Multi-planar dual adversarial network based on dynamic 3D features for MRI-CT head and neck image synthesis.

Objective.Head and neck radiotherapy planning requires electron densities from different tissues for dose calculation. Dose calculation from imaging modalities such as MRI remains an unsolved problem since this imaging modality does not provide information about the density of electrons.Approach.We propose a generative adversarial network (GAN) approach that synthesizes CT (sCT) images from T1-weighted MRI acquisitions in head and neck cancer patients. Our contribution is to exploit new features that are relevant for improving multimodal image synthesis, and thus improving the quality of the generated CT images. More precisely, we propose a Dual branch generator based on the U-Net architecture and on an augmented multi-planar branch. The augmented branch learns specific 3D dynamic features, which describe the dynamic image shape variations and are extracted from different view-points of the volumetric input MRI. The architecture of the proposed model relies on an end-to-end convolutional U-Net embedding network.Results.The proposed model achieves a mean absolute error (MAE) of18.76±5.167in the target Hounsfield unit (HU) space on sagittal head and neck patients, with a mean structural similarity (MSSIM) of0.95±0.09and a Frechet inception distance (FID) of145.60±8.38. The model yields a MAE of26.83±8.27to generate specific primary tumor regions on axial patient acquisitions, with a Dice score of0.73±0.06and a FID distance equal to122.58±7.55. The improvement of our model over other state-of-the-art GAN approaches is of 3.8%, on a tumor test set. On both sagittal and axial acquisitions, the model yields the best peak signal-to-noise ratio of27.89±2.22and26.08±2.95to synthesize MRI from CT input.Significance.The proposed model synthesizes both sagittal and axial CT tumor images, used for radiotherapy treatment planning in head and neck cancer cases. The performance analysis across different imaging metrics and under different evaluation strategies demonstrates the effectiveness of our dual CT synthesis model to produce high quality sCT images compared to other state-of-the-art approaches. Our model could improve clinical tumor analysis, in which a further clinical validation remains to be explored.

Dynamic pH regulation drives Nitrosomonas for high-rate stable acidic partial nitritation.

How to intensify the ammonia oxidation rate (AOR) is still a bottleneck impeding the technology development for the innovative acidic partial nitritation because the eosinophilic ammonia-oxidizing bacteria (AOB), such as Nitrosoglobus or Nitrosospira, were inhibited by the high-level free nitrous acid (FNA) accumulation in acidic environments. In this study, an innovative approach of dynamic acidic pH regulation control strategy was proposed to realize high-rate acidic partial nitritation driven by common AOB genus Nitrosomonas. The acidic partial nitrification process was carried out in a laboratory-scale sequencing batch moving bed biofilm reactor (SBMBBR) for long-term (700 days) to track the effect of dynamic acidic pH on nitrifying bacterial activity. The results indicated that the influent NH4+-N concentration was about 100 mg/L, the nitrite accumulation ratio was exceeding 90%, and the maximum AOR can reach 14.5 ± 2.6 mg N L-1h-1. Although the half-saturation inhibition constant of NOB (KI_FNA(AOB)) reached 0.37 ± 0.10 mg HNO2N/L and showed extreme adaptability in FNA, the inactivation effect of FNA (6.1 mg HNO2N/L) for NOB was much greater than that of AOB, with inactivation rates of 0.61 ± 0.08 h-1 and 0.06 ± 0.01 h-1, respectively. The effluent pH was gradually reduced to 4.5 by ammonia oxidation process and the periodic FNA concentration reached 6.5 mg HNO2N/L to inactivate nitrite-oxidizing bacteria (NOB) without negatively affecting Nitrosomonas during long-term operation. This result provides new insights for the future implementation of high-rate stabilized acidic partial nitritation by Nitrosomonas.

Unveiling temporal dynamics of PTSD and its functional impairments: A longitudinal study in UK healthcare workers.

PTSD has been associated with negative long-term consequences, including social and occupational impairments. Yet, a nuanced understanding of the interplay between PTSD symptoms and distinct domains of impairments on a short-term basis (weeks/ months) at the within-person level remains underexplored. In a large sample (nwave 1 = 1096, nwave 7 = 304) of UK healthcare workers assessed across seven assessment waves during the COVID-19 pandemic (spaced 6 weeks apart), we employed exploratory graphical vector autoregression models (GVAR) models to discern within-person temporal (across time) and contemporaneous (within same time window) dynamics between PTSD symptoms and functional impairment domains. The contemporaneous network highlighted strong co-occurrences between different symptoms and impairments. The temporal network revealed a mutually reinforcing cycle between intrusion and avoidance symptoms. Intrusion symptoms showed the highest out-strength (i.e., most predictive symptom), predicting avoidance symptoms, elevated sense of current threat, and various functional impairments. Avoidance symptoms, elevated after increased levels of intrusions, predicted work impairments that in turn were associated with difficulties in fulfilling other obligations. Our findings underscore the dynamics between perceived threat and intrusions, and the role intrusions may play in predicting a cascade of adverse effects. Targeted interventions aimed at mitigating intrusions may disrupt this negative cycle.

Spatial correlation between in vivo imaging and immunohistochemical biomarkers: A methodological study.

In this study, we present a method that enables voxel-by-voxel comparison of in vivo imaging to immunohistochemistry (IHC) biomarkers. As a proof of concept, we investigated the spatial correlation between dynamic contrast enhanced (DCE-)CT parameters and IHC biomarkers Ki-67 (proliferation), HIF-1α (hypoxia), and CD45 (immune cells). 54 whole-mount tumor slices of 15 laryngeal and hypopharyngeal carcinomas were immunohistochemically stained and digitized. Heatmaps of biomarker positivity were created and registered to DCE-CT parameter maps. The adiabatic approximation to the tissue homogeneity model was used to fit the following DCE parameters: Ktrans (transfer constant), Ve (extravascular and extracellular space), and Vi (intravascular space). Both IHC and DCE maps were downsampled to 4 × 4 × 3 mm[3] voxels. The mean values per tumor were used to calculate the between-subject correlations between parameters. For the within-subject (spatial) correlation, values of all voxels within a tumor were compared using the repeated measures correlation (rrm). No between-subject correlations were found between IHC biomarkers and DCE parameters, whereas we found multiple significant within-subject correlations: Ve and Ki-67 (rrm = -0.17, P < .001), Ve and HIF-1α (rrm = -0.12, P < .001), Ktrans and CD45 (rrm = 0.13, P < .001), Vi and CD45 (rrm = 0.16, P < .001), and Vi and Ki-67 (rrm = 0.08, P = .003). The strongest correlation was found between IHC biomarkers Ki-67 and HIF-1α (rrm = 0.35, P < .001). This study shows the technical feasibility of determining the 3 dimensional spatial correlation between histopathological biomarker heatmaps and in vivo imaging. It also shows that between-subject correlations do not reflect within-subject correlations of parameters.

Integrated aerobic-anaerobic digestion of highly solids-loaded corn stover and swine manure under dynamic aeration: Temperature rise, physicochemical characteristics, and methane production.

This research aimed to design an integrated aerobic-anaerobic reactor with dynamic aeration that was automatically regulated based on real-time oxygen concentration and investigate the aerobic pretreatment and subsequent dry co-anaerobic digestion (co-AD) characteristics of highly solids-loaded corn stover and swine manure in terms of temperature rise, physiochemical characteristics, and methane production. The high-temperature feedstocks from the aerobic pretreatment phase rapidly entered the AD phase without transportation and effectively improved the start-up and methane production of the co-AD. Oxygen concentration range, aeration rate, and pretreatment time affected the cumulative aeration time, temperature rise, and organic matter removal interactively during aerobic pretreatment, and a low aeration rate was relatively preferable. Although the lignocellulose removal increased with the increase in pretreatment duration, the maximal lignin elimination efficiency only reached 1.30%. The inoculum injection in the transition phase from aerobic pretreatment to co-AD and the leachate reflux during co-AD were also critical for producing methane steadily apart from aerobic pretreatment. The cold air weakened the temperature rise of aerobic pretreatment, and the low-temperature leachate reduced the methane production in the co-AD process. An oxygen concentration range of 13%-17%, aeration rate of 0.10 m3/(min·m3), pretreatment time of 84 h, inoculum loading of 40%, leachate refluxing thrice per day, and double-layer inoculation were optimum for improving the integrated aerobic-anaerobic digestion system's ability to resist low temperatures and achieving high methane production. The maximal cumulative and volatile solids (VS) methane yields of corn stover and swine manure reached 444.58 L and 266.30 L/kg VS.

Enhancing dynamic flood risk assessment and zoning using a coupled hydrological-hydrodynamic model and spatiotemporal information weighting method.

Climate change and intensified human activities are exacerbating the frequency and severity of extreme precipitation events, necessitating more precise and timely flood risk assessments. Traditional models often fail to dynamically and accurately assess flood risks due to their static nature and limited handling of spatiotemporal variations. This study confronts these challenges head-on by developing a novel coupled hydrological-hydrodynamic model integrated with a Block-wise use of the TOPMODEL (BTOP) and the Rainfall-Runoff-Inundation (RRI) model. This integrated approach enables the rapid acquisition of high-precision flood inundation simulation results across large-scale basins, addressing a significant gap in dynamic flood risk assessment and zoning. A critical original achievement of this research lies in developing and implementing a comprehensive vertical-horizontal combined weighting method that incorporates spatiotemporal information for dynamic evaluation indicators, significantly enhancing the accuracy and rationality of flood risk assessments. This innovative method successfully addresses the challenges posed by objective and subjective weighting methods, presenting a balanced and robust framework for flood risk evaluation. The findings from the Min River Basin in China, as a case study, demonstrate the effectiveness of the BTOP-RRI model in capturing the complex variations in runoff and the detailed simulations of flood processes. The model accurately identifies the timing of these peaks, offering insights into the dynamic evolution of flood risks and providing a more precise and timely assessment tool for policymakers and disaster management authorities. The flood risk assessment results demonstrate good consistency with the actual regional conditions. In particular, high-risk areas exhibit distinct characteristics along the river channel, with the distribution area significantly increasing with a sudden surge in runoff. Intense precipitation events expand areas classified as moderate and high risk, gradually shrinking as precipitation levels decrease. This study significantly advances flood risk assessment methodologies by integrating cutting-edge modeling techniques with comprehensive weighting strategies. This is essential for improving the scientific foundation and decision-making processes in regional flood control efforts.

pH-Responsive, Wide Color Gamut Dynamic Color Display Enabled by PDMAEMA Brush-Based Fabry-Perot Resonant Cavity.

Dynamic color-changing materials have attracted broad interest due to their widespread applications in visual sensing, dynamic color display, anticounterfeiting, and image encryption/decryption. In this work, we demonstrate a novel pH-responsive dynamic color-changing material based on a metal-insulator-metal (MIM) Fabry-Perot (FP) cavity with a pH-responsive poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) brush layer as the responsive insulating layer. The pH-responsive PDMAEMA brush undergoes protonation at a low pH value (pH < 6), which induces different swelling degrees in response to pH and thus refractive index and thickness change of the insulator layer of the MIM FP cavity. This leads to significant optical property changes in transmission and a distinguishable color change spanning the whole visible region by adjusting the pH value of the external environment. Due to the reversible conformational change of the PDMAEMA and the formation of covalent bonds between the PDMAEMA molecular chain and the Ag substrate, the MIM FP cavity exhibits stable performance and good reproducibility. This pH-responsive MIM FP cavity establishes a new way to modulate transmission color in the full visible region and exhibits a broad prospect of applications in dynamic color display, real-time environment monitoring, and information encryption and decryption.

Dynamic Spectral Metafabric with Unidirectional Moisture Transport Property for Personal Thermal Management.

Personal thermal management technology, which adjusts the heat exchange between the human body and the environment, can passively heat or cool the body to maintain a comfortable core temperature, thereby enhancing comfort and reducing energy consumption. However, most existing personal thermal management materials have static properties, such as fixed solar reflectance and infrared emissivity, which do not support real-time dynamic temperature regulation. Moreover, sweat accumulation on the skin surface, while contributing to temperature regulation, can significantly reduce comfort. This study constructs a unidirectional moisture-permeable intelligent thermal management fabric system to achieve superior thermal and moisture comfort in complex environments. The fabric incorporates thermochromic microcapsules into PAN nanofibers by using electrospinning technology for intelligent thermal management. Subsequent hydrophobic treatment of the fiber film surface imparts the fabric with unidirectional wetting properties. The nanofibrous structure provides intrinsic elasticity and breathability. In heating mode, the fabric's average sunlight reflectance is 42.1%, which increases to 82.2% in cooling mode, resulting in a reflectance difference of approximately 40%. The hydrophobic treatment endows the fabric with excellent moisture absorption and perspiration properties, demonstrated by a unidirectional moisture transport index of 696.63 and a perspiration evaporation rate of 5.88 mg/min. When the fabric temperature matches the ambient temperature, the photothermal conversion power difference of the Janus metafabric in two modes reaches 248.37 W m-2. Additionally, Janus metafabrics show the potential for temperature-responsive design and repeated writing applications. The outstanding wearability and dynamic spectral properties of these metafabrics open new pathways for sustainable energy, smart textiles, and thermal-moisture comfort applications.

Spatial Organization of Lipid Nanoparticle siRNA Delivery Systems Revealed by an Integrated Magnetic Resonance Approach.

Lipid nanoparticles (LNPs) are increasingly finding applications in targeted drug delivery, including for subcutaneous, intravenous, inhalation, and vaccine administration. While a variety of microscopy techniques are widely used for LNP characterization, their resolution does not allow for characterization of the spatial organization of different components, such as the excipients, targeting agents, or even the active ingredient. Herein, an approach is presented to probe the spatial organization of individual constituent groups of LNPs used for siRNA-based drug delivery, currently in clinical trials, by multinuclear solid-state magic-angle-spinning nuclear magnetic resonance (MAS NMR) spectroscopy. Dynamic nuclear polarization is exploited (DNP) for sensitivity enhancement, together with judicious 2H labeing, to detect functionally important LNP constituents, the siRNA and the targeting agent (<1-2 w/v%), respectively, and achieve a structural model of the LNP locating the siRNA in the core, the targeting agent below the surface, and the sugars above the lipid bilayer at the surface. The integrated approach presented here is applicable for structural analysis of LNPs and can be extended more generally to other multi-component biological formulations.

[N2O Emission Factors from Wastewater Treatment Plants Based on Literature Statistics and Model Fitting].

The emission of nitrous oxide （N2O） during wastewater treatment cannot be ignored. The analysis of statistical data from literature based on 126 empirical studies revealed that the geographical factors of wastewater treatment plants （WWTPs） had a significant impact on N2O emission factors. However, the N2O emission factors of WWTPs in all regions of the world were generally lower than the Intergovernmental Panel on Climate Change （IPCC） recommended values. In China, the N2O emission factors （in N2O-N/Ninfluent） of WWTPs were approximately 0.000 35-0.065 20 kg·kg-1. Meanwhile, the N2O emission factors of different wastewater treatment processes were also significantly different, especially since the sequencing batch reactor （SBR） process had higher emissions. The use of uniform default emission factors for accounting was prone to overestimate N2O emissions, and it is recommended that countries conduct actual monitoring or modeling studies to develop categorical emission factors suitable for local conditions. In addition, the N2O emission factor based on total nitrogen （TN） removal was weakly negatively correlated with TN removal in 126 empirical data, which was more in line with bioprocessing stoichiometry and could provide an accurate accounting method for N2O. To this end, a digital twin model was developed to dynamically simulate a case anaerobic-anoxic-aerobic （AAO） WWTP to comprehensively quantify the dynamic emission behavior of N2O, which demonstrated that N2O emissions had significant seasonal and daily variability and were only equivalent to 11% of the calculated value of the emission factor based on the IPCC recommendation. Comparing the scatter linear fitting and categorical mean exponential fitting methods, it was found that the latter could more accurately reflect the negative correlation between the N2O emission factors and the TN removal rate, and an exponential regression equation between the average N2O emission factor based on the amount of TN removed and the TN removal rate was further developed to predict the N2O emission. The dynamic simulation and categorical index fitting methods provided in this study are important references for the accurate accounting of N2O emissions in similar WWTPs and provide help for understanding and responding to the N2O emission problems.

Analysis of the Application Value of Dynamic Navigation Guidance in Oral Implantation.

OBJECTIVE: To investigate the application of dynamic navigation guidance technology in different implantation scenarios, and to provide a scientific basis for the innovation and advancement of implantation techniques. METHODS: Fifteen cases of patients with malocclusions admitted between January 2021 and February 2023 were selected as the study subjects. All patients underwent dynamic navigation-guided oral implantation interventions. CBCT scans were taken after implantation surgery to record deviations of implantation points, including implantation point deviation, endpoint deviation, and angle deviation. RESULTS: Dynamic navigation guidance effectively improves the reliability and stability of implantation in oral implant patients. CBCT effectively evaluated the state of the patient's periodontal implant, analyzed the state of the patient's lesion area, and improved the quality of implant intervention through CBCT guidance. The implantation point deviation was (0.407±0.193) mm, the endpoint deviation was (0.492±0.201) mm, and the implant angle deviation was (2.162±0.283)°. There was no significant difference in implantation point deviation in the anterior and posterior parts of the upper and lower jaws after intervention (P>0.05). However, there were significant differences in endpoint deviation and implant angle deviation among the anterior and posterior parts of the upper and lower jaws (P<0.05). CONCLUSION: Dynamic navigation guidance effectively improves the reliability and stability of implantation in oral implant patients. However, there is relatively greater endpoint deviation and implant angle deviation in the posterior part of the upper jaw.

SIRT4 Protects Müller Glial Cells Against Apoptosis by Mediating Mitochondrial Dynamics and Oxidative Stress.

SIRT4 is a member of the sirtuin family, which is related to mitochondrial function and possesses antioxidant and regulatory redox effects. Currently, the roles of SIRT4 in retinal Müller glial cells, oxidative stress, and mitochondrial function are still unclear. We confirmed, by immunofluorescence staining, that SIRT4 is located mainly in the mitochondria of retinal Müller glial cells. Using flow cytometry and Western blotting, we analyzed cell apoptosis, intracellular reactive oxygen species (ROS) levels, apoptotic and proapoptotic proteins, mitochondrial dynamics-related proteins, and mitochondrial morphology and number after the overexpression and downregulation of SIRT4 in rMC-1 cells. Neither the upregulation nor the downregulation of SIRT4 alone affected apoptosis. SIRT4 overexpression reduced intracellular ROS, reduced the BAX/BCL2 protein ratio, and increased the L-OPA/S-OPA1 ratio and the levels of the mitochondrial fusion protein MFN2 and the mitochondrial cleavage protein FIS1, increasing mitochondrial fusion. SIRT4 downregulation had the opposite effect. Mitochondria tend to divide after serum starvation for 24 h, and SIRT4 downregulation increases mitochondrial fragmentation and oxidative stress, leading to aggravated cell damage. The mitochondrial division inhibitor Mdivi-1 reduced oxidative stress levels and thus reduced cell damage caused by serum starvation. The overexpression of SIRT4 in rMC-1 cells reduced mitochondrial fragmentation caused by serum starvation, leading to mitochondrial fusion and reduced expression of cleaved caspase-3, thus alleviating the cellular damage caused by oxidative stress. Thus, we speculate that SIRT4 may protect retinal Müller glial cells against apoptosis by mediating mitochondrial dynamics and oxidative stress.

Time-varying effect in older patients with early-stage breast cancer: a model considering the competing risks based on a time scale.

Background: Patients with early-stage breast cancer may have a higher risk of dying from other diseases, making a competing risks model more appropriate. Considering subdistribution hazard ratio, which is used often, limited to model assumptions and clinical interpretation, we aimed to quantify the effects of prognostic factors by an absolute indicator, the difference in restricted mean time lost (RMTL), which is more intuitive. Additionally, prognostic factors of breast cancer may have dynamic effects (time-varying effects) in long-term follow-up. However, existing competing risks regression models only provide a static view of covariate effects, leading to a distorted assessment of the prognostic factor. Methods: To address this issue, we proposed a dynamic effect RMTL regression that can explore the between-group cumulative difference in mean life lost over a period of time and obtain the real-time effect by the speed of accumulation, as well as personalized predictions on a time scale. Results: A simulation validated the accuracy of the coefficient estimates in the proposed regression. Applying this model to an older early-stage breast cancer cohort, it was found that 1) the protective effects of positive estrogen receptor and chemotherapy decreased over time; 2) the protective effect of breast-conserving surgery increased over time; and 3) the deleterious effects of stage T2, stage N2, and histologic grade II cancer increased over time. Moreover, from the view of prediction, the mean C-index in external validation reached 0.78. Conclusion: Dynamic effect RMTL regression can analyze both dynamic cumulative effects and real-time effects of covariates, providing a more comprehensive prognosis and better prediction when competing risks exist.

Kneadable dough-type hydrogel transforming from dynamic to rigid network to repair irregular bone defects.

Irregular bone defects, characterized by unpredictable size, shape, and depth, pose a major challenge to clinical treatment. Although various bone grafts are available, none can fully meet the repair needs of the defective area. Here, this study fabricates a dough-type hydrogel (DR-Net), in which the first dynamic network is generated by coordination between thiol groups and silver ions, thereby possessing kneadability to adapt to various irregular bone defects. The second rigid covalent network is formed through photocrosslinking, maintaining the osteogenic space under external forces and achieving a better match with the bone regeneration process. In vitro, an irregular alveolar bone defect is established in the fresh porcine mandible, and the dough-type hydrogel exhibits outstanding shape adaptability, perfectly matching the morphology of the bone defect. After photocuring, the storage modulus of the hydrogel increases 8.6 times, from 3.7 kPa (before irradiation) to 32 kPa (after irradiation). Furthermore, this hydrogel enables effective loading of P24 peptide, which potently accelerates bone repair in Sprague-Dawley (SD) rats with critical calvarial defects. Overall, the dough-type hydrogel with kneadability, space-maintaining capability, and osteogenic activity exhibits exceptional potential for clinical translation in treating irregular bone defects.

Progressive endergonic synthesis of Diels-Alder adducts driven by chemical energy.

The overwhelming majority of artificial chemical reaction networks respond to stimuli by relaxing towards an equilibrium state. The opposite response - moving away from equilibrium - can afford the endergonic synthesis of molecules, of which only rare examples have been reported. Here, we report six examples of Diels-Alder adducts accumulated in an endergonic process and use this strategy to realize their stepwise accumulation. Indeed, systems respond to repeated occurrences of the same stimulus by increasing the amount of adduct formed, with the final network distribution depending on the number of stimuli received. Our findings indicate how endergonic processes can contribute to the transition from responsive to adaptive systems.

Facile Preparation of Tough, Puncture-Resistant Antibacterial Polyrotaxane Hydrogel.

Slide-ring hydrogels containing polyrotaxane structures have been widely developed, but current methods are more complex, in which modified cyclodextrins, capped polyrotaxanes, and multistep reactions are often needed. Here, a simple one-pot method dissolving the pseudopolyrotaxane (pPRX) in a mixture of acrylamide and boric acid to form a slide-ring hydrogel by UV light is used to construct a tough, puncture-resistant antibacterial polyrotaxane hydrogel. As a new dynamic ring cross-linking agent, boric acid effectively improves the mechanical properties of the hydrogel and involves the hydrogel with fracture toughness. The polyrotaxane hydrogel can withstand 1 MPa compression stress and maintain the morphology integrity, showing 197.5 mJ puncture energy under a sharp steel needle puncture. Meanwhile, its significant antibacterial properties endow the hydrogel with potential applications in the biomedical field.

Differentiation between primary central nervous system lymphomas and gliomas according to pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging.

Purpose: It is difficult to differentiate between primary central nervous system lymphoma and primary glioblastoma due to their similar MRI findings. This study aimed to assess whether pharmacokinetic parameters derived from dynamic contrast-enhanced MRI could provide valuable insights for differentiation. Methods: Seventeen cases of primary central nervous system lymphoma and twenty-one cases of glioblastoma as confirmed by pathology, were retrospectively analyzed. Pharmacokinetic parameters, including Ktrans, Kep, Ve, and the initial area under the Gd concentration curve, were measured from the enhancing tumor parenchyma, peritumoral parenchyma, and contralateral normal parenchyma. Statistical comparisons were made using Mann-Whitney U tests for Ve and Matrix Metallopeptidase-2, while independent samples t-tests were used to compare pharmacokinetic parameters in the mentioned regions and pathological indicators of enhancing tumor parenchyma, such as vascular endothelial growth factor and microvessel density. The pharmacokinetic parameters with statistical differences were evaluated using receiver-operating characteristics analysis. Except for the Wilcoxon rank sum test for Ve, the pharmacokinetic parameters were compared within the enhancing tumor parenchyma, peritumoral parenchyma, and contralateral normal parenchyma of the primary central nervous system lymphomas and glioblastomas using variance analysis and the least-significant difference method. Results: Statistical differences were observed in Ktrans and Kep within the enhancing tumor parenchyma and in Kep within the peritumoral parenchyma between these two tumor types. Differences were also found in Matrix Metallopeptidase-2, vascular endothelial growth factor, and microvessel density within the enhancing tumor parenchyma of these tumors. When compared with the contralateral normal parenchyma, pharmacokinetic parameters within the peritumoral parenchyma and enhancing tumor parenchyma exhibited variations in glioblastoma and primary central nervous system lymphoma, respectively. Moreover, the receiver-operating characteristics analysis showed that the diagnostic efficiency of Kep in the peritumoral parenchyma was notably higher. Conclusion: Pharmacokinetic parameters derived from dynamic contrast-enhanced MRI can differentiate primary central nervous system lymphoma and glioblastoma, especially Kep in the peritumoral parenchyma.

Characteristics of pain empathic networks in healthy and primary dysmenorrhea women: an fMRI study.

Pain empathy enables us to understand and share how others feel pain. Few studies have investigated pain empathy-related functional interactions at the whole-brain level across all networks. Additionally, women with primary dysmenorrhea (PDM) have abnormal pain empathy, and the association among the whole-brain functional network, pain, and pain empathy remain unclear. Using resting-state functional magnetic resonance imaging (fMRI) and machine learning analysis, we identified the brain functional network connectivity (FNC)-based features that are associated with pain empathy in two studies. Specifically, Study 1 examined 41 healthy controls (HCs), while Study 2 investigated 45 women with PDM. Additionally, in Study 3, a classification analysis was performed to examine the differences in FNC between HCs and women with PDM. Pain empathy was evaluated using a visual stimuli experiment, and trait and state of menstrual pain were recorded. In Study 1, the results showed that pain empathy in HCs relied on dynamic interactions across whole-brain networks and was not concentrated in a single or two brain networks, suggesting the dynamic cooperation of networks for pain empathy in HCs. In Study 2, PDM exhibited a distinctive network for pain empathy. The features associated with pain empathy were concentrated in the sensorimotor network (SMN). In Study 3, the SMN-related dynamic FNC could accurately distinguish women with PDM from HCs and exhibited a significant association with trait menstrual pain. This study may deepen our understanding of the neural mechanisms underpinning pain empathy and suggest that menstrual pain may affect pain empathy through maladaptive dynamic interaction between brain networks.

Novel PATL2 variants cause female infertility with oocyte maturation defect.

PURPOSE: Oocyte maturation defect (OOMD) is a rare cause of in vitro fertilization failure characterized by the production of immature oocytes. Compound heterozygous or homozygous PATL2 mutations have been associated with oocyte arrest at the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as morphological changes. METHODS: In this study, we recruited three OOMD cases and conducted a comprehensive multiplatform laboratory investigation. RESULTS: Whole exome sequence (WES) revealed four diagnostic variants in PATL2, nonsense mutation c.709C > T (p.R237*) and frameshift mutation c.1486_1487delinsT (p.A496Sfs*4) were novel mutations that have not been reported previously. Furthermore, the pathogenicity of these variants was predicted using in silico analysis, which indicated detrimental effects. Molecular dynamic analysis suggested that the A496S variant disrupted the hydrophobic segment, leading to structural changes that affected the overall protein folding and stability. Additionally, biochemical and molecular experiments were conducted on cells transfected with wild-type (WT) or mutant PATL2 (p.R237* and p.A496Sfs*4) plasmid vectors. CONCLUSIONS: The results demonstrated that PATL2A496Sfs*4 and PATL2R237* had impacts on protein size and expression level. Interestingly, expression levels of specific genes involved in oocyte maturation and early embryonic development were found to be simultaneously deregulated. The findings in our study expand the variation spectrum of the PATL2 gene, provide solid evidence for counseling on future pregnancies in affected families, strongly support the application of in the diagnosis of OOMD, and contribute to the understanding of PATL2 function.

Assessment of the Efficacy and Durability of IncobotulinumtoxinA in the Treatment of the Upper Face in Adult Women.

INTRODUCTION: IncobotulinumtoxinA (Xeomin®) is used in the treatment of dynamic wrinkles and the aesthetic repositioning of facial structures. The duration of its muscular effect typically extends for around 4 months. However, the residual aesthetic benefit can be observed for a longer period. To date, the long-term aesthetic benefit of incobotulinumtoxinA in facial aesthetics has not been systematically evaluated. This study aimed to evaluate longitudinally the duration and aesthetic benefits of incobotulinumtoxinA in the treatment of the upper face in adult women. METHODS: A quasi-experimental, evaluator-blind, clinical trial involving 28 adult women (30-60 years old) with facial movement lines, undergoing treatment of the upper face with incobotulinumtoxinA by two injectors, following an individualized protocol (ONE21 and glabellar contraction patterns) was performed. Participants were evaluated on the day of the intervention (day 0) and days 30, 120, 180, and 240, and subjected to standardized photographs. The following outcomes were evaluated blindly at each visit: Merz Aesthetics Facial Contraction Scale (MAS), GAIS (Global Aesthetic Improvement Scale), and patient satisfaction. Adverse effects were evaluated at each visit. RESULTS: Participants ranged in age from 30 to 60 years, 93% were self-declared white, and most of their baseline MAS scores for dynamic lines were moderate and severe. All the parameters presented significative reduction from baseline until day 180. At day 240, the dynamic MAS scores were lower than baseline for forehead lines in 15.4% (95% confidence interval (CI) 0.8-30.0%) of the participants, for glabellar lines in 38.5% (95% CI 18.8-58.1%), and for crow's feet lines in 26.9% (95% CI 9.0-44.8%). Aesthetic improvement compared to baseline was identified in 35% (CI 95% 23‒50%) of the participants at day 240, and 62% (CI 95% 42‒81%) of the sample kept reporting some satisfaction with the procedure. CONCLUSION: The aesthetic treatment of the upper face with incobotulinumtoxinA demonstrates enduring clinical benefits, and patient satisfaction lasting up to 180 days in most participants. The length of efficacy, which exceeded those reported in the literature, may be attributed to the use of techniques based on individualized assessment such as ONE21 and glabellar patterns of contraction.