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The green algal genus Picochlorum is of biotechnological interest because of its robust response to multiple environmental stresses. We compared the metabolic performance of P. SE3 and P. oklahomense to diverse microbial phototrophs and observed exceptional performance of photosystem II (PSII) in light energy conversion in both Picochlorum species. The quantum yield (QY) for O 2 evolution is the highest of any phototroph yet observed, 32% (20%) by P. SE3 (P. okl) when normalized to total PSII subunit PsbA (D1) protein, and 80% (75%) normalized per active PSII, respectively. Three factors contribute: (1) an efficient water oxidizing complex (WOC) with the fewest photochemical misses of any organism; (2) faster reoxidation of reduced (PQH 2 ) B in P. SE3 than in P. okl. (period-2 Fourier amplitude); and (3) rapid reoxidation of the plastoquinol pool by downstream electron carriers (Cyt b 6 f/PETC) that regenerates PQ faster in P. SE3. This performance gain is achieved without significant residue changes around the Q B site and thus points to a pull mechanism involving faster PQH 2 reoxidation by Cyt b 6 f/PETC that offsets charge recombination. This high flux in P. SE3 may be explained by genomically encoded plastoquinol terminal oxidases 1 and 2, whereas P. oklahomense has neither. Our results suggest two distinct types of PSII centers exist, one specializing in linear electron flow and the other in PSII-cyclic electron flow. Several amino acids within D1 differ from those in the low-light-descended D1 sequences conserved in Viridiplantae, and more closely match those in cyanobacterial high-light D1 isoforms, including changes near tyrosine Y z and a water/proton channel near the WOC. These residue changes may contribute to the exceptional performance of Picochlorum at high-light intensities by increasing the water oxidation efficiency and the electron/proton flux through the PSII acceptors (Q A Q B )., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Small cell lung cancer (SCLC) is an aggressive form of neuroendocrine neoplasm known for its striking initial response to treatment, followed by fast relapse and refractoriness in response to additional lines of therapy. New advances in immunotherapy are paving the way for more effective treatment strategies and have promising results with early clinical trial data. While SCLC rarely harbors actionable mutations, the receptor DLL3 is extensively present in SCLC, making it a potential target for immunotherapy. Three emerging therapeutic options include bispecific T cell engagers targeting DLL3, chimeric antigen receptor T cells (CAR-T cells), and antibody-drug conjugates. Several phase II and phase III clinical trials for bispecific T cell engagers show promise. Additionally, the first CAR-T cell trials in humans for SCLC are currently underway., Competing Interests: Competing interests: ZH and RM are clinical investigators on study NCT05680922., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

The association between Medically Assisted Reproduction (MAR) and thromboembolic complications has been reported widely in multiple published studies. Although venous thromboembolism (VTE) is not thought to be a common complication of MAR, it is associated with high morbidity and is often preventable. Since VTE usually occurs after completion of MAR treatment and is often managed outside of the treating fertility unit, these complications are likely to be underreported and there may be limited awareness of the risks among clinicians. As we continue to see a rise in the total number of MAR treatment cycles, particularly in women over 40 years of age, along with a steady increase in the number of fertility preservation cycles for both medical and social indications, it is likely that we will see an increase in absolute numbers of VTE complications. Currently, there is a lack of management guidance and reporting of VTE events associated with assisted conception treatment. The aim of this guidance is to provide clinicians with information on VTE risk factors, guidance on assessing VTE risk and the best practice recommendations on risk reducing strategies for individuals at risk of VTE undergoing ovarian stimulation and embryo transfer cycles.

Much of the literature on insider threat assumes, explicitly or implicitly, a binary, perimeter-based notion of an insider. However, it is generally accepted that this notion is unrealistic. The Attribute-Based Group Access Control (ABGAC) framework is a generalization of Role-Based Access Control (RBAC) which allows us to define a non-binary notion of "insiderness". In this paper, we illustrate how to use AB-GAC to perform insider threat analysis of high-risk resources with three case studies. This precise yet flexible identification of high-risk resources and associated insiders allows organizations to understand where to target efforts towards defending against the insider problem. © 2009 IEEE.

Abstract: In newly diagnosed transplant-ineligible patients with myeloma, daratumumab has improved outcomes when added to the standard-of-care regimens. In a randomized trial, we tested whether similar improvements would be observed when daratumumab was added to the bortezomib, cyclophosphamide, and dexamethasone (VCD) regimen. Transplant-ineligible patients with untreated myeloma were randomized to receive VCD or VCD plus daratumumab (VCDD). A total of 121 patients were randomized: 57 in the VCD arm and 64 in the VCDD arm. Baseline characteristics were balanced between the 2 arms. The median progression-free survival (PFS) was 16.8 months (95% confidence interval [CI], 15.3-21.7) and 25.8 months (95% CI, 19.9-33.5) in the VCD and VCDD arms, respectively (hazard ratio, 0.67; log-rank test P = .066). In a preplanned analysis, it was demonstrated that the daratumumab-containing arm showed a significant improvement in PFS from 18 months onward, based on estimates at fixed time points after randomization. The proportions of patients who were progression-free at the following time points were: 18 months, 48% vs 68% (P = .0002); 24 months, 36% vs 52% (P = .0001); and 30 months, 27% vs 41% (P < .0001) in the VCD and VCDD arms, respectively. The best overall response and very good partial response rate were significantly higher in the daratumumab arm compared with the VCD and VCDD arms, respectively (65% vs 86%, P = .007; and 28% vs 52%, P = .009). Seventy-two percent of the VCDD patients completed the 9 cycles of induction therapy with no grade 3 or 4 peripheral neuropathy adverse events. This study supports VCDD as an option for the initial treatment of transplant-ineligible patients with myeloma. This trial was registered at the Australian New Zealand Clinical Trials Registry (ACTRN12617000202369)., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Primary human airway epithelial cells demonstrate altered rhythmic gene expression in cytokine-related pathways in asthma with intact core circadian gene expression https://bit.ly/3v9lOC6., Competing Interests: Conflicts of interest: All authors declare no conflicts of interest., (Copyright ©The authors 2024.)

Absorption spectroscopy probing transitions from shallow-core d and f orbitals in lanthanides and actinides reveals information about bonding and the electronic structure in compounds containing these elements. However, spectroscopy in this photon energy range is challenging because of the limited availability of light sources and extremely short penetration depths. In this work, we address these challenges using a tabletop extreme ultraviolet (XUV), ultrafast, laser-driven, high harmonic generation light source, which generates femtosecond pulses in the 40-140 eV range. We present reflection spectroscopy measurements at the N 4,5 (i.e., predominantly 4d to 5f transitions) and O 4,5 (i.e., 5d to 5f transitions) absorption edges on several lanthanide and uranium oxide crystals. We compare these results to density functional theory calculations to assign the electronic transitions and predict the spectra for other lanthanides. This work paves the way for laboratory-scale XUV absorption experiments for studying crystalline and molecular f-electron systems, with applications ranging from surface chemistry, photochemistry, and electronic or chemical structure determination to nuclear forensics.

Background: Mesenchymal stem cells (MSCs) have alluring interest for clinical use in orthopaedics based on their therapeutic potential through directed pluripotent differentiation. While many studies and reviews have discussed the importance of this approach, few have reduced it to practice using reproducible criteria. This study was designed to systematically review and synthesize current evidence regarding clinical use of clearly defined MSCs in orthopaedics., Methods: Studies of any level of evidence and sample size, regardless of MSC source, orthopaedic pathology, and patient population, were reviewed. In vitro and animal studies, and articles written in a language other than English, were excluded. Studies were then screened for final inclusion based on documented MSC verification using testing of the therapeutic cellular population for at least one of the following phenotypic markers: CD 73, CD 90, and CD 105. In addition, therapeutic cellular populations could not have higher percentages of CD34, CD45, CD14, HLA-DR, CD11b, or CD19 markers compared to the aforementioned markers. From each studies' results, sample size, procedural methods, radiographic outcomes, clinical outcomes, patient-report outcomes (PROs), and adverse events were tabulated., Results: Overall, 43 studies were included. Twenty-three studies (53.5 %) derived their MSCs from iliac crest bone marrow while 12 (27.9 %) studied adipose-derived MSCs. Included studies explored MSC use in Osteoarthritis, Cartilage Defects, Osteonecrosis, Bone Defects and Nonunions, Spine, and Other. MSC use in all pathologies led to improvement of studied radiographic, clinical, and patient-reported outcomes., Conclusions: Mesenchymal stem cells have proven to have successful and safe uses in multiple orthopaedic applications, including treating chondral defects, osteoarthritis, and osteonecrosis. A stringent and reproducible process for evaluating obtained human stem cells using CD markers for clinical use is necessary to both evaluate previous studies and continue to evaluate for future uses., Level of Evidence: Level V., Competing Interests: None., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.0/3.0-4.0, respectively), has well-recognized limitations. Direct oral anticoagulants have several advantages over warfarin, and the potential role of high-dose direct oral anticoagulants vs high-intensity warfarin in this setting merits investigation., Objectives: The Rivaroxaban for Stroke patients with APS trial (RISAPS) seeks to determine whether high-dose rivaroxaban could represent a safe and effective alternative to high-intensity warfarin in adult patients with APS and previous ischemic stroke, transient ischemic attack, or other ischemic brain manifestations., Methods: This phase IIb prospective, randomized, controlled, noninferiority, open-label, proof-of-principle trial compares rivaroxaban 15 mg twice daily vs warfarin, target INR range 3.0-4.0. The sample size target is 40 participants. Triple antiphospholipid antibody-positive patients are excluded. The primary efficacy outcome is the rate of change in brain white matter hyperintensity volume on magnetic resonance imaging, a surrogate marker of presumed ischemic damage, between baseline and 24 months follow-up. Secondary outcomes include additional neuroradiological and clinical measures of efficacy and safety. Exploratory outcomes include high-dose rivaroxaban pharmacokinetic modeling., Conclusion: Should RISAPS demonstrate noninferior efficacy and safety of high-dose rivaroxaban in this APS subgroup, it could justify larger prospective randomized controlled trials., (© 2024 The Author(s).)

U(VI) peroxide phases (studtite and meta-studtite) are found throughout the nuclear fuel cycle and exist as corrosion products in high radiation fields. Peroxides are part of a family of reactive oxygen species (ROS) that include hydroperoxyl and superoxide species and are produced during alpha radiolysis of water. While U(VI) peroxides have been thoroughly investigated, the incorporation and stability of ROS species within studtite have not been validated. In the current study, electron paramagnetic resonance (EPR) spectroscopy was used to identify the presence of free radicals within a series of U(VI) peroxide samples containing depleted, highly enriched, and natural uranium. Density functional theory calculations indicated that the predicted EPR signals matched well with a superoxide (O 2 - ⋅) species incorporated into the studtite structure, confirming the presence of ROS in the material. Further analysis of samples that were synthesized between 1945 and 2023 indicated that there is a correlation between the radical signal and the product of specific activity multiplied by age of the sample., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Ultrapurified Photosystem II complexes crystalize as uniform microcrystals (PSIIX) of unprecedented homogeneity that allow observation of details previously unachievable, including the longest sustained oscillations of flash-induced O 2 yield over > 200 flashes and a novel period-4.7 water oxidation cycle. We provide new evidence for a molecular-based mechanism for PSII-cyclic electron flow that accounts for switching from linear to cyclic electron flow within PSII as the downstream PQ/PQH 2 pool reduces in response to metabolic needs and environmental input. The model is supported by flash oximetry of PSIIX as the LEF/CEF switch occurs, Fourier analysis of O 2 flash yields, and Joliot-Kok modeling. The LEF/CEF switch rebalances the ratio of reductant energy (PQH 2 ) to proton gradient energy (H + o /H + i ) created by PSII photochemistry. Central to this model is the requirement for a regulatory site (Q C ) with two redox states in equilibrium with the dissociable secondary electron carrier site Q B . Both sites are controlled by electrons and protons. Our evidence fits historical LEF models wherein light-driven water oxidation delivers electrons (from Q A - ) and stromal protons through Q B to generate plastoquinol, the terminal product of PSII-LEF in vivo. The new insight is the essential regulatory role of Q C . This site senses both the proton gradient (H + o /H + i ) and the PQ pool redox poise via e - /H + equilibration with Q B . This information directs switching to CEF upon population of the protonated semiquinone in the Qc site (Q - H + ) C , while the WOC is in the reducible S2 or S3 states. Subsequent photochemical primary charge separation (P + Q A - ) forms no (QH 2 ) B , but instead undergoes two-electron backward transition in which the Q C protons are pumped into the lumen, while the electrons return to the WOC forming (S1/S2). PSII-CEF enables production of additional ATP needed to power cellular processes including the terminal carboxylation reaction and in some cases PSI-dependent CEF., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Retinal diseases like diabetic retinopathy and age-related macular degeneration affect millions of individuals worldwide and often lead to vision loss. Vitreous fluid abuts the retina, is accessible for sampling, and contains many proteins related to retinal disease. Therefore, analysis of vitreous is an important tool for studying retinal disease. Because it is rich in proteins and extracellular vesicles, mass spectrometry-based proteomics is an excellent method for vitreous analysis. Here, we discuss important variables to consider when performing vitreous proteomics via mass spectrometry., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G&#95;{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G&#95;{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Purpose: To evaluate the impact of an evidence-based standardized bedside report within a pediatric ambulatory surgery center on length of handoff time, registered nurse (RN) workflow, and patient and family satisfaction., Design: Quality improvement project using an evidence-based standardized bedside report intervention with pre- and postimplementation evaluation of process and outcome measures., Methods: In January 2019, a unit-based task force evaluated ways to improve current report process and consistency of communication between staff and families. Time from admit into Phase II until nursing handoff was measured pre- and postimplementation. Nursing workflow was measured by time to first RN assessment after admit to Phase II and the postimplementation nursing survey. Patient and family satisfaction were measured pre- and postimplementation from National Research Council Health., Findings: Postimplementation, average handoff times decreased by 30%; average time from admit to the Phase II unit until the nursing handoff decreased by 28%. From the postimplementation RN survey, 100% RNs: (1) felt standardized bedside report had a positive impact on their workflow, (2) expressed confidence in giving and receiving reports, and (3) reported they had critical information to safely care for patients. Overall patient satisfaction was measured by How likely would you be to recommend this facility to your family and friends; 11.6% improvement over baseline scores was reported. Improved percentages of score improvement from baseline included: nurses explained things (4.42%), nurses listened carefully (4.3%), patient and family received consistent information (2.46%), care providers explained things (2.22%), and patient and family trusted nurses with care (1.74%)., Conclusions: Implementation of standardized bedside report resulted in (1) more expeditious times to handoff and first RN assessment, (2) overall positive impact on nursing workflow, and (3) improvements in patient and family satisfaction., (Published by Elsevier Inc.)

Many sexual health programs transitioned to virtual implementation during the COVID-19 pandemic. Despite its devastation, the pandemic provided an opportunity to learn about virtual compared to in-person implementation of a sexual health promotion program-El Camino. This study assessed differences in program attendance, engagement, quality, and student ratings for virtual versus in-person implementation of El Camino as part of a rigorous evaluation in high schools with high Latino populations in Maryland. Drawing on positive youth development practices, El Camino helps participants identify personal goals and learn about sexual reproductive health and healthy relationships. This mixed-methods study incorporates data from performance measures, baseline and post-intervention participant surveys, observations, monthly implementation reports, and debriefs with facilitators to describe and compare virtual and in-person program implementation. At baseline, participants were an average of 16.2 years old; between 8 and 12 th grade; 61% female; 79% Hispanic, Latino, or of Spanish origin; and 54% spoke mostly Spanish at home. Recruitment and retention of students outside of school classes were challenging for both forms of implementation. However, attendance was higher during in-person implementation and in schools where the organization implementing El Camino had a strong presence before the pandemic. Findings indicate high fidelity, excellent quality ratings, and positive student perceptions of the program and facilitators in both the virtual and in-person cohorts, which suggest that both forms of implementation were comparable and furthermore highlight the strength of the virtual adaptation of the El Camino program., (© 2023. The Author(s).)

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Despite the availability of multiple screening options, CRC screening is underutilized. We conducted a survey of patients (n = 2973) who were prescribed the multi-target stool DNA (mt-sDNA) screening test (commercialized as Cologuard ® and manufactured by Exact Sciences Corporation) to understand attitudes and experiences that influence test completion and likelihood of future test completion. Using exploratory factor analyses, we developed three scales: Perceived Effectiveness, Perceived Ease of Use, and Perceived Comfort., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Chloride (Cl - ) is essential for O 2 evolution during photosynthetic water oxidation. Two chlorides near the water-oxidizing complex (WOC) in Photosystem II (PSII) structures from Thermosynechococcus elongatus (and T. vulcanus) have been postulated to transfer protons generated from water oxidation. We monitored four criteria: primary charge separation flash yield (P* → P + Q A - ), rates of water oxidation steps (S-states), rate of proton evolution, and flash O 2 yield oscillations by measuring chlorophyll variable fluorescence (P* quenching), pH-sensitive dye changes, and oximetry. Br-substitution slows and destabilizes cellular growth, resulting from lower light-saturated O 2 evolution rate (-20 %) and proton release (-36 % ΔpH gradient). The latter implies less ATP production. In Br- cultures, protonogenic S-state transitions (S 2  → S 3  → S 0 ') slow with increasing light intensity and during O 2 /water exchange (S 0 ' → S 0  → S 1 ), while the non-protonogenic S 1  → S 2 transition is kinetically unaffected. As flash rate increases in Cl - cultures, both rate and extent of acidification of the lumen increase, while charge recombination is suppressed relative to Br - . The Cl - advantage in rapid proton escape from the WOC to lumen is attributed to correlated ion-pair movement of H 3 O + Cl - in dry water channels vs. separated Br - and H + ion movement through different regions (>200-fold difference in Bronsted acidities). By contrast, at low flash rates a previously unreported reversal occurs that favors Br - cultures for both proton evolution and less PSII charge recombination. In Br - cultures, slower proton transfer rate is attributed to stronger ion-pairing of Br - with AA residues lining the water channels. Both anions charge-neutralize protons and shepherd them to the lumen using dry aqueous channels., Competing Interests: Declaration of competing interest G. Charles Dismukes reports financial support was provided by US Department of Energy. G. Charles Dismukes reports financial support was provided by National Science Foundation., (Copyright © 2023. Published by Elsevier B.V.)