Study on the Influence of Runner and Overflow Area Design on Flow-Fiber Coupling in a Multi-Cavity System.

Fiber-reinforced composites (FRPs) are characterized by their lightweight nature and superior mechanical characteristics, rendering them extensively utilized across various sectors such as aerospace and automotive industries. Nevertheless, the precise mechanisms governing the interaction between the fibers present in FRPs and the polymer melt during industrial processing, particularly the manipulation of the flow-fiber coupling effect, remain incompletely elucidated. Hence, this study introduces a geometrically symmetrical 1 × 4 multi-cavity mold system, where each cavity conforms to the ASTM D638 Type V standard specimen. The research utilizes theoretical simulation analysis and experimental validation to investigate the influence of runner and overflow design on the flow-fiber coupling effect. The findings indicate that the polymer melt, directed by a geometrically symmetrical runner, results in consistent fiber orientation within each mold cavity. Furthermore, in the context of simulation analysis, the inclusion of the flow-fiber coupling effect within the system results in elevated sprue pressure levels and an expanded core layer region in comparison to systems lacking this coupling effect. This observation aligns well with the existing literature on the subject. Moreover, analysis of fiber orientation in different flow field areas reveals that the addition of an overflow area alters the flow field, leading to a significant delay in the flow-fiber coupling effect. To demonstrate the impact of overflow area design on the flow-fiber effect, the integration of fiber orientation distribution analysis highlights a transformation in fiber arrangement from the flow direction to cross-flow and thickness directions near the end-of-fill region in the injected part. Additionally, examination of the geometric dimensions of the injected part reveals asymmetrical geometric shrinkage between upstream and downstream areas in the end-of-fill region, consistent with microscopic fiber orientation changes influenced by the delayed flow-fiber coupling effect guided by the overflow area. In brief, the introduction of the overflow area extends the duration in which the polymer melt exerts control in the flow direction, consequently prolonging the period in which the fiber orientation governs in the flow direction (A11). This leads to the impact of fiber orientation on the flow of the polymer melt, with the flow reciprocally affecting the fibers. Subsequently, the interaction between these two elements persists until a state of equilibrium is achieved, known as the flow-fiber coupling effect, which is delayed.

Radiocontrast medium induces histamine release in association with upregulation of miR­19a­3p and miR­362­3p expression.

In Taiwan, the use of radiocontrast medium for clinical image diagnosis recently surpassed one million times and the overall prevalence of radiocontrast hypersensitivity was ~7%. A microRNA (miRNA/miRs) is a small non-coding RNA molecule that mostly plays a suppressor role in cells. However, the roles of miRNA expression in radiocontrast-induced mast cells activation remains to be elucidated. The aim of the present study was to investigate the role of miRNA on radiocontrast-induced mast cell activation. Computed tomography radiocontrast, ultravist and mouse mast cell line, P815, were used in the present study. Cell viability was detected by CCK-8 experiment. Levels of histamine and ß-hexosaminidase were measured by ELISA. miRNA expression was detected by miRNA sequencing and reverse transcription-quantitative PCR. The results showed that ultravist could increase histamine release and reduce intracellular ß-hexosaminidase levels of mast cells. A total of 102 miRNAs could be significantly upregulated by ultravist stimulation. Selected candidate miRNAs for the validation included miR-19a-3p and miR-362-3p which were also increased expression following stimulation with ultravist. In conclusion, ultravist could induce mast cell activation through upregulation of miR-19a-3p and miR-362-3p. Thus, miR-19a-3p and miR-362-3p could be promising candidates for development as novel targets for preventing radiocontrast-induced allergy in the future.

The Evaluation of Teleost-Derived Antimicrobial Peptides Against Neisseria gonorrhoeae.

Introduction Gonorrhea has become an emerging sexually transmitted infection worldwide. The multi-antibiotic resistance facilitates the transmission; thus, new antibiotics or alternatives are needed. Antimicrobial peptides (AMP) are antimicrobials naturally secreted by the host as a defense material. Teleost-derived AMP have gained attention over the past two decades due to their potent efficacy toward microorganisms. This study examines teleost-derived AMP against Neisseria gonorrhoeae (GC), the responsible bacteria for gonorrhea, to evaluate the antibiotic potential as a future alternative for preventing gonorrhea. Methods Minimal inhibitory concentration (MIC) and time-killed assay were conducted to evaluate the inhibition concentration of each AMP. Transmission electron microscopy was used to confirm the potential mode of action. The inhibition of microcolony formation and adherence to epithelial cells were examined to assess the infection inhibition. Results Pardaxin-based (flatfish pardaxin {PB2}) and piscidin-based (striped bass piscidin 1 {PIS} and tilapia piscidin {TP} 4) AMP were effective toward GC under or equal to 7.5 µg/mL as of minimal inhibitory concentration. Transmission electron microscopy images revealed that these AMP attack bacterial membranes as membrane blebbing and breakage were observed. These AMP also effectively reduced the GC biofilm formation, as well as their adherence to human endocervical epithelial cells. Conclusion Pardaxin-based (PB2) and piscidin-based (PIS and TP4) teleost-derived AMP can inhibit GC and potentially serve as the new antibiotic alternative for preventing GC colonization and infection. This study will shed some light on the future development of teleost-derived AMP in treating gonorrhea and maintaining reproductive health.

Vascular compactness of unruptured brain arteriovenous malformation predicts risk of hemorrhage after stereotactic radiosurgery.

The aim of the study was to investigate whether morphology (i.e. compact/diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients receiving Stereotactic Radiosurgery (SRS) for unruptured bAVMs. This retrospective study included 262 adult patients with unruptured bAVMs who underwent upfront SRS. Hemorrhagic events were defined as evidence of blood on CT or MRI. The morphology of bAVMs was evaluated using automated segmentation which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as the ratio of vessel to brain tissue, categorized bAVMs into compact and diffuse types based on the optimal cutoff. Cox proportional hazard model was used to identify the independent factors for post-SRS hemorrhage. The median clinical follow-ups was 62.1 months. Post-SRS hemorrhage occurred in 13 (5.0%) patients and one of them had two bleeds, resulting in an annual bleeding rate of 0.8%. Multivariable analysis revealed bAVM morphology (compact versus diffuse), bAVM volume, and prescribed margin dose were significant predictors. The post-SRS hemorrhage rate increased with larger bAVM volume only among the diffuse nidi (1.7 versus 14.9 versus 30.6 hemorrhage per 1000 person-years in bAVM volume < 20 cm3 versus 20-40 cm3 versus > 40 cm3; p = 0.022). The significantly higher post-SRS hemorrhage rate of Spetzler-Martin grade IV-V compared with grade I-III bAVMs (20.0 versus 3.3 hemorrhages per 1000 person-years; p = 0.001) mainly originated from the diffuse bAVMs rather than the compact subgroup (30.9 versus 4.8 hemorrhages per 1000 person-years; p = 0.035). Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. The post-SRS hemorrhage rate exceeded 2.2% annually within the diffuse and large (> 40 cm3) bAVMs and the diffuse Spetzler-Martin IV-V bAVMs. These findings may help guide patient selection of SRS for the unruptured bAVMs.

Formation of Carbon-Induced Nitrogen-Centered Radicals on Titanium Dioxide under Illumination.

Titanium dioxide is the most studied photocatalytic material and has been reported to be active for a wide range of reactions, including the oxidation of hydrocarbons and the reduction of nitrogen. However, the molecular-scale interactions between the titania photocatalyst and dinitrogen are still debated, particularly in the presence of hydrocarbons. Here, we used several spectroscopic and computational techniques to identify interactions among nitrogen, methanol, and titania under illumination. Electron paramagnetic resonance spectroscopy (EPR) allowed us to observe the formation of carbon radicals upon exposure to ultraviolet radiation. These carbon radicals are observed to transform into diazo- and nitrogen-centered radicals (e.g., CHxN2• and CHxNHy•) during photoreaction in nitrogen environment. In situ infrared (IR) spectroscopy under the same conditions revealed C-N stretching on titania. Furthermore, density functional theory (DFT) calculations revealed that nitrogen adsorption and the thermodynamic barrier to photocatalytic nitrogen fixation are significantly more favorable in the presence of hydroxymethyl or surface carbon. These results provide compelling evidence that carbon radicals formed from the photooxidation of hydrocarbons interact with dinitrogen and suggest that the role of carbon-based "hole scavengers" and the inertness of nitrogen atmospheres should be reevaluated in the field of photocatalysis.

Impact of patient characteristics on innate immune responses and inflammasome activation in ex vivo human lung tissues infected with influenza A virus.

Background: Influenza A virus (IAV) infection poses a persistent global health challenge, necessitating a nuanced grasp of host immune responses for optimal interventions. While the interplay between aging, immunosenescence, and IAV is recognized as key in severe lower respiratory tract infections, the role of specific patient attributes in shaping innate immune reactions and inflammasome activity during IAV infection remains under-investigated. In this study, we utilized an ex vivo infection model of human lung tissues with H3N2 IAV to discern relationships among patient demographics, IAV nucleoprotein (NP) expression, toll-like receptor (TLR) profiles, PD-1/PD-L1 markers, and cytokine production. Methods: Our cohort consisted of thirty adult patients who underwent video-assisted thoracoscopic surgery during 2018-2019. Post-surgical lung tissues were exposed to H3N2 IAV for ex vivo infections, and the ensuing immune responses were profiled using flow cytometry. Results: We observed pronounced IAV activity within lung cells, as indicated by marked NP upregulation in both epithelial cells (P = 0.022) and macrophages (P = 0.003) in the IAV-exposed group relative to controls. Notably, interleukin-2 levels correlated with variations in TLR1 expression on epithelial cells and PD-L1 markers on macrophages. Age emerged as a modulating factor, dampening innate immune reactions, as evidenced by reduced interleukin-2 and interferon-γ concentrations (both adjusted P < 0.05). Intriguingly, a subset of participants with pronounced tumor necrosis factor-alpha post-mock infection (Cluster 1) showed attenuated cytokine responses in contrast to their counterparts in Cluster 2 and Cluster 3 (all adjusted P < 0.05). Individuals in Cluster 2, characterized by a low post-mock infection NP expression in macrophages, exhibited reduced variations in both NP and TLR1-3 expressions on these cells and a decreased variation in interleukin-2 secretion in comparison to their Cluster 3 counterparts, who were identified by their elevated NP macrophage expression (all adjusted P < 0.05). Conclusion: Our work elucidates the multifaceted interplay of patient factors, innate immunity, and inflammasome responses in lung tissues subjected to ex vivo H3N2 IAV exposure, reflecting real-world lower respiratory tract infections. While these findings provide a foundation for tailored therapeutic strategies, supplementary studies are requisite for thorough validation and refinement.

Progress in Photochemical and Electrochemical C-N Bond Formation for Urea Synthesis.

ConspectusHere, we discuss recent advances and pressing challenges in achieving sustainable urea synthesis. Urea stands out as the most prevalent nitrogen-based fertilizer used across the globe, making up over 50% of all manufactured fertilizers. Historically, the Bosch-Meiser process has been the go-to chemical manufacturing method for urea production. This procedure, characterized by its high-temperature and high-pressure conditions, reacts ammonia with carbon dioxide to form ammonium carbamate. Subsequently, this ammonium carbamate undergoes dehydration, facilitated by heat, producing solid urea. A concerning aspect of this method is its dependency on fossil fuels, as nearly all the process heat comes from nonrenewable sources. Consequently, the Bosch-Meiser process leaves behind a considerable carbon footprint. Current estimates predict that unchecked, carbon emissions from urea production alone might skyrocket, reaching a staggering 286 MtCO2,eq/yr by 2050. Such projections paint a clear picture regarding the necessity for more eco-friendly, sustainable urea production methods. Recently, the scientific community has shown growing interest in forming C-N bonds using alternative methods. Shifting toward photochemical or electrochemical processes, as opposed to traditional thermal-based processes, promises the potential for complete electrification of urea synthesis. This shift toward process electrification is not just an incremental change; it represents a groundbreaking advancement, the first of many steps, toward achieving deep decarbonization in the chemical manufacturing sector. Since the turn of 2020, there has been a surge in research focusing on photochemical and electrochemical urea synthesis. These methods capitalize on co-reduction of carbon dioxide with nitrogenous reactants like NOx and N2. Despite the progress, there are significant challenges that hinder these processes from reaching their full potential. In this comprehensive review, we shed light on the advances made in electrified C-N bond formation. More importantly, we focus on the invaluable insights gathered over the years, especially concerning catalytic reaction mechanisms. We have dedicated a section to underline key focal areas for up-and-coming research, emphasizing catalyst, electrolyte, and reactor design. It is undeniable that catalyst design remains at the heart of the matter, as managing the co-reduction of two distinct reactants (CO2 and nitrogenous species) is complex. This process results in a myriad of intermediates, which must be adeptly managed to both maintain catalyst activity and avoid catalyst deactivation. Moreover, the electrolytes play a pivotal role, essentially dictating the creation of optimal microenvironments that drive reaction selectivity. Finally, reactor engineering stands out as crucial to ensure optimal mass transport for all involved reactants and subsequent products. We touch upon the broader environmental ramifications of urea production and bring to light potential obstacles for alternative synthesis routes. A notable mention is the urgency of accelerating the uptake and large-scale implementation of renewable energy sources.

Effect of Arsenate and p-Phenylenediamine on the Expression of Aquaporins in Cultured Human Urothelial Cells.

BACKGROUND: Exposure to arsenic (As) or p­phenylenediamine (PPD) can lead to dysfunction, or even cancer, in various types of organs, including the urinary bladder, yet the underlying mechanisms remain unclear. Aquaporins (AQPs) are widely expressed small water channel proteins that provide the major route for the transport of water and other small molecules across plasma membranes in diverse cell types. Altered expression of AQPs has been associated with pathologies in all major organs, including the urinary bladder. OBJECTIVE: The present in vitro study was performed as a first step towards exploring the possible involvement of AQPs in As- and PPD­induced bladder diseases. METHODS: An immortalized normal human urothelial cell line was employed. Cells were exposed to different concentrations of sodium arsenate (0­20 µM) or PPD (0­200 µM) for 48 h. Cell viability was subsequently assessed. The mRNA and protein expression levels of AQPs (specifically, AQP3, 4, 7, 9, and 11) were analyzed using reverse transcription­quantitative polymerase chain reaction and Western blot analyses, respectively. RESULTS: The viability of the cells was decreased in a concentration-dependent manner upon exposure to arsenate. The mRNA and protein expression levels of AQP3, 4, 7, and 9 were substantially reduced, whereas the expression of AQP11 was largely unchanged. As for the experiments with PPD, treatment with increasing concentrations of PPD induced a gradual decrease in cell viability. The mRNA and protein expression levels of AQP3, 4, and 11 were generally unaltered; however, a marked reduction in the expression levels of AQP7 was observed, contrasting with a gradual concentration-dependent decrease in the expression of AQP9. CONCLUSION: The importance of the differential expression profiles of the AQPs induced by arsenate and PPD requires further investigation; nevertheless, the findings of the present study suggest that AQPs have a role in As­ and PPD­induced bladder diseases.

Cotrimoxazole as a Preventative Intervention for Pneumocystis Pneumonia in Pemphigus Patients Treated with Rituximab: A Retrospective Study.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) is a severe, life-threatening complication in patients treated with rituximab. However, there is no consensus on the primary prophylaxis for it in rituximab-treated pemphigus patients. Therefore, we sought to investigate the prophylactic efficacy and safety profile of cotrimoxazole for reducing the risk of developing PJP in pemphigus patients receiving rituximab. METHODS: This single-center retrospective study investigated 148 pemphigus patients undergoing a first cycle of rituximab between 2008 and 2021 at a tertiary referral center in northern Taiwan. Patients were divided into the prophylaxis group (N = 113) and the control group (N = 35) according to whether or not cotrimoxazole was administered. The primary outcome was the 1-year incidence of PJP in the two groups, while the secondary outcome was the incidence of cotrimoxazole-related adverse events. RESULTS: Of the 148 patients enrolled in this study, three patients, all in the control group, developed PJP during the 1-year follow-up. The incidence of PJP (8.6%) in the control group was significantly higher than that in the prophylaxis group (0%) (p = 0.012). The incidence of cotrimoxazole-related adverse events was 2.7%, and none of the cases were associated with life-threatening conditions. In addition, the cumulative prednisolone dose was associated with a trend of a higher risk of PJP (p = 0.0483). CONCLUSIONS: Prophylactic cotrimoxazole significantly reduces the risk of PJP in a certain high-risk population and has a tolerable safety profile.

A rotating ring disc electrode study of photo(electro)catalyst for nitrogen fixation.

There are numerous reports of photo(electro)catalysts demonstrating activity for nitrogen reduction to ammonia and a few reports of photo(electro)catalysts demonstrating activity for nitrogen oxidation to nitric acid. However, progress in advancing solar-to-fertilizer applications is slow, due in part to the pace of catalyst screening. Most evaluations of photo(electro)catalysts activity occur using batch reactors. This is because common product analyses require accumulation of ammonia or nitric acid in the reactor to overcome instrument detection limits. The primary aim here is to examine the use of an electroanalytical method, rotating ring disk electrode voltammetry (RRDE), to detect ammonia produced by a nitrogen fixing photo(electro)catalyst. To examine the potential for RRDE, we investigated a photo(electro)catalyst known to reduce nitrogen to ammonia (titania), while varying the applied electrochemical potential and degree of illumination on the disk. We show that the observed ammonia oxidation at the ring electrode corresponds strongly with ammonia measurements obtained from the bulk electrolyte. Indicating that RRDE may be effective for catalyst screening. The chief limitation of this approach is the need for an alkaline electrolyte. In addition, this approach does not rule out the presence of adventitious ammonia.

Study on the Flow, Foaming Characteristics and Structural Strength of Polypropylene Structural Foam Injection Molding by Innovative Nitrogen and Molten Plastic Mixing Mechanism.

Plastic foam molding methods include thermoforming, extrusion and injection molding. Injection foam molding is a one-time molding method with high production efficiency and good product quality. It is suitable for foamed plastic products with complex shapes and strict size requirements. It is also the main method for producing structural bubbles. In this investigation, we developed a structural foam injection molding technology using the gas supply equipment connected to the unique plasticizing mechanism of the injection machine and studied its influence on the specimens' melt rheology quality and foam structures. In the experiment, the forming material was polypropylene (PP), and the gas for mixing/forming foaming characteristics was nitrogen (N2). Additionally, in order to observe the rheological properties of N2/melt mixing, a melt flow specimen mold cavity was designed and the change in the melt viscosity index was observed using a melt pressure sensing element installed at the nozzle position. With the nitrogen supply equipment connected to a unique plasticizing mechanism, the mixing of gas and molten plastic can be achieved at the screw plasticizing stage, where the foaming effect is realized during the melt-filling process due to the thermodynamic instability of the gas. It was also found that an increase in N2 fill content increased melt fluidity, and the trend of melt pressure and melt viscosity index showed that the higher the gas content, the lower the trend. The foaming characteristic depends on the gas thermodynamic instability and the pressure release, so it can be seen from the melt fill path that, the greater the pressure near the gate, the lower the foaming amount and the internal structure (SEM) after molding; the farther from the gate, the greater the relative increase in the foaming growth/amount. This phenomenon will be more obvious when the N2 fill content is increased.

Differential characteristics among asymptomatic and symptomatic meibomian gland dysfunction and those with dry eye.

PURPOSE: To identify the characteristics of asymptomatic meibomian gland dysfunction (MGD), symptomatic MGD, and MGD coexisting with dry eye disease (DED). METHODS: This cross sectional study enrolled a total of 153 eyes of 87 MGD patients. Participants filled in ocular surface disease index (OSDI) questionnaires. Age, gender, Schirmer's test, meibomian gland (MG) related parameters, lipid layer thickness (LLT) and blinking were compared among patients with asymptomatic MGD, symptomatic MGD, and MGD with DED. Multivariate regression was used to analyze the significant factor of DED in MGD. Spearman's rank correlation analysis was used to evaluate the association between the significant factors and MG function. RESULTS: There was no difference in age, Schirmer's test, lid changes, MG secretion, and MG morphology among three groups. The OSDI of asymptomatic MGD, symptomatic MGD and MGD coexisting with DED were 8.5 ± 2.9, 28.5 ± 12.8 and 27.9 ± 10.5, respectively. Patients with MGD coexisting with DED exhibited more frequent eye blinking than that of patients with asymptomatic MGD (8.1 ± 4.1 vs. 6.1 ± 3.5 blinks/20 sec, P = 0.022), and reduced LLT than that of patients with asymptomatic MGD (68.6 ± 17.2 vs. 77.6 ± 14.5 nm, P = 0.010) and symptomatic MGD (78.0 ± 17.1 nm, P = 0.015). Multivariate analysis identified LLT (per nm, OR = 0.96, 95% CI = 0.93-0.99, P = 0.002) as a significant factor associated with DED development in MGD. The number of expressible MG was positively correlated with LLT (Spearman's correlation coefficient = 0.299, P = 0.016) but negatively correlated with the number of blinking (Spearman's correlation coefficient = -0.298, P = 0.016) in MGD patients with DED, and these findings were not identified in those without DED. CONCLUSIONS: Asymptomatic MGD, symptomatic MGD, and MGD coexisting with DED share similar characteristics, including meibum secretion and morphology, but MGD patients coexisting with DED exhibited significantly reduced LLT.

Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.

A submillimeter bundled microtubular flow battery cell with ultrahigh volumetric power density.

Flow batteries are a promising energy storage solution. However, the footprint and capital cost need further reduction for flow batteries to be commercially viable. The flow cell, where electron exchange takes place, is a central component of flow batteries. Improving the volumetric power density of the flow cell (W/Lcell) can reduce the size and cost of flow batteries. While significant progress has been made on flow battery redox, electrode, and membrane materials to improve energy density and durability, conventional flow batteries based on the planar cell configuration exhibit a large cell size with multiple bulky accessories such as flow distributors, resulting in low volumetric power density. Here, we introduce a submillimeter bundled microtubular (SBMT) flow battery cell configuration that significantly improves volumetric power density by reducing the membrane-to-membrane distance by almost 100 times and eliminating the bulky flow distributors completely. Using zinc-iodide chemistry as a demonstration, our SBMT cell shows peak charge and discharge power densities of 1,322 W/Lcell and 306.1 W/Lcell, respectively, compared with average charge and discharge power densities of <60 W/Lcell and 45 W/Lcell, respectively, of conventional planar flow battery cells. The battery cycled for more than 220 h corresponding to >2,500 cycles at off-peak conditions. Furthermore, the SBMT cell has been demonstrated to be compatible with zinc-bromide, quinone-bromide, and all-vanadium chemistries. The SBMT flow cell represents a device-level innovation to enhance the volumetric power of flow batteries and potentially reduce the size and cost of the cells and the entire flow battery.

Compactness index: a radiosurgery outcome predictor for patients with unruptured brain arteriovenous malformations.

OBJECTIVE: The goal of the study was to define and quantify brain arteriovenous malformation (bAVM) compactness and to assess its effect on outcomes after Gamma Knife radiosurgery (GKRS) for unruptured bAVMs. METHODS: Unsupervised machine learning with fuzzy c-means clustering was used to differentiate the tissue constituents of bAVMs on T2-weighted MR images. The percentages of vessel, brain, and CSF were quantified. The proposed compactness index, defined as the ratio of vasculature tissue to brain tissue, categorized bAVM morphology into compact, intermediate, and diffuse types according to the tertiles of this index. The outcomes of interest were complete obliteration and radiation-induced changes (RICs). RESULTS: A total of 209 unruptured bAVMs treated with GKRS were retrospectively included. The median imaging and clinical follow-up periods were 49.2 and 72.3 months, respectively. One hundred seventy-three bAVMs (82.8%) achieved complete obliteration after a median latency period of 43.3 months. The rates of RIC and permanent RIC were 76.1% and 3.8%, respectively. Post-GKRS hemorrhage occurred in 14 patients (6.7%), resulting in an annual bleeding risk of 1.0%. Compact bAVM, smaller bAVM volume, and exclusively superficial venous drainage were independent predictors of complete obliteration. Diffuse bAVM morphology, larger bAVM volume, and higher margin dose were independently associated with RICs. CONCLUSIONS: The compactness index quantitatively describes the compactness of unruptured bAVMs. Moreover, compact bAVMs may have a higher obliteration rate and a smaller risk of RICs than diffuse bAVMs. This finding could help guide decision-making regarding GKRS treatment for patients with unruptured bAVMs.

Titers and breadth of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: A single-blinded, randomized clinical trial.

OBJECTIVES: We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19. METHODS: HCW who had at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2 (30 µg), half-dose mRNA-1273 (50 µg), mRNA-1273 (100 µg), and MVC-COV1901 (15 µg). The primary outcomes were humoral and cellular immunogenicity and secondary outcomes assessed safety and reactogenicity at 28 days post-booster. RESULTS: MVC-COV1901 Three hundred and forty HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. The fold-rise of anti-spike IgG geometric mean titer was 8.4 (95% CI 6.8-10.4) for MVC-COV1901, 32.2 (27.2-38.1) for BNT162b2, 47.6 (40.8-55.6) for half-dose mRNA-1273 and 63.2 (53.6-74.6) for mRNA-1273. The live virus microneutralization assays (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron BA.1 variant were 6.4 to 13.5 times lower than those against the wild type. All booster vaccines induced a comparable T cell response. CONCLUSIONS: Third dose booster not only increases neutralizing antibody titer but also enhances antibody breadth against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those who received primary series of ChAdOx1 nCov-19.

Determinants of Antibody Response to SARS-CoV-2 Vaccines in Liver Transplant Recipients: The Role of Immunosuppression Reduction.

Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1−2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT50 ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse.

Relating Darcy-Scale Chemical Reaction Order to Pore-Scale Spatial Heterogeneity.

Due to spatial scaling effects, there is a discrepancy in mineral dissolution rates measured at different spatial scales. Many reasons for this spatial scaling effect can be given. We investigate one such reason, i.e., how pore-scale spatial heterogeneity in porous media affects overall mineral dissolution rates. Using the bundle-of-tubes model as an analogy for porous media, we show that the Darcy-scale reaction order increases as the statistical similarity between the pore sizes and the effective-surface-area ratio of the porous sample decreases. The analytical results quantify mineral spatial heterogeneity using the Darcy-scale reaction order and give a mechanistic explanation to the usage of reaction order in Darcy-scale modeling. The relation is used as a constitutive relation of reactive transport at the Darcy scale. We test the constitutive relation by simulating flow-through experiments. The proposed constitutive relation is able to model the solute breakthrough curve of the simulations. Our results imply that we can infer mineral spatial heterogeneity of a porous media using measured solute concentration over time in a flow-through dissolution experiment.