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Rat Spine Fusion Models for Preclinical Research: Opportunities and Challenges
No full textRodent models have gained popularity for assessing the efficacy and safety of experimental spine fusion methods in preclinical research, but variability in surgical technique, graft materials, and outcome assessment has limited standardization across studies. This review highlights key developments in rat spinal fusion models, focusing on the strengths and limitations of the surgical techniques applied and advancements in quantitative and qualitative outcome measures, aiming to identify opportunities for increased consistency in experimental designs. A comprehensive literature review was performed by using PubMed to include studies utilizing rat models for spinal fusion. Posterolateral intertransverse fusion remains the most widely used model, often employing autografts or biologically enhanced scaffolds as controls, while the Wiltse paraspinal approach is chosen when minimal invasiveness is favored. Functional fusion outcome assessments have evolved from manual palpation and traditional radiography to sophisticated microcomputed tomography (μCT) analyses along with histological scoring and serum marker analyses. Consensus biomechanical analyses of rodent spine fusion outcomes remain lacking. Emerging rodent data on the effects of pharmacologic agents, systemic conditions, and biologic implants on fusion show wide-ranging fusion rates from 0% to 100% across studies. Overall, this review points to the need for standardization in surgical technique, control bone grafts, and multimodal outcome assessment to enhance the rigor, reproducibility, and translational relevance of rat spine fusion models for the early stage research and development of novel therapeutic interventions.No embarg
Perceived Importance of Obstetric Quality Measures to Veterans Receiving Community-Based Obstetric Care
No full textBACKGROUND: Racial and ethnic disparities in obstetric care persist in the United States. Veterans enrolled in Department of Veterans Affairs (VA) care receive obstetric care from community providers enrolled in the VA Community Care Network (CCN), yet little is known about Veterans' prenatal care decision-making. This study described how Black, Indigenous, and People of Color (BIPOC) Veterans select prenatal care providers and perceive hospital-level obstetric quality measures.
METHODS: Pregnant BIPOC Veterans (n = 27) were identified from a community-based doula pilot (N = 29) at two VA medical centers. During semi-structured telephone surveys conducted around 20 weeks gestation, Veterans described factors influencing provider selection and rated the importance of three Joint Commission obstetric quality measures-cesarean birth, unexpected complications in term newborns, and exclusive breast milk feeding-on a 3-point scale ("not," "somewhat," or "very" important). Open-ended responses contextualized these ratings, and participants were asked if they knew how to access hospital-level quality data.
RESULTS: Participants (mean age = 33 years) were predominantly Black (85.2%) and multiparous (70.4%). Provider selection was most influenced by geographic proximity (48.2%) and VA insurance coverage (44.4%). Hospital-level unexpected complications in term newborns was rated "very important" by 66.7%, followed by cesarean birth (48.1%) and exclusive breast milk feeding (40.7%). Most Veterans valued measures perceived as related to infant well-being. However, 74.1% did not know how to access quality data.
CONCLUSIONS FOR PRACTICE: BIPOC Veterans valued hospital-level obstetric quality measures related to infant outcomes and prioritized geographic accessibility and insurance coverage when selecting providers. Relevant, accessible quality information may allow Veterans to make better informed prenatal care decisions.No embarg
Human-Centered Design Development and Acceptability Testing of a Goal Concordant Prescribing Program in Hospice
Get PDFHome hospice medication management ideally addresses symptoms, reduces unnecessary medication use, and optimizes quality of life. Grounding decisions in goals of care is critical. How to ascertain and align patients', families', and clinicians' goals for medication management remains challenging. To describe the iterative development and acceptability testing of a structured, interdisciplinary approach to goal concordant prescribing (GCP). We started with a previously developed deprescribing curriculum that followed a three-step process: review, align, and simplify. We utilized human-centered design and adult learning experts to translate the existing curriculum into tools and training that addressed gaps identified in an environmental scan (see Supplementary Data for a review of existing tools). Weekly multidisciplinary design team meetings revealed the need for tools to facilitate medication-focused and goal-oriented communication. The revised GCP program includes three clinician-facing tools: (1) GCP Person-Centered Medication Reconciliation worksheet, (2) Goal Assessment and Priorities (GAP) Tool, and (3) GCP Conversation Guide. Acceptability was tested with nursing and social work staff at a not-for-profit hospice who completed two 2-hour GCP training sessions. We used a content analytic approach to evaluate written and verbal feedback that was collected after each session. Participants felt that framing deprescribing in positivist language that connected medication changes to goals was innovative and a useful conversation skill. Participants also felt that GCP training was acceptable, the GAP tool and skill practice were useful, the GCP Program added value to clinical practice, and medication review in relation to prioritized goals was innovative and useful without adding to clinician workload. GCP supports alignment of patient and family priorities with medication management. This nurse-delivered intervention involves the interdisciplinary team and employs novel tools. Pilot testing indicates GCP tool and training acceptability to facilitate medication management conversations.No embarg
Perspectives of veterans with spinal cord injuries and disorders and their providers on impacted healthcare during the COVID-19 pandemic
No full textObjective: Veterans with spinal cord injuries and disorders (SCI/D) reported experiencing challenges from disrupted and deferred health services during the COVID-19 pandemic, including disrupted care coordination, supply chain, and essential services, such as wheelchair repair. This study used qualitative methods to examine the perspectives of Veterans with SCI/D (VSCI/D) and SCI/D healthcare providers on how the COVID-19 pandemic impacted health services.
Design/setting/participants: Virtual focus groups were conducted with both VSCI/D who received care at the Veterans Health Administration (VHA) and VHA SCI/D providers who provided services for VSCI/D between March 2020 and March 2022.
Outcome measures: Topics assessed COVID-19 pandemic experiences including healthcare access and needs, Veteran and provider perspectives of Veterans' experiences during the pandemic, Veterans' coping strategies, and future emergency preparedness strategies.
Results: There were 11 Veterans and 11 providers who participated in focus groups. Five themes were identified: (1) challenges with healthcare, care coordination, and homecare; (2) supply chain issues; (3) adapting to virtual platforms for support and therapy; (4) communication and reliable information about COVID-19; and (5) challenges with isolation and limited independence.
Conclusion: This study highlights challenges VSCI/D faced during the COVID-19 pandemic. Recommendations to enhance VHA support for VSCI/D during future emergencies include strengthening home care support, system level changes to supply management to be more flexible, and interdisciplinary town halls to transparently share comprehensive information. Virtual peer support groups may address challenges with isolation and limited independence.No embarg
Singletrome enhances detection of long noncoding RNAs in single cell transcriptomes
Get PDFSingle cell RNA sequencing (scRNA-seq) has revolutionized the study of gene expression in individual cell types, but scRNA-seq studies have focused primarily on expression of protein-coding genes. Long noncoding RNAs (lncRNAs) are more diverse than protein-coding genes, yet remain underexplored in part because they are underrepresented in reference annotations applied to scRNA-seq. Merging annotations containing protein-coding and lncRNA genes is not sufficient, because the addition of lncRNA genes that overlap in sense and antisense with protein-coding genes will affect how reads are counted for both protein-coding and lncRNA genes. Here, we introduce Singletrome, a Singularity image that integrates protein-coding and lncRNA gene transfer format (GTF) annotations to generate enhanced annotations that take into account the sense and antisense overlap of annotated genes, maps scRNA-seq data, and produces files for downstream analysis and visualization. With Singletrome, we detected thousands of lncRNAs not included in GENCODE, clustered cell types based solely on lncRNA expression, and demonstrated that machine learning can predict cell type and disease through lncRNAs alone. This comprehensive annotation will allow mapping of lncRNA expression across cell types of the human body, facilitating the development of an atlas of human lncRNAs in health and disease with the ability to integrate new lncRNA annotations as they become available.No embarg
Parent and Child Perceived Barriers to Health Behavior Change in a Family-Centered Obesity Intervention
No full textPurposeWe sought to explore perceived barriers to engaging in weight-related health behavior change among parent child dyads.DesignThis is a secondary analysis of data from a cluster-randomized controlled trial investigating the effectiveness of Fitline telephonic coaching vs Fitline workbook at improving weight-related health behaviors and body mass index for children 8-12 years old with overweight and obesity.SettingThe trial which the present data comes from was conducted within 20 pediatric primary care practices in Central Massachusetts.SampleData from 499 parent-child dyads were included.MeasuresBarriers to weight-related health behavior changes were assessed via 10 survey items answered by parents and the enrolled child at baseline, 6- and 12-month.AnalysisWe used frequencies to describe the distribution of parent and child reported behavior-change barriers as well as McNemar's and Bowker's tests to compare distributions of behavior-change barriers at baseline and change in report of behavior-change barriers at 6-month.ResultsWe found that barriers to weight-related health behavior change varied within parent child dyads with up to 30% of dyads disagreeing on behavior-change barrier perception at baseline. Additionally, up to 37% of dyads were not aligned on reported change in barriers to health behavior change at 6-month.ConclusionOur findings support the potential benefit of integrating behavior-change barrier assessment from both the parent and child perspectives into intervention delivery when developing and tailoring family-centered interventions.No embarg
UMCCTS Newsletter, March 2025
No full textThis is the March 2025 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.Supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grants UL1 TR001453, TL1 TR001454 and KL2 TR001455.No embarg
Multilevel determinants of medication preferences for opioid use disorder among criminal-legal-involved populations: Insights from a scoping review
Get PDFBACKGROUND: Individuals with opioid use disorder (OUD) hold varying perceptions of the three medications to treat OUD (MOUD). Data on these perceptions among those with criminal-legal involvement is limited. To optimize MOUD service delivery, especially in criminal-legal settings, it is essential to explore the preferences and attitudes of those with legal involvement.
METHODS: We conducted a scoping review of literature published via PubMed, Embase, Web of Science, Scopus, PsycInfo, and SocINDEX (January 1, 2014-September 17, 2024). Three-stage screening process was employed by two reviewers: title/abstract (n = 2085 articles), full-text (n = 88), and data extraction of 44 articles included in the final sample. Content analysis was used to understand preferences/attitudes toward MOUD and related influential factors.
RESULTS: Factors that influenced MOUD preferences/attitudes were clustered in positive (n = 39 articles; i.e., like), negative (n = 38; i.e., dislike), or mixed (n = 20; both positive and negative) valences. Methadone was the most referenced (n = 30), with more articles noting negative attitudes than positive. Fewer studies focused on oral buprenorphine (n = 18), with balanced positive and negative views. Seven articles on injectable MOUD highlighted mostly positive attitudes. Factors shaping preferences/attitudes spanned from individual to structural levels. Common factors associated with negative preferences included MOUD program rules, side or adverse effects, and drug-free ideology. Positive preferences were often engendered by flexible MOUD delivery and beliefs about MOUD. Influential factors differed by MOUD type.
CONCLUSIONS: Preferences/attitudes toward MOUD among criminal-legal-involved populations are shaped by intersecting multilevel determinants and differ by MOUD type. Identified factors might serve as intervention targets to better meet individuals' needs.No embarg
Tomtom-lite: Accelerating Tomtom enables large-scale and real-time motif similarity scoring
Get PDFSummary: Pairwise sequence similarity is a core operation in genomic analysis, yet most attention has been given to sequences made up of discrete characters. With the growing prevalence of machine learning, calculating similarities for sequences of continuous representations, e.g. frequency-based position-weight matrices (PWMs) and attribution-based contribution-weight matrices, is taking on newfound importance. Tomtom has previously been proposed as an algorithm for identifying pairs of PWMs whose similarity is statistically significant, but the implementation remains inefficient for both real-time and large-scale analysis. Accordingly, we have re-implemented Tomtom as a numba-accelerated Python function that is natively multi-threaded, avoids cache misses, more efficiently caches intermediate values, and uses approximations at compute bottlenecks. Here, we provide a detailed description of the original Tomtom method (see Appendix 1) and present results demonstrating that our re-implementation can achieve over a thousand-fold speedup compared with the original tool on reasonable tasks (see Appendix 2).
Availability and implementation: Our implementation of Tomtom is freely available as a Python package at https://github.com/jmschrei/memesuite-lite, which can be downloaded via pip install memelite or at https://zenodo.org/records/17008952.No embarg
Versatile Polypeptide-Anchored Antifouling Dip-Coatings for Common Medical Implant Materials
No full textImplant-associated infections represent a critical global healthcare challenge, exacerbated by recalcitrant biofilm formation and rising antimicrobial resistance. While antifouling polymer coatings could deter bacterial adhesion, common grafting methods such as surface-initiated polymerization face scalability and regulatory challenges. Dip-coating of antifouling polymers, facilitated by catechol-mediated anchorage to common medical implants, serves as a translationally appealing alternative. Although 3,4-dihydroxyphenylalanine (DOPA)-lysine-based oligopeptides were shown to exhibit mussel adhesive-like properties, they are not suitable for tethering high-molecular-weight (MW) antifouling polymers required for achieving adequate surface coverage. To facilitate unbiased screening for robust higher MW surface anchors, we synthesized a library of azide-terminated polypeptides─composed of DOPA alone or copolymerized with lysine, glutamate, or both randomly or in blocks in varying ratios─using N-carboxyanhydride ring-opening polymerization, achieving narrow polydispersity and excellent compositional control. These polypeptides were dip-coated onto Ti6Al4V and poly(ether ether ketone) substrates and conjugated with high-MW zwitterionic poly(sulfobetaine methacrylate) (pSBMA) by strain-promoted azide-alkyne cycloaddition. Using surface hydrophilicity as a readout of dip-coating efficiency and validated by X-ray photoelectron spectroscopy, we identified DOPA homopolymers as the optimal surface anchor for both substrates, significantly outperforming all copolymers containing lysine, glutamate, or both. The resulting pSBMA coatings resisted nonspecific protein adsorption or bacterial colonization and remained stable over one month in aqueous buffer at physiological pH and temperature. This DOPA homopolypeptide-mediated dip-coating strategy was also successfully extended to other implant substrates such as polyethylene terephthalate and silicone, establishing it as a potential universal implant surface modification approach.No embarg