8,096 research outputs found

    E(n) Equivariant Graph Neural Network for Learning Interactional Properties of Molecules

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    We have developed a multi-input E(n) equivariant graph convolution-based model designed for the prediction of chemical properties that result from the interaction of heterogeneous molecular structures. By incorporating spatial features and constraining the functions learned from these features to be equivariant to E(n) symmetries, the interactional-equivariant graph neural network (IEGNN) can efficiently learn from the 3D structure of multiple molecules. To verify the IEGNN's capability to learn interactional properties, we tested the model's performance on three molecular data sets, two of which are curated in this study and made publicly available for future interactional model benchmarking. To enable the loading of these data sets, an open-source data structure based on the PyTorch Geometric library for batch loading multigraph data points is also created. Finally, the IEGNN's performance on a data set consisting of an unknown interactional relationship (the frictional properties resulting between monolayers with variable composition) is examined. The IEGNN model developed was found to have the lowest mean absolute percent error for the predicted tribological properties of four of the six data sets when compared to previous methods.</p

    Source‐based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome

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    22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1‐weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source‐based morphometry (SBM) pipeline (SS‐Detect) to generate structural brain patterns (SBPs) that capture co‐varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV‐SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel‐based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism

    Tropical field stations yield high conservation return on investment

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    Conservation funding is currently limited; cost-effective conservation solutions are essential. We suggest that the thousands of field stations worldwide can play key roles at the frontline of biodiversity conservation and have high intrinsic value. We assessed field stations’ conservation return on investment and explored the impact of COVID-19. We surveyed leaders of field stations across tropical regions that host primate research; 157 field stations in 56 countries responded. Respondents reported improved habitat quality and reduced hunting rates at over 80% of field stations and lower operational costs per km2 than protected areas, yet half of those surveyed have less funding now than in 2019. Spatial analyses support field station presence as reducing deforestation. These ‘earth observatories’ provide a high return on investment; we advocate for increased support of field station programs and for governments to support their vital conservation efforts by investing accordingly

    The establishment, maintenance, and adaptation of high- and low-impact chronic pain: a framework for biopsychosocial pain research

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    We present a framework for the study of states of chronic pain and transitions between those states. We capture in the framework the dynamic nature of pain: people live with pain that changes over time. First, we offer definitions of both acute and chronic pain and explore the contextual considerations related to the common use of this temporal dichotomy. Second, we promote the importance of incorporating the impact pain has on a person's life. Finally, we discuss the challenges and opportunities inherent in implementing this common approach. Our goal is to produce a framework for the study of the development, maintenance, and resolution of chronic pain. Whether a single brief event or a constant feature of life, pain interrupts to prioritise protection, interferes with activity, reduces quality of life, and can alter identity.44 Protection is achieved by escape from harm, avoidance of perceived danger, withdrawal for respite and repair, and communication of incapacity and environmental risk; longer-term protection is achieved by learning the cues for pain and injury.53 From this perspective, pain is most usefully considered a need state, fundamentally a motivational drive to protect.49 This approach centres our attention on the consequences of pain for the person in their context, on its duration and its impact

    Are null segregants new combinations of heritable material and should they be regulated?

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    Through genome editing and other techniques of gene technology, it is possible to create a class of organism called null segregants. These genetically modified organisms (GMOs) are products of gene technology but are argued to have no lingering vestige of the technology after the segregation of chromosomes or deletion of insertions. From that viewpoint regulations are redundant because any unique potential for the use of gene technology to cause harm has also been removed. We tackle this question of international interest by reviewing the early history of the purpose of gene technology regulation. The active ingredients of techniques used for guided mutagenesis, e.g., site-directed nucleases, such as CRISPR/Cas, are promoted for having a lower potential per reaction to create a hazard. However, others see this as a desirable industrial property of the reagents that will lead to genome editing being used more and nullifying the promised hazard mitigation. The contest between views revolves around whether regulations could alter the risks in the responsible use of gene technology. We conclude that gene technology, even when used to make null segregants, has characteristics that make regulation a reasonable option for mitigating potential harm. Those characteristics are that it allows people to create more harm faster, even if it creates benefits as well; the potential for harm increases with increased use of the technique, but safety does not; and regulations can control harm scaling.publishedVersio

    Evaluating the dose-response relationship of the number of sessions of "It Takes Two to TalkÂź" in young children with language delay

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    Purpose: To evaluate the dose–response relationship between the number of It Takes Two to Talk¼ (ITTT) sessions attended and the language outcomes of young children with language delay and their parent’s responsivity in a multicultural clinical population. Method: A clinical caseload of 273 early language delayed children (mean age 29.2 months, SD 7.8) and their families participated in parent group workshops and individual coaching sessions of the parent responsivity program ITTT. The children’s vocabulary and early syntax, collected using the MacArthur-Bates Communicative Development Inventories and mean length of the three longest utterances respectively, were collated from pre- and post-intervention from pre-existing clinical data. Parental responsivity was evaluated utilising the Parent–Child Interaction checklist at three time points. Multilevel regression was used to determine the relationship between the number of sessions attended and outcomes, while accounting for covariates such as age and language spoken. Result: ITTT dosage did not predict child language outcomes. Rather, vocabulary and early syntax outcomes were predicted by age, pre-scores and parent responsivity at the beginning of treatment. A higher dosage of ITTT did however positively predict parent responsivity, as did speaking only English at home. Socioeconomic status, gender and presence of receptive language difficulties did not contribute significantly to either child or parent outcomes. Conclusion: A lower dosage of the intervention may be considered for parents and children with fewer known risk factors without significant implications

    Genetic reversal of the globin switch concurrently modulates both fetal and sickle hemoglobin and reduces red cell sickling

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    We previously reported initial clinical results of post-transcriptional gene silencing of BCL11A expression (NCT 03282656) reversing the fetal to adult hemoglobin switch. A goal of this approach is to increase fetal hemoglobin (HbF) expression while coordinately reducing sickle hemoglobin (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications. Here we report results of exploratory single-cell analysis of patients in which BCL11A is targeted molecularly and compare results with cells of patients treated with hydroxyurea (HU), the current standard of care. We use single-cell assays to assess HbF, HbS, oxygen saturation, and hemoglobin polymer content in RBCs for nine gene therapy trial subjects (BCLshmiR, median HbF% = 27.9) and compare them to 10 HU-treated subjects demonstrating high and comparable levels of HbF (HU High Responders, median HbF% = 27.0). All BCL11A patients achieved the primary endpoint for NCT 03282656, which was defined by an absolute neutrophil count greater than or equal to 0.5 × 109 cells/L for three consecutive days, achieved within 7 weeks following infusion. Flow cytometric assessment of single-RBC HbF and HbS shows fewer RBCs with high HbS% that would be most susceptible to sickling in BCLshmiR vs. HU High Responders: median 42% of RBCs with HbS%>70% in BCLshmiR vs. 61% in HU High Responders (p = 0.004). BCLshmiR subjects also demonstrate more RBCs resistant to HbS polymerization at lower physiologic oxygen tension: median 32% vs. 25% in HU High Responders (p = 0.006). Gene therapy-induced BCL11A down-regulation reverses the fetal-to-adult hemoglobin switch and induces RBCs with higher HbF%, lower HbS%, and greater resistance to deoxygenation-induced polymerization in clinical trial subjects compared with a cohort of highly responsive hydroxyurea-treated subjects