Biomedical subjects

Susan Walsh

Publications and source records attributed to Susan Walsh.

11 recordsLinked to original sources

PubMed2025

Clustering individuals using INMTD: a novel versatile multi-view embedding framework integrating omics and imaging data.

MOTIVATION: Combining omics and images can lead to a more comprehensive clustering of individuals than classic single-view approaches. Among the various approaches for multi-view clustering, nonnegative matrix tri-factorization (NMTF) and nonnegative Tucker decomposition (NTD) are advantageous in learning low-rank embeddings with promising interpretability. Besides, there is a need to handle unwanted drivers of clusterings (i.e. confounders). RESULTS: In this work, we introduce a novel multi-view clustering method based on NMTF and NTD, named INMTD, which integrates omics and 3D imaging data to derive unconfounded subgroups of individuals. According to the adjusted Rand index, INMTD outperformed other clustering methods on a synthetic dataset with known clusters. In the application to real-life facial-genomic data, INMTD generated biologically relevant embeddings for individuals, genetics, and facial morphology. By removing confounded embedding vectors, we derived an unconfounded clustering with better internal and external quality; the genetic and facial annotations of each derived subgroup highlighted distinctive characteristics. In conclusion, INMTD can effectively integrate omics data and 3D images for unconfounded clustering with biologically meaningful interpretation. AVAILABILITY AND IMPLEMENTATION: INMTD is freely available at https://github.com/ZuqiLi/INMTD.

Cluster Analysis↗

PubMed2025

Optimized phenotyping of complex morphological traits: enhancing discovery of common and rare genetic variants.

Genotype-phenotype (G-P) analyses for complex morphological traits typically utilize simple, predetermined anatomical measures or features derived via unsupervised dimension reduction techniques (e.g. principal component analysis (PCA) or eigen-shapes). Despite the popularity of these approaches, they do not necessarily reveal axes of phenotypic variation that are genetically relevant. Therefore, we introduce a framework to optimize phenotyping for G-P analyses, such as genome-wide association studies (GWAS) of common variants or rare variant association studies (RVAS) of rare variants. Our strategy is two-fold: (i) we construct a multidimensional feature space spanning a wide range of phenotypic variation, and (ii) within this feature space, we use an optimization algorithm to search for directions or feature combinations that are genetically enriched. To test our approach, we examine human facial shape in the context of GWAS and RVAS. In GWAS, we optimize for phenotypes exhibiting high heritability, estimated from either family data or genomic relatedness measured in unrelated individuals. In RVAS, we optimize for the skewness of phenotype distributions, aiming to detect commingled distributions that suggest single or few genomic loci with major effects. We compare our approach with eigen-shapes as baseline in GWAS involving 8246 individuals of European ancestry and in gene-based tests of rare variants with a subset of 1906 individuals. After applying linkage disequilibrium score regression to our GWAS results, heritability-enriched phenotypes yielded the highest SNP heritability, followed by eigen-shapes, while commingling-based traits displayed the lowest SNP heritability. Heritability-enriched phenotypes also exhibited higher discovery rates, identifying the same number of independent genomic loci as eigen-shapes with a smaller effective number of traits. For RVAS, commingling-based traits resulted in more genes passing the exome-wide significance threshold than eigen-shapes, while heritability-enriched phenotypes lead to only a few associations. Overall, our results demonstrate that optimized phenotyping allows for the extraction of genetically relevant traits that can specifically enhance discovery efforts of common and rare variants, as evidenced by their increased power in facial GWAS and RVAS.

Humans↗

PubMed2006

Challenges in design and transition to a private room model in the neonatal intensive care unit.

As the need for neonatal intensive care units (NICU) continues to increase, a growing body of evidence on the developmentally appropriate healing environment for neonates suggests that changes are needed in NICU design. The private room NICU model is emerging as an alternative to large multi-bed wards; however, some have suggested that such a radical design change may be difficult to implement. This article presents the experience of one unit in the design and transition from a traditional setting to the private room model. Using change theory, this model was developed with staff input throughout the entire design and implementation process, resulting in a successful transition, as suggested by preliminary data on patient outcomes, family experiences, and nursing staff satisfaction.

Continuity of Patient Care↗

PubMed2006

A clinical pilot study: high frequency chest wall oscillation airway clearance in patients with amyotrophic lateral sclerosis.

Respiratory complications are common in patients with amyotrophic lateral sclerosis (ALS) with respiratory failure representing the most common cause of death. Ineffective airway clearance resultant from deficient cough frequently contributes to these abnormalities. We sought to evaluate the effectiveness of high frequency chest wall oscillation (HFCWO) administered through the Vest Airway Clearance System when added to standard care in preventing pulmonary complications and prolonging the time to death in patients with ALS. This is a single center study performed at the Penn State Milton S. Hershey Medical Center (HMC). Nine patients with a diagnosis of ALS and concurrently receiving non-invasive ventilatory support with bi-level positive airway pressure (BiPAP) were recruited from the outpatient clinic at HMC. Four patients were randomized to receive standard care and five patients to receive standard care plus the addition of HFCWO administered twice-daily for 15 min duration. Longitudinal assessments of oxyhemoglobin saturation, forced vital capacity (FVC), and adverse events were obtained until time of death. Pulmonary complications of atelectasis, pneumonia, hospitalization for a respiratory-related abnormality, and tracheostomy with mechanical ventilation were monitored throughout the study duration. No differences were observed between treatment groups in relation to the rate of decline in FVC. The addition of HFCWO airway clearance failed to improve time to death compared to standard treatment alone (340 days +/- 247 vs. 470 days +/- 241; p = 0.26). The random allocation of HFCWO airway clearance to patients with ALS concomitantly receiving BiPAP failed to attain any significant clinical benefits in relation to either loss of lung function or mortality. This study does not exclude the potential benefit of HFCWO in select patients with ALS who have coexistent pulmonary diseases, pre-existent mucus-related pulmonary complications, or less severe levels of respiratory muscle weakness.

Adult↗

PubMed2004

Factors supporting quality of life over time for individuals with amyotrophic lateral sclerosis: the role of positive self-perception and religiosity.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease with no known cure. Maintaining quality of life (QOL) as the disease progresses is an important treatment goal. PURPOSE: the purpose of this study is to identify factors that support QOL as ALS progresses. METHODS: Changes in QOL were monitored in 162 individuals with ALS at 3- to 4-month intervals. Forty-nine of the participants survived in the study for over 1 year and were included in a longitudinal comparison. The 49 long-term participants were younger and stronger at Time 1 than were the participants who died before reaching the 1-year point. The McGill Quality of Life Scale demonstrated a high and stable QOL despite physical deterioration. RESULTS: Patients maintained a positive self-perception of their health despite the physical deterioration. Over time, self-perception of health and religiosity were shown to be significantly correlated with QOL. CONCLUSIONS: Results support the need for better instrumentation to enable future studies to more precisely measure multiple dimensions of ALS-related QOL, to identify reference points for self-ratings of both health and QOL, and to capture the religious and spiritual mechanisms related to QOL as individuals face the end of life.

Adult↗

PubMed2004

An examination of parenting experiences in male perpetrators of domestic violence: a qualitative study.

Early experiences have been found to have an enduring long-term impact on adult relationships. The coexistence of love and violence is evident in attachment patterns across the life-span, and in adulthood is particularly apparent in domestically violent partnerships. The aim of the study was to examine in depth the early parenting experiences of men who are domestically violent. Seven male participants who were on probation orders for domestic violence were interviewed using the Adult Attachment Interview. The data were analysed qualitatively and the results indicated that all of the men had experienced unloving, rejecting and dangerous parenting. Participants minimized their own violence upon their female partners despite having recently completed an anti-violence training intervention. Clinical implications, particularly the need to examine the efficacy of treatment with domestically violent men, are discussed.

Adult↗

PubMed2003

PP1 control of M phase entry exerted through 14-3-3-regulated Cdc25 dephosphorylation.

It has been known for over a decade that inhibition of protein phosphatase 1 (PP1) activity prevents entry into M phase, but the relevant substrate has not been identified. We report here that PP1 is required for dephosphorylation of the Cdc2-directed phosphatase Cdc25 at Ser287 (of Xenopus Cdc25; Ser216 of human Cdc25C), a site that suppresses Cdc25 during interphase. Moreover, PP1 recognizes Cdc25 directly by interacting with a PP1-binding motif in the Cdc25 N-terminus. We have also found that 14-3-3 binding to phospho-Ser287 protects Cdc25 from premature dephosphorylation. Upon entry into M phase, 14-3-3 removal from Cdc25 precedes Ser287 dephosphorylation, suggesting the existence of a phosphatase- independent pathway for 14-3-3 removal from Cdc25. We show here that this dissociation of 14-3-3 from Cdc25 requires the activity of the cyclin-dependent kinase Cdk2, providing a molecular explanation for the previously reported requirement for Cdk2 in promoting mitotic entry. Collectively, our data clarify several steps important for Cdc25 activation and provide new insight into the role of PP1 in Cdc2 activation and mitotic entry.

14-3-3 Proteins↗

PubMed2003

STRO-1, HOP-26 (CD63), CD49a and SB-10 (CD166) as markers of primitive human marrow stromal cells and their more differentiated progeny: a comparative investigation in vitro.

There is widespread interest in the use of bone marrow stromal cells (BMSC) for tissue reconstruction and repair and for gene therapy. BMSC represent the differentiated progeny of CFU-F, which however comprise a developmentally heterogeneous population as is reflected in the cellular heterogeneity of the cell populations to which they give rise. We have compared the efficacy of monoclonal antibodies recognising a series of stromal antigens, viz. STRO-1, HOP-26, CD49a and SB-10/CD166, as tools for the enrichment of CFU-F prior to culture and as developmental markers for culture-expanded BMSC. In freshly isolated bone marrow mononuclear cells (BMMNC), the proportion of antigen-positive cells was 27%, 46%, 5% and 19% for STRO-1, HOP-26, CD49a and CD166, respectively. All CD49a(+) cells co-expressed STRO-1. The degree of CFU-F enrichment obtained with anti-CD49a (approximately 18-fold) by a one-pass immunoselection strategy was significantly greater than that of all other antibodies tested. BMSC expressed higher levels of all antigens investigated (except for HOP-26) compared with BMMNC. Expression of STRO-1 and CD49a remained restricted to a subset of BMSC, whereas all BMSC were SB-10/CD166 positive. Treatment with dexamethasone (10 nM), which promotes the differentiation and further maturation of cells of the osteogenic lineage in this cell culture system, increased the expression of CD49a and HOP-26. The CD49a(+) and HOP-26(+) fractions of BMSC were further subdivided by dual-labelling with anti-STRO-1 and B4-78 (an antibody recognising the B/L/K isoform of the enzyme alkaline phosphatase), respectively. By using a variety of criteria, the HOP-26 antigen was identified as CD63, a member of the tetraspanin family of proteins thought to modulate integrin compartmentalisation and signalling.

Activated-Leukocyte Cell Adhesion Molecule↗

PubMed2003

TGFbeta1 limits the expansion of the osteoprogenitor fraction in cultures of human bone marrow stromal cells.

Currently, there is considerable interest in the possibility of using cultured human bone marrow stromal cells (BMSCs) for skeletal tissue engineering. However, the factors that regulate their ex vivo expansion and promote their osteogenic maturation remain poorly defined. Using BMSCs obtained from a large cohort of adult donors, the effects of transforming growth factor (TGF)beta1 on these processes have been determined. BMSCs were found to express TGFbeta receptors (TbetaRs) I, II, III (betaglycan) and CD105/endoglin. The expression of TbetaRs I and II, but not TbetaR III or endoglin, was linked to the cells' state of maturation. Treatment with TGFbeta increased the colony-forming efficiency (CFE) of marrow cell suspensions but reduced the median diameter of the colonies that formed and the number of cells harvested at the end of primary culture. Treatment with TGFbeta also resulted in a significant downregulation in the expression of the developmental markers alkaline phosphatase (AP) and STRO-1. The reduction in AP was due to a decrease in the absolute number of cells expressing this enzyme and in the level (sites/cell) at which it was expressed. Overall, the changes in the expression of STRO-1 and AP are consistent with TGFbeta acting to decrease the size of the osteoprogenitor fraction, and hence the potential clinical utility of the cultured cell population.

Adult↗

PubMed2003

Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and Plx.

The cyclin B1/Cdc2 complex regulates many of the dramatic cellular rearrangements observed at mitosis. Although predominantly cytoplasmic during interphase, this kinase complex translocates precipitously to the nucleus at the G(2)-M transition. The interphase cytoplasmic location of cyclin B1/Cdc2 reflects continuous, albeit slow, nuclear import and much more rapid nuclear export. In contrast, the sudden nuclear accumulation of the complex before entry into mitosis reflects a marked increase in the import rate, with a concomitant inhibition of cyclin B1 nuclear export. These dynamic changes in cyclin B1/Cdc2 localization are regulated by phosphorylation of four serines within a region of cyclin B1 known as the cytoplasmic retention sequence (CRS). Phosphorylation of all four serines is required for rapid nuclear entry, whereas phosphorylation of only the last in the series (Ser 113) is required to prevent nuclear export by CRM1. As these residues represent key loci of regulation, it is important to identify the kinases acting on these sites. Here we report that Xenopus cyclin B1 is regulated by both Erk and Plx kinases, and that Cdc2, counter to previous speculation, is not required for CRS phosphorylation. Phosphorylation of the first two of the CRS serines (Ser 94 and Ser 96) is catalyzed by Erk in the Xenopus system. Although it was previously reported that Ser 113 is a Plx substrate, we were unable to observe phosphorylation of this residue in isolation by purified Plx. Rather, in contrast to previously published data, we have found that the penultimate CRS serine (Ser 101) is a Plx substrate. Collectively, these data demonstrate a new role for Erk in mitotic regulation, identify the Ser 101-directed kinase, and provide a picture of cyclin B1/Cdc2 regulation by the combinatorial action of distinct kinases.

Amino Acid Sequence↗

PubMedDate not supplied

Formulation of a plan of care for culturally diverse patients.

PURPOSE: To formulate a plan of care for a culturally diverse population and develop a resource for the healthcare team in providing culturally competent care. DATA SOURCES: Books, journal articles. DATA SYNTHESIS: Healthcare workers are challenged to provide appropriate care for an increasingly diverse population. A cluster of nursing diagnoses were used to develop a plan of care addressing the unique challenges of caring for a diverse population served by a community hospital. CONCLUSION: A care plan was devised and inserted into the nursing diagnosis-based nursing documentation computer system for easy access when needed. PRACTICE IMPLICATIONS: A care plan for a diverse population can promote respectful and excellent care for every patient.

Adaptation, Psychological↗