194341 research outputs found
Sort by
Psychosis/disorganised symptoms measured with ecological momentary assessment: changes over a 12-month treatment trial of xanomeline and trospium chloride in schizophrenia
No full textPerformance of a blood-biomarker test for early detection of pancreatic ductal adenocarcinoma (PDAC) across all stages of disease versus a mixed control population
No full text659 Background: Early detection of pancreatic ductal adenocarcinoma (PDAC) has a significant impact on pancreatic cancer outcomes. Despite this, 4 in 5 patients are diagnosed at later disease stage where surgery is no longer an option. There is a need for more accurate and less burdensome testing methodology. We previously conducted two independent clinical validation studies (CLARITI and VERIFI) where PancreaSure, a serum-based early detection test for PDAC, showed high accuracy in differentiating early-stage disease versus high-risk control patients. To further understand the performance of the test across a varied patient population, we set out to determine test performance in Stage I-IV PDAC and in healthy controls. Methods: PancreaSure, a biomarker signature comprising a mathematical summation of ICAM-1, THSB1, CTSD, TIMP1, and CA19-9 values with a predefined cutoff to differentiate Stage I and Stage II PDAC from controls at high-risk due to genetic/familial background, was assessed for sensitivity and specificity in detecting Stage III and IV PDAC and in normal, healthy controls. Pooled analysis was conducted to determine weighted performance across all stages of PDAC and in high-risk and healthy controls. Results: The study comprised 317 Stage I-II (early stage) and 152 Stage III-IV (late stage) PDAC cases, 1134 high-risk controls, and 295 healthy controls that were collected from US and European sites. PancreaSure overall weighted sensitivity was 79.8% (73.3-86.4% 95% CI). Sensitivity was 77.6% (73.0-82.2%, 95% CI) in early-stage PDAC and 88.2% (81.8-93.0%, 95% CI) in late-stage PDAC. Overall weighted specificity was 90.8% (87.8-93.8% 95% CI). Specificity was 92.2% (90.6-93.7%, 95% CI) in high-risk controls and 97.7% (95.3-99.1%, 95% CI) in healthy controls. Conclusions: Across a robust clinical experience of almost 1900 patients, PancreaSure showed high accuracy across Stage I-IV PDAC, with improved performance in late-stage disease and in healthy controls. These results support the robustness of the test’s performance and can serve as a tool for both early-stage and late-stage PDAC detection in patients at high and normal risk of pancreatic cancer
Perceived Value, Ownership, and Barriers to Smart Home Technology for Individuals with Spinal Cord Injury and Disease
No full textTo investigate the categories of Mainstream Smart Home technology (MSHT) that are commonly owned by individuals with spinal cord injury and disease (SCI/D), their perceived benefits, and barriers to obtaining or utilizing.
Cross-sectional.
SCI Model Systems.
Individuals (N=417) 18 years of age or older enrolled in a participating SCI Model Systems Center between October 2022 and May 2025.
Not applicable.
Participants were surveyed on 18 categories of MSHT and indicated for each ownership status, perceived benefit of owning (yes, no, unsure), acquisition method, satisfaction, and barriers to ownership or use.
The median number of MSHT categories owned per participant was 4 (interquartile ratio [IQR] 2-6), with 7 (IQR 3-10) categories perceived as beneficial but not owned. Most devices (88.4%) were acquired through self-pay. Common barriers to ownership were cost (63.6%) and installation difficulty (35.2%). Individuals with greater upper extremity (UE) impairment were significantly more likely to perceive benefit from voice assistants, smart plugs, smart bed controls, and smart televisions. Multivariate logistic regression identified higher education (odds ratio [OR]=1.97, p=0.03), higher income (OR=2.25, p<0.01), and greater UE impairment (OR=1.75, p=0.03) as significant predictors for owning ≥4 categories of MSHT.
MSHT was highly valued among individuals with SCI/D, though the rate of ownership of MSHT was low, especially for costlier or more complex devices. Barriers stem largely from affordability and limited support for installation and training. Integrating MSHT training into rehabilitation programs and improving funding, education, and service delivery could enhance access and autonomy for people with SCI/D
MDX-2001-101 study protocol: a phase I/IIa, multicenter, first-in-human, open-label clinical trial evaluating MDX2001 monotherapy in patients with advanced solid tumors
No full textMDX2001 is a tetraspecific T-cell engager-expander antibody engineered to recognize four distinct antigens: cellular mesenchymal-epithelial transition factor (c-MET) and trophoblast antigen 2 (TROP2) to direct T cells to tumor cells, CD3 to activate T cells, and CD28 to enhance T-cell survival and proliferation. MDX2001 has demonstrated potent antitumor activity in nonclinical studies over a wide range of tumor types. Here, we present the protocol design for study MDX-2001-101, a multicenter, open-label, phase I/IIa clinical trial designed to evaluate the safety, tolerability, and antitumor effects of MDX2001 in patients with advanced solid tumors. The study comprises a phase Ia dose escalation guided by a Bayesian optimal interval design with a targeted maximum tolerated dose toxicity rate of 30%, a phase Ib dose expansion, and a phase IIa indication expansion
Synergistic intragenic epigenetic deregulation by IDH2 and SRSF2 mutations causes mis-splicing of key transcriptional regulators
No full textGenes affecting DNA methylation (DNAme) are frequently comutated with splicing factors in acute myeloid leukemia (AML) and associate with more aggressive phenotypes. To elucidate the underlying molecular mechanisms, we deeply profiled wild-type and
single- or double-mutant AMLs. We find a unique set of mis-spliced genes and differentially methylated CpGs in double mutants. Mis-spliced exons are enriched in CCNG splicing enhancers and in the corresponding DNAme changes. Using a machine learning model, we can accurately predict exon inclusion levels from proximal CpGs. These CpGs are more likely to overlap footprints of RNA binding and chromatin-modifying complexes but not transcription factors. We also report unique gene expression profiles associated with each genotype; however, the differentially expressed genes do not overlap with mis-spliced transcripts. Instead, the mis-spliced genes encode for proteins that interact with the complexes regulating these differentially expressed genes. Thus, aberrant DNAme and splicing lead to the mis-splicing of key regulatory complexes, resulting in the aberrant gene expression profiles characteristic of these AMLs
Multilevel selection theory informs context-dependent mycorrhizal functioning
Get PDFArbuscular mycorrhizal (AM) fungi form widespread, ancient, and critically important symbioses with plants, but their functioning and beneficial effects are highly context-dependent. This variability stems from eco-evolutionary dynamics operating across multiple levels of biological organization (e.g., genes to holobionts), making generalizable predictions about mycorrhizal outcomes challenging. Multilevel selection theory (MLST), which posits that selection acts simultaneously on multiple levels of biological organization including in opposite directions, can serve as a powerful framework for interpreting this variability in mycorrhizal functional phenotypes. Here, we outline the key principles of MLST and explore how its application to AM fungal symbioses can improve our understanding of this ubiquitous symbiosis. We highlight how four levels of biological organization important to AM symbioses – genes, nuclei, spores, and holobionts – can serve as one or more units of selection under a tripartite framework for the units of selection. We then examine how ecological contexts, such as stress, spatial structure, and community composition, can modulate the balance of selective forces across levels, ultimately shaping the degree of cooperation among symbiotic partners. We conclude by proposing future research directions using MLST to generate deeper insights into the complexity and adaptability of this globally important symbiosis
Mapping melanoma mortality hot spots: A geographic spatial analysis of socioeconomic and provider disparities (vol 93, pg 477, 2025)
No full textChapter 7 - Race, socioeconomic position and sleep
No full textThe objective of this chapter is to describe the current landscape in health disparities science in the United States. After providing a brief overview of health disparities, we summarized the available influential published studies on inadequate sleep duration, poor sleep quality, and a group of commonly reported sleep disorders including insomnia, Obstructive Sleep Apnea, Narcolepsy, Restless Leg Syndrome, and Periodic Limb Movement. Overall, despite the heterogeneity in methodology measures and study population, black men and women report the shortest objective sleep duration relative to their white counterparts; while specific Hispanic subgroups may have been particularly at high risk for sleep disordered breathing. Several critical gaps remain with respect to other racial/ethnic groups and sexual minorities. Overall, we underlined the complex relationship between SES measures and perceived sleep health that may vary by racial/ethnic background. Finally, after exploring the potential influence on sleep health among minorities of acculturation, discrimination, worry and risk perception, and sleep opportunity, we later identified gaps in the literature and provided suggestions for future inquiry, including importance of personalized efficacious treatments adapted to the needs of vulnerable populations, and inclusion of sexual minorities
Common Vulvar and Vaginal Complaints
No full textVulvovaginal concerns remain one of the most common reasons prepubertal patients present for gynecologic care. This chapter addresses vulvovaginal disorders resulting from anatomical and structural differences, as well as vulvovaginal disorders that present as vaginal discharge and prepubertal vaginal bleeding.
Anatomical and structural conditions discussed in this chapter include labial adhesions, labial hypertrophy, and hymenal variants. This chapter will introduce a new classification system for labial adhesions to better guide management. Labial hypertrophy and hymenal variants will be reviewed, including identification compared to normal anatomy and conservative management versus surgical management. Discussion of vulvar angiomyxomas and potential clinical implications will also be presented.
This chapter will review the common etiology of vulvovaginitis in the prepubescent and adolescent patient and the appropriate evaluation and management. Vulvar ulcerations (vulvar aphthous ulcers) that are not associated with sexually transmitted infections will also be discussed. To conclude the chapter, rare but clinically significant conditions that present as vaginal bleeding in the prepubescent population will be reviewed
