Up-regulation of CREB-1 regulates tendon adhesion in the injury tendon healing through the CREB-1/TGF-ß3 signaling pathway.

AIM: To explore the mechanism of the healing of tendon tissue and anti-adhesion, and to discuss the role of the transforming growth factor-ß3 (TGF-ß3)/cAMP response element binding protein-1 (CREB-1) signaling pathway in the healing process of tendons. METHOD: All mice were divided into four groups of 1, 2, 4, and 8 weeks respectively. Each time group was divided into four treatment groups: the amplification group, the inhibition group, the negative group, and the control group. When the tendon injury model was established, the CREB-1 virus was injected into the tendon injury parts. A series of methods such as gait behaviourism, anatomy, histological examination, immunohistochemical examination and collagen staining were employed to assess the tendon healing and the protein expression of TGF-ß3, CREB-1, Smad3/7 and type I/III collagen (COL-I/III). CREB-1 virus was sent to tendon stem cells to assess the protein expression of TGF-ß1, TGF-ß3, CREB-1, COL-I/III by methods such as immunohistochemistry and Western blot. RESULTS: The amplification group showed better gait behaviourism than the inhibition group in the healing process. The amplification group also had less adhesion than the negative group. Hematoxylin-eosin (HE) staining of tendon tissue sections showed that the number of fibroblasts in the amplification group was less than the inhibition group, and the immunohistochemical results indicated that the expression of TGF-ß3, CREB-1, and Smad7 at each time point was higher than the inhibition group. The expression of COL-I/III and Smad3 in the amplification group was lower than the inhibition group at all time points. The collagen staining indicated that the ratio of type I/III collagen in the amplification group was higher than the negative group at 2,4,8 week. The CREB-1 amplification virus could promote the protein expression of TGF-ß3, CREB-1 and inhibit the protein expression of TGF-ß1 and COL-I/III in the tendon stem cells. CONCLUSION: In the process of tendon injury healing, CREB-1 could promote the secretion of TGF-ß3, so as to promote the tendon healing and have the effect of anti-adhesion in tendons. It might provide new intervention targets for anti-adhesion treatment of tendon injuries.

Gait analysis combined with the expression of TGF-ß1, TGF-ß3 and CREB during Achilles tendon healing in rat.

PURPOSE: To observe the changes of gait behavior and the expression of wound healing factors of transforming growth factor-ß1 (TGF-ß1), TGF-ß3 and cAMP response element binding protein-1 (CREB-1) during the healing of Achilles tendon in a rat model, and to investigate whether gait analysis can be used to evaluate the tendon healing. METHODS: Achilles tendon of 40 healthy male Sprague-Dawley rats were transected and sutured to establish the Achilles tendon injury (ATI) model. They were randomly divided into 4 groups based on the observational time point at 1, 2, 4 and 6 weeks after injury (n = 10 for each group). Before modeling, 9 rats were randomly selected for CatWalk gait analysis, which contained step cycle, single stance time and average speed. Data were recorded as the normal controls. After then, ATI models were established in the left hind limbs of the all 40 rats (ATI group), while the right hind limbs were only cut and sutured without injury of the Achilles tendon (sham operation group). At 1, 2, 4 and 6 weeks after injury, the gait behavior of the corresponding group of rats (n = 9) as observed and recorded by CatWalk platform. After then, the rats were sacrificed and Achilles tendon of both limbs was harvested. The tendon healing was observed by gross anatomy and histological examination, and the protein and mRNA expression of TGF-ß1, TGF-ß3, CREB-1 were observed by immunohistochemistry and qPCR. The results of tendon gross grading were analyzed by Wilcoxon rank sum test, and other data were analyzed by one-way analysis of variance among multiple groups. RESULTS: Compared with normal controls, all gait indexes (step cycle, single stance time and average speed) were greatly affected following ATI, which however improved with time. The step cycle was significantly lower at 1, 2 and 4 weeks after ATI (compared with normal controls, all p < 0.05), but almost returned to the normal level at 6 weeks ((0.694 ± 0.102) vs. (0.503 ± 0.094) s, p > 0.05). The single stance time of the ATI group was significantly shorter at 1 and 2 weeks after operation ((0.078 ± 0.010) s at 1 week, (0.078 ± 0.020) s at 2 weeks, all p < 0.001) and revealed no significant difference at 4 weeks (p = 0.120). The average speed of ATI group at 1, 2, 4, 6 weeks was significantly lower than that in the normal control group (all p < 0.001). Gross observation showed that the grade of local scar adhesion in ATI group increased significantly at 2, 4 and 6 weeks, compared with the sham operation group (all p < 0.001). Extensive adhesion was formed at 6 weeks after ATI. The results of HE staining showed that the number of fibroblast increased gradually and arranged more orderly in ATI group at 1, 2 and 4 weeks (all p < 0.001), and decreased at 6 weeks, but it was still significantly higher than that of the sham operation group (p < 0.001). Immunohistochemistry showed that the positive expression of TGF-ß1, TGF-ß3, CREB-1 in ATI group was higher than that in the sham operation group at 4 time points (all p < 0.05), which reached the peak at 2 weeks after operation and decreased at 4 weeks (p = 0.002, p < 0.001, p = 0.041, respectively). The results of qPCR suggested that the mRNA expression of TGF-ß1, TGF-ß3, CREB-1 in ATI group was higher than that in the sham operation group at all-time points (all p < 0.05), which reached the peak at 2 weeks after operation, decreased at 4 weeks, and significantly decreased at 6 weeks (all p < 0.001). CONCLUSION: Gait behavior indexes are associated with Achilles tendon healing. The study gives an insight of TGF-ß1, TGF-ß3, CREB-1 changes in the coursing of Achilles tendon healing and these cytokines may be able to be used to regulate the Achilles tendon healing.

[A study on quality of Paridis Rhizoma and consideration on standards of Paridis Rhizoma in Chinese Pharmacopoeia].

Thin layer chromatography, high performance liquid chromatography and multivariate statistical analysis were integrated in current study to provide a basis for the quality evaluation and the standard improvement of Paridis Rhizoma(Chinese name: Chong-lou). The results demonstrated that the primary saponins in the two authorized sources of Paridis Rhizoma were polyphyllinsⅠ, Ⅱ and Ⅶ, while the rhizome of Trillium tschonoskii an adulterant of Paridis Rhizoma was rich of polyphyllin Ⅵ. Therefore, the apparent content of polyphyllin Ⅵ plays a determinant role towards the source authentication of raw materials and decoction slices of Paridis Rhizoma, whose adulterants frequently occur in the market. Moreover, the contents of polyphyllin Ⅵ in the two authorized sources could meet the requirements of Chinese Pharmacopoeia. Therefore, we suggested that polyphyllin Ⅵ should not be omitted from the quality standard of Paridis Rhizoma in the Chinese Pharmacopoeia, and on the other side, polyphyllinsⅠ, Ⅱ and Ⅶ should be the eligible quality indicators. The study aims to sound information and evidences for the quality evaluation of Paridis Rhizoma, and also to provide a theoretical basis for the standard revision of Paridis Rhizoma in the future Chinese Pharmacopoeia.

Structure elucidation and NMR assignment of two new eudesmane derivatives from Merremia yunnanensis.

Two new eudesmane derivatives, 1α,6ß,9ß-trihydroxy-eudesm-3-ene-1-O-ß-d-glucopyranoside (1) and 1α,6ß,9ß-trihydroxy-eudesm-3-ene-1-(6-cinnamoyl)-O-ß-d-glucopyranoside (2) were discovered from Merremia yunnanensis. The structures were elucidated by analysis of their spectroscopic data including HR-ESI-MS, 1D, and 2D NMR. It should be noted that this is the first report about structure elucidation and NMR assignment of compounds from M. yunnanensis.

Evaluation of a newly developed chemiluminescence immunoassay for detecting cardiac troponin T.

BACKGROUND: To evaluate the performance of a chemiluminescence detection kit for cardiac troponin T (cTnT). METHODS: According to the "Guiding principles on performance analysis of diagnostic reagents in vitro" and the Clinical and Laboratory Standards Institute (CLSI) Guidelines, we assessed the detection limit, linear range, reportable range, accuracy, precision, cross reactivity, interference factors, and matrix effect of the kit, and compared these parameters with that of the commercial electrochemiluminescence detection kit for cTnT (Roche). RESULTS: The minimum detection limit of the kit was 0.01 ng/mL. The linear range was 0.01 ng/mL-25 ng/mL. The reportable range was from 0.01 ng/mL to 100 ng/mL. Precision within the batch was 2.9%-6.4%, and precision between batches was 6.0%; the accuracy was good and the recovery rate reached 96.2%. The cross-reaction test demonstrated that there was no reactivity between cTnT and a variety of troponins. Test results deviated by less than ±10% in the presence of hemoglobin ≤1000 µg/mL, bilirubin ≤250 µg/mL, triglycerides ≤11.25 mg/mL, and rheumatoid factor ≤206 U/mL, suggesting that kit results were not significantly interfered with these factors. Results from the matrix-effect assessment revealed absence of a matrix effect in the tested serum samples. Correlation study revealed that the performance of the kit was very consistent with that of the Roche electrochemiluminescence detection kit (Kappa = 0.900, P < .001) with a high correlation (r = .903, P < .001) and a total matching rate of 95.00%. CONCLUSION: The performance of the evaluated chemiluminescence immunoquantitation kit for cTnT detection was acceptable in all tested parameters, fulfilling requirements for clinical applications.

Acclimatization to middle altitude hypoxia protects against developmental and cognitive deficits caused by acute fetal hypoxia in mice.

Acute fetal hypoxia (AFH) can elicit postnatal motor deficits and cognitive impairments. To test whether lifelong acclimatization to middle altitude (MA) hypoxia has protective effects on the impairments caused by AFH, ICR mice bred at 1 900 m altitude for 6-7 generations were evaluated under AFH. On gestation day 9 (GD 9), 13 (GD 13) or 17 (GD 17), pregnant mice received a single exposure to acute hypoxia (7% O2, 6 h). Physiological and neurodevelopmental behaviors, motor function (open field), spatial learning and memory (Morris water maze), and anxiety level (elevated plus maze) were examined in the offspring from neonate to adulthood. In the neonatal age, among all the physiological and behavioral landmarks, almost no differences were found in the hypoxia groups. In the juvenile period, no obvious impairments of motor function and anxiety level were found in the hypoxia groups. In the adult period, no obvious impairment of motor function was found in hypoxia groups; Interestingly, AFH groups' offspring showed normal or enhanced long-term spatial memory ability after AFH. These data suggest that AFH cause little abnormalities in the offspring of MA-adapted mice. To further investigate the underlying mechanisms, the neuronal numbers in behavior-related brain areas (accumbens nucleus, basal amygdala and hippocampus) were counted, and the physiological parameters of the blood were measured. The morphological data showed that no obvious neuronal necrosis was found in all hypoxia groups. In addition, blood tests showed that red blood corpuscle count, hemoglobin concentration and hematocrit levels in mice raised at MA were markedly higher in both males and females, compared with controls raised at the sea level. These data suggest that lifelong acclimatization to MA hypoxia has protective effects against development delay, motor deficits and spatial learning and memory impairments induced by AFH, and the protective effects may be due to higher hemoglobin concentration and hematocrit levels in the blood. The findings may provide a better understanding of fetal hypoxia and potential intervention treatments.

Toxicity of cerium and thorium on Daphnia magna.

Cerium (Ce) and thorium (Th) are always thought to be chemically similar and have comparable toxic properties on living organisms. In the present study, the acute and chronic toxicity of these two elements to freshwater crustacean Daphnia magna were investigated in the modified reconstituted water (6mg/L KCl, 123mg/L MgSO4·7H2O, and 294mg/L CaCl2·2H2O in Milli-Q water, pH 7.8). It seemed that Ce and Th had comparable acute toxicity on Daphnia: 24/48h EC50 for Th and Ce were 7.3/4.7µM and 16.4/10.7µM, respectively. However, Ce was present as soluble ions while all of Th was present as particulate ThO2 in the exposure medium. Considering their different chemical forms and bioavailability, the toxic mechanisms of Ce3+ and ThO2 on Daphnia would be totally different. To our knowledge, this is the first time to investigate the aquatic toxicity of thorium and cerium based on their actual chemical speciation in the exposure medium. The results also suggest that more attention should be paid on the detrimental effect of Th in the form of particulate ThO2.

Diterpenoid alkaloids from the roots of Aconitum brachypodum Diels.

A new diterpenoid alkaloid, named bullatine H (1), along with 10 known diterpenoid alkaloids were isolated from the roots of Aconitum brachypodum Diels (Ranunculaceae). The structure of 1 was elucidated by analysis of its spectroscopic data. It should be noted that compound 1 is the first example with 11, 13-dioxygenated denudatine-type diterpenoid alkaloid isolated from Aconitum brachypodum.

Antibacterial Properties of Tebipenem Pivoxil Tablet, a New Oral Carbapenem Preparation against a Variety of Pathogenic Bacteria in Vitro and in Vivo.

AIMS: To systemically investigate the in vitro and in vivo antibacterial properties of tebipenem pivoxil tablet. In addition, acute toxicity of this preparation was also studied. METHODS: In vitro, minimum inhibitory concentration (MIC) or minimal inhibitory concentration (MBC) were determined by using the serial 2-fold broth or agar dilution methods. Further, cumulative MIC inhibition curves were then made to assess the antibacterial effects of the drug at various concentrations. In vivo, minimum lethal dose (MLD) in combination with maximum tolerance dose (MTD) was used to measure the acute toxicity of the tebipenem pivoxil tablet in mice. After that, sepsis mouse models challenged with Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, respectively, were established to evaluate the anti-infective effect of this preparation. RESULTS: The MIC90 values of tebipenem pivoxil against Gram-positive bacteria such as methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus epidermidis (MSSE), methicillin-resistant Staphylococcus epidermidis (MRSE), Pyogenic streptococcus, and Enterococcus faecalis were ≤ 0.125, 16, 0.5, 8, ≤ 0.125, and 32 µg/mL, respectively. Correspondingly, the MIC90 values of tebipenem pivoxil against Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Haemophilus influenzae, Pseudomonas aeruginosa, and Acinetobacter baumannii were 1, 0.5, ≤ 0.125, 0.25, 64, 64 µg/mL, respectively. The MBC values of tebipenem pivoxil against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae were 0.016-2, 0.063-32, 0.031-32 µg/mL, respectively. The acute toxicity study showed that the MLD of the tebipenem pivoxil tablet was 4.00 g/kg and the MTD was 3.40 g/kg in mice. In all the sepsis mouse models, the simultaneous administration of the tebipenem pivoxil tablets significantly reduced mortality of the sepsis-model mice as compared with the control. Furthermore, the survival rate in the tebipenem pivoxil tablet group was remarkably higher than that in the meropenem group in all the sepsis mouse models tested. In the sepsis model challenged with Staphylococcus aureus ATCC29213, Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC27853, and Pseudomonas aeruginosa clinical strain, respectively, tebipenem pivoxil tablet (100 mg/kg) displayed a better protective effect than tebipenem pivoxil granules (100 mg/kg). CONCLUSIONS: In summary, tebipenem pivoxil displays an excellent antibacterial activity against a variety of pathogenic bacteria in vitro. Importantly, tebipenem pivoxil tablet significantly protects the sepsis mice challenged with various pathogenic bacteria, which may provide a potential approach to treating bacterial sepsis in clinic.

Expression and prognostic significance of TCTN1 in human glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common and lethal intracranial malignancy in adults, with dismal prognosis despite multimodal therapies. Tectonic family member 1 (TCTN1) is a protein involved in a diverse range of developmental processes, yet its functions in GBM remain unclear. This study aims to investigate expression profile, prognostic value and effects of TCTN1 gene in GBM. METHODS: Protein levels of TCTN1 were assessed by immunohistochemical staining using a tissue microarray constructed by a Chinese cohort of GBM patients (n=110), and its mRNA expression was also detected in a subset of this cohort. Kaplan-Meier analysis and Cox regression were performed to estimate the prognostic significance of TCTN1. Similar analyses were also conducted in another two independent cohorts: The Cancer Genome Atlas (TCGA) cohort (n=528) and the Repository for Molecular Brain Neoplasia Data (REMBRANDT) cohort (n=228). For the TCGA cohort, the relationships between TCTN1 expression, clinical outcome, molecular subtypes and genetic alterations were also analysed. Furthermore, proliferation of TCTN1 overexpressed or silenced GBM cells was determined by CCK-8 assays. RESULTS: As discovered in three independent cohorts, both mRNA and protein levels of TCTN1 expression were markedly elevated in human GBMs, and higher TCTN1 expression served as an independent prognostic factor predicting poorer prognosis of GBM patients. Additionally, in the TCGA cohort, TCTN1 expression was dramatically decreased in patients within the proneural subtype compared to other subtypes, and significantly influenced by the status of several genetic aberrations such as CDKN2A/B deletion, EGFR amplification, PTEN deletion and TP53 mutation. The prognostic value of TCTN1 was more pronounced in proneural and mesenchymal subtypes, and was also affected by several genetic alterations particularly PTEN deletion. Furthermore, overexpression of TCTN1 significantly promoted proliferation of GBM cells, while its depletion evidently hampered cell growth. CONCLUSIONS: TCTN1 is elevated in human GBMs and predicts poor clinical outcome for GBM patients, which is associated with molecular subtypes and genetic features of GBMs. Additionally, TCTN1 expression impacts GBM cell proliferation. Our results suggest for the first time that TCTN1 may serve as a novel prognostic factor and a potential therapeutic target for GBM.

Granular estimation of user cognitive workload using multi-modal physiological sensors.

Mental workload (MWL) is a crucial area of study due to its significant influence on task performance and potential for significant operator error. However, measuring MWL presents challenges, as it is a multi-dimensional construct. Previous research on MWL models has focused on differentiating between two to three levels. Nonetheless, tasks can vary widely in their complexity, and little is known about how subtle variations in task difficulty influence workload indicators. To address this, we conducted an experiment inducing MWL in up to 5 levels, hypothesizing that our multi-modal metrics would be able to distinguish between each MWL stage. We measured the induced workload using task performance, subjective assessment, and physiological metrics. Our simulated task was designed to induce diverse MWL degrees, including five different math and three different verbal tiers. Our findings indicate that all investigated metrics successfully differentiated between various MWL levels induced by different tiers of math problems. Notably, performance metrics emerged as the most effective assessment, being the only metric capable of distinguishing all the levels. Some limitations were observed in the granularity of subjective and physiological metrics. Specifically, the subjective overall mental workload couldn't distinguish lower levels of workload, while all physiological metrics could detect a shift from lower to higher levels, but did not distinguish between workload tiers at the higher or lower ends of the scale (e.g., between the easy and the easy-medium tiers). Despite these limitations, each pair of levels was effectively differentiated by one or more metrics. This suggests a promising avenue for future research, exploring the integration or combination of multiple metrics. The findings suggest that subtle differences in workload levels may be distinguishable using combinations of subjective and physiological metrics.

DSP-KD: Dual-Stage Progressive Knowledge Distillation for Skin Disease Classification.

The increasing global demand for skin disease diagnostics emphasizes the urgent need for advancements in AI-assisted diagnostic technologies for dermatoscopic images. In current practical medical systems, the primary challenge is balancing lightweight models with accurate image analysis to address constraints like limited storage and computational costs. While knowledge distillation methods hold immense potential in healthcare applications, related research on multi-class skin disease tasks is scarce. To bridge this gap, our study introduces an enhanced multi-source knowledge fusion distillation framework, termed DSP-KD, which improves knowledge transfer in a dual-stage progressive distillation approach to maximize mutual information between teacher and student representations. The experimental results highlight the superior performance of our distilled ShuffleNetV2 on both the ISIC2019 dataset and our private skin disorders dataset. Compared to other state-of-the-art distillation methods using diverse knowledge sources, the DSP-KD demonstrates remarkable effectiveness with a smaller computational burden.

The CuSCN layer between BiVO4 and NiFeOx for facilitating photogenerated carrier transfer and water oxidation kinetics.

Modification of oxygen evolution co-catalyst (OEC) on the surface of bismuth vanadate (BiVO4) can effectively improve the kinetics of water oxidation, but it is still limited by the small hole extraction driving force at the BiVO4/OEC interface. Modulating the BiVO4/OEC interface with a hole transfer layer (HTL) is expected to facilitate hole transport from BiVO4 to the OEC surface. Herein, a copper(I) thiocyanate (CuSCN) HTL is inserted between BiVO4 and NiFeOx OEC to create BiVO4/CuSCN/NiFeOx photoanode, resulting in a significant enhancement of photoelectrochemical (PEC) water splitting performance. From electrochemical analyses and density functional theory (DFT) simulations, the markedly enhanced PEC performance is attributed to the insertion of CuSCN as an HTL, which promotes the extraction of holes from BiVO4 surface and boosts the water oxidation kinetics. The optimal photoanode achieves a photocurrent density of 5.6 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (vs. RHE) and an impressive charge separation efficiency of 96.2 %. This work offers valuable insights into the development of advanced photoanodes for solar energy conversion and emphasizes the importance of selecting an appropriate HTL to mitigate recombination at the BiVO4/OEC interface.

Accuracy of Femoral Tunnel Localization With Mixed Reality Technology-Assisted Single-Bundle ACL Reconstruction.

Background: It is clinically challenging to accurately drill femoral and tibial tunnels to reconstruct the anterior cruciate ligament (ACL). Mixed reality (MR) technology, a further development of virtual reality technology, presents virtual scene information in real time and establishes an interactive feedback information loop among the real world, the virtual world, and the user. Purpose/Hypothesis: The purpose of this study was to investigate the structural and early clinical outcomes of ACL reconstruction assisted by MR technology. It was hypothesized that MR technology would improve the accuracy of tunnel localization. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 44 patients at a single institution who underwent arthroscopic single-bundle ACL reconstruction between June 2020 and March 2022. Reconstruction with the aid of MR technology was performed in 21 patients (MR group), and conventional arthroscopic reconstruction was performed in 23 patients. Postoperatively, the parameters related to the bone tunnel positioning were compared by computed tomography imaging with 3-dimensional (3D) reconstruction, and 12-month postoperative clinical outcomes were assessed with the Lysholm and International Knee Documentation Committee scores. Results: There was no statistically significant difference in projection angles in the coronal, axial, or sagittal plane between the preoperative virtually created tunnel guide pin and the actual tunnel (P > .05 for all). In the MR group, the center of the femoral tunnel exit was closer to the apex of the lateral femoral condyle along the proximal-distal axis (14.07 ± 4.12 vs 17.49 ± 6.24 mm for the conventional group; P < .05) and the graft bending angle was lower (117.71° ± 8.08° vs 127.81° ± 11.91° for the conventional group; P < .05). The scatterplot of the femoral tunnel location distribution showed that the entrance and exit points in the MR group were more concentrated and closer to the ideal location of the preoperative design than in the conventional group. Patients in both groups had significant preoperative-to-postoperative improvement based on outcome scores (P < .001 for all), with no significant difference between groups. Conclusion: ACL reconstruction with the aid of MR technology allowed for more accurate positioning and orientation of the femoral tunnel during surgery when compared with conventional reconstruction.

CAPNet: Context attention pyramid network for computer-aided detection of microcalcification clusters in digital breast tomosynthesis.

BACKGROUND AND OBJECTIVE: Computer-aided detection (CADe) of microcalcification clusters (MCs) in digital breast tomosynthesis (DBT) is crucial in the early diagnosis of breast cancer. Although convolutional neural network (CNN)-based detection models have achieved excellent performance in medical lesion detection, they are subject to some limitations in MC detection: 1) Most existing models employ the feature pyramid network (FPN) for multi-scale object detection; however, the rough feature sharing between adjacent layers in the FPN may limit the detection ability for small and low-contrast MCs; and 2) the MCs region only accounts for a small part of the annotation box, so the features extracted indiscriminately within the whole box may easily be affected by the background. In this paper, we develop a novel CNN-based CADe method to alleviate the impacts of the above limitations for the accurate and rapid detection of MCs in DBT. METHODS: The proposed method has two parts: a novel context attention pyramid network (CAPNet) for intra-layer MC detection in two-dimensional (2D) slices and a three-dimensional (3D) aggregation procedure for aggregating 2D intra-layer MCs into a 3D result according to their connectivity in 3D space. The proposed CAPNet is based on an anchor-free and one-stage detection architecture and contains a context feature selection fusion (CFSF) module and a microcalcification response (MCR) branch. The CFSF module can efficiently enrich shallow layers' features by the complementary selection of local context features, aiming to reduce the missed detection of small and low-contrast MCs. The MCR branch is a one-layer branch parallel to the classification branch, which can alleviate the influence of the background region within the annotation box on feature extraction and enhance the ability of the model to distinguish MCs from normal breast tissue. RESULTS: We performed a comparison experiment on an in-house clinical dataset with 648 DBT volumes, and the proposed method achieved impressive performance with a sensitivity of 91.56 % at 1 false positive per DBT volume (FPs/volume) and 93.51 % at 2 FPs/volume, outperforming other representative detection models. CONCLUSIONS: The experimental results indicate that the proposed method is effective in the detection of MCs in DBT. This method can provide objective, accurate, and quick diagnostic suggestions for radiologists, presenting potential clinical value for early breast cancer screening.

DB-DCAFN: dual-branch deformable cross-attention fusion network for bacterial segmentation.

Sputum smear tests are critical for the diagnosis of respiratory diseases. Automatic segmentation of bacteria from sputum smear images is important for improving diagnostic efficiency. However, this remains a challenging task owing to the high interclass similarity among different categories of bacteria and the low contrast of the bacterial edges. To explore more levels of global pattern features to promote the distinguishing ability of bacterial categories and maintain sufficient local fine-grained features to ensure accurate localization of ambiguous bacteria simultaneously, we propose a novel dual-branch deformable cross-attention fusion network (DB-DCAFN) for accurate bacterial segmentation. Specifically, we first designed a dual-branch encoder consisting of multiple convolution and transformer blocks in parallel to simultaneously extract multilevel local and global features. We then designed a sparse and deformable cross-attention module to capture the semantic dependencies between local and global features, which can bridge the semantic gap and fuse features effectively. Furthermore, we designed a feature assignment fusion module to enhance meaningful features using an adaptive feature weighting strategy to obtain more accurate segmentation. We conducted extensive experiments to evaluate the effectiveness of DB-DCAFN on a clinical dataset comprising three bacterial categories: Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The experimental results demonstrate that the proposed DB-DCAFN outperforms other state-of-the-art methods and is effective at segmenting bacteria from sputum smear images.

Percutaneous Cavopulmonary Assist: From Design to 96 Hour Survival in Lethal Cavopulmonary Failure Sheep.

We are developing a clinically practical percutaneous double lumen cannula (DLC)-based cavopulmonary assist (CPA) system to support failing Fontan patients. In this study, our CPA DLC was redesigned for even blood flow, minimal recirculation, and easy insertion/deployment. After bench testing, this new CPA system was evaluated for 4 hours (n = 10) and 96 hours (n = 5) in our clinically relevant lethal cavopulmonary failure (CPF) sheep model for ease of cannulation/deployment, reversal of CPF hemodynamics/end-organ hypoperfusion, and durability/biocompatibility. Cavopulmonary failure was achieved in all sheep. All DLCs were successfully inserted/deployed into Fontan anatomy. Cavopulmonary assist reversed CPF with normalized central venous pressure and cardiac output. All survival sheep were ambulatory with normal eating/drinking. One sheep was euthanized after 6 hours from cannula kinking, and one sheep died of hypokalemia after 8 hours. Three sheep survived 96 hours with normal hemodynamics. Free hemoglobin was only 3.7 ± 1.2 mg/dl at 96 hours, indicating negligible hemolysis. Creatinine, blood urea nitrogen, and lactate increased from hypoperfusion but normalized by 72 hours CPA. Necropsy showed only a small, immobilized thrombus ring at umbrella attachment to DLC. Our DLC-based system provided total ambulatory CPA in a lethal CPF sheep model with 96 hour survival and complete reversal of hemodynamics and end-organ hypoperfusion.

Human Factors Considerations and Metrics in Shared Space Human-Robot Collaboration: A Systematic Review.

The degree of successful human-robot collaboration is dependent on the joint consideration of robot factors (RF) and human factors (HF). Depending on the state of the operator, a change in a robot factor, such as the behavior or level of autonomy, can be perceived differently and affect how the operator chooses to interact with and utilize the robot. This interaction can affect system performance and safety in dynamic ways. The theory of human factors in human-automation interaction has long been studied; however, the formal investigation of these HFs in shared space human-robot collaboration (HRC) and the potential interactive effects between covariate HFs (HF-HF) and HF-RF in shared space collaborative robotics requires additional investigation. Furthermore, methodological applications to measure or manipulate these factors can provide insights into contextual effects and potential for improved measurement techniques. As such, a systematic literature review was performed to evaluate the most frequently addressed operator HF states in shared space HRC, the methods used to quantify these states, and the implications of the states on HRC. The three most frequently measured states are: trust, cognitive workload, and anxiety, with subjective questionnaires universally the most common method to quantify operator states, excluding fatigue where electromyography is more common. Furthermore, the majority of included studies evaluate the effect of manipulating RFs on HFs, but few explain the effect of the HFs on system attributes or performance. For those that provided this information, HFs have been shown to impact system efficiency and response time, collaborative performance and quality of work, and operator utilization strategy.

Pharmacokinetics of Veratramine and Jervine from Alcohol Extracts of Radix Veratri.

Background: Chinese Materia Medica and Jiangsu New Medical College record that Radix Veratri root is Liliaceae Veratrum taliense Loses. f. and the root of Veratrum stenophyllum Diels. According to traditional Chinese medicine (TCM) example, Radix Veratri is a Liliaceae plant Veratrum taliense. Another literature pointed out that the aliases of Veratrum taliense and Veratrum angustifolia are both Radix Veratri, and their effects are basically the same. The main active ingredient of Veratrum is veratramine, of which veratramine and Jervine are higher in content, reaching 24.60% and 21.28% of the total alkaloids, respectively. Veratrum alkaloids are both toxic and effective ingredients. In addition to its good clinical efficacy, attention should also be paid to its pharmacokinetic characteristics in vivo. It is particularly important to study the pharmacokinetic characteristics of veratramine and Jervine in vivo. Objective: The goal of this study was to develop a simple and effective method for measuring veratramine and Jervine in rat plasma at the same time. This method was used to study the pharmacokinetic characteristics of veratramine and Jervine in the alcohol extract of Radix Veratri in rats, to provide a reasonable basis for the clinical use of Radix Veratri. Methods: Eighteen SD rats were randomly assigned into three groups, half male and half female, and were given 0.04 g/kg, 0.08g/kg, and 0.16 g/kg Radix Veratri alcohol extract, respectively. Blood samples were collected at different time points and were analyzed by LC-MS/MS after protein precipitation. Bullatine was set as the internal standard; the plasma samples were extracted with ethyl acetate. After the sample was processed, acetonitrile-10 mM ammonium acetate, whose pH was adjusted to 8.8 with ammonia water, was taken as the mobile phase. Veratramine quantitative ion pair was 410.1⟶295.1m/z, Jervine quantitative ion pair was 426.2⟶114.1m/z, and Bullatine B (IS) quantitative ion pair was 438.2⟶420.1m/z. In the positive ion mode, the multireaction monitoring (MRM) mode was used to determine the blood concentration of veratramine and Jervine. DAS 3.3.0 was used to calculate the relevant pharmacokinetic parameters. Results: Veratramine had a good linear relationship in the concentration range of 0.0745~18.2 ng/mL, and that of Jervine was 1.11~108 ng/mL. The correlation coefficient r of three consecutive batches of the standard curve was greater than 0.995. Veratramine's lower quantification limit was 0.745 ng/mL, Jervine's was 1.11 ng/mL, and precision and accuracy were both less than 15%. The accuracy of veratramine was between 88.96% and 101.85%, and the accuracy of Jervine was between 92.96% and 104.50%. This method was adopted for the pharmacokinetic study of alcohol extracts of Radix Veratri. The results showed that only C max of veratramine female rats did not show linear kinetic characteristics in the dose range of Radix Veratri alcohol extract from 0.04 g/kg to 0.16 g/kg. For AUC0-t and C max of veratramine and Jervine, it could not determine whether the Radix Veratri alcohol extract showed linear kinetic characteristics within the dosage range of 0.04 g/kg~0.16 g/kg. Veratramine and Jervine showed obvious gender differences in the absorption and elimination stages. The absorption rate of veratramine and Jervine by male mice was about 10 times higher than that of female mice, and the elimination rate of male mice is about 20 times lower than that of female mice. It was suggested that the clinical application of the steroidal alkaloids veratramine and Jervine in Radix Veratri required rational use of drugs based on gender. Conclusion: An LC-MS/MS analysis method suitable for the pharmacokinetic study of veratramine and Jervine in Radix Veratri in SD rats was established to provide a basis for in vivo pharmacokinetic studies. The pharmacokinetic characteristics of veratramine and Jervine in the alcohol extract of Radix Veratri were significantly different in female and male rats. During the clinical use of Radix Veratri, it should pay close attention to the obvious gender differences that may occur after the medication.

NCRNet: Neighborhood Context Refinement Network for skin lesion segmentation.

Accurate skin lesion segmentation plays a fundamental role in computer-aided melanoma analysis. Recently, some FCN-based methods have been proposed and achieved promising results in lesion segmentation tasks. However, due to the variable shapes, different scales, noise interference, and ambiguous boundaries of skin lesions, the capabilities of lesion location and boundary delineation of these works are still insufficient. To overcome the above challenges, in this paper, we propose a novel Neighborhood Context Refinement Network (NCRNet) by using the coarse-to-fine strategy to achieve accurate skin lesion segmentation. The proposed NCRNet contains a shared encoder and two different but closely related decoders for locating the skin lesions and refining the lesion boundaries. Specifically, we first design the Parallel Attention Decoder (PAD), which can effectively extract and fuse the local detail information and global semantic information on multiple levels to locate skin lesions of different sizes and shapes. Then, based on the initial lesion location, we further design the Neighborhood Context Refinement Decoder (NCRD), aiming at leveraging the fine-grained multi-stage neighborhood context cues to refine the lesion boundaries continuously. Furthermore, the neighborhood-based deep supervision used in the NCRD can make the shared encoder pay more attention to the lesion boundary areas and promote convergence of the segmentation network. The public skin lesion segmentation dataset ISIC2017 is adopted to validate the effectiveness of the proposed NCRNet. Comprehensive experiments prove that the proposed NCRNet reaches the state-of-the-art performance than the other nine competitive methods and gets 78.62%, 86.55%, and 94.01% on Jaccard, Dice, and Accuracy, respectively.