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An active neural mechanism for relational learning and fast knowledge reassembly.

How do we gain general insights from limited novel experiences? Humans and animals have a striking ability to learn relationships between experienced items, enabling efficient generalization and rapid assimilation of new information. One fundamental instance of such relational learning is transitive inference (learn A>B and B>C, infer A>C), which can be quickly and globally reorganized upon learning a new item (learn A>B>C and D>E>F, then C>D, and infer B>E). Despite considerable study, neural mechanisms of transitive inference and fast reassembly of existing knowledge remain elusive. Here we adopt a meta-learning ("learning-to-learn") approach. We train artificial neural networks, endowed with synaptic plasticity and neuromodulation, to be able to learn novel orderings of arbitrary stimuli from repeated presentation of stimulus pairs. We then obtain a complete mechanistic understanding of this discovered neural learning algorithm. Remarkably, this learning involves active cognition: items from previous trials are selectively reinstated in working memory, enabling delayed, self-generated learning and knowledge reassembly. These findings identify a new mechanism for relational learning and insight, suggest new interpretations of neural activity in cognitive tasks, and highlight a novel approach to discovering neural mechanisms capable of supporting cognitive behaviors.

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Open Access
Feasibility and Acceptability of LNG 1.5 mg as an On-Demand Pericoital Contraceptive in Ghana.

Globally, there is a need for more family planning method options as currently, available options do not adequately meet the needs of women, specifically those who have infrequent sex. Levonorgestrel (LNG) 1.5 mg is widely available as emergency contraception pills (ECP), and recent research has shown that certain women take it as their main form of contraception. Furthermore, limited studies have found repeat, on-demand use safe and efficacious. This 12-month prospective, single-arm, interventional study in Ghana tested whether a single LNG 1.5 mg on-demand or pericoital ("around the time of sex") dose contraceptive was acceptable to women who have infrequent sex and if pharmacy provision was feasible. The study sample (1,890) comprised women of reproductive age recruited from urban areas, having infrequent sex (i.e., coital frequency ≤ 6× per month), and not using any other modern methods except condoms or ECP at the time of study inclusion. Results indicated that there is demand and acceptability for a pericoital pill and that pharmacy provision is feasible. Furthermore, precoital use of the pill had high levels of satisfaction and was popular with new users. Adding LNG 1.5 mg for pericoital use to the family planning method mix has the potential to address an important segment of the population currently underserved, decreases unwanted pregnancies, and increases modern contraceptive prevalence rates.

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Open Access
"The Name of This is Fourth Trimester. A Lot of People Don't Know About it": A Qualitative Analysis to Inform the Development of a Web-Based Tool.

The purpose of this qualitative study is to understand the pregnant and postpartum experiences of Black women in the United States to inform the development of a web-based mobile tool. Participants were recruited through Facebook Groups. There were a total of 19 women that participated in one of five focus group discussions. Participants ranged from being in their 3rd trimester of pregnancy through 6 months postpartum. Thematic content analysis was performed to identify emerging themes. Four themes emerged from the focus group discussions: beliefs about postpartum motherhood, experiences during pregnancy, experiences of the postpartum period, and tool recommendations. Key results from these themes demonstrated the difficulties that women faced in having their concerns resolved by healthcare professionals, receiving adequate educational and social support during the COVID-19 pandemic, and having adequate information to help breastfeed and cope with changes they experienced throughout the postpartum period. The results highlight the difficulties that Black women experienced throughout pregnancy and the postpartum period. The main findings show that women lacked support in receiving information about the postpartum period, had their concerns dismissed by healthcare professionals, and received inadequate support. These findings can inform the practice of healthcare professionals and inform the development of other non-clinical, digital resources to fill in these gaps. Future research in this area is planned to further develop and pilot the tool among a broader population of women.

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Open Access
Evaluation of Cellular Immune Response to Adeno-Associated Virus-Based Gene Therapy.

The number of approved or investigational late phase viral vector gene therapies (GTx) has been rapidly growing. The adeno-associated virus vector (AAV) technology continues to be the most used GTx platform of choice. The presence of pre-existing anti-AAV immunity has been firmly established and is broadly viewed as a potential deterrent for successful AAV transduction with a possibility of negative impact on clinical efficacy and a connection to adverse events. Recommendations for the evaluation of humoral, including neutralizing and total antibody based, anti-AAV immune response have been presented elsewhere. This manuscript aims to cover considerations related to the assessment of anti-AAV cellular immune response, including review of correlations between humoral and cellular responses, potential value of cellular immunogenicity assessment, and commonly used analytical methodologies and parameters critical for monitoring assay performance. This manuscript was authored by a group of scientists involved in GTx development who represent several pharma and contract research organizations. It is our intent to provide recommendations and guidance to the industry sponsors, academic laboratories, and regulatory agencies working on AAV-based GTx viral vector modalities with the goal of achieving a more consistent approach to anti-AAV cellular immune response assessment.

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Open Access
The Power and Promise of Postpartum Self Care: Evaluation of a Web-Based Tool for Underserved Women.

Joyuus is a culturally diverse, comprehensive online tool designed to address the self-care needs of underserved postpartum women. The tool provides actionable self-care information, knowledge, and skills to improve postpartum health and identifies red flags for when self-care shifts to seeking care. We employed a mixed-methods multiphase design to evaluate the Joyuus prototype, including a pre-post evaluation (N = 87) to assess behavioral health outcomes before and after using the tool for a one-month period. 91% completed the post-test (N = 79). The analysis focused on estimation of treatment effect (via 95% confidence intervals) and fitness of instruments in this population. Participants were between 6months pregnant and one year postpartum, a mean age of 30years, 100% female, 99% Black, with nearly equal distribution of married (55%) and not married (44%), and above (47%) and below (46%) annual income of $60K. Key measures saw significant improvement from pre- (mean = 26.44, SD = 5.39) to post (mean = 28.29, SD = 5.26) on the Connor-Davidson Resilience Scale (p < 0.001) Trends toward improvement (not statistically significant) were noted for Depression (EPDS) (p = 0.624) and Anxiety (STAI) (p = 0.286), and no meaningful change on MOS Social Support or COVID-19 Mental Health Impacts Measures. This pilot study demonstrates that a self-care mobile tool has the potential to address significant health outcomes related to maternal morbidity and mortality. By providing a continuously available companion addressing physical, mental, and real-life questions, it creates value during postpartum for mothers who can often feel overwhelmed or isolated.

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Open Access