Durable Effects Research Articles

Absorption, Metabolism, and Excretion of [14C]-Tolebrutinib After Oral Administration in Humans, Contribution of the Metabolites to Pharmacological Activity.

Tolebrutinib is a covalent inhibitor of Bruton's tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are thought to be major drivers of inflammation in multiple sclerosis. This excretion balance and metabolism study evaluated the metabolite profile of tolebrutinib in healthy male volunteers. Six healthy volunteers received a 60-mg oral dose of [14C]-tolebrutinib, and metabolite profiling of 14C-labeled metabolites was performed using a combination of liquid chromatography, mass spectrometry, and radioactivity assay methods. Tolebrutinib was rapidly and completely absorbed from the gastrointestinal tract, followed by rapid and extensive metabolism. Excretion via feces was the major elimination pathway of the administered radioactivity (78%). Tolebrutinib was highly metabolized, with 19 metabolites identified in human plasma. Phase 1 biotransformations were primarily responsible for the circulating metabolites in plasma. Seven metabolites that achieved exposure in plasma similar to or higher than the parent compound were characterized biochemically for inhibition of Bruton's tyrosine kinase activity. Metabolite M8 exceeded the exposure threshold of 10% (18%) of the total radioactivity but had little if any pharmacological activity. Metabolite M2 (4% of circulating radioactivity) retained the ability to irreversibly and potently inhibit Bruton's tyrosine kinase in vitro, similar to the parent compound. Tolebrutinib and metabolite M2 had short (3.5-h) half-lives but durable pharmacodynamic effects as expected for an irreversible antagonist. Tolebrutinib was extensively metabolized to multiple metabolites. The hydroxylated metabolite M2 demonstrated similar inhibitory potency toward Bruton's tyrosine kinase as the parent compound. Both tolebrutinib and metabolite M2 likely contributed to pharmacological activity in vivo.

Modelling monetary policy’s impact on labour markets under Covid-19

This paper investigates the effectiveness of monetary policy on macroeconomic and labour market variables in the US, taking into account the impact of the Covid-19 pandemic. Using a medium scale Bayesian VAR that explicitly incorporates the exceptionally large shocks during the pandemic, we find that expansionary monetary policy has more pronounced and durable effects on labour market variables, in comparison to a non-pandemic setup for the same sample. Additionally, our analysis suggests that a non-pandemic setup, would result in rises in income inequality. In contrast, our proposed setup predicts a significant reduction in income inequality due to an increase in the income share of the bottom 50%.

Open-label study of consecutive ibogaine and 5-MeO-DMT assisted-therapy for trauma-exposed male Special Operations Forces Veterans: prospective data from a clinical program in Mexico

ABSTRACT Background: Research in psychedelic medicine has focused primarily on civilian populations. Further study is needed to understand whether these treatments are effective for Veteran populations. Objectives: Here, we examine the effectiveness of psychedelic-assisted therapy among trauma-exposed Special Operations Forces Veterans (SOFV) seeking treatment for cognitive and mental health problems in Mexico. Methods: Data were collected from an ibogaine and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) clinical treatment program for SOFV with a history of trauma exposure. This clinical program collects prospective clinical program evaluation data, such as background characteristics, symptom severity, functioning (e.g., satisfaction with life, posttraumatic stress disorder symptoms, depression symptoms, anxiety symptoms, sleep disturbance, psychological flexibility, disability in functioning, cognitive functioning, neurobehavioral symptoms, anger, suicidal ideation), and substance persisting/enduring effects through online surveys at four timepoints (baseline/pre-treatment, one-, three-, and six-months after treatment). Results: The majority of the sample (n = 86; Mean Age = 42.88, SD = 7.88) were Caucasian (87.2%), non-Hispanic (89.5%), and males (100%). There were significant and large improvements in self-reported PTSD symptoms (p < .001, d = .414), depression (p < .001, d = .275), anxiety (p < .001, d = .276), insomnia severity (p < .001, d = .351), and post-concussive symptoms (p < .001, d = .389) as well as self-reported satisfaction with life (p < .001, d = .371), psychological flexibility (p < .001, d = .313) and cognitive functioning (p < .001, d = .265) from baseline to one-month follow-up. Conclusions: Data suggest combined ibogaine and 5-MeO-DMT assisted therapy has potential to provide rapid and robust changes in mental health functioning with a signal of durable therapeutic effects up to 6-months. Future research in controlled settings is warranted.

Lipid-based nanoparticles for cancer immunotherapy.

As the fourth most important cancer management strategy except surgery, chemotherapy and radiotherapy, cancer immunotherapy has been confirmed to elicit durable antitumor effects in the clinic by leveraging the patient's own immune system to eradicate the cancer cells. However, the limited population of patients who benefit from the current immunotherapies and the immune related adverse events hinder its development. The immunosuppressive microenvironment is the main cause of the failure, which leads to cancer immune evasion and immunity cycle blockade. Encouragingly, nanotechnology has been engineered to enhance the efficacy and reduce off-target toxicity of their therapeutic cargos by spatiotemporally controlling the biodistribution and release kinetics. Among them, lipid-based nanoparticles are the first nanomedicines to make clinical translation, which are now established platforms for diverse areas. In this perspective, we discuss the available lipid-based nanoparticles in research and market here, then describe their application in cancer immunotherapy, with special emphasis on the T cells-activated and macrophages-targeted delivery system. Through perpetuating each step of cancer immunity cycle, lipid-based nanoparticles can reduce immunosuppression and promote drug delivery to trigger robust antitumor response.

Clinical Trials with Mesenchymal Stem Cell Therapies for Osteoarthritis: Challenges in the Regeneration of Articular Cartilage.

Osteoarthritis (OA) is a whole-joint disease primarily characterized by the deterioration of hyaline cartilage. Current treatments include microfracture and chondrocyte implantation as early surgical strategies that can be combined with scaffolds to repair osteochondral lesions; however, intra-articular (IA) injections or implantations of mesenchymal stem cells (MSCs) are new approaches that have presented encouraging therapeutic results in animal models and humans. We critically reviewed clinical trials with MSC therapies for OA, focusing on their effectiveness, quality, and outcomes in the regeneration of articular cartilage. Several sources of autologous or allogeneic MSCs were used in the clinical trials. Minor adverse events were generally reported, indicating that IA applications of MSCs are potentially safe. The evaluation of articular cartilage regeneration in human clinical trials is challenging, particularly in the inflammatory environment of osteoarthritic joints. Our findings indicate that IA injections of MSCs are efficacious in the treatment of OA and the regeneration of cartilage, but that they may be insufficient for the full repair of articular cartilage defects. The possible interference of clinical and quality variables in the outcomes suggests that robust clinical trials are still necessary for generating reliable evidence with which to support these treatments. We suggest that the administration of just-sufficient doses of viable cells in appropriate regimens is critical to achieve effective and durable effects. In terms of future perspectives, genetic modification, complex products with extracellular vesicles derived from MSCs, cell encapsulation in hydrogels, and 3D bioprinted tissue engineering are promising approaches with which to improve MSC therapies for OA.

BiTE secretion by adoptively transferred stem-like T cells improves FRα+ ovarian cancer control

BackgroundCancer immunotherapies can produce complete therapeutic responses, however, outcomes in ovarian cancer (OC) are modest. While adoptive T-cell transfer (ACT) has been evaluated in OC, durable effects are rare. Poor...

Handshake stewardship on adult acute-care surgical services

Background: Handshake stewardship is a variation of prospective audit and feedback that entails the individual review of patient charts by a physician–pharmacist collaborative team followed by in-person feedback to primary teams to communicate recommendations regarding optimal antibiotic use. Handshake stewardship has been shown to have durable effects in reducing antimicrobial use in children’s hospitals, but data regarding this intervention in adult hospitals are scarce. In particular, no data are available regarding the impact of this type of stewardship intervention on adult surgical units. We examined the effect of a handshake stewardship intervention at a large academic medical center on adult trauma and acute- and critical-care surgery (ACCS) units. Methods: The antimicrobial stewardship program (ASP) at Barnes-Jewish Hospital launched a handshake stewardship intervention targeting surgical floor teams in January 2022. These teams included the ACCS teams and a number of other surgical services. The intervention consisted of once weekly reviews and in-person rounds with the surgical floor teams along with the establishment of a 7 day per week “hotline” in which the surgical teams could contact an ID physician or pharmacist with questions regarding antibiotic use. Patients with formal ID consultations were not reviewed. Recommendations were tracked including the type, the antibiotic targeted, and recommendation acceptance or rejection. Descriptive statistics were performed to analyze these results. At the end of 12 months, antibiotic use in the floors covered by the ACCS teams were pulled from the NHSN AU module to perform an interrupted time-series analysis 12 months before and after the intervention. Results: Overall, 3,127 charts were reviewed during the intervention period and 637 recommendations were made to all the surgical teams. Opportunities for antibiotic use optimization were identified in ~20% of antibiotic orders. The overall recommendation acceptance rate was 71%. In the ACCS units, 272 interventions were recommended, with an acceptance rate of 67%. The most frequent recommendations were for antibiotic discontinuation (37%), antibiotic de-escalation (17%), shortening duration (12%), and broadening coverage (12%). Antibiotic usage trends (Fig. 1) on the ACCS floors, which were showing a nonsignificant increasing trend (P = .70) before and after the intervention, now show a nonsignificant decreasing trend (P = .20). Conclusions: There are numerous opportunities for antibiotic optimization on adult surgical floors. Although handshake stewardship is a labor-intensive intervention, preliminary findings after 1 year show that, on ACCS units, there may be a trend toward a sustained impact.Disclosures: None

PEGylated Manganese–Zinc Ferrite Nanocrystals Combined with Intratumoral Implantation of Micromagnets Enabled Synergetic Prostate Cancer Therapy via Ferroptotic and Immunogenic Cell Death (Small 22/2023)

Synergetic Prostate Cancer Therapies In article number 2207077, Li Zhang, Yunjiao Zhang, Chaozhao Liang, and co-workers propose intratumoral implantation of micromagnets to actively attract intravenously-injected magnetic PEGylated manganese-zinc ferrite nanocrystals (PMZFNs) from blood vessels into tumor tissue. PMZFNs exert relatively durable tumoricidal effects by inducing ferroptotic/immunogenic cell death, eventually achieving synergetic prostate cancer therapy. This study provides a new approach to overcoming the limitations of conventional anti-tumor therapies.

ADJUBIL: A phase II study of immunotherapy with durvalumab and tremelimumab in combination with capecitabine or without capecitabine in adjuvant situation for biliary tract cancer.

TPS4187 Background: Despite improvements in multidisciplinary management, patients with biliary tract cancer (BTC) have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. Data regarding pure adjuvant chemotherapy in BTC’s are conflicting and the SOC of the western world is currently capecitabine according to the British BILCAP- trial, even though BILCAP was formally negative. Based on the positive data for durvalumab in the TOPAZ- 1 – trial in BTC and for STRIDE- regimen in HCC according to the Himalaya- data, evaluation of IO- combination in the adjuvant setting seems to be promising. Preclinical studies indicate that the antibody combination results in stronger and more durable anti-tumor effects than single therapies by synergistically modulating the immunosuppressive tumor microenvironment which is particularly rich in cholangiocarcinoma. The aim of this study is the assessment of the clinical activity of the anti-PD-L1 (programmed- death 1-ligand) antibody durvalumab and the anti-CTLA-4 (cytotoxic T- lymphocyte-associated antigen 4) antibody tremelimumab in combination with or without capecitabine in patients with respectable BTC in the adjuvant situation. This is a randomized phase II study as a proof-of-concept for a potentially larger research program. Methods: The ADJUBIL trial is an open-label, multicenter phase II study, including patients with BTC after curative surgery with no previous systemic treatment. Patients are randomly assigned to receive tremelimumab (300mg, one dose) plus durvalumab (1500mg every 4 weeks; STRIDE, for a maximum of 12 months), with or without capecitabine (for 8 cycles). Forty evaluable patients will be enrolled in the study (1:1) to receive anticancer treatment until disease recurrence or intolerable toxicities. Primary objective is to assess the anti-tumor activity of the treatment in both arms by the recurrence-free survival rate after 12 months (RFS@12). Secondary endpoints are recurrence-free survival, overall survival, toxicity, and quality of life. Exploratory endpoints: Explore predictive biomarkers for recurrence-free survival and overall survival. Study start of the ADJUBIL trial was in June 2021. By January 2023, 12 centers across Germany have been initiated and a total of 8 out of 40 planned patients (1:1) have been enrolled. The study is currently ongoing. Clinical trial information: EUCTR2021-002389-41 .

A three-layer superhydrophobic coatings inspired by human scalp structure with excellent anti-reflection and durable effects for photovoltaic applications

Self-cleaning mechanisms of photovoltaic panels is a research hotspot in recent years, but the preparation of superhydrophobic coatings with excellent anti-reflection effect and durability for photovoltaic panels is still a problem to be solved. Inspired by the human scalp structure, we propose an interconnected three layer coatings (ITSC), which can produce self-cleaning effect on photovoltaic panels. Specifically, the prepared ITSC, owning porous three-dimensional network structure, consists of three layers with similar and cross-linked materials to ensure continuity and good adhesion among layers. Based on the experimental results, it can be concluded that the coating has an average transmittance that is 6.44% higher compared with bare glass. The bandwidth of high light transmittance (>91%) is almost 4 times that of bare glass. The pencil hardness test grade of the coating is 5 H, and the tape adhesion test grade is 5 B. In three simulated severe environmental stability tests (acid rain, high temperature and low temperature), the proposed coating can still maintain long term superhydrophobicity. Compared with uncoated photovoltaic panels, the maximum output power of coated one is 2.61 times that of the blank panel after the deposition of saline laterite under simulated drizzle conditions. The proposed coatings provide a promising solution for improving the performance of photovoltaic panels, reducing the negative impact of dust deposition, and improving the power output efficiency of photovoltaic power plants.

Cardiac Surgery 2022 Reviewed.

PubMed displayed almost 37,000 hits for the search term "cardiac surgery AND 2022." As before, we used the PRISMA approach and selected relevant publications for a results-oriented summary. We focused on coronary and conventional valve surgery, their overlap with interventional alternatives, and briefly assessed surgery for aorta or terminal heart failure. In the field of coronary artery disease (CAD), key manuscripts addressed prognostic implications of invasive treatment options, classically compared modern interventions (percutaneous coronary intervention [PCI]) with surgery (coronary artery bypass grafting [CABG]), and addressed technical aspects of CABG. The general direction in 2022 confirms the superiority of CABG over PCI in patients with anatomically complex chronic CAD and supports an infarct-preventative effect as underlying mechanism. In addition, the relevance of proper surgical technique to achieve durable graft patency and the need for optimal medical treatment in CABG patients was impressively illustrated. In structural heart disease, the comparisons of interventional and surgical techniques have been characterized by prognostic and mechanistic investigations underscoring the need for durable treatment effects and reductions of valve-related complications. Early surgery for most valve pathologies appears to provide significant survival advantages, and two publications on the Ross operation prototypically illustrate an inverse association between long-term survival and valve-related complications. For surgical treatment of heart failure, the first xenotransplantation was certainly dominant, and in the aortic surgery field, innovations in arch surgery prevailed. This article summarizes publications perceived as important by us. It cannot be complete nor free of individual interpretation, but provides up-to-date information for decision-making and patient information.

Recyclable Biophenolic Nanospheres for Sustainable and Durable Multifunctional Applications in Thermosets

Nanomaterials have a critical role in functional materials engineering; however, their efficient recycling, durable use, and multifunctional integration remain a huge challenge for sustainable development. Herein, we report multifunctional biophenolic nanospheres that exploit stimuli-responsive reversible assembly based on multiple directional interactions, allowing for closed-loop recycling and durability, even in complex systems of thermosets. The biobased nanospheres can serve long-term in various environments (high temperature, water, acid, surfactant solutions, etc.). By matching disassembly conditions, the nanospheres can be circularly dissociated into precursors, removed from application systems, reassembled, and reused sustainably. The corresponding mechanism is illustrated by experimental characterization and theoretical simulation. We further demonstrate the recycling and durable multifunctional effects of the nanospheres in thermoset foams. The reproducible nanospheres with diverse radical scavenging abilities endow nanocomposites with excellent mechanical enhancement, aging resistance, and durable flame retardancy. This study paves the way for tackling the pressing issue of high-value functional nanomaterial sustainability.

Immune checkpoint B7-H3 is a therapeutic vulnerability in prostate cancer harboring PTEN and TP53 deficiencies.

Checkpoint immunotherapy has yielded meaningful responses across many cancers but has shown modest efficacy in advanced prostate cancer. B7 homolog 3 protein (B7-H3/CD276) is an immune checkpoint molecule and has emerged as a promising therapeutic target. However, much remains to be understood regarding B7-H3's role in cancer progression, predictive biomarkers for B7-H3-targeted therapy, and combinatorial strategies. Our multi-omics analyses identified B7-H3 as one of the most abundant immune checkpoints in prostate tumors containing PTEN and TP53 genetic inactivation. Here, we sought in vivo genetic evidence for, and mechanistic understanding of, the role of B7-H3 in PTEN/TP53-deficient prostate cancer. We found that loss of PTEN and TP53 induced B7-H3 expression by activating transcriptional factor Sp1. Prostate-specific deletion of Cd276 resulted in delayed tumor progression and reversed the suppression of tumor-infiltrating T cells and NK cells in Pten/Trp53 genetically engineered mouse models. Furthermore, we tested the efficacy of the B7-H3 inhibitor in preclinical models of castration-resistant prostate cancer (CRPC). We demonstrated that enriched regulatory T cells and elevated programmed cell death ligand 1 (PD-L1) in myeloid cells hinder the therapeutic efficacy of B7-H3 inhibition in prostate tumors. Last, we showed that B7-H3 inhibition combined with blockade of PD-L1 or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) achieved durable antitumor effects and had curative potential in a PTEN/TP53-deficient CRPC model. Given that B7-H3-targeted therapies have been evaluated in early clinical trials, our studies provide insights into the potential of biomarker-driven combinatorial immunotherapy targeting B7-H3 in prostate cancer, among other malignancies.

Tapinarof ameliorates rejection in a human skin grafted model of face transplantation

Abstract T cell mediated immune rejection is the primary barrier to broader implementation of face transplants (vascularized composite allografts, VCA). Our bulk and single cell transcriptional profiling of human face transplant rejection demonstrated that VCA rejection is an INFγ driven cytotoxic process with unique induction of skin specific immunoregulatory pathways including SOCS1, KIR3DL2, and LY9. Tapinarof is a novel small-molecule topical aryl hydrocarbon receptor agonist and antioxidant that is effective in treating psoriasis and atopic dermatitis. Patients who cleared on once a day topical tapinarof remained clear for an average of four months after discontinuation, suggesting it has durable immunoregulatory effects in skin. We modeled VCA by grafting NSG mice with freshly excised, living, immunologically intact adult human skin. Once healed, 5×10 6allogeneic PBMCs from a second unrelated human donor were infused via tail vein. The inflamed skin mimicked VCA rejection after 21 days, with grafts showing epidermal injury, T cell infiltration, dyskeratosis, and genetic signatures of cytotoxicity, antigen presentation, and INFγ signaling. Topical tapinarof ameliorated this inflammation, with fewer T cells and reduced antigen-specific T cell activation. Induction of immunoregulatory pathways was also noted, including upregulation of SOCS1 signaling, TREX1 mediated reductions in cytosolic nucleotide sensing, and IL1RN inhibition of IL-1 mediated inflammation. Tapinarof could be a novel therapy for VCA rejection that does not require systemic immune suppression. Our results suggest that strengthening immunoregulatory networks in skin is a viable approach to combat inflammation and promote tolerance in VCA rejection. NIH T32 Training Grant 2T32AR007098-47 Dept. of Dermatology, Harvard Medical School RT170025 (P.I. Rachael A. Clark) Department of Defense - congressionally Directed Medical Research Programs; "T cells and Rejection in Vascularized Composite Allografts).

Relevant Choices Affecting the Fatigue Analysis of Ni-Ti Endovascular Devices.

Ni-Ti alloys are widely used for biomedical applications due to their superelastic properties, which are especially convenient for endovascular devices that require minimally invasive insertion and durable effects, such as peripheral/carotid stents and valve frames. After crimping and deployment, stents undergo millions of cyclic loads imposed by heart/neck/leg movements, causing fatigue failure and device fracture that can lead to possibly severe consequences for the patient. Standard regulations require experimental testing for the preclinical assessment of such devices, which can be coupled with numerical modeling to reduce the time and costs of such campaigns and to obtain more information regarding the local state of stress and strain in the device. In this frame, this review aimed to enlighten the relevant choices that can affect the outcome of the fatigue analysis of Ni-Ti devices, both from experimental and numerical perspectives.

Semiconductive (Cu–S)n metal–organic framework incorporated polyimide nanocomposite coatings forming an oxide barrier for durable anticorrosion effects

A semiconductive (Cu–S)n metal–organic framework (MOF) possesses redox property, which enables polyimide (PI)/(Cu–S)n MOF nanocomposite coatings to form a passivation layer on a metal substrate to prevent corrosion. This study successfully synthesised (Cu–S)n MOF nanorods by using a one-pot microwave-assisted reaction. The functionalised (Cu–S)n MOF nanorods exhibited excellent dispersion in solution and could polymerise with the PI matrix through chemical bonding to form PI/functionalised (Cu–S)n MOF (PI/FMOF) nanocomposites. The as-prepared nanocomposites exhibited multifunctional properties with remarkable flexibility and excellent thermal, mechanical, and corrosion protection effect, as well as anticorrosion against high temperatures. The nanocomposites exhibited a corrosion rate and corrosion protection efficiency of 4.66 × 10−3 milli-inches per year and 99.93 %, respectively. Furthermore, long-term (21 days) anticorrosion durability tests revealed that the PI/FMOF nanocomposites maintained their anticorrosion performance throughout the tests. This study is the first to use polymer/redox MOF–based nanocomposites in anticorrosion applications, successfully reducing the corrosion rate and inhibiting corrosion through the induction of a passivation barrier.

Abstract 6390: N17350 is an emerging therapeutic modality that selectively kills cancer cells and stimulates anti-tumor immunity

Abstract INTRODUCTION: Cancer is a disease driven by variable genetic mutations. Overcoming this variability while sparing normal cells has stymied broad-acting therapy development. Our innate immune system evolved to clear genetically diverse pathogens and limit host toxicity, raising the possibility that it can produce similar effects in cancer. Previous studies showed that neutrophil elastase (ELANE) - a neutrophil-derived serine protease - killed a wide range of cancer cells without harming non-cancer cells by cleaving CD95, the FAS receptor (Cui et al.,Cell, 2021). ELANE attenuated primary tumor growth and produced a CD8+T cell-mediated abscopal effect to attack metastases. Here we leveraged this ELANE-mediated pathway to produce an optimized N17350 biologic and tested its effects on tumor development, both as a monotherapy and in combination with checkpoint inhibitors. Our findings underscore the viability of N17350 as a new therapeutic modality leveraging innate immunity. METHODS: Anti-cancer effects of N17350 were examined in vitro and in vivo and compared with standard of care (SoC) agents. For in vitro studies, cells were treated with N17350 and viability was quantified by calcein-AM and immunogenic cell death (ICD) markers. Cancer/non-cancer cells included human/murine cell lines and primary cells isolated from healthy donors and ovarian cancer patients. We further tested the ability of cancer cells to develop resistance to N17350 and FAS-L. For in vivo studies, a single dose of N17350 was delivered intratumorally into CT26 (colon) and 4T1 (metastatic breast) tumors. Effects on primary and metastatic tumor growth, immunology, and survival were assessed in comparison to SoC agents (oxaliplatin, cyclophosphamide) or in combination with a checkpoint inhibitor (anti-CTLA4). RESULTS: N17350 killed and induced ICD markers in all cancer cell types tested without harming non-cancer cells, while SoC agents were similarly toxic to both cell types. Repeatedly killing E0771 cancer cells with N17350 did not produce resistance, which was observed with a FAS-L that targets CD95 via a distinct mechanism. A single intra-tumoral dose of N17350 produced durable effects in the 4T1 and CT26 models (CT26:75%-100% tumor-free). N17350 induced a robust innate/adaptive immune profile, abscopal effect to limit 4T1 lung metastasis, and synergized with anti-CTLA4 in cold (4T1) and hot (CT26) tumors. Finally, N17350 showed markedly improved efficacy over SoC agents in both models. CONCLUSIONS: Taken together, our data suggest that N17350 selectively kills cancer cells, produces complete responses in a subset of mice, induces favorable innate and adaptive immunology, and combines with checkpoint inhibitors in cold and hot tumors. Its ability to escape resistance, produce abscopal effects, and outperform SoC chemotherapies warrants further studies of this unique therapeutic modality in a clinical setting. Citation Format: Ravindra Gujar, Chang Cui, Lilibet Valdovinos, Christine Lee, Arezoo Arjmand, Nicole Grigaitis, Asna Khalid, Catherine A. Reardon, Kelly Q. Schoenfelt, Sonia Feau, Chris Twitty, Lev Becker. N17350 is an emerging therapeutic modality that selectively kills cancer cells and stimulates anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6390.

A prosocial fake news intervention with durable effects

The present online intervention promoted family-based prosocial values—in terms of helping family members—among young adults to build resistance against fake news. This preregistered randomized controlled trial study is among the first psychological fake news interventions in Eastern Europe, where the free press is weak and state-sponsored misinformation runs riot in mainstream media. In this intervention, participants were endowed with an expert role and requested to write a letter to their digitally less competent relatives explaining six strategies that help fake news recognition. Compared to the active control group there was an immediate effect (d = 0.32) that persisted until the follow-up four weeks later (d = 0.22) on fake news accuracy ratings of the young, advice-giving participants. The intervention also reduced the bullshit receptivity of participants both immediately after the intervention and in the long run. The present work demonstrates the power of using relevant social bonds for motivating behavior change among Eastern European participants. Our prosocial approach with its robust grounding in human psychology might complement prior interventions in the fight against misinformation.

Introduction to Special Issue: Interventions to Modify Psychological Well-Being and Population Health.

Psychological ill-being is on the rise, with 1 in 5 Americans suffering from a mental disorder in any given year. Additional evidence demonstrates that psychological well-being has also decreased over time. These trends are particularly worrisome given the substantial and growing body of evidence demonstrating that psychological ill-being (e.g., depression, anxiety, anger) is associated with an elevated risk of developing chronic diseases and premature mortality, while aspects of psychological well-being (e.g., positive affect, sense of purpose and meaning, life satisfaction) are independently associated with improved physical health outcomes. An underexplored but promising approach to enhancing both psychological and physical health is through developing a set of tools that specifically target psychological well-being (often referred to as positive psychological interventions (PPIs) although many interventions developed outside the field of positive psychology also achieve these goals). Such interventions hold promise as a strategy for improving population health. However, critical knowledge gaps hold us back, and we have not yet developed a robust set of intervention strategies that can improve psychological well-being in meaningful, durable, and scalable ways that would also have downstream effects on physical health. The goal of this special issue is to help address these knowledge gaps by bringing together current conceptual frameworks, critical examination of key constructs, and novel empirical evidence needed to identify and examine interventions that can modify psychological well-being, particularly those that have the potential to be scaled at the population level and with durable effects.

FDA Approves Second Antibody Therapy for Alzheimer’s

FDA Approves Second Antibody Therapy for Alzheimer’s