testing standards for children use the same peak linear acceleration threshold as for adults. It is unclear whether this is reasonable and otherwise what thresholds should be. To answer these questions, helmet-protected head responses for different ages are needed which is however lacking today. In this study, we apply continuously scalable PIPER child head models of 1.5, 3, and 6 years old (YO), and an upgraded 18YO to study child helmet protection under extensive linear and oblique impacts. The results of this study reveal an age-dependence trend in both global kinematics and tissue response, with younger children experiencing higher levels of acceleration and velocity, as well as increased skull stress and brain strain. These findings indicate the need for better protection for younger children, suggesting that youth helmets should have a lower linear kinematic threshold, with a preliminary value of 150g for 1.5-year-old helmets. However, the results also show a different trend in rotational kinematics, indicating that the threshold of rotational velocity for a 1.5YO is similar to that for adults. The results also support the current use of small-sized adult headforms for testing child helmets before new child headforms are available.

Development of personalizable female and male pedestrian SAFER human body models.

OBJECTIVES: Vulnerable road users are globally overrepresented as victims of road traffic injuries. Developing biofidelic male and female pedestrian human body models (HBMs) that represent diverse anthropometries is essential to enhance road safety and propose intervention strategies. METHODS: In this study, 50th percentile male and female pedestrians of the SAFER HBM were developed via a newly developed image registration-based mesh morphing framework. The performance of the HBMs was evaluated by means of a set of cadaver experiments, involving subjects struck laterally by a generic sedan buck. RESULTS: In simulated whole-body pedestrian collisions, the personalized HBMs effectively replicate trajectories of the head and lower body regions, as well as head kinematics, in lateral impacts. The results also demonstrate the personalization framework's capacity to generate personalized HBMs with reliable mesh quality, ensuring robust simulations. CONCLUSIONS: The presented pedestrian HBMs and personalization framework provide robust means to reconstruct and evaluate head impacts in pedestrian-to-vehicle collisions thoroughly and accurately.

The White Matter Fiber Tract Deforms Most in the Perpendicular Direction During In Vivo Volunteer Impacts.

White matter (WM) tract-related strains are increasingly used to quantify brain mechanical responses, but their dynamics in live human brains during in vivo impact conditions remain largely unknown. Existing research primarily looked into the normal strain along the WM fiber tracts (i.e., tract-oriented normal strain), but it is rarely the case that the fiber tract only endures tract-oriented normal strain during impacts. In this study, we aim to extend the in vivo measurement of WM fiber deformation by quantifying the normal strain perpendicular to the fiber tract (i.e., tract-perpendicular normal strain) and the shear strain along and perpendicular to the fiber tract (i.e., tract-oriented shear strain and tract-perpendicular shear strain, respectively). To achieve this, we combine the three-dimensional strain tensor from the tagged magnetic resonance imaging with the diffusion tensor imaging (DTI) from an open-access dataset, including 44 volunteer impacts under two head loading modes, i.e., neck rotations (N = 30) and neck extensions (N = 14). The strain tensor is rotated to the coordinate system with one axis aligned with DTI-revealed fiber orientation, and then four tract-related strain measures are calculated. The results show that tract-perpendicular normal strain peaks are the largest among the four strain types (p < 0.05, Friedman's test). The distribution of tract-related strains is affected by the head loading mode, of which laterally symmetric patterns with respect to the midsagittal plane are noted under neck extensions, but not under neck rotations. Our study presents a comprehensive in vivo strain quantification toward a multifaceted understanding of WM dynamics. We find that the WM fiber tract deforms most in the perpendicular direction, illuminating new fundamentals of brain mechanics. The reported strain images can be used to evaluate the fidelity of computational head models, especially those intended to predict fiber deformation under noninjurious conditions.

A method for generating case-specific vehicle models from a single-view vehicle image for accurate pedestrian injury reconstructions.

Developing vehicle finite element (FE) models that match real accident-involved vehicles is challenging. This is related to the intricate variety of geometric features and components. The current study proposes a novel method to efficiently and accurately generate case-specific buck models for car-to-pedestrian simulations. To achieve this, we implemented the vehicle side-view images to detect the horizontal position and roundness of two wheels to rectify distortions and deviations and then extracted the mid-section profiles for comparative calculations against baseline vehicle models to obtain the transformation matrices. Based on the generic buck model which consists of six key components and corresponding matrices, the case-specific buck model was generated semi-automatically based on the transformation metrics. Utilizing this image-based method, a total of 12 vehicle models representing four vehicle categories including family car (FCR), Roadster (RDS), small Sport Utility Vehicle (SUV), and large SUV were generated for car-to-pedestrian collision FE simulations in this study. The pedestrian head trajectories, total contact forces, head injury criterion (HIC), and brain injury criterion (BrIC) were analyzed comparatively. We found that, even within the same vehicle category and initial conditions, the variation in wrap around distance (WAD) spans 84-165 mm, in HIC ranges from 98 to 336, and in BrIC fluctuates between 1.25 and 1.46. These findings highlight the significant influence of vehicle frontal shape and underscore the necessity of using case-specific vehicle models in crash simulations. The proposed method provides a new approach for further vehicle structure optimization aiming at reducing pedestrian head injury and increasing traffic safety.

Prediction of skull fractures in blunt force head traumas using finite element head models.

Traumatic head injuries remain a leading cause of death and disability worldwide. Although skull fractures are one of the most common head injuries, the fundamental mechanics of cranial bone and its impact tolerance are still uncertain. In the present study, a strain-rate-dependent material model for cranial bone has been proposed and implemented in subject-specific Finite Element (FE) head models in order to predict skull fractures in five real-world fall accidents. The subject-specific head models were developed following an established image-registration-based personalization pipeline. Head impact boundary conditions were derived from accident reconstructions using personalized human body models. The simulated fracture lines were compared to those visible in post-mortem CT scans of each subject. In result, the FE models did predict the actual occurrence and extent of skull fractures in all cases. In at least four out of five cases, predicted fracture patterns were comparable to ones from CT scans and autopsy reports. The tensile material model, which was tuned to represent rate-dependent tensile data of cortical skull bone from literature, was able to capture observed linear fractures in blunt indentation loading of a skullcap specimen. The FE model showed to be sensitive to modeling parameters, in particular to the constitutive parameters of the cortical tables. Nevertheless, this study provides a currently lacking strain-rate dependent material model of cranial bone that has the capacity to accurately predict linear fracture patterns. For the first time, a procedure to reconstruct occurrences of skull fractures using computational engineering techniques, capturing the all-in-all fracture initiation, propagation and final pattern, is presented.

Receptor for activated C kinase 1 (RACK1) inhibits function of transient receptor potential (TRP)-type channel Pkd2L1 through physical interaction.

Pkd2L1 (also called TRPP3) is a non-selective cation channel permeable to Ca(2+), Na(+), and K(+) and is activated by Ca(2+). It is also part of an acid-triggered off-response cation channel complex. We previously reported roles of the Pkd2L1 C-terminal fragments in its channel function, but the role of the N terminus remains unclear. Using a yeast two-hybrid screening, we found that the Pkd2L1 N terminus interacts with the receptor for activated C kinase 1 (RACK1), a scaffolding/anchoring protein implicated in various cellular functions. This interaction requires the last two Trp-Asp (WD) motifs of RACK1 and fragment Ala(19)-Pro(45) of Pkd2L1. The interaction was confirmed by GST pulldown, blot overlay, and co-immunoprecipitation assays. By (45)Ca tracer uptake and two-microelectrode voltage clamp electrophysiology, we found that in Xenopus oocytes with RACK1 overexpression Pkd2L1 channel activity is abolished or substantially reduced. Combining with oocyte surface biotinylation experiments, we demonstrated that RACK1 inhibits the function of Pkd2L1 channel on the plasma membrane in addition to reducing its total and plasma membrane expression. Overexpressing Pkd2L1 N- or C-terminal fragments as potential blocking peptides for the Pkd2L1-RACK1 interaction, we found that Pkd2L1 N-terminal fragment Met(1)-Pro(45), but not Ile(40)-Ile(97) or C-terminal fragments, abolishes the inhibition of Pkd2L1 channel by overexpressed and oocyte-native RACK1 likely through disrupting the Pkd2L1-RACK1 association. Taken together, our study demonstrated that RACK1 inhibits Pkd2L1 channel function through binding to domain Met(1)-Pro(45) of Pkd2L1. Thus, Pkd2L1 is a novel target channel whose function is regulated by the versatile scaffolding protein RACK1.

Meta-analysis: serious adverse events in Crohn's disease patients treated with TNF-alpha inhibitors.

BACKGROUND/AIMS: It remains a question whether anti-TNF-a treatment is associated with an increase of serious adverse events (SAE) in Crohn's Disease (CD) patients. This study aims to assess the risk of SAE of anti-TNF-a treatment in CD patients. METHODOLOGY: Literature search of EMBASE, PubMed, ScienceDirect, Cochrane Library and ClinicalTrials.gov until June 2012 was conducted. Eligible studies were randomized controlled trials (RCTs) ofTNF-a inhibitors treated for at least 24 weeks in CD patients. RESULTS: Thirteen RCTs, involving 4,257 patients with CD were included in analysis. SAE were reported in 364 patients (14.26%) in treatment groups and 263 patients (15.43%) in control groups. The proportion of patients with SAE was lower with TNF-a inhibitors than with placebo (OR, 0.80; 95% CI, 0.67-0.96; p=0.01). Compared with controls, the risks of malignancy and serious infection treated with TNF-a inhibitors showed no significant difference (p>0.05). CONCLUSIONS: In CD patients, anti-TNF-a treatment, especially for adalimumab, could decrease the incidence of SAE, without an increased risk of malignancy or serious infection. TNF-a inhibitors are safe in treatment of CD patients. To assess the risk of SAE, larger samples of randomized control trials with long term follow-up are needed.

The clinical significance of HER-2 and NF-KB expression in gastric cancer.

BACKGROUND/AIMS: To investigate the expression of human epidermal growth factor 2 (HER-2) and Nuclear factor-Kb (NF-KB) in gastric cancer, and the relation of these two parameters with stage, grade and metastasis of gastric cancer. METHODOLOGY: The serum level of HER-2 in 75 gastric cancer patients and control participants were determined by enzyme-linked immunosorbent assay (ELISA) kits. Expression of HER-2 and NF-KB protein were detected by immunohistochemical staining (SP method) of paraffin-embedded tissues in 75 tumors (observed group) and 22 normal gastric specimens. The clinical pathological data was statistically analyzed. RESULTS: Serum HER-2 level were significantly increased in study group compared with those in the control group (p<0.001). The HER-2 level of 8.2 ng/mL as the cutoff value has a 79% sensitivity and an 82% specificity for predicting gastric cancer. The positive rate of HER-2 and NF-KB in the observed group was 24.00% (18/75) and 62.67% (47/75) respectively. The expression of HER-2 and NF-KB were not correlated with age and gender, but with stage, grade and metastasis (p<0.05). The expression of NF-KB was correlated with tumor size (p<0.05), while HER-2 was not (p<0.05). When HER-2 was positive, N F-KB had a positive rate of 94.44% (17/18), but a positive rate of 52.63% (30/57) when HER-2 was negative. Expression of NF-KB in gastric cancer tissue was correlated with HER-2 expression (X2 = 8.514, p<0.01). CONCLUSIONS: These data suggest that the expression of NF-KB in gastric cancer tissue is correlated with HER-2 expression, and they may play a very important role in the progress of gastric cancer.

Personalization of human body models and beyond via image registration.

Finite element human body models (HBMs) are becoming increasingly important numerical tools for traffic safety. Developing a validated and reliable HBM from the start requires integrated efforts and continues to be a challenging task. Mesh morphing is an efficient technique to generate personalized HBMs accounting for individual anatomy once a baseline model has been developed. This study presents a new image registration-based mesh morphing method to generate personalized HBMs. The method is demonstrated by morphing four baseline HBMs (SAFER, THUMS, and VIVA+ in both seated and standing postures) into ten subjects with varying heights, body mass indices (BMIs), and sex. The resulting personalized HBMs show comparable element quality to the baseline models. This method enables the comparison of HBMs by morphing them into the same subject, eliminating geometric differences. The method also shows superior geometry correction capabilities, which facilitates converting a seated HBM to a standing one, combined with additional positioning tools. Furthermore, this method can be extended to personalize other models, and the feasibility of morphing vehicle models has been illustrated. In conclusion, this new image registration-based mesh morphing method allows rapid and robust personalization of HBMs, facilitating personalized simulations.

Increased strain levels and water content in brain tissue after decompressive craniotomy.

BACKGROUND: At present there is a debate on the effectiveness of the decompressive craniotomy (DC). Stretching of axons was speculated to contribute to the unfavourable outcome for the patients. The quantification of strain level could provide more insight into the potential damage to the axons. The aim of the present study was to evaluate the strain level and water content (WC) of the brain tissue for both the pre- and post-craniotomy period. METHODS: The stretching of brain tissue was quantified retrospectively based on the computerised tomography (CT) images of six patients before and after DC by a non-linear image registration method. WC was related to specific gravity (SG), which in turn was related to the Hounsfield unit (HU) value in the CT images by a photoelectric correction according to the chemical composition of brain tissue. RESULTS: For all the six patients, the strain level showed a substantial increase in the brain tissue close to the treated side of DC compared with that found at the pre-craniotomy period and ranged from 24 to 55 % at the post-craniotomy period. Increase of strain level was also observed at the brain tissue opposite to the treated side, however, to a much lesser extent. The mean area of craniotomy was found to be 91.1 ± 12.7 cm(2). The brain tissue volume increased from 27 to 127 ml, corresponding to 1.65 % and 8.13 % after DC in all six patients. Also, the increased volume seemed to correlate with increased strain level. Specifically, the overall WC of brain tissue for two patients evaluated presented a significant increase after the treatment compared with the condition seen before the treatment. Furthermore, the Glasgow Coma Scale (GCS) improved in four patients after the craniotomy, while two patients died. The GCS did not seem to correlate with the strain level. CONCLUSIONS: We present a new numerical method to quantify the stretching or strain level of brain tissue and WC following DC. The significant increase in strain level and WC in the post-craniotomy period may cause electrophysiological changes in the axons, resulting in loss of neuronal function. Hence, this new numerical method provides more insight of the consequences following DC and may be used to better define the most optimal size and area of the craniotomy in reducing the strain level development.

Fiber orientation downsampling compromises the computation of white matter tract-related deformation.

Incorporating neuroimaging-revealed structural details into finite element (FE) head models opens vast new opportunities to better understand brain injury mechanisms. Recently, growing efforts have been made to integrate fiber orientation from diffusion tensor imaging (DTI) into FE models to predict white matter (WM) tract-related deformation that is biomechanically characterized by tract-related strains. Commonly used approaches often downsample the spatially enriched fiber orientation to match the FE resolution with one orientation per element (i.e., element-wise orientation implementation). However, the validity of such downsampling operation and corresponding influences on the computed tract-related strains remain elusive. To address this, the current study proposed a new approach to integrate voxel-wise fiber orientation from one DTI atlas (isotropic resolution of 1 mm3) into FE models by embedding orientations from multiple voxels within one element (i.e., voxel-wise orientation implementation). By setting the responses revealed by the newly proposed voxel-wise orientation implementation as the reference, we evaluated the reliability of two previous downsampling approaches by examining the downsampled fiber orientation and the computationally predicted tract-related strains secondary to one concussive impact. Two FE models with varying element sizes (i.e., 6.4 ± 1.6 mm and 1.3 ± 0.6 mm, respectively) were incorporated. The results showed that, for the model with a large voxel-mesh resolution mismatch, the downsampled element-wise fiber orientation, with respect to its voxel-wise counterpart, exhibited an absolute deviation over 30° across the WM/gray matter interface and the pons regions. Accordingly, this orientation deviation compromised the computation of tract-related strains with normalized root-mean-square errors up to 30% and underestimated the peak tract-related strains up to 10%. For the other FE model with finer meshes, the downsampling-induced effects were lower, both on the fiber orientation and tract-related strains. Taken together, the voxel-wise orientation implementation is recommended in future studies as it leverages the DTI-delineated fiber orientation to a larger extent than the element-wise orientation implementation. Thus, this study yields novel insights on integrating neuroimaging-revealed fiber orientation into FE models and may better inform the computation of WM tract-related deformation.

Trends in antimicrobial resistance in bloodstream infections at a large tertiary-care hospital in China: a 10-year retrospective study (2010-2019).

OBJECTIVES: Bloodstream infections (BSIs) are a major cause of morbidity and mortality worldwide. This study aimed to explore the distribution and antimicrobial resistance of BSI pathogens at a tertiary-care hospital in China. METHODS: Surveillance blood cultures were routinely taken from patients with fever or suspected sepsis from 2010-2019 at the First Affiliated Hospital of Zhengzhou University. Isolate identification was performed by VITEK®2 Compact and/or VITEK® MS. Antimicrobial susceptibility testing was carried out by MIC determination and/or disk diffusion. RESULTS: Totally, 18 180 strains were isolated from blood cultures, the most common being Escherichia coli (21.7%), followed by coagulase-negative staphylococci (CoNS) (18.8%), Klebsiella pneumoniae (13.0%) and Staphylococcus aureus (6.6%). Escherichia coli resistance rates to ceftazidime, ceftriaxone, cefepime and aztreonam showed a significant declining trend, and the frequency of carbapenem-resistant E. coli was <6.0% over time. Noteworthy, the proportion of carbapenem-resistant K. pneumoniae exhibited a sharp upward trend (from 6.7% to 56.7%). The prevalence of carbapenem-resistant A. baumannii remained at a high level (>75%). Pseudomonas aeruginosa resistance rates against all tested agents were <25%, and resistance rates to aminoglycosides and fluoroquinolones showed a significant downward trend. The frequency of methicillin-resistant CoNS maintained a high level (>70%), however the isolation rate of MRSA ranged from 58.0% to 34.7%, showing a significant decline. CONCLUSION: The dramatic increase in carbapenem-resistant K. pneumoniae during 10 years was noteworthy. Effective infection control measures and stewardship efforts should be taken to prevent their spread. Our results indicate the importance of active surveillance for aetiology and resistance of BSI isolates.

Study on the Prognostic Values of TTC36 Correlated with Immune Infiltrates and Its Methylation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains an incurable disease with a very poor clinical outcome. The purpose of this article was to investigate whether the expression or methylation of tetrapeptide repeat domain 36 (TTC36) could be used as a prognostic marker in hepatocellular carcinoma. TCGA database was used to obtain information on HCC gene expression and the associated clinical features of HCC patients. Differentially expressed genes (DEGs) were screened between 374 HCC specimens and 50 nontumor specimens. The expression and prognostic value of TTC36 were analyzed. The correlations between TTC36 and cancer immune infiltrates were investigated via TIMER. In this study, HCC specimens and nontumor specimens were compared and 35 DEGs were found between them. Among the 35 DEGs, the expression of TTC36 was significantly reduced in HCC samples compared with nontumor samples. Survival tests revealed that patients with low TTC36 expression had a shorter overall survival than patients with high TTC36 expression. TTC36 was found to be an independent predictive factor for HCC in both univariate and multivariate regression analyses. TTC36 was negatively regulated by TTC36 methylation, leading to its low expression in HCC tissues. Immune analysis revealed that TTC36 expression has significant correlations with B cell, T cell CD4+, neutrophil, macrophage, and myeloid dendritic cell. Finally, TTC36 expression was dramatically reduced in HCC cells, and overexpression greatly suppressed HCC cell proliferation and invasion, according to our experimental results. Overall, our data suggested that TTC36 could be applied as a prognostic marker for predicting outcome and immune infiltration in HCC.