A Guide to Using Case-Based Learning in Biochemistry Education Verena Kulak Genevieve Newton* From the Department of Human Health and Nutritional Sciences, University of Guelph, Ontario N1G 2W1, Canada Abstract Studies indicate that the majority of students in undergraduate biochemistry take a surface approach to learning, associated with rote memorization of material, rather than a deep approach, which implies higher cognitive processing. This behavior relates to poorer outcomes, including impaired course performance and reduced knowledge retention. The use of case-based learning (CBL) into biochemistry teaching may facilitate deep learning by increasing student engagement and interest. Abundant literature on CBL exists but clear guidance on how to design and implement case studies is not readily available. This guide provides a representative review of CBL uses in science and describes the process of developing CBL modules to be used in biochemistry. Included is a framework to implement a directed CBL assisted with lectures in a contentdriven biochemistry course regardless of class size. Moreover, this guide can facilitate adopting CBL to other courses. Consequently, the information presented herein will be of value to undergraduate science educators with C 2014 by The an interest in active learning pedagogies. V International Union of Biochemistry and Molecular Biology, 42(6):457–473, 2014. Keywords: case-based learning; nutrition; biochemistry; active learning Introduction An ongoing challenge for science educators is to find effective ways to facilitate the successful achievement of learning outcomes by undergraduate students. Beyond the learning of content, there is a general need to develop problem-solving, critical thinking, and communication skills. Herreid [1] and Darabi et al. [2] describe that effective problem solving is related to asking for evidence, practicing cognitive flexibility, seeing alternative strategies, and attempting creativity. Developing and exercising these traits require a high-level of student engagement that is commonly associated with a deep learning approach, first € ljo € [3] and further discussed by defined by Marton and Sa others [4–6]. To achieve these goals, scholarly research on active learning models using cooperative techniques such as case-based learning (CBL) has increased. *Address for correspondence to: Human Health and Nutritional Sciences Department, University of Guelph, Guelph, Ontario N1G 2W1, Canada. E-mail: newton@uoguelph.ca Conflict of Interest: none. Received 25 September 2013; Accepted 7 September 2014 DOI 10.1002/bmb.20823 Published online 23 October 2014 in Wiley Online Library (wileyonlinelibrary.com) Biochemistry and Molecular Biology Education In science education, CBL aims at teaching content while actively engaging students in real-life case study scenarios, in order to expose students to the scientific process [7]. Evidence shows that CBL can encourage students to: (a) gather and apply information to solve problems, (b) facilitate relevant information retention, and (c) refine communication [5]. It can also expose learners to decision-making roles and the teamwork typical of professional environments. Lastly, CBL can encourage students to develop the skills necessary for life-long learning [8]. However, lecturing is still the favored method of science teaching. Lecturing at the undergraduate level typically includes an emphasis on memorizing facts and a dismissal of concept application, which leads learners to be disenchanted with science [9]. Most learners subjected to these conditions opt to use lower order cognitive skills, which are associated with a surface learning approach [5]. Moreover, the tendency toward a surface approach has been remarked around the world in diverse fields such as nursing [10], speech pathology [11], anatomy [12, 13], chemistry [14], physics [15], and biochemistry [16–20]. These findings underline a need to encourage instructors to implement alternative pedagogies such as CBL that may facilitate a higher level of student engagement [21]. CBL has increased in popularity particularly among biology instructors, but its use in other sciences is less significant [15]. Specifically, it is speculated that traditional 457 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Article lecturers are unfamiliar with the evidence on CBL or do not find it compelling. Indeed, there are several questions that remain unanswered. For instance, there is still limited evidence regarding the specific effect of CBL on promoting a deep learning approach. To pursue this question, some concerns need to be addressed. First, there is a lack of detailed guidance and consensus on how to design cases that can be used as research instruments. Second, effective implementation of CBL is challenging. It requires systematic development of clearly defined learning objectives [17], workload, and time limits [18]. It should also account for the instructors’ teaching style and their willingness to facilitate students’ self-teaching [5]. Therefore, proper guidance on case implementation is needed. Third, it is important to provide an accessible introduction to CBL theory and practice to effectively engage novice instructors in the research process. This article seeks to fill the aforementioned gap by presenting a representative review of CBL, a cohesive stepby-step strategy to design and incorporate CBL into biochemistry education, and some insight into methods of determining the outcomes of including such techniques into biochemistry courses. General Description of CBL Definition of a Case A case is the teaching medium in CBL. A case can often be presented as a narrative resembling real-life situations that provide a clear context and a central character, specimen, or element, where a difficulty needs to be resolved [22, 23]. Therefore, the presentation of a problem is the initial step in the learning process [24]. The narrative can be accompanied by supporting information or scaffolding tools that facilitate knowledge construction; tools such as research articles, laboratory results, or video screenings [8, 18, 25]. Case descriptions can be ambiguous but should contain enough detail to elicit active analysis and interpretation [26, 27]. Cases can be integrated with lectures or other pedagogies thereby assisting in teaching content [28]. Cases can be provided in advance of lectures and laboratories, although they may also be presented after relevant lectures or in any other sequences that suit the instructor’s style or learning outcomes. This strategic placement allows the students to structure their learning and to base the initial case analysis on prior knowledge or through their own research [29–31]. Definitions of CBL and PBL CBL is mainly rooted in the cooperative learning premise in which the instructor acts as a facilitator in the construction of knowledge. The instructor helps to direct students away from an exclusively passive, in-class lecture-driven mode [32]. Some authors consider CBL as a derivative model of Problem-Based Learning (PBL), a popular pedagogic strategy that is widely used in medicine and law [33–35]. Other workers use the terms interchangeably and simply refer to 458 a case as a problem [36–38]. Therefore, there is currently a lack of clear distinction between PBL and CBL in the literature [39]. This adds difficulty to gathering specific evidence on CBL benefits and potential uses, which may in turn discourage instructors from introducing CBL to suit their own courses. The present guide agrees with a distinction between CBL and the classic PBL curriculum model as described in Heinrichs [40]. The following paragraphs define this distinction in more detail. PBL commonly presents complex, open-ended problems about topics previously unknown to the students. In the classic PBL model, solutions result almost exclusively from group effort and self-teaching. Learned content depends on what the students determine their own knowledge deficiencies are, so solutions may vary from group to group [41, 42]. Lectures are almost non-existent in PBL, and since group discussion is so important, there is a general requirement for “fluid” classroom layouts with boardroom style tables and movable chairs, which can be expensive to provide [43]. During problem processing, the instructor mediates students’ discussion within each group instead of delivering information [44]. On the contrary, Grauer et al. [45] indicated that in CBL, cases are more structured, shorter, and less complex than in PBL. Discussion does not normally dominate in-class time; therefore there is less dependency on specific classroom layouts. Most CBL users aim to connect concepts by addressing predetermined learning issues or knowledge deficiencies [46]. Both PBL and CBL aim at teaching material on a “need to know” basis: students become researchers and gather further information, integrate it, and then decide among themselves, which are the best solutions [36]. Medical schools use PBL or CBL variants in preclinical courses including introductory biochemistry. However, the classical PBL method with very little lecturing is time intensive for instructors [29]. Adapting this model to undergraduate biochemistry courses outside of medicine presents specific challenges. Student audiences in undergraduate biochemistry continue into varied science majors, so curricula are content-driven instead of focusing on open-ended clinical diagnoses. In a large class context, it may be unrealistic to expect a fair investment of instructor’s time at the group level. To date, most publications on undergraduate case studies refer to the instructor’s role as a facilitator at the whole class level [28, 47]. In CBL, the instructor presents the case to the class and generally does not interact intensively with each group during case processing. Instead, the instructor may facilitate consensus with the class as a whole to generate an integrated solution after each group has worked on their own [34]. Hence, the degree of instructors’ engagement at group level has been interpreted as a methodology difference between PBL and CBL [39]. Types of CBL Approaches Cases can be processed in different ways depending on topic, timelines, and learning outcomes. For instance, CBL in Biochemistry Education 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Biochemistry and Molecular Biology Education timelines for case processing can vary from one to several weeks [7]. Heinrichs [40] described four stages in solving a case: (a) hypothesis generation to identify the cause; (b) gathering of data and supporting information; (c) establishment of secondary learning issues and performing selfdirected study; and (d) hypothesis reassessment and merging of answers to reach an overall conclusion. Variations on how these stages are attained give rise to several types of case studies. Case types can be seen as part of a spectrum in regards to the degree of variation in elements such as student involvement, group work, integration with lectures, case complexity, supporting information, and the role of the instructor. Herein, PBL is interpreted as being at one extreme of the spectrum of case study scenarios, with a very high degree of self-directed learning, none or minimal didactic lecturing, a high level of case complexity, and a collaborative learning environment guided by a trained mediator. The variants of case studies discussed here— lecture-based [22, 35], directed [7], interrupted [1], jigsaw [48], and PBL [36]—differ primarily in the degree to which students are self-guided and the degree of group interaction as shown in Fig. 1. The characteristics of each type are described in Table 1. History of Use Herreid [22] postulates that the use of cases as an educational tool arises from the human appeal for story telling. Kulak and Newton The first recorded accounts of teaching with cases at the university level date back from 1870 at Harvard Law School, where Christopher Langdell introduced the Socratic Method combined with original cases. Students were asked to draw their own conclusions to imitate practicing lawyers instead of memorizing law textbooks. Harvard Business School also adapted this approach to emphasize discussions following lectures [49]. During the early 1900’s, James Lorraine Smith, Clifford Albutt, and Richard Cabot independently used clinical cases in lectures to teach pathology in medical schools at Edinburgh, Cambridge, and Harvard respectively, following the precedent of the Paris school of medicine from the late 1800’s [50]. By the end of the 20th century most law, business, and medical schools globally integrated cases to illustrate or apply content from lectures in their curricula [49]. In science teaching, during the 1940’s, Conant [51] was the first to publish a variation on the lecture-case method. He narrated case stories to transfer scientific principles to the general public. During the 1960’s, Eakin [52] would appear as a well-known scientist in front of student audiences and by way of monologues reasoned out loud how scientific principles were elucidated in their historical context. In the West, during the 1970’s and 1980’s, constructivism and developmental psychology inspired the transformation of education at all levels. This led to a more “student-centered” approach, including an emphasis on group work to construct explanatory models 459 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License CBL types classified based on the degree of group work, self-direction, use of lectures, and case complexity. FIG 1 TABLE 1 Characteristics of the CBL types discussed in this article (Reproduced from Refs. 1, 7, 22, 35, 36, and 48) Type of CBL Lecture-based Main characteristics Instructor enacts or describes case and solution as part of regular lecture. Students are passive (audience members) but can be asked to connect case to lecture material. Directed Allows for blended teaching: group work plus lectures or other pedagogies. Supporting material is provided (figures, tables, texts, videos, etc.). Specific questions accompany case and answers are close-ended. Instructor facilitates discussion of the general solution with the whole class. Suitable to introductory courses, prior knowledge is provided in lectures. Interrupted Progressive disclosure of information to groups: First stage: just a few clues are provided and students must generate a tentative solution. Following stage(s): more details are provided to further develop solution. Helps to illustrate how the scientific process works (handling incomplete data, generating tentative hypotheses, encountering difficulties). Instructor facilitates discussion of the general solution with the whole class. Suitable to advanced courses where prior knowledge is required. Jigsaw Students form groups and become experts at only one question and then the expert groups disband. New groups form with one expert member for each question. Solution results from integrating the contributions of each expert. PBL Groups are provided complex cases without many clues. No supporting information is given. Students come up with their own questions to solve. Solution is open-ended and depends on where each group decides to focus their efforts. Instructor is trained in mediation to facilitate discussion at group level. of phenomena instead of memorizing facts [53, 54]. Additionally, there was recognition in academia of the information-surge in many fields and the resulting need for life-long learning, plus the need to develop interpersonal skills [36, 55]. Consequently, McMaster University developed a PBL curriculum to train medical students in solving complex situations and to offset increasing student dissatisfaction with more traditional methods of teaching [56]. Student groups were expected to solve clinical cases by searching for the information themselves. This represented a shift from the traditional pedagogical paradigm that relied on lectures to transfer most of the information and to rely instead on other methods that facilitate developing the ability to ask relevant questions and make decisions on how to use information to generate appropriate solutions. Early evidence on these alternative techniques reflected a renewed enthusiasm in the classroom environment by instructors and students alike. This assisted in the dispersion of cooperative learning tools in science education [57]. At present, versions of PBL or CBL have been adopted worldwide to teach medicine, dentistry, nursing, engineering, general sciences, and the humanities [24, 58]. 460 Pedagogical Impact of CBL & PBL Like many other active learning techniques, CBL and PBL derive from constructivist and other contemporary cognitive evidence indicating that experiences and contextualization promote knowledge transfer and the retention of information [4, 41, 59]. Evidence shows that CBL facilitates accessing Bloom’s [60] higher-order cognitive skills such as application, analysis, synthesis, and evaluation more than lecturing alone [7, 18, 61–63]. CBL and PBL also provide opportunities to practice and self-evaluate discipline-specific content [21, 28, 64]. Additionally, problem solving in a face-to-face group setting has been shown to decrease failure rates [65]. In most variants of case studies, small groups of students are challenged to listen and to make trade-offs with others while confronting their own assumptions and values related to a topic, hence developing effective team work and improving communication skills [27, 66]. It should be noted, however, that some researchers have found no effect of the implementation of PBL on encouraging a deep learning approach [67, 68]. Therefore, no generalizations can be made so far, as careful analyses of the parameters measured vary greatly among studies. Reports often lack information concerning the specific PBL CBL in Biochemistry Education 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Biochemistry and Molecular Biology Education How to Develop a Case Study Effects of CBL/PBL in Biochemistry The success of a case depends on how effectively it facilitates acquiring, integrating and applying information and how engaging it is to the students [73]. Case length, realism, and level of intrigue are important for gathering initial attention, creating student involvement and promoting an appropriate depth of discussion [9, 24, 74]. Cases can be fact-driven and deductive with exact single solutions (closeended questions) [75], or they can be context-driven and open-ended so that multiple solutions are reasonable [22]. Factors to consider when selecting, designing or implementing cases are class size, complexity of topic, allotted time, academic level, and desired learning outcomes [76]. The level of difficulty or case complexity depends on the amount of data and level of analysis required. In addition, the expertise of the instructor as a group facilitator should be considered, particularly because introducing CBL pedagogies may result in resistance from students unfamiliar with them. To address this challenge it is helpful to provide the case to the students along with a general framework of CBL for them to follow, as well as a timeline and the goals of the activity [66]. Struyven et al. [77] identified poor instructional planning as the main cause of failure. The success of CBL can also depend on the alignment of a case with its assessment. For detailed guidance on this process, refer to Biggs and Tang [5] and their suggestions on holistic case study assessment. Short-answer questions or multiple choice questions can be implemented in exams aligned with CBL units. However, the emphasis should be on judging higher levels of cognitive learning such as understanding of contextual factors, problem analysis, and problem solving [78]. Some examples on the type of questions suitable to accompany case studies are discussed in section “Learning issues.” Other suggestions on how to assess students under a CBL environment are presented in section “The Directed Case Method”. Biochemistry and molecular biology are interdisciplinary fields where a large amount of information is integrated into an overall view of life processes. Biochemistry teaching tends to be content-dense and lecture-driven. Assessment is commonly done via multiple-choice tests focusing on fact-recollection. Typically, these courses follow a lecturetextbook-laboratory format where lectures deliver 80% of content to large student cohorts [16, 17]. This teaching context has lead to a lack of understanding of chemical interactions and their role in metabolic pathways [18, 19]. Additionally, Anderson et al. [69] indicated that in large biochemistry classes, individual interactions between faculty and their many students is limited. This environment does not provide opportunities to implement active learning and does not discourage students from rote learning. Biochemistry is considered to be a difficult subject for most students in part because it contains abstract concepts that are difficult to understand if relationships to everyday experiences are not demonstrated [20, 70, 71]. Normally, undergraduate curricula are composed of one or two biochemistry courses presenting the main pathways that are then integrated into a general view of cell metabolism. Cornely [47] reported that in lecture-based courses, students were able to handle the individual metabolic paths fairly easily but had trouble making connections among them and relied on memorizing content to prepare for tests. This has been interpreted as the result of student’s inability to analyze, integrate, and apply previous knowledge. It has also been reported that students in introductory courses often lack critical thinking skills as well as personal and social responsibility skills [16]. These findings demonstrate a need to motivate students to understand rather than memorize material as well as a need to foster interest in active learning. The literature is punctuated with examples of instructors using a student-centered or active learning approach as an alternative to lecture-dominated courses. Dods [44] described an early example of using PBL in biochemistry and found that it promoted more effective learning of content than lectures. Rosing [72] indicated that there was a higher level of satisfaction among students and instructors using PBL in clinical biochemistry. Anderson et al. [69] used a PBL curriculum in an introductory biochemistry course and found that compared with non-PBL there was an improvement in standardized test scores and that students had a more positive attitude toward the learning experience. Hartfield [8] found similar results when using CBL in an advanced biochemistry teaching unit. This evidence shows that increased student satisfaction and reduction in failure rates can result from applying CBL or PBL to biochemistry courses. Kulak and Newton Characteristics of a Good Case What to Include/What not to Include Successful case design is labor intensive, as it should include up-to-date and evidence based content and a nonlinear descriptive vignette that reflects real-life scenarios. A vignette may include a description of symptoms, the progression of a disorder, or a disturbance in the environment as experienced by the main character [28]. The description should be presented in one or two paragraphs with an engaging context. In most CBL types, the initial information may have very specific guidance items and questions to be provided to students. It is counterproductive to design cases that are too long and provide tangential or irrelevant information that may confuse students, especially if time to solve the case is limited and students have no prior knowledge of the subject [47]. In undergraduate science courses, it is not recommended to design vignettes about political or 461 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License or CBL method used and the complexity and degree of difficulty of the topics presented. Good case features and their cognitive advantage. (Reproduced from Refs. 29, 40, 41, and 59). FIG 2 religious views that may disengage the students from the science themes to be explored. In addition, a vignette that is too short will not motivate students to find out what happened next. For example, when introducing a case discussing a Salmonella infection via a food source, avoid simplified statements such as “A 25 year old male was admitted to a hospital suffering from suspected kidney failure.” This sentence provides a lot of information in a fairly impersonal manner. A more suitable introduction would be “On a Friday night after work, Tom and his friends headed to a local pub to celebrate his 25th birthday. Tom decided to have some fresh made chicken tapas to start up.” This can be followed by specific details on eventual symptoms that 462 led to kidney failure. A narrative that provides a name and a setting is more likely to engage undergraduate students from the beginning. It is also advised to avoid re-using cases or related questions that post solutions easily found online to prevent students from simply copying answers. A compilation of good case features to include and their cognitive advantage is shown in Fig. 2. Learning Outcomes The first steps in case design include a careful consideration of the learning goals and the main route of action that directs the students towards achieving them through case analysis. In addition, when learning goals are being CBL in Biochemistry Education 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Biochemistry and Molecular Biology Education Learning Issues During case processing, students need to define knowledge deficiencies, also called learning issues, relative to a particular topic. Learning issues can be provided by the instructor via specific questions or can be developed by the students themselves depending on what the learning goals are [46]. For instance, during the initial stages of case processing, students should determine what is going to help them with solving the case “Which types of molecules, cells, tissues, and organs are involved? What is considered their normal functioning, physiology? What caused the physiological, metabolic problems?” These types of questions allow for interpretation and integration of concepts. Other questions requiring synthesis and evaluation can follow “Why is a particular co-enzyme important in this system? How can this system be restored? Why these symptoms indicate impaired metabolism in this character?” Careful selection of questions or guiding items is important to define the level of difficulty or degree of analysis that the instructor expects the case to provide. This follows reports from Anderson et al. [69] indicating that knowledge application and integration are required in scenario-type questions leading to conclusions instead of fact recollection. More specifically, an introduction to glycolysis can be done with a case on galactosemia in humans (an inborn error of metabolism causing an inability to convert galactose to glucose). If the vignette provides a series of symptoms and a diagnosis, learning issues related to glycolysis can be initiated by close-ended descriptive questions that require knowledge and comprehension, for instance: (a) What is causing the accumulation of galactose? (b) What Kulak and Newton are the biochemical effects of galactosemia? These can be followed by questions requiring analysis, synthesis, and evaluation: Galactolipids are necessary for myelin formation. Explain how a patient on a galactose free diet would synthesize galactolipids. When teaching photosynthesis, a case involving a disturbance in a phytoplankton community can be designed. For marine autotrophs, a case on carbon fixation could be accompanied by a series of questions such as (a) Explain how CO2 is used in photosynthesis, (b) Discuss the effect that iron-rich waters have on marine phytoplankton and how this ultimately affects the marine food chain, (c) Construct a concept map of the complete carbon cycle, its relationship to atmospheric CO2 formation and release of CO2 by burning fossil fuels, (d) How would all this affect a phytoplankton community living in Artic waters? Herein, the first question requires knowledge and comprehension while the second, third, and fourth questions require analysis, synthesis, and evaluation of facts. For content-heavy courses, such as biochemistry, a series of cases can be presented throughout the academic term to cover various topics [80]. For instance, multiple cases can be sequenced to illustrate the different metabolic paths, each presenting relevant learning issues to each path. Case contexts and protagonists can differ to allow for multiple voices and perspectives that intrigue the students and keep them motivated. For instance, for humans and other heterotrophs, carbohydrate metabolism can be taught via five cases, covering glycolysis, the electron transport chain (ETC), the citric acid cycle, as wells as gluconeogenesis and glycogen metabolism. For autotrophs, a case on carbon fixation could be followed by others on cellular respiration. Fermentation pathways could be emphasized in microbiology or advanced biochemistry courses. Step-by-Step Case Design Careful design results from the constructive alignment or integration between the different pedagogical elements imbedded in case studies [31]. This relieves some of the pressure and workload that is experienced by students and mitigates negativity in students’ perceptions of CBL. The instructor should write the case and envision how the students may go about processing the data and learning issues. Moust et al. [29] discussed problem solving and its associated cognitive processing. These workers described the case as a trigger to learning in a relevant context, with the initial analysis helping the student to activate prior knowledge and to define knowledge deficiencies. The problem solving process is hypothesized to stimulate growth via self-study and group work and to lead to synthesis and evaluation that aids in solving the case. In most PBL where cases are open-ended, consensus on the solution may come from group discussion mediated by the instructor. In CBL types where cases are close-ended, solutions are more straightforward and providing an answer key can facilitate 463 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License established in a CBL environment, case design should include how those goals would be shared with students [79]. The instructor should consider what the students are expected to know, practice or value by the end of the case. For instance, in a biochemistry course, a main goal regarding content is not to simply memorize the chemical structure of glucose or the end products of glycolysis, but to determine the value of knowing the structure of glucose or how glycolysis is achieved or regulated. In a CBL environment, where a disruption to the normal carbohydrate metabolism is introduced, the students would have to know the structure of glucose in order to determine how or why glucose interacts with other biochemical molecules for glycolysis to occur. By processing a case, students can go further by explaining how the glucose molecule is affected within a system and if it is relevant to alter the supply of glucose or other factors to modify certain metabolic circumstances. So, students are required to relate and analyze facts to explain a cause and effect context. Beyond the learning of content, students are expected to exercise other attributes like communication, teamwork, and professional ethics. It is important to emphasize to students that these are relevant learning goals. Flow chart of case development. (Reproduced from Refs. 29, 80, and 123). FIG 3 consensus. The instructor should generate a possible solution for open-ended cases or a detailed answer key for close-ended cases beforehand to confirm that the learning issues are covered effectively. If questions are provided by the instructor and are close-ended, their solutions should not be overlapping. Figure 3 schematizes a process to follow in case design. Figure 4 shows a representative case based on up-todate evidence on the ETC and integrates the features mentioned above. This case integrates the biochemical basis of ETC and what happens when a systemic disturbance is introduced in a human subject. The condition afflicting the main protagonist, Avery, relates to intake of a dietary supplement and its eventual negative physiological effect: liver failure, an obvious clinical manifestation. This case stems out of real clinical cases where supplements containing usnic acid were the cause of metabolic injury. Some published clinical cases, which are likely to be found by the students while doing their own research, are on the prodC and LipoKinetixV C . The inclusion of these ucts SomalyzV products in the representative case was purposely avoided because they contained antioxidants and were blends of several bioactives. This was done to prevent cognitive frustration. Note that the fictitious supplement BulkFX is a blend of a pharmacological dose of usnic acid, a small dose of caffeine and the polysaccharide inulin. The case and the accompanying learning issues nest concepts within concepts: each learning issue has a specific objective and there is a progression in cognitive complexity that the students should address. Students are not merely exposed to what the ETC is or the cascade reactions that occur under normal circumstances, but how the pathway is affected by the introduction of a disruptor and why the disruption affects whole-body homeostasis. Learning issues one and two help to build a specific biochemical perspective that relates the ETC to oxidative phosphorylation. 464 Issues three to six allow for a progression to a broader biochemical-physiological perspective by integrating the disturbance on ETC as a trigger for tissue, organ, and systemic failure. Moreover, issues four to six should encourage students to determine if the metabolic path affected could be modified by other elements, which requires synthesis and evaluation skills. To conclude, the case solution results from looking at the ETC from three perspectives. First, students would be concerned with only the biochemical details and the role of the compounds cited from test results thereby relating the biochemical pathway to the clinical outcomes, or simply put, to describe the symptoms from a straightforward biochemical perspective. Second, students should be able to interconnect the character’s condition to other biochemical pathways demonstrating a deeper understanding of how processes are interconnected and highly integrated even though seemingly segregated and compartmentalized within the living cell. In other words, students should value the role that the ETC and oxidative phosphorylation play in cellular respiration. Third, students are asked to consider the broader physiological impact of changes to normal biochemical processes. Students should be able to discuss that ingesting the given dietary supplement over time, triggered the observable symptoms, and disrupted the normal processes in Avery’s body. Overall, students are asked to look at the ETC from an increasingly broader perspective: from a disruption in the pathway, to its impact on cells starting with the mitochondria, to further consequences on organs and tissues that provide observable outcomes and health risks (Fig. 5). This provides the opportunity to perceive a biochemistry topic beyond a static compilation of data and more as an opportunity to acquire, integrate, analyze, and interpret biochemical data that can assist in solving real-life dilemmas. To illustrate how the same case can be modified and implemented onto the different types of CBL, refer to Table CBL in Biochemistry Education 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Biochemistry and Molecular Biology Education 2 for the resulting versions. It can be noted that the lecture-based method does not use group work and students have a passive stand, so they might not be engaged to the same degree in the case as with other CBL types. The instructor shares all solutions as the case unfolds, so Kulak and Newton there is little opportunity for students to integrate knowledge themselves. The jigsaw method works well with topics that are not content-heavy, when students have prior knowledge or when there is generous time for class discussion. This is because each student develops expertise at 465 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License ETC representative case. Case was adapted from several primary references 118–122. FIG 4 FIG 5 Concept integration for the ETC representative case. only one question and it needs to be enough time for concept integration. With content-heavy introductory courses, the learning issues need to be adapted in a way that allows for each member to work on the basics independently to avoid knowledge deficiencies. For instance, the learning issues in the representative case would require that all members develop knowledge progression from biochemical into physiological concepts on the ETC. The interrupted method expects students to handle inconclusive evidence in stages, so it may be more suitable to advanced courses where students have prior knowledge and may be more capable of handling progressive knowledge construction [1]. The case when adapted into PBL becomes open-ended so each group may have diverse learning issues and proposed solutions, therefore the knowledge acquired will vary from group to group. This may not be advantageous for introductory, content-heavy courses or complex subjects such as the ETC when time is limited. In addition, there is a need for a trained facilitator who can invest significant amount of time with each group to mediate discussion [43]. Several workers have found that the directed CBL method proved advantageous to teach introductory biochemistry and other content heavy disciplines due to its specificity and ease of alignment with lectures [28, 46, 74, 81–83]. The following section discusses the directed CBL in more detail. The Directed Case Method Directed CBL along with lectures is well suited to introductory courses such as biochemistry, where students have limited prior knowledge and timelines are short. Learning issues are provided to students via questions constructed to have single predetermined answers, so this method allows for content-dense topics to be covered directly and specifically [28], resulting in homogeneity of taught content. The representative case from Fig. 4 fits well into a directed CBL aligned with a lecture on ETC. It can be used as a module or unit on carbohydrate metabolism and its implementation may follow the proposed framework shown in Fig. 6. The directed CBL framework described in Fig. 6 allows for the ETC unit to span over two sessions in one week. The first session includes group randomization, case presentation and initial discussions plus a 60 min lecture. Students are expected to meet outside class and solve the questions with the aid of textbooks and online resources. In 466 directed CBL, it is advantageous to provide students with some specific references to maintain focus during case development. During the final in-class session, students present the group answers to the class or hand in a written report. The instructor facilitates consensus so the whole class will have access to the same unifying answers. The representative ETC case provides six questions, suitable to be processed by groups of six students. However, it is at the discretion of the instructor to provide less or more questions to suit the learning goals of a specific course. Another modality would be to provide all groups of six students with three questions and then ask each group to develop three more questions specific to their learning needs. This encourages more initiative, reflection, and higher student involvement with the process. To assess the unit, the presentation or written report yields the same grade for the group. To account for variable contributions by group members, students may be asked to confidentially evaluate other group members by submitting their estimated percentage contributions so these can be averaged by the instructor and applied to the grade on the unit. Challenges of Implementing CBL Case implementation faces several challenges. Mozert and Sudzina [66] described that the initial step of forming subgroups no larger than six students is advantageous for CBL to allow for equal opportunity participation in peer instruction. In the example case, a group of six allows for each student to focus on one question or learning issue and negotiate integrated answers via group work. If students or instructors are unfamiliar with CBL, time to adjust may be necessary with a slow flow and depth of discussion at the beginning. This is particularly important if students do not find group work attractive. Ineffective group activation and peer instruction may be a key impediment in the success of case studies [29, 84]. Providing a set of basic rules may help in this respect. For instance, it is helpful to explain why working in groups is a valuable skill to develop. Instructors should make an effort to memorize students’ names and to present the case with enthusiasm to facilitate group activation [85]. To encourage understanding, students should be given clear tips on how to approach the case and how to construct their answers, stressing not to copy from books or articles but paraphrasing instead. Written communication deficiencies become apparent when students find difficulty in articulating and summarizing conclusions, which should be clear and brief [28]. The instructor should obtain beforehand expertise in the case and should facilitate focused discussion to avoid diverting from the main topic and to alleviate time constraints, particularly if directed CBL with a lecture is the chosen method. Using CBL in Large Classes Large-class environments are prevalent in undergraduate settings across disciplines. Although there is no consensus CBL in Biochemistry Education 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Biochemistry and Molecular Biology Education ETC case adaptation into the five CBL types discussed in this article Type Case implementation Lecture-based Session one: Instructor becomes a protagonist and enacts the case as the ER physician treating Avery. Case, test results, learning issues, and reasoning are all integrated into the story and described out loud by the physician in a monologue. Case is given as an example to complement a lecture on ETC. Instructor may ask students to connect case to lecture. Directed Session one: Case scenario is fully described: all data and references are provided. All learning issues are provided as directed questions. A lecture on ETC is given. Everyone gets the same information. Each group solves all questions outside class. Session two: Group answers are presented and the instructor facilitates a general discussion with the whole class to find answers and consensus. Interrupted Session one: Avery’s case is not entirely described and learning issues 1 and 2 are given as questions 1 and 2. Small in-class discussion or homework is done within groups to develop tentative solutions. Session two: More details on Avery’s condition are given; Derek’s case and learning issues 4, 5, and 6 are given to groups to further develop the topic. Information from both sessions is integrated and case concluded. Jigsaw Session one: Avery’s case is provided to six groups. Each group receives only one of the six learning issues. Each group solves their question so they become “experts” at it. All groups should have a clear view of the ETC basics. Requires previous knowledge because groups solving issues 4–6 handle integration of the ETC into physiology. Session two: New groups are formed with one “expert” from previous groups, so each member shares their answer to one question and the group integrates all answers into a general solution to the case. PBL Session one: A full or briefer version of Avery’s case is given out, depending on learning goals. No questions are provided to any group and there is no lecture on ETC. Subsequent sessions: Case development depends on students’ initiative and contributions. Each group develops their own questions. It might be used entirely without lectures. Requires clear definition of what is known, what is unknown and what needs to be known. Learning issues may go beyond ETC, that is, body building diets, supplements use in body builders, and self-medication. of what constitutes a large class, the term has been applied to classes over 50, 60, or 100 students [86, 87]. There are numerous reports on the use of case studies in large classes. The lecture-method resembles traditional lectures and can be used with large audiences but it promotes a passive-learning approach [53]. PBL can be implemented to large classes if appropriate physical and human resources are available to support case processing allowing close interaction between students and small-group facilitators. However, limitation of resources may prevent the adoption of the classic PBL as a new pedagogy [55]. Several workers have reported successful implementation of different small group models of CBL as well as modified versions of PBL in large science classes [88, 89]. Reddy [90] found an improved performance in standardised exams when implementing case studies with modified lectures that used Quick-Thinks (brief question periods Kulak and Newton imbedded in lectures). Nicholl and Lou [91] developed a modified PBL with lectures and found that there was positive acceptance from faculty and students and there were improved learning outcomes compared with classes using the classic PBL at a reduction of the cost. Klegeris and Hurren [92] chose a tutor-less PBL model to assist students in learning biochemical and physiological processes in a large class. They found that the model had a significant positive effect on student motivation to attend and participate in the course work and that it was superior to a traditional lecture format with regard to the understanding of course content and retention of information. They also demonstrated that student problem-solving skills were significantly improved, but commented that additional controlled studies were needed to determine how much the PBL exercises contributed to this improvement. This research question led the authors to a second study showing that there 467 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License TABLE 2 Proposed framework of a Directed CBL plus lecture with one case per week. FIG 6 was indeed a statistically significant improvement in generic problem solving skills [93]. Ochsendorf et al. [94] reported that small-group case studies implemented with weekly large class lectures generated greater student satisfaction than a lecture driven class. Their model used two tutors that interacted with students at the large class level. One tutor was a content expert and the other was a case processing facilitator. Qin et al. [95] used a similar model and found that the experience was positive for students and facilitators. Active learning has also been used in blended teaching models where students and instructors interact online and in-class. Potter and Overton [14] designed a chemistry course in the context of sport and used concept mapping tools, case studies, and web-based independent learning. The student’s response to the learning resources and presentation of material was positive. Davidson [96] incorporated web-based cases, images, videos, and formative assessment into a large class of first year undergraduates and reported that blended teaching was successful at increasing student’s acceptance of diverse instructional 468 methods noting that the benefits of active learning supported by online resources were dependent on the comfort that instructors had with online software. Prunuske et al. [97] followed an alternative strategy by designing online lectures that could be watched ahead of class time. This allowed for class time to be used for active learning activities. For successful implementation, instructors should address issues such as motivation to interact [98], socialization processes [99] and paths to moderate online presence and discussions [100]. Bridges et al. [101] found that Course Management Systems and Learning Management Systems assisted in the successful implementation of case studies and lectures. Students were presented with various online resources like lecture capture, discussions via SkyC peV and discussion boards. Howe and Schnabel [102] explained that case processing using face-to-face contact C , Desire2LearnV C , BlackboardV C , and webas well as WebCTV blogs can be beneficial if the blend suits the teaching/learning style of both teachers and students. Supporting resources that provide scaffolding for case processing can be transferrable to online platforms. The ETC directed case CBL in Biochemistry Education 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Biochemistry and Molecular Biology Education Creating Engaging Topics for Biochemistry Education Despite its intricate links to nutrition, the biochemistry found in most textbooks and teaching sessions describes pathways as a set of molecules and not in direct context to diet. Introducing nutritional elements in a CBL-based biochemistry course may allow increased student engagement with the material, enhancing its relevance to students’ lives and thereby promoting higher-order cognitive skills. Some evidence shows that this novel approach yields positive pedagogical outcomes, particularly in teaching macronutrient metabolism [7, 63, 103, 104]. Previous studies have described the benefits of linking human nutrition to metabolic biochemistry understanding in active learning settings that make material relatable to students’ lives. An early report using CBL with nutrition elements is found in Cornely [47], where most students had a positive reaction to use of this technique. Hermes-Lima et al. [105] found that student seminars on clinical applications like obesity, diabetes, and iron metabolism increased concept integration and application among medical and nutrition students. Similarly, Johnson et al. [106] noted that students using a combined PBL-lecture format were better at integrating biochemical concepts in an applied nutrition class. The topics included anorexia, energy requirements for a triathlete, vitamin D deficiency, and dietary implications of cystic fibrosis. Students also showed greater satisfaction with the course, a greater appreciation of the need to study and a better appreciation of nutrition as an integrated field. Davies [7] incorporated CBL as a supplement to lectures to integrate metabolic pathways and nutritional disorders and reported that this format yielded better scores than a lecture-based course. Feinman and Makowske [107] and Pogozelski et al. [103] designed cases on the effect of lowcarbohydrate diets and found an increased level of discussion and interest among students. Heidemann and Urquhart [104] designed a case based on the dietary components of energy drinks to review biochemical principles. The case was adapted to high school and undergraduate classrooms with positive reception by instructors. Shaw et al. [108] designed a case in sports nutrition where students analysed an athlete’s daily meal intake and reflected upon protein requirements and suitability of nutritional supplements. Macaulay et al. [109] introduced dietetic cases into biochemical laboratory practice and reported Kulak and Newton that a majority of students found the experience intellectually stimulating. Other examples include Passos et al. [64] who taught integrative metabolism to medical students by using the students themselves as subjects in a real-life experiment. In this study, student-subjects were fed one of two diets, one hyperglicidic based on pasta, and one hyperlipidic based on pizza. Blood test results were then used to generate a PBL to elucidate metabolic events. The authors also aligned the final exam with a PBL format so students were presented with a problem to be solved in an open– book setting. Results showed an increased tendency by students to discuss data in terms of metabolic interpretations rather than simply stating memorized pathways. Since biochemistry usually includes a wide variety of undergraduate majors, nutritional elements may not be the only strategy to engage students’ attention. Other authors teaching human biochemistry have designed cases based on physical activity or non-nutritional clinical correlations. For instance, cases dealing with alcoholism in young adults to teach body fluid homeostasis [82], the effects of thalidomide to introduce the concept of chiral molecules [81], the effect of environmental toxins like rotenone poisoning to teach ETC [83], or the use of the fat substitute Olestra to discuss lipid structure [74]. Millard [73] designed a series of cases based on popular television medical dramas where characters were patients at the ER suffering from drug overuse; here, the cases were aimed at teaching enzyme inhibition and lipid metabolism. Fardilha et al. [18] introduced a case with the screening of a feature film on Lorenzo’s oil. This was used to trigger case engagement on inborn errors of metabolism. The authors concluded that using a combined PBL-seminar-laboratory approach surpassed the traditional lecture-based method in facilitating students’ ability to understand fatty acid metabolism. CBL has also been adapted in pre-clinical veterinary education. Schoeman et al. [110] reported that student’s ability to connect basic science to enhance clinical literacy increased when cases on horses and dogs were used. In addition, Ertmer et al. [111] found that CBL facilitated student’s ability to apply biochemical principles to pre-clinical veterinary practice. Primary source articles can also be used as references to write cases. For instance, Kim et al. [112] provides a study using lactic bacteria found in Kimchi that suppress the growth of pathogens by affecting pH values. This paper can be a starting point to develop a case on food science and biochemistry. Several case databases with miscellaneous topics are available from educational institutions such as the University of Buffalo and the University of Delaware [74]. These databases include a wide variety of science topics. However, the narratives can serve as departing points to design new cases to suit biochemistry’s learning goals. For instance, there is a case loosely based on the 1982 Chicago Tylenol deaths caused by Tylenol capsules contaminated with cyanide and its effects on the ETC [83]. Using the 469 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License framework used in this article can be implemented in large classes and the access to web-based resources as described above can assist students during case processing. For instance, the learning issues or questions can be provided to students in-class for initial discussion and their group responses can be posted online. A general discussion board can be made available to small groups to prevent scheduling issues outside class time and lessen the dependency on meeting room requirements. published cases available from these databases is a valid option; however, careful consideration of learning outcomes and type of CBL used should be observed because these cases vary in the educational level being targeted. Both databases also provide answer keys that can be accessed by registered instructors. It is strongly encouraged that instructors interested in active learning seek interaction with the CBL community via online gateways and journals. The National Science Teachers Association in their Journal of College Science Teaching publishes cases in every issue on diverse science topics. The case design models in these cases differ from the one suggested in sections above. Each author explains the teaching rationale behind their case along with objectives and an implementation format. For instance, Diener [113] wrote a case to introduce digestion and metabolism. The information was presented in the form of a social network’s online dialogue between two friends in lieu of a formal narrative. The protagonists were young adults discussing weight loss, which is an engaging topic for this age group. Other resources include Barnes et al. [114, 115], which describes the pedagogical background of case writing and implementation as developed at Harvard Business School. The University of Wisconsin has taken case processing further by organizing case competitions among undergraduate students. Another of their projects is called Case It! This is a collaborative CBL support project to teach molecular biology [116]. Their case repertoire may be a starting point for biochemistry cases as it includes inborn errors of metabolism. Conclusion This article presents a review of CBL and the potential benefits of its use in biochemistry education. It also provides concise and clear steps to help alleviate some of the challenges in case design. In turn, its contribution may facilitate implementing cases as pedagogical aids and as research instruments. Furthermore, the authors hope to spark a dialogue on case preparation standards to be used in science teaching. This is important because most authors reporting on CBL use do not disclose how their own cases were developed. Thistlethwaite et al. [39] raise the point that there is no research examining the process by which cases are prepared and presented. Additionally, it is possible that a lack of detailed guidance and consensus on case preparation is preventing instructors from considering CBL as a teaching aid. Current evidence on CBL comes from diverse research questions, as well as varied sample sizes, student demographics and course level. For the most part, published results do not disclose the level of difficulty of the implemented cases. These variations make comparisons and generation of new evidence difficult. So far, evidence from systematic reviews and meta-analyses on CBL indicate that 470 student motivation and satisfaction with these pedagogies is positive. There are strong indicators that: (a) students enjoy CBL, (b) students perceive CBL as an enhancement to their learning, and (c) teachers enjoy teaching with CBL because it engages students. This means that most reports focus on outcomes largely dependent on overall experience indicators (i.e. students found the experience enjoyable). However, reported experiences are often based on anecdotes or student’s interviews. Although such feedback is very informative, there is a need to corroborate such findings with statistically sound research instruments such as validated student and teacher questionnaires [117]. The potential benefits of CBL seem to be many; however, its successful implementation in undergraduate science education and its effects on learning approaches remains largely unquantified. The interest in moving away from lecture-dominated curricula into active learning or hybrid paradigms has generated numerous strategies and conceptual frameworks available across disciplines. At present, there is no consensus that a single teaching method is superior to others. Different methods bring in advantages and disadvantages that have not yet been measured in a manner that allows for unbiased comparison. Lundeberg and Yadav [117] pointed out that measurement is not as precise in pedagogical research as it is in the sciences. Quantitative measurement may limit methodology and research questions, so evidence comparison is generated slowly. Overall, this context creates several difficulties. First, CBL may facilitate a direct and active cognitive experience in the learner but its long-term effects are yet to be measured. Second, there is also a lack of comprehensive research on the effectiveness of CBL over other active learning techniques or traditional lectures. Third, there is an absence of evidence regarding the degree of success of CBL at teaching content. These difficulties may hinder the willingness of instructors to embrace change and to introduce CBL in their courses. This change implies a new cognitive pattern versus the one promoted by traditional lectures: a shift from relying on memorization alone to embracing the effort to analyze, synthesize, and evaluate scientific content. There is a lack of consensus in the literature on the definitions of CBL and PBL. The present review discusses CBL and PBL as part of a spectrum following ideas from Heinrichs [40] and Eberlein et al. [41] based on the level of student engagement. A clear effort was made to integrate the cognitive advantages and the good case features compiled from currently published evidence. More specifically, the case design discussed and the proposed directed CBL framework, aim at providing a cognitive platform for integration and evaluation of biochemical concepts encountered in lectures and textbooks. By having a real-life context where students are challenged to consider perturbations of biochemical pathways as a possible cause CBL in Biochemistry Education 15393429, 2014, 6, Downloaded from https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.20823 by SEA ORCHID (Thailand), Wiley Online Library on [07/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Biochemistry and Molecular Biology Education References [1] Herreid, C.F. (2004) Can case studies be used to teach critical thinking? J. Coll. Sci. Teach. 33, 12–14. [2] Darabi, A., Hemphill, J., Nelson, D. W., Boulware, W., and Liang X. (2010) Mental model progression in learning the electron transport chain: Effects of instructional strategies and cognitive flexibility. Adv. Health Sci. Educ. 15, 479–489. €ljo € , R. 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