Deep phosphotyrosine characterisation of primary murine T cells using broad spectrum optimisation of selective triggering.

Sequencing the tyrosine phosphoproteome using MS-based proteomics is challenging due to the low abundance of tyrosine phosphorylation in cells, a challenge compounded in scarce samples like primary cells or clinical samples. The broad-spectrum optimisation of selective triggering (BOOST) method was recently developed to increase phosphotyrosine sequencing in low protein input samples by leveraging tandem mass tags (TMT), phosphotyrosine enrichment, and a phosphotyrosine-loaded carrier channel. Here, we demonstrate the viability of BOOST in T cell receptor (TCR)-stimulated primary murine T cells by benchmarking the accuracy and precision of the BOOST method and discerning significant alterations in the phosphoproteome associated with receptor stimulation. Using 1 mg of protein input (about 20 million cells) and BOOST, we identify and precisely quantify more than 2000 unique pY sites compared to about 300 unique pY sites in non-BOOST control samples. We show that although replicate variation increases when using the BOOST method, BOOST does not jeopardise quantitative precision or the ability to determine statistical significance for peptides measured in triplicate. Many pY previously uncharacterised sites on important T cell signalling proteins are quantified using BOOST, and we identify new TCR responsive pY sites observable only with BOOST. Finally, we determine that the phase-spectrum deconvolution method on Orbitrap instruments can impair pY quantitation in BOOST experiments.

Should SARS-CoV-2 serological testing be used in the decision to deliver a COVID-19 vaccine booster? A pro-con assessment.

Anti-SARS-CoV-2 vaccination has saved millions of lives in the past few years. To maintain a high level of protection, particularly in at-risk populations, booster doses are recommended to counter the waning of circulating antibody levels over time and the continuous emergence of immune escape variants of concern (VOCs). As anti-spike serology is now widely available, it may be considered a useful tool to identify individuals needing an additional vaccine dose, i.e., to screen certain populations to identify those whose plasma antibody levels are too low to provide protection. However, no recommendations are currently available on this topic. We reviewed the relevant supporting and opposing arguments, including areas of uncertainty, and concluded that in most populations, spike serology should not be used to decide about the administration of a booster dose. The main counterarguments are as follows: correlates of protection are imperfectly characterised, essentially owing to the emergence of VOCs; spike serology has an intrinsic inability to comprehensively reflect the whole immune memory; and booster vaccines are now VOC-adapted, while the commonly available commercial serological assays explore antibodies against the original virus.

Modeling and virtual simulation of the boost chopper by DCM using the optimal PIDF control.

This work introduces an improved method for modeling and simulating the Boost Converter utilizing Duty Cycle Modulation (DCM) regulated by an optimum PIDF (Proportional-Integral-Derivative with Filter) regulator. We optimized the characteristic parameters of the PIDF regulator for a second-order system generated from its transfer function by using a mix of theoretical study and simulation using the Matlab/LQR tool. The conventional PID parameters in the time domain were converted into their corresponding LQR (Linear Quadratic Regulator) counterparts, allowing for the solution of the Riccati problem and the creation of an optimum state trajectory model. The results of analog virtual simulations done in a Multisim environment indicate that the system has improved dependability. It maintains a high level of accuracy in a stable condition, with no static error and a reaction time of 1.5 ms, without any overshooting. The effectiveness of the optimum PIDF control in regulating the DCM Boost Converter is highlighted by the system's strong ability to handle changes in load during transient states within a time frame of 300 ms. This study represents a substantial enhancement compared to conventional PID-based approaches, providing valuable knowledge about the possible uses in power electronics and control systems.

Design Photocatalysts to Boost Carrier Dynamics in Plastics Photoconversion into Fuels.

Solar-driven plastics conversion into valuable fuels has attracted broad attention in recent years, which has enormous potential for plastics recycling in the future. However, it usually encounters low conversion efficiency, where one of the reasons is attributed to the poor carrier dynamics in the photocatalytic process. In this Perspective, we critically review the developed strategies, involving defect engineering, doping engineering, heterojunction engineering, and composite construction, for boosted carrier separation efficiency. In addition, we provide an outlook for more potential strategies to engineer catalysts for promoted carrier dynamics. Finally, we also propose prospects for the future research direction of plastics photoconversion into fuels.

Dose Contribution to the Regional Lymph-Node Metastases and Point B from Intracavity and Interstitial Hybrid Brachytherapy in Locally Advanced Cervical Cancer.

PURPOSE: Analyzing dose distributions to regional lymph-node metastases (RLNMs) in locally advanced cervical cancer (LACC) patients undergoing intracavitary and interstitial hybrid brachytherapy (IC/IS). METHODS: Dose distributions of eleven LACC patients with 38 RLNMs, and who received 38 IC/IS sessions were analyzed in EQD2, considering RLNM positions and ipsilateral interstitial needles; these RLNMs, excepting the para-aortic region, were classified into four groups. RESULTS: RLNMs had a median of two ipsilateral interstitial needles per session. Significant differences were observed in total RLNM D90, depending on whether the position was cranial or caudal of the uterine base (85.5 vs. 378.9 cGy, p < 0.0001), and whether the RLNM D90 was associated with a number of ipsilateral interstitial needles between 0-1 or 2 or more (68.4 vs. 112.2 cGy, p = 0.006) per session. At each session, Group 1 RLNMs (cranial of the uterine base, 0-1 ipsilateral interstitial needle) had a mean D90 of 21.1 cGy; Group 2 (cranial, 2 or more), 73.8; Group 3 (caudal, 0-1), 94.7; and Group 4 (caudal, 2 or more), 136.1. CONCLUSION: RLNMs located caudal of the uterine base associated with two or more ipsilateral interstitial needles in IC/IS had a higher dose contribution, which should be considered when calculating the RLNMs' dose of external beam boost irradiation.

Whole-brain radiation therapy plus simultaneous integrated boost for brain metastases from breast cancers.

Background: The effect of whole-brain radiation therapy (WBRT) plus simultaneous integrated boost (SIB) in brain metastasis from breast cancers has not been demonstrated. Method: In this single-center retrospective study, we reviewed consecutive breast cancer patients who developed brain metastasis and were treated with hypofractionated radiation therapy plus WBRT using intensity-modulated radiation therapy (IMRT)-SIB approaches. We analyzed clinical outcomes, prognostic factors and patterns of treatment failure. Result: A total of 27 patients were eligible for analysis. Four (14.8%) patients achieved clinical complete response and 14 (51.9%) had partial response of brain lesions. The other nine patients were not evaluated for brain tumor response. The median brain progression-free survival was 8.60 (95% CI [6.43-13.33]) months and the median overall survival was 16.8 (95% CI [13.3-27.7]) months. Three patients had in-field failure, five had out-field failure and two had in-field and out-field failure. Conclusion: WBRT plus SIB led to improved tumor control and clinical outcome in breast cancer patients with brain metastasis.

Efficacy of Whole-Brain Radiotherapy Plus Simultaneous Integrated Boost (SIB-WBRT) for Lung Cancer Brain Metastases.

Objective: To investigate the outcomes of SIB-WBRT in patients with brain metastases and analyze the impact of some factors on prognosis. Materials and Methods: This single-arm retrospective study analyzed patients with brain metastases who were treated with SIB-WBRT at Peking Union Medical College Hospital from September 2015 to December 2021. The primary endpoint was intracranial progression free survival (iPFS). Secondary endpoints included overall survival (OS), intracranial new foci, and tumor control. The Kaplan-Meier method was then used to depict and estimate iPFS, OS, intracranial neoplasia, and tumor control. Finally, the Cox model was used to analyze the association between some relevant factors and outcomes. Results: A total of 107 patients were included and the median iPFS in these patients treated with SIB-WBRT was 13.4 (95% CI: 4.2-22.6) months, with 68.0% (95% CI: 57.4%-78.6%) and 50.8% (95% CI: 38.3%-63.3%) iPFS at 6- and 12-months. The median local control was 37.6 (95% CI: 28.3-46.8) months, with local control rates of 84.3% (95% CI: 80.6%-88.0%) and 73.3% (95% CI: 68.2%-78.4%) at 6- and 12-months. The median time to appearance of new intracranial foci was 17.4 (95% CI: 14.1-20.8) months, and the 6- and 12-month control rates were 74.5% (95% CI: 64.5%-84.5%) and 61.5% (95% CI: 49.0%-74.0%). The number of brain metastases in patients before treatment was significantly associated with iPFS (HR=0.4, 95% CI: 0.2-0.973, P=0.043). Conclusions: The iPFS, local control, and intracranial new foci of patients with brain metastases after treatment with SIB-WBRT were acceptable. In addition, the number of brain metastases in patients before treatment may be associated with iPFS.

Fault causes and its detection in standalone PV system using ANN and GEO technique.

Power generation systems using photovoltaic (PV) technology have become increasingly popular due to their high production efficiency. A partial shading defect is the most common defect in this system under the process of production, diminishing both the amount and quality of energy produced. This paper proposes an Artificial Neural Network and Golden Eagle Optimization based prediction of the fault and its detection in a standalone PV system to recover the optimum performance and diagnosis of the PV system. The proposed technique combines the Artificial Neural Network (ANN) and Golden Eagle Optimization (GEO) algorithm. The major contribution of this work is to raise PV systems' performance. The result is a defect in the classification and identification of an ANN is used. The use of GEO provides an efficient optimization technique for ANN training, which reduces the training time and improves the accuracy of the model. The proposed technique is executed on the MATLAB site and contrasted with different present techniques, like genetic algorithm (GA),Elephant Herding Optimization (EHO) and Particle Swarm Optimization (PSO). The findings displays that the proposed technique is more accurate and effective than the existing methodologies for detecting and diagnosing defects in PV systems.

A comparative analysis of deep learning and hybrid iterative reconstruction algorithms with contrast-enhancement-boost post-processing on the image quality of indirect computed tomography venography of the lower extremities.

PURPOSE: To examine whether there is a significant difference in image quality between the deep learning reconstruction (DLR [AiCE, Advanced Intelligent Clear-IQ Engine]) and hybrid iterative reconstruction (HIR [AIDR 3D, adaptive iterative dose reduction three dimensional]) algorithms on the conventional enhanced and CE-boost (contrast-enhancement-boost) images of indirect computed tomography venography (CTV) of lower extremities. MATERIALS AND METHODS: In this retrospective study, seventy patients who underwent CTV from June 2021 to October 2022 to assess deep vein thrombosis and varicose veins were included. Unenhanced and enhanced images were reconstructed for AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images were obtained using subtraction software. Objective and subjective image qualities were assessed, and radiation doses were recorded. RESULTS: The CT values of the inferior vena cava (IVC), femoral vein ( FV), and popliteal vein (PV) in the CE-boost images were approximately 1.3 (1.31-1.36) times higher than in those of the enhanced images. There were no significant differences in mean CT values of IVC, FV, and PV between AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images. Noise in AiCE, AiCE-boost images was significantly lower than in AIDR 3D and AIDR 3D-boost images ( P < 0.05). The SNR (signal-to-noise ratio), CNR (contrast-to-noise ratio), and subjective scores of AiCE-boost images were the highest among 4 groups, surpassing AiCE, AIDR 3D, and AIDR 3D-boost images (all P < 0.05). CONCLUSION: In indirect CTV of the lower extremities images, DLR with the CE-boost technique could decrease the image noise and improve the CT values, SNR, CNR, and subjective image scores. AiCE-boost images received the highest subjective image quality score and were more readily accepted by radiologists.

Successful transport across continents of GMP-manufactured and cryopreserved culture-expanded human fetal liver-derived mesenchymal stem cells for use in a clinical trial.

Introduction: Cell therapy has been increasingly considered to treat diseases, but it has been proven difficult to manufacture the same product at multiple manufacturing sites. Thus, for a wider implementation an alternative is to have one manufacturing site with a wide distribution to clinical sites. To ensure administration of a good quality cell therapy product with maintained functional characteristics, several obstacles must be overcome, which includes for example transfer of knowledge, protocols and procedures, site assessment, transportation and preparation of the product. Methods: As the preparatory work for a clinical trial in India using fetal mesenchymal stem cells (fMSCs) developed and manufactured in Sweden, we performed a site assessment of the receiving clinical site, transferred methods, developed procedures and provided training of operators for handling of the cell therapy product. We further developed a Pharmacy Manual to cover the management of the product, from ordering it from the manufacturer, through transport, reconstitution, testing and administration at the clinical site. Lastly, the effect of long-distance transport on survival and function of, as well as the correct handling of the cell therapy product, was evaluated according to the pre-determined and approved Product Specification. Results: Four batches of cryopreserved human fetal liver-derived fMSCs manufactured according to Good Manufacturing Practice and tested according to predetermined release criteria in Sweden, were certified and transported in a dry shipper at -150 °C to the clinical site in India. The transport was temperature monitored and took three-seven days to complete. The thawed and reconstituted cells showed more than 80% viability up to 3 h post-thawing, the cell recovery was more than 94%, the cells displayed the same surface protein expression pattern, differentiated into bone, had stable chromosomes and were sterile, which conformed with the data from the manufacturing site in Sweden. Conclusions: Our study shows the feasibility of transferring necessary knowledge and technology to be able to carry out a clinical trial with a cell therapy product in distant country. It also shows that it is possible to transport a cryopreserved cell therapy product over long distances and borders with retained quality. This extends the use of cryopreserved cell therapy products in the future.

Hippocampal avoidance whole-brain radiotherapy with simultaneous integrated boost in lung cancer brain metastases and utility of the Hopkins verbal learning test for testing cognitive impairment in Chinese patients: a prospective phase II study.

BACKGROUND: This study aimed to evaluate the efficiency of hippocampal avoidance whole-brain radiotherapy with a simultaneous integrated boost (HA-WBRT-SIB) treating brain metastases (BM) and utility of the Hopkins Verbal Learning Test-Revised (HVLT-R) (Chinese version) in Chinese lung cancer patients. METHODS: Lung cancer patients with BM undergone HA-WBRT-SIB at our center were enrolled. Brain magnetic resonance imaging, The HVLT total learning score, and side effects were evaluated before radiotherapy and 1, 3, 6, and 12 months after radiotherapy. This study analyzed the overall survival rate, progression-free survival rate, and changes in HVLT-R immediate recall scores. RESULTS: Forty patients were enrolled between Jan 2016 and Jan 2020. The median follow-up time was 14.2 months. The median survival, progression-free survival, and intracranial progression-free survival of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis indicated that male sex and newly diagnosed stage IV disease were associated with poor overall survival and progression-free survival, respectively. HVLT-R scores at baseline and 1, 3, and 6 months after radiotherapy were 21.94 ± 2.99, 20.88 ± 3.12, 20.03 ± 3.14, and 19.78 ± 2.98, respectively. The HVLT-R scores at 6 months after radiotherapy decreased by approximately 9.8% compared with those at baseline. No grade 3 toxicities occurred in the entire cohort. CONCLUSIONS: HA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.

Effects of Chlorich®EnergyBoost on Enhancing Physical Performance and Anti-Fatigue Properties in Mice.

Chlorich®EnergyBoost, a water extract obtained from Chlorella sorokiniana, has been proposed to enhance physical performance and provide anti-fatigue effects. This study assessed the impact of Chlorich®EnergyBoost supplementation on physical performance and its anti-fatigue properties. Twenty-four mice were allocated into four groups: (1) the control group receiving only water,;(2) the 1X group (49.2 mg/kg/day); (3) the 2X group (98.4 g/kg/day); and (4) the 5X group (246 g/kg/day). All groups were orally administered the supplements for four consecutive weeks. The evaluation included grip strength, swimming endurance, an exhaustion test, and serum biochemistry analysis. Additionally, the study examined the bioactive peptides through matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) and conducted bacterial reverse mutation and acute oral toxicity tests for safety assessment. The findings indicated that Chlorich®EnergyBoost supplementation led to a significant reduction in serum lactate levels by 14.08% to 22.54% and blood urea nitrogen levels by 12.23% to 16.76%, an increase in the lactate clearance rate by 0.28 to 0.35, an enhancement of muscle glycogen storage by 1.10 to 1.44-fold, and hepatic glycogen storage by 1.41 to 1.47-fold. These results demonstrated dose-dependent effects. MALDI-TOF analysis revealed the expression of dihydrolipoamide dehydrogenase and superoxide dismutase. Both the bacterial reverse mutation and acute oral toxicity tests showed no adverse effects.

Contrast enhancement boost improves the image quality of CT angiography derived from 80-kVp cerebral CT perfusion data.

RATIONALE AND OBJECTIVE: To investigate the impact of the contrast enhancement boost (CE-boost) technique on the image quality of CT angiography (CTA) derived from 80-kVp cerebral CT perfusion (CTP) data, and to compare it with conventional CTApeak as well as other currently employed methods for enhancing CTA images, such as CTAtMIP and CTAtAve extracted from CTP. MATERIALS AND METHODS: The data of forty-seven patients who underwent CTP at 80 kVp were retrospectively collected. Four sets of images: CTApeak, CTAtMIP, CTAtAve, and CE-boost images. The CTApeak image represents the arterial phase at its peak value, captured as a single time point. CTAtMIP and CTAtAve are 4D CTA images that provide maximum density projection and average images from the three most prominent time points. CE-boost is a postprocessing technique used to enhance contrast in the arterial phase at its peak value. We compared the average CT value, standard deviation (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the internal carotid artery (ICA) and basilar artery (BA) among the four groups. Image quality was evaluated using a 5-point scale. RESULTS: The CE-boost demonstrated and CNR in the ICA and BA (all p < 0.001). Compared with the other three CTA reconstructed images, the CE-boost images had the best subjective image quality, with the highest scores of 4.77 ± 0.43 and 4.87 ± 0.34 for each reader (all p < 0.001). CONCLUSION: Compared with other currently used techniques,CE-boost enhances the image quality of CTA derived from 80-kVp CTP data, leading to improved visualization of intracranial arteries.

Brachytherapy based microboosting to the dominant intraprostatic lesion in prostate cancer: A systematic review on treatment outcomes and toxicities.

PURPOSE: Whether brachytherapy based microboosting of the dominant intraprostatic lesion (DIL) improves outcomes over standard approaches is not known. The purpose of this study is to perform a systematic review on brachytherapy microboosting of the DIL to evaluate clinical outcomes and toxicities with this treatment approach. MATERIALS AND METHODS: This review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Databases including Pubmed, Embase, and Google Scholar were queried. About 16 studies met our inclusion criteria. These studies reported PSA control and/or toxicities based on standardized scales. RESULTS: There were 10 studies (two monotherapy, eight combination) that used HDR microboosting on a total of 516 patients. HDR dose (EQD2 assuming alpha/beta of 1.5) to the DIL ranged from 90 to 180 Gy. Most patients were low/intermediate risk. PSA control rates at 5-8 years ranged from 69% to 100%. Acute/late G3-G4 GU/GI toxicities ranged from 0% to 12%. There were six studies (five monotherapy, one combination) that used LDR microboosting on a total of 1041 patients. Studies performed a microboost of 130-150% of the whole gland prescription to the DIL. Most patients were low/intermediate risk. PSA control rates at 5 years ranged from 69% to 98%. Acute/late G3-4 GU/GI toxicities ranged from 0% to 4%. CONCLUSIONS: Over 1000 patients have been treated with a brachytherapy based microboost in published series. Severe acute/late toxicities appear limited. PSA control rates with more than 5 years of follow-up are limited. Longer-term follow-up is needed to determine ideal utilization of this approach.

Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing.

Protein nanoparticles are effective platforms for antigen presentation and targeting effector immune cells in vaccine development. Encapsulins are a class of protein-based microbial nanocompartments that self-assemble into icosahedral structures with external diameters ranging from 24 to 42 nm. Encapsulins from Myxococcus xanthus were designed to package bacterial RNA when produced in E. coli and were shown to have immunogenic and self-adjuvanting properties enhanced by this RNA. We genetically incorporated a 20-mer peptide derived from a mutant strain of the SARS-CoV-2 receptor binding domain (RBD) into the encapsulin protomeric coat protein for presentation on the exterior surface of the particle, inducing the formation of several nonicosahedral structures that were characterized by cryogenic electron microscopy. This immunogen elicited conformationally relevant humoral responses to the SARS-CoV-2 RBD. Immunological recognition was enhanced when the same peptide was presented in a heterologous prime/boost vaccination strategy using the engineered encapsulin and a previously reported variant of the PP7 virus-like particle, leading to the development of a selective antibody response against a SARS-CoV-2 RBD point mutant. While generating epitope-focused antibody responses is an interplay between inherent vaccine properties and B/T cells, here we demonstrate the use of orthogonal nanoparticles to fine-tune the control of epitope focusing.

Machine Learning Approaches for Stroke Risk Prediction: Findings from the Suita Study.

Stroke constitutes a significant public health concern due to its impact on mortality and morbidity. This study investigates the utility of machine learning algorithms in predicting stroke and identifying key risk factors using data from the Suita study, comprising 7389 participants and 53 variables. Initially, unsupervised k-prototype clustering categorized participants into risk clusters, while five supervised models including Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), Extreme Gradient Boosting (XGBoost), and Light Gradient Boosted Machine (LightGBM) were employed to predict stroke outcomes. Stroke incidence disparities among identified risk clusters using the unsupervised k-prototype clustering method are substantial, according to the findings. Supervised learning, particularly RF, was a preferable option because of the higher levels of performance metrics. The Shapley Additive Explanations (SHAP) method identified age, systolic blood pressure, hypertension, estimated glomerular filtration rate, metabolic syndrome, and blood glucose level as key predictors of stroke, aligning with findings from the unsupervised clustering approach in high-risk groups. Additionally, previously unidentified risk factors such as elbow joint thickness, fructosamine, hemoglobin, and calcium level demonstrate potential for stroke prediction. In conclusion, machine learning facilitated accurate stroke risk predictions and highlighted potential biomarkers, offering a data-driven framework for risk assessment and biomarker discovery.

SARS-CoV-2 Vaccines: The Advantage of Mucosal Vaccine Delivery and Local Immunity.

Immunity against respiratory pathogens is often short-term, and, consequently, there is an unmet need for the effective prevention of such infections. One such infectious disease is coronavirus disease 19 (COVID-19), which is caused by the novel Beta coronavirus SARS-CoV-2 that emerged around the end of 2019. The World Health Organization declared the illness a pandemic on 11 March 2020, and since then it has killed or sickened millions of people globally. The development of COVID-19 systemic vaccines, which impressively led to a significant reduction in disease severity, hospitalization, and mortality, contained the pandemic's expansion. However, these vaccines have not been able to stop the virus from spreading because of the restricted development of mucosal immunity. As a result, breakthrough infections have frequently occurred, and new strains of the virus have been emerging. Furthermore, SARS-CoV-2 will likely continue to circulate and, like the influenza virus, co-exist with humans. The upper respiratory tract and nasal cavity are the primary sites of SARS-CoV-2 infection and, thus, a mucosal/nasal vaccination to induce a mucosal response and stop the virus' transmission is warranted. In this review, we present the status of the systemic vaccines, both the approved mucosal vaccines and those under evaluation in clinical trials. Furthermore, we present our approach of a B-cell peptide-based vaccination applied by a prime-boost schedule to elicit both systemic and mucosal immunity.

Enhancing PEM fuel cell efficiency with flying squirrel search optimization and Cuckoo Search MPPT techniques in dynamically operating environments.

This study looks into how to make proton exchange membrane (PEM) fuel cells work more efficiently in environments that change over time using new Maximum Power Point Tracking (MPPT) methods. We evaluate the efficacy of Flying Squirrel Search Optimization (FSSO) and Cuckoo Search (CS) algorithms in adapting to varying conditions, including fluctuations in pressure and temperature. Through meticulous simulations and analyses, the study explores the collaborative integration of these techniques with boost converters to enhance reliability and productivity. It was found that FSSO consistently works better than CS, achieving an average increase of 12.5% in power extraction from PEM fuel cells in a variety of operational situations. Additionally, FSSO exhibits superior adaptability and convergence speed, achieving the maximum power point (MPP) 25% faster than CS. These findings underscore the substantial potential of FSSO as a robust and efficient MPPT method for optimizing PEM fuel cell systems. The study contributes quantitative insights into advancing green energy solutions and suggests avenues for future exploration of hybrid optimization methods.

High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function.

Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory.

Acute and Long-Term Toxicity after Planned Intraoperative Boost and Whole Breast Irradiation in High-Risk Patients with Breast Cancer-Results from the Targeted Intraoperative Radiotherapy Boost Quality Registry (TARGIT BQR).

In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1-120, 20.4% dropped out), with a median age of 61 years (range 30-90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation.