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1.
NPJ Precis Oncol ; 8(1): 207, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39289482

ABSTRACT

Genomic alterations in fibroblast growth factor receptor (FGFR) genes are present in a small number of metastatic pancreatic ductal adenocarcinomas (PDAC) and may represent an emerging subgroup of patients likely to benefit from FGFR targeted therapies. Here we present four FGFR2 fusion-positive metastatic PDAC patients who exhibited durable responses or disease control to FGFR kinase inhibitors. Utilizing our custom FGFR focused cell-free DNA assay, FGFR-Dx, we serially monitored variant allele fractions of FGFR2 fusions during FGFR inhibitor treatment and observed dynamic changes correlating with clinical responses. Genomic analysis of 30,229 comprehensively profiled pancreatic cancers revealed FGFR1-3 fusions in 245 cases, an incidence of 0.81%. FGFR fusions were generally mutually exclusive from other known oncogenes. Our findings provide clinical evidence for identifying and treating FGFR2 fusion-positive PDAC patients with FGFR targeted therapy.

2.
medRxiv ; 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39252898

ABSTRACT

Commercial liquid biopsy assays are routinely used by oncologists to monitor disease response and resistance to therapy. Additionally, in cases where tumor tissue is not available, clinicians may rely on cell-free DNA (cfDNA) testing as a surrogate for comprehensive tumor testing. While some gene rearrangements are well detected, current commercial liquid biopsy assays exhibit low sensitivity for fibroblast growth factor receptor ( FGFR ) rearrangements. FGFRs are altered in ∼2.5% of all cancers, including FGFR2 rearrangements in 10% of intrahepatic cholangiocarcinoma and FGFR3 point mutations and rearrangements in 10-15% of urothelial carcinoma. Therefore, we developed and analytically validated FGFR-Dx, an FGFR -focused cfDNA assay with improved sensitivity for FGFR rearrangements. FGFR-Dx comprehensively targets the introns in FGFR1-3 previously shown to be involved in gene fusions as well as all coding exons. Custom FGFR synthetic reference standards representing both single nucleotide variants (SNVs) and gene rearrangements were utilized at a range of variant frequencies and revealed a detection limit of 0.5% with sensitivities of 97.2% and 92.9% for SNVs and rearrangements, respectively. Furthermore, FGFR-Dx detected rearrangements and identified the intronic breakpoints from cfDNA collected from 13 of 15 patients with known FGFR fusions.

3.
J Am Psychiatr Nurses Assoc ; : 10783903241271273, 2024 Aug 18.
Article in English | MEDLINE | ID: mdl-39155585

ABSTRACT

BACKGROUND: Alcohol use disorder (AUD) is common and deadly. Naltrexone is a treatment for AUD. Previous research examined factors that predict Ohio Advanced Practice Registered Nurses' (APRNs) utilization of naltrexone to treat AUD. Inclusion criteria included APRNs' endorsing receipt of the X-waiver, a designation indicating providers' receipt of substance use disorder education. In 2023, the X-waiver was eliminated. The purpose of this study was to replicate the previous research design in respondents without an X-waiver and compare findings. AIMS: The aims of this study were three-fold: (1) assess whether race, age, practice setting, years in practice, or work experience with an addiction specialist physician predicted prescription of naltrexone for AUD, (2) assess whether the goal of abstinence or reduced alcohol use as desired treatment affected the likelihood of naltrexone prescription for AUD, and (3) compare differences between the answers in the current respondent group without X-waiver and the previous study's X-waivered respondents. METHOD: All Ohio APRNs were sent surveys. Eighty-eight responses were included in analysis. Descriptive statistics, logistic regression, and chi-square results were reported. RESULTS: Work experience with an addiction specialist physician was negatively associated with prescribing naltrexone for AUD. Respondents from the previous study of X-waivered APRNs were significantly more likely to prescribe naltrexone for reduced alcohol consumption as a treatment outcome than the respondents in this study. CONCLUSION: The recent policy change eliminating the X-waiver provides important context for research, adding to the substance use disorder literature.

4.
J Hosp Palliat Nurs ; 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39213417

ABSTRACT

Despite initiatives to increase palliative care awareness, referrals in primary care settings are still primarily based on provider judgment, causing a lack of appropriate referrals and disparities in access to palliative care resources. The purpose of this quality improvement project was to develop and implement an evidence-based, standardized palliative care referral protocol to increase the palliative care referral rate for eligible patients at a primary care clinic. The project used a preimplementation and postimplementation design with the use of the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to successfully implement and evaluate the standardized referral process. Over the 10-month project period, the palliative care referral rate increased from 2% (4/193) preimplementation to 11% (16/147) postimplementation of the standardized referral process, which is an increase of 9%. Taking into consideration the potential impact of multiple extraneous variables, there was an overall decrease of 69% in emergency room visits and 73% in hospitalizations for patients who received a palliative care referral. These outcomes support expansion of the standardized referral process throughout other primary care clinics to increase palliative care referrals and sustain a high level of quality patient care.

5.
J CME ; 13(1): 2370746, 2024.
Article in English | MEDLINE | ID: mdl-38952925

ABSTRACT

The COVID-19 pandemic has had disruptive effects on all parts of the health-care system, including the continuing education (CE) landscape. This report documents, what has happened in six different CE accreditation systems to CE activities as well as learners. Complete lockdown periods in the first part of the COVID-19 pandemic have inevitably led to reductions in numbers of the then predominant format of education, i.e. onsite in-person meetings. However, with impressive speed CE providers have switched to online educational formats. With regard to learner interactions this has compensated, and in some systems even overcompensated, the loss of in-person educational opportunities. Thus, our data convincingly demonstrate the resilience of CPD in times of a global health crisis and offer important insights in how CPD might become more effective in the future.

6.
Article in English | MEDLINE | ID: mdl-38958596

ABSTRACT

KEY POINTS: A persistent type 2 endotype signature exists in recalcitrant chronic rhinosinusitis with nasal polyps mucosa on dupilumab. Revision sinus surgery immediately prior to dupilumab reduces long-term interleukin (IL)-4/IL-13 tissue mRNA. Pre-dupilumab revision surgery is associated with reduced tissue eosinophils and GATA-3+ cells.

7.
Int J Behav Med ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009797

ABSTRACT

BACKGROUND: Interventions that use the Health Action Process Approach (HAPA) model show promise for increasing PA frequency, duration, and intensity. However, there is limited understanding of how HAPA model variables have been operationalized for PA interventions in chronic disease to promote behavior change and sustained PA or whether the phase or continuous form of the HAPA model was used. The aim of this scoping review is to describe how the HAPA model variables for PA interventions were operationalized and provide details of implementation. METHOD: We searched five databases to identify studies published between January 1992 and March 2024. We aimed to describe (1) the characteristics of interventions including setting, delivery mode, duration, and content; (2) which HAPA variables were operationalized and the strategies used; and (3) the physical activity measures and outcome effects. RESULTS: The search identified 23 interventions in 30 papers (12 protocols, 3 quasi-experimental studies, and 15 randomized controlled trials (RCTs)). Seven of the 15 RCTs reported significant positive effects of the HAPA model on PA behavior outcomes. Interventions operationalized between three and nine HAPA constructs showed significant variability in how the HAPA model is used in intervention research. PA measures varied from self-report to validated objective instruments. CONCLUSION: We found a lack of clarity in decisions about which HAPA constructs were included in interventions. The wide variability in operationalized HAPA constructs made it challenging to compare interventions. Researchers should provide more detail about intervention design and implementation procedures to enhance transparency.

8.
Neuro Oncol ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39082676

ABSTRACT

BACKGROUND: The frequency and significance of IDH mutations in glioma across age groups is incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes. METHODS: Clinical, histologic, and sequencing data from patients with IDH-mutant, grade 2-4 gliomas, were collected from collaborating institutions between 2013-2019. Patients were categorized as pediatric (<19y), YA (19-39y) or older adult (≥40y). Clinical presentation, treatment, histologic, and molecular features were compared across age categories using Fisher's exact test or analysis-of-variance. Cox proportional-hazards regression was used to determine association of age and other covariates with overall (OS) and progression-free survival (PFS). RESULTS: We identified a cohort of 379 patients (204 YA) with IDH-mutant glioma with clinical data. There were 155 (41%) oligodendrogliomas and 224 (59%) astrocytomas. YA showed significantly shorter PFS and shorter median time-to-malignant transformation (MT) compared to pediatric and adult groups, but no significant OS difference. Adjusting for pathology type, extent of resection, and upfront therapy in multivariable analysis, the YA group was independently prognostic of shorter PFS than pediatric and adult groups. Among astrocytomas, CDK4/6 copy number amplifications were associated with both shorter PFS and shorter OS. Among oligodendrogliomas, PIK3CA and CDKN2A/2B alterations were associated with shorter OS. CONCLUSIONS: IDH-mutant glioma YA patients had significantly shorter PFS and time to MT but did not differ in OS compared to pediatric and adult groups. Treatment approach varied significantly by patient age and warrant further study as addressable age-associated outcome drivers.

9.
JMIR Form Res ; 8: e51943, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39028554

ABSTRACT

BACKGROUND: Spaced retrieval is a learning technique that involves engaging in repeated memory testing after increasingly lengthy intervals of time. Spaced retrieval has been shown to improve long-term memory in Alzheimer disease (AD), but it has historically been difficult to implement in the everyday lives of individuals with AD. OBJECTIVE: This research aims to determine, in people with mild cognitive impairment (MCI) due to AD, the efficacy and feasibility of a mobile app that combines spaced retrieval with a machine learning algorithm to enhance memory retention. Specifically, the app prompts users to answer questions during brief daily sessions, and a machine learning algorithm tracks each user's rate of forgetting to determine the optimal spacing schedule to prevent anticipated forgetting. METHODS: In this pilot study, 61 participants (young adults: n=21, 34%; healthy older adults: n=20, 33%; people with MCI due to AD: n=20, 33%) used the app for 4 weeks to learn new facts and relearn forgotten name-face associations. Participation during the 4-week period was characterized by using the app once per day to answer 15 questions about the facts and names. After the 4-week learning phase, participants completed 2 recognition memory tests approximately 1 week apart, which tested memory for information they had studied using the app as well as information they had not studied. RESULTS: After using the mobile app for 1 month, every person with MCI due to AD demonstrated improvements in memory for new facts that they had studied via the app compared to baseline (P<.001). All but one person with MCI due to AD (19/20, 95%) showed improvements of more than 10 percentage points, comparable to the improvements shown by young adults and healthy older adults. Memory for name-face associations was similarly improved for all participant groups after using the app but to a lesser degree. Furthermore, for both new facts and name-face associations, we found no memory decay for any participant group after they took a break of approximately 1 week from using the app at the end of the study. Regarding usability, of the 20 people with MCI due to AD, 16 (80%) self-adhered to the app's automated practice schedule, and half of them (n=10, 50%) expressed an interest in continuing to use it. CONCLUSIONS: These results demonstrate early evidence that spaced retrieval mobile apps are both feasible for people with early-stage AD to use in their everyday lives and effective for supporting memory retention of recently learned facts and name-face associations.

10.
Neurooncol Adv ; 6(1): vdae074, 2024.
Article in English | MEDLINE | ID: mdl-38903142

ABSTRACT

Background: Fibroblast growth factor receptor 1 (FGFR1) mutations have been associated with poorer prognoses in pediatric central nervous system tumor patients. A recent study highlighted a link between FGFR1 mutations and spontaneous intracranial hemorrhage (ICH), demonstrating that all patients with an FGFR1 alteration experienced hemorrhage at some point during their course of treatment. Methods: The current study examined 50 out of 67 pediatric patients with low-grade gliomas (LGGs) who had genomic testing between 2011 and 2022 at our institution to determine whether a correlation exists between FGFR1 mutations and spontaneous ICH. Results: We found that of the 50 patients with genomic data, 7 (14%) experienced ICH, and an additional spontaneous hemorrhage was recorded; however, no genomic testing was performed for this case. Five of the seven patients (71.4%) had an FGFR1 modification. In our patient population, 6 expressed a detectable FGFR1 mutation (66.7% [4/6] had N546K alteration, 16.7% [1/6] FGFR1 exons duplication, and 16.7% [1/6] had a variant of unknown significance [VUS]). The patient with the FGFR1 VUS had no reported spontaneous hemorrhage. Statistical analysis found a significant association between FGFR1 and spontaneous intracranial hemorrhage (P-value = < .0001). In the patient population, all cases of PTPN11 alterations (n = 3) co-occurred with FGFR1 mutations. Conclusions: Our case series highlights this link between the FGFR1 mutation and spontaneous intracranial hemorrhage in pediatric LGGs.

11.
BMJ Open ; 14(6): e085125, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830746

ABSTRACT

INTRODUCTION: Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective. METHODS AND ANALYSIS: The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement. ETHICS AND DISSEMINATION: The trial was approved by the London-Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. TRIAL REGISTRATION NUMBER: ISRCTN87336549.


Subject(s)
Randomized Controlled Trials as Topic , Humans , Cost-Benefit Analysis , Multicenter Studies as Topic , Meniscectomy , Menisci, Tibial/surgery , Menisci, Tibial/transplantation , Tibial Meniscus Injuries/surgery , Tibial Meniscus Injuries/therapy , Tibial Meniscus Injuries/rehabilitation
12.
Acta Neuropathol ; 147(1): 78, 2024 05 02.
Article in English | MEDLINE | ID: mdl-38695952

ABSTRACT

Aging is associated with cell senescence and is the major risk factor for AD. We characterized premature cell senescence in postmortem brains from non-diseased controls (NDC) and donors with Alzheimer's disease (AD) using imaging mass cytometry (IMC) and single nuclear RNA (snRNA) sequencing (> 200,000 nuclei). We found increases in numbers of glia immunostaining for galactosidase beta (> fourfold) and p16INK4A (up to twofold) with AD relative to NDC. Increased glial expression of genes related to senescence was associated with greater ß-amyloid load. Prematurely senescent microglia downregulated phagocytic pathways suggesting reduced capacity for ß-amyloid clearance. Gene set enrichment and pseudo-time trajectories described extensive DNA double-strand breaks (DSBs), mitochondrial dysfunction and ER stress associated with increased ß-amyloid leading to premature senescence in microglia. We replicated these observations with independent AD snRNA-seq datasets. Our results describe a burden of senescent glia with AD that is sufficiently high to contribute to disease progression. These findings support the hypothesis that microglia are a primary target for senolytic treatments in AD.


Subject(s)
Alzheimer Disease , Cellular Senescence , Transcriptome , Alzheimer Disease/pathology , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Humans , Cellular Senescence/physiology , Cellular Senescence/genetics , Aged , Male , Aged, 80 and over , Female , Microglia/pathology , Microglia/metabolism , Brain/pathology , Brain/metabolism , Amyloid beta-Peptides/metabolism , Neuroglia/pathology , Neuroglia/metabolism
13.
J Dent Educ ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695763

ABSTRACT

PURPOSE: The purpose of this study was to explore dental hygiene students' and recent graduates' awareness, attitudes, perceived barriers, motivators, and intentions to pursue a career in academia as a dental hygiene educator. METHODS: Cross-sectional survey research was conducted with a non-probability sample of dental hygiene students and recent graduates (n = 451). The survey included sections for familiarity regarding academic careers for dental hygienists, attitudes toward academic careers, barriers and motivating factors for this career path, and future academic career intentions. Analysis included descriptive, correlations, and regression. RESULTS: Of 451 surveys started, 296 were at least 80% complete for a completion rate of 66%. The most reported barrier to a career in academia was the cost to obtain the required degree to become an educator (67.6%, n = 200), and for motivating factors was a sense of accomplishment (62.8%, n = 186). Regression analysis of likelihood to pursue a higher education degree showed two main predictors; belief that higher education would advance the dental hygiene profession (ß = 0.35, p < 0.001) and willingness to take a pay cut to become an educator (ß = 0.24, p < 0.001). CONCLUSIONS: Overall dental hygiene students and recent graduates were familiar with and had a positive view of careers in academia. However, barriers included cost and time for obtaining a higher degree, as well as the pay differential between academia and private practice. The educator shortage in dental hygiene may be alleviated by providing educators with loan forgiveness and offering salaries comparable to clinical practice.

15.
AIDS Patient Care STDS ; 38(3): 144-150, 2024 03.
Article in English | MEDLINE | ID: mdl-38471093

ABSTRACT

There is an unmet need for HIV prevention among Black cisgender women. From January to November 2020, we conducted formative research to develop locally informed implementation strategies to enhance pre-exposure prophylaxis (PrEP) uptake among Black cisgender women in New Orleans, Louisiana. Following an iterative process, we conducted in-depth interviews (IDIs) with Black women who were not taking PrEP and used those findings to inform IDIs with Black women taking PrEP. We asked about PrEP awareness, social support, PrEP-related norms, medical mistrust, motivation to take PrEP, and potential implementation strategies. Data were analyzed using applied thematic analysis. We established the Black Women and PrEP (BWAP) Task Force-a diverse group of 25 Black female community representatives who reviewed the IDI findings and identified strategies to address these determinants of PrEP uptake. We interviewed 12 Black women who were not taking PrEP and 13 Black women who were taking PrEP. Two main PrEP uptake barriers were identified from the IDI findings and Task Force discussions. First, Black women do not know of other Black women taking PrEP. Women perceived PrEP as a drug for gay men. Most said that testimonials from Black women taking PrEP would make its use more relatable. Second, Black women are not frequently offered PrEP by their providers. Many preferred accessing PrEP through women's health providers. The Task Force identified two strategies to address these barriers: a social media campaign for women and an educational initiative to train providers to discuss and prescribe PrEP. These implementation strategies require further study.


Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Male , Humans , Female , HIV Infections/drug therapy , New Orleans , Trust , Anti-HIV Agents/therapeutic use , Health Knowledge, Attitudes, Practice , Louisiana
16.
Nat Commun ; 15(1): 2243, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38472200

ABSTRACT

Brain perfusion and blood-brain barrier (BBB) integrity are reduced early in Alzheimer's disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD and non-diseased control brains to characterise pathological transcriptional signatures responsible for this. We show that endothelial cells (EC) are enriched for expression of genes associated with susceptibility to AD. Increased ß-amyloid is associated with BBB impairment and a dysfunctional angiogenic response related to a failure of increased pro-angiogenic HIF1A to increased VEGFA signalling to EC. This is associated with vascular inflammatory activation, EC senescence and apoptosis. Our genomic dissection of vascular cell risk gene enrichment provides evidence for a role of EC pathology in AD and suggests that reducing vascular inflammatory activation and restoring effective angiogenesis could reduce vascular dysfunction contributing to the genesis or progression of early AD.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/metabolism , Blood-Brain Barrier/metabolism , Endothelial Cells/metabolism , Angiogenesis , Brain/metabolism , Amyloid beta-Peptides/metabolism , Gene Expression Profiling
17.
J Clin Invest ; 134(8)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38483537

ABSTRACT

SARS-CoV-2 infection of the upper airway and the subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying infection of human biopsies in vitro and in a hamster model in vivo, we demonstrated a transition in nasal tropism from olfactory to respiratory epithelium as the virus evolved. Analyzing each variant revealed that SARS-CoV-2 WA1 or Delta infect a proportion of olfactory neurons in addition to the primary target sustentacular cells. The Delta variant possessed broader cellular invasion capacity into the submucosa, while Omicron displayed enhanced nasal respiratory infection and longer retention in the sinonasal epithelium. The olfactory neuronal infection by WA1 and the subsequent olfactory bulb transport via axon were more pronounced in younger hosts. In addition, the observed viral clearance delay and phagocytic dysfunction in aged olfactory mucosa were accompanied by a decline of phagocytosis-related genes. Further, robust basal stem cell activation contributed to neuroepithelial regeneration and restored ACE2 expression postinfection. Together, our study characterized the nasal tropism of SARS-CoV-2 strains, immune clearance, and regeneration after infection. The shifting characteristics of viral infection at the airway portal provide insight into the variability of COVID-19 clinical features, particularly long COVID, and may suggest differing strategies for early local intervention.


Subject(s)
COVID-19 , Common Cold , Animals , Cricetinae , Humans , Aged , SARS-CoV-2/genetics , Post-Acute COVID-19 Syndrome , COVID-19/genetics , Axons
18.
Mol Psychiatry ; 29(5): 1453-1464, 2024 May.
Article in English | MEDLINE | ID: mdl-38321120

ABSTRACT

Smell deficits and neurobiological changes in the olfactory bulb (OB) and olfactory epithelium (OE) have been observed in schizophrenia and related disorders. The OE is the most peripheral olfactory system located outside the cranium, and is connected with the brain via direct neuronal projections to the OB. Nevertheless, it is unknown whether and how a disturbance of the OE affects the OB in schizophrenia and related disorders. Addressing this gap would be the first step in studying the impact of OE pathology in the disease pathophysiology in the brain. In this cross-species study, we observed that chronic, local OE inflammation with a set of upregulated genes in an inducible olfactory inflammation (IOI) mouse model led to a volume reduction, layer structure changes, and alterations of neuron functionality in the OB. Furthermore, IOI model also displayed behavioral deficits relevant to negative symptoms (avolition) in parallel to smell deficits. In first episode psychosis (FEP) patients, we observed a significant alteration in immune/inflammation-related molecular signatures in olfactory neuronal cells (ONCs) enriched from biopsied OE and a significant reduction in the OB volume, compared with those of healthy controls (HC). The increased expression of immune/inflammation-related molecules in ONCs was significantly correlated to the OB volume reduction in FEP patients, but no correlation was found in HCs. Moreover, the increased expression of human orthologues of the IOI genes in ONCs was significantly correlated with the OB volume reduction in FEP, but not in HCs. Together, our study implies a potential mechanism of the OE-OB pathology in patients with psychotic disorders (schizophrenia and related disorders). We hope that this mechanism may have a cross-disease implication, including COVID-19-elicited mental conditions that include smell deficits.


Subject(s)
Disease Models, Animal , Inflammation , Olfactory Bulb , Olfactory Mucosa , Psychotic Disorders , Schizophrenia , Animals , Olfactory Mucosa/pathology , Olfactory Mucosa/metabolism , Psychotic Disorders/pathology , Mice , Humans , Male , Inflammation/metabolism , Inflammation/pathology , Olfactory Bulb/pathology , Olfactory Bulb/metabolism , Female , Schizophrenia/pathology , Schizophrenia/metabolism , Schizophrenia/physiopathology , Schizophrenia/genetics , Olfaction Disorders/etiology , Olfaction Disorders/physiopathology , Smell/physiology , Adult , Mice, Inbred C57BL , Neurons/metabolism , Neurons/pathology
19.
Neuro Oncol ; 26(6): 1109-1123, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38334125

ABSTRACT

BACKGROUND: Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing a senesecence-associated secretory phenotype. However, a detailed analysis of these characteristics has yet to be completed. METHODS: We analyzed primary tissue samples from ACP patients using single-cell, single-nuclei, and spatial RNA sequencing. We performed various analyses, including gene expression clustering, inferred senescence cells from gene expression, and conducted cytokine signaling inference. We utilized LASSO to select essential gene expression pathways associated with senescence. Finally, we validated our findings through immunostaining. RESULTS: We observed significant diversity in gene expression and tissue structure. Key factors such as NFKB, RELA, and SP1 are essential in regulating gene expression, while senescence markers are present throughout the tissue. SPP1 is the most significant cytokine signaling network among ACP cells, while the Wnt signaling pathway predominantly occurs between epithelial and glial cells. Our research has identified links between senescence-associated features and pathways, such as PI3K/Akt/mTOR, MYC, FZD, and Hedgehog, with increased P53 expression associated with senescence in these cells. CONCLUSIONS: A complex interplay between cellular senescence, cytokine signaling, and gene expression pathways underlies ACP development. Further research is crucial to understand how these elements interact to create novel therapeutic approaches for patients with ACP.


Subject(s)
Cellular Senescence , Craniopharyngioma , Machine Learning , Pituitary Neoplasms , Humans , Craniopharyngioma/metabolism , Craniopharyngioma/pathology , Craniopharyngioma/genetics , Pituitary Neoplasms/pathology , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Phenotype , Gene Expression Regulation, Neoplastic , Child , Male , Female
20.
Child Dev ; 95(2): 481-496, 2024.
Article in English | MEDLINE | ID: mdl-37767574

ABSTRACT

The early language environment, especially high-quality, contingent parent-child language interactions, is crucial for a child's language development and later academic success. In this secondary analysis study, 89 parent-child dyads were randomly assigned to either the Music Together® (music) or play date (control) classes. Children were 9- to 15-month old at baseline, primarily white (86.7%) and female (52%). Measures of conversational turns (CTs) and parental verbal quality were coded from parent-child free play episodes at baseline, mid-intervention (month 6), and post-intervention (month 12). Results show that participants in the music group had a significantly greater increase in CT measures and quality of parent verbalization post-intervention. Music enrichment programs may be a strategy to enhance parent-child language interactions during early childhood.


Subject(s)
Music , Humans , Female , Child, Preschool , Child , Infant , Child Language , Parent-Child Relations , Language Development , Parents
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