Origin of photoinduced DC current and two-level population dynamics in a single molecule.

Studying the photoinduced changes of materials with atomic-scale spatial resolution can provide a fundamental understanding of light-matter interaction. A long-standing impediment has been the detrimental thermal effects on the stability of the tunneling gap from intensity-modulated laser irradiation of the scanning tunneling microscope junction. Photoinduced DC current transduces photons to an electric current and is widely applied in optoelectronics as switches and signal transmission. Our results revealed the origin of the light-induced DC current and related it to the two-level population dynamics and related nonlinearity in the conductance of a single molecule. Here, we compensated for the near-visible laser-induced thermal effects to demonstrate photoinduced DC current spectroscopy and microscopy and to observe the persistent photoconductivity of a two-level pyrrolidine molecule. The methodology can be generally applied to the coupling of light to scan probes to investigate light-matter interactions at the atomic scale.

In Situ Formation of a LiBO2 Coating Layer and Spinel Phase for Ni-Rich Cathode Materials from a Boric Acid-Etched Precursor.

Ni-rich cathode materials exhibit superior energy densities and have attracted interest among both research and industrial fields; whereas, their practical application is hindered by the intrinsic drawbacks brought by the high nickel content such as structural instability and rapid capacity fading. Herein, in situ formation of a LiBO2 coating layer and spinel phase layer is achieved on the surface of a Ni-rich cathode material via a boric acid etching method at the precursor state. The spinel phase is considered to have a 3D lithium diffusion tunnel and hence faster diffusion kinetics. Moreover, the LiBO2 layer possesses excellent (electro)chemical inertness and can suppress electrolyte decomposition, resulting in a more inorganic and stable cathode-electrolyte interface. The surface reconstructed sample exhibits better cyclic stability (93.3% capacity retention vs 85.3% for the pristine sample at 1 C for 100 cycles) and rate performance. The superiority of this surface reconstruction is demonstrated by a series of electrochemical techniques and characterization methods including high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), post-mortem X-ray photoelectron spectroscopy (XPS) analysis, and density functional theory (DFT) calculations.

Single-cell metabolic fingerprints discover a cluster of circulating tumor cells with distinct metastatic potential.

Circulating tumor cells (CTCs) are recognized as direct seeds of metastasis. However, CTC count may not be the "best" indicator of metastatic risk because their heterogeneity is generally neglected. In this study, we develop a molecular typing system to predict colorectal cancer metastasis potential based on the metabolic fingerprints of single CTCs. After identification of the metabolites potentially related to metastasis using mass spectrometry-based untargeted metabolomics, setup of a home-built single-cell quantitative mass spectrometric platform for target metabolite analysis in individual CTCs and use of a machine learning method composed of non-negative matrix factorization and logistic regression, CTCs are divided into two subgroups, C1 and C2, based on a 4-metabolite fingerprint. Both in vitro and in vivo experiments demonstrate that CTC count in C2 subgroup is closely associated with metastasis incidence. This is an interesting report on the presence of a specific population of CTCs with distinct metastatic potential at the single-cell metabolite level.

Simultaneous quantification of multiple single nucleotide variants in PIK3CA ctDNA using mass-tagged LCR probe sets.

Circulating tumor DNA (ctDNA) in blood carries genetic variations associated with tumors. There is evidence indicating that the abundance of single nucleotide variant (SNV) in ctDNA is correlated well with cancer progression and metastasis. Thus, accurate and quantitative detection of SNVs in ctDNA may benefit clinical practice. However, most current methods are unsuitable for the quantification of SNV in ctDNA that usually differentiates from wild-type DNA (wtDNA) only by a single base. In this setting, ligase chain reaction (LCR) coupled with mass spectrometry (MS) was developed to simultaneously quantify multiple SNVs using PIK3CA ctDNA as a model. Mass-tagged LCR probe set for each SNV including mass-tagged probe and three DNA probes was firstly designed and prepared. Then, LCR was initiated to discriminate SNVs specifically and amplify the signal of SNVs in ctDNA selectively. Afterward, a biotin-streptavidin reaction system was used to separate the amplified products, and photolysis was initiated to release mass tags. Finally, mass tags were monitored and quantified by MS. After optimizing conditions and verifying performance, this quantitative system was applied for blood samples from breast cancer patients, and risk stratification for breast cancer metastasis was also performed. This study is among the first to quantify multiple SNVs in ctDNA in a signal amplification and conversion manner, and also highlights the potential of SNV in ctDNA as a liquid biopsy marker to monitor cancer progression and metastasis.

Accurate, Sensitive, and Rapid Detection of Pseudomonas aeruginosa Based on CRISPR/Cas12b with One Fluid-Handling Step.

Pseudomonas aeruginosa is a major bacterial pathogen causing nosocomial infections and accounts for morbidity and mortality among patients with cystic fibrosis. An accurate, sensitive, and rapid method to detect P. aeruginosa is critical for the early control of infection and patient management. In this study, we established a P. aeruginosa clustered regularly interspaced short palindromic repeats testing in one pot (CRISPR-top) assay which detected P. aeruginosa with one fluid-handling step in one tube. The reaction was performed isothermally within 1 h; thus, specific instruments were not required. The optimal reaction conditions of this assay were determined to be a temperature of 55°C; working concentrations of 1 µM for the forward inner primer and backward inner primer, 0.5 µM for the loop forward primer and loop backward primer, and 0.25 µM for the forward outer primer and backward outer primer; as well as a 2 µM concentration single-stranded DNA reporter molecules. In terms of specificity, our assay showed 100% inclusivity and exclusivity among 48 strains, including 15 P. aeruginosa clinical isolates and 33 non-P. aeruginosa strains. The limit of detection of our method was 10 copies per reaction mixture. Forty-six human sputum specimens from patients with respiratory symptoms were tested. Using the results of quantitative real-time PCR as the gold standard, our method showed 85.3% (29/34) sensitivity, 100% (12/12) specificity, a positive predictive value of 100% (29/29), and a negative predictive value of 70.6% (12/17). In summary, the P. aeruginosa CRISPR-top assay developed in the present study is a high-efficiency alternative tool for the accurate and rapid detection of P. aeruginosa, especially in resource-limited settings. IMPORTANCE This study reports a P. aeruginosa CRISPR-top assay which can precisely identify P. aeruginosa using nucleic acids from pure cultures or clinical samples in one pot with one fluid-handling step. The P. aeruginosa CRISPR-top reaction is suitable for on-site testing, and its diagnostic performance can be compared with that of qPCR.

Epidemiological Investigation of Hospital Transmission of Corynebacterium striatum Infection by Core Genome Multilocus Sequence Typing Approach.

Corynebacterium striatum has recently received increasing attention due to its multiple antimicrobial resistances and its role as an invasive infection/outbreak agent. Recently, whole-genome sequencing (WGS)-based core genome multilocus sequence typing (cgMLST) has been used in epidemiological studies of specific human pathogens. However, this method has not been reported in studies of C. striatum. In this work, we aim to propose a cgMLST scheme for C. striatum. All publicly available C. striatum genomes, 30 C. striatum strains isolated from the same hospital, and 1 epidemiologically unrelated outgroup C. striatum strain were used to establish a cgMLST scheme targeting 1,795 genes (hereinafter referred to as 1,795-cgMLST). The genotyping results of cgMLST showed good congruence with core genome-based single-nucleotide polymorphism typing in terms of tree topology. In addition, the cgMLST provided a greater discrimination than the MLST method based on 6 housekeeping genes (gyrA, gyrB, hsp65, rpoB, secA1, and sodA). We established a clonal group (CG) threshold based on 104 allelic differences; a total of 56 CGs were identified from among 263 C. striatum strains. We also defined an outbreak threshold based on seven allelic differences that is capable of identifying closely related isolates that could give clues on hospital transmission. According to the results of analysis of drug-resistant genes and virulence genes, we identified CG4, CG5, CG26, CG28, and CG55 as potentially hypervirulent and multidrug-resistant CGs of C. striatum. This study provides valuable genomic epidemiological data on the diversity, resistance, and virulence profiles of this potentially pathogenic microorganism. IMPORTANCE Recently, WGS of many human and animal pathogens has been successfully used to investigate microbial outbreaks. The cgMLST schema are powerful genotyping tools that can be used to investigate potential epidemics and provide classification of the strains precise and reliable. In this study, we proposed the development of a cgMLST typing scheme for C. striatum, and then we evaluated this scheme for its applicability to hospital transmission investigations. This report describes the first cgMLST schema for C. striatum. The analysis of hospital transmission of C. striatum based on cgMLST methods has important clinical epidemiological significance for improving nosocomial infection monitoring of C. striatum and in-depth understanding of its nosocomial transmission routes.

Three novel Cas12a orthologs with robust DNA cleavage activity suitable for nucleic acid detection.

Developing rapid and accurate pathogen detection methods is increasingly important, and CRISPR-Cas system can be optimized for this purpose. CRISPR-Cas12a is a single RNA-guided endonuclease system with the potential for nucleic acid detection. There is a broad diversity among Cas12a nucleases with robust detection capability. Herein, we characterised three Cas12a orthologs (ObCas12a, MbCas12a, and ScCas12a), including cis- and trans-cleavage activities, the identification of PAM, single-base resolution ability, and the application for nucleic acid detection. These Cas12a orthologs displayed robust cis- and trans-cleavage activities, and performed well in terms of specificity and sensitivity for nucleic acid detection. Furthermore, they have subtle differences in single-base resolution and recognised PAM sites in vitro. Therefore, these Cas12a nucleases are candidate proteins for CRISPR-based diagnostic methods. Addition of these enzymes to the nucleic acid detection toolbox will further expand the utility of this powerful technology.

Immunoprotective Analysis of the NFA49590 Protein from Nocardia farcinica IFM 10152 Demonstrates Its Potential as a Vaccine Candidate.

Nocardia is emerging as a serious and easily neglected pathogen in clinical practice with multidrug resistance that extends the treatment period for months or even years. This has led to the investigation of a vaccine approach to prevent Nocardia infections. However, studies on the protective proteins of Nocardia have not yet been carried out. In the present work, over 500 proteins in the supernatant of N. farcinica IFM10152 were identified by LC−MS/MS. In silico analysis of these proteins with a high content (score > 2000) predicted that NFA49590 was one of the conserved proteins in N. farcinica strains with potential antigenicity. After the rNFA49590 protein was cloned and expressed in E. coli (DE3) and purified using a Ni-NTA column, its good antigenicity was confirmed with sera from mice immunized with different Nocardia species by Western blot. Then we confirmed its ability to activate innate immunity by examining the phosphorylation status of ERK1/2, JNK, p38, and p65 and the cytokine levels of IL-6, TNF-α, and IL-10. Finally, we evaluated its immunoprotective effect in BALB/c mice, and we found that mice immunized with rNFA49590 protein exhibited high antibody titers, enhanced bacterial clearance ability, and generated robust protective effects from the N. farcinica challenge. These results offer strong support for the use of NFA49590 protein as a vaccine candidate and open the possibilities for the exploration of a large array of immunoprotective proteins.

The Direct Anterior Approach versus the Posterolateral Approach on the Outcome of Total Hip Arthroplasty: A Retrospective Clinical Study.

OBJECTIVE: To compare the clinical results of the direct anterior approach (DAA) and posterolateral approach (PLA) in total hip arthroplasty (THA) patients. METHODS: From January 2017 to September 2019, 80 patients who received primary THA in our hospital were retrospectively selected based on the propensity score matching (PSM) method. Baseline characteristics of patients who underwent the DAA and PLA were collected. Moreover, the incision length, intraoperative blood loss, operative time, length of stay, and Harris hip score were compared between patients in the two groups. The CK level was used to assess muscle damage between patients in the DAA and PLA groups. The complications of these two approaches were also evaluated at patients' 12-month follow-up evaluation. RESULTS: There was no significant difference in baseline characteristics between patients in the two groups (p > 0.05). The patients in the DAA group had a shorter incision length (9.2 ± 0.2 vs 14.7 ± 0.5, respectively; p < 0.05) and shorter length of hospital stay (9.5 ± 0.7 vs 12.9 ± 0.8, respectively, p < 0.05) than patients in the PLA group. Moreover, the DAA was associated with a decrease in intraoperative blood loss compared with the PLA (109.1 ± 12.6 vs 305.1 ± 14.1 ml, respectively, p < 0.05). However, the operation time was longer in patients in the DAA group (130.7 ± 1.7) than in patients in the PLA group (112.6 ± 1.3 min, p < 0.05). The CK level of patients in the DAA group was lower than that of patients in the PLA group (p < 0.05). The CK level at 48 h post-surgery was negatively correlated with the Harris hip scores at 6 months after THA (r = -0.538, p = 0.000). Compared with patients in the PLA group, the muscle strength of patients in the DAA group was significantly higher than that of patients in the DAA group at 4 days (p < 0.05) and 7 days (p < 0.05) after THA. The Harris hip scores of patients in the DAA group and PLA group were 81.0 ± 0.8 vs 70.8 ± 0.7 at 6 weeks, 93.4 ± 0.9 vs 86.4 ± 0.6 at 3 months, and 96.8 ± 1.1 vs 93.4 ± 0.8 at 6 months, respectively, both p < 0.05. There was no significant difference in the incidence of complications between patients in the DAA and PLA groups (p > 0.05). CONCLUSION: DAA was superior to the PLA in improving hip function after THA. Compared with the PLA, the DAA could reduce muscle damage, which is negatively correlated with hip function. Further multi-institution studies are required with longer follow-up durations, and larger patient populations are needed to provide more definitive conclusions.

Atomic-Scale Rectification and Inelastic Electron Tunneling Spectromicroscopy.

The phenomenon of rectification describes the emergence of a DC current from the application of an oscillating voltage. Although the origin of this effect has been associated with the nonlinearity in the current-voltage I(V) relation, a rigorous understanding of the microscopic mechanisms for this phenomenon remains challenging. Here, we show the close connection between rectification and inelastic electron tunneling spectroscopy and microscopy for single molecules with a scanning tunneling microscope. While both techniques are based on nonlinear features in the I(V) curve, comprehensive line shape analyses reveal notable differences that highlight the two complementary techniques of nonlinear conductivity spectromicroscopy for probing nanoscale systems.

A Computationally Efficient Approach to Simulate Heart Rate Effects Using a Whole Human Heart Model.

Computational modeling of the whole human heart has become a valuable tool to evaluate medical devices such as leadless pacemakers, annuloplasty rings and left ventricular assist devices, since it is often difficult to replicate the complex dynamic interactions between the device and human heart in bench-top and animal tests. The Dassault Systèmes Living Heart Human Model (LHHM) is a finite-element model of whole-human-heart electromechanics that has input parameters that were previously calibrated to generate physiological responses in a healthy heart beating at 60 beat/min (resting state). This study demonstrates that, by adjusting only six physiologically meaningful parameters, the LHHM can be recalibrated to generate physiological responses in a healthy heart beating at heart rates ranging from 90−160 beat/min. These parameters are as follows: the sinoatrial node firing period decreases from 0.67 s at 90 bpm to 0.38 s at 160 bpm, atrioventricular delay decreases from 0.122 s at 90 bpm to 0.057 s at 160 bpm, preload increases 3-fold from 90 bpm to 160 bpm, body resistance at 160 bpm is 80% of that at 90 bpm, arterial stiffness at 160 bpm is 3.9 times that at 90 bpm, and a parameter relating myofiber twitch force duration and sarcomere length decreases from 238 ms/mm at 90 bpm to 175 ms/mm at 160 bpm. In addition, this study demonstrates the feasibility of using the LHHM to conduct clinical investigations in AV delay optimization and hemodynamic differences between pacing and exercise. AV delays in the ranges of 40 ms to 250 ms were simulated and stroke volume and systolic blood pressure showed clear peaks at 120 ms for 90 bpm. For a heart during exercise, the increase in cardiac output continues to 160 bpm. However, for a heart during pacing, those physiological parameter adjustments are removed that are related to changes in body oxygen requirements (preload, arterial stiffness and body resistance). Consequently, cardiac output increases initially with heart rate; as the heart rate goes up (>100 bpm), the increasing rate of cardiac output slows down and approaches a plateau.

Left Ventricle Biomechanics of Low-Flow, Low-Gradient Aortic Stenosis: A Patient-Specific Computational Model.

This study aimed to create an imaging-derived patient-specific computational model of low-flow, low-gradient (LFLG) aortic stenosis (AS) to obtain biomechanics data about the left ventricle. LFLG AS is now a commonly recognized sub-type of aortic stenosis. There remains much controversy over its management, and investigation into ventricular biomechanics may elucidate pathophysiology and better identify patients for valve replacement. ECG-gated cardiac computed tomography images from a patient with LFLG AS were obtained to provide patient-specific geometry for the computational model. Surfaces of the left atrium, left ventricle (LV), and outflow track were segmented. A previously validated multi-scale, multi-physics computational human heart model was adapted to the patient-specific geometry, yielding a model consisting of 91,000 solid elements. This model was coupled to a virtual circulatory system and calibrated to clinically measured parameters from echocardiography and cardiac catheterization data. The simulation replicated key physiologic parameters within 10% of their clinically measured values. Global LV systolic myocardial stress was 7.1 ± 1.8 kPa. Mean stress of the basal, middle, and apical segments were 7.7 ± 1.8 kPa, 9.1 ± 3.8 kPa, and 6.4 ± 0.4 kPa, respectively. This is the first patient-specific computational model of LFLG AS based on clinical imaging. Low myocardial stress correlated with low ejection fraction and eccentric LV remodeling. Further studies are needed to understand how alterations in LV biomechanics correlates with clinical outcomes of AS.

The responses of harmful dinoflagellate Karenia mikimotoi to simulated ocean acidification at the transcriptional level.

The HAB-forming, toxic dinoflagellate Karenia mikimotoi, previously found to benefit from ocean acidification (OA), was cultivated to investigate its transcriptional response to simulated OA for 30 generations. Batch cultures were grown under two CO2 concentrations, 450 (control) and 1100 (simulated OA) µatm, and physiological parameters [growth, pigments, catalase (CAT), glutathione reductase (GR), and superoxide dismutase (SOD) activity], as well as transcriptomes (obtained via RNA-seq), were compared. Chlorophyll a (Chl a) and carotenoid (Caro) contents, as well as CAT and GR activities, were significantly increased under OA conditions. Transcriptomic analysis revealed 2,490 differentially expressed unigenes in response to OA, which comprised 1.54% of all unigenes. A total of 1,121 unigenes were upregulated, and 1,369 unigenes were downregulated in OA compared to control conditions. The downregulated expression of bicarbonate transporter and carbonic anhydrase genes was a landmark of OA acclimation. Key genes involved in energy metabolism, e.g., photosynthesis, tricarboxylic acid cycle, oxidative phosphorylation, and nitrogen metabolism, were highly upregulated under OA, contributing to increases in the Chl a (55.05%) and Caro (28.37%). The enhanced antioxidant enzyme activities (i.e. CAT, GR) and upregulated genes (i.e. glutathione peroxidase, ascorbate peroxidase, heat shock protein, 20S proteasome, aldehyde dehydrogenase, and apolipoprotein) benefit cells against the potential lower pH stress condition under OA. In addition, the downregulation of four genes associated with motility suggested that the preserved energy could further boost growth. In conclusion, the present study suggests that K. mikimotoi exhibits efficient gene expression regulation for the utilization of energy and resistance to OA-induced stress. Taken together, K. mikimotoi appeared as a tolerant species in response to OA. Thus, more extensive algal blooms that threaten marine organisms are likely in the future. These findings expand current knowledge on the gene expression of HAB-forming species in response to future OA.

Application of Multiparametric Magnetic Resonance Imaging to Monitor the Early Antitumor Effect of CuS@GOD Nanoparticles in a 4 T1 Breast Cancer Xenograft Model.

BACKGROUND: We have developed hybrid nanoparticles (NPs) by co-loading copper sulfide (CuS) NPs and glucose oxidase (GOD) (CuS@GOD NPs) to explore their antitumor properties. PURPOSE: To investigate the feasibility of using multiparametric magnetic resonance imaging (MRI) including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and R2 * mapping to quantitatively assess the early antitumor effect of CuS@GOD NPs. STUDY TYPE: Prospective. ANIMAL MODEL: The orthotopic BALB/c mice 4 T1 breast cancer model. The 4 T1 xenografts in group 1 mice received normal saline, group 2 received CuS@GOD NPs, group 3 received CuS NPs plus laser, and group 4 received CuS@GOD NPs plus laser (n = 28 for each group). FIELD STRENGTH/SEQUENCE: A 3.0 T/IVIM-DWI MRI single-shot echo-planar imaging, R2 * mapping spoiled gradient recalled echo (SPGR) sequence, T2-weighted images (T2WI) and T1-weighted images (T1WI) fast spin echo (FSE) sequence. ASSESSMENT: The IVIM-DWI and R2 * mapping were performed before and after treatment at 0 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, and 24 hours in four groups and the MRI parameters were obtained. Correlation analysis between the MRI parameters and histological analyses was conducted. STATISTICAL TESTS: One-way ANOVA, Pearson's correlation analysis, two independent samples t test, intraclass correlation coefficient. P < 0.05 was considered to be statistically significant. RESULTS: In group 4, the tumoral D value was significantly higher than that of group 2 at 24 hours (0.541 ± 0.065 vs. 0.492 ± 0.051). The f value of group 4 was significantly lower than that of groups 1 and 2 at 2 hours (10.83 ± 2.16 vs. 14.28 ± 1.86, 16.67 ± 3.53, respectively). The R2 * value was significantly increased at 0 hour in group 4 compared to that of groups 1 and 2 (64.552 ± 4.663 vs. 42.441 ± 1.516, 43.165 ± 1.709, respectively). D, f, and R2 * were correlated with the histological staining results (r = 0.695-0.970). DATA CONCLUSION: The IVIM-DWI-derived D and f and R2 * mapping-derived R2 * could monitor early response to CuS@GOD NPs treatment in vivo. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Multiscale finite element musculoskeletal model for intact knee dynamics.

BACKGROUND AND OBJECTIVE: The dynamic characteristics of the intact knee joint are valuable for treating knee osteoarthritis and designing knee prostheses. However, it remains a challenge to elucidate the detailed dynamics of the knee due to its complexity of anatomical structure and complex interaction with body dynamics. METHODS: In this study, a unique subject-specific musculoskeletal model with a concurrent high-accuracy intact finite element knee model was created and used to simultaneously evaluate the kinematics and mechanics of an intact knee joint during the gait cycle. RESULTS: A medial pivot motion with external rotation, and a large parallel anterior translation were observed in the stance and swing phases, respectively, which is consistent with the in vivo fluoroscopy measurements. The maximum axial contact force on the knee joint, observed at 45% of the gait cycle, is approximately 2.89 times the body weight. The medial cartilage bears 65.7% of the total axial contact force. The results demonstrate that the cartilage-cartilage contact bears most of the joint load (62.5%) compared to the cartilage-meniscus-cartilage contact (37.5%). Regarding contact mechanics, the maximum contact pressure on both sides of the tibial cartilage (8.2 MPa) is almost similar to the first axial loading peak (14%) of the gait cycle. Additionally, the maximum contact pressure (6.01 MPa) was observed during the stance phase of the gait cycle on the patellofemoral joint. CONCLUSIONS: The predicted results on the tibiofemoral and patellofemoral joints provide a theoretical basis for the treatment of knee joint diseases and knee prosthesis design. Moreover, this approach presents a comprehensive tool to evaluate the mechanics at both the body and tissue levels. Therefore, it has a high potential for application in human biomechanics.

Microplastics impacts in seven flagellate microalgae: Role of size and cell wall.

The toxicity of microplastic particles (MPs) on aquatic environments has been widely reported; however, their effects on protists are still contradictory. For example, it is unclear if cell size and cell wall have a role in shaping the response of flagellates to MPs. In this study, seven marine flagellated microalgae (six Dinoflagellates and one Raphidophyceae) were incubated with 10 mg L-1 MPs (polystyrene plastic micro-spheres, 1 µm diameter) to address the above question by measuring different response variables, i.e., growth, optimal photochemical efficiency (Fv/Fm), chlorophyll-a (Chl-a) content, superoxide dismutase (SOD) activity, and cell morphology. The effect of MPs on growth and Fv/Fm showed species-specificity effects. Maximum and minimum MPs-induced inhibitions were detected in Karenia mikimotoi (76.43%) and Akashiwo sanguinea (10.16%), respectively, while the rest of the species showed intermediate responses. The presence of MPs was associated with an average reduction of Chl-a content in most cases and with a higher superoxide dismutase activity in all cases. Seven species were classified into two groups by the variation of Chl-a under MPs treatment. One group (Prorocentrum minimum and Karenia mikimotoi) showed increased Chl-a, while the other (P. donghaiense, P. micans, Alexandrium tamarense, Akashiwo sanguinea, Heterosigma akashiwo) showed decreased Chl-a content. The MPs-induced growth inhibition was negatively correlated with cell size in the latter group. SEM images further indicated that MPs-induced malformation in the smaller cells (e.g., P. donghaiense and K. mikimotoi) was more severe than the bigger cells (e.g., A. sanguinea and P. micans), probably due to a relatively higher ratio of the cell surface to cell volume in the former. These results implicate that the effect of MPs on marine flagellated microalgae was related to the cell size among most species but not cell wall. Thus plastic pollution may have size-dependent effects on phytoplankton in future scenarios.

How viscous is the beating heart?: Insights from a computational study.

Understanding tissue rheology is critical to accurately model the human heart. While the elastic properties of cardiac tissue have been extensively studied, its viscous properties remain an issue of ongoing debate. Here we adopt a viscoelastic version of the classical Holzapfel Ogden model to study the viscous timescales of human cardiac tissue. We perform a series of simulations and explore stress-relaxation curves, pressure-volume loops, strain profiles, and ventricular wall strains for varying viscosity parameters. We show that the time window for model calibration strongly influences the parameter identification. Using a four-chamber human heart model, we observe that, during the physiologically relevant time scales of the cardiac cycle, viscous relaxation has a negligible effect on the overall behavior of the heart. While viscosity could have important consequences in pathological conditions with compromised contraction or relaxation properties, we conclude that, for simulations within the physiological range of a human heart beat, we can reasonably approximate the human heart as hyperelastic.

Mitral Valve Atlas for Artificial Intelligence Predictions of MitraClip Intervention Outcomes.

Severe mitral regurgitation (MR) is a cardiac disease that can lead to fatal consequences. MitraClip (MC) intervention is a percutaneous procedure whereby the mitral valve (MV) leaflets are connected along the edge using MCs. The outcomes of the MC intervention are not known in advance, i.e., the outcomes are quite variable. Artificial intelligence (AI) can be used to guide the cardiologist in selecting optimal MC scenarios. In this study, we describe an atlas of shapes as well as different scenarios for MC implantation for such an AI analysis. We generated the MV geometrical data from three different sources. First, the patients' 3-dimensional echo images were used. The pixel data from six key points were obtained from three views of the echo images. Using PyGem, an open-source morphing library in Python, these coordinates were used to create the geometry by morphing a template geometry. Second, the dimensions of the MV, from the literature were used to create data. Third, we used machine learning methods, principal component analysis, and generative adversarial networks to generate more shapes. We used the finite element (FE) software ABAQUS to simulate smoothed particle hydrodynamics in different scenarios for MC intervention. The MR and stresses in the leaflets were post-processed. Our physics-based FE models simulated the outcomes of MC intervention for different scenarios. The MR and stresses in the leaflets were computed by the FE models for a single clip at different locations as well as two and three clips. Results from FE simulations showed that the location and number of MCs affect subsequent residual MR, and that leaflet stresses do not follow a simple pattern. Furthermore, FE models need several hours to provide the results, and they are not applicable for clinical usage where the predicted outcomes of MC therapy are needed in real-time. In this study, we generated the required dataset for the AI models which can provide the results in a matter of seconds.

Breast myeloid sarcoma presenting as a palpable breast lump after allogeneic stem cell transplantation for acute myelomonocytic leukemia: a rare case report.

BACKGROUND: Myeloid sarcoma (MS) is a tumor secondary to myeloid leukemia that consists of immature granulocytes with or without mature granulocytes and is a rare extramedullary manifestation of acute myeloid leukemia (AML). CASE PRESENTATION: We report a case of a 34-year-old woman diagnosed with AML-M4 who achieved remission after chemotherapy and received allogeneic stem cell transplantation (allo-SCT) for consolidation. Her past medical history showed that she received bilateral breast implants 7 years ago. This patient underwent ultrasound examination of the breast and multiple bilateral breast nodules were revealed that were not considered by clinicians to be concerning. Several months later, the patient's bilateral nodules rapidly progressed to large palpable masses. Ultrasound-guided biopsy revealed diffuse infiltration of undifferentiated tumor cells and immunohistochemistry (IHC) indicated that the tumor was positive for myeloperoxidase (MPO), cluster of differentiation (CD) 34, CD43, CD68, CD117, and Ki67. The pathological diagnosis was extramedullary recurrence of AML as MS of breast. After the diagnosis, the patient received systemic chemotherapy and drugs containing cytarabine, azacitidine, and methotrexate. However, 1 year after achieving partial remission, the patient died from intracranial invasion of leukemia, brain herniation, and respiratory failure. CONCLUSION: It is necessary for the specialist to have a high suspicion index by careful inquiry of the patient's medical history if a patient presents at the breast clinic with a breast tumor as the chief complaint. Combining information from the patient's medical history with a tumor biopsy is critical for obtaining the correct diagnosis of the disease.

Current opinions on the mechanism, classification, imaging diagnosis and treatment of post-traumatic osteomyelitis.

Post-traumatic osteomyelitis (PTO) is a worldwide problem in the field of orthopaedic trauma. So far, there is no ideal treatment or consensus-based gold standard for its management. This paper reviews the representative literature focusing on PTO, mainly from the following four aspects: (1) the pathophysiological mechanism of PTO and the interaction mechanism between bacteria and the body, including fracture stress, different components of internal fixation devices, immune response, occurrence and development mechanisms of inflammation in PTO, as well as the occurrence and development mechanisms of PTO in skeletal system; (2) clinical classification, mainly the etiological classification, histological classification, anatomical classification and the newly proposed new classifications (a brief analysis of their scope and limitations); (3) imaging diagnosis, including non-invasive examination and invasive examination (this paper discusses their advantages and disadvantages respectively, and briefly compares the sensitivity and effectiveness of the current examinations); and (4) strategies, including antibiotic administration, surgical choices and other treatment programs. Based on the above-mentioned four aspects, we try to put forward some noteworthy sections, in order to make the existing opinions more specific.