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Open Access Publications from the University of California

Scholarly Works (8 results)

  • Thesis
  • Peer Reviewed
UC Riverside Electronic Theses and Dissertations (2017)

Robust gene expression is crucial for proper embryonic development, and yet it is

subject to extrinsic and intrinsic sources of noise. We investigated mechanisms by which

the C. elegans embryo buffers these stochastic variations in gene expression during

endoderm specification. In this system, the factors that contribute to the specification and

differentiation of the intestine’s progenitor are known, allowing us to probe effects of

upstream stochasticity on known downstream events. The ability of this system to buffer

noise during early embryogenesis was tested by targeting early acting inputs in the

endoderm gene regulatory cascade and measuring its effect on tissue specification and

commitment to differentiate. To study the downstream effects of animals that were on the

verge of not committing to making gut cells and nearly missing endoderm differentiation,

we utilized a series of allelic mutants. These mutant strains specify varied numbers of gut

cells, between 0%-100% of the time. Using these strains, we are currently investigating E

lineage phenotypes during early and mid-embryogenesis, as well as the young adult stage.

We have screened for maternal factors to identify potential modifiers of gut specification,

and showed that specification of endoderm is not an all-or-none event at the level of E

blastomere. Instead, it can be displaced as a binary choice at later time points within the E

lineage – a phenomenon that we are calling "stratified specification". Last, we find that

fully differentiated intestine retains a memory of their “near-miss” specification, which

results in abnormal adult phenotype, due to differential expression of genes in the intestine.

Thus far, we have found that several diverse maternal pathways, including transcription

regulation, metabolism, and apoptosis influence the ability of progeny embryos to make

gut, suggesting that embryonic gene expression is highly sensitive to many sources of

variation. Collectively our data show that gut specification is not an "all-or-none" event,

and that if specification does not occur properly, defects can manifest into adulthood. The

results have implications in other developmental pathways in C. elegans and in any

metazoan system in which gene regulatory networks drive developmentally important

events.

    Cover page: Robustness of Gut Development in the Nematode, Caenorhabditis elegans
    • Article
    • Peer Reviewed
    UC Riverside Previously Published Works (2015)
    The MED-1,2 GATA factors contribute to specification of E, the progenitor of the Caenorhabditis elegans endoderm, through the genes end-1 and end-3, and in parallel with the maternal factors SKN-1, POP-1 and PAL-1. END-1,3 activate elt-2 and elt-7 to initiate a program of intestinal development, which is maintained by positive autoregulation. Here, we advance the understanding of MED-1,2 in E specification. We find that expression of end-1 and end-3 is greatly reduced in med-1,2(-) embryos. We generated strains in which MED sites have been mutated in end-1 and end-3. Without MED input, gut specification relies primarily on POP-1 and PAL-1. 25% of embryos fail to make intestine, while those that do display abnormal numbers of gut cells due to a delayed and stochastic acquisition of intestine fate. Surviving adults exhibit phenotypes consistent with a primary defect in the intestine. Our results establish that MED-1,2 provide robustness to endoderm specification through end-1 and end-3, and reveal that gut differentiation may be more directly linked to specification than previously appreciated. The results argue against an "all-or-none" description of cell specification, and suggest that activation of tissue-specific master regulators, even when expression of these is maintained by positive autoregulation, does not guarantee proper function of differentiated cells.
      Cover page: MED GATA factors promote robust development of the C. elegans endoderm
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2021)

      Objectives

      To evaluate ultrasound (US) features associated with successful noninvasive management for suspected retained products of conception (RPOC).

      Methods

      In this IRB-approved retrospective study, the radiology report database was queried for pelvic US with keywords of postpartum hemorrhage (PPH) and/or RPOC over a 2-year period. Follow-up exams, US exams without clinical follow-up, suboptimal image quality, and > 1 year from delivery or pregnancy termination were excluded. Charts were reviewed for clinical presentation and management. Two radiologists reviewed images for endometrial thickness, endometrial echogenicity, endometrial vascularity, and enhanced myometrial vascularity (EMV), as well as inner myometrial peak systolic velocity (PSV) and resistive index (RI) where available. Features were assessed for associations with management approach, and test characteristics were calculated.

      Results

      Initial query yielded 196 exams, and 48 were excluded. A total of 148 patients were included. Mean age was 34.2 years (21-47), and mean time from delivery or pregnancy termination was 40.4 days (0-223). 81 (55%) underwent noninvasive management: 72 (48%) expectant and 9 (6%) medical. 67 (45%) underwent invasive management: 60 (41%) surgical and 7 (5%) uterine artery embolization. There was substantial inter-reader agreement for assessment of EMV (K = 0.78) and endometrial vascularity (K = 0.72). Thin endometrial stripe, avascular endometrium, and absence of EMV were associated with successful noninvasive management (p < 0.05). Thin endometrium (< 10 mm) had specificity (90%), PPV (88%), and likelihood ratio (5.91) in predicting successful noninvasive management.

      Conclusion

      Endometrial thickness < 10 mm, avascular endometrium, and absence of EMV are the sonographic features associated with successful noninvasive management for PPH or suspected RPOC.
        Cover page: Ultrasound features help identify patients who can undergo noninvasive management for suspected retained products of conception: a single institutional experience.Creative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2024)
        Purpose To assess adherence to the US Liver Imaging Reporting and Data System (LI-RADS) recommendations for hepatocellular carcinoma (HCC) surveillance and associated patient-level factors in a vulnerable, diverse patient sample. Materials and Methods The radiology report database was queried retrospectively for patients who underwent US LI-RADS-based surveillance examinations at a single institution between June 1, 2020, and February 28, 2021. Initial US and follow-up liver imaging were included. Sociodemographic and clinical data were captured from electronic medical records. Adherence to radiologist recommendation was defined as imaging (US, CT, or MRI) follow-up in 5-7 months for US-1, imaging follow-up in 3-6 months for US-2, and CT or MRI follow-up in 2 months for US-3. Descriptive analysis and multivariable modeling that adjusted for age, sex, race, and time since COVID-19 pandemic onset were performed. Results Among 936 patients, the mean age was 59.1 years; 531 patients (56.7%) were male and 544 (58.1%) were Asian or Pacific Islander, 91 (9.7%) were Black, 129 (13.8%) were Hispanic, 147 (15.7%) were White, and 25 (2.7%) self-reported as other race. The overall adherence rate was 38.8% (95% CI: 35.7, 41.9). The most common liver disease etiology was hepatitis B (60.6% [657 of 936 patients]); 19.7% of patients (183 of 936) had current or past substance use disorder, and 44.8% (416 of 936) smoked. At adjusted multivariable analysis, older age (odds ratio [OR], 1.20; P = .02), male sex (OR, 1.62; P = .003), hepatology clinic attendance (OR, 3.81; P < .001), and recent prior US examination (OR, 2.44; P < .001) were associated with full adherence, while current smoking (OR, 0.39; P < .001) was negatively associated. Conclusion Adherence to HCC imaging surveillance was suboptimal, despite US LI-RADS implementation. Keywords: Liver, Ultrasound, Screening, Abdomen/GI, Cirrhosis, Metabolic Disorders, Socioeconomic Issues Supplemental material is available for this article. © RSNA, 2024.
          Cover page: Assessing Adherence to US LI-RADS Follow-up Recommendations in Vulnerable Patients Undergoing Hepatocellular Carcinoma Surveillance.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2022)
          The objective is to determine patients' utilization rate of radiology image viewing through an online patient portal and to understand its impact on radiologists. IRB approval was waived. In this two-part, multi-institutional study, patients' image viewing rate was retrospectively assessed, and radiologists were anonymously surveyed for the impact of patient imaging access on their workflow. Patient access to web-based image viewing via electronic patient portals was enabled at 3 institutions (all had open radiology reports) within the past 5 years. The number of exams viewed online was compared against the total number of viewable imaging studies. An anonymized survey was distributed to radiologists at the 3 institutions, and responses were collected over 2 months. Patients viewed 14.2% of available exams - monthly open rate varied from 7.3 to 41.0%. A total of 254 radiologists responded to the survey (response rate 32.8%); 204 were aware that patients could view images. The majority (155/204; 76.0%) felt no impact on their role as radiologists; 11.8% felt negative and 9.3% positive. The majority (63.8%) were never approached by patients. Of the 86 who were contacted, 46.5% were contacted once or twice, 46.5% 3-4 times a year, and 4.7% 3-4 times a month. Free text comments included support for healthcare transparency (71), concern for patient confusion and anxiety (45), and need for attention to radiology reports and image annotations (15). A small proportion of patients viewed their radiology images. Overall, patients' image viewing had minimal impact on radiologists. Radiologists were seldom contacted by patients. While many radiologists feel supportive, some are concerned about causing patient confusion and suggest minor workflow modifications.
            Cover page: Multi-institutional Experience with Patient Image Access Through Electronic Health Record Patient Portals
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2022)
            While mature cystic teratomas are relatively common ovarian neoplasms typically comprising of multiple embryologic cell types, a specific monodermal subtype involving thyroid tissue, struma ovarii, can rarely be seen. This case reviews typical imaging characteristics with MRI and ultrasound of struma ovarii and details possible complications from these masses with intraoperative and histologic correlation.
              Cover page: Boba sign with a twist – A variant presentation of a mature cystic teratoma complicated by torsion and rupture
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2019)
              The US Liver Imaging Reporting and Data System (LI-RADS) was released in 2017 and is the newest of the four American College of Radiology (ACR) LI-RADS algorithms. US LI-RADS provides standardized terminology, technical recommendations, and a reporting framework for US examinations performed for screening or surveillance in patients at risk for developing hepatocellular carcinoma (HCC). The appropriate patient population for screening and surveillance includes individuals who are at risk for developing HCC but do not have known or suspected cancer. This includes patients with cirrhosis from any cause and subsets of patients with chronic hepatitis B virus infection in the absence of cirrhosis. In an HCC screening or surveillance study, US LI-RADS recommends assigning two scores that apply to the entire study: the US category, which determines follow-up, and a visualization score, which communicates the expected level of sensitivity of the examination but does not affect management. Three US categories are possible: US-1 negative, a study with no evidence of HCC; US-2 subthreshold, a study in which an observation less than 10 mm is depicted that is not definitely benign; and US-3 positive, a study in which an observation greater than or equal to 10 mm or a new thrombus in vein is identified, for which diagnostic contrast material-enhanced imaging is recommended. Three visualization scores are possible: A (no or minimal limitations), B (moderate limitations), and C (severe limitations). ©RSNA, 2019.
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2023)

                Background

                Patients with cirrhosis and subcentimeter lesions on liver ultrasound are recommended to undergo short-interval follow-up ultrasound because of the presumed low risk of primary liver cancer (PLC).

                Aims

                The aim of this study is to characterize recall patterns and risk of PLC in patients with subcentimeter liver lesions on ultrasound.

                Methods

                We conducted a multicenter retrospective cohort study among patients with cirrhosis or chronic hepatitis B infection who had subcentimeter ultrasound lesions between January 2017 and December 2019. We excluded patients with a history of PLC or concomitant lesions ≥1 cm in diameter. We used Kaplan Meier and multivariable Cox regression analyses to characterize time-to-PLC and factors associated with PLC, respectively.

                Results

                Of 746 eligible patients, most (66.0%) had a single observation, and the median diameter was 0.7 cm (interquartile range: 0.5-0.8 cm). Recall strategies varied, with only 27.8% of patients undergoing guideline-concordant ultrasound within 3-6 months. Over a median follow-up of 26 months, 42 patients developed PLC (39 HCC and 3 cholangiocarcinoma), yielding an incidence of 25.7 cases (95% CI, 6.2-47.0) per 1000 person-years, with 3.9% and 6.7% developing PLC at 2 and 3 years, respectively. Factors associated with time-to-PLC were baseline alpha-fetoprotein >10 ng/mL (HR: 4.01, 95% CI, 1.85-8.71), platelet count ≤150 (HR: 4.90, 95% CI, 1.95-12.28), and Child-Pugh B cirrhosis (vs. Child-Pugh A: HR: 2.54, 95% CI, 1.27-5.08).

                Conclusions

                Recall patterns for patients with subcentimeter liver lesions on ultrasound varied widely. The low risk of PLC in these patients supports short-interval ultrasound in 3-6 months, although diagnostic CT/MRI may be warranted for high-risk subgroups such as those with elevated alpha-fetoprotein levels.
                  Cover page: Recall patterns and risk of primary liver cancer for subcentimeter ultrasound liver observations: a multicenter study.Creative Commons 'BY' version 4.0 license
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