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Per Food and Drug Administration (FDA) regulation, pembrolizumab can be administered as a 200mg dose every 3 weeks (Q3W) or as a 400mg dose every 6 weeks (Q6W) for various cancers. Little to no literature exists on time toxicity and transportation-related out-of-pocket expenditure for patients when considering the frequency of pembrolizumab infusions. We aimed to model differences in time toxicity and transportation costs between the status quo and institutionalized transitions to Q6W infusions for patients receiving care at United States (US) Veteran's Affairs (VA) hospitals using a simulation-based approach. Data was extracted from VA medical records of patients who received pembrolizumab infusions with or without chemotherapy or a tyrosine kinase inhibitor (TKI). Extracted data included driving distance from patient residence to the hospital, driving duration, type of infusion (pembrolizumab ± chemotherapy ± TKI), location of infusion site, and infusion dates. Distance and time data was extrapolated into scenarios defined by 1) pembrolizumab ± chemotherapy ± TKI transitioning to Q6W, i.e. "universal Q6W infusions" and 2) pembrolizumab-only infusions transitioning to Q6W, i.e. "monotherapy Q6W infusions." Gasoline expenditure was calculated as a multiplied product of patient driving distance, location-specific, monthly average gasoline price data from 2003 to 2023 and average light-duty US car fuel efficiency data published by US government agencies. Time toxicity was calculated as the sum of cumulative and per-infusion driving durations with published estimates of pembrolizumab infusion duration and associated duration of patient visits in the Q3W and Q6W setting. 7891 patients spanning 102 VA hospitals underwent treatment with pembrolizumab, comprising a total of 58639 infusions. Each hospital treated, on average, 77 (± 55) patients and delivered an average of 575 (± 421) infusions. Compared to the status quo, the mean total driving time for a complete treatment course was 71.4 minutes less per patient with a transition to universal Q6W infusions and 70.1 minutes less per patient with a transition to monotherapy Q6W infusions. Compared to the status quo, transitioning to universal and monotherapy Q6W infusions saved an average of 9.09 USD and 8.96 USD per patient respectively in gasoline costs for an entire treatment course. Additionally, transitioning to universal and monotherapy Q6W infusions saved an average of 361 minutes and 332 minutes per patient respectively for a complete treatment course. Our models show that transitioning from Q3W to Q6W infusions of pembrolizumab ± chemotherapy ± TKI lowers both transportation-related costs and time toxicity in VA patients. As such, Q6W infusions may represent a more cost-effective means of treatment delivery if deemed clinically appropriate. [ABSTRACT FROM AUTHOR]

We report on the electrical, ferroelectric, and magnetic properties of BiFeO3 (BFO)-La0.7Sr0.3MnO3 heterostructures deposited epitaxially onto Si(100) substrates. Temperature dependent (200-350 K) current-voltage (I-V), switching spectroscopy piezo-response force microscopy (SSPFM), and temperature dependent (5-300 K) anisotropic magnetization measurements have been performed. The BFO (100-nm thick)-based device structures were fabricated with a 250nm thick La0.7Sr0.3MnO3 bottom electrode and 200 lm circular top Pt electrodes. I-V measurements performed at various temperatures indicated that the devices retained their as-deposited characteristics and exhibited non-leaky behavior up to at least 50 cycles. The temperature-dependent measurements showed clear diode-like behavior and resistive (hysteretic) switching behaviour. Characteristic butterfly loops (of several cycles) were observed in the PFM amplitude signals of the BFofilm. In addition, the phase signal indicated a clear (180°) switching behavior at the switching voltage of 4-5V, providing unambiguous evidence for the occurrence of ferroelectricity in BFofilms integrated on Si (100). The temperature- and angledependent zerofield cooled isothermal (5 K) magnetization measurements were consistent with the presence of uniaxial magnetic anisotropy. This work makes an important step for the fabrication of CMOS-compatible BFO devices for memory applications. [ABSTRACT FROM AUTHOR]

Abstract The nervous system of the Asteroidea (starfish or seastar) consists of radial nerve cords (RNCs) that interconnect with a ring nerve. Despite its relative simplicity, it facilitates the movement of multiple arms and numerous tube feet, as well as regeneration of damaged limbs. Here, we investigated the RNC ultrastructure and its molecular components within the of Pacific crown-of-thorns starfish (COTS; Acanthaster sp.), a well-known coral predator that in high-density outbreaks has major ecological impacts on coral reefs. We describe the presence of an array of unique small bulbous bulbs (40–100 μm diameter) that project from the ectoneural region of the adult RNC. Each comprise large secretory-like cells and prominent cilia. In contrast, juvenile COTS and its congener Acanthaster brevispinus lack these features, both of which are non-corallivorous. Proteomic analysis of the RNC (and isolated neural bulbs) provides the first comprehensive echinoderm protein database for neural tissue, including numerous secreted proteins associated with signalling, transport and defence. The neural bulbs contained several neuropeptides (e.g., bombyxin-type, starfish myorelaxant peptide, secretogranin 7B2-like, Ap15a-like, and ApNp35) and Deleted in Malignant Brain Tumor 1-like proteins. In summary, this study provides a new insight into the novel traits of COTS, a major pest on coral reefs, and a proteomics resource that can be used to develop (bio)control strategies and understand molecular mechanisms of regeneration.

We report the formation of NiO based single crystalline p-n junctions with enhanced photocatalytic activity induced by pulsed laser irradiation. The NiO epilayers were grown on Si(001) substrates buffered with cubic yttria-stabilized zirconia (c-YSZ) by using pulsed laser deposition. The NiO/c-YSZ/Si heterostructures were subsequently laser treated by 5 pulses of KrF excimer laser (pulse duration = 25 × 10-9 s) at lower energies. Microstructural studies, conducted by X-ray diffraction (θ-2θ and φ techniques) and high resolution transmission electron microscope, showed a cube-on-cube epitaxial relationship at the c-YSZ/Si interface; the epitaxial relationship across the NiO/c-YSZ interface was established as NiO<111 >||c-YSZ<001> and in-plane NiO<110>||c-YSZ<100>. Electron microscopy studies showed that the interface between the laser annealed and the pristine region as well as the NiO/c-YSZ interface was atomically sharp and crystallographically continuous. The formation of point defects, namely oxygen vacancies and NiO, due to the coupling of the laser photons with the NiO epilayers was confirmed by XPS. The p-type electrical characteristics of the pristine NiO epilayers turned to an n-type behavior and the electrical conductivity was increased by one order of magnitude after laser treatment. Photocatalytic activity of the pristine (p-NiO/c-YSZ/Si) and the laser-annealed (n-NiO/p-NiO/c-YSZ/Si) heterostructures were assessed by measuring the decomposition rate of 4-chlorophenol under UV light. The photocatalytic reaction rate constants were determined to be 0.0059 and 0.0092 min-1 for the as-deposited and the laser-treated samples, respectively. The enhanced photocatalytic efficiency was attributed to the suppressed charge carrier recombination in the NiO based p-n junctions and higher electrical conductivity. Besides, the oxygen vacancies ease the adsorption of 4-chlorophenol, hydroxyl, and water molecules to the surface. Thus, n-NiO/p-NiO single crystalline catalysts can be introduced as a potent candidate to remediate the environmental pollution. [ABSTRACT FROM AUTHOR]

Some promoters, termed Epromoters, can display enhancer activity and regulate distal genes in their endogenous context. Here the authors report the broad involvement of Epromoters in the coordinated activation of interferon (IFN) response. They show activation of a number of IFN-inducible genes is a result of Epromoters regulating expression of an entire IFN response gene cluster.

Ascidians accumulate extremely high levels of vanadium (V) in their blood cells. Several V-related proteins, including V-binding proteins (vanabins), have been isolated from V-accumulating ascidians. In this study, to obtain a deeper understanding of vanabins, we performed de novo transcriptome analysis of blood cells from a V-rich ascidian, Ascidia sydneiensis samea, and constructed a database containing 8532 predicted proteins. We found a novel vanabin with a unique acidic amino acid–rich C-terminal domain, designated VanabinX, in the database and studied it in detail. Reverse-transcription polymerase chain reaction analysis revealed that VanabinX was detected in all adult tissues examined, and was most prominent in blood cells and muscle tissue. We prepared recombinant proteins and performed immobilized metal ion affinity chromatography and a NADPH-coupled V(V)-reductase assay. VanabinX bound to metal ions, with increasing affinity for Cu(II) > Zn(II) > Co(II), but not to V(IV). VanabinX reduced V(V) to V(IV) at a rate of 0.170 μM per micoromolar protein within 30 min. The C-terminal acidic domain enhanced the reduction of V(V) by Vanabin2 to 1.3-fold and of VanabinX itself to 1.7-fold in trans mode. In summary, we constructed a protein database containing 8532 predicted proteins expressed in blood cells; among them, we discovered a novel vanabin, VanabinX, which enhances V reduction by vanabins.

All the currently used type A botulinum neurotoxins for clinical uses are of subtype A1. We compared the efficacy and safety for the first time head-to-head between a novel botulinum toxin A2NTX prepared from subtype A2 and onabotulinumtoxinA (BOTOX) derived from A1 for post-stroke spasticity. We assessed the modified Ashworth scale (MAS) of the ankle joint, the mobility scores of Functional Independence Measure (FIM), and the grip power of the unaffected hand before and after injecting 300 units of BOTOX or A2NTX into calf muscles. The procedure was done in a blinded manner for the patient, the injecting physician, and the examiner. Stroke patients with chronic spastic hemiparesis (15 for A2NTX and 16 for BOTOX) were enrolled, and 11 for A2NTX and 13 for BOTOX (MAS of ankle; > or = 2) were entered for the MAS study. Area-under-curves of changes in MAS (primary outcome) were greater for A2NTX by day 30 (p = 0.044), and were similar by day 60. FIM was significantly improved in the A2NTX group (p = 0.005), but not in the BOTOX group by day 60. The hand grip of the unaffected limb was significantly decreased in the BOTOX-injected group (p = 0.002), but was unaffected in the A2NTX-injected group by day 60, suggesting there was less spread of A2NTX to the upper limb than there was with BOTOX. Being a small-sized pilot investigation with an imbalance in the gender of the subjects, the present study suggested superior efficacy and safety of A2NTX, and warrants a larger scale clinical trial of A2NTX to confirm these preliminary results.