Microbial community assembly in engineered bioreactors.

Microbial community assembly (MCA) processes that shape microbial communities in environments are being used to analyze engineered bioreactors such as activated sludge systems and anaerobic digesters. The goal of studying MCA is to be able to understand and predict the effect of design and operation procedures on bioreactor microbial composition and function. Ultimately, this can lead to bioreactors that are more efficient, resilient, or resistant to perturbations. This review summarizes the ecological theories underpinning MCA, evaluates MCA analysis methods, analyzes how these MCA-based methods are applied to engineered bioreactors, and extracts lessons from case studies. Furthermore, we suggest future directions in MCA research in engineered bioreactor systems. The review aims to provide insights and guidance to the growing number of environmental engineers who wish to design and understand bioreactors through the lens of MCA.

Modeling antibody drug conjugate potential using a granzyme B antibody fusion protein.

BACKGROUND: Antibody drug conjugates (ADCs) constitute a promising class of targeted anti-tumor therapeutics that harness the selectivity of monoclonal antibodies with the potency of cytotoxic drugs. ADC development is best suited to initially screening antibody candidates for desired properties that potentiate target cell cytotoxicity. However, validating and producing an optimally designed ADC requires expertise and resources not readily available to certain laboratories. RESULTS: In this study, we propose a novel approach to help streamline the identification of potential ADC candidates by utilizing a granzyme B (GrB)-based antibody fusion protein (AFP) for preliminary screening. GrB is a non-immunogenic serine protease expressed by immune effector cells such as CD8 + T cells that induces apoptotic activity and can be leveraged for targeted cell killing. CONCLUSIONS: Our innovative model allows critical antibody parameters (including target cell binding, internalization, and cytotoxic potential) to be more reliably evaluated in vitro through the creation of an ADC surrogate. Successful incorporation of this AFP could also significantly expand and enhance ADC development pre-clinically, ultimately leading to the accelerated translation of ADC therapies for patients.

Listeria-based vaccination against the pericyte antigen RGS5 elicits anti-vascular effects and colon cancer protection.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality despite efforts to improve standard interventions. As CRC patients can benefit from immunotherapeutic strategies that incite effector T cell action, cancer vaccines represent a safe and promising therapeutic approach to elicit protective and durable immune responses against components of the tumor microenvironment (TME). In this study, we investigate the pre-clinical potential of a Listeria monocytogenes (Lm)-based vaccine targeting the CRC-associated vasculature. CRC survival and progression are reliant on functioning blood vessels to effectively mediate various metabolic processes and oxygenate underlying tissues. We, therefore, advance the strategy of initiating immunity in syngeneic mouse models against the endogenous pericyte antigen RGS5, which is a critical mediator of pathological vascularization. Overall, Lm-based vaccination safely induced potent anti-tumor effects that consisted of recruiting functional Type-1-associated T cells into the TME and reducing tumor blood vessel content. This study underscores the promising clinical potential of targeting RGS5 against vascularized tumors like CRC.

Targeting the pericyte antigen DLK1 with an alpha type-1 polarized dendritic cell vaccine results in tumor vascular modulation and protection against colon cancer progression.

Despite the availability of various treatment options, colorectal cancer (CRC) remains a significant contributor to cancer-related mortality. Current standard-of-care interventions, including surgery, chemotherapy, and targeted agents like immune checkpoint blockade and anti-angiogenic therapies, have improved short-term patient outcomes depending on disease stage, but survival rates with metastasis remain low. A promising strategy to enhance the clinical experience with CRC involves the use of dendritic cell (DC) vaccines that incite immunity against tumor-derived blood vessels, which are necessary for CRC growth and progression. In this report, we target tumor-derived pericytes expressing DLK1 with a clinically-relevant alpha type-1 polarized DC vaccine (αDC1) in a syngeneic mouse model of colorectal cancer. Our pre-clinical data demonstrate the αDC1 vaccine's ability to induce anti-tumor effects by facilitating cytotoxic T lymphocyte activity and ablating the tumor vasculature. This work, overall, provides a foundation to further interrogate immune-mediated mechanisms of protection in order to help devise efficacious αDC1-based strategies for patients with CRC.

Teaching Medical Students Health Care Failure Mode and Effect Analysis: A Case Study of Inpatient Pain Management Computerized Decision Support.

There is a pressing need to provide health professional leaners experiential learning opportunities in health systems science and quality improvement. Moreover, there are several published tools to diagnose and treat health system vulnerabilities and hazards. The Health Care Failure Mode and Effect AnalysisTM (HFMEA) is a systems-engineering tool that the military and aerospace industries developed to proactively identify potential errors. While this technique has been used in a range of healthcare settings, there are few reports where health professional educators have used it with learners to teach quality improvement and systems engineering methods. We describe herewith an application of HFMEA in a medical informatics professional student rotation. In this manuscript, we briefly review HFMEA theory and methods, illustrate its application to address a quality improvement initiative, and reflect upon its value - and limitations - when used in an educational context.

Adherence to physical activity guidelines in breast cancer survivors.

Physical activity in breast cancer survivors has been shown to improve outcomes. This study evaluated breast cancer patients' adherence to physical activity guidelines in a population-based study. Data from the 2007 National Health Interview Survey were used to compare adherence to physical activity guidelines in patients with breast cancer with the general population. Statistical analyses were performed using SUDAAN software. In 2007, 327 breast cancer survivors and 23,030 others from the general population were surveyed. Breast cancer survivors were significantly older than the general population (mean age 64.9 vs. 45.6 years, P < 0.001) and tended to be female (99.4 vs. 51.2%, P < 0.001). Despite being significantly more likely to have interacted with a healthcare professional within the past year (96.7 vs. 82.1%, P < 0.001), fewer breast cancer survivors reported following physical activity guidelines than nonbreast cancer survivors (4.64 vs. 12.0%, P < 0.001). Controlling for age, gender, and interaction with healthcare providers, breast cancer survivors were no more likely to follow physical activity guidelines than the general population (OR: 0.73; 95% CI: 0.41-1.30, P = 0.282). Despite more interaction with healthcare providers, breast cancer survivors are no more likely to adhere to activity guidelines than the general population.

The role of sentinel node biopsy in women undergoing prophylactic mastectomy.

BACKGROUND: Sentinel lymph node (SLN) biopsy in patients undergoing prophylactic mastectomy (PM) remains controversial. We sought to determine the incidence of finding occult cancer and the frequency of SLN positivity in patients undergoing contralateral PM. METHODS: Medical records of patients undergoing bilateral mastectomy at our institution from 2003 to 2008 were reviewed (n = 115). Eight patients (6.9%) had known bilateral cancer; an additional eight patients (6.9%) underwent BPM for risk reduction. The remaining 99 patients who had ipsilateral breast cancer and underwent contralateral PM formed the cohort of interest for this study. Univariate and multivariate analyses to determine factors correlating with occult malignancy and SLN positivity in the PM specimen were performed using SPSS ver. 17 (SPSS Inc., Chicago, IL). RESULTS: The median patient age was 50 y, and median ipsilateral tumor size was 1.7 cm. Occult contralateral malignancy was found in eight (8.1%); of these, six (75.0%) had DCIS only. A positive SLN was found on the prophylactic side in 2 (2.0%) patients. Both had ipsilateral inflammatory cancer, and over 15 positive ipsilateral lymph nodes post-neoadjuvant chemotherapy. Ipsilateral inflammatory breast cancer was correlated with the finding of invasive cancer in the contralateral PM (P = 0.006), and both the finding of ipsilateral inflammatory breast cancer and number of positive lymph nodes correlated with the finding of a positive contralateral SLN. CONCLUSION: The incidence of occult malignancy in PM is low (2%). However, patients with ipsilateral inflammatory cancer are at high risk of contralateral malignancy; SLN biopsy on the prophylactic side in these patients may be warranted.