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"Stop, Think, and Appreciate": A Qualitative Exploration of a Challenge Coin Suicide Prevention Intervention among Farmers
No full textFarmers are at increased risk for suicide compared to the general population, with estimates 56% higher among males in agriculture/forestry/fishing roles than the male working population. This study explored a farmer-developed suicide prevention intervention using an adapted military challenge coin for agriculture. An agricultural community member shared a message of appreciation with the farmer recipient. Farmers recently receiving a challenge coin were purposively sampled. Semi-structured interviews via telephone/videoconference explored farmers' challenge coin experiences and perceptions. Interviews were transcribed verbatim and de-identified before thematic coding. Participants (n = 14) were aged 28-68 years. All interviewees were non-Hispanic White, and 71% had off-farm jobs. Themes included the reception of the challenge coin, feelings elicited, and protective nature of the challenge coin against suicide, encouraging farmer connectedness and demonstrating appreciation. These data provide initial exploration of challenge coins adapted for farmer suicide prevention, developed within a farming community. Additional research regarding the impact is needed
Global Resource Disparities Between Pulmonary Hypertension Centers: Results From the International Survey by the PVRI IDDI Access to Care Workstream
No full textThere is a limited understanding of how pulmonary hypertension (PH) patients are managed worldwide. The Pulmonary Vascular Research Institute (PVRI) Innovative Drug Discovery Initiative (IDDI) global survey attempted to obtain insights into access to PH care in diverse international regions to pave future action plans. Responses from 151 centers (19.9% from Europe, 3.9% Middle East, 6% South Asia, 17.9% East Asia, 2% Sub-Saharan Africa, 31.8% Latin America, and 18.5% North America) were received. Most respondents had access to electrocardiography, echocardiography, and right heart catheterization but less availability to pulmonary function tests, ventilation/perfusion scans, and genetic testing. Phosphodiesterase type 5 (PDE-5) inhibitors were available in almost all centers but there was limited access to oral, inhaled, and parenteral prostacyclin therapy, riociguat, and selexipag. Cluster analysis of middle-high- and high income countries demonstrated significant variability in PH care delivery and disparities in therapeutic resources across the three clusters. The most common limitations identified that contribute to delayed PH diagnosis were insufficient financial resources, insufficient staff, and limited time. Survey respondents requested access to webinars with content experts (45%), access to content experts for consultation and review of complex cases via video chat (55%), resources to attend a conference (67.5%), and provision of a mentorship program (33.1%) along with greater availability of medications, remote conference access, clinical trial availability, and increased advocacy for patients. Survey results suggest significant disparities across the globe. Further research is needed to understand access to PH care and therapies in non-expert/academic centers and regional disparities within countries
BRD4 Phosphorylation Regulates the Structure of Chromatin Nanodomains
No full textThe interplay between chromatin structure and phase-separating proteins is an emerging topic in cell biology with implications for understanding disease states. Here, we investigate the functional relationship between bromodomain protein 4 (BRD4) and chromatin architecture. By combining molecular dynamics simulations with live-cell imaging, we demonstrate that BRD4, when mutated at specific N-terminus sites, significantly impacts the organization and dynamics of chromatin nanodomains, known as nucleosome clutches. Our findings reveal that a constitutively phosphorylated mutant of BRD4 condenses nucleosome clutches, while treatment with (+)-JQ1 increases the diffusion dynamics of single nucleosomes and decondenses nucleosome clutches. Simultaneously, we demonstrate that BRD4 mutations can alter localization of BRD4 to chromatin as well as modify single nucleosome dynamics. These results suggest that both chromatin binding and phase separation of BRD4 could co-regulate the nanoscale chromatin architecture and the chromatin microenvironment. Our observations shed light on the nuanced regulation of chromatin structure by BRD4, offering insights into its role in maintaining the nuclear architecture and transcriptional activity
Advancing global dementia research through equity and inclusion
No full textDespite the global burden of dementia, research remains dominated by high-income, Western populations, limiting the generalizability and equity of findings. In this Perspective, we highlight the importance of diversity and inclusion in dementia research, not only in study participants but also in the researchers, study design, and funding priorities. We describe how the lack of representation creates knowledge gaps and delays progress in prevention, diagnosis, and treatment. We also present examples of initiatives that are working to change this, including the Alzheimer's Disease Data Initiative and the William H. Gates Sr. Fellowship program, which supports open science, international collaboration, and early-career researchers from underrepresented regions. These efforts demonstrate that diversity is not only an ethical goal, but a scientific need. More inclusive and global research could lead to discoveries that are more generalizable, more globally applicable, and better able to inform strategies to address dementia across all communities. HIGHLIGHTS: Prioritize representation in datasets across ethnicity, geography, sex/gender, and socio-economic status. Support early-career researchers from underrepresented regions with long-term funding and mentorship. Standardize and adapt tools (cognitive, clinical, genomic) across cultural and linguistic contexts. Promote open science through equitable, federated data sharing platforms, and embed community engagement from research design to dissemination. Value diversity as a driver of discovery, not as a confounder
A practical approach for health system leaders to implement early detection of mild cognitive impairment and dementia in primary care
No full textPrimary care offers an important pathway for timely diagnosis and treatment of mild cognitive impairment and dementia. Transformative changes require a structured approach to implementation of early diagnosis workflows. Planning, designing, implementing, and sustaining are important aspects of these improvements. A practical approach for health system leaders is provided
Retrospective analysis of cutaneous immune‐related adverse events following checkpoint inhibitor therapy in melanoma patients reveals increased risk associated with the HLA‐B*51:01 allele
No full textBackground: While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.
Methods: A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as monotherapy or in combination, and had HLA typing available. This analysis spans from 2003 to 2023 with a focus on cutaneous irAEs. Statistical analyses were conducted to assess the association between HLA alleles and irAEs.
Results: Our analysis revealed that the HLA-B*51:01 allele was associated with a higher risk of cutaneous irAEs after adjusting for ICI regimen (hazard ratio: 1.71 [95% CI, 1.12-2.61], p = .013.) CONCLUSION: This is the largest study to link an HLA allele with ICI-induced cutaneous irAEs. The findings may support the use of HLA typing as an initial screen for developing irAEs, providing a simple, straightforward metric that can be rapidly performed on patients prior to initiation of ICIs. However, further research is needed across different cancer and toxicity types
Correction to: Granulopoietic Dysregulation in a Patient-Tailored Mouse Model of Barth Syndrome
No full textCorrection to: Stem Cell Reviews and Reports (2025) 21:2170–2187
10.1007/s12015-025-10945-1
The original published version of this article unfortunately contained a mistake.
In this article, Simon J. Conway should also be denoted as a corresponding author. The error occurred during the typesetting and proofing process.
The original article has been corrected
Risk biomarkers of chronic GVHD in children aged 10 years or younger and children/adults older than 10 years
No full textAssessment of risk biomarkers of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) in pediatric patients is lacking. We conducted a prospective study of 318 patients (129 children aged ≤10 years and 189 children/adults aged >10 years). Six plasma biomarkers (C-X-C motif chemokine ligand 9 [CXCL9], interleukin-1 receptor-like 1 [IL1RL1], regenerating islet-derived 3-α [REG3α], matrix metallopeptidase-3 [MMP3], dickkopf-WNT signaling pathway inhibitor-3 [DKK3], and sCD163) were assessed at day 100 after HCT. We performed day-100 landmark analyses for cGVHD, stratifying at age ≤10 years vs >10 years and dichotomizing markers using the Youden index. IL1RL1 associated with future cGVHD in both age groups, as did DKK3. CXCL9, REG3α, and MMP3 are associated with cGVHD in patients aged >10 years. This 5-marker panel has an area under the curve (AUC) of 0.71 in children aged ≤10 years and 0.72 in children/adults aged >10 years for cGVHD risk, and an AUC of 0.86 in children aged ≤10 years and 0.80 in children/adults aged >10 years for moderate/severe cGVHD risk. A 5-biomarker panel (IL1RL1, REG3α, MMP3, DKK3, and sCD163) was associated with transplant-related mortality (TRM) in both age groups. Biomarkers measured 3 months post-HCT predict susceptibility and/or are prognostic for cGVHD and TRM in both children aged ≤10 years and children/adults aged >10 years, allowing for additional risk stratification
Indiana's 2024 Behavioral Health and Human Services Workforce Snapshot: Licensed Addiction Counselors
No full textThis document is a 2024 data snapshot of actively practicing Licensed Addiction Counselors (LACs) in Indiana within the Behavioral Health and Human Services workforce. It reports a very small active workforce (56 LACs) and identifies primary practice settings, most commonly in criminal justice or correctional facilities and specialized substance abuse outpatient treatment facilities. The document highlights core services provided, primarily addiction counseling, frequently delivered through telehealth, and identifies key populations served, with a strong emphasis on adults, incarcerated individuals, and individuals in recovery
Categorization of chronic pain subtypes and contributing biomarkers in heart failure
No full textAims: Pain is common among adults with heart failure (HF), but pain subtypes and associated biomarkers are understudied. The aims were to: 1) characterize chronic pain severity, neuropathic pain quality, locations, and subtypes; and 2) compare pain severity and levels of biomarkers among pain subtypes. An exploratory aim was to correlate levels of biomarkers with pain severity.
Methods: This pilot descriptive study included cross-sectional data from 60 adults with HF and chronic pain. Pain was evaluated using the PainDETECT questionnaire. Blood biomarkers included interleukin (IL)-10, IL-18, IL-1β, IL-33, IL-6, IL-8, tumor necrosis factor (TNF)-α, brain-derived neurotrophic factor, leptin, adiponectin, and C-reactive protein. Descriptive statistics, Chi-square test of homogeneity, one-way analysis of variance, and Spearman correlation were used for analyses.
Results: The mean age was 70.45 (SD 7.92) years. The sample consisted of 63.3% women and 65.0% White race. Participants primarily reported nociceptive pain only (73.3%) with fewer reporting neuropathic pain only (6.7%) and mixed pain (20.0%). Current and 4-week mean pain severity scores were highest in the mixed pain subtype (p both <.05). No biomarkers were significantly different across the pain subtypes, but lower lL-10 (p=.049), and IL-33 (p=.014), were associated with higher pain severity.
Conclusions: In this study, chronic pain and its association with underlying biomarkers were characterized. Future research with a larger sample is needed to understand the unique contributions of biomarkers with targeted pain phenotypes.This study was supported by funding from the Center for Enhancing Quality of Life in Chronic Illness at Indiana University School of Nursing. We acknowledge the Regenstrief institute which aided with participant screening