Sequential Strategy Research Articles

Wireless sequential dual light delivery for programmed PDT in vivo

Using photodynamic therapy (PDT) to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light. Polymeric nanocarriers are widely used for photosensitizer delivery, while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy. Furthermore, the generated short-lived reactive oxygen spieces (ROS) can hardly diffuse out of nanocarriers, resulting in low PDT efficacy. Therefore, a smart nanocarrier system which can be degraded by light, followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy. A light-sensitive polymer nanocarrier encapsulating photosensitizer (RB-M) was synthesized. An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer. Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently. Optimal irradiation time, dose, and RB-M concentration were determined using an agent-based digital simulation method. In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose, which is a clinically significant event that enhances treatment safety.

Spatial multi-omics at subcellular resolution via high-throughput in situ pairwise sequencing.

Technology for spatial multi-omics aids the discovery of new insights into cellular functions and disease mechanisms. Here we report the development and applicability of multi-omics in situ pairwise sequencing (MiP-seq), a method for the simultaneous detection of DNAs, RNAs, proteins and biomolecules at subcellular resolution. Compared with other in situ sequencing methods, MiP-seq enhances decoding capacity and reduces sequencing and imaging costs while maintaining the efficacy of detection of gene mutations, allele-specific expression and RNA modifications. MiP-seq can be integrated with in vivo calcium imaging and Raman imaging, which enabled us to generate a spatial multi-omics atlas of mouse brain tissues and to correlate gene expression with neuronal activity and cellular biochemical fingerprints. We also report a sequential dilution strategy for resolving optically crowded signals during in situ sequencing. High-throughput in situ pairwise sequencing may facilitate the multidimensional analysis of molecular and functional maps of tissues.

Non-surgical Techniques for Combined Rheumatic Severe Aortic and Mitral Stenosis – Case Series and Brief Review of Literature

Rheumatic heart disease persists as a significant concern in developing regions, often resulting in multivalvular heart conditions. Treatment options are limited, though percutaneous transvenous mitral commissurotomy effectively addresses rheumatic mitral stenosis. Non-surgical interventions for aortic stenosis include balloon aortic valvotomy and Transcatheter aortic valve replacement (TAVR), tailored to patient factors like age and comorbidities. We describe two cases of Rheumatic multivalvular disease which were managed non-surgical. The first case is a pioneering procedure performed on a young patient combined percutaneous transvenous mitral commissurotomy with balloon aortic valvotomy, guided by 4-dimensional transoesophageal echocardiography (4D TEE). This represents the first documented instance in medical literature, showcasing the potential of integrated interventions and advanced imaging techniques. In the second challenging case involving a heavily calcified, retrovirus, and Hepatitis B positive 55-year-old, a staged approach was adopted, involving percutaneous transvenous mitral commissurotomy followed by Transcatheter aortic valve replacement (TAVR). Despite complexities, this sequential strategy demonstrates the adaptability of transcatheter techniques in managing complex valvular pathologies. These cases highlight the evolving landscape of interventional cardiology and underscore the importance of tailored, multidisciplinary approaches in optimizing outcomes for patients with rheumatic heart disease and multivalvular involvement, especially in resource-limited settings. Further exploration and dissemination of such innovative strategies hold promise for enhancing cardiac care quality and expanding treatment options globally.

Vertical Control in Molar Distalization by Clear Aligners: A Systematic Review and Meta-Analysis.

Background: Molar distalization is used to correct molar relationships or to create space for mild anterior crowding. However, whether clear aligners can provide proper vertical control with the sequential distalization strategy has been highly debated. Thus, the current study aimed to systematically review the amount of dentoskeletal changes in the vertical dimension that results from sequential molar distalization in clear aligner therapy without temporary anchorage devices (TADs). Methods: Registered with PROSPERO (CRD42023447211), relevant original studies were screened from seven databases and supplemented by a manual search by two investigators independently. Articles were screened against inclusion and exclusion criteria, and a risk of bias assessment was conducted for each included article. Relevant data were extracted from the included articles and meta-analysis was performed using RStudio. Results: Eleven articles (nine for maxillary distalization and two for mandibular distalization) were selected for the final review. All studies have a high or medium risk of bias. For maxillary molar distalization, the meta-analysis revealed 0.26 mm [0.23 mm, 0.29 mm] of maxillary first molar intrusion based on post-distalization dental model analysis, as well as 0.50 mm [-0.78 mm, 1.78 mm] of maxillary first molar intrusion and 0.60 mm [-0.42 mm, 1.62 mm] of maxillary second molar intrusion based on post-treatment lateral cephalometric analysis. Skeletally, there was a -0.33° [-0.67°, 0.02°] change in the SN-GoGn angle, -0.23° [-0.30°, 0.75°] change in the SN-MP angle, and 0.09° [-0.83°, 1.01°] change in the PP-GoGn angle based on post-treatment lateral cephalometric analysis. There was insufficient data for meta-analysis for mandibular molar distalization. Conclusions: No significant changes in vertical dimension were observed, both dentally and skeletally, after maxillary molar distalization with a sequential distalization strategy. However, further studies on this topic are needed due to the high risk of bias in the currently available studies.

Analysis of quantum key distribution based on unified model of sequential state discrimination strategy

The quantum key distribution for multiparty is one of the essential subjects of study. Especially, without using entangled states, performing the quantum key distribution for multiparty is a critical area of research. For this purpose, sequential state discrimination, which provides multiparty quantum communication and quantum key distribution for multiple receivers, has recently been introduced. Moreover, the sequential state discrimination is applicable for the security analysis against an eavesdropper’s attack. In this work, we provide the security analysis of quantum key distribution by proposing a unified model of sequential state discrimination including an eavesdropper. In this model, the success probability of eavesdropping is used as a figure of merit for the security analysis. Moreover, we obtain a non-zero secret key rate between the sender and receiver, which implies that the sender and receiver can share a secret key despite the eavesdropper’s scheme that optimizing the success probability of eavesdropping. Further, we propose an experimental methodology for the proposed model, which is implementable with linear optics. We observe that the secret key between the sender and receiver can be non-zero, even with imperfections.

Digital Media and Secondary Education Students: Inclusion or Exclusion?

Inclusion of students with marginalization tendencies has been one of the demands in the field of education over the last decades, but it remains unrealized. At the same time, our daily lives appear to have changed rapidly because of extensive use of digital media. This fact may have both positive and negative consequences. So, we were inspired to investigate the relationship between teenagers who may be marginalized and the use of digital media, as well as the degree to which they promote or prevent inclusion, by the foregoing considerations. We chose mixed methodological approach as the most appropriate. Specifically, sequential exploratory strategy was used to collect the data, while grounded theory was used for their analysis. The quantitative part sample consists of 600 Secondary Education students. Accordingly, the sample of the qualitative part of the research was 138 Secondary Education students. The survey was conducted over a period of three months (from October 2019 to December 2019). By completing the research project, we concluded that the use of digital media and especially the engagement of adolescent students who show marginalizing tendencies with social media, digital games and distance education leads to their inclusion.

Dynamic simulation of DALS test facility cryoplant

Dalian Advanced Light Source (DALS) test facility program requires a 370 W cryoplant to meet the cooling requirements of four testbenches. The utilization of dynamic simulation holds significant potential for diverse applications such as process design, control logic optimization, and virtual commissioning. These applications are helpful in facilitating the subsequent stages of commissioning and operation. This paper describes the establishment of a model for the DALS test facility cryoplant based on the Ecosimpro software. The model includes the main components of the cryoplant, incorporating most control loops and sequential control strategies. The simulation encompasses three operation modes, namely liquefaction mode, refrigeration mode and fast cooldown mode. The simulation results match the Temperature-Entropy (T-S) diagram from the manufacturer well. This model will be used in the upcoming commissioning of the cryoplant for resolving challenges that may arise in future operation.

DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice

As of December 2022, 2603 laboratory-identified Middle East respiratory syndrome coronavirus (MERS-CoV) infections and 935 associated deaths, with a mortality rate of 36%, had been reported to the World Health Organization (WHO). However, there are still no vaccines for MERS-CoV, which makes the prevention and control of MERS-CoV difficult. In this study, we generated two DNA vaccine candidates by integrating MERS-CoV Spike (S) gene into a replicating Vaccinia Tian Tan (VTT) vector. Compared to homologous immunization with either vaccine, mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses. The immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012, England1 and KNIH strains of MERS-CoV. Prime-Boost immunization also induced strong MERS-S specific T cells responses, with high memory and poly-functional (CD107a-IFN-γ-TNF-α) effector CD8+ T cells. In conclusion, the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S. This study not only provides a promising set of MERS-CoV vaccine candidates, but also proposes a heterologous sequential immunization strategy worthy of further development.

Evaluation of in vitro bioaccessibility of Cu, Fe, Mn, and Zn from cooked Uruguayan pink shrimp by microwave induced plasma atomic emission spectrometry

Microwave induced plasma atomic emission spectrometry (MP-AES) was evaluated as a strategy for the analysis of simulated gastrointestinal solutions to estimate the in vitro bioaccessibility of essential elements in cooked pink shrimp. Operational conditions such as pump speed, nitrogen flow, and viewing position were thoroughly optimized for each element. Afterwards the validation of the analytical method was performed. Limits of quantification ranged from 0.005 mg kg−1 (Mn) to 0.106 mg kg−1 (Zn). Accuracy was evaluated by using a certified reference material and performing a mass-balance study. Suitable mass balances within the range 95–105% were obtained. In vitro bioaccessibility in cooked shrimp samples ranged from 14.7% (Fe) to 48.1% (Zn), in agreement with previous data from other shrimp species. The proposed procedure proved to be an outstanding sequential analytical strategy for elemental bioaccessibility studies, providing simplicity and high sample throughput compared to conventional approaches. Furthermore, this work constitutes the first work regarding the optimization of an elemental bioaccessibility study on animal protein employing MP-AES.

Strategy for Improving Competency and Presenting Quality Development News on Indonesian Television Media

Objective: This research aims to investigate the strategies used by media organizations to improve the competence of journalists in the digital era and improve the quality of news delivery and development content. Method: This research uses mixed methods with a sequential strategy explanation approach. The research population consists of television journalists with news segmentation. The research sample consisted of 60 journalists representing national television media. Quantitative data analysis is used in this research using a regression model with SPSS (Statistic Package for the Social Sciences). Results and conclusion: The research results show that (1) organizational support from dependent media turns out to provide professional awards needed by journalists as a form of appreciation; (2) the function of controlling news and mediating problems between journalists and stakeholders also receives high attention from the media crew. Journalists need more independent media organizations to maintain security and support the implementation of the journalist profession; (2) professionally, journalists always do research before reporting, while journalists' communication competence is still weak in articulating and conveying information. Specific competencies for the media industry, journalists are considered to have mastered their profession, especially in presenting news, and writing scientific papers in the field of education, and journalists are adept at writing about history with social orientation competencies; (3) Regarding the quality of development messages, journalists always pay attention to the appropriateness of the type of information journalists convey development policy information to maintain the quality of development messages so that they remain meaningful, journalists try to adapt themselves to their duties to ensure news is more meaningful and factual; (3) news diversity is a concern in presenting news in maintaining the quality of the news, explaining the chronology, paying attention to the relevance of the truth of the information, news written in language that is easy to understand, according to the facts, in favor of the public interest.

Enzymatic Hydrolysis of Salmon Frame Proteins Using a Sequential Batch Operational Strategy: An Improvement in Water-Holding Capacity.

The meat industry uses phosphates to improve the water-holding capacity (WHC) of meat products, although excess phosphates can be harmful to human health. In this sense, protein hydrolysates offer an alternative with scientific evidence of improved WHCs. Salmon frames, a byproduct rich in protein, must be processed for recovery. Enzymatic technology allows these proteins to be extracted from muscle, and the sequential batch strategy significantly increases protein nitrogen extraction. This study focused on evaluating the WHC of protein hydrolysates from salmon frames obtained through double- and triple-sequential batches compared to conventional hydrolysis. Hydrolysis was carried out for 3 h at 55 °C with 13 mAU of subtilisin per gram of salmon frames. The WHC of each hydrolysate was measured as the cooking loss using concentrations that varied from 0 to 5% (w/w) in the meat matrix. Compared with those obtained through conventional hydrolysis, the hydrolysates obtained through the strategy of double- and triple-sequence batches demonstrated a 55% and 51% reduction in cooking loss, respectively, when they were applied from 1% by weight in the meat matrix. It is essential to highlight that all hydrolysates had a significantly lower cooking loss (p ≤ 0.05) than that of the positive control (sodium tripolyphosphate [STPP]) at its maximum allowable limit when applied at a concentration of 5% in the meat matrix. These results suggest that the sequential batch strategy represents a promising alternative for further improving the WHC of hydrolysates compared to conventional hydrolysis. It may serve as a viable substitute for polyphosphates.

A sequential macrophage activation strategy for bone regeneration: A micro/nano strontium-releasing composite scaffold loaded with lipopolysaccharide

Effective tissue repair relies on the orchestration of different macrophage phenotypes, both the M2 phenotype (promotes tissue repair) and M1 phenotype (pro-inflammatory) deserve attention. In this study, we propose a sequential immune activation strategy to mediate bone regeneration, by loading lipopolysaccharide (LPS) onto the surface of a strontium (Sr) ions -contained composite scaffold, which was fabricated by combining Sr-doped micro/nano-hydroxyapatite (HA) and dual degradable matrices of polycaprolactone (PCL) and poly (lactic-co-glycolic acid) (PLGA). Our strategy involves the sequential release of LPS to promote macrophage homing and induce the expression of the pro-inflammatory M1 phenotype, followed by the release of Sr ions to suppress inflammation. In vitro and in vivo experiments demonstrated that, the appropriate pro-inflammatory effects at the initial stage of implantation, along with the anti-inflammatory effects at the later stage, as well as the structural stability of the scaffolds conferred by the composition, can synergistically promote the regeneration and repair of bone defects.

Enzymatic production of xylose esters using degummed soybean oil fatty acids following a hydroesterification strategy

The enzymatic synthesis of xylose fatty acid esters was carried out in two steps: hydrolysis of degummed soybean oil (DSO) and esterification of the produced and purified free fatty acids (FFA) with xylose. Different lipases immobilized on a hydrophobic support were evaluated in the hydrolysis of DSO and an experimental design was used to optimize the reaction. Eversa® Transform 2.0 (EV-Purolite) yielded 93% conversion after 6 h using biocatalyst load of 6.53 wt%, water/oil mass ratio of 5.5 and temperature of 48.4 °C. High operational stability for EV-Purolite was found using a sequential batch strategy and the possibility of concentrating glycerol. In the esterification stage, lipase from Thermomyces lanuginosus (TLL-Purolite) and lipase B from Candida antarctica showed better performance than lipase from porcine pancreas and EV-Purolite. About 17% of FFAs (0.85 molecules of FAA per xylose molecule) was consumed using an enzyme load of 5 wt% of TLL-Purolite and FFA/xylose molar ratio of 5. Sequential esterification batches showed low operational stability of TTL-Purolite due to the desorption of TLL from the support. The final mixture of the reaction medium containing xylose fatty acid esters showed emulsifying properties similar to those of commercial surfactant.

Passivating Defects via Retarding the Reaction Rate of FAI and PbI2 Enables Stable Perovskite Solar Cells.

The two-step sequential deposition strategy has garnered widespread usage in the fabrication of high-performance perovskite solar cells based on FAPbI3. However, the rapid reaction between FAI and PbI2 during preparation often leads to incomplete reactions, reducing the device efficiency and stability. Herein, we introduced a multifunctional additive, 2-thiophenyl trifluoroacetone (TTA), into the FAI precursor. The incorporation of TTA has proven to be highly effective in slowing the reaction rate between FAI and PbI2, resulting in increased perovskite formation and improved efficiency and stability of the devices. TTA's CF3 groups interact with FAI via hydrogen bonding, effectively suppressing FA+ defects. The S and C═O groups share lone pair electrons with uncoordinated Pb2+, leading to a reduction in perovskite film defects and suppressing nonradiative recombination. Additionally, the CF3 groups impart hydrophobicity, protecting the perovskite film from moisture-induced erosion. As a result, the TTA-modified perovskite film achieves a Champion efficiency of 23.42% compared to the control's 21.52, with 20.58% efficiency for a 25 cm2 solar module. Remarkably, the unencapsulated Champion device retains 86% of its initial PCE after 1080 h under dark conditions (60 ± 5 °C, 35 ± 5% RH), indicating enhanced long-term stability. These findings offer a promising and cost-effective tactic for high-quality perovskite film fabrication.

Implementation of the sequential optimal design strategy in Type-II progressive censoring with the GLM-based mechanism

Implementation of the sequential optimal design strategy in Type-II progressive censoring with the GLM-based mechanism

An active machine learning approach for optimal design of magnesium alloys using Bayesian optimisation

In the pursuit of magnesium (Mg) alloys with targeted mechanical properties, a multi-objective Bayesian optimisation workflow is presented to enable optimal Mg-alloy design. A probabilistic Gaussian process regressor model was trained through an active learning loop, while balancing the exploration and exploitation trade-off via an acquisition function of the upper confidence bound. New candidate alloys suggested by the optimiser within each iteration were appended to the training data, and the performance of this sequential strategy was validated via a regret analysis. Using the proposed approach, the dependency of the prediction error on the training data was overcome by considering both the predictions and their associated uncertainties. The method developed here, has been packaged into a web tool with a graphical user-interactive interface (GUI) that allows the proposed optimal Mg-alloy design strategy to be deployed.

Parallelization of adaptive Bayesian cubature using multimodal optimization algorithms

PurposeBayesian cubature (BC) has emerged to be one of most competitive approach for estimating the multi-dimensional integral especially when the integrand is expensive to evaluate, and alternative acquisition functions, such as the Posterior Variance Contribution (PVC) function, have been developed for adaptive experiment design of the integration points. However, those sequential design strategies also prevent BC from being implemented in a parallel scheme. Therefore, this paper aims at developing a parallelized adaptive BC method to further improve the computational efficiency.Design/methodology/approachBy theoretically examining the multimodal behavior of the PVC function, it is concluded that the multiple local maxima all have important contribution to the integration accuracy as can be selected as design points, providing a practical way for parallelization of the adaptive BC. Inspired by the above finding, four multimodal optimization algorithms, including one newly developed in this work, are then introduced for finding multiple local maxima of the PVC function in one run, and further for parallel implementation of the adaptive BC.FindingsThe superiority of the parallel schemes and the performance of the four multimodal optimization algorithms are then demonstrated and compared with the k-means clustering method by using two numerical benchmarks and two engineering examples.Originality/valueMultimodal behavior of acquisition function for BC is comprehensively investigated. All the local maxima of the acquisition function contribute to adaptive BC accuracy. Parallelization of adaptive BC is realized with four multimodal optimization methods.

Optimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance.

The optimal sequential strategy for antibody-drug conjugates (ADCs) in breast cancer remains uncertain. This study aimed to evaluate the efficacy and potential resistance of second ADC (ADC2) following the first ADC (ADC1) in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low MBC. This retrospective, multicenter, real-world study enrolled patients with MBC who received at least 2 different types of ADCs in 3 hospitals in China between July 1, 2017 and May 1, 2023. Outcomes included the objective response rate (ORR) for ADC1 and ADC2, progression free survival 2 (PFS2), defined as the time from initiation of ADC2 to progression, and overall survival (OS). Seventy-nine female patients were included, 64 of whom had HER2-positive disease. The ORR for ADC2 with similar payload of ADC1 was found to be 5.3%. When switching to a different payload, the ORR of ADC2 increased to 22.6%. The PFS2 for ADC2 remained similar regardless of whether the payload was similar or different. Switching to different payload showed a higher ORR in patients with rapid progression and a durable response longer than 6 months (41.2% vs 15.0%). Specifically, significantly longer PFS2 and OS were seen in patients treated with trastuzumab deruxtecan (T-Dxd) compared to those treated with disitamab vedotin (RC48) after progression from trastuzumab emtansine (T-DM1; median PFS2 5.37 months vs 3.30 months, HR = 0.40, 95% CI 0.17-0.93, P = .034; median OS 50.6 months vs 20.2 months, HR = 0.27, 95% CI 0.08-0.91, P = .034). For patients who progressed after T-Dxd, the median PFS2 was 6.05 months for those treated with RC48 versus 0.93 months for those treated with T-DM1 (HR = 0.03, 95% CI 0.002-0.353, P = .0093). Genomic analysis revealed that alternation of retinoblastoma1 was significantly associated with superior PFS. The alternation of payload achieves different responses in different settings. T-Dxd followed by RC48 may be a potentially beneficial strategy in HER2-positive disease. Further research is needed to elucidate the mechanism of cross-resistance.

A hydroesterification reaction system to produce octyl esters using degummed soybean oil as substrate: Combining reusable free and immobilized lipases

This study shows the enzymatic synthesis of octyl alcohol-based biolubricants carried out in two catalytic steps: degummed soybean oil (DSO) hydrolysis and esterification of the produced and purified free fatty acids (FFA). Several lipases were evaluated as catalysts in the hydrolysis of DSO. Under optimal conditions, lipase from Pseudomonas fluorescens (PFL) yielded 97 % conversion after 23 h using 50 U/g oil and DSO:water mass ratio of 1:0.5. Sequential batch strategies have been developed for the recovery and reuse of free enzyme in further hydrolysis cycles. When hexane was used in the separation between the FFA-rich phase and the phase composed of water, enzyme and glycerol, there was better PFL recovery and FFA-conversion of 65 % was still achieved after five 24-hour hydrolytic cycles. In the esterification step, the potential of four lipases (commercial Lipozym-435, and lipase B from Candida antarctica (CALB), lipase from porcine pancreas (PPL) and Eversa® Transform 2.0 (EV) immobilized on Purolite Lifetech EC8806F) were evaluated in the production of octyl esters in a solvent-free medium (FFA/octanol molar ratio of 1:2.5) using screw-capped glass bottles as reactor. The immobilized EV gave the best ester yield (∼87 wt%). When EV-Purolite was used in a vortex flow reactor, a yield of around 94 wt% was reached after 3 h of reaction using a biocatalyst load of 1 % (w/v) and FFA/octanol molar ratio of 1:2.5. The immobilized lipase could be reused for five consecutive 3 h-batches of esterification, maintaining the octyl esters yield of the first batch.

Implementasi Budaya Ketaqwaan Bagi Mahasiswa Di STAI Al-Hidayah Bogor

This research aims to examine implementing a culture of devotion to increase the spiritual intelligence of students at the Al-Hidayah Bogor Islamic College (STAI). This research collects data through observation, interviews, and document study using a qualitative approach. The results of the research revealed 19 forms of devotional culture that were applied, such as tahfidz tahsin Al-Qur'an, infaq, smile-greeting-greeting, politeness, dhuha prayer, dhikr, pilgrimage rituals, and tolerance. Implementing a culture of devotion is carried out using an instructive sequential strategy based on structural aspects, including school policy, the commitment of the school community, creating an atmosphere of devotion, internalization of values, example, and habituation. The commitment of school leaders, the gradual process of internalizing values, an exemplary and persuasive approach, and habituation are the keys to successful implementation. The positive impact can be seen in the behavior of students who have good morals, high tolerance, a spirit of mutual help, self-confidence, honesty, discipline, a broad understanding of religion, and deep faith and devotion. The results of this research strengthen the theory regarding the importance of implementing the values ??of devotion to form spiritual intelligence and can be a reference for other educational institutions in designing similar strategies.