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Symmetry-adapted perturbation theory (SAPT) is an ab initio approach that directly computes noncovalent interaction energies in terms of electrostatics, exchange repulsion, induction/polarization, and London dispersion components. Due to its high computational scaling, routine applications of even the lowest order of SAPT are typically limited to a few hundred atoms. To address this limitation, we report here the addition of electrostatic embedding to the SAPT (EE-SAPT) and ISAPT (EE-ISAPT) methods. We illustrate the embedding scheme using water trimer as a prototype example. Then, we show that EE-SAPT/EE-ISAPT can be applied for efficiently and accurately computing noncovalent interactions in large systems, including solvated dimers and protein–ligand systems. In the latter application, particular care must be taken to properly handle the quantum mechanics/molecular mechanics boundary when it cuts covalent bonds. We investigate various schemes for handling charges near this boundary and demonstrate which are most effective in the context of charge-embedded SAPT. [ABSTRACT FROM AUTHOR]

IntroductionPatients are uniquely positioned to identify issues and to provide innovative solutions to problems impacting their care. Yet, patient engagement in quality improvement (QI) and health care governance remains limited and underexplored. In the Veterans Health Administration, the work of women's health managers (WHMs) includes engaging women veterans, a numerical minority with unique health care needs, in QI. We aimed to understand the extent to which WHMs engage women veterans along a continuum, highlight challenges to engagement, and identify potential strategies to facilitate multilevel patient engagement.MethodsData were generated from a multisite evaluation to improve delivery of comprehensive women's health care in Veterans Health Administration primary care sites. We conducted 39 semistructured interviews with WHMs across 21 sites. Guided by Carman et al.'s patient engagement framework, we analyzed the interviews using rapid-qualitative and content analysis methods.ResultsWhen effectively engaged, women veterans were important champions and partners in QI activities to improve the structure and delivery of care. However, most WHMs engaged women veterans in mainly informal or passive ways-that is, solicited feedback through comment cards, surveys, focus groups, and townhall meetings-and did not report pursuing more in-depth or long-term forms of engagement. WHMs also identified a variety of facilitators and challenges to engaging women veterans in QI.ConclusionsThere may be unanticipated benefits to health care policy from engaging patients in QI, especially for patients with unique health care needs who represent a minority within the health care system. However, managers require training and workflow integration of patient engagement tasks to increase their efficiency and allow for meaningful patient engagement.

The COVID-19 pandemic has exacerbated the adverse influence of structural racism and discrimination experienced by historically marginalized communities (e.g., Black, Latino/a/x, Indigenous, and transgender people). Structural racism contributes to trauma-induced health behaviors, increasing exposure to COVID-19 and restricting access to testing and vaccination. This intersection of multiple disadvantages has a negative impact on the mental health of these communities, and interventions addressing collective healing are needed in general and in the context of the COVID-19 pandemic. The Share, Trust, Organize, and Partner COVID-19 California Alliance (STOP COVID-19 CA), a statewide collaborative of 11 universities and 75 community partners, includes several workgroups to address gaps in COVID-19 information, vaccine trial participation, and access. One of these workgroups, the Vaccine Hesitancy Workgroup, adopted an anti-racist community-partnered praxis to implement restorative circles in historically marginalized communities to facilitate collective healing due to structural racism and the COVID-19 pandemic. The project resulted in the development of a multilevel pre-intervention restorative process to build or strengthen community-institutional partnerships when procurement of funds has been sought prior to community partnership. This article discusses this workgroup's role in advancing health justice by providing a community-based mental health intervention to marginalized communities in Southern California while using an antiracist praxis tool to develop a successful community-institutional partnership and to live up to the vision of community-based participatory research.

Abstract Background The rapid advancement of new genomic sequencing technology has enabled the development of multi-omic single-cell sequencing assays. These assays profile multiple modalities in the same cell and can often yield new insights not revealed with a single modality. For example, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) simultaneously profiles the RNA transcriptome and the surface protein expression. The surface protein markers in CITE-Seq can be used to identify cell populations similar to the iterative filtration process in flow cytometry, also called “gating”, and is an essential step for downstream analyses and data interpretation. While several packages allow users to interactively gate cells, they often do not process multi-omic sequencing datasets and may require writing redundant code to specify gate boundaries. To streamline the gating process, we developed CITEViz which allows users to interactively gate cells in Seurat-processed CITE-Seq data. CITEViz can also visualize basic quality control (QC) metrics allowing for a rapid and holistic evaluation of CITE-Seq data. Results We applied CITEViz to a peripheral blood mononuclear cell CITE-Seq dataset and gated for several major blood cell populations (CD14 monocytes, CD4 T cells, CD8 T cells, NK cells, B cells, and platelets) using canonical surface protein markers. The visualization features of CITEViz were used to investigate cellular heterogeneity in CD14 and CD16-expressing monocytes and to detect differential numbers of detected antibodies per patient donor. These results highlight the utility of CITEViz to enable the robust classification of single cell populations. Conclusions CITEViz is an R-Shiny app that standardizes the gating workflow in CITE-Seq data for efficient classification of cell populations. Its secondary function is to generate basic feature plots and QC figures specific to multi-omic data. The user interface and internal workflow of CITEViz uniquely work together to produce an organized workflow and sensible data structures for easy data retrieval. This package leverages the strengths of biologists and computational scientists to assess and analyze multi-omic single-cell datasets. In conclusion, CITEViz streamlines the flow cytometry gating workflow in CITE-Seq data to help facilitate novel hypothesis generation.

This article reports on a 3-year longitudinal study focused on the impact of cross-sector, collective impact approaches to creating cultures of campus health. The study sought to understand the integration of health and well-being concepts into university operations, including business practices and policies, as well as the contribution of public health initiatives focused on health-promoting universities to creating cultures of campus health for students, staff, and faculty. Research was carried out from spring 2018 to spring 2020 via focus group data collection and rapid qualitative analysis involving template and matrix analysis. A total of 18 focus groups were conducted across the 3-year study, six with students, eight with staff, and four with faculty. The initial cohort included 70 participants: 26 students, 31 staff, and 13 faculty. Qualitative analysis findings indicate a general pattern of change over time from a primary focus on well-being characterized by programs and services (e.g., fitness classes) to policy and structural-level interventions (e.g., stairwell beautification and hydration stations) promoting well-being for all. Grass-top and grassroots leadership and action were instrumental to changes in working and learning environments, policies, and campus environment/infrastructure. This work contributes to the growing literature on health-promoting universities and colleges and demonstrates the critical role of both top-down and ground-up approaches and leadership efforts to create more equitable and sustainable cultures of campus health and well-being.

BACKGROUND: The Latinx population experiences some of the highest rates of chronic disease, including obesity and type II diabetes. Such conditions may be especially burdensome in rural Latinx communities that often face barriers to accessing disease prevention resources and public health programs. METHODS: Diverse stakeholders (i.e., patients, community members, system of healthcare clinics, community food bank) tailored an existing cookbook, based on the U.S. Department of Agriculture MyPlate healthy eating and dietary guidelines, for local ingredients, health literacy, and language for rural Latinx and Indigenous Latin Americans. The cookbook recipes were disseminated widely via virtual cooking demonstrations, food distribution events, and social media. Pre- and posttest surveys were used to assess changes in diabetes knowledge measured by the 24-item American Diabetes Association Diabetic Knowledge Questionnaire and confidence in dietary behavior change over time measured by 4 questions of the 17-item Mediterranean Diet Index. A mixed effects, repeated measures analysis was conducted with gender ID, age range and educational attainment included as covariates and assessment interval as the predictor (pretest vs posttest) and change in confidence about adhering to four specific components of the Mediterranean diet. Focus groups elicited information on participants motivation and ability to use the recipes and eat healthy foods following the virtual cooking demonstration participation. RESULTS: A total of 20 virtual cooking demonstrations were conducted and 60 participants completed a pretest survey and 54 a posttest survey, a subsample (n = 19) participated in one of three focus groups. Most participants were female, identified as Latinx/Hispanic, were between the ages of 40-49, and spoke Spanish. 17% identified as Indigenous Latin American specifically as Purépecha, an indigenous group from Michoacán, Mexico. Survey and focus group findings indicated at posttest an increase in diabetes knowledge among participants with no prior diagnosis of chronic health conditions and more confidence in limiting sugary beverages and refined wheat pasta/white rice among indigenous participants. Focus group discussions explicated the quantitative findings. CONCLUSION: This study brought together patients and key stakeholders committed to addressing the social determinants of health and it mobilized the community to develop culturally vetted health education materials. The findings indicate the need for increased access to evidence-based nutrition education and to culturally appropriate food products that can be easily incorporated into daily food preparation.

BackgroundA novel coronavirus, SARS-CoV-2 (known as COVID-19), spread rapidly around the world, affecting all and creating an ongoing global pandemic. Across the United States, Latinx and Indigenous populations have been disproportionately affected by COVID-19 cases and death rates. An examination of the perceptions and beliefs about the spread of the virus, COVID-19 testing, and vaccination amongst racial-ethnic minority groups, specifically Latinx and Indigenous Latin American immigrant communities, is needed to alleviate the widespread disparity in new cases and deaths.MethodsThis study was carried out from August 2020 to January 2021 and used community-based participatory research to engage community partners and build the capacity of community health workers (i.e., promotores de salud) and pre-medical and medical students in conducting qualitative research. The objective of the study was to examine the structural and social determinants of health on perceptions of the coronavirus, its spread, and decisions around COVID-19 testing and vaccination. Data collection included ethnography involving observations in public settings and focus groups with members of Latinx and Indigenous Mexican farm-working communities in the Eastern Coachella Valley, located in the Inland Southern California desert region. A total of seven focus groups, six in Spanish and one in Purépecha, with a total of 55 participants were conducted. Topics covered include perceptions of the coronavirus and its spread, as well as COVID-19 testing and vaccination.ResultsUsing theme identification techniques, the findings identify structural and social factors that underly perceptions held by Latinx and Indigenous Mexican immigrants about the virus and COVID-19, which, in turn, shape attitudes and behaviors related to COVID-19 testing and vaccination. Common themes that emerged across focus groups include misinformation, lack of trust in institutions, and insecurity around employment and residency.ConclusionsThis immigrant population is structurally vulnerable to historical and present-day inequalities that put them at increased risk of COVID-19 exposure, morbidity, and mortality. Study findings indicate a significant need for interventions that decrease structural vulnerabilities by addressing issues of (dis)trust in government and public health among this population.

Rapid antigen test (RAT) is widely used for SARS-CoV-2 infection diagnostics. However, test sensitivity has decreased recently due to the emergence of the Omicron variant and its sublineages. Here we developed a panel of SARS-CoV-2 nucleocapsid protein (NP) specific mouse monoclonal antibodies (mAbs) and assessed their sensitivity and specificity to important SARS-CoV-2 variants. We identified seven mAbs that exhibited strong reactivity to SARS-CoV-2 variants and recombinant NP (rNP) by Western immunoblot or ELISA. Their specificity to SARS-CoV-2 was confirmed by negative or low reactivity to rNPs from SARS-CoV-1, MERS, and common human coronaviruses (HCoV-HKU1, HCoV–CO43, HCoV-NL63, and HCoV-229E). These seven mAbs were further tested by immunoplaque assay against selected variants of concern (VOCs), including two Omicron sublineages, and five mAbs (F461G13, F461G7, F459G7, F457G3, and F461G6), showed strong reactions, warranting further suitability testing for the development of diagnostic assay.

Introduction Huntington’s disease (HD) is an inherited neurodegenerative disease causing progressive cognitive and motor decline, largely due to basal ganglia (BG) atrophy. Rhythmic training offers promise as therapy to counteract BG-regulated deficits. We have developed HD-DRUM, a tablet-based app to enhance movement synchronisation skills and improve cognitive and motor abilities in people with HD. This paper outlines a randomised controlled unblinded trial protocol to determine the feasibility of a larger effectiveness trial for HD-DRUM. Additionally, the trial investigates cognitive and motor function measures, along with brain microstructure, aiming to advance our understanding of the neural mechanisms underlying training effects.Methods, design and analysis 50 individuals with HD, confirmed by genetic testing, and a Total Functional Capacity (TFC) score of 9–13, will be recruited into a two-arm randomised controlled feasibility trial. Consenting individuals with HD will be randomised to the intervention group, which entails 8 weeks of at-home usage of HD-DRUM or a usual-activity control group. All participants will undergo cognitive and motor assessments, alongside ultra-strong gradient (300 mT/m) brain microstructural MRI before and after the 8-week period. The feasibility assessment will encompass recruitment, retention, adherence and acceptability of HD-DRUM following prespecified criteria. The study will also evaluate variations in cognitive and motor performance and brain microstructure changes resulting from the intervention to determine effect size estimates for future sample size calculations.Ethics and dissemination The study has received favourable ethical opinion from the Wales Research Ethics Committee 2 (REC reference: 22/WA/0147) and is sponsored by Cardiff University (SPON1895-22) (Research Integrity, Governance and Ethics Team, Research & Innovation Services, Cardiff University, second Floor, Lakeside Building, University Hospital of Wales, Cardiff, CF14 4XW). Findings will be disseminated to researchers and clinicians in peer-reviewed publications and conference presentations, and to participants, carers and the general public via newsletters and public engagement activities. Data will be shared with the research community via the Enroll-HD platform.Trial registration number ISRCTN11906973.

Metal-based additive manufacturing offers potential to disrupt the manufacturing process across multiple industries. However, the vast majority of modern alloys are incompatible with the complex thermal histories of additive manufacturing. For example, the high gamma prime forming nickel-based superalloys are of considerable commercial interest owing to their properties; however, their gamma prime content renders them non-weldable and prone to cracking during additive manufacturing. Computational materials modeling and big data analytics is becoming an increasingly valuable tool for developing new alloys for additive manufacturing. This work reports the use of such tools toward the design of a high gamma prime superalloy with reduced cracking susceptibility while maintaining similar hardness to CM247. Experimental fabrication and characterization of the candidate alloys is performed. Results show the candidate alloys have improved printability, up to 41x reduction in crack density (mm/mm2) compared with CM247, and good agreement with the modeled predictions.

The growth of online learning has created a need for instructors who can competently teach online. This literature review explores the research questions, program recommendations, and future research suggestions related to professional development for online instructors. Articles were selected and coded based on date of publication and the context of the professional development. Results indicate that most research questions focused on (a) professional development programs, (b) instructors, and (c) instructors' online courses. Most program recommendations focused on (a) professional development programs, (b) context of professional development, and (c) instructors' activity during professional development. Future recommendations for research topics focused on professional development programs and instructors, while future recommendations for research methods focused on research design and institutional settings. The findings suggest that while professional development for online instructors is important, consistency in both design and delivery is lacking. Future research is needed to provide guidance to programs, instructors, and institutions leading to satisfaction and success for more online students.

In Huntington’s disease (HD), wearable inertial sensors could capture subtle changes in motor function. However, disease-specific validation of methods is necessary. This study presents an algorithm for walking bout and gait event detection in HD using a leg-worn accelerometer, validated only in the clinic and deployed in free-living conditions. Seventeen HD participants wore shank- and thigh-worn tri-axial accelerometers, and a wrist-worn device during two-minute walk tests in the clinic, with video reference data for validation. Thirteen participants wore one of the thigh-worn tri-axial accelerometers (AP: ActivPAL4) and the wrist-worn device for 7 days under free-living conditions, with proprietary AP data used as reference. Gait events were detected from shank and thigh acceleration using the Teager-Kaiser energy operator combined with unsupervised clustering. Estimated step count (SC) and temporal gait parameters were compared with reference data. In the clinic, low mean absolute percentage errors were observed for stride (shank/thigh: 0.6/0.9%) and stance (shank/thigh: 3.3/7.1%) times, and SC (shank/thigh: 3.1%). Similar errors were observed for proprietary AP SC (3.2%), with higher errors observed for the wrist-worn device (10.9%). At home, excellent agreement was observed between the proposed algorithm and AP software for SC and time spent walking (ICC $_{{2},{1}}\gt 0.975$ ). The wrist-worn device overestimated SC by 34.2%. The presented algorithm additionally allowed stride and stance time estimation, whose variability correlated significantly with clinical motor scores. The results demonstrate a new method for accurate estimation of HD gait parameters in the clinic and free-living conditions, using a single accelerometer worn on either the thigh or shank.

Postural instability is associated with disease status and fall risk in Persons with Multiple Sclerosis (PwMS). However, assessments of postural instability, known as postural sway, leverage force platforms or wearable accelerometers, and are most often conducted in laboratory environments and are thus not broadly accessible. Remote measures of postural sway captured during daily life may provide a more accessible alterative, but their ability to capture disease status and fall risk has not yet been established. We explored the utility of remote measures of postural sway in a sample of 33 PwMS. Remote measures of sway differed significantly from lab-based measures, but still demonstrated moderately strong associations with patient-reported measures of balance and mobility impairment. Machine learning models for predicting fall risk trained on lab data provided an Area Under Curve (AUC) of 0.79, while remote data only achieved an AUC of 0.51. Remote model performance improved to an AUC of 0.74 after a new, subject-specific k-means clustering approach was applied for identifying the remote data most appropriate for modelling. This cluster-based approach for analyzing remote data also strengthened associations with patient-reported measures, increasing their strength above those observed in the lab. This work introduces a new framework for analyzing data from remote patient monitoring technologies and demonstrates the promise of remote postural sway assessment for assessing fall risk and characterizing balance impairment in PwMS.

The Soft X-ray Imager (SXI) is part of the scientific payload of the Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission. SMILE is a joint science mission between the European Space Agency (ESA) and the Chinese Academy of Sciences (CAS) and is due for launch in 2025. SXI is a compact X-ray telescope with a wide field-of-view (FOV) capable of encompassing large portions of Earth’s magnetosphere from the vantage point of the SMILE orbit. SXI is sensitive to the soft X-rays produced by the Solar Wind Charge eXchange (SWCX) process produced when heavy ions of solar wind origin interact with neutral particles in Earth’s exosphere. SWCX provides a mechanism for boundary detection within the magnetosphere, such as the position of Earth’s magnetopause, because the solar wind heavy ions have a very low density in regions of closed magnetic field lines. The sensitivity of the SXI is such that it can potentially track movements of the magnetopause on timescales of a few minutes and the orbit of SMILE will enable such movements to be tracked for segments lasting many hours. SXI is led by the University of Leicester in the United Kingdom (UK) with collaborating organisations on hardware, software and science support within the UK, Europe, China and the United States.

This essay reviews Thomas Irvine’s 2021 book “Listening to China: Sound and the Sino-Western Encounter, 1770–1839”. The author highlights the central tenets of Irvine’s work (published by the University of Chicago Press), and considers its implications for histories of Sino-Western cultural exchange more broadly.

Study Objectives: The Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System contains individual-patient-level traumatic brain injury (TBI) data, which when combined, allows for the examination of rates and outcomes for key subpopulations at risk for developing sleep disturbance. Methods: This proof-of-concept study creates a model system for harmonizing data (i.e., combining and standardizing data) across FITBIR studies for participants with and without a history of TBI to estimate rates of sleep disturbance and identify risk factors. Results: Three studies were eligible for harmonization (N = 1753). Sleep disturbance was common among those with a history of mild TBI (63%). Individuals with mild TBI were two to four times more likely to have sleep disturbance compared to those with no history of TBI. Conclusions: This study established methods, harmonization code, and meta-databases that are publicly available on the FITBIR website. We demonstrated how the harmonization of FITBIR studies can answer TBI research questions, showing that associations between TBI and sleep disturbance may be influenced by demographic factors.

PurposeManagers and leaders have a critical role to play in sexual and gender-based harassment prevention within organizations. Although the Veterans Health Administration has committed to eliminating harassment through national directives and training programs, it is unclear how aware local-level managers and leaders are about public harassment at their facilities and how they perceive sexual and gender-based harassment. We examined middle managers' and leaders' views about whether harassment is perceived as a problem locally, and what policies and procedures (if any) are in place to address public harassment.MethodsWe conducted 69 semistructured telephone interviews with middle managers and facility leaders before implementation of an evidence-based quality improvement project designed to improve delivery of comprehensive women's health care. Transcripts were coded using the constant comparative method and analyzed for overarching themes.ResultsPerceptions of the prevalence of sexual and gender-based public harassment varied among middle managers and leaders. A little more than one-half of respondents were unaware of facility-level policies and procedures to address public harassment between patients. To decrease patient-to-patient harassment, both groups generally supported the creation of separate clinical spaces for women. However, middle managers also stated that education was needed to change patient harassing behavior, which they tied to male military culture.ConclusionsAligning divergent perspectives of what constitutes sexual and gender-based harassment and how to address it is a necessary step towards tackling harassment at the local level. Managers and leaders should continue to assess environments of care and share findings widely among employees and leadership to improve awareness and inform a unified response.

There has been substantial progress in the development of regenerative medicine strategies for CNS disorders over the last decade, with progression to early clinical studies for some conditions. However, there are multiple challenges along the translational pipeline, many of which are common across diseases and pertinent to multiple donor cell types. These include defining the point at which the preclinical data are sufficiently compelling to permit progression to the first clinical studies; scaling-up, characterization, quality control and validation of the cell product; design, validation and approval of the surgical device; and operative procedures for safe and effective delivery of cell product to the brain. Furthermore, clinical trials that incorporate principles of efficient design and disease-specific outcomes are urgently needed (particularly for those undertaken in rare diseases, where relatively small cohorts are an additional limiting factor), and all processes must be adaptable in a dynamic regulatory environment. Here we set out the challenges associated with the clinical translation of cell therapy, using Huntington's disease as a specific example, and suggest potential strategies to address these challenges. Huntington's disease presents a clear unmet need, but, importantly, it is an autosomal dominant condition with a readily available gene test, full genetic penetrance and a wide range of associated animal models, which together mean that it is a powerful condition in which to develop principles and test experimental therapeutics. We propose that solving these challenges in Huntington's disease would provide a road map for many other neurological conditions. This white paper represents a consensus opinion emerging from a series of meetings of the international translational platforms Stem Cells for Huntington's Disease and the European Huntington's Disease Network Advanced Therapies Working Group, established to identify the challenges of cell therapy, share experience, develop guidance and highlight future directions, with the aim to expedite progress towards therapies for clinical benefit in Huntington's disease.

Introduction: Comprehensive sexuality education (CSE) is associated with positive sexual and reproductive health (SRH) outcomes, including increased contraceptive use, lower rates of unintended pregnancy and prevention of sexual violence. However, implementation of and requirements for CSE vary across the United States which can negatively impact students, both during and beyond high school, including among college students. Methods: and Analysis: This paper describes the research protocol for a multi-staged approach for designing, implementing and evaluating an SRH course for up to 60 undergraduate students at a public university in California. Before the class is offered, we will conduct 20 in-depth interviews with current students, educators and course design experts to learn from their experiences and seek their guidance on course design. To evaluate the course, enrolled students will complete a pre-course and a post-course survey before and after class is taught, to assess students’ attitudes and values relevant to educational concepts and the format and delivery of the course and its modules and activities. Approximately 20 students will take part in an in-depth exit interview, after completing the course, to gather perceptions about how the course impacted their knowledge and behavior. The goal is to refine materials for future in-person course offerings and develop a prototype for a fully online version of the course. Discussion: This study introduces a novel university-level course to provide young adult students comprehensive, evidence-based education on sexual and reproductive health from a public health perspective. The program leverages existing CSE efforts, enhancing them with academic rigor, inclusive content and digital inclusion. This approach, inclusive of diverse sexual orientations, content on pleasure and sexual violence prevention, aims to fill existing gaps in university curricula and also set a new standard in CSE. The project's innovative and multidisciplinary design offers a model for broader impact within a large public university system and beyond.