Citations

Diabetes self-management education (DSME) programs are evidence-based interventions that improve glycemic control and self-care behaviors, yet their effectiveness may be limited by unaddressed health-related social needs (HRSN) (e.g., food insecurity, housing or utility instability, transportation barriers). This qualitative multiple case study examined the feasibility of integrating HRSN assessments into DSME delivery within three community-based organizations (CBOs) across urban and rural U.S. settings. Guided by the Consolidated Framework for Implementation Research, semi-structured interviews were conducted with 15 DSME facilitators and program leadership to identify contextual factors influencing implementation. Findings revealed that while DSME’s structured, manualized design promotes fidelity and client autonomy, it constrains responsiveness to the client’s HRSN. Facilitators expressed openness to integrating HRSN screening, particularly during intake, yet cited limited infrastructure, role clarity, and training as key barriers. CBOs were recognized as trusted, accessible spaces for holistic care, but growing expectations to address HRSN without adequate resources for referral created sustainability concerns. Participants recommended a parallel support model involving navigators or community health workers to manage HRSN screening and referrals alongside DSME sessions. Integrating HRSN assessment processes into DSME may enhance engagement, reduce attrition, and extend the reach of diabetes education to populations most affected by HRSN. However, successful implementation requires dedicated funding, workforce development, and cross-sector coordination. Findings underscore the importance of supporting CBOs as critical partners in bridging diabetes education and social care to advance whole-person, chronic disease management.

ABSTRACT Condition Overview Clonal hematopoiesis (CH) refers to the presence of somatic variants in hematopoietic stem and progenitor cells (HSPC) that result in expansion over time. Diagnosis CH of indeterminate potential (CHIP) is operationally defined as pathogenic variants in oncogenic driver genes occurring in HSPCs at variant allele frequencies ≥ 2%. Clinical Associations CH is associated with increased risk for progressive cytopenias (also called clonal cytopenia of undetermined significance), hematological (predominantly myeloid but also lymphoid) neoplasms, cytosis (including monocytosis), and nonhematological conditions such as atherosclerotic cardiovascular and cerebrovascular disease. CH is linked to numerous other diseases including venous thromboembolism, type 2 diabetes mellitus, chronic obstructive pulmonary disease, osteoporosis, and gout, with a potential protective impact in Alzheimer's disease (AD). Management Recommendations CH detection is becoming increasingly common due to the ubiquitous use of somatic and germline sequencing in clinical practice, particularly, in oncology. The clinical implications of CH are most relevant in therapy‐related myeloid neoplasms (t‐MN), with antecedent CH clones in genes such as TP53, PPM1D, and/or CHEK2 having a clear selection advantage. Furthermore, genetic predisposition to CH has provided some clarity on the origin and evolution of CH. We are currently defining the role for CH assessment in individuals with persistent (≥ 4 months) unexplained cytopenias, in patients with malignancies prior to adjuvant cytotoxic chemotherapy and/or radiation or radionuclide therapy, screening prior to autologous hematopoietic stem cell transplantation or chimeric antigen receptor T cell (CAR‐T) therapy, and to work‐up potentially germline mosaic variants.

The treatment landscape for multiple myeloma (MM) is evolving rapidly and includes several new options. The management must be tailored to the individual. The NCCN Guidelines for MM provide a framework to base decisions regarding diagnosis, workup, treatment, and follow-up of both newly diagnosed and previously treated relapsed/refractory MM. This manuscript outlines the recommendations from NCCN Guidelines for MM specific to newly diagnosed MM (NDMM).

The Concise Guide to Pharmacology 2025/26 marks the seventh edition in this series of biennial publications in the British Journal of Pharmacology. Presented in landscape format, the guide provides a comparative overview of the pharmacology of drug target families. The concise nature of the Concise Guide refers to the style of presentation, being clear, accessible, and well‐structured, rather than the scope of the content, which spans approximately 500 pages. The Concise Guide summarises the key pharmacological properties of around 1900 human drug targets, and nearly 7000 interactions, involving around 4400 ligands. While the content is a substantially condensed version of the more detailed information and links available at the www.guidetopharmacology.org website, the printed guide serves as a permanent, citable, point‐in‐time record, that remains stable despite ongoing updates to the online database. The full contents of this publication can be found at https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70233 . The Concise Guides provide expert‐curated recommendations of ‘Gold Standard’ selective pharmacological tools, available either commercially or as donations, which enable the identification of individual drug targets or families of drug targets. While the Concise Guide offers a more streamlined overview, more comprehensive information, including detailed pharmacological profiles and links to multiple online databases, is available through the Guide to Pharmacology website. The 2025/26 edition of the Concise Guide is based on material current as of mid‐2025, and supersedes all previous editions, including the 2023/24 Guide, and earlier Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), and as such provides official IUPHAR classification and nomenclature for human drug targets, where applicable. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. Each section includes nomenclature guidance, concise summaries, information of the best available pharmacological tools, key references, and suggestions for further reading.

Abstract Bone marrow is the primary immune organ responsible for stem cell maintenance and hematopoiesis. However, the contribution of the bone marrow niche for the generation of adaptive immune responses is less well-understood. We therefore assessed the capacity of virus antigen-specific CD8 T cells to be generated and expanded in bone marrow following acute neurotropic virus infection. Intracranial infection with the neurotropic Theiler’s Murine Encephalomyelitis Virus (TMEV) results in an acute infection in the C57BL/6 mouse which is cleared within 4 weeks post infection due to the generation of an antigen-specific CD8 T cell response against the immunodominant epitope VP2 121-130 . We determined that 1-10% of CD8 T cells present in the femoral, and sternal bone marrow were virus antigen-specific 5-7 days after intracranial TMEV infection. We determined that antigen-specific CD8 T cells were generated in the bone marrow with similar kinetics to that of conventional responses in the secondary lymphoid organs. Importantly, continuous treatment with FTY720, which sequesters T cells outside of the blood, did not eliminate antigen-specific CD8 T cells in the bone marrow compartment indicating generation within the bone marrow niche. Similarly, injection of Poly I:C admixed with fluorescently labeled ovalbumin into the brain generated a similar antigen-specific CD8 T cell response in the bone marrow indicating these responses occur following various brain insults. This model also identified the likely antigen presenting cell (APC) responsible for scavenging antigens from the brain and trafficking into the bone marrow as a migratory myeloid-derived APC. Moreover, following clearance of TMEV infection, CD8 T cells in the bone marrow established durable memory. Antigen-specific memory CD8 T cells in the bone marrow reactivated and expanded upon cognate antigen reencounter. Antigen-specific reactivation of memory CD8 T cells within the bone marrow caused a concurrent increase in Lineage-, Sca-1+, c-Kit+ (LSK) and CD11b+ MHCII+ myeloid cells. This increase in the LSKs and myeloid cells in the bone marrow niche was abrogated with CD8 T cell depletion. We conclude that brain viral infections induce in situ effector and memory T cell responses within the bone marrow compartment. Memory recall CD8 T cell responses induce niche dysregulation by expanding LSK cells and lead to an influx of MHCII+ myeloid cells. Our data pave the way for crucial studies of bone marrow resident antigen-specific CD8 T cells in health and diseases.

Abstract Background The National Institute on Aging Alzheimer's Disease Family Based Study (NIA‐ AD FBS) is a multi‐site, longitudinal study aimed to be a data and bio sample resource for investigators worldwide. Since its inception in 2002 the FBS goal has been to promote greater cooperation and sharing of clinical and biological resources among researchers. Methods The focus of the Family Based Study (FBS) has been the recruitment of families with at least two affected individuals and a third first degree relative with or without dementia and willing to participate. Participants are from different ethnic backgrounds including Caucasian, African American and Hispanics. The FBS study is actively recruiting both late onset (LOAD) and early onset Alzheimer's Disease (EOAD) families as well as conducting follow up evaluations every two years, approximately. Uniform assessments are completed across all sites and include DNA, Plasma, PaXgene and PBMC samples collection and brain autopsies whenever possible. We conduct both in person and remote evaluations and use the services of a mobile phlebotomy company to collect bio samples. In addition, we’ve created a protocol for genetic testing on the proband for EOAD families where an additional sample is sent to a CLIA approved lab and after genetic counseling, the presence or not of AD related mutations is disclosed to the families. Results To date, this cohort has recruited 1,756 families and acquired data from 9,682 family members. Families are from Caucasian, African Americans and Hispanics ethnic groups. The cohort has longitudinal clinical data, cognitive assessment, family history and bio samples available for sharing. Genotype data includes APOE, GWAS, WES, WGS, brain methylation, RNA sequencing and biomarkers data. Conclusion The NIA‐LOAD FBS study is the largest collection of familial Alzheimer's Disease worldwide and many genetic studies of Alzheimer's disease (AD) have included cases and controls from this dataset. Over 140 publications have used data and/or samples from FBS to address the genetics of Alzheimer's Disease. The enriched resources provided by this cohort are invaluable to the scientific community.

Abstract Background To determine if dose escalation improves outcomes for chondrosarcomas (CHS) of the base of the skull (BOS) and the cervical spine (CS). Methods A prospective, randomized, dose-escalation trial was designed for patients with CHS of the BOS and CS. Patients were randomly assigned to 70 Gy (RBE) or 76 Gy (RBE). The primary endpoint was local failure (LF). Secondary endpoints included overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and treatment-related toxicities. Results Between 1987 and 2007, 105 patients were randomized, median follow-up was 29.2 years (IQR, 26.7-32.4). Forty-six patients were assigned to 70 Gy (RBE) and 59 were assigned to 76 Gy (RBE). LF at 5-, 10-, and 20 years were 7%, 9%, and 11% for 70 Gy (RBE), and 10%, 15%, and 19% for 76 Gy (RBE) (P = .16). Like LF rates, there was no benefit in dose escalation for OS (P = .28) and CSS (P = .22). Progression-free survival at 5-, 10-, and 20 years was 93%, 89%, and 77% for the low-dose group and 83%, 71%, and 59% for the high-dose group (P = .069). Late RT injury ≥ grade 3 was reported in a total of 19 (18%) patients across both dose levels, with 11% in the low-dose group and 24% in the high-dose group (P = .13). Conclusions This is the first and largest trial of patients with grade I/II BOS and CS CHS evaluating dose escalation for tumor control. Proton-based RT is effective and safe for these tumors, but there is no apparent benefit in dose escalation. Clinical Trial Information NCT00592748.

Objective: To evaluate the ethical implications, clinical benefits, and challenges associated with centralizing the surgical care of vestibular schwannoma (VS) care. Databases reviewed: PubMed, Embase, CINAHL, Web of Science, Cochrane, Scopus. Methods: A scoping review was conducted per the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. A comprehensive search of 6 electronic databases yielded 1,231 articles using keywords related to vestibular schwannoma, centralization of care, centers of excellence, and ethical considerations. After removing duplicates (n=344) and screening titles and abstracts (n=887), 17 full-text articles were reviewed. Two additional articles were identified through manual screening. A total of 15 studies were included in the final analysis. Results: Hospitals were categorized by surgical case volume (high, medium, low) to compare patient demographics and clinical outcomes. Patients seen at low-volume hospitals (LVHs) were generally older and more racially diverse, and more likely to have public insurance (Medicare or Medicaid), whereas high-volume hospitals (HVHs) served a younger, predominantly White, and privately insured population. Of the 14 studies evaluating outcomes, 12 demonstrated a positive association between higher surgical volume and improved outcomes, including reduced complications, lower mortality, shorter length of stay, and decreased hospitalization costs. High-volume hospitals also had significantly higher rates of routine discharge. Conclusion: Centralization of vestibular schwannoma care to high-volume centers is associated with improved clinical outcomes and reduced health care costs. However, these benefits must be carefully weighed against potential ethical concerns, including disparities in access related to socioeconomic status, insurance coverage, and geographic location.

Background: Carriers of a pathogenic variant (PV) in BRCA1 face a high risk of breast cancer. This study estimated the risk of developing breast cancer according to mutation type and location. Methods: BRCA1 carriers with no personal history of breast cancer or bilateral mastectomy were included. Detailed information on clinical and family history was collected by questionnaire. Survival analysis was used to estimate 15-year cumulative risk according to PV type and location. Results: A total of 3677 BRCA1 carriers were followed for a mean of 7.2 years (range 0.1–15.0 years); 481 incident breast cancers were documented. Overall, the 15-year cumulative incidence was 25%. Risk estimates varied by exon, ranging from 9% (exon 21) to 19% (exon 12) to 36% (exon 15); however, strata were small. Carriers of four founder mutations common in Eastern Europe (c.5263_5264insC, c.181T > G, c.66_67delAG and c.4034delA) experienced a lower-than-expected cancer risk (15.9–24.4%) compared to other PVs (28.8%) (p = 0.02). Conclusions: Although our data suggests some variability in penetrance based on specific BRCA1 PV, this was based on a large number of founder mutations. Breast cancer management strategies should continue to be based on comprehensive risk assessment.