Parallel Phase Research Articles

Research on a High-Dynamics Acquisition Algorithm for New Binary Offset Carrier Signal in UAV Communication

As unmanned aerial vehicles (UAVs) are widely used in various fields, there is an increasing demand for UAV anti-jamming, multipath mitigation, and covert secrecy. Frequency-hopping binary offset carrier (FH-BOC) signals possess higher anti-jamming and multipath mitigation capabilities than direct-sequence spread spectrum (DSSS) and binary offset carrier (BOC) signals. A prerequisite for constructing communication links between UAVs using FH-BOC signals is the design of efficient acquisition algorithms to capture the signals successfully. In this paper, the modulation and characteristics of the FH-BOC signal are introduced. The maximum relative velocity between UAVs is 5.5 km/s, the maximum acceleration is 50 g, and the maximum plus acceleration is 20 g/s. In this high dynamic environment, the parameters for the parallel code phase and Partial Matched Filter–Fast Fourier Transform (PMF-FFT) acquisition algorithms targeting FH-BOC(10,1) signals are designed, and the acquisition performance of these algorithms is comparatively analyzed. The acquisition time for the first and second algorithms is 4.3317 s and 6.137 s. The number of real additions required by the first and second algorithms is approximately 10.9×109 and 8.9×109, and the number of real multiplications is approximately 7.6×109 and 6.7×109. This helps in selecting the acquisition algorithm when FH-BOC signals are used to build inter-UAV communication links.

EFFICACY AND SAFETY OF THE PROPOSED BIOSIMILAR AFLIBERCEPT, SDZ-AFL, IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results From the Phase 3 Mylight Study.

The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL]). Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks. The primary endpoint was mean change in best-corrected visual acuity score from baseline to Week 8. Secondary endpoints included anatomical outcomes, best-corrected visual acuity at Weeks 24 and 52, safety, and pharmacokinetics. Similarity in mean change in best-corrected visual acuity score was established between SDZ-AFL (n = 235) and Ref-AFL (n = 226) at Week 8 (difference: -0.3 [90% CI, -1.5 to 1.0]) and Week 52. No clinically meaningful differences occurred between groups in anatomical outcomes. Safety profiles were similar, with comparable incidences of treatment-related adverse events (SDZ-AFL: 2.5%; Ref-AFL: 2.9%). The incidence of anti-drug antibodies was similar between groups. Systemic free aflibercept concentrations 24 hours postdose were low and comparable between SDZ-AFL and Ref-AFL. Proposed biosimilar aflibercept matched reference aflibercept in efficacy, safety, and pharmacokinetics in participants with neovascular age-related macular degeneration. Therefore, this Phase 3 study confirmed biosimilarity of SDZ-AFL to Ref-AFL.

Hydroxyurea mobile directly observed therapy versus standard monitoring in patients with sickle cell anemia: a phase 2 randomized trial

BackgroundSickle cell anemia (SCA) prevalence remains high in sub-Saharan Africa. Long-term treatment with hydroxyurea (HU) increases survival, however, poor adherence to treatment could limit effectiveness. Whilst HU treatment adherence is currently high, this might decrease over time.MethodsWe conducted a single-center, randomized, open-label, parallel group phase 2 controlled clinical trial to determine whether mobile Directly Observed Therapy (m-DOT) increases HU treatment adherence (NCT02844673). Eligible participants were adults with homozygous SCA. People on a chronic blood transfusion program, with hemoglobin (Hb) A levels greater than 20% of the total Hb, total Hb less than 4 g/dL, pregnant or HIV positive were excluded. After a 3-month pre-treatment period participants were randomized to either m-DOT or standard monitoring arm. All participants received smart mobile phones and were treated with HU (15 mg/kg) daily for three months. In the m-DOT arm, drug intake was video recorded on cell phone by the participant and the video sent to the study team. The primary objective was to evaluate the effect of m-DOT on adherence to HU treatment by medication possession ratio (MPR).ResultsOf the 86 participants randomized, 76 completed the trial (26.13 ± 6.97 years, 63.5 % female). Adherence was high (MPR > 95 %) in both groups, 29 (80.6 %) in m-DOT versus 37 (94.9 %) in the standard monitoring arm (P = 0.079). No HU treatment was withheld from participants due to safety concerns.Conclusionsm-DOT did not increase adherence to HU treatment. We recommend that further testing in larger trials with a longer follow up period be undertaken.

Preclinical study and parallel phase II trial evaluating antisense STAT3 oligonucleotide and checkpoint blockade for advanced pancreatic, non-small cell lung cancer and mismatch repair-deficient colorectal cancer

ObjectiveTo evaluate signal transducer and activator of transcription 3 (STAT3) inhibition we conducted a co-clinical trial testing danvatirsen, a STAT3 antisense oligonucleotide (ASO) and checkpoint inhibition in conjunction with preclinical...

Regulating phase ratios and mechanical properties of polysynthetic twinned TiAl single crystals via annealing

Polysynthetic twinned (PST) TiAl single crystal specifically refers to a fully lamellar TiAl single crystal with parallel phase interfaces and twin interfaces grown by directional solidification. In this paper, PST single crystals with different phase ratios are obtained by annealing at specific temperatures and holding times. The results show that the diffusion rates of Ti and Al elements at various temperatures directly trigger and propel the surface recrystallization and variation in the internal phase ratio. When the temperature is lower than 1448 K, the diffusion rate of Ti is obviously higher than that of Al, which causes one dense α2 recrystallized layer to form on the surface of TiAl single crystals. Meanwhile, as more Ti elements migrate to the surface, the α2 phase ratio inside the TiAl single crystal thereby decreases. When the temperature exceeds 1448 K, the diffusion rate of Al gradually reverses to exceed that of Ti, which forms the surface sandwiched recrystallization dominated by γ phase and simultaneously increases α2 phase ratio inside the TiAl single crystal. The variation in the two-phase ratio directly induces a significant change in the lamellae thickness, which exhibits different tensile behaviors of PST-TiAl single crystal. When the α2 phase content is less than 20 %, wider γ lamellae make it easier for dislocations to be activated within its lamellae and continuously move across the γ/α2 interfaces, thereby obtaining better tensile plasticity. As the α2 phase content exceeds 30 %, finer γ lamellae inhibit the dislocation initiation, resulting in the fracture occurrence of TiAl single crystal before yielding. No matter how the phase ratio changes, the crack preferentially initiates within α2 lamellae. However, the crack propagation follows different paths based on various γ lamella thicknesses. The fracture mode of PST-TiAl single crystal also changes from shear fracture along slip bands within the γ lamella to brittle fracture along the {11¯00} planes within α2 lamella.

Efficacy and safety of mixture of ivy leaf extract and coptidis rhizome in the treatment of acute bronchitis: multicenter, randomized, double-blinded, active-controlled, parallel, therapeutic confirmatory clinical trial

Background Acute bronchitis is the most common respiratory disease. Mixture of Ivy Leaf Extract and Coptidis rhizome syrup has shown good treatment efficacy against chronic bronchitis and acute respiratory infections. This study aimed to evaluate the efficacy and safety of Mixture of Ivy Leaf Extract and Coptidis rhizome compared with those of Pelargonium sidoides extract, for the treatment of acute bronchitis. Methods We performed a multicenter, randomized, double-blind, active-controlled, parallel phase III study in 220 patients with acute bronchitis. The participants were offered either Mixture of Ivy Leaf Extract and Coptidis rhizome syrup (AGS) and placebo of P. sidoides tablet or placebo syrup and active tablet of P. sidoides (AGU) for 7 days. The primary endpoint was the change in the Bronchitis Severity Score (BSS) from the baseline visit (visit 2) to day 7 (visit 3). Results For the primary outcome, there was no significant difference in the change of total BSS between visits 2 and 3 (−4.10 ± 1.93 vs. −4.24 ± 1.85, p = 0.5125), and since the upper limit of the confidence interval (1.00) was smaller than the predetermined non-inferiority margin (1.17), it was confirmed that the AGS group was non-inferior to the AGU group. The changes in each symptom in the BSS between visits 2 and 3 also showed no significant differences. The overall improvement rate measured by the investigator (91.7 vs. 89.7%; p = 0.3506) and the satisfaction rate of the participants at visit 3 also showed no significant differences (97.2 vs. 94.4%; p = 0.4388). Regarding safety issues, adverse reactions were noted in both groups similarly, with no serious adverse events (4.55 vs. 3.64%, p > 0.999). Conclusion Mixture of Ivy Leaf Extract and Coptidis rhizome syrup is as effective and safe as P. sidoides in controlling symptoms of acute bronchitis.

Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months

Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials. To analyze the association between pegcetacoplan and consensus GA SD-OCT end points. This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023. Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month. The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal). Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month. These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors. ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

In-depth investigation of microstructure and optical properties of tri-phase TiO2 nanoparticles at varied calcination temperatures for dye sensitized solar cells (DSSCs) applications

Tri-phase TiO2 nanoparticles are synthesized by facile hydrothermal method and calcinated within a temperature range of 450 °C–1050 °C. These nanoparticles are utilized as photoanode material in dye-sensitized solar cell (DSSC) applications. The device fabricated by utilizing TiO2 NPs calcinated at 600 °C reveals a maximum power conversion efficiency (η) of 3.79 %, with a current density (Jsc) of 7.83 mA cm−2 under one sun illumination among all tested devices. This exceptional achievement is related to the synergistic effect of 49 wt % anatase, 39 wt % rutile and 12 wt % brookite content in triphasic TiO2 NPs. The anatase emerges as the most active phase providing a sufficient surface area for dye adsorption, and in parallel rutile phase enhances the scattering of light that potentially boosts mobility and injection of photogenerated electrons (e-s) from the LUMO level (ELUMO = −3.8 eV) of N719 dye to the conduction band (ECB = −4.28 eV). Simultaneously, the presence of the brookite phase reduces the charge-carriers ((e−), (h+)) recombination rate at the TiO2 photoelectrode/electrolyte interfaces because brookite has an inherent resistance to back electron transfer. The effective light-harvesting capabilities of triphasic TiO2 NPs position them as promising contenders for dye-sensitized solar cells (DSSCs).

Алгоритм определения намагниченностей подрешеток двухподрешеточного ферримагнетика с точкой компенсации. Часть 1. Фазовая диаграмма

The calculation algorithm of sublattice magnetizations in two-lattice ferromagnet with compensation point is proposed. On the basis of preceding works review it is put the task about calculation of sublattices in individuality. It is investigated the general scheme of whole ferrimagnet magnetization forming which contains two magnetic sublattices both connected by exchange interaction. In geometry of axis symmetry along constant field direction it is investigated the orientational dependence of sublattices magnetization from applied field. It is found the forming conditions of anti-parallel and parallel collinear phases and corner phase between its. It is proposed the model presentation of magnetization dependence from temperature which contain the degree index dependence of general temperature to Curie temperature relation for each sublattice individual. For the simplicity and clear appearance of presentation the power index was choose. It is established the conditions which are necessary for forming the temperature compensation point. It is found the dependencies of deflection corners of each sublattices magnetization from field direction in accounting the given temperature. The decision of proposed excitation for magnetic field allows to find the boundaries of sublattice system transition between phases. On the basis of proposed temperature dependencies of critical transition fields it is drawing the phase diagram of two-sublattice ferrimagnet. It is found two settled on field one above other branches. The lower branch correspond to anti-parallel phase and upper branch correspond to parallel phase. It is found that lower branch contain sufficient quantity of information for to determine the individual both sublattice magnetization. It is proposed the methodic for calculation the individual sublattice magnetization based on the character temperature values and summary magnetizations. On the lower branch marked four character points which correspond to four temperatures and two values of summary magnetization. With using these points it is founded the equation system which allows to determinate the individual magnetizations values. It is proposed some recommendations for further development of investigations.

E071 Bimekizumab demonstrates sustained improvement in quality of life up to week 52 in patients across the full spectrum of axial spondyloarthritis: results from two phase 3 studies

Abstract Background/Aims Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, has demonstrated rapid and clinically meaningful improvements in disease activity in patients across the full spectrum of axial spondyloarthritis (axSpA; active non-radiographic axSpA [nr-axSpA; BE MOBILE 1, NCT03928704] and ankylosing spondylitis [AS]/ radiographic axSpA [r-axSpA; BE MOBILE 2, NCT03928743]). Here we report health-related quality of life (HRQoL) outcomes (ASQoL, SF-36 and EQ-5D-3L) from the two parallel phase 3 studies up to Week (Wk)52. Methods BE MOBILE 1 and 2 have similar study designs: 16-Wk double-blind placebo (PBO)-controlled period followed by 36-Wk maintenance period. Patients were randomised (1:1 in BE MOBILE 1; 2:1 in BE MOBILE 2) to receive BKZ 160 mg Q4W or PBO. All patients received BKZ 160 mg Q4W from Wk16 to Wk52. We report ASQoL, SF-36 - physical component summary (PCS) and SF-36 - mental component summary (MCS) scores up to Wk52 and proportion of patients with ’no problem’ in each of the 5 EQ- 5D-3L domains (mobility, selfcare, usual activity, pain/discomfort, and anxiety/ depression). The results are presented as observed cases (OC), and missing data were imputed using multiple imputation (MI). Results 254 nr-axSpA (BKZ: 128; PBO: 126) and 332 r-axSpA(BKZ: 221; PBO: 111) patients were randomised with 86.6% and 89.8% completing to Wk52, respectively. At Wk16, BKZ treated patients reported greater improvements in ASQoL and SF-36 PCS compared to PBO (p &amp;lt; 0.001, all comparisons, using Analysis of Covariance [ANCOVA]). By Wk52, these improvements across all HRQoL outcomes were sustained in BKZ treated patients and improved in patients who switched to BKZ at Wk16. (Table). The baseline SF-36 MCS levels indicated that on average patients had normal scores which remained unchanged throughout the study. The proportion of patients reporting ‘no problem’ across all five EQ-5D-3L domains improved over time up to Wk52. In patients with ASQoL ≥4 at baseline, &amp;gt;60% of patients had ≥4-point improvement in ASQoL at Wk52. Conclusion Across the axSpA disease spectrum, treatment with BKZ compared with PBO at Wk16 significantly improved quality of life outcomes measured by EQ-5D-3L, ASQoL and SF-36 PCS scores which were sustained to Wk52. Disclosure N.D. McKay: Consultancies; NDM has received consultancy fees from Gilead and UCB Pharma. Other; NDM has received a registration fees for attendance at a conference from Abbvie, Novartis and UCB Pharma, NDM has received a fee for lecturing from Gilead, NDM has taken part in education meetings, programmes and examinations for a wide range of pharmaceutical companies. A. Bennett: Honoraria; AB received teaching honorarium from Abbvie Ltd, Pfizer, UCB Pharma, Novartis and Biogen. Grants/research support; AB received research grants from Pfizer. Other; AB received advisory board fees from Abbvie Ltd, Pfizer, UCB Pharma, MSD, Novartis and Lilly. N. Goodson: Honoraria; NG has received honoraria from UCB Pharma and Novartis. C. Fleurinck: Other; CF is an employee of UCB Pharma. C. de la Loge: Consultancies; CdlL is a consultant to UCB Pharma, Brussels, Belgium. U. Massow: Other; UM is an employee of UCB Pharma. V. Taieb: Other; VT is employee of UCB Pharma. H. Marzo-Ortega: Grants/research support; HMO has received grants/research support from Janssen, Novartis and UCB Pharma. Other; HMO has received honoraria and/or consultancy and/or speaker fees from Abbvie, Biogen, Celgene, Janssen, Eli-Lilly, Moonlake, Novartis, Pfizer and UCB Pharma. K. Gaffney: Shareholder/stock ownership; KG is a shareholder of Rheumatology Events. Grants/research support; KG has received grants/research support from NASS, Versus Arthritis, AbbVie, Pfizer, UCB Pharma, Norvartis, Eli Lilly, Cellgene, Celltrion, Janssen, Gilead and Biogen. Other; KG has received honoraria/ consultation fees from Novartis, AbbVie, UCB Pharma, Lilly and Pfizer, KG has received speaker’s bureau from Novartis, UCB Pharma, AbbVie and Lilly; meeting expenses from AbbVie, Lilly, Roche, Novartis, Pfizer and UCB Pharma.

A Protocol for Patients' Education Based on Andragogy: A Convergent Parallel Mixed Methods Study

Background: Patients' education is a key factor in patients' care. The purpose of this study is to design a protocol for a convergent parallel mixed methods study to explore the experiences of patients about their received educations based on andragogy model. Methods: This convergent parallel mixed method study includes two parallel quantitative and qualitative phases. During the quantitative phase, a cross-sectional survey will be conducted on 350 adult patients who had the history of hospitalization and received patient education from selected hospitals of Tehran, Iran. Sampling method will be random, and data collection tool will be a researcher-made questionnaire based on the principles of andragogy. The questionnaire’s validity and reliability are also measured, and data will be analyzed using SPSS 16. The qualitative phase will be conducted on adult patients who will be recruited purposively with maximum variation from the selected hospitals. Data will be gathered through semi-structured interviews and analyzed by directed content analysis. With regard to mixed method and using aligning convergence method, the results of the two sets of data will be compared or merged to see if the findings confirm or disconfirm each other. In this parallel section, the similarities between quantitative and qualitative results for assessing patient education are discussed and adapted to suit each other based on andragogy. Conclusions: The findings of this study will provide information regarding defects in patient education, suggesting that the principles of andragogy will develop patient education programs.

Measuring the in-plane thermal diffusivity of anisotropic solids by lock-in infrared thermography: Laser-spot vs laser-line heating

A method is proposed to measure the in-plane thermal diffusivity of anisotropic solids along an arbitrary direction using laser-line lock-in thermography. In this method, the sample is heated by an intensity-modulated laser beam, which impinges on the sample surface with the shape of a narrow strip. The resulting temperature oscillations are recorded by a thermographic camera and a phase thermogram is obtained by lock-in processing the image sequence. The thermal diffusivity along the direction perpendicular to the laser line can be determined from the linear dependence of phase lag with the distance to the heating line using the slope method. Unlike laser-spot lock-in thermography, in which the slope method only provides the thermal diffusivity along the principal directions, in this configuration, the thermal diffusivity can be measured experimentally along any direction, just selecting the relative orientation of the sample with respect to the laser line. Moreover, this configuration allows averaging several parallel phase profiles leading to more reliable thermal diffusivity values. The experimental results are presented for a highly anisotropic material, namely, a unidirectional carbon fiber-reinforced polymer plate.

Electromagnetic Landau Resonance: MMS Observations

AbstractTheoretical analysis has revealed a specific resonance that shares the same condition as Landau resonance, but instead involves wave electromagnetic fields rather than traditionally electrostatic fields. While this resonance, referred to as electromagnetic Landau resonance due to its properties, is considered significant for magnetospheric dynamics, rare reports or evaluations based on observations have been made thus far. Here, we present an event detected by the Magnetospheric Multiscale mission near the dayside magnetopause. During this event, ∼748‐eV protons are observed to be in resonance with a wave. Detailed data analysis demonstrates the resonant velocity closely matches the wave's parallel phase speed, which, combined with the significant work done by wave perpendicular electric field, confirms this interaction as electromagnetic Landau resonance. Further investigation indicates these protons are being secularly accelerated within this resonance. Consequently, our observations provide the first empirical evidence supporting the previously suggested theoretical importance of the electromagnetic Landau resonance.

A randomized, blind, parallel controlled phase I clinical trial to evaluate the safety and preliminary immunogenicity of 23-valent pneumococcal polysaccharide vaccine in healthy people aged 2 years and older

BackgroundDespite some progress in pneumococcal immunization, the global burden of pneumococcal infection remains high, and pneumococcal disease remains a public health concern. Studies in China and abroad have found that 23-valent pneumococcal polysaccharide vaccine (PPV23) vaccination can effectively prevent invasive pneumococcal disease. This phase Ⅰ clinical study assessed the safety and immunogenicity of a PPV23 vaccine candidate. MethodsAll subjects were randomly assigned to receive one dose intramuscular injection of experimental vaccine or control vaccine at a ratio of 1:1. The incidence of any adverse events was observed within 30 min, 0–7 days and 8–28 days post vaccination and the incidence of abnormal blood biochemical and blood routine indicators were tested on the 4th day post vaccination, the incidence of serious adverse events (SAEs) at 6 months post vaccination was recorded. Blood samples were collected prior to vaccination and on the 28th day post vaccination, and serum antibodies were detected by enzyme linked immunosorbent assay (ELISA). ResultsThe most common adverse reaction was pain at the injection site, followed by erythema. There was no significant difference of the incidence of systemic adverse reactions between the two vaccine groups. The adverse reactions observed in the trial were all common vaccination-related reactions, and no serious adverse reactions were observed. Compared to pre-vaccination, the (geometric mean concentrations) GMCs of IgG (immunoglobulin G) specific antibody against each serotype were all increased in the experimental group and the control group, there were statistical differences in seroconversion rates of serotypes 4 and 20 between the two vaccine groups. ConclusionThis clinical study showed good safety of the PPV23 vaccine candidate produced by Ab&b Biotechnology Co., Ltd.JS had good safety after vaccination in people aged 2 years and older. At the same time, good immunogenicity was also demonstrated.

Investigation of Polylactic Acid Nanofibers as Enhanced Plant Growth Medium by Improved Melt-Blowing Method

An improved melt-blowing method have developed to manufacture the organic nonwoven nanofibers through our previous study. As a parallel phase, this study explores the potential of polylactic acid (PLA) nanofibers as a plant growth substrate, emphasizing the unique properties and performance when mixed with pellets. Preliminary experiments comparing different fiber materials, cultivated crops, and fiber diameters demonstrate the favorable characteristics of PLA, such as wettability and growth promotion. Comparative experiment with rockwool, a commonly used medium, shows that PLA nanofibers exhibit superior growth performance. On the other hand, a solidified PLA medium is produced and tested. Hydroponic tests using solidified medium configurations with varying fiber diameters and soil conditioners further confirm the benefits of PLA as a medium for plant growth. The findings suggest that PLA nanofibers have the potential to revolutionize cultivation practices, providing sustainable and environmentally friendly alternatives to traditional substrates.

CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results.

Chimeric antigen receptor (CAR) T cells targeting CD22 (CD22-CAR) provide a therapeutic option for patients with CD22+ malignancies with progression after CD19-directed therapies. Using on-site, automated, closed-loop manufacturing, we conducted parallel Phase 1b clinical trials investigating a humanized CD22-CAR with 41BB costimulatory domain in children and adults with heavily treated, relapsed/refractory (r/r) B-ALL. Of 19 patients enrolled, 18 had successful CD22-CAR manufacturing, and 16 patients were infused. High grade (3-4) cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS) each occurred in only one patient; however, three patients experienced immune-effector-cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Twelve of 16 patients (75%) achieved CR with an overall 56% MRD-negative CR rate. Duration of response was overall limited (median 77 days), and CD22 expression was downregulated in 4/12 (33%) available samples at relapse. In summary, we demonstrate that closed-loop manufacturing of CD22-CAR T cells is feasible and is associated with a favorable safety profile and high CR rates in pediatric and adult r/r B-ALL, a cohort with limited CD22-CAR reporting.

Comparative analysis of hippocampal extracellular space uncovers widely altered peptidome upon epileptic seizure in urethane-anaesthetized rats

BackgroundThe brain extracellular fluid (ECF), composed of secreted neurotransmitters, metabolites, peptides, and proteins, may reflect brain processes. Analysis of brain ECF may provide new potential markers for synaptic activity or brain damage and reveal additional information on pathological alterations. Epileptic seizure induction is an acute and harsh intervention in brain functions, and it can activate extra- and intracellular proteases, which implies an altered brain secretome. Thus, we applied a 4-aminopyridine (4-AP) epilepsy model to study the hippocampal ECF peptidome alterations upon treatment in rats.MethodsWe performed in vivo microdialysis in the hippocampus for 3–3 h of control and 4-AP treatment phase in parallel with electrophysiology measurement. Then, we analyzed the microdialysate peptidome of control and treated samples from the same subject by liquid chromatography-coupled tandem mass spectrometry. We analyzed electrophysiological and peptidomic alterations upon epileptic seizure induction by two-tailed, paired t-test.ResultsWe detected 2540 peptides in microdialysate samples by mass spectrometry analysis; and 866 peptides—derived from 229 proteins—were found in more than half of the samples. In addition, the abundance of 322 peptides significantly altered upon epileptic seizure induction. Several proteins of significantly altered peptides are neuropeptides (Chgb) or have synapse- or brain-related functions such as the regulation of synaptic vesicle cycle (Atp6v1a, Napa), astrocyte morphology (Vim), and glutamate homeostasis (Slc3a2).ConclusionsWe have detected several consequences of epileptic seizures at the peptidomic level, as altered peptide abundances of proteins that regulate epilepsy-related cellular processes. Thus, our results indicate that analyzing brain ECF by in vivo microdialysis and omics techniques is useful for monitoring brain processes, and it can be an alternative method in the discovery and analysis of CNS disease markers besides peripheral fluid analysis.

Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies

ObjectivesBimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial...

Abstract IA006: Multifaceted effects of DNA damage response inhibitors on radiation responses of glioblastoma and the normal brain

Abstract PARP inhibitors (PARPi) and ATM inhibitors (ATMi) enhance radiation sensitivity in multiple cancer models, both in vitro and in vivo. Our observation that the radiosensitizing properties of PARPi are most pronounced in rapidly proliferating cells is reflected in early phase clinical trial data showing exacerbation of acute radiation toxicity in rapidly proliferating tissues such as oropharyngeal and esophageal mucosa. Lack of radiosensitization in late responding, slowly proliferating normal tissues indicates that PARPi may be more effectively combined with radiation therapy (RT) in patients with brain tumors. ATMi are much more potent radiosensitizers than PARPi but less is known about their impact on normal tissue toxicity since they have only recently progressed to the clinic, although preclinical in vivo data are encouraging. We are evaluating the oral PARPi olaparib and the oral ATMi AZD1390 in combination with RT +/- temozolomide (TMZ) in the treatment of glioblastoma (GBM), the most prevalent and most aggressive primary brain tumor. Patients with GBM experience very poor outcomes in terms of both median survival (c.1 year) and neurocognitive decline, which is caused primarily by RT. Early phase testing of the olaparib-RT combination is underway in three populations of patients with newly diagnosed GBM. Patients aged &amp;gt;65 with MGMT unmethylated GBM are being recruited to a randomized, placebo-controlled phase II study (PARADIGM, ISRCTN52658296) after a phase I dose escalation study showed that olaparib (200 mg twice daily) was extremely well tolerated when combined with brain irradiation (40 Gray in 15#). Good performance status patients aged under 70 are being recruited to PARADIGM-2 (ISRCTN51253312) which comprises two parallel phase I dose escalation studies: patients with MGMT unmethylated tumors are receiving daily olaparib with RT (60 Gy in 30#) without TMZ, while patients with MGMT methylated tumors are receiving intermittent olaparib with standard chemoradiation. AZD1390 is being evaluated in a first-in-human phase I dose escalation study (NCT03423628) in combination with re-irradiation (35 Gy in 10#) in patients with recurrent GBM, and with first-line radical radiotherapy (60 Gy in 30#) in patients with newly diagnosed, MGMT unmethylated GBM. In parallel, we are undertaking preclinical studies to investigate the impact of PARPi and ATMi on RT induced neurotoxicity. In vivo imaging studies support the emerging concept that RT induced neuroinflammation is important in the pathogenesis of neurotoxicity, and we have generated preliminary behavioral data indicating that both PARPi and ATMi can alleviate the neurotoxic effects of RT. Ongoing experiments are defining the roles of microglia, astrocytes and neurogenesis in this phenomenon. We will present these diverse datasets in the context of our hypothesis that combining PARPi or ATMi with RT has potential to improve outcomes for GBM patients by enhancing tumor control while simultaneously suppressing neuroinflammation and alleviating RT related neurocognitive decline. Citation Format: Anthony J. Chalmers. Multifaceted effects of DNA damage response inhibitors on radiation responses of glioblastoma and the normal brain [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr IA006.

Constructal design of a rectangular parallel phase change microchannel in a three-dimensional electronic device

Constructal design of a rectangular parallel phase change microchannel in a three-dimensional electronic device