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Baseline characteristics of participants in the Biomarkers for Evaluating Spine Treatments clinical trial: a sequential multiple assignment randomized trial for chronic low back pain†
Get PDFOBJECTIVE: Chronic low back pain (cLBP) is a significant public health problem in the United States. A method to identify treatments that are most likely effective for an individual patient based on their unique characteristics is needed. METHODS: The Biomarkers for Evaluating Spine Treatments (BEST) Trial is a sequential, multiple assignment, randomized trial designed to estimate an optimal treatment or combination of treatments to reduce pain intensity and interference at 24 weeks in individuals with cLBP. RESULTS: We describe the patient-reported characteristics of the BEST Trial at the Baseline visit. Data collection for extensive required phenotyping is reported. We analyzed the run-in period of the BEST Trial to evaluate predictors of run-in failure. The BEST Trial enrolled 1019 participants and randomized 805 participants (61.6% female, mean age 50.4, 12.5% Black or African American) to the first stage of treatment. We collected extensive required phenotyping on all 805 randomized BEST Trial participants, and additional optional phenotyping on 510 (63.4%) participants. CONCLUSIONS: The BEST Trial successfully enrolled a racially and geographically diverse sample of chronic low back pain patients and completed rich phenotypic assessments to inform our primary goal of identifying in whom different treatments show optimal response. We demonstrated the feasibility of collecting extensive phenotypic assessments in a multi-site clinical trial of cLBP. CLINICAL TRIAL REGISTRATION NUMBER: The Biomarkers for Evaluating Spine Treatments (BEST) Trial is registered on ClinicalTrials.gov. Registration number: NCT05396014 (https://clinicaltrials.gov/study/NCT05396014)
T2 Hyperintensities in Gracile Tracts of Cervical Spinal Cord in Giant Axonal Neuropathy (GAN)
Get PDFIntroduction/Aims Giant axonal neuropathy (GAN) is a hereditary neurodegenerative disease due to the absence or loss of function of the gigaxonin gene. Pathologic findings in GAN are those of “dying‐back” axonal degeneration, in which the distal axon degenerates but the more proximal axon and neuronal cell body remain intact. Aims of this study were to (1) document imaging abnormalities that may occur in the spinal cords of GAN patients; and (2) assess histologically the spinal cords of GAN rodent models. Methods A clinical trial of intrathecal ( IT ) scAAV9 / JeT ‐ GAN gene transfer provided a cohort of GAN patients for study. We examined spinal magnetic resonance imaging ( MRI ) studies from a subset of pretreatment GAN patients ages 6–14 years. For radiologic‐pathologic correlation, we examined histologically spinal cords from GAN rodent models with pathological features of human GAN . Results Of 10 GAN ‐patient spinal MRIs , 7 showed cervical or diffuse cord atrophy. Five MRIs additionally showed hyperintense, T2 ‐signal abnormalities bilaterally in the cervical gracile tracts. Microscopy of GAN ‐rodent spinal cords revealed many actively degenerating axons in the cervical gracile tracts but few degenerating axons elsewhere in the cord. Discussion The localization of spinal T‐2 signal abnormalities to the cervical gracile tracts in GAN patients mirrors the localization of active dying‐back axonal degeneration in GAN rodent models and suggests that these T2‐signal abnormalities may be used as a surrogate marker of active axonal degeneration in the long tracts of the spinal cord in GAN and possibly other dying‐back neurodegenerative diseases involving the spinal cord
Ecotone Might Provide Key Refugium for Sky Island Mammals in the Southern Appalachian Mountains
Get PDFSky islands, ecosystems found on geographically isolated mountain peaks, are among the most biodiverse ecosystems in the world but face a disproportionately high threat from climate change. High‐elevation, montane ecosystems, which are already at their upper altitudinal limits, are predicted to severely contract in response to climate change. The identification and conservation of refugia is an increasingly important approach for protecting biodiversity associated with imperiled ecosystems. We explored the spruce‐fir–northern hardwood ecotone as a possible refugium for mammals in the Southern Appalachian red spruce (Picea rubens)‐Fraser fir (Abies fraseri) sky islands. We conducted livetrapping, camera trapping, and ultrasonic acoustic surveys to characterize mammal diversity across the spruce‐fir–northern hardwood forest gradient on Grandfather Mountain and Roan Mountain Highlands in western North Carolina, USA. We detected four out of the five spruce‐fir‐associated small mammal species in both spruce‐fir and ecotone habitats. Mammal species richness, alpha diversity, and bat activity tended to be higher in the ecotone than in the other forest types on both mountains. Next, the abundance of small mammals associated with spruce‐fir was higher in the spruce‐fir and ecotone forests for one of the three species we were able to estimate. Together, our results suggest that the spruce‐fir–northern hardwood ecotone might serve as refugium for mammal species that are associated with spruce‐fir sky islands in the Southern Appalachian Mountains and mammalian conservation efforts in this biodiversity hotspot should consider focusing on the ecotone in addition to the adjacent spruce‐fir ecosystem. Sky islands are among the most biodiverse ecosystems in the world but face a disproportionately high threat from climate change. We examined the spruce‐fir–northern hardwood ecotone as a possible refugium for mammals in the Southern Appalachian red spruce (Picea rubens)–Fraser fir (Abies fraseri) sky islands. We detected spruce‐fir‐associated small mammal species in both spruce‐fir and ecotone habitats, wherein mammal species richness, alpha diversity, and bat activity tended to be higher in the ecotone than in the other forest types on both mountains. Together, our results suggest that the spruce‐fir–northern hardwood ecotone may serve as a key refugium for mammal species that are associated with spruce‐fir sky islands in the Southern Appalachian Mountains, and mammalian conservation efforts in this biodiversity hotspot should consider focusing on this ecotone in addition to the adjacent spruce‐fir ecosystem
Can an Algorithm Tell How Spiritual You Are? Using Generative Pretrained Transformers for Sophisticated Forms of Text Analysis.
Get PDFText analysis is a form of psychological assessment that involves converting qualitative information (text) into quantitative data. We tested whether automated text analysis using Generative Pre-trained Transformers (GPTs) can match the "gold standard" of manual text analysis, even when assessing a highly nuanced construct like spirituality.In Study 1, N = 2199 US undergraduates wrote about their goals (N = 6597 texts) and completed self-reports of spirituality and theoretically related constructs (religiousness and mental health). In Study 2, N = 357 community adults wrote short essays (N = 714 texts) and completed trait self-reports, 5 weeks of daily diaries, and behavioral measures of spirituality. Trained research assistants and GPTs then coded the texts for spirituality.The GPTs performed just as well as human raters. Human- and GPT-generated scores were remarkably consistent and showed equivalent associations with other measures of spirituality and theoretically related constructs.GPTs can match the gold standard set by human raters, even in sophisticated forms of text analysis, but require a fraction of the time and labor
Polybacterial intracellular macromolecules shape single-cell inflammatory profiles in upper airway epithelia
Get PDFMucosal epithelial cells of the upper airways are continuously exposed to microbes throughout life. Specialized niches such as the anterior nares and the tooth are especially susceptible to dysbiosis and chronic inflammatory diseases. Here, we reanalyzed our v1-Human Periodontal Atlas, identifying polybacterial signatures (20% Gram-positive; 80% Gram-negative) and distinct responses of bacterial-associated epithelia. Fluorescence microscopy detected numerous persistent polybacterial intracellular macromolecules (PIMs) within human oral keratinocytes (HOKs), including bacterial rRNA, mRNA, and glycolipids. PIM levels directly correlated with enhanced receptor-ligand signaling in vivo. Inflammatory “keratokines” targeting immune cells were synergistically upregulated in lipopolysaccharide-challenged HOKs, while endogenous lipoteichoic acid (LTA) correlated with CXCL1/8 expression in vitro and in vivo. Application of Drug2Cell suggested altered drug efficacy predictions based on PIM detection—agnostic of disease state. CXCL1/8 expression again correlated with LTA in epithelial cells of the nasal cavity, oropharynx, and trachea. Thus, PIMs shape epithelial single-cell profiles across upper airway mucosae
Mental, social, and economic impacts of environmental health services in healthcare facilities in low- and middle-income countries
No full textEnvironmental health services in healthcare facilities include water, sanitation, hygiene, waste management, and cleaning. This systematic scoping review aimed to identify and synthesize evidence for the mental, social, and economic impacts of environmental health services for patients and workers in low- and middle-income country healthcare facilities. We conducted a systematic literature search in 2023 and updated it in 2025. After title-abstract and full-text screening, we identified 231 studies that measured mental, social, and/or economic impacts of environmental health services in healthcare facilities in low- or middle-income countries. Most of the identified studies (91%; n = 209) described impacts on patients, whereas only 12% (n = 28) described impacts on healthcare workers. The most commonly reported impacts were patient satisfaction (reported by 141 studies), healthcare utilization (28 studies) and patient-perceived quality of care (22 studies). Few studies reported on economic impacts or examined impacts arising from hygiene and waste management services. While most studies (78%; n = 180) used quantitative measures, fewer than half used pretested or validated measurement tools. Findings demonstrate the multitude of mental, social, and economic impacts that arise from environmental health services in healthcare facilities
Evaluating the reliability of large language models in answering FAQs for cataract surgery
Get PDFCataract surgery is one of the most common and effective surgeries performed worldwide, yet patient education remains a challenge due to limitations in health literacy among the general population. Our study evaluated the reliability of different large language models (LLMs) in providing accurate, complete, and clear responses to frequently asked questions (FAQs) related to cataract surgery. A comprehensive list of 20 FAQs about cataract surgery were submitted sequentially as a prompt to nine different LLMs. All 180 answers were recorded and scored by two expert ophthalmologists, blinded to the model type, on a 5-point scale measuring the degree of accuracy, completeness, and clarity. Interrater agreement was measured using a weighted kappa coefficient and model performances were compared using the Friedman test and post-hoc analysis. Our results showed all models performed well responding to FAQs (79% of responses scored “excellent”), serving as effective tools in answering patient FAQs. LLaMA 4 and Copilot scored lower on average relative to other models (p < .05), however, they remained effective at FAQ responses overall. Potential expansion of LLMs as patient education tools into clinical settings should be considered, as they exhibit effectiveness in providing clear, accurate, and complete responses to cataract surgery FAQs
Methylation of Arsenic by Human and Murine Arsenic Methyltransferases
Get PDFEnzymatic methylation catalyzed by arsenic (As) methyltransferase (AS3MT) is the central pathway for the metabolism and detoxification of inorganic As (iAs). In both mice and humans, AS3MT converts iAs to monomethyl-As (MAs) and dimethyl-As (DMAs) using S-adenosylmethionine as a methyl group donor. However, mice are much more efficient in methylating iAs than humans. What causes this difference remains unclear. To explore this question, I studied the Michaelis-Menten kinetics of iAs methylation and the methylation of its intermediate metabolite, MAs, by human and murine AS3MTs. Michaelis-Menten kinetics were characterized in-vitro for recombinant human and murine AS3MTs and in primary hepatocytes from wild-type (WT) and humanized (Hu) C57BL/6N mice that express murine and human AS3MT.The rates of iAs and MAs methylation and the proportions of methylated metabolites differed between the murine and humanized in vitro and cell culture systems. In the in vitro system, only small differences in Michaelis-Menten constants (Km and Vmax) were found between the murine and human enzymes using iAsIII or MAsIII as a substrate. However, there were major differences in Michaelis-Menten kinetics between WT and humanized hepatocytes. In WT hepatocytes, iAsIII was quickly converted to DMAs while humanized hepatocytes produced only negligible amounts of DMAs. The kinetics data suggests that humanized hepatocytes have higher affinity (i.e., lower Km) for iAsIII than WT hepatocytes, but lower capacity (i.e., lower Vmax) to methylate iAs to DMAs. In comparison, WT hepatocytes had both greater affinity and methylation capacity for MAsIII. Overall, the methylation kinetics in the in-vitro systems did not correlate with what was observed in the hepatocyte cultures. PCR analysis showed that WT hepatocytes expressed significantly more AS3MT mRNA than humanized hepatocytes.These results suggest that the known differences in the primary structure of murine and human AS3MTs have only a minor effect on iAs methylation efficiency, and that AS3MT expression is a key factor responsible for the difference in iAs methylation in primary hepatocytes. Other cellular factors and processes (e.g., endogenous cofactors of AS3MT or membrane transporters) may also play a role in influencing As metabolism in hepatocytes, though these factors were not investigated in the present study.Master of Scienc
STANDARDIZING GUIDELINES FOR THE POST ADMINISTRATION OF THE GAD-7 SCREENING TOOL AT A VETERANS’ RESIDENTIAL FACILITY
Get PDFABSTRACTBrittney Bowman: Standardizing Guidelines for the Post Administration of the GAD-7 Screening Tool at a Veterans’ Residential Facility(Under the direction of Ann-Marie Jones)ProblemGeneralized Anxiety Disorder (GAD) is described as excessive worry that is uncontrolled and affects the functions of daily living. GAD is highly prevalent among U.S. adults, with rates increasing due to stressors such as the COVID-19 pandemic. Veterans, a vulnerable subgroup population of US adults, face an even greater risk of suffering from GAD due to pre-existing mental health conditions, social isolation, and economic instability. Veterans face unique risk factors that increase their likelihood of developing GAD, including combat exposure, PTSD, and challenges in transitioning to civilian life. PurposeThe purpose of this quality improvement project was to systematically incorporate the GAD-7 screening tool with a score-based notification algorithm based on the GAD-7 into every new intake appointment, at the Veteran’s Life Center in Butner, NC, aiming to facilitate early identification and intervention of generalized anxiety disorder and treatment. MethodsA 45-day intervention in which staff implemented an algorithm post-admission to a veterans’ facility included the administration of the GAD-7 screening tool upon admission to the Veterans Life Center. The nurse administered and scored the completed GAD-7, thus triggering the symptoms-related algorithm. The algorithm included how often the resident was seen by the NP and appropriate follow-up appointment scheduling.ResultsFollowing the implementation of the Post administration of the GAD-7 Screening Algorithm, data was collected on six veterans admitted to the veterans’ residential facility during the 45-day intervention period. All six veterans received their initial GAD-7 screening upon admission. In contrast to the retrospective cohort, 100% of these veterans received a documented H&P assessment within 10 days, reflecting a 50% improvement in timely initial evaluation. Additionally, the algorithm introduced a structured response protocol whereby elevated GAD-7 scores triggered chart flagging by nursing staff and prompted direct communication to the NP for clinical review.Discussion and Further ConsiderationsProject outcomes showed significant data improvement. Continued evaluation is needed to address and resolve the barriers to using a structured approach to recognizing and treating GAD according to Evidence Based Practice. With continued assessment and change, marked improvement and sustainability over time are achievable.Doctor of Nursing Practic
CAR-T CELL THERAPY FOR TRIPLE-NEGATIVE BREAST CANCER: PRECLINICAL INSIGHTS FOR IMMUNOTHERAPY OPTIMIZATION IN OBESITY
Get PDFImmunotherapy is a type of treatment that harnesses a patient’s immune system to target diseases like cancer. Chimeric antigen receptor (CAR)-T cell therapy relies on T cells engineered to target antigens expressed on cancer cells and has radically improved treatment for some hematological cancers and is gaining traction in solid tumors. For CAR-T cell therapy to be effective, cancers must express the appropriate antigen. B7-H3 is an immunosuppressive protein often expressed by cancer cells that is targetable with B7-H3.CAR-T cell therapy. Obesity-derived inflammatory signals promote tumor growth, dampen antitumor immunity, and promote expression of immunosuppressive proteins. However, the potential for obesity to alter efficacy of CAR-T cell therapy is unknown. Hence, we sought to understand whether obesity affects activity and durability of B7-H3.CAR-T cell therapy, and whether obesity relies on the immunosuppressive protein, B7-H3, for triple-negative breast cancer (TNBC) growth.We utilized preclinical models to determine the relationship between obesity-associated cytokine signaling and B7-H3. We discovered that cytokines like TNF and IFNγ upregulate B7-H3 in both human and murine TNBC cell lines. We used B7-H3 suppressed cells to determine that obesity promotes TNBC growth by suppressing antitumor immunity through B7-H3 expression. Next, we demonstrated that obesity impairs both B7-H3.CAR-T cell therapy activity and durability. We showed that B7-H3.CAR-T cell therapy can control tumor growth in a syngeneic model of TNBC and that despite similar in vitro cell killing activity, T cells from obese mice harbor important transcriptomic and phenotypic differences. We also show that obesity impairs the formation of tissue-resident memory-like T cells and that obesity is detrimental to survival following rechallenge. Taken together this work demonstrates that obesity is an important but understudied determinant of B7-H3.CAR-T cell therapy response and durability, thus paving the way for future research to study obesity as a variable in large scale clinical immunotherapy settings.Doctor of Philosoph