Comparing Functional Trend and Learning among Groups in Intensive Binary Longitudinal Eye-Tracking Data using By-Variable Smooth Functions of GAMM.

This paper presents a model specification for group comparisons regarding a functional trend over time within a trial and learning across a series of trials in intensive binary longitudinal eye-tracking data. The functional trend and learning effects are modeled using by-variable smooth functions. This model specification is formulated as a generalized additive mixed model, which allowed for the use of the freely available mgcv package (Wood in Package 'mgcv.' https://cran.r-project.org/web/packages/mgcv/mgcv.pdf , 2023) in R. The model specification was applied to intensive binary longitudinal eye-tracking data, where the questions of interest concern differences between individuals with and without brain injury in their real-time language comprehension and how this affects their learning over time. The results of the simulation study show that the model parameters are recovered well and the by-variable smooth functions are adequately predicted in the same condition as those found in the application.

Comprehension of Miranda warnings in adults with chronic, moderate-severe traumatic brain injury.

INTRODUCTION: To compare comprehension of Miranda rights in adults with traumatic brain injury (TBI) versus adults without TBI as measured by response accuracy on the Miranda Right Comprehension Instruments. METHODS: Data were collected virtually via teleconferencing from July 2022 to February 2023. Participants included 25 adults with moderate-severe TBI (12 females, 13 males) and 25 adults without TBI (12 females, 13 males), ages 20-55 years. In this observational study, both groups (with and without TBI) completed the Miranda Right Comprehension Instruments (MRCI), which includes four instruments including Comprehension of Miranda Rights, Comprehension of Miranda Rights-Recognition, Function of Rights in Interrogation, Comprehension of Miranda Vocabulary instruments. Response accuracy on the MRCI was compared across groups. RESULTS: The TBI group was significantly less accurate when responding to questions on the MRCI compared to the NC group. CONCLUSION: Individuals with chronic moderate-severe TBI underperform their non-injured peers on the Miranda Rights Comprehension Instruments, a tool used in legal settings when there is doubt about an individual's understanding of their Miranda rights. TBI is a risk factor for disruptions in comprehension of language in legal contexts that may, in part, contribute to the increased interaction with the criminal justice system and incarceration for individuals with TBI. Implications for policy, advocating, and intervention are discussed.

Temporal organization of narrative recall is present but attenuated in adults with hippocampal amnesia.

Studies of the impact of brain injury on memory processes often focus on the quantity and episodic richness of those recollections. Here, we argue that the organization of one's recollections offers critical insights into the impact of brain injury on functional memory. It is well-established in studies of word list memory that free recall of unrelated words exhibits a clear temporal organization. This temporal contiguity effect refers to the fact that the order in which word lists are recalled reflects the original presentation order. Little is known, however, about the organization of recall for semantically rich materials, nor how recall organization is impacted by hippocampal damage and memory impairment. The present research is the first study, to our knowledge, of temporal organization in semantically rich narratives in three groups: (1) Adults with bilateral hippocampal damage and severe declarative memory impairment, (2) adults with bilateral ventromedial prefrontal cortex (vmPFC) damage and no memory impairment, and (3) demographically matched non-brain-injured comparison participants. We find that although the narrative recall of adults with bilateral hippocampal damage reflected the temporal order in which those narratives were experienced above chance levels, their temporal contiguity effect was significantly attenuated relative to comparison groups. In contrast, individuals with vmPFC damage did not differ from non-brain-injured comparison participants in temporal contiguity. This pattern of group differences yields insights into the cognitive and neural systems that support the use of temporal organization in recall. These data provide evidence that the retrieval of temporal context in narrative recall is hippocampal-dependent, whereas damage to the vmPFC does not impair the temporal organization of narrative recall. This evidence of limited but demonstrable organization of memory in participants with hippocampal damage and amnesia speaks to the power of narrative structures in supporting meaningfully organized recall despite memory impairment.

Contraception Use and Pregnancy Risk Among Adolescents in Pediatric Emergency Departments.

Importance: Unintended pregnancy is a major health risk for adolescents in the US, and adolescents face many barriers to obtaining effective and reliable contraception. Objective: To measure and describe the use of contraception, pregnancy risk index (PRI), and emergency contraception (EC) prescriptions among female adolescents accessing the emergency department (ED) for care. Design, Setting, and Participants: This cross-sectional study is a planned secondary analysis of a multicenter trial from April 2021 through April 2022 that used a tablet-based, content-validated, confidential sexual health survey at 6 urban, pediatric tertiary care EDs affiliated with the Pediatric Emergency Care Applied Research Network. Participants were individuals aged 15 to 21 years presenting to the ED who completed the confidential sexual health survey and indicated female sex assigned at birth and prior penile-vaginal sexual intercourse. Data analysis was performed from January 2023 to February 2024. Main Outcomes and Measures: The primary outcomes were the type and proportion of contraception use, the PRI, and provision of EC. Separate multivariable logistic regression models were performed to identify sociodemographic factors associated with these outcomes. Results: A total of 1063 participants (median [IQR] age, 17.5 [16.5-18.3] years) were included in this analysis; 219 (20.8%) identified as Hispanic, 464 (44.1%) identified as non-Hispanic Black, 308 (29.3%) identified as non-Hispanic White, and 61 (5.8%) identified as other races and ethnicities. In total, 756 participants (71.1%) reported contraception use during their last sexual encounter. Long-acting reversible contraception use (LARC) was the least used (164 participants [15.4%]), and 307 (28.9%) reported no contraception use. Sociodemographic factors associated with overall contraception use, and LARC use specifically, included insurance and race and ethnicity. The overall PRI was 7.89, or an expected 8 pregnancies per 100 female individuals per year. Although 108 participants (10.2%) were eligible for EC, EC was ordered for only 6 (5.6%) of those eligible. Conclusions and Relevance: In this cross-sectional study of sexually active adolescents presenting to the ED, the majority of participants reported using at least 1 form of contraception; however, LARCs were the least used option, and 28.9% of participants reported no contraceptive use. The unintended pregnancy risk was almost 8% in the study population. Few patients eligible for EC received it. These data suggest a high need and potential opportunity for provision of contraception services in the ED setting.

Memory for Conversation in Traumatic Brain Injury: A Feasibility Study and Preliminary Findings.

PURPOSE: Despite common clinical complaints about memory for conversation after traumatic brain injury (TBI), the nature and severity of this deficit are unknown. In this research note, we report feasibility and preliminary data from a new conversation memory study protocol. METHOD: Participants in this feasibility study were 10 pairs, each including an adult with chronic, moderate-to-severe TBI and their chosen familiar conversation partner. The experiment began with a naturalistic conversation between participants with TBI and their conversation partners. After a filled delay, participants next completed verbal recall for the conversation, which we transcribed and coded for their accuracy relative to the original conversation. Participants also read chosen statements from their original conversation and predicted what each partner would remember in a week. One week later, participants completed a posttest about who said each of the chosen statements, allowing direct comparison to their predictions. RESULTS: We successfully collected conversation memory data from all 10 pairs, suggesting that this protocol is feasible for future study. In this preliminary sample, people with TBI and their conversation partners did not differ in the accuracy of their recall for the conversation about 20 min after it occurred. When asked to predict their partner's delayed memory, conversation partners were less accurate than participants with TBI because they underestimated how much their partners with TBI would remember. CONCLUSION: Measuring memory for conversation in TBI is feasible and may advance the characterization of cognitive-communication impairment in TBI, and its heterogeneity, in everyday contexts. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25927513.

Flt3 agonist enhances immunogenicity of arenavirus vector-based simian immunodeficiency virus vaccine in macaques.

Arenaviral vaccine vectors encoding simian immunodeficiency virus (SIV) immunogens are capable of inducing efficacious humoral and cellular immune responses in nonhuman primates. Several studies have evaluated the use of immune modulators to further enhance vaccine-induced T-cell responses. The hematopoietic growth factor Flt3L drives the expansion of various bone marrow progenitor populations, and administration of Flt3L was shown to promote expansion of dendritic cell populations in spleen and blood, which are targets of arenaviral vectors. Therefore, we evaluated the potential of Flt3 signaling to enhance the immunogenicity of arenaviral vaccines encoding SIV immunogens (SIVSME543 Gag, Env, and Pol) in rhesus macaques, with a rhesus-specific engineered Flt3L-Fc fusion protein. In healthy animals, administration of Flt3L-Fc led to a 10- to 100-fold increase in type 1 dendritic cells 7 days after dosing, with no antidrug antibody (ADA) generation after repeated dosing. We observed that administration of Flt3L-Fc fusion protein 7 days before arenaviral vaccine increased the frequency and activation of innate immune cells and enhanced T-cell activation with no treatment-related adverse events. Flt3L-Fc administration induced early innate immune activation, leading to a significant enhancement in magnitude, breadth, and polyfunctionality of vaccine-induced T-cell responses. The Flt3L-Fc enhancement in vaccine immunogenicity was comparable to a combination with αCTLA-4 and supports the use of safe and effective variants of Flt3L to augment therapeutic vaccine-induced T-cell responses.IMPORTANCEInduction of a robust human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell response through therapeutic vaccination is considered essential for HIV cure. Arenaviral vaccine vectors encoding simian immunodeficiency virus (SIV) immunogens have demonstrated strong immunogenicity and efficacy in nonhuman primates. Here, we demonstrate that the immunogenicity of arenaviral vectors encoding SIV immunogens can be enhanced by administration of Flt3L-Fc fusion protein 7 days before vaccination. Flt3L-Fc-mediated increase in dendritic cells led to robust improvements in vaccine-induced T- and B-cell responses compared with vaccine alone, and Flt3L-Fc dosing was not associated with any treatment-related adverse events. Importantly, immune modulation by either Flt3L-Fc or αCTLA-4 led to comparable enhancement in vaccine response. These results indicate that the addition of Flt3L-Fc fusion protein before vaccine administration can significantly enhance vaccine immunogenicity. Thus, safe and effective Flt3L variants could be utilized as part of a combination therapy for HIV cure.

Attentional Orienting and Disfluency-Related Memory Boost Are Intact in Adults With Moderate-Severe Traumatic Brain Injury.

PURPOSE: Traumatic brain injury (TBI) is associated with a range of cognitive-communicative deficits that interfere with everyday communication and social interaction. Considerable effort has been directed at characterizing the nature and scope of cognitive-communication disorders in TBI, yet the underlying mechanisms of impairment are largely unspecified. The present research examines sensitivity to a common communicative cue, disfluency, and its impact on memory for spoken language in TBI. METHOD: Fifty-three participants with moderate-severe TBI and 53 noninjured comparison participants listened to a series of sentences, some of which contained disfluencies. A subsequent memory test probed memory for critical words in the sentences. RESULTS: Participants with TBI successfully remembered the spoken words (b = 1.57, p < .0001) at a similar level to noninjured comparison participants. Critically, participants with TBI also exhibited better recognition memory for words preceded by disfluency compared to words from fluent sentences (b = 0.57, p = .02). CONCLUSIONS: These findings advance mechanistic accounts of cognitive-communication disorder by revealing that, when isolated for experimental study, individuals with moderate-severe TBI are sensitive to attentional orienting cues in speech and exhibit enhanced recognition of individual words preceded by disfluency. These results suggest that some aspects of cognitive-communication disorders may not emerge from an inability to perceive and use individual communication cues, but rather from disruptions in managing (i.e., attending, weighting, integrating) multiple cognitive, communicative, and social cues in complex and dynamic interactions. This hypothesis warrants further investigation.

Molecular mechanism of choline and ethanolamine transport in humans.

Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome2-7. Earlier studies concluded that FLVCR1 may function as a haem exporter8-12, whereas FLVCR2 was suggested to act as a haem importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14-16. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation-π interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle.

Solid-State Oxidation of Alcohols in Gold-Coated Milling Vessels via Direct Mechanocatalysis.

This paper presents a novel approach for the selective oxidation of alcohols to their corresponding aldehydes through direct mechanocatalysis, employing a gold-coated milling vessel as catalyst and air as the oxidation agent. By adjusting milling frequency, media, and duration, high catalytic efficiencies and selectivities are achieved. Remarkably, yields of up to 99 % are obtained for specific substrates, with a turnover number (TON) of 8200 and a turnover frequency (TOF) of 0.77 s-1, surpassing existing alternatives. Confirmation of the catalytic reaction indeed occurring on the milling tool surface was achieved through X-ray photoelectron spectroscopy (XPS).

Benign synthesis of terpene-based 1,4-p-menthane diamine.

Terpenes represent a promising renewable feedstock for the substitution of fossil resources in the synthesis of renewable platform chemicals, like diamines. This work describes the synthesis and full characterization of 1,4-p-menthane diamine (1,4-PMD) obtained from α-terpinene (1). A two-step procedure using dibenzyl azodicarboxylate (DBAD) and H2 as rather benign reagents was employed under comparatively mild conditions. Both C-N bonds were formed simultaneously during a visible-light mediated Diels-Alder reaction, which was investigated in batch or flow, avoiding regioselectivity issues during the amination steps that are otherwise typical for terpene chemistry. Heterogeneously catalyzed quadruple hydrogenation of the cycloadduct (2a) yielded 1,4­PMD (3). While the intermediate cycloadduct was shown to be distillable, the target diamine can be sublimed, offering sustainable purification methods.

CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV.

Eosinophil recruitment is a pathological hallmark of many allergic and helminthic diseases. Here, we investigated chemokine receptor CCR3-induced eosinophil recruitment in sialyltransferase St3gal4-/- mice. We found a marked decrease in eosinophil extravasation into CCL11-stimulated cremaster muscles and into the inflamed peritoneal cavity of St3gal4-/- mice. Ex vivo flow chamber assays uncovered reduced adhesion of St3gal4-/- compared to wild type eosinophils. Using flow cytometry, we show reduced binding of CCL11 to St3gal4-/- eosinophils. Further, we noted reduced binding of CCL11 to its chemokine receptor CCR3 isolated from St3gal4-/- eosinophils. This was accompanied by almost absent CCR3 internalization of CCL11-stimulated St3gal4-/- eosinophils. Applying an ovalbumin-induced allergic airway disease model, we found a dramatic reduction in eosinophil numbers in bronchoalveolar lavage fluid following intratracheal challenge with ovalbumin in St3gal4-deficient mice. Finally, we also investigated tissue-resident eosinophils under homeostatic conditions and found reduced resident eosinophil numbers in the thymus and adipose tissue in the absence of ST3Gal-IV. Taken together, our results demonstrate an important role of ST3Gal-IV in CCR3-induced eosinophil recruitment in vivo rendering this enzyme an attractive target in reducing unwanted eosinophil infiltration in various disorders including allergic diseases.

Preclinical evaluation of two phylogenetically distant arenavirus vectors for the development of novel immunotherapeutic combination strategies for cancer treatment.

BACKGROUND: Engineered arenavirus vectors have recently been developed to leverage the body's immune system in the fight against chronic viral infections and cancer. Vectors based on Pichinde virus (artPICV) and lymphocytic choriomeningitis virus (artLCMV) encoding a non-oncogenic fusion protein of human papillomavirus (HPV)16 E6 and E7 are currently being tested in patients with HPV16+ cancer, showing a favorable safety and tolerability profile and unprecedented expansion of tumor-specific CD8+ T cells. Although the strong antigen-specific immune response elicited by artLCMV vectors has been demonstrated in several preclinical models, PICV-based vectors are much less characterized. METHODS: To advance our understanding of the immunobiology of these two vectors, we analyzed and compared their individual properties in preclinical in vivo and in vitro systems. Immunogenicity and antitumor effect of intratumoral or intravenous administration of both vectors, as well as combination with NKG2A blockade, were evaluated in naïve or TC-1 mouse tumor models. Flow cytometry, Nanostring, and histology analysis were performed to characterize the tumor microenvironment (TME) and T-cell infiltrate following treatment. RESULTS: Despite being phylogenetically distant, both vectors shared many properties, including preferential infection and activation of professional antigen-presenting cells, and induction of potent tumor-specific CD8+ T-cell responses. Systemic as well as localized treatment induced a proinflammatory shift in the TME, promoting the infiltration of inducible T cell costimulator (ICOS)+CD8+ T cells capable of mediating tumor regression and prolonging survival in a TC-1 mouse tumor model. Still, there was evidence of immunosuppression built-up over time, and increased expression of H2-T23 (ligand for NKG2A T cell inhibitory receptor) following treatment was identified as a potential contributing factor. NKG2A blockade improved the antitumor efficacy of artARENA vectors, suggesting a promising new combination approach. This demonstrates how detailed characterization of arenavirus vector-induced immune responses and TME modulation can inform novel combination therapies. CONCLUSIONS: The artARENA platform represents a strong therapeutic vaccine approach for the treatment of cancer. The induced antitumor immune response builds the backbone for novel combination therapies, which warrant further investigation.

Linguistic features of spontaneous speech predict conversational recall.

Empirical studies of conversational recall show that the amount of conversation that can be recalled after a delay is limited and biased in favor of one's own contributions. What aspects of a conversational interaction shape what will and will not be recalled? This study aims to predict the contents of conversation that will be recalled based on linguistic features of what was said. Across 59 conversational dyads, we observed that two linguistic features that are hallmarks of interactive language use-disfluency (um/uh) and backchannelling (ok, yeah)-promoted recall. Two other features-disagreements between the interlocutors and use of "like"-were not predictive of recall. While self-generated material was better remembered overall, both hearing and producing disfluency and backchannels improved memory for the associated utterances. Finally, the disfluency-related memory boost was similar regardless of the number of disfluencies in the utterance. Overall, we conclude that interactional linguistic features of conversation are predictive of what is and is not recalled following conversation.

Teletherapy Used to Breakdown Access Barriers.

The studies presented in this literature review reveal the numerous ways that teletherapy can be used to treat patients with mental health issues. The literature includes six research articles from published scientific journals that span from 2005 to 2020. The three types of telehealth therapy reviewed include mobile telehealth, telephone, and video technology. The six research articles focus on the ways that telehealth can reach communities of lower socioeconomic status (SES) and those suffering from access barriers. The benefits of teletherapy include cost savings, time efficiency, easier access, and a reduction in recidivism. Challenges include access barriers, financial difficulties, anxiety, and fear of stigmatization. Limitations of the studies presented include a lack of accessibility to internet and technology, privacy issues, and insurance coverage. Overall, results show that teletherapy provides an affordable, accessible alternative to traditional in-person mental health therapy, especially in reaching lower SES groups, Veterans, and patients with access restrictions.

Alcohol and common ground: The effects of intoxication on linguistic markers of shared understanding during social exchange.

OBJECTIVE: Most alcohol consumption takes place in social contexts, and the belief that alcohol enhances social interactions has been identified as among the more robust predictors of alcohol use disorder (AUD) development. Yet, we know little of how alcohol affects mental representations of others-what we share and do not share-nor the extent to which intoxication might impact the development of shared understanding (i.e., common ground) between interaction partners. Employing a randomized experimental design and objective linguistic outcome measures, we present two studies examining the impact of alcohol consumption on the development and use of common ground. METHOD: In Study 1, groups of strangers or friends were administered either alcohol (target Breath Alcohol Content = .08%) or a control beverage, following which they completed a task requiring them to develop a shared language to describe ambiguous images and then describe those images to either a knowledgeable or a naïve partner. The same procedures were completed in Study 2 using a within-subjects alcohol administration design and all-stranger groups. RESULTS: Study 1 findings did not reach significance but suggested that alcohol may facilitate common ground development selectively among stranger groups. This effect emerged as significant in the context of the within-subjects design of Study 2, b = -0.19, p = .007, with participants demonstrating greater facility in establishing common ground during alcohol versus control sessions. CONCLUSIONS: Results suggest that alcohol facilitates the development of shared linguistic understanding in novel social spaces, indicating common ground as one potential mechanism to consider in our broader examination of alcohol reinforcement and AUD etiology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A replicating LCMV-based vaccine for the treatment of solid tumors.

Harnessing the immune system to eradicate tumors requires identification and targeting of tumor antigens, including tumor-specific neoantigens and tumor-associated self-antigens. Tumor-associated antigens are subject to existing immune tolerance, which must be overcome by immunotherapies. Despite many novel immunotherapies reaching clinical trials, inducing self-antigen-specific immune responses remains challenging. Here, we systematically investigate viral-vector-based cancer vaccines encoding a tumor-associated self-antigen (TRP2) for the treatment of established melanomas in preclinical mouse models, alone or in combination with adoptive T cell therapy. We reveal that, unlike foreign antigens, tumor-associated antigens require replication of lymphocytic choriomeningitis virus (LCMV)-based vectors to break tolerance and induce effective antigen-specific CD8+ T cell responses. Immunization with a replicating LCMV vector leads to complete tumor rejection when combined with adoptive TRP2-specific T cell transfer. Importantly, immunization with replicating vectors leads to extended antigen persistence in secondary lymphoid organs, resulting in efficient T cell priming, which renders previously "cold" tumors open to immune infiltration and reprograms the tumor microenvironment to "hot." Our findings have important implications for the design of next-generation immunotherapies targeting solid cancers utilizing viral vectors and adoptive cell transfer.

PhenoID, a language model normalizer of physical examinations from genetics clinical notes.

Background: Phenotypes identified during dysmorphology physical examinations are critical to genetic diagnosis and nearly universally documented as free-text in the electronic health record (EHR). Variation in how phenotypes are recorded in free-text makes large-scale computational analysis extremely challenging. Existing natural language processing (NLP) approaches to address phenotype extraction are trained largely on the biomedical literature or on case vignettes rather than actual EHR data. Methods: We implemented a tailored system at the Children's Hospital of Philadelpia that allows clinicians to document dysmorphology physical exam findings. From the underlying data, we manually annotated a corpus of 3136 organ system observations using the Human Phenotype Ontology (HPO). We provide this corpus publicly. We trained a transformer based NLP system to identify HPO terms from exam observations. The pipeline includes an extractor, which identifies tokens in the sentence expected to contain an HPO term, and a normalizer, which uses those tokens together with the original observation to determine the specific term mentioned. Findings: We find that our labeler and normalizer NLP pipeline, which we call PhenoID, achieves state-of-the-art performance for the dysmorphology physical exam phenotype extraction task. PhenoID's performance on the test set was 0.717, compared to the nearest baseline system (Pheno-Tagger) performance of 0.633. An analysis of our system's normalization errors shows possible imperfections in the HPO terminology itself but also reveals a lack of semantic understanding by our transformer models. Interpretation: Transformers-based NLP models are a promising approach to genetic phenotype extraction and, with recent development of larger pre-trained causal language models, may improve semantic understanding in the future. We believe our results also have direct applicability to more general extraction of medical signs and symptoms. Funding: US National Institutes of Health.

Alternating Arenavirus Vector Immunization Generates Robust Polyfunctional Genotype Cross-Reactive Hepatitis B Virus-Specific CD8 T-Cell Responses and High Anti-Hepatitis B Surface Antigen Titers.

Hepatitis B Virus (HBV) is a major driver of infectious disease mortality. Curative therapies are needed and ideally should induce CD8 T cell-mediated clearance of infected hepatocytes plus anti-hepatitis B surface antigen (HBsAg) antibodies (anti-HBs) to neutralize residual virus. We developed a novel therapeutic vaccine using non-replicating arenavirus vectors. Antigens were screened for genotype conservation and magnitude and genotype reactivity of T cell response, then cloned into Pichinde virus (PICV) vectors (recombinant PICV, GS-2829) and lymphocytic choriomeningitis virus (LCMV) vectors (replication-incompetent, GS-6779). Alternating immunizations with GS-2829 and GS-6779 induced high-magnitude HBV T cell responses, and high anti-HBs titers. Dose schedule optimization in macaques achieved strong polyfunctional CD8 T cell responses against core, HBsAg, and polymerase and high titer anti-HBs. In AAV-HBV mice, GS-2829 and GS-6779 were efficacious in animals with low pre-treatment serum HBsAg. Based on these results, GS-2829 and GS-6779 could become a central component of cure regimens.