Annotated Bibliography for Nursing 6: Healthcare Research Studies

This annotated bibliography presents a compilation of research papers spanning various critical areas within healthcare and nursing. The included studies delve into topics such as fecal microbiota transplantation for metabolic disorders, the applications and limitations of split green fluorescent proteins in molecular biology, and the efficacy of personalized antiplatelet therapy based on pharmacogenomics for stroke patients. Additional papers explore the potential of 3D bioprinting for creating functional tissue models in drug screening and disease modeling, the use of adeno-associated virus (AAV) vectors in gene therapy, and the role of pluripotent stem cells in cardiovascular regenerative medicine. Each entry provides a concise summary of the study's purpose, key findings, significance, and recommendations, offering a comprehensive overview of current research and its implications for future advancements in healthcare practices and treatments. The bibliography covers a range of innovative technologies and therapeutic approaches, highlighting the dynamic and evolving nature of medical research.

Running head: NURSING
Nursing
Name of the student:
Name of the University:
Author’s note

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Annotated bibliography
Aron-Wisnewsky, J., Clément, K., & Nieuwdorp, M. (2019). Fecal Microbiota Transplantation: a
Future Therapeutic Option for Obesity/Diabetes?. Current diabetes reports, 19(8), 51.
This review gave an overview of current data related to the metabolic effects fecal
microbiata transplantation (FMT) and present findings particularly related to the impact of FMT
on obesity and glucose metabolisms in humans. The study gave insight into several findings
from the recent research literatures. The key findings were that gut microbiota dysbiosis is a
common characteristics in obesity and metabolic disease and evidence from experiments done in
mouse model indicated that dysbiosis is associated with improvement in metabolism. The paper
also gave overview of possible interventions that could reduce the problem. Dietary interventions
should be accompanies by complete or partial restoration of dysbiosis and this can be combined
with weight reduction and metabolic improvement strategies. The paper described different
factors that modulated FMT response such as microbiota engraftment upon donor FMT,
composition of donor microbiota and donot FMT success. The significance of the review is that
it has a detailed focus and the author is not just looking at problem but also innovative and
effective solutions to the issues. Some positive recommendations from the study included the
evidence on impact of dietary interventions and its effect on donor FMT effect. The clinical
effect of FMT was facilitated by donor’s diet. The key conclusion from the study was that FMT
has the potential to improve metabolic state and influence the effect of FMT on weight loss in
obese subjects. The significance of the study is that it recommends several steps that can be used
improve management of metabolic disorders. These recommendations included investigating
about FMT impact on patient with TSD, conducting future research to understand gender effect

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and interpret the optimal mode of donor selection. Hence, future research in the above areas is
likely to enhance the work towards microbiota related therapy developments.
Romei, M. G., & Boxer, S. G. (2019). Split green fluorescent proteins: scope, limitations, and
outlook. Annual review of biophysics, 48, 19-44.
The main purpose of this study was to review the scope and limitations of split green
fluorescent proteins (GFPs) and its application in various areas as molecular glues and
optogenetic tools. Split proteins are those proteins that lack activity of each fragment and that
restores activity upon fragment reconstitution. In some case, split GFPs have a role in detecting
the interactions of proteins that is attached to the split fragrance by GFP flourescence. Despite
several benefits of GFPs, the significance of this article was it highlighted about limitations of
the bimolecular fluorescence (BiFC) complementation. The first limitation reported by the study
was that by irreversible bindings, the split FP fragments resulted in detection of weak PPIs. The
difficulty associated with this form of interaction is that it results in accumulation of the
fluorescent signal that could misinform researchers about the behaviour of PPIs. The second
limitation discussed in the study was that due to split FP complementation, there is unavoidable
delay in interactions between the test protein and the fluorescent readout. The third limitation
covered in the article was that the split fragments have unique binding affinity thus suggesting
the need of effective quantitative controls when implementing any BiFC experiments. The study
gave overview of studies that worked to improve these limitations too. The first limitation was
found to be addressed by engineering a split infrared FP. The study also suggested the need to
shorten assay time so that reliable results could be obtained. Furthermore, to minimize the
complications from fragment self-assembly, the author gave example of a study where heavily
engineered system was used to produce small fusion tags. The study gave many important

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implications such as expanding the scope of the split GFP proximity sensor and using
mechanistic insights to help guide efforts to develop optogenetic tools.
Zhang, X. G., Zhu, X. Q., Xue, J., Li, Z. Z., Jiang, H. Y., Hu, L., & Yue, Y. H. (2019).
Personalised antiplatelet therapy based on pharmacogenomics in acute ischaemic minor stroke
and transient ischaemic attack: study protocol for a randomised controlled trial. BMJ open, 9(5),
e028595.
The study investigated about the efficacy of individualized antiplatelet therapy (IAT) on
patients with acute ischemic minor stroke (AIMS) or transient ischemic stroke (TIA). The main
rationale for conducting this study was given by review of various research papers which showed
the promise of genetic testing that allows clinicians to personalize anti-platelet therapy. As no
clinical trial had investigated about the genetic and clinical factors that influences clopidogrel
responses, randomized controlled trial was conducted to validate whether IAT selected based on
genetic information and patient’s clinical features could lead to better outcomes in patient or not.
The study protocol suggested that it will recruit 2382 patients with AIMS or TIA and randomly
assign them to the pharmacogentic group and standard group in 1:1 ratio. Both patients were
given 300mg aspirin and clopidogrel on day 1 followed by 100 mg aspirin on data 2. The
primary efficacy point was a new stroke event within 1 year and the secondary efficacy point
included new clinical vascular event such as ischaemic stroke, myocardial infarction and
haemorrhagic stroke. There were certain criteria for inclusion in the study. This included 18
years of age and diagnosis of an AIMs or TIA. The exclusion criteria included exclusion of those
patients which had haemorrhage, vascular malformation, systemic infectious diseases,
autoimmune disease, liver and kidney diseases and contradindications to use of aspirin. The
sample size estimated for the study was 1191 patients and this was done by doing appropriate

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calculation on sample size. The study proposed conducting statistical analysis of data using chi
square test and 95% confidence interval. This study is likely to confirm whether pharmacogentic
data can be successful in implementing IAT intervention or not. By collecting patients from a
heterogenous group of data, the study is likely to give reliable results. However, one of the
limitation of this study is that it will be done only in Chinese population that can affect the
generalizability of the findings.
Ma, X., Liu, J., Zhu, W., Tang, M., Lawrence, N., Yu, C., ... & Chen, S. (2018). 3D bioprinting
of functional tissue models for personalized drug screening and in vitro disease
modeling. Advanced drug delivery reviews, 132, 235-251.
3D bioprinting is a promising technology for fabricating tissue constructs with tailored
biological components and mechanical properties. The significance of this article is that the
study reviewed recent research literature regarding the 3D bioprinting techniques and the choice
of cell source in implementing personalized drug screening and disease modelling process. The
key advantage of 3D bioprinting discussed in the article was that it had the benefit of
reconstructing complex structures from MRI scans. The article reported about the availability of
various types of 3D bioprinting technology such as inkjet-based bioprintin, extrusion based
bioprinting, light assisted bioprinting, TPP based bioprinting and DLP based bioprinting. Some
of the cell source and preparation needed for this technology included cell seeding on printed
scaffolds and directly seeding sources with a carrier matrix like collagen. However, the review of
recent studies on these aspects of preparation revealed that cellularization approach depended on
various factors like the main purpose of the study, method employed for printing and the type of
cells used. In addition, the cell sources that were found reliable to build 3D printed tissue models
include primary cells, cell lines and stem cell-derived cells. The application of the technology

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was found in various areas such as liver models, heart and muscle models, vascularised tissue
models and cancer models. For example, in case of cancer model, the positive implication of 3D
printing technology was found in studying tumor-stroma interactions and studying metastatic
progression. However, the discussion related to challenges and future outlook is the most
important section of the article as it provides the scope to further improve the quality and
efficacy of 3D printing technology. The summary of the challenges included difficulty in
recapitulating the cellular organization, technological challenges in increasing resolution and
biocompatibility and limitations on materials used for the technology. Thus, research related and
technological advancement in the field of biomedical engineering is likely to support proper
utilization of 3D bioprinting.
Wang, D., Tai, P. W., & Gao, G. (2019). Adeno-associated virus vector as a platform for gene
therapy delivery. Nature Reviews Drug Discovery, 18(5), 358-378.
This study explored the role of adeno-associated virus (AAV) in the context of gene
delivery for the treatment of various human diseases. The study reported about various
preclinical and clinical successes in AAV-mediated gene replacement, gene silencing and gene
editing. It discussed about the use of AAV vectors to deliver therapeutic genes and the existing
challenges to transitioning these drug platforms. AAV was identified as an important vector in
vivo gene delivery. The vector design was dependent on capsid development which is possible
through three approaches such as natural discovery, rational design and directed evolution.
However, the limitation identified in the rational design approach was lack of proper knowledge
regarding AAV cell surface binding, internalization and gene expressions. Hence, directed
evolution approach was found to be useful in this situation as it depends on simulation of natural
evolution and capsids are able to yield genetic variants based on selective pressure. The article

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reported about some exemplary translational applications and successes too. For instance, AAV
has the scope to target multiple muscle types thus enabling gene therapies to be delivered for
various type of muscle diseases. Some advanced AAV gene therapy strategies found in the
article were gene replacement that delivers gene product to compensate for loss of function
mutation, gene silencing therapy to deal with monogenic diseases such as Hungtington disease,
gene addition therapy to tackle complex genetic diseases and gene editing therapy to directly
repair mutations in human diseases. Despite the clinical benefits and advantage of AAV in
implementing various gene therapies, certain challenges in applying the procedure in medical
field were found. For example, affordability and high cost was a major concern due to
productivity cost associated with developing a vector to treat a target organ. Other challenges
included assay standardizing assay, improving quality of assay and immunological barriers to
rAAV gene delivery. Thus, study gives exciting ideas regarding areas where scientist can work
and fully tap into the benefits of rAAV gene therapy.
Abou-Saleh, H., Zouein, F. A., El-Yazbi, A., Sanoudou, D., Raynaud, C., Rao, C., ... & Eid, A.
H. (2018). The march of pluripotent stem cells in cardiovascular regenerative medicine. Stem cell
research & therapy, 9(1), 201.
The main purpose of this study to describe different types of stem cells and discuss about
the properties induced pluripotent stem cells (iPSC). The article discussed about the useful
methods for converting somatic cells to iPSC and iPSC to cardiomyocytes. The limitation and
advantages of these methods were discussed too. The review of the study indicated that
classification of stem cell is mostly done by potency or differentiation potential. Multipotent
stem cells were found to maintain homeostasis of mature cell tissues and the ability regenerate
damaged organs. The utility of iPSCs was found for transforming fully differentiated adult

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somatic cells into pluripotent stem cells. Some non-integrating reprogramming methods
discussed in the article included viral non-integrating method and non-viral non-integrating
methods. The first method involved developing iPSCs using non-integrating viruses such as
adenoviruses and the second method involved deriving iPSCs through virus free and transgene
free techniques. The clinical utility of the study is that it suggested several ways to improve the
differentiation and maturation of IPSC derived CMs. The genetic strategies included the lack of
knockdown of certain genes, hypotoxic culture conditions, bioreactors, controlled feeding
strategies and chemical supplementation variations. After differentiation of these cells,
purification of IPSC derived cells and characterization of Ipsc derived CMs. The characterization
mainly involved reviewing structural and function properties of cells using techniques like HPLC
mass spectrometry, molecular biology, electrophysiology and liver cell imaging. Moreover, the
discussion regarding the application of iPSC in drug screening and other areas are effective as it
suggest how the stem cell could properly utilized to enhance drug development process. Drug
development is an expensive process and animal models of immortalized human cells are
effective in evaluating the safety and efficacy of these drugs. Overall, the overall discussions
give important lessons on ways to enable rapid application of iPSCs to cell therapy and
interpreting new therapeutic targets.

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References:
Abou-Saleh, H., Zouein, F. A., El-Yazbi, A., Sanoudou, D., Raynaud, C., Rao, C., ... & Eid, A.
H. (2018). The march of pluripotent stem cells in cardiovascular regenerative
medicine. Stem cell research & therapy, 9(1), 201.
Aron-Wisnewsky, J., Clément, K., & Nieuwdorp, M. (2019). Fecal Microbiota Transplantation: a
Future Therapeutic Option for Obesity/Diabetes?. Current diabetes reports, 19(8), 51.
Ma, X., Liu, J., Zhu, W., Tang, M., Lawrence, N., Yu, C., ... & Chen, S. (2018). 3D bioprinting
of functional tissue models for personalized drug screening and in vitro disease
modeling. Advanced drug delivery reviews, 132, 235-251.
Romei, M. G., & Boxer, S. G. (2019). Split green fluorescent proteins: scope, limitations, and
outlook. Annual review of biophysics, 48, 19-44.
Wang, D., Tai, P. W., & Gao, G. (2019). Adeno-associated virus vector as a platform for gene
therapy delivery. Nature Reviews Drug Discovery, 18(5), 358-378.
Zhang, X. G., Zhu, X. Q., Xue, J., Li, Z. Z., Jiang, H. Y., Hu, L., & Yue, Y. H. (2019).
Personalised antiplatelet therapy based on pharmacogenomics in acute ischaemic minor
stroke and transient ischaemic attack: study protocol for a randomised controlled
trial. BMJ open, 9(5), e028595.