Digital Commons Network^™

Ancient Pathogens Provide A Window Into Health And Well-Being, Cecil M. Lewis Jr., Mercy Y. Akinyi, Sharon Dewitte, Anne C. Stone

Faculty Publications

This perspective draws on the record of ancient pathogen genomes and microbiomes illuminating patterns of infectious disease over the course of the Holocene in order to address the following question. How did major changes in living circumstances involving the transition to and intensification of farming alter pathogens and their distributions? Answers to this question via ancient DNA research provide a rapidly expanding picture of pathogen evolution and in concert with archaeological and historical data, give a temporal and behavioral context for heath in the past that is relevant for challenges facing the world today, including the rise of novel pathogens.

The Human Gut Microbiome, Tammy J. Ladue

InterProfessional Education Research and Scholarship

Although the gut microbiome has been known for many years, it wasn’t until the mid-1970’s that a relationship was hypothesized in medical journals. With the advent of the Human Genome Project in 2001 (Adak & Khan, 2019) further investigation into the types and relationship of the microbes in the GI tract were seriously studied.

Utilizing DNA & RNA tracking and culture techniques found during the Genome Project, more information was found on the Gut Microbiome. It was as of 2017 that the knowledge on the Microbiome began to show promise. It has been speculated that the GI tract has approximately …

Covid-19 Vaccination Up-Take In Three Districts Of Nepal, Tara Nath Pokhrel, Kshitij Karki, Bhim Singh Tinkari, Shyam Raj Upreti, Shikha Upadhyaya Khatiwada, Rakchya Amatya, John Zervos, Linda M. Kaljee, Kate Zenlea, Tyler Prentiss, Gina Maki, Anita B. Shallal, Seema Joshi, Marcus J. Zervos, Katie Latack, Bidushi Pokhrel, Alina Upreti, Bibek Kumar Lal, Sagar Dahal, Jhalak Sharma Gautam, Dipendra Raman Singh, Deepak C. Bajracharya

Infectious Diseases Articles

Vaccine hesitancy during the COVID-19 pandemic continues to be an issue in terms of global efforts to decrease transmission rates. Despite high demand for the vaccines in Nepal, the country still contends with challenges related to vaccine accessibility, equitable vaccine distribution, and vaccine hesitancy. Study objectives were to identify: 1) up-take and intention for use of COVID-19 vaccines, 2) factors associated with vaccine up-take, and 3) trusted communication strategies about COVID-19 and the vaccines. A quantitative survey was implemented in August and September 2021 through an initiative at the Nepali Ministry of Health and Population Department of Health Services, Family …

Multisite Detection Of Tn1549-Mediated Vanb Vancomycin Resistance In Multidrug-Resistant Enterococcus Faecalis St6 In Texas And Florida, Shelby R Simar, Truc T Tran, Kirsten B Rydell, Diana Panesso, German A Contreras, Jose M Munita, Renzo O Cifuentes, Lilian M Abbo, Pranoti Sahasrabhojane, An Q Dinh, Dierdre B Axell-House, Tor Savidge, Samuel A Shelburne, Blake M Hanson, Cesar A Arias

Faculty, Staff and Student Publications

In the United States, vanB-mediated resistance in enterococci is rare. We characterized three sequence type (ST) 6, vancomycin-resistant Enterococcus faecalis isolates causing bacteremia in unique patients in spatiotemporally distinct settings. Isolates were recovered between 2018 and 2020 in two cities in the United States (Houston, TX; Miami, FL). The isolates harbored the vanB operon on a chromosomally located Tn1549 transposon, and epidemiological data suggested multiple introductions of the vanB gene cluster into ST6 E. faecalis.

A Novel Defined Tlr3 Agonist As An Effective Vaccine Adjuvant, Kwang Hyun Ko, Seung Bin Cha, Seung-Hwan Lee, Hyun Shik Bae, Chul Soo Ham, Min-Gyu Lee, Dong-Ho Kim, Seung Hyun Han

Faculty, Staff and Student Publications

Synthetic double-stranded RNA analogs recognized by Toll-like receptor 3 (TLR3) are an attractive adjuvant candidate for vaccines, especially against intracellular pathogens or tumors, because of their ability to enhance T cell and antibody responses. Although poly(I:C) is a representative dsRNA with potent adjuvanticity, its clinical application has been limited due to heterogeneous molecular size, inconsistent activity, poor stability, and toxicity. To overcome these limitations, we developed a novel dsRNA-based TLR3 agonist named NexaVant (NVT) by using PCR-coupled bidirectional in vitro transcription. Agarose gel electrophoresis and reverse phase-HPLC analysis demonstrated that NVT is a single 275-kDa homogeneous molecule. NVT appears to …

Going Back In Time: Increasing Penicillin Susceptibility Among Methicillin-Susceptible Staphylococcus Aureus Osteoarticular Infections In Children, J Chase Mcneil, Lauren M Sommer, Jesus G Vallejo, Mary Boyle, Kristina G Hulten, Sheldon L Kaplan, Stephanie A Fritz

Faculty, Staff and Students Publications

In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children’s and St. Louis Children’s Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ …

Covid-19 Newsletter (Vol. 153), Center For Disaster Medicine, New York Medical College

COVID-19 Newsletter

No abstract provided.

E. Coli Catheter-Associated Urinary Tract Infections Are Associated With Distinctive Virulence And Biofilm Gene Determinants, Zongsen Zou, Robert F. Potter, William H. Mccoy, John A. Wildenthal, George L. Katumba, Peter J. Mucha, Gautam Dantas, Jeffrey P. Henderson

2020-Current year OA Pubs

Urinary catheterization facilitates urinary tract colonization by E. coli and increases infection risk. Here, we aimed to identify strain-specific characteristics associated with the transition from colonization to infection in catheterized patients. In a single-site study population, we compared E. coli isolates from patients with catheter-associated asymptomatic bacteriuria (CAASB) to those with catheter-associated urinary tract infection (CAUTI). CAUTI isolates were dominated by a phylotype B2 subclade containing the multidrug-resistant ST131 lineage relative to CAASB isolates, which were phylogenetically more diverse. A distinctive combination of virulence-associated genes was present in the CAUTI-associated B2 subclade. Catheter-associated biofilm formation was widespread among isolates and …

Defining Variability In Evaluation And Management Of Children With Chronic Osteomyelitis, Ganga S. Moorthy, Angelique E. Boutzoukas, Daniel K. Benjamin, Philip M. Polgreen, Susan E. Beekmann, John S. Bradley, Walter Dehority

Pediatrics Research and Scholarship

Pediatric chronic osteomyelitis is a rare, debilitating condition lacking management guidelines. In a national survey of 162 pediatric infectious disease physicians through the Emerging Infections Network, tremendous variability in diagnostic approaches and management were noted, highlighting a need for prospective study to better define the spectrum of pathogens and disease.

Impact Of High-Fidelity Simulation On Confidence Level Of Nursing Students In The Care Of Covid-19 Patients, Faith A. Paine

Dissertations

The COVID-19 pandemic impacted the education of nursing students across the world. Nursing students were unable to care for patients with COVID-19 at the beginning and potentially throughout nursing school depending on the facility and nursing school restrictions. It was not known how the participation in a high-fidelity simulation will impact the confidence level of nursing students in the care of patients with COVID-19. A mixed methods phenomenological qualitative and survey design was utilized to determine the confidence level of nursing students after participation in a high-fidelity simulation of a patient diagnosed with COVID-19.

The Impacts Of Immune Challenges On Fish Behavior And Physiology, Teisha King

LSU Doctoral Dissertations

For species living in dominance hierarchies, social rank dictates access to resources and often contributes to reproductive success. To ensure survival, individuals constantly evaluate trade- offs between crucial biological systems, like the reproductive and immune systems, depending on their social rank and physiological state. Little is known about how social species balance interactions between immune system function, fluctuations in social status and reproductive fitness, and the performance of behaviors necessary for maintaining social status when sick, particularly in fishes, the largest and most diverse group of vertebrates. My dissertation research uses a whole animal approach to examine how physiological profiles …

Experiences Of Covid-19 Recovered Patients: A Qualitative Case Study From A Hotspot In Saudi Arabia, Abdulrahman Alhajjaji Alhajjaji, Ahmad Kurdi, Sultan Faqeh, Safwan Alansari, Akrm Abdulaziz, Moayad Allihyani, Omar Almaghamsi, Ejaz Cheema, Majid Ali

The Qualitative Report

It is difficult to maintain social distancing in highly populated areas where people live in proximity. This study aimed to qualitatively explore experiences of COVID-19 recovered patients residing in one such area. We employed semi-structured face-to-face interviews. An interview guide was developed, validated, piloted, and minor changes were made. People living in this area, above 18 years of age, and recovered from COVID-19 were approached for the interviews, 11 of them were recruited to be interviewed, and their verbal informed consent was audio recorded. The interviews were conducted in the Arabic language in a semi-private area of the community center, …

Liability For Deadly Failure: Rejecting The Push For Prep Act Preemption And Restraining Prep Act Immunity For Senior Living Facilities And Nursing Homes, Mai R. Contino

Pepperdine Law Review

In the wake of COVID-19, there has been a surge of wrongful death cases filed by plaintiff families in state courts. These families allege that their loved one contracted and died from COVID-19 because the nursing home or senior living facility at which their loved one resided failed to take proper COVID-19 prevention measures. In response, defendant facilities have removed these actions to federal court, arguing that the PREP Act preempts plaintiffs’ state law claims and grants facilities immunity from liability for loss related to qualified actions taken during a public health emergency. This Comment rejects facilities’ push for preemption …

Working Within Constraints: Managing African Savannas For Animal Production And Biodiversity, J. T. Du Toit

IGC Proceedings (1977-2023)

The mean density of livestock biomass on African rangelands now greatly exceeds that of indigenous large herbivores, although livestock cannot fully substitute for wildlife with respect to co-evolved ecosystem processes involving herbivory. The dominance of livestock in semi-arid rangelands is largely due to water provision, which uncouples livestock population dynamics from the rainfall-driven trajectories followed by indigenous ungulate species in wildlife areas. Ecological sustainability cannot be achieved with a few exotic species maintained at unprecedented biomass densities in savanna ecosystems, which are evolutionarily adapted for species-rich communities of ungulates of a wise range of sizes. Integrating wildlife and livestock in …

Exploring Permanency Of Pandemic Influenced Changes In Habitual Consumption Behaviour, Ray Titus, Sejal Valera, Debashish Sengupta

Arab Economic and Business Journal

The pandemic has universally disrupted the way people live and socialise. People’s behavioural patterns have also been significantly influenced by the Covid-19 pandemic. A study conducted in Singapore found evidence of at least 17 behavioural changes triggered by Covid-19 pandemic. Another study done in Italy found that there was a high intention to adopt protective behaviours post the Covid-19 lockdown. Similarly, a study done in South Africa indicated enhanced behavioural responses to Covid-19 and consequently the evolution of preventive behaviours. The behavioural changes triggered by Covid-19 pandemic are likely to extend into consumption territory and impact consumer behaviour significantly. A …

Factors In Primary Care Use Among Young Adult Refugees From Burma And Bhutan In Early Resettlement: Findings From Colorado, Sarah Brewer, Jini Puma

Journal of Refugee & Global Health

Background: Young adult refugees have suboptimal primary care use in early resettlement—domains of integration influence primary care engagement during this time.

Methods: Adjusted logistic regression models were used to estimate odds of (1) having a primary care exam and (2) identification of a primary care provider (PCP) as predicted by domains of integration among young adult refugees (n=154) from Burma and Bhutan across four years following resettlement.

Results: Overall integration and predisposing factors, such as language and cultural knowledge, were lower odds of having a primary care provider. Enabling factors such as having insurance and knowing how to make an …

2022 Research Fronts: Development Trends And Key Research Questions In 11 Broad Research Areas, Jiaofeng Pan, Haixia Wang, Fuhai Leng, Feng Zhang, Fan Yang, Jianxia Yuan, Ying Xing, Weiwei Fan, Qiuju Zhou, Wenyue Bian, Chaoxing Zhang, Longguang Huang, Haiming Wang, Lin Han, Ruimin Pei

Bulletin of Chinese Academy of Sciences (Chinese Version)

In 2022, Institutes of Science and Development, Chinese Academy of Sciences (CASISD), the National Science Library, CAS, and Clarivate Analytics released their joint report Research Fronts 2022. The report utilized the Essential Science Indicators (ESI) database to do co-citation analysis. The 2022 report started from 12 610 research fronts in ESI and identified a total of 165 research fronts, including hot and emerging specialties spanning 11 broad research areas in sciences and social sciences. With the 165 research fronts and the related core papers and citing papers as the basis for analysis, this study summarized 8 development trends in science …

Depletion Of Hiv Reservoir By Activation Of Isr Signaling In Resting Cd4+T Cells, Dajiang Li, Lilly M. Wong, Yuyang Tang, Brigitte Allard, Katherine S. James, George R. Thompson, Satya Dandekar, Edward P. Browne, Qingsheng Li, Jeremy M. Simon, Nancie M. Archin, David M. Margolis, Guochun Jiang

School of Biological Sciences: Faculty Publications

HIV reservoirs are extremely stable and pose a tremendous challenge to clear HIV infection. Here, we demonstrate that activation of ISR/ATF4 signaling reverses HIV latency, which also selectively eliminates HIV+ cells in primary CD4⁺T cell model of latency without effect on HIV-negative CD⁴⁺T cells. The reduction of HIV+ cells is associated with apoptosis enhancement, but surprisingly is largely seen in HIV-infected cells in which gag-pol RNA transcripts are detected in HIV RNA-induced ATF4/IFIT signaling. In resting CD4⁺ (rCD4⁺) T cells isolated from people living with HIV on antiretroviral therapy, induction of ISR/ATF4 signaling …

On Limitations Of Uniplex Networks For Modeling Multiplex Contagion, Nicholas W. Landry, Jimi Adams

Faculty Publications

Many network contagion processes are inherently multiplex in nature, yet are often reduced to processes on uniplex networks in analytic practice. We therefore examine how data modeling choices can affect the predictions of contagion processes. We demonstrate that multiplex contagion processes are not simply the union of contagion processes over their constituent uniplex networks. We use multiplex network data from two different contexts- (1) a behavioral network to represent their potential for infectious disease transmission using a "simple"epidemiological model, and (2) users from online social network sites to represent their potential for information spread using a threshold-based "complex"contagion process. Our …

Personalized Matched Targeted Therapy In Advanced Pancreatic Cancer: A Pilot Cohort Analysis, Justin Shaya, Shumei Kato, Jacob J. Adashek, Hitendra Patel, Paul T. Fanta, Gregory P. Botta, Jason K. Sicklick, Razelle Kurzrock

School of Veterinary and Biomedical Sciences: Faculty Publications

Despite progress, 2-year pancreatic cancer survival remains dismal. We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board). Targeted agents administered/ patient = 2.5 (median) (range, 1–4); first-line therapy (N = 5); second line, (N = 13). Comparing patients (high versus low degrees of matching) (matching score ≥50% versus <50%; reflecting number of alterations matched to targeted agents divided by number of pathogenic alterations), survival was significantly longer (hazard ratio [HR] 0.24 (95% confidence interval [CI], 0.078–0.76, P = 0.016); clinical benefit rates (CBR) (stable disease ≥6 months/partial/complete response) trended higher (45.5 vs 0.0%, P = 0.10); progression-free survival, HR, 95% CI, 0.36 (0.12–1.10) (p = 0.075). First versus ≥2nd-line therapy had higher CBRs (80.0 vs 7.7%, P = …

A Simple Seir-V Model To Estimate Covid-19 Prevalence And Predict Sars-Cov-2 Transmission Using Wastewater-Based Surveillance Data, Tin Phan, Samantha Brozak, Bruce Pell, Anna Gitter, Amy Xiao, Kristina D Mena, Yang Kuang, Fuqing Wu

Faculty, Staff and Student Publications

Wastewater-based surveillance (WBS) has been widely used as a public health tool to monitor SARS-CoV-2 transmission. However, epidemiological inference from WBS data remains understudied and limits its application. In this study, we have established a quantitative framework to estimate COVID-19 prevalence and predict SARS-CoV-2 transmission through integrating WBS data into an SEIR-V model. We conceptually divide the individual-level viral shedding course into exposed, infectious, and recovery phases as an analogy to the compartments in a population-level SEIR model. We demonstrated that the effect of temperature on viral losses in the sewer can be straightforwardly incorporated in our framework. Using WBS …

Substrate Electronics Dominate The Rate Of Reductive Dehalogenation Promoted By The Flavin-Dependent Iodotyrosine Deiodinase, Jeffrey M Carlson, Ayzsa Tannis, Kate R Woodworth, Megan R Reynolds, Neha Shinde, Breanne Anderson, Keivon Hobeheidar, Aisha Praag, Kristen Campbell, Cynthia Carpentieri, Teri Willabus, Elizabeth Burkhardt, Elizabeth Torrone, Kevin P O'Callaghan, Kathryn Miele, Dana Meaney-Delman, Suzanne M Gilboa, Emily O'Malley Olsen, Van T Tong

Faculty, Staff and Student Publications

Despite universal prenatal syphilis screening recommendations and availability of effective antibiotic treatment, syphilis prevalence during pregnancy and the incidence of congenital syphilis have continued to increase in the United States (1,2). Concurrent increases in methamphetamine, injection drug, and heroin use have been described in women with syphilis (3). CDC used data on births that occurred during January 1, 2018-December 31, 2021, from two states (Arizona and Georgia) that participate in the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET) to describe the prevalence of substance use among pregnant persons with syphilis by congenital syphilis pregnancy outcome (defined …

Fluorescence Angiography With Dual Fluorescence For The Early Detection And Longitudinal Quantitation Of Vascular Leakage In Retinopathy, Benjamin Pomeroy, Alexander W Venanzi, Wei Li, Abigail S Hackam, Midhat H Abdulreda

Faculty, Staff and Students Publications

BACKGROUND: Diabetic retinopathy (DR) afflicts more than 93 million people worldwide and is a leading cause of vision loss in working adults. While DR therapies are available, early DR development may go undetected without treatment due to the lack of sufficiently sensitive tools. Therefore, early detection is critically important to enable efficient treatment before progression to vision-threatening complications. A major clinical manifestation of early DR is retinal vascular leakage that may progress from diffuse to more localized focal leakage, leading to increased retinal thickness and diabetic macular edema (DME). In preclinical research, a hallmark of DR in mouse models is …

Investigating Stigma During The Early Stages Of A Pandemic Through The Lens Of Covid-19, Zach Thornton, Bethany Hodge, Sheridan Langford

The University of Louisville Journal of Respiratory Infections

Background: Individuals face stigma associated with numerous health conditions. Stigma can arise rapidly during the early spread of a new disease, adding to the burden felt by those affected. COVID-19 can be used as an example to study stigma during the early phases of a pandemic. This narrative review is a descriptive analysis that tracks the ways in which COVID-19 stigma was discussed in the scholarly literature during the first year of the pandemic to understand how stigma was viewed in the context of a rapidly spreading pandemic.

Methods: PubMed was used as a non-exhaustive sample of the literature. Searches …

Integrated Mrna Sequence Optimization Using Deep Learning, Haoran Gong, Jianguo Wen, Ruihan Luo, Yuzhou Feng, Jingjing Guo, Hongguang Fu, Xiaobo Zhou

Faculty, Staff and Student Publications

The coronavirus disease of 2019 pandemic has catalyzed the rapid development of mRNA vaccines, whereas, how to optimize the mRNA sequence of exogenous gene such as severe acute respiratory syndrome coronavirus 2 spike to fit human cells remains a critical challenge. A new algorithm, iDRO (integrated deep-learning-based mRNA optimization), is developed to optimize multiple components of mRNA sequences based on given amino acid sequences of target protein. Considering the biological constraints, we divided iDRO into two steps: open reading frame (ORF) optimization and 5' untranslated region (UTR) and 3'UTR generation. In ORF optimization, BiLSTM-CRF (bidirectional long-short-term memory with conditional random …

Impact Of Adherence To Procalcitonin Antibiotic Prescribing Guideline Recommendations For Low Procalcitonin Levels On Antibiotic Use, Brian E Malley, Jonathan G Yabes, Elizabeth Gimbel, Chung-Chou H Chang, Donald M Yealy, Michael J Fine, Derek C Angus, David T Huang, Proact Investigators

Faculty, Staff and Student Publications

BACKGROUND: The Procalcitonin Antibiotic Consensus Trial (ProACT) found provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians did not reduce antibiotic use. Possible reasons include clinician reluctance to follow the guideline, with an observed 64.8% adherence rate. In this study we sought to determine the threshold adherence rate for reduction in antibiotic use, and to explore opportunities to increase adherence.

METHODS: This study is a retrospective analysis of ProACT data. ProACT randomized 1656 patients presenting to 14 U.S. hospitals with suspected lower respiratory tract infection to usual care or provision of procalcitonin assay results and an antibiotic prescribing guideline …

Usage Statistics: Project Counter R5 Tr_J1 Report Fy2022 - Journal Requests (Excluding Oa_Gold) By Title, Andrée J. Rathemacher

Technical Services Reports and Statistics

Project COUNTER R5 Report TR_J1 for the University of Rhode Island for the period from July 1, 2021 - June 30, 2022. The TR_J1 report is defined as "Journal Requests (Excluding OA_Gold)." This report presents an annual total only and only includes those platforms successfully configured for automated harvesting via SUSHI.

File for download is Excel spreadsheet generated by Alma Analytics.

Results:

Total Item Requests - 771,947

Unique Item Requests - 578,437

Utilizing Neoantigen-Specific Cd4* T Cells And Immune Checkpoint Modulation To Advance Adoptive Cell Therapy With Tumor-Infiltrating Lymphocytes For Metastatic Melanoma Patients, Maclean Scott Hall

USF Tampa Graduate Theses and Dissertations

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a promising immunotherapeutic approach for patients with advanced solid tumors. Metastatic melanoma is a tumor type amenable to immunotherapy in part due to the presence of antigen-specific TIL. These T cells can be activated and expanded for ACT, which has resulted in relatively high rates of clinical responses. While numerous advances have been made, the inclusion of neoantigen-specific CD4+ T cells within TIL infusion products remains underexplored and therefore offers a significant opportunity for progress. Similarly, immune checkpoint inhibitors, specifically PD-1 blocking antibodies, augment antitumor immunity and may improve the outcomes …

To Use Or Not Use: Understanding Chinese Consumers' Intention Toward “Serving Chopsticks”, Qian Chen, Rong Huang, Aiping Zhang, Yingzhi Guo

Plymouth Business School

Serving chopsticks (or “community-use chopsticks”) refers to chopsticks that are used to serve food from a shared dish to an individual's plate, they are used because of concerns about hygiene. This study aims to examine consumers' perceived values toward serving chopsticks and provide an insight into the formation of consumers' intentions to use serving chopsticks. A mixed-method approach was utilized to collect data; interviews were conducted with 62 consumers, followed by a web-based survey with 630 consumers. Qualitative analysis and structural equation modeling analysis were used in the data analysis. Qualitative analysis highlighted four dimensions that contribute to consumers' perceived …

Dynamic Imine Bonding Facilitates Mannan Release From A Nanofibrous Peptide Hydrogel, Brett H Pogostin, Gabriel Saenz, Carson C Cole, Erin M Euliano, Jeffrey D Hartgerink, Kevin J Mchugh

Faculty, Staff and Student Publications

Recently, there has been increased interest in using mannan as an immunomodulatory bioconjugate. Despite notable immunological and functional differences between the reduced (R-Man) and oxidized (O-Man) forms of mannan, little is known about the impact of mannan oxidation state on its in vivo persistence or its potential controlled release from biomaterials that may improve immunotherapeutic or prophylactic efficacy. Here, we investigate the impact of oxidation state on the in vitro and in vivo release of mannan from a biocompatible and immunostimulatory multidomain peptide hydrogel, K2(SL)6K2 (abbreviated as K2), that has been previously used for the controlled release of protein and …