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Ganoderic Acid (GA), a major bioactive compound isolated from the East Asian medicinal mushroom Ganoderma tsugae, is traditionally believed to have significant medicinal properties. GA is poorly soluble in water, which poses several challenges in terms of its formulation. In this study, Ganoderma tsugae extracts obtained through ethanol extraction were encapsulated in nanodispersions via ultrasonic cavitation and solvent evaporation to increase their bioavailability. The preparation route was thoroughly analyzed using Response Surface Methodology (RSM) to determine the interactions between the variables. Based on the results, the Hydrophilic–Lipophilic Balance (HLB) and the evaporation temperature significantly influenced the resulting particle size. In the optimized nanodispersions, GA was incorporated into a hydrophobic core with a particle size no greater than 200 nm and a very narrow particle distribution (namely, a polydispersity index of 0.289). Due to the high negative zeta potential (−45.9 mV), a very slow particle growth rate of 0.239% over short-term storage (14 days) was achieved. In addition, the zeta average remained virtually unchanged for 14 days at room temperature in solutions at different pH levels. In summary, this paper provides the first-ever demonstration that ultrasound cavitation in conjunction with solvent evaporation can be used to generate GA nanodispersions.

In this study, valuable low-gluten flour and gum were fractionated simultaneously from durian seed via a green and safe aqueous extraction method at maximum atom economy. As the extraction process significantly affected the properties and hence, the application of the flour and gum, the process-properties relationship of extraction temperature and W/S ratio were investigated and presented in this paper. The demucilaged durian seed flour (DDSF) and durian seed gum (DSG) solubilities and water absorption capacity (WAC) were found improved at higher extraction temperature (85 °C) due to bond cleavage and retention of amylose and hydrophilic amino acids. Furthermore, DSG with a solubility of 46.67% was the highest that can be achieved by current aqueous extraction method as further increase of W/S ratio and DSG yield exerted no effect on the solubility. Besides, the oil absorption capacity (OAC) of DSG was found higher than the DDSF due to the presence of nonpolar amino acids and fatty acids that tended to bind with the hydrophobic oil. OAC was mainly determined by the extraction yield and distribution of these hydrophobic fraction, instead of the degree of degradation. Higher overall yield was found at higher extraction temperature of 85 °C for simultaneous extraction of DDSF and DSG. While lower W/S ratio at 1:1 was preferable to obtain higher yield of DDSF, a higher W/S ratio at 5:1 was required for higher yield of DSG. Other than the extraction temperature, drying temperature and duration were key factors determining the colour of the extracted DDSF and DSG.

Mirror modes are large amplitude, non-propagating compressive structures often observed in the magnetosheath. They appear in the form of quasi-sinusoidal oscillations in the magnetic field, with clear magnetic dropouts (‘dips’) or enhancements (‘peaks’). Mirror modes are usually accompanied by a corresponding, anticorrelated signature in plasma density. Typically, the growth of mirror mode fluctuations is triggered when magnetized plasma traverses the bow shock (BS) or draping of the magnetic field around the magnetopause (MP), producing anisotropic ion distribution functions in a high plasma β environment.In this work, nine years of in-situ Cassini data and the latest published catalogue of BS and MP crossings at Saturn were used to perform a detailed statistical analysis of magnetic fluctuations associated with mirror mode structures in Saturn’s magnetosheath. 182 single traversals through the magnetosheath between the bow shock and the magnetopause were used to study the evolution of mirror mode structures across Saturn’s outer and inner magnetosheath and to assess the effects of magnetic shear at the MP on the mirror mode structures near the MP. Violante et al. (1995) analysed two MP crossings at Saturn by Voyagers 1 and 2 and found that in the high magnetic shear MP, mirror waves appear with increasing amplitude and decreasing frequency until the MP, whilst in the other low magnetic shear case, the mirror waves ceased to grow in the presence of a plasma depletion layer but are still present, albeit with smaller amplitude.The amplitude and frequency of mirror waves near the magnetopause are also examined against signs of magnetic reconnection. Tsurutani et al. (1982) suggested that the amplitude of mirror wave structures could impact magnetic reconnection at the MP boundary as alternating high and low regions and the plasma temperature anisotropies may lead to patchy and sporadic reconnection.

Ganoderic Acid (GA), a major bioactive compound isolated from an oriental medicinal mushroom, i.e. Ganoderma tsugae, has traditionally been found to have significant medicinal properties. As a result of GA's poor solubility in water, formulation poses several challenges. Additionally, the traditional method of administering it via alcohol always results in unfavorable patient side effects. In order to overcome these problems, Ganoderma Tsugae extracts obtained by ethanol extraction were encapsulated in nanodispersions by ultrasonic cavitation and solvent evaporation to maximise bioavailability. Resultant nanodispersions contained Ganoderic acid in a hydrophobic core with a mean particle size of no more than 200 nm and a very narrow particle distribution. An analysis of the interactions between the control variables and the process optimisation was conducted using the Response Surface Methodology (RSM). Based on the results of the experiment, it was found that the particle size of nanodispersions was influenced by the Hydrophilic-Lipophilic Balance (HLB) number and the evaporation temperature. Moreover, the physical stability of micellar systems is generally determined by the organic phase within them. Regarding formulation stability, the zeta average of the nanodispersions remained virtually unchanged in solutions with different pH levels and short-term storage (14 days) at room temperature. Overall, it has been demonstrated that Ganoderic acid nanodispersions can be efficiently generated by combining ultrasound cavitation and solvent evaporation.

Triple negative breast carcinoma (TNBC) is a rapid progressive tumor and has a poor overall survival. Therefore, it is crucial to find out effective molecular targets and develop optimal therapeutic strategies for TNBC. In this study, immunohistochemical staining was used to detect expressions of programmed death-ligand 1 (PD-L1) and phosphatase and tensin homolog (PTEN) in 136 breast carcinomas including 50 TNBC. The effect of PTEN on regulation of PD-L1 expression was assessed in vitro in the PTEN knockdown TNBC cells. We found that PD-L1(SP142) positive rate in TNBC (48.0%) was significantly higher than non-TNBC (23.3%). PTEN negative rate was 42% in TNBC. The inverse correlation between PTEN and PD-L1(SP142) expression in TNBC was statistically significant (P

Systematic quantitative structure-retention relationship studies of nucleic acid bases were carried out by the combined use of multivariate analysis and experimental chromatographic technique. The results revealed a multiple linear relationship between the chro- matographic retention and the molecular structural parameters yield- ing a regression R 2 value of 0.8113 (cross-validated Q 2 = 0.6945). Five molecular descriptors, viz., moment of inertia (Ix,Iy and Iz), molar volume, and polar surface area, are able to account for the retention behavior of the compounds. Principal component analysis and factor analysis results indicate that the descriptors moment of inertia and molar volume have a primary influence on the chromato- graphic retention. The results provide useful insights for the future experimental and theoretical studies on the medicinal research of nucleic acid-base compounds.

The Hospitality and Food Service (HaFS) sectors are notoriously known for their contribution to the food waste problem. Hence, there is an urgent need to devise strategies to reduce food waste in the HaFS sectors and to decarbonise their operation to help fight hunger, achieve food security, improve nutrition and mitigate climate change. This study proposes three streams to decarbonise the staff cafeteria operation in an integrated resort in Macau. These include upstream optimisation to reduce unserved food waste, midstream education to raise awareness amongst staff about the impact of food choices on the climate and health, and finally downstream recognition to reduce edible plate waste using a state-of-the-art computer vision system. Technology can be an effective medium to facilitate desired behavioural change through nudging, much like how speed cameras can cause people to slow down and help save lives. The holistic and data-driven approach taken revealed great potential for organisations or institutions that offer catering services to reduce their food waste and associated carbon footprint whilst educating individuals about the intricate link between food, climate and well-being.

Background: The ATEMPT trial primary analysis found that one year of adjuvant trastuzumab emtansine (T-DM1) achieved a 3-year iDFS of 97.8% for patients with stage I HER2+ breast cancer, but was not associated with fewer clinically relevant toxicities (CRTs) compared with paclitaxel and trastuzumab (TH). In this end-of-study analysis, we report 5-year survival outcomes and correlative analyses from the trial. Methods: Patients with stage I centrally confirmed HER2+ breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for one year or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or paclitaxel 80 mg/m2 IV with weekly trastuzumab IV followed by trastuzumab for 9 months. The co-primary objectives were to compare the incidence of CRTs between the 2 arms and to evaluate iDFS in patients receiving T-DM1. To investigate proteomic correlates of recurrence, spatial proteomic analyses were performed on samples from 13 patients experiencing iDFS events (cases) and 24 matched controls using the NanoString GeoMx Digital Spatial Profiler. The impact of HER2 heterogeneity on outcomes was investigated among 17 cases and 51 matched controls by fluorescence in-situ hybridization (FISH). HER2 genetic heterogeneity was assessed by scrutinizing the whole tumor area and defined as the occurrence of HER2 gene amplification in >5% but < 50% invasive tumor cells. The risk of recurrence was evaluated centrally with the HER2DX genomic assay from 225 primary tumor samples. Germline whole genome sequencing (WGS) was conducted among 55 patients experiencing T-DM1-induced thrombocytopenia and/or bleeding and 55 matched controls to identify genomic correlates for this side effect. Results: A total of 497 patients who initiated protocol therapy were included in this analysis (383 T-DM1 and 114 TH). After a median follow up 5.8 years, among patients receiving T-DM1 there were a total of 11 iDFS events, with 3 distant recurrences. The 5-year iDFS for T-DM1 was 97.0% (95% CI, 95.3-98.8%), the 5-year recurrence-free interval (RFI) was 98.6% (95% CI: 97.4-99.8%) and the 5-year overall survival (OS) for T-DM1 was 97.8 % (95% CI, 96.3-99.3%). Although the study was not powered to evaluate the efficacy of TH, among the 114 patients receiving TH, a total of 9 iDFS events were observed, including 2 distant events; the 5-year iDFS with TH was 91.3% (95% CI: 86.0-96.9%), 5-year RFI was 93.3% (95% CI: 88.6-98.2%) and 5-year OS was 97.9% (95% CI: 95.2-100%). A total of 56 samples were evaluable for heterogeneity analyses, among which 14% (n=8) harbored HER2 genetic heterogeneity. Spatial proteomic analyses found that NF1 (adjusted p=0.72 × 10-6) and CTLA-4 (adjusted p=0.15 × 10-3) were significantly upregulated in primary samples from cases, while cleaved caspase 9, CD25, GITR, ICOS, p53 and PD-L2 were significantly upregulated in controls (all with adjusted p< 0.05). Germline WGS found that the top gene associations with thrombocytopenia and thrombocytopenia or bleeding were ALMS1 (p=0,19 × 10-3) and APBA3 (p=0,23 × 10-3), respectively, although none reaching the threshold for genome wide significance. rs62143195 and rs114169776 were the top single nucleotide polymorphisms associated with thrombocytopenia and thrombocytopenia or bleeding, respectively. Data on the impact of HER2 heterogeneity and of HER2DX score on survival outcomes will be presented. Conclusion: With longer follow-up, adjuvant T-DM1 confirmed outstanding long-term outcomes among patients with stage I HER2+ breast cancer, demonstrating a 5-year RFI of 98.6%. Spatial proteomic analyses identified a potential association between NF1 and CTLA-4 expression with recurrence. Details on the impact of HER2 heterogeneity and HER2DX assay on prognosis will be presented. Citation Format: Paolo Tarantino, Nabihah Tayob, Chau T Dang, Denise Yardley, Steven J. Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, Ron Bose, Douglas Weckstein, Antonio C. Wolff, Katherine Reeder-Hayes, Hope Rugo, Bhuvaneswari Ramaswamy, Dan Zuckerman, Lowell Hart, Vijayakrishna K. Gadi, Michael Constantine, Kit Cheng, Audrey Merrill Garrett, Paul K. Marcom, Kathy S. Albain, Patricia DeFusco, Nadine Tung, Blair Ardman, Rita Nanda, Rachel C. Jankowitz, Mothaffar Rimawi, Vandana Abramson, Paula R. Pohlmann, Catherine Van Poznak, Andres Forero-Torres, Minetta C. Liu, Kathryn Ruddy, Yue Zheng, Romualdo Barroso-Sousa, Adrienne Waks, Michelle K. DeMeo, Molly K. DiLullo, Giuseppe Curigliano, Harold Burstein, Ann Partridge, Eric Winer, Giuseppe Viale, Winnie Hui, Elizabeth A. Mittendorf, Bryan P. Schneider, Aleix Prat, Ian Krop, Sara Tolaney. Adjuvant Trastuzumab Emtansine Versus Paclitaxel plus Trastuzumab for Stage I HER2+ Breast Cancer: 5-year results and correlative analyses from ATEMPT (TBCRC033) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-01.

In this article, we present a simple and low-cost experimental setup for thermoelectric effect measurements of thin film materials near room temperature, which can be used to determine their conductivity types. Bi2Te3 and Sb2Te3 thin films grown by the molecular beam epitaxy technique were used as the tested samples. Their Seebeck coefficients were determined to be $(-141\pm 1)\,{\mathrm{\mu V/K}}$ and $(39\pm 2)\,{\mathrm{\mu V/K}}$ , respectively, confirming that the former is an n-type material and the latter is a p-type material. A heterostructure composed of Sb2Te3 and Bi2Te3 was characterized by electrical transport measurements. Data fitting was carried out for its current–voltage characteristics with the Shockley diode model and a real diode model proposed by Cataldo et al. , and some physical parameters of the heterostructure were extracted, including its ideality factor and saturation current. Based on its rectifying current–voltage behavior, we confirm that the aforementioned heterostructure is a p-n junction, which echoes the contrast in the conductivity types of Sb2Te3 and Bi2Te3 as determined by the thermoelectric effect measurements.

Phonocardiogram (PCG) is a type of acoustic signal collected from the heartbeat sound. PCG signals collected in the form of wave files and collected type of heart sound with a specific period. The difficulty of the binomial class in supervised machine learning is the steps-by-steps workflow. The consideration and decision make for every part are importantly stated so that misclassification will not occur. For the heart murmurs classification, data extraction has highly cared for it as we might have fault data consisting of outside signals. Before classifying murmurs in binomial, it will involve multiple features for selection that can have a better classification of the heart murmurs. Nevertheless, since classification performance is vital to conclude the results, models are needed to compare the research's output. The main objective of this study is to classify the signal of the murmur via time-domain based EEG signals. In this study, significant time-domain features were identified to determine the best features by using different feature selection methods. It continues with the classification with different models to compete for the highest accuracy as the performance for murmur classification. A set of Michigan Heart Sound and Murmur database (MHSDB) was provided by the University of Michigan Health System with chosen signals listening with the bell of the stethoscope at the apex area by left decubitus posture of the subjects. The PCG signals are pre-processed by segmentation of three seconds, downsampling eight thousand Hz and normalized to -1, +1. Features are extracted into ten features: Root Mean Square, Variance, Standard Deviation, Maximum, Minimum, Median, Skewness, Shape Factor, Kurtosis, and Mean. Two cross-validation methods applied, such as data splitting and k-fold cross-validation, were used to measure this study's data. Chi-Square and ANOVA technique practice to identify the significant features to improve the classification performance. The classification learners are enrolled and compared by Ada Boost, Random Forest (RF) and Support Vector Machine (SVM). The datasets will separate into a ratio of 70:30 and 80:20 for training and testing data, respectively. The chi-Square selection method was the best features selection method and 80:20 data splitting with better performance than the 70:30 ratio. The best classification accuracy for the models significantly come by SVM with all the categories with 100% except 70:30 test on test data with 97.2% only.

Aims and objectives\ud To develop and evaluate the psychometric properties of an instrument that measures nurses' Attitudes Towards Recognising Early and Noticeable Deterioration (ATREND).\ud \ud Background\ud General ward nurses play an important role in recognising patient deterioration. However, their attitudes towards early recognition of clinical deterioration have not been adequately explored due to the lack of a valid and reliable scale.\ud \ud Design\ud An instrument development and validation study.\ud \ud Methods\ud A three-phase structure that followed the STROBE checklist was used: (1) item generation, (2) content and face validity assessment and (3) psychometric properties evaluation. The scale items were developed based on a comprehensive literature review and content validity assessment by 15 international experts from five countries. The psychometric properties of the ATREND scale were tested on 434 registered nurses, with retest evaluations (n = 100) at two hospitals. Exploratory and confirmatory factor analyses were used to examine the factor structure of the scale. The scale was also evaluated for its internal consistency, test–retest reliability and convergent validity.\ud \ud Results\ud The scale's content validity was 0.95. A 3-factor solution was identified from the final 11 items: (1) beliefs about importance of patient observation, (2) use of broader patient assessment skills and (3) confidence in recognising clinical deterioration. The internal consistency reliability of the scale was supported with an acceptable Cronbach's alpha value of 0.745. Test–retest reliability of the scale was excellent, with an intraclass correlation coefficient of 0.825. The ATREND scale shows evidence of good convergent validity.\ud \ud Conclusion\ud The final 11-item ATREND scale demonstrates adequate initial evidence of reliability and validity for use in acute ward settings.\ud \ud Relevance to clinical practice\ud Nursing educators and clinicians may use this scale to assess ward nurses' attitudes and practices towards early recognition of clinical deterioration and then enhance their competencies and behaviours in the recognition of clinical deterioration.

Hydrogels provide a solution-mimicking environment for the interaction with living systems that make them desirable for various biomedical and technological applications. Because relevant biologica...

A method for synthesising cyclopenta[b]pyran-2-ones through direct (3 + 2) cycloaddition between 2-pyrones and vinyl cyclopropanes is described. In the presence of Pd2(dba)3/dppe in toluene, a series of 2-pyrones undergo chemoselective (3 + 2) cycloaddition with vinyl cyclopropanes and afford cyclopenta[b]pyran-2-ones in high yields (78–96%). The trans/cis ratio of the cycloadducts has been optimised up to 10 : 1. The proposed mechanism of this cycloaddition has been rationalised by computational studies.

(4 + 3) cycloadditions between allenyl ethers and furans are described. The reaction features an in situ formation of oxygen-stabilized oxyallyls via epoxidations of allenyl ethers in the presence of H2PO4−. The multiple interactions between the oxygen-stabilized oxyallyl species and H2PO4− were studied using DFT calculations for rationalization of the regio- and diastereoselectivity of this cycloaddition. The utilities of this cycloaddition have been demonstrated by converting the (4 + 3) cycloadduct into the cyclohepta[b]benzofuran skeleton of frondosin B in two steps.

Genomic instability is considered as one of the key hallmark during cancer development and progression. Cellular mechanisms, such as DNA replication initiation, DNA damage and repair response, apoptosis etc are observed to block progression of genomic instability and thereby induce protective effects against cancer. DNA replication initiation protein MCM10 has been previously observed to have an increased expression in different cancer subtypes. However, MCM10 association with genomic instability, cancer development and its relevant mechanisms remain unknown. Here, using a breast cancer model, we observe a significant association of MCM10 with the degree of clinical aggressiveness in breast cancer patients. By overexpression of MCM10, we observed that MCM10 promotes tumorigenic properties in immortal non-tumorigenic mammary cells by increasing proliferation, shortening the cell cycle, and promoting tumorigenic characters in

In the absence of nationwide mass testing for an emerging health crisis, alternative approaches could provide necessary information efficiently to aid policy makers and health bodies when dealing with a pandemic. The following work presents a methodology by which Twitter data surrounding the first wave of the COVID-19 pandemic in the UK is harvested and analysed using two main approaches. The first is an investigation into localized outbreak predictions by developing a prototype early-warning system using the distribution of total tweet volume. The temporal lag between the rises in the number of COVID-19 related tweets and officially reported deaths by Public Health England (PHE) is observed to be 6–27 days for various UK cities which matches the temporal lag values found in the literature. To better understand the topics of discussion and attitudes of people surrounding the pandemic, the second approach is an in-depth behavioural analysis assessing the public opinion and response to government policies such as the introduction of face-coverings. Using topic modelling, nine distinct topics are identified within the corpus of COVID-19 tweets, of which the themes ranged from retail to government bodies. Sentiment analysis on a subset of mask related tweets revealed sentiment spikes corresponding to major news and announcements. A Named Entity Recognition (NER) algorithm is trained and applied in a semi-supervised manner to recognise tweets containing location keywords within the unlabelled corpus and achieved a precision of 81.6%. Overall, these approaches allowed extraction of temporal trends relating to PHE case numbers, popular locations in relation to the use of face-coverings, and attitudes towards face-coverings, vaccines and the national ‘Test and Trace’ scheme.

Background: One area of biomedical research concerns is applying new treatments to cure human diseases, moving bench-side research to the bedside practice. While using animal models is crucial in the research process, researchers should strictly adhere to the moral 4R framework to protect animal welfare—replacement, reduction, refinement, and responsibility. Virtual reality (VR) applies computer technology to create a simulated environment, allowing players to immerse and interact with animated 3D contexts. We developed a virtual animal-holding simulator (ViSi) using immersive virtual reality technology for students studying in the undergraduate biomedical sciences programme. The specific objectives of the paper are to 1) describe the development of the VR courseware for animal training and 2) describe the learning experience among students.Method and Result: An evaluation of the courseware was conducted among Year one and two biomedical sciences students. Students who participated in ViSi responded positively about their involvement in the virtual environment experience and their concentration on the assigned task.Discussion: ViSi is a reliable simulation technology that can train animal handling skills, which replaces real animals, while learners’ multi-cognition could still be enhanced with simulation training. Thus, the impact of immersive VR technology integrated into skills training is promising, although few technical problems are to be resolved.

Introduction Anti-angiogenic treatment in adjunct with chemotherapy is widely used for the treatment of various cancers. These agents inhibit vascular endothelial growth factor (VEGF) signaling thereby inhibiting tumor proliferation and invasion. Dysphonia, or voice changes, has been documented, but is an underreported side effect of anti-angiogenic agents. We report a case of intermittent dysphonia in a patient with metastatic, platinum-refractory ovarian cancer treated with bevacizumab. Case report A 48-year-old female with high grade mixed type ovarian adenocarcinoma and concurrent left sided breast cancer was transitioned to palliative therapy with gemcitabine-bevacizumab for her ovarian cancer. At a follow-up visit after three cycles of the new therapy, the patient complained of intermittent changes in her voice, describing periods of hoarseness or softness in her voice after the chemotherapy—sometimes to the point that her voice was inaudible. Management and outcome: A new pelvic thrombus was discovered upon assessment of the patient’s disease. Bevacizumab was held and she was referred to ear, nose, and throat evaluation for dysphonia. Laryngoscopic examination showed normal vocal cord, with normal movements and no lesion or necrosis. During subsequent follow-up, the patient reported improvement in her voice with no additional dysphonia. Discussion Vocal adverse effects of anti-VEGF agents have been documented in landmark trials and case reports; however, clinicians are often unaware of this rare side effect. Although VEGF-induced dysphonia may be rare and may not impede the patient’s quality of life in some cases, it is critical to acknowledge and not underestimate this adverse effect.

An oxidative cascade cyclization of β-keto esters has been developed for the construction of the tricyclic picrotoxane motif in a single step, and DFT calculations suggested a possible cationic cyclization mechanism. This cascade cyclization can be operated on a 20 g scale to obtain a 77% total yield of the tricyclic products, which in turn can be converted to versatile intermediates for further elaboration to picrotoxanes and their structurally related compounds.

We report studies on the role of a ZnTe buffer in determining the crystalline phase of MBE-grown MnSe1−xTex alloy thin films. It was found that MBE growth of MnSe and MnTe directly onto a zincblende GaAs substrate usually result in their corresponding stable phases, which are rocksalt and hexagonal, respectively. A set of zincblende MnSe1−xTex alloy thin films with Te composition covering from 0.27 to 1 were fabricated on zincblende ZnTe buffer layers. We have addressed the lattice distortion issue due to thin film effect for these films. A combination of several structural characterizations demonstrates that a perfect lattice matched MnSe1−xTex/ZnTe heterostructure can indeed be realized. The results of this study pave the way for realizing a double-barrier MnSe1−xTex/ZnTe/MnSe1−xTex resonant tunneling diode structure with perfect lattice match as a candidate for a promising THz emitter.

With the aging population becoming increasingly severe, one of the outstanding problems focuses on the elderly foot care and safety. In this paper, two technologies are developed and applied for the proposed wearable electronic shoes design, which are 3D customized shoes design with data mining, location tracking function with GPS and RFID technologies respectively. The proposed technologies are integrated and applied in the prototypes with the customized shoes design. The newly developed smart shoes were successfully prototyped. It demonstrated that the proposed shoes do not only provide the elderly foot care service with customized smart design but also the elderly safety service with location tracking function effectively.

T-cells engineered with a chimeric antigen receptor (CAR) to acquire tumour specificity provide a possible new treatment approach for childhood brain tumours. Durable clinical remissions have been achieved with CD19-directed CAR T-cells in refractory B-cell malignancies including control of leptomeningeal disease and parenchymal deposits. Early clinical data of CAR-T cells in adult glioblastoma and diffuse midline glioma (DMG) further support the rationale for development of CAR-T cell therapy for paediatric high-grade gliomas (pHGG) and other high-risk childhood brain tumours. IL13RA2 provides a suitable CAR target. It is expressed in the majority of pHGG including DMGs while expression is absent on normal (paediatric) brain tissue. Early results with CAR T-cell therapy for adult HGG has shown that IL13RA2 can be safely targeted, and potent anti-tumour activity is possible. However, responses are variable and ultimately transient. This is likely due to the immunosuppressive environment encountered by CAR T-cells at tumour sites which hampers persistent tumour-directed immunity. Here we develop a next generation CAR approach engineering T-cells with both a CAR and a cytokine signal which supports persistent anti-tumour immunity. We have generated novel IL13RA2-specific antibodies and used these to construct CARs. Using a functional screening approach assessing target-specific cytolytic function, T-cell proliferation and cytokine release, we selected the optimal IL13RA2-CAR design. Then, we generated a next generation CAR construct co-expressing inflammatory cytokine IL-15 with the IL13RA2-CAR. In a PDX model of DMG, T-cells transduced with IL13RA2-CARIL-15, in contrast to IL13RA2-CAR alone, induced long-term tumour clearance. Further in vitro testing of IL13RA2-CARIL-15 showed enhanced proliferation and resistance to immune-suppressive secreted factors such as TGF-β. In conclusion, co-expression of IL-15 with IL13RA2-CAR enhances CAR T-cell proliferation and in vivo persistence and achieves durable tumour clearance. IL13RA2-CARIL-15 is being translated into a phase I clinical trial for patients with DMG.

Chemotherapy-related amenorrhea (CRA) is a surrogate for ovarian toxicity and associated risk of infertility and premature menopause. Here, we compare CRA rate with paclitaxel (T)-trastuzumab (H) to that with ado-trastuzumab emtansine (T-DM1). Patients with T1N0 HER2 + early-stage breast cancer (eBC) enrolled on the ATEMPT trial and were randomized 3:1 to T-DM1 3.6 mg/kg IV every (q) 3 weeks (w) × 17 vs. T 80 mg/m2 with H IV qw × 12 (4 mg/kg load → 2 mg/kg), followed by H (6 mg/kg IV q3w × 13). Enrollees who self-reported as premenopausal were asked to complete menstrual surveys at baseline and every 6–12 months for 60 months. 18-month CRA (no periods reported during prior 6 months on 18-month survey) was the primary endpoint of this analysis. Of 512 ATEMPT enrollees, 123 who began protocol therapy and answered baseline and at least one follow-up menstrual survey were premenopausal at enrollment. 76 had menstrual data available at 18 months without having received a gonadotropin-releasing hormone agonist or undergone hysterectomy and/or oophorectomy. Median age was 45 (range 23–53) among 18 who had received TH and 46 (range 34–54) among 58 who had received T-DM1. The 18-month rate of CRA was 50% after TH and 24% after T-DM1 (p = 0.045). Amenorrhea at 18 months was less likely in recipients of adjuvant T-DM1 than TH. Future studies are needed to understand how T-DM1 impacts risk of infertility and permanent menopause, and to assess amenorrhea rates when T-DM1 is administered after standard HER2-directed chemotherapy regimens.

Background: The magnetopause (MP) boundary is formed by the solar wind plasma flow interacting with a planetary magnetic field. Magnetic reconnection is an important process at this boundary as it energises plasma via release of magnetic energy. Reconnection of the IMF and internal magnetic field of the planet produces an “open” magnetosphere allowing solar wind and magnetosheath particles to directly enter the magnetosphere. At Saturn, the nature of MP reconnection remains unclear. Masters et al. (2012) hypothesised that viable reconnection under a large difference in plasma β across the MP also requires a high magnetic shear (i.e. magnetic fields either side of the boundary close to anti-parallel). Objective: The current study uses bulk electron heating at MP crossings (‘events’) as a reconnection signature to test the following hypotheses, suggested by the study of Masters et al. (2012). 1) Events where the boundary is locally closed would have essentially no observed temperature change, whereas most events with locally open boundary should have observed change close to the theoretical prediction. 2) Events with evidence of plasma energization should be in the ‘reconnection possible’ regime, whereas those without such evidence should be in the ‘reconnection suppressed’ regime. Methods: We analysed 70 MP crossings made by the Cassini spacecraft from April 2005 to July 2007, previously reported by Masters et al. (2012). These 70 events have a determined plasma β on both sides of the MP. Magnetic field and particle data were used to characterize the crossings. The bulk temperature was determined using three different methods, related to properties of the observed energy distribution (including methods from Lewis et al. 2008). We compared the observed heating of magnetosheath electrons with the prediction based on reconnection, using the semi-empirical relationship proposed by Phan et al. (2013) which relates the degree of bulk electron heating to the inflow Alfven speed. Results: Plots of observed versus predicted electron temperature change for all 70 crossings showed that there is positive correlation between the two when the 1d moment method (Lewis et al. 2008) was used to calculate heating (Figure 1). We do see a tendency of better agreement with prediction for the locally ‘open’ boundary cases based on the threshold Bn/B >= 0.1 for the minimum variance component of the magnetic field. For the case of locally ‘closed’ boundary (Bn/B < 0.1), we observe a cluster of points near dT=0, but also numerous cases of significant heating. We find five cases where the observed heating exceeds prediction significantly (>3eV). These results suggest that although a large portion of events fit our hypothesis 1 within uncertainty, there are some which do not. Based on the magnetic shear measured locally by the spacecraft either side of the MP, we find 81% of events with no energisation were situated in the ‘reconnection suppressed’ regime, and 43% of events with energization lay in the ‘reconnection possible’ regime (Figure 2). These results support hypothesis 2 to some extent. Conclusion: A statistical study of observed and theoretical electron bulk heating was performed at the magnetopause based on 70 magnetopause crossings detected by the Cassini spacecraft. Our results support both hypotheses 1 and 2 to some extent. One reason why some events do not fit our hypotheses is because we are assuming local conditions to be indicative of the putative reconnection site. However, the spacecraft could be quite distant from this site, and still magnetically connected to it. Another reason is temporal variability in the near-magnetopause environment. We plan to analyse the dataset further in future work, by taking these aspects into account. Figure 1 (Left): Observed against predicted bulk electron temperature change for all 70 crossings. First column: Heating based on 3d moment method for full energy distribution. Second column: Heating based on 3d moment method for the cold energy distribution. Third column: Heating based on 1d moment method for the peak of the energy distribution. Top panels: locally ‘closed’ boundary based on threshold Bn/B < 0.1. Bottom panels: locally ‘open’ boundary based on threshold Bn/B > 0.1. Red markers: Steady transitions with field rotation. Green markers: Turbulent transitions with field rotation. Blue markers: Transitions without field rotation. Figure 2 (Right): Assessment of diamagnetic suppression of reconnection using the 70 MP crossings. Colour represents observed heating using 1d moment method. The solid curve corresponds to a current sheet thickness L = 1 di, and the dashed curves on the left and right of it correspond to L = 0.5 di and L = 2 di, respectively. ‘x’ markers: Steady transitions with field rotation. ‘o’ markers: Turbulent transitions with field rotation. ‘v’ markers: Transitions without field rotation.

Ginsenoside 20(R/S)‐Rg3, as a natural peroxisome proliferator‐activated receptor gamma (PPARγ) ligand, has been reported to exhibit differential biological effects. It is of great interest to understand the stereochemical selectivity of 20(R/S)‐Rg3 and explore whether differential PPARγ activation by Rg3 stereoisomers, if it exists, could lead to differential physiological outcome and therapeutic effects in diabetic atherosclerosis. Here, we investigated the binding modes of 20(R/S)‐Rg3 stereoisomers in the PPARγ ligand‐binding domain (PPARγ‐LBD) using molecular modelling and their effects on smooth muscle cell proliferation and migration induced by advanced glycation end products (AGEs). The results revealed that 20(S)‐Rg3 exhibited stronger antiproliferative and antimigratory effects due to stronger PPARγ activation. To validate the in vitro results, we used a mice model with diabetic atherosclerosis and obtained that 20(S)‐Rg3 markedly reduced the plaque size secondary to reducing the proliferation and migration of VSMCs, while the plaques were more stable due to improvements in other plaque compositions. The results shed light on the structural difference between Rg3 stereoisomers that can lead to significant differential physiological outcome, and the (S)‐isomer seems to be the more potent isomer to be developed as a promising drug for diabetic atherosclerosis.

A compact solid-state UV flame sensing system is developed and tested. We have addressed two approaches for obtaining additional six orders of long-wavelength rejection power on top of that of the built-in UV sensor based on a wide-bandgap II–VI Schottky-barrier structure. An op-amp-based amplification circuit with an average gain of 16 600 is used for signal amplification. It is demonstrated that the developed sensing system could detect a standard butane-air flame with excellent solar-blind characteristics, potentially capable for monitoring industrial boilers. Several feasible approaches were discussed for further improvement in the performance of the developed sensing system targeting its general usage in fire-safety applications.

e17555 Background: Over the last few years, targeted therapy has become the mainstay maintenance treatment of patients with ovarian cancer including patients with BRCA1 or BRCA2 mutations. Poly ADP ribose polymerase (PARP) inhibitors are effective in the treatment of patients who are in complete or partial remission. PARP inhibitors are known to cause hematological adverse events (AEs), but have not been compared directly to each other. Methods: We conducted a single institution, IRB approved, retrospective study on patients who were treated with PARP inhibitors from December 2016 to October 2020. Patients were stratified according to which PARP inhibitor they received. Our primary objective was to assess the incidence of hematological and non-hematological adverse events associated with the use of PARP inhibitor therapy used in patients with ovarian cancer. Data from absolute neutrophil count, hemoglobin and platelet count during the first 2 cycles were graded for hematologic toxicity according to CTCAE v 5.0. Results: A total of 126 patients received a PARP inhibitor during the study time frame. 34 were excluded and 92 patients were included for analysis. Median age of patients were 64.3 (range, 33.8 to 92.3) years, 66 (71.7%) white, and 84 (91.3%) had an ECOG PS of 0/1. Thirty-one (33.7%) of patients received niraparib and 61 (66.3%) of patients received olaparib. Patients in the niraparib group experienced more hematologic AEs, with 11 (35.5%) (95% CI 19.2-54.6), 20 (64.5%) (95% CI 45.4-80.8), and 18 (58.1%) (95% CI 39.1-75.5) experiencing neutropenia, anemia, thrombocytopenia, respectively. Eight (13.1%) (95% CI 5.8-24.2), 24 (39.3%) (95% CI 27.1-52.7), 16 (26.2%) (95% CI 15.8-39.1) patients in the olaparib group experienced neutropenia, anemia, thrombocytopenia, respectively. Conclusions: This single institution retrospective study outlines the hematological toxicities observed between two PARP inhibitors. Although there are four PARP inhibitors approved by FDA, our data compared only two of the four (as they were the most commonly prescribed PARP inhibitors in our institution). Our results suggested that niraparib tended to be associated with a higher risk for hematologic toxicities than olaparib. Our data showed anemia as the most common hematologic toxicity which was consistent with what has been widely documented in the literature.