*3.1. Polysaccharides*

Seaweeds have a significant carbohydrate component in their cell membranes, or these polysaccharides are unique to every variety from algae: Brown alginate contains fucoidan; green Ulvan or red agar contains carrageenan. Polysaccharides are becoming increasingly popular as a result of their physicochemical properties [27]. Polysaccharides are biopolymers created from natural resources that have developed as a sustainable and environmentally friendly alternative to typical polymers and plastics. They are also known as an energy store and structural molecules in a variety of species, including plants and marine organisms. Polysaccharides are the major macromolecule in seaweed, accounting for more than 80% of its weight. Polysaccharides are classified into two types based on where they are found in seaweeds: cell-membrane polysaccharides or storage polysaccharides. With the exception of accumulating carbohydrates found in cell plastids, the majority of seaweed polysaccharides are cell-membrane polysaccharides. At present, they can be classed as food-grade or non-food-grade polysaccharides, depending on how they are used [28].


*3.1. Solid-Alkali Catalyst Preparation*

A sample of bauxite was converted into bauxite ash by heat-treating them at 500 ◦C for 4 h in a mu ffle furnace. After washing the bauxite ash using deionized water and filtration, the bauxite ash was dried at 120 ◦C for 16 h. The catalyst was prepared by grinding bauxite ash and Li2CO3 (Shimakyu's Pure Chemicals, Osaka, Japan), thoroughly mixing them in a crucible for calcination for 4 h in a mu ffle furnace, and then cooling them to room temperature.


*Article* **Feasibility Study to Assess the Impact of a Lifestyle Intervention during Colorectal Cancer Screening in France**

**Inge Huybrechts 1,\* , Nathalie Kliemann 1 , Olivia Perol 2 , Anne Cattey-Javouhey 2 , Nicolas Benech 3 , Aurelia Maire 2 , Tracy Lignini 1 , Julien Carretier 2 , Jean-Christophe Saurin 3 , Beatrice Fervers 2 and Marc J. Gunter 1**

**Abstract:** Current evidence suggests that 30–50% of cancers are attributable to established lifestyle risk factors. Cancer-screening has been identified as an opportunity for delivering advice on lifestyle behaviour change for cancer prevention. This study aimed to evaluate the feasibility and acceptance of promoting advice on the latest evidence-based lifestyle recommendations for cancer prevention at the time of colorectal cancer screening at two hospitals in Lyon, France. This feasibility study included 49 patients (20 men and 29 women) who were invited for colonoscopy. Patients received a leaflet with lifestyle recommendations for cancer prevention, accompanied with a logbook to plan and monitor their behavioural changes. Feedback from patients, hospital staff, and researchers was received via evaluation questionnaires (*n* = 26) completed after testing the educational material for at least two weeks and via two focus group discussions (*n* = 7 and *n* = 9 respectively) organized at the end of the study. All interviewed patients were interested in lowering their cancer risk, and the majority felt ready to change their lifestyle (88%), although most did not know how to decrease their risk of cancer (61%). All patients found the educational material easy to understand and sufficiently attractive and 50% of the patients reported having achieved at least one of the healthy behaviours recommended within the two weeks following the intervention. All hospital staff and almost all patients (92%) involved found that the screening program and the visits planned for colonoscopy was an appropriate moment to provide them with the educational material. This feasibility study has shown that the content, paper-based format, and time of delivery of the intervention were adequate. Health professionals seem to be willing to provide lifestyle recommendations, and patients appear interested in receiving advice for lowering their cancer risk during screening visits.

**Keywords:** feasibility; lifestyle intervention; colorectal cancer screening; hospital setting; France

#### **1. Introduction**

Colorectal cancer (CRC) is the fourth most commonly diagnosed malignancy and the third leading cause of cancer death in the world, accounting for around 1.9 million new cases and almost 935,000 deaths in 2020 [1]. Given current demographic projections, the global burden of CRC is anticipated to increase by 60% to over 3 million new cases and 1.6 million cancer deaths annually by 2040 [2]. The incidence of CRC varies widely across geographic regions with the highest incidence in higher income countries [3]. In France, for example, CRC is the second most common cancer and the second leading cause of cancer death, accounting for more than 48,061 new cases and 20,953 deaths in 2020 [1].

**Citation:** Huybrechts, I.; Kliemann, N.; Perol, O.; Cattey-Javouhey, A.; Benech, N.; Maire, A.; Lignini, T.; Carretier, J.; Saurin, J.-C.; Fervers, B.; et al. Feasibility Study to Assess the Impact of a Lifestyle Intervention during Colorectal Cancer Screening in France. *Nutrients* **2021**, *13*, 3685. https://doi.org/10.3390/nu13113685

Academic Editor: Carlos Vasconcelos

Received: 18 September 2021 Accepted: 16 October 2021 Published: 20 October 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

CRC is a complex disease with a number of recognised risk factors. Advancing age, male sex, family history of CRC, inflammatory bowel disease, smoking, excessive alcohol drinking, overweight and obesity, low levels of physical activity and sedentary lifestyle, diabetes and high consumption of red and processed meat are established risk factors [4–7]. Decades of research have specifically focused on dietary factors: some studies have suggested a protective effect of diets rich in fruit, vegetables, fish, fibre and whole grains, calcium and dairy products against colorectal cancer [5]. Overall, it has been estimated that lifestyle factors could account for up to 40% of CRC cases worldwide [8]. Recent estimates indicate that in France, 56% of CRC cases in men and 74% of CRC cases in women are attributable to modifiable risk factors. Thus, up to 19,000 CRC cases per year could be prevented in France by improving unhealthy lifestyle behaviours [9].

The World Cancer Research Fund's (WCRF) Continuous Update Project (CUP) is the world's largest source of scientific research on cancer prevention and survivorship through diet and physical activity. The CUP analyses global research on how diet and other lifestyle factors are associated with the risk of developing CRC [10], to provide a basis for lifestyle recommendations. More recently, in 2018, the WCRF updated its latest lifestyle recommendations for cancer prevention [10], providing the most up-to-date evidence-based lifestyle recommendations for preventing CRC as well as other cancers. Recent longitudinal studies have demonstrated that adherence to the WCRF recommendations for cancer prevention are associated with 5–17% reductions in CRC incidence and 10–13% reductions in CRC mortality [11–15]. Therefore, developing effective and sustainable interventions promoting lifestyle changes for CRC prevention is of high public health interest. Cancer-screening has been identified as an important milestone that could provide an ideal opportunity for delivering advice on behaviour change for cancer prevention [16]. Berstad and colleagues recently highlighted the importance of including lifestyle counselling as a part of CRC screening since individuals with a positive screening result may be inclined to a less healthy lifestyle compared with those who had a negative screening result [17].

Screening attendance represents a time-window whereby patients may be more receptive to advice on lifestyle change, which has been described as a 'teachable moment' [16]. Screening attendance may influence an individual's perception of their personal risk for CRC, which in turn may prompt motivation to change behaviour. Indeed, a recent study showed that adults eligible for cancer screening and who were not adhering to guidelines were willing to receive lifestyle advice during screening, regardless of its results [18]. While there is little evidence to support the idea that screening prompts spontaneous behaviour change [19], interventions delivered at CRC and mammography screening in the U.K have shown promising results, such as weight loss and increased physical activity [20,21]. However, these interventions were very intensive and there is still a need to test the effect of brief interventions that promote long-term behaviour change as part of screening programs to allow widespread implementation. A recent brief habit-based weight loss intervention promoting a set of everyday healthy eating and physical activity behaviours associated with cancer prevention in patients with obesity from primary care in the UK has shown promising results, such as the maintenance of a significant weight loss over 24 months [22]. Since habit formation advice is simple, easily scalable, and a recommended approach to be used with patients [23], it may be a feasible approach to deliver evidence-based lifestyle recommendations in the cancer screening context.

The CRC screening program in France may be an ideal setting for delivering advice on lifestyle behaviours. This is a population-based nationwide cancer screening program which has been rolling out since 2009. In 2015, the immunochemical test (FIT) replaced the conventional guaiac faecal occult blood test (gFOBT), improving the participation rate [24,25]. The programme targets those aged 50 to 74 years old, who often have other lifestyle related comorbidities, such as obesity, type 2 diabetes mellitus, and cardiovascular disease. Therefore, promoting healthy lifestyle advice to the screened population has the potential to reduce the risk of cancer as well as other related comorbidities and improve prognosis and quality of life. When developing and testing a lifestyle intervention for CRC prevention, it would be the most efficient to first target higher risk population groups before expanding the intervention to the entire screening population. High risk patients include those with positive FIT, a family history of CRC, or patients who score positive (≥5) for a validated score consisting of simple clinical factors that successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients [26].

Despite this, there is still little evidence on the impact of promoting the evidencebased lifestyle recommendations during CRC screening among individuals at higher risk. There is also a need to extend our efforts to gain understanding of the potential pathways that can explain how lifestyle factors may prevent CRC development [27]. Therefore, the LIFE-SCREEN intervention trial aims to investigate the hypothesis that advice on lifestyle recommendations for cancer prevention at CRC screening among individuals classified as higher risk will promote greater adherence to cancer prevention recommendations, as well as improve the quality of life, biomarkers of cancer risk, physical fitness, and body weight. The current feasibility study presented in this manuscript aimed to evaluate the feasibility and acceptance of the LIFE-SCREEN intervention. Specific objectives were to obtain information on (i) participants' and health professionals' feedback on the educational material; (ii) health professionals' willingness to recruit participants, and (iii) participants' awareness of the risk factors for CRC and willingness to change their lifestyles. In addition, we aimed to conduct focus group meetings with patients, health professionals, and experts in the field in order to explore their feedback on the intervention content, format and delivery in great detail.

#### **2. Materials and Methods**

#### *2.1. Study Design and Setting*

This study was a single arm, two-center feasibility study of the LIFE-SCREEN intervention that aims to provide advice on evidence-based lifestyle recommendations for cancer prevention at CRC screening among individuals at higher risk of CRC. The feasibility study was carried out in 2019 at two hospitals in Lyon, France, L'hôpital Edouard Herriot (HEH) and Centre Léon Bérard (CLB). The LIFE-SCREEN intervention is registered with clinicaltrials.gov (Ref ClinicalTrials.gov Record PP201907-26) where more details on the feasibility study design and methods can be found. The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of International Agency for Re-search on Cancer (IEC Project No. 19-26; reviewed and approved on 3 February 2020).

#### *2.2. Participants*

Considering the feasibility study objectives we aimed to recruit at least 30 participants [28]. Eligible patients were adults >18 years without previous cancer diagnosis, who were capable to provide informed consent, and that were attending for colonoscopy as part of CRC screening.

#### *2.3. Lifestyle Intervention*

The LIFE-SCREEN intervention aimed to deliver lifestyle advice based upon the most recent recommendations for cancer prevention published by the World Cancer Research Fund (WCRF) [8]. These recommendations entail the following target behaviours: (1) be a healthy weight; (2) move more; (3) enjoy more grains, vegetables, fruits, fish, and dairy products; (4) avoid high-calorie foods rich in fat, salt, and sugar; (5) limit consumption of red and processed meat; (6) limit alcoholic drinks; (7) limit consumption of sugarsweetened drinks; (8) do not rely on supplements. The behavioural approaches were informed by relevant behaviour change theories and models, such as the Teachable Moments Heuristic model and the Habit formation theory. The concept of Teachable Moments (TMs), that is, naturally occurring life or health events that may prompt risk-reducing health behaviours [16], has been considered a strong foundation for widely-accepted health behaviour models. In addition, the intervention was based on the habit formation theory, in

order to promote lasting healthy lifestyle behaviours. Habit-based interventions promote the repetition of target behaviours in a consistent context in order to make them become more automatic and habitual [29–31]. They also promote self-regulatory skills (e.g., goalsetting, planning, self-monitoring, and feedback on performance) in order to translate the intended behaviour into action and override unwanted automated responses [29,32].

The intervention was delivered as a self-coaching leaflet and booklet materials containing the advice on lifestyle recommendations together with strategies on how to achieve and maintain these behaviours. The material also contained instructions on how to set up specific goals (e.g., including what, how, where, and when) to achieve the target behaviours and repeat them at the same time and in the same place in order to improve the patient's likelihood of forming habits and maintaining their behaviour changes. It also provided the participants with instructions on how to track their progress (e.g., using printed booklets to monitor their behaviour), and to amend their plans when these seem inefficient in reaching their target goals.

Health professionals introduced the intervention to eligible patients during precolonoscopy (HEH) or post-colonoscopy visit (CLB), depending on the hospital and provided the informed consent letter. During the consultation, health professionals briefly endorsed the importance of the intervention for helping them to achieve and maintain healthy lifestyles and in turn to reduce their colorectal cancer risk. Interested patients, who signed the informed consent for this feasibility study, were provided with the educational material and were instructed to follow the intervention for at least 2 weeks before completing the feasibility evaluation questionnaire.

#### *2.4. Measurements*

At baseline, participants were required to answer questions on socio-demographics, reason for the colonoscopy and the type of appointment (pre- or post-colonoscopy), their interest and knowledge on how to reduce colorectal cancer risk, readiness to change their behaviours and interest in following the intervention. At the end of the two-week intervention, participants were invited to complete a feasibility evaluation questionnaire containing closed and open questions to obtain their feedback on the educational material, format, and delivery as well as questions on compliance to the intervention over 15 days. Participants were asked to post their completed evaluation questionnaire back using the pre-paid return envelope or to bring it with them during the focus group meetings. It should be noted that no objective measures were used to control the patient's behaviours in this feasibility study; all measures were self-reported by the patients. Health professionals were also requested to complete an evaluation questionnaire on the intervention delivery and content.

In addition, two focus group discussions were conducted at the end of the feasibility study to discuss in depth the feedback on the intervention content, format, and delivery. One focus group gathered the researchers and (para-)medical staff involved in the feasibility study and the second one invited all the patients who took part in the study. These focus group meetings were logistically organized at one of the hospitals involved in the intervention and moderated by the researcher coordinating the LIFE-SCREEN intervention. Each session began with a PowerPoint presentation that provided an overview of the LIFE-SCREEN study, design, and methods. Next the moderator asked the participants for feedback on the intervention content, format, and delivery. Both focus groups were audio recorded and lasted over one hour each. Participants were offered a free lunch meal to thank them for taking part.

#### *2.5. Data Analysis*

Descriptive analysis of the study population was performed. No association analysis was undertaken given the small sample, which was not powered to detect significant differences. Two researchers involved in the study independently assessed the audios and minutes from the focus groups and identified the main suggestions and feedback received. They met to discuss aspects such as recruitment and delivery acceptability, barriers for lifestyle intervention, content of the educational material and any other issue that should be considered when conducting the full RCT. A consensus list of improvements was then defined and used to optimize the study protocol further.

#### **3. Results**

This feasibility study included 49 patients (20 men and 29 women), aged from 23 to 75 years (Table 1). Most of the patients received the invitation and the educational material at their post-colonoscopy visit (84%). All patients who participated in the feasibility study were interested in lowering their CRC risk, although most of them did not know how to decrease their risk (61%). Eighty-eight percent of the respondents felt ready to change their lifestyles with the aim to lower their CRC risk.

**Table 1.** Baseline information (*n* = 49).

\* Mean and median age were equal (57 years).

At two-week's follow-up, a total of 26 patients (53%) completed the evaluation questionnaire. Regarding compliance to the intervention, presented in Table 2, half of the patients (50%) reported having achieved at least one target behaviour using the monitoring sheets. Most of them made plans to achieve at least one behaviour (58%) and made amendments to the plans when necessary (58%). Importantly, the majority of patients intended to continue following the intervention after the end of the study (74%).

**Table 2.** Follow-up information on compliance to the intervention over 15 days (*n* = 26).

Table 3 shows patients feedback on the intervention delivery and content collected through evaluation questionnaires. All patients said they easily understood the information included in the educational material and most of them found the material sufficiently attractive, complete and in line with their expectations (88%). Although most patients (92%) found the material covered the kind of information they would expect, some reported having suggestions to improve it (27%). Suggestions were made such as providing more plant-based and vegetarian recipes and practical tips on how to achieve their goals (e.g., examples of activities adapted to an ageing population to maintain their fitness, etc.). Interestingly, 54% of the patients preferred to stick to the non-digital (e.g., paper-pencil) tools to monitor their behaviours rather than using digital tools. Most of them found that the CRC screening program and the visits planned for colonoscopy were right/appropriate moments to provide them with the educational material (92%). Similar feedback was obtained in the patients' focus group, composed of three patients (two women and one man) involved in the feasibility study.

**Table 3.** Follow up information on intervention delivery and content collected via evaluation questionnaires (*n* = 26).

**Table 3.** *Cont.*

Feedback from experts and health professionals involved in the study was obtained via focus group discussions and evaluation questionnaires. The focus group was conducted with four health professionals and three experts in the field. They suggested to screen participants for their current adherence to the recommendations for cancer prevention at baseline and exclude those with a high score (complying with the recommendations), as they would not have much room to improve their behaviours. However, they emphasized that the study protocol must ensure that the extra work for the surgeons and other health professionals is kept to the minimum (~5 min/patient) to ensure intervention feasibility. They also underlined the importance of testing participants on knowledge about healthy lifestyles and 'knowledge change', as the knowledge of many patients seemed rather low. Regarding the time of the delivery, it was concluded that both pre- and post-colonoscopy are possible. Although it was concluded that both pre- and post-colonoscopy are possible, it was agreed that the most optimal time to deliver the educational material was during the pre-colonoscopy visit, followed by a follow-up intervention (referring to the educational material received at baseline) taking place during the post-colonoscopy visit. Experts and health professionals found that the material could be improved by providing patients with fridge magnets containing messages about the recommendations; recipe books with low-cost vegetarian recipe ideas; and more tips on how to get more active (especially for older patients). They also suggested that the recommendation for quitting smoking should be more prominent.

#### **4. Discussion**

The importance of promoting lifestyle changes to prevent cancer has been highlighted in the scientific literature as well as in the lay press [33,34]. Although the time at which an individual undergoes cancer screening could be considered as a teachable moment [20,21], so far evidence regarding the effectiveness of evidence-based lifestyle advice administered during cancer screening is still scarce. Nevertheless, the necessity and importance of

including lifestyle counselling as a part of CRC screening has been demonstrated in particular among individuals with a positive screening result, as they may be inclined to a less favourable lifestyle compared with those who tested negative at screening [17]. Therefore, this feasibility study was set up to evaluate the feasibility of an intervention study aimed at delivering evidence-based lifestyle advice during CRC screening among individuals at higher CRC risk, as this may have high public health potential.

In summary, this feasibility study showed that the content, paper-based format, and time of delivery of the intervention (both pre- and post-colonoscopy) were adequate and well accepted by the health professionals and patients.

Previous studies already investigated the impact of lifestyle interventions during cancer screening, though with mixed results [35–40]. Although the colorectal cancer screening has already been evaluated as a potential teachable moment for lifestyle interventions [35], the interventions evaluated so far were rather intensive and personalised lifestyle interventions that require important time investments of (para)-medical staff. Here, our results suggest that a simple, well-documented intervention before or after colonoscopy may be sufficient to impact patient lifestyle. Indeed, following our intervention, half of the patients reported having achieved at least one of the healthy behaviours recommended within the two weeks after the first visit. These results should be confirmed in a larger randomised controlled trial.

Patients and health professionals provided valuable suggestions and feedback for further improvement of the study protocol and educational material, leading us to include a "recipe and practical tips book". The paper-based format of the intervention will be maintained, but patients will also have the option to get access to the electronic (e.g., pdf) version of all documents. Patients will also be allowed to choose whether they wish to receive reminders of the recommendations sent by text-messages and/or emails during the 12-month follow-up. The delivery of the intervention will take place during the pre-colonoscopy visit and a follow-up intervention (referring to the educational material received at baseline) will take place during the post-colonoscopy visit. However, the inclusion in the study will be conditional to the colonoscopy results, as patients who receive CRC diagnosis during the post-colonoscopy visit are not considered eligible for the intervention study that aims at patients at higher risk.

The proposed intervention is expected to promote greater adherence to cancer prevention recommendations and have an effect on quality of life, biomarkers of cancer risk, physical fitness, and body weight among higher CRC risk population groups. The integration of these well-established continuous frameworks, namely the CRC screening program and the WCRF-CUP cancer prevention program that continuously updates the evidence on lifestyle risk factors and cancer risk, ensures the sustainability of this intervention program and the potential for further expansion to other cancer screening programs in France and beyond. If successful, this intervention trial could inspire similar initiatives for other cancer types that have well established cancer screening programs and can be expanded to the full screening population.

The fact that the intervention will be implemented in hospitals, alongside the CRC screening routine procedures, makes the access to blood, faecal, and tissue samples from participants easier and will allow us to explore the effect of the intervention on nutritional, inflammation, metabolic health and microbial biomarkers that could provide important information on the mechanisms of CRC development and prevention targets.

#### **5. Future Perspectives**

As stated previously, no standardised protocols or recommendations are available for individuals at higher risk of CRC. If this evidence-based lifestyle intervention confirms the hypothesis that adherence to the latest evidence-based lifestyle guidelines improves following such an intervention, which in turn reduces CRC risk and improves the quality of life, then the intervention can be implemented nationwide and beyond. The recommendations will be developed as a visual representation that is interpretable by non-literate

patients to consider and guarantee social equality among the target population. In addition, the lifestyle advice given in this intervention is aimed to limit the burden for the hospital staff involved to a minimum so that it can easily replace routine care when upscaling to a nation-wide intervention.

In the future, this intervention protocol could also be tested in primary care by providing the healthy lifestyle advice to all participants involved in CRC screening, regardless of their FIT test result.

In addition to cancer, rates of other non-communicable diseases (NCDs) continue to rise, affecting the poorest and most vulnerable populations. The intervention targets a higher CRC risk population aged 35 or over, who often have other lifestyle related comorbidities, such as obesity, type 2 diabetes mellitus, and cardiovascular disease. These diseases share common risk factors, as for example, altered lipid levels, inflammation and abnormal glucose metabolism [41,42]. Hence, promoting healthy lifestyle advice to this population has the potential to also reduce the risk of other related NCDs.

Lastly, this intervention will also shed light on changes in biomarkers relevant for cancer prevention, allowing a better understanding of the putative mechanisms involved.

#### **6. Conclusions**

This feasibility study has shown that the content, paper-based format, and timing of delivery of the intervention (pre- and/or post-colonoscopy) were adequate and wellaccepted by both the health professionals and patients. Health professionals seem to be willing to provide lifestyle recommendations and patients seem interested in receiving advice for lowering their cancer risk during screening visits. Considering the interesting finding that more than half of the patients made plans and adjustments to achieve one of the healthy behaviours recommended in the educational material and that half of the patients reported having achieved at least one of the healthy behaviours recommended within two weeks of receiving the intervention, this LIFE-SCREEN intervention is expected to promote greater adherence to cancer prevention recommendations. Therefore, this LIFE-SCREEN intervention will now be evaluated within the context of a funded randomisedcontrolled trial.

**Author Contributions:** Conceptualization, I.H.; M.J.G. and N.K.; methodology, I.H.; N.K.; O.P.; N.B.; A.C.-J.; A.M.; J.C.; J.-C.S.; B.F. and M.J.G.; formal analysis, I.H. and N.K.; Data collection, O.P.; N.B.; A.C.-J. and A.M.; writing—original draft preparation, I.H.; writing—review and editing, I.H.; N.K.; O.P.; N.B.; A.C.-J.; A.M.; J.C.; J.-C.S.; B.F. and M.J.G.; project administration, I.H. and T.L. funding acquisition, I.H.; N.K.; O.P.; N.B.; A.C.-J.; A.M.; J.-C.S.; B.F. and M.J.G. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by Institut National du Cancer, grant number INCA RISP20-028.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of International Agency for Research on Cancer (IEC Project No. 19-26; reviewed and approved on reviewed on 3 February 2020).

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** Access to anonymized data and the intervention/educational material can be requested via email through the corresponding author.

**Acknowledgments:** The authors would like to thank the, L'hôpital Edouard Herriot (HEH), Centre Léon Bérard (CLB) and l'Institut du Cancer for their support in conducting this study. The authors would also like to thank Corrine Casagrande, Genevieve Nicolas, and Karine Racinoux for their support in translations, data entry and analysis.

**Conflicts of Interest:** The authors declare no conflict of interest.

**IARC Disclaimer:** Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization.

#### **References**


**1. Introduction**

Over recent decades there has been a growing scientific interest towards the use of naturally occurring materials for drug delivery purposes. This is mainly due to their numerous advantages over synthetic materials, namely biocompatibility, biodegradability, and low immunogenicity [1]. Moreover, natural materials produce non-toxic metabolites, unlike synthetic polymers which can be contaminated with unreacted toxic monomers and crosslinkers [2]. Due to their specific structure and corresponding features, naturally occurring materials such as polysaccharides and peptides are widely used for the formulation of micro- and nanoparticulate drug delivery systems. These carriers can provide controlled and targeted release, thus improving the therapeutic performance of the encapsulated drug and minimizing the risk of side effects [3]. Amongst the potential biopolymers, proteins are preferred as natural drug delivery systems due to the relatively easy preparation processes and production of well-defined structures, which enables surface modification and may provide modified and targeted release [1]. Among proteins, casein (CAS) is considered a suitable biopolymer for the preparation of nanoparticulate drug delivery systems due to its structural and physicochemical characteristics [2].

Casein is a collective term used to define a family of calcium (phosphate)-binding phosphoproteins commonly found in mammalian milk [4]. Casein from bovine milk

**Citation:** Zahariev, N.; Marudova, M.; Milenkova, S.; Uzunova, Y.; Pilicheva, B. Casein Micelles as Nanocarriers for Benzydamine Delivery. *Polymers* **2021**, *13*, 4357. https://doi.org/10.3390/ polym13244357

Academic Editors: Ariana Hudita and Bianca Galˇ a¸ˇteanu

Received: 24 November 2021 Accepted: 10 December 2021 Published: 13 December 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

is composed of four peptides, namely αs1, αs2, β, and k, which differ in the content of amino acids, phosphorus, and carbohydrates, but they are all amphiphilic in nature [5]. Cysteine amino acid residues that allow the formation of disulfide bonds are found only in the polypeptide chains of k-casein. In general, the peptide surface is negatively charged due to phosphorylation [1]. The lack of secondary structures because of the proline-rich amino acid sequence [6] and the tendency for binding amorphous calcium phosphate cause electrostatic, hydrogen, and hydrophobic interactions, leading to self-assembly of the casein peptides into stable agglomerates known as casein micelles [7]. The inner part of the micelle is composed of αs1, αs2, and β caseins, whereas the outer layer that stabilizes the micelle contains glycosylated k-casein [8]. Casein micelles exhibit pH-dependent behavior. Their structure tightens when the negative surface charge of casein molecules decreases, and expands with increasing surface charge, which leads to electrostatic repulsion between the molecules [9–11]. Given the amphiphilic properties and pH-dependent behavior of casein, and its ability to participate in hydrophobic and hydrophilic interactions, it is clear why this biopolymer has found a place in scientific research as a potential nanoparticle drug delivery carrier.

Various methods have been reported for the preparation of casein nanoparticles for drug delivery, including pH-shifting [12], high pressure homogenization [13–18], electrostatic complexation [19], solvent displacement [20], emulsification solvent evaporation [21], and spray drying [22–24]. Nano spray drying, a variation of the established spray drying technology used to convert liquids into solid powders, is a relatively new technique adopted for the preparation of nanosized drug delivery systems. The method is based on the use of a revolutionary sprayer developed by the Swiss Büchi Labortechnik AG, which is equipped with a piezoelectric vibrating spray mesh head, allowing the formation of fine droplets, which are dried and electrostatically collected [25]. As a result, spherical submicron structures of particle size below 1000 nm with improved biopharmaceutical behavior are obtained [26–33]. Although spray drying of proteins has been reported in numerous scientific papers [34–37], no data on nano spray drying of casein have been found in the literature. The technology was therefore a research challenge. For the present study, benzydamine hydrochloride (BZ) was used as a model drug.

Benzydamine hydrochloride is a nonsteroidal anti-inflammatory drug with local anesthetic and analgesic properties for pain relief and treatment of inflammatory conditions of the mouth and throat such as oral mucositis, postoperative sore throat and mucosal ulcers. The mechanism of the anti-inflammatory effect of benzydamine has not yet been fully understood. According to Quane et al. [38], the anti-inflammatory activity of benzydamine may be due to its membrane-stabilizing or inhibitory effect of the synthesis of TNF-α. Unlike NSAIDs, which have acidic properties, benzydamine is a weak base, highly lipidsoluble in its unionized form [39].

According to Beckett et al. [40] and Bickel et al. [41], only a limited amount of weak, basic, lipid-soluble drugs is absorbed into buccal tissue via mouthwash application. The small degree of absorption into buccal tissue is confirmed by the poor systemic availability (5%) [42]. To enhance absorption and thus bioavailability, benzydamine hydrochloride was incorporated into nanoparticles. Due to the specific binding properties and pHdependent drug release, casein is considered a promising biopolymer for the preparation of benzydamine loaded casein nanoparticles.

The aim of the present work was to optimize the process parameters of the nano spray drying technique for the formulation of BZ-loaded casein nanoparticles. Furthermore, an investigation of the effect of process variables on structural and morphological characteristics and release behavior was conducted.

#### **2. Materials and Methods**

Benzydamine hydrochloride (Mw 345.87 g/mol), sodium caseinate (from bovine milk) and CaCl2·2H2O (Mw 147.01 g/mol) were purchased from Sigma-Aldrich (St. Louis, MO, USA). All other reagents were of analytical grade.

#### *2.1. Preparation of Blank Casein Nanoparticles and BZ-Loaded Casein Nanoparticles*

The blank casein nanoparticles where prepared via coacervation followed by spray drying using nano spray dryer Büchi B-90 (Büchi Labortechnik AG, Flawil, Switzerland), as previously reported by Gandhi et al. [2]. A certain amount of sodium caseinate was dissolved in 100 mL deionized water, previously adjusted to pH 2 with 1M hydrochloric acid. Then, the crosslinking agent CaCl2·2H2O (2 μL/mL) was added dropwise to the casein solution under high-speed homogenization at 25,000 rpm (Miccra MiniBatch D-9, MICCRA GmbH, Heitersheim, Germany) for 15 min and casein micelles were produced. The obtained nanosuspension was then stirred on a magnetic stirrer at 500 rpm for 30 min) to allow effective crosslinking of casein molecules. Finally, the suspension was spray dried using nano spray dryer Büchi B-90 under the following predetermined conditions: mesh size of 4.0 μm, inlet temperature 40 ◦C, solution feed rate 50%, spray intensity 70%, drying gas speed 120 L/min, pressure 30 nbar. To study the effect of different formulation variables on the produced particles, 32 full factorial design was applied. Nine batches of formulations were prepared at varied protein and crosslinker concentrations (Table 1).

**Table 1.** Composition and characteristics of blank casein nanoparticles (n = 3, PDI (polydispersity index), Dv10, Dv50 and Dv90 (10, 50 and 90% of the total volume of particles, respectively, are with size below the indicated value).

BZ-loaded casein nanoparticles were prepared following the methodology described in the previous paragraph. Briefly, protein aqueous solution (1.5% *w*/*v*) was prepared by dissolving a certain amount of sodium caseinate in deionized water, previously acidified to pH 2 using 1N hydrochloric acid. Then, BZ was added to the solution, followed by protein crosslinking with CaCl2·2H2O (2 μL/mL) at a stirring rate of 25,000 rpm. The procedure continued as previously described. Four batches of drug-leaded formulations were developed at varied drug–polymer ratios. The composition of the batches is presented in Table 2.

**Table 2.** Composition of BZ-loaded casein nanoparticles of various batches.


**Abstract**

Implementations of high-field nuclear magnetic resonance (NMR) facilities into metabolomics studies are unfortunately restricted by their large dimensions, high costings, and specialist technical staff requirements. Therefore, here the application and practical advantages offered by low-field (60 MHz), compact NMR spectrometers for probing the metabolic profiles of human saliva was explored, as was their value in salivary metabolomics studies. Saliva samples were collected from cigarette smoking (n = 11) and non-smoking (n = 31) human participants. 1 H NMR spectra were acquired on both low-field (60 MHz) and medium-field (400 MHz) spectrometers. Metabolomics analyses were employed to evaluate the consistencies of salivary metabolite levels determined, and their abilities to distinguish between smokers and non-smokers. Low-field 1 H NMR analysis detected up to 15, albeit permitted the reliable quantification of 5, potentially key diagnostic biomolecules simultaneously (LLOQ values 250–400 μmol/L), although these were limited to those with the most prominent resonances. Such low-field profiles were also found to be suitable for salivary metabolomics investigations, which confirmed the successful discrimination between smoking and non-smoking participant sample donors. Differences observed between these groups were largely ascribable to upregulated salivary levels of methanol, and its metabolite formate, in the smoking group, but higher smoking-mediated concentrations of acetate, propionate and glycine may arise from a diminished salivary flow-rate in these participants. In conclusion, determination of salivary biomolecules using low-field, benchtop 1 H NMR analysis techniques were found to be valuable for bioanalytical and metabolomics investigations. Future perspectives for the applications of this non-stationary NMR technique, for example for the on-site 'point-of-care' testing of saliva samples for diagnostic oral disease screening purposes at dental surgeries and community pharmacies, are considered.

**Keywords:** compact low-field NMR analysis, NMR spectroscopy, NMR-linked metabolomics, bioanalytical chemistry, saliva, salivary biomarkers, oral diseases, tobacco smoking, salivary biomarkers for smoking, methanol

### **1. Introduction**

'State-of-the-art' developments of novel devices and facilities for the metabolic screening of biofluids through 'omics'strategies provide an encouraging and thoroughly emerging outlook for future healthcare management prospects, including those focused on the diagnosis of diseases and/or their prognostic stratification [1]. Indeed, high-field (HF) nuclear magnetic resonance (NMR) facilities are routinely used for metabolomics investigations in order to rapidly recognize unusual metabolic patterns in patients suffering from a wide range of diseases. However, deployments in healthcare settings have been prohibitively impacted by the large sizes and costs of the instrumentation required for these purposes [2].

Imbalances in the human metabolome have long been associated with healthmediated disturbances, with ancient societies employing very crude methods to assess biofluids [3], including the smell and taste of urine samples to detect urinary ketone bodies and glucose, respectively, in cases of diabetes, for example. However, more recently there have been many notable developments in this research area, and these have given rise to the development of multicomponent metabolic profile analysis by many researchers since the early 1970s [4–7]. Whilst tandem liquid-chromatographicand gas-chromatographic-mass spectrometric methods (LC-MS and GC-MS, respectively) can be employed for the reliable and sensitive determination of low concentrations of metabolites in biofluids, these approaches suffer from issues associated with matrix effects, and both are destructive techniques, which usually require a substantial knowledge of sample composition, and the likely identities of key biomarker analytes, prior to analysis [8]. Conversely, high-resolution NMR-based metabolomics analysis offers a highly selective means of simultaneously identifying a wide range of biomolecules present in complex biofluids at a minimal detectable concentration of ≤5 μM, providing an untargeted methodology ideal for the analysis of a very large number of biomolecules simultaneously [9] (up to 120 or so and *ca.* 80 in human urine and saliva, respectively at operating frequencies of ≥600 MHz). Therefore, the multicomponent 1 H NMR analysis of biofluids such as blood plasma, urine and saliva, and tissue biopsies, offers a high level of potential regarding the investigation of metabolic processes, and when coupled with conventional and/or newlydeveloped multivariate (MV) data analysis techniques, serves as an extremely powerful means of probing the biochemical basis of human disease aetiology [1–5]. Indeed, this form of combined multianalyte-MV analysis is generally classified as metabolomics, and has been extensively applied in a very wide range of biomedical and clinical investigations, including the identification of diagnostic or prognostic biomarkers for a very wide range of diseases.

Although previous applications of low-field (LF) rather than HF NMR spectroscopy to the multicomponent analysis of intact or near-intact biofluids, or other biological media, have been severely limited, our laboratory has paved the way forward for the performance of such studies. Indeed, one of our recent investigations explored the ability of a LF (60 MHz) NMR spectrometer to provide valuable urinary

#### *Metabolomics Distinction of Cigarette Smokers from Non-Smokers Using Non-Stationary… DOI: http://dx.doi.org/10.5772/intechopen.101414*

metabolite data for the monitoring of type 2 diabetes (T2D) in humans [10]. Indeed, this application displayed a high level of chemopathological classification success, although this is perhaps not completely unexpected, since uncontrolled or poorly controlled T2D samples all contain quite high levels of glucose (both 1 H NMRdistinguishable α- and β-anomers), along with the ketone bodies acetoacetate, acetone and 3-D-hydroxybutyrate, whereas little or none of these biomolecules are normally detectable in healthy control samples. However, one of the major advantages of the 1 H NMR technique is that it can simultaneously detect and monitor abnormal levels of a range of further metabolites involved in human disease pathology and associated comorbidities, for example excessive urinary creatinine concentrations arising from kidney dysfunction and damage in T2D, together with hypoglycaemic drugs such as metformin [11].

Saliva serves as a multifunctional biofluid which plays important roles in facilitating the chewing, swallowing and tasting of foods, and also the regulation of oral flora; hence, it is of much importance for the maintenance of overall health in humans. Indeed, human saliva comprises an agglomerate hypertonic 'solution' which contains oral mucosal exudates, salivary acini and gingival crevicular fluid (GCF) [12]. Since this biofluid is readily accessible, it offers much potential as a medium for the identification and monitoring of established or potential biomarkers for human diseases, particularly oral health conditions, but not exclusively so. Indeed, it's collection can be self-performed by participants with minimal training and without clinical supervision. Therefore, here we have employed optimized LF NMR-based metabolic profiling strategies for the global analysis of human saliva in order to assess the viabilities of these compact instruments for biomedical applications in metabolic profiling, metabolomics, oral health assessments, and potentially future screenings of the efficacies of oral healthcare products. Coupling of this LF salivary analysis technique to MV analysis strategies may indeed serve to facilitate the development of favourable outcome strategies for such investigations, and therefore here we also demonstrate, for the first time, the applications of LF NMR-based metabolomics protocols to the distinction of saliva samples collected from non-smoking and tobacco cigarettesmoking subjects. The future clinical monitoring applications of this novel technique are discussed.


Preface

Blood transfusion and hematology are associated with significant advances in science and technology. This book provides a comprehensive overview of some clinically significant blood group systems, hemolytic blood transfusion reactions, and hemoglobinopathies. The aim of this book is to empower biomedical, clinical, and allied medical professionals with the tools required for evidenced-based best practice in the field of blood transfusion and management of hemoglobinopathies.

> **Osaro Erhabor,** Professor, Usmanu Danfodiyo University Sokoto, Nigeria

> > **Anjana Munshi** Central University of Punjab, India

Section 1

Disorders

**1**

Section 1 Disorders

**Chapter 1**

**Abstract**

**1. Introduction**

childhood mortality in Africa.

antimalarial drugs [3].

**3**

deaths occurred in sub-Saharan Africa [2].

death due to malaria in some populations [4–6].

Inherited Disorders of

*falciparum* Malaria

Hemoglobin and *Plasmodium*

*Edith Christiane Bougouma and Sodiomon Bienvenu Sirima*

An estimated 300,000 babies are born each year with severe Inherited Disorders of Hemoglobin (IDH). Despite major advances in the understanding of the molecular pathology, control, and management of the IDH thousands of infants and children with these diseases are dying due to the accessibility to appropriate medical care. In addition, as malaria has been the principal cause of early mortality in several parts of the world for much of the last 5000 years, as a result, it is the strongest force for selective pressure on the human genome. That is why, in the world, there is an overlap of malaria endemicity and IDH. Over the past twenty years several studies have shown that IDH such us hemoglobin and/or red cell membrane abnormalities confer resistance to malaria reducing hence the mortality during the first years of life. This has led to the selection of populations with IDH in malariaendemic areas. This may explain the overlap between these two pathologies. This chapter aims to present the relationship between IDH and malaria susceptibility, make an overview of the current state of knowledge and the burden of IDH, and

highlight steps that require to be taken urgently to improve the situation.

Despite health better care and new strategies of disease control of, mortality remains high in many countries and worldwide [1]. Malaria is the biggest cause of

In 2018, malaria was the cause of about 405 000 deaths, More than 90% of these

Malaria parasites enter red blood cells during key stages of their life cycle so that there is no surprise that a change of red blood structures or make-up could affect malaria infection. Some changes of red blood cells make more resistant to malaria infection whereas others create the potential for a harmful reaction to certain

*Falciparum* malaria has had a profound effect on human evolution, evidenced by the high frequencies of malaria protective mutations observed in populations from historically malarious regions. This big pressure has resulted in the selection of many genetic variants that confer protection against severe malaria and reducing

**Keywords:** Hemoglobin, Inherited Disorders, malaria, host genetics


**3.3 3D computers graphics and architecture symbiotic relationship**

The design process is initially done with a pencil, a ruler, a scale rule, and paper. Then, the process takes a longer time, and relatively inaccurate and significantly limited. Yet they are marvelous works of the likes of Frank Floyd Wright, and alike. Conversely, limitations were significantly broken with new construction materials, and computer aided design (CAD) gave birth to a greater freedom evidenced in architectural expression clustered under Deconstructivism [41, 42]. Libeskind, Zaha Hadid are few Deconstructivists, see **Figure 1**. The use of modern technologies extends throughout the entire design with distorted surfaces, odd leanings, and fractured wall surfaces. Indeed, possible due to speed, fluidity, and accuracy delivered by CAD which significantly relieved architects of time required for complex forms; for more quality family life or creative endeavors. Also, architectural studios are looking very different compared to a decade ago [42]. In Nigeria, the studios are sluggishly adapting, see **Figure 2**.

Indeed, things have changed with the introduction of CAD and significant architectural practice uses CAD: few are ArchiCAD, Revit, BIM, Chief Architect,

**Figure 1.** *A fit for Deconstructivism by Zaha Hayed. Credit UNSPLASH.*

**Figure 2.** *Architecture studio: sleepless nights. Credit: Allison.*

*Leveraging on Data Sciences: Review of Architectural Practice and Education in Nigeria DOI: http://dx.doi.org/10.5772/intechopen.103097*

Lumen360, and Sketchup. These tools make easy the organization of data to be more meaningful visually. Thus, in use more commonly among young people who are quick to practice even as students, heavily patronized by clients seeking for cheap labor and thus, compounding the problem of quackery in Nigeria.

More, 5G, 7D are merging to further reshape the design terrains and how architects work. In [43] the symbiotic partnership (man-computer) will enable "men will set the goals, formulate the hypothesis, determine the criteria, and perform the evaluations. Computing machines will do the routinizable work that must be done to prepare the way for insights and decisions in technical and scientific thinking." Design process is not linear, but cyclic for user experience designer because efforts are continually made satisfy the users leaving assumption behind and uncover alternative solutions" [44]. The CAD tools have made the iterative processes easy because design for real people not machines and robots imply understanding complex processes [41, 44]. Further, it empowers the client to make more informed contribution to the design process. From the lens of digital humanities and national development, 3D Computer Graphics is, for example, contributed to the restored sense of pride and patriotism among Chinese young people [45]. The regeneration of the Summer Palace from ruin has turned the once idle ruins into tourist site. With 3D computer graphics the beauty and splendor of the Summer Palace has been fully animated. The ruin site thronged with Chinese young people restored, reliving the past, appreciating the true stories of Summer Palace [45].

All above, 3D computer graphic is important, and noteworthy is the important role played by architects in identifying standardizing, creating symbols, and elements for extracted from ethnographic studies by architects in use by 3D computer graphic community. The standard elements, symbols, minimum dimensions, and other research driven data stored and published in the 680-page Neufert Architects Data authored by an architect, Ernst Neufert indeed testify to interdependent and mutually benefit from each other's progress (see [38]). More benefits are on the horizon, with Metaverse and creator economy is one the fastest growing sector; in terms of income generation, job creation, and export earnings [20]. View supported in [46] as Internet of value ((IoV), Web3.0, discussed the "risky necessity" "datafication," "dematerialization," "platformisation," in addition to social and resource value awareness" (see [44, 46]) architects as potentially key benefactor will have increasing role to play.

#### **3.4 Architect, as data scientist**

Architectural production includes: cities, homes, furniture, and more. In addition, it takes a minimum range of 5-6 year to be qualified to pursue full professional or chartered membership in Nigeria. Thus, architecture is a rigorous and highly educated profession [33] and in [47] architecture as toughest major in America from 2017 survey of global students'survey by students. An architectural study is one with high incidence of sleep deprivation among students, **Figure 2**. While architects rely on quantitative and qualitative analysis of data to recommend and make decisions, architectures consume about 55% global electricity and contribute about 38% of total global energy related Carbon IV Oxide (CO2) waste into the environment [48]. As by-product of architecture, big data is elucidated below focusing on waste paper generated in office activities and how big data can be captured for recycling.

The consulting office is involved in design through tender processes to construction, including post-construction activities. The activities are usually accompanied the shredded waste papers which remain useless not until the following action is carried out:

For instance, assuming the office used and trashed a ton of A4 papers from design to completion of a 1500 square meter floor areas shopping mall. Then, a useful data/ information is "1 metric tons of paper wasted per 1500square meter floor area shopping mall; also, 0.67 kilogram of paper per square meter floor area." Another data or information has environmental implications. For example, if producing A4 paper consumes 2-13 litre of clean water (as in [49]) and 52 Kilojoules of electricity in 2015 (as in [50]). Then, the hidden environmental cost of 1 metric ton of A4 paper equals: 0.4–2.6 millions liters of clean water and 10.4 million Kilojoules of electricity to produce 200000 A4 papers as trash). Further, (see Appendix 1) complex data table can be developed by substituting, one at a time, paper with electricity, gasoline, diesel, water, ink, timber off cuts, and more. Comprehensive and AI-Blockchain integrated smart table can predict, recommend, and support decisions, including climate change mitigation strategies. For example, in [51] was business case for Blockchain Carbon trading.

Methodology:

The architect's systematic process is with a loop of thinking, making (build detailed and engaging models), breaking (open to criticism) and repeating (gathering feedback) [52]. Like all sciences, architecture has laws, principles, and theories guiding actions including the manipulations of *numeric and categorial data, structured and unstructured data.* For example:

Supporting the claim of the science and statistic skills demanded of the architects is in [53, 54]. The use SPSS, graph and reports, of *z-score, t-score, normal distribution*

#### *Leveraging on Data Sciences: Review of Architectural Practice and Education in Nigeria DOI: http://dx.doi.org/10.5772/intechopen.103097*

*curve* to generalize findings by architects is common. Architects perform *regression analysis* to determine relationship between architectural productions and users' demographics. Indeed, scholars disagree architecture is more complex than machines because humans are not machines. These are useful for decision making [54, 55]: as consultant, public policy maker. For example,

Finally, the architect is *open to criticism, creative*, *team player, analytical, numerate*, with products aimed at making *impact in society*. The data gathered and generated from the above are appropriately managed and stored in the cloud (Google, IBM provide cloud storage services), Dropbox, and alike for easy access and use, including updating data outside the office. Each circle yields more data and progressively better the Design; called iterations. The point is, the architects collect the data, analyze it, label and classify it, and store it safely. He or she also retrieve and use the same for future project or training manual. All these involve using modern tools. They are consistent requirements of a data scientist [56].

#### **3.5 The city**

#### • Smart city

A term that has been the tonic with the political, built-up space, but most commonly the Smart city is understood to mean only a sophisticated computer driven city or even a "laboratory" in [57]. Conversely, other scholars think smart city is not all about a computer city, but that "the value lies in how this technology is used rather how much of it is used" [58]. In support, the chapter point at the intersection of using computer to identify appropriate data and use of such data appropriately. For instance, **Figure 3** indicates smartness rather than poverty; knowing what is sustainable, available, and using it rather than using what is sophisticated, yet on loan, and not sustainable. In other word, to deliver responsiveness in demand, justice, sense of belonging and wellbeing among city users in addition to availability of internet is smartness. In cities, it implies shared risk, wealth, collective decision making were the individual differences of the majority are significantly respected, rather than being over ruled by a few. In [58] data availability, integrity, confidentiality, accountability and operation laws were identified as canonical. Indeed, these requirements are significantly possible by use of AI-Blockchain technologies which is inspiring the big data sciences. As in [5] so, cities'safety and security can be preserved from detrimental

**Figure 3** *Ijaw stilt house: smart and simple.*

behaviors by data analytics of appropriate big data (extracts of terrorists, cells, deviants). City's infrastructures can be more responsive and preserved by citizens when infrastructures associated decisions, policy and laws are democratic in origin [59].

Poor data can impact cities negatively as earlier demonstrated. With disadvantageous data, subjectivation of the city: (a) cities abating crimes, (b) assume wrong identity, (c) anti-citizenship. The fact, AI-Blockchain can also learn the wrong stuff, if errors are not immediately corrected. In that sense, no matter the level of computer sophistications such cities are not "smart". Increasingly as symbols of exploitation, and battlefields of the winner take it all. Yet worsen by financialization and capitalism. Indeed, worst is the thinking of cities as "laboratory" which may justify why extremist as leaders can imagine turning cities into "radioactive ash" [60].

• Leadership Failure and Impact.

Considering architects' big data capacity, so why the disillusionment? Poor motivation. In a conversation the authors had with scholars of the Port Harcourt Polytechnic O. Wodike, G. Irighmah, C. Chendu, F. Dimabo blamed client's unwillingness to financially commit adequately for architectural services as reason for lack "focused research" required for "every project is unique." Thus, the attendant weak "architectural language" development, and repetitive narrative in cities. Besides, clients do not exclude the government while the "digital transformation is no longer optional" [61]. Therefore, poor data in addition to fragmented data culture in Nigeria's construction industry has enabled the impunity and bad image of the sector. In [62] Executive Director of Project in the Niger Delta Development Commission (NDDC) created to provide infrastructural gap in the Niger Delta region, described winning NNDC contract as a winning lottery to emphasize the impunity in the sector. Politicians have hijacked the data management weakness and unrestricted entry.

Today, politicians and public officials seamlessly inflate building and construction projects with a 2021 survey reported 56,000 abandoned projects valued about N12trillion, scattered across Nigerian cities as a result [63]. The construction sector's porosity, simulating a zero knowledge-based sector, has enable misfits into the sector's strategic leadership. Unlike with the health (Federal Ministry of Health), and justice sectors (Federal Ministry of Justice) that allow only doctors and lawyers as ministers and commissioners to head the ministries. In Nigeria, the Ministry of Housing and

*Leveraging on Data Sciences: Review of Architectural Practice and Education in Nigeria DOI: http://dx.doi.org/10.5772/intechopen.103097*

Works, Ministry of Transport, and Niger Delta with huge infrastructural budget have lawyers as ministers with so much power. Expectedly, the misfit may account for the huge "debt implication", "lambasting,' politicizing human right (e.g. right to descent shelter), and corruption [64–66] with impunity. A misfit issue becomes important, with a disadvantageous data management system yet securing infrastructure financing loans from the likes of China [67]. Thus, the demanding leadership and accountability from the construction industry leaders as in **Video** [68].

More details of poor performance:

The Ministry of Transport construction of a USD 1.9 billion standard gauge railway from Kano to the Niger Republic is causing uproar in the Senate, including the citizens [66]. Relative to the dreadful roads plaguing the industrial and commercial hubs, including Wes Africa largest market Onitsha (South east of Nigeria), the Kano-Niger Republic railway is economically disadvantageous; indeed a symbol of marginalization and insecurity as illustrated in **Figure 3** [66]. In Guardian November 10, 2021 , the Nigerian Institute of Surveyor "Call For Subsidence Monitoring & Deformation Study of High Rise Structures" following incessant building and overpass collapses in Nigeria [63].

#### **3.6 Possible information and telecommunication technologies for students**

As matter of emphasis, it is necessary to dedicate a subsection dealing with possible IT technologies. Architects must constantly seek ways to improve their communication tools and channels to clients and all stakeholders. Thus, this subsection will offer in specific and significant detail the possible data technologies for both students and architects; now and into the future. The list of possible IT technologies cannot be exhausted as more are emerging and others evolving fast too. Below paragraph are few in use and to be use by Architecture students and architects:

Excel, Google form, Mind Mapping tools, Google Earth, others for common graphics editors are: Photoshop, Illustrator, Paint Shop Pro, CorelDRAW, cloud strorage. In addition, the Apple Photos plug-in from Macphun, Adobe Lightroom, Digital Image Suite, Canva, and related programs. For designs and animation, 3D data works are Revit, ArchiCAD, BIM, Sketchup, and Mind Mapping software (e.g. Microsoft Mesiere, Yed, see **Figure 4**). While the aforementioned are already in use, the future increasing immersion and free-hand experiences have Microsoft HoloLens 2, SketchUpViewer, demonstrated in Vieo-6. Blockchain, NLP, 7D, 6G, and Digital Twins (DT) as IT technologies the architects will depend in everyday service delivery. A few technologies are discussed next (**Figure 5**).

#### • *Excel*:

In [69] is "a software program created by Microsoft that uses spreadsheets to organize numbers and data with formulas and functions," according to Corporate Finance Institute (CFI). In [70] Excel was described "as a way to create nice looking tables of data – things like building programs or drawing lists." Also, it has mathematical formulas with capacity to analyzing and computing data. ArchiDaily, in the same [70] listed twelve useful Excel formulas for architects few are: SUM, IF, SUMIF, COUNTCOUNTIF, COUNTBLANK, AVERAGE, and more. SUM will enable the performance of mathematical operations on data (i.e. parametric data). "IF" will enable architecture student perform conditional analysis, e.g. IF income is income higher than N300000 monthly group data as "middle income." SUMIF will enable addition of specific group of data if specific condition if fulfilled, e.g. SUM the number clients,

#### **Figure 4.**

*Bubble diagram achieved by 3D computer graphics with arrows indicating human circulation. Credit: Anita Bala.*

#### **Figure 5.**

*3D graphics and Data use is serving as an essential component of computer-assisted learning system. Mix-reality, a future .But current in market at USD45000 with Microsoft HoloLens 2 which is mix- reality headset will be increasingly use for interaction.*

IF income is above N300000monthly. The COUNT function counts specified element in cells, like none parametric data- "Female", "Married" and as such. In addition, Excel makes easy the non-pleasurable aspects in real estate. For instance, the

*Leveraging on Data Sciences: Review of Architectural Practice and Education in Nigeria DOI: http://dx.doi.org/10.5772/intechopen.103097*

management of land related complex and multiple sales demands involve keeping track of different measurable areas, associated varied facilities, areas for outright and installment purchases, and lease areas.

Kilkelly further acknowledged, Excel offered, "a lean and mean Excel spreadsheet accurately calculated the leasable area. Using the formulas I had built, we could quickly play out scenarios for our client" [70]. The point is, Excel is suitable for: Data input, Data management, Accounting, Financial analysis and analytics, Charting and graphing, Programming, Time management, and Task management (as in [69]).

• Tablet and Digital Art

Other than desktop, Laptop, powerful tablets have emerged to take make digital arts easy and handy. Apple Pencil, Gamon PD1560 15.6, Wacom Cintiq 22, Xp-Pen Artist Display 22R Pro, HuionKamvas Pro-Pro 22, while in [71] listed top ten "architecture apps (that) have completely altered the working habits of architects" to include: (a) DroneDeploy "developed to care to the growing need for aerial site intelligent software," (b) "ArchiSnapper is a field reporting App that allows users to efficiently draft a report during site visits- users can take photo, draft and comment and the app generates seamlessly the report,"[71] others are Shapr3D(IOS), and RoomScan Pro. The 3D modeling process produces a digital object of value that can be sold, hired for fee, transferred as valuable gift. One of such object as None Fungible Token (NFT) like rear art can be sold for thousands to millions of dollars. In [72], for instance, the "Artist Beeple's Crossroad fetched \$6.6 million on Nifty." Few architects are now specializing in building NFTs: owning virtual estates, including cartoon characters, and football stadium, like in the real world.

• Blockchain

Looking at HoloLens 2 and SketchUpViewer demonstration, blockchain value emerges as it can permanently keep track of all changes, clients approvals, and serve as basis for undertaking contract. Thus eliminating copyright violation issue, and providing evidence for contract violation. In future, a combination Microsoft Hololens 2, SketchUpViewer, digital twin (DT) technologies, and additive manufacturing or printing all on Blockchain would make it impossible to violate construction in terms of design and specifications. A very common trend in Nigeria: roads built without drainage, kerb removed, and asphalt thickness highly compromised.

• Photoshop, Lightroom, and Adobe Illustrator.

Architectural profession involve the use of photography which good marketing tools and skill. Students are taught photography as core course. It is important in content creation for books, magazines, gallery, and graphical objects enhancement. A picture "is a thousand word" declared wisdom; even so, the quality matters. Adobe Photoshop is one such powerful tool for high quality photo editing. The Lightroom as an editor and organizer is judged much better than most photo editing alternatives tools, including photoshop for easy and light manipulations. For example, with over 100 possible different filters settings Lightroom can improve a given poor quality image to great photograph for different themes: landscape, food, city view at night day, construction sites, presentations, and more. Nevertheless, alternatives to

photoshop are many. Adobe Illustrator, according to the Graphic Design Institute's publication also facilitates creating stunning art.


**2. Methods**

This trial was an open-label, randomized, clinical trial which enrolled 315 patients undergoing coronary artery bypass grafting with arteries (internal mammary, radial, gastroepiploic) or inverted saphenous veins in a single center (Cardiac Surgery Department of "Prof. Dr. C. C. Iliescu" Emergency Institute of Cardiovascular Diseases, Bucharest, Romania) between January 1st, 2006 and December 31st, 2007. Surgical management and treatment of the patients were based on a common standard protocol.


*Edited by Cuneyt Narin*

This book considers mainly the current perioperative care, as well as progresses in new cardiac surgery technologies. Perioperative strategies and new technologies in the field of cardiac surgery will continue to contribute to improvements in postoperative outcomes and enable the cardiac surgical society to optimize surgical procedures. This book should prove to be a useful reference for trainees, senior surgeons and nurses in cardiac surgery, as well as anesthesiologists, perfusionists, and all the related health care workers who are involved in taking care of patients with heart disease which require surgical therapy. I hope these internationally cumulative and diligent efforts will provide patients undergoing cardiac surgery with meticulous perioperative care methods.

ISBN 978-953-51-0148-2

Special Topics in Cardiac Surgery

Photo by wildpixel / iStock