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Purpose@#The mean platelet volume (MPV) is regarded as a marker for thrombosis, atherosclerosis, and inflammation in various vascular diseases. However, it still remains unclear whether plasma MPV is associated with cerebral white matter hyperintensities (WMH) and cerebral microvascular pathology in the elderly population. @*Materials and Methods@#We examined whether MPV level is associated with the presence of cerebral WMH on brain magnetic resonance imaging from 870 non-stroke outpatient subjects. The subjects were divided into three groups according to the consecutive level of MPV (low T1, middle T2, and high T3 MPV tertile groups). To determine the association of MPV levels with the WMH, logistic regression and receiver operating characteristic curve analyses were conducted. @*Results@#Subjects with higher MPV level were older and more likely to have hypertension, diabetes mellitus, and low renal function. Cerebral WMH were more prevalent in subjects with higher MPV level. After adjusting for confounding factors, moderate to severe cerebral WMH were significantly associated with high MPV tertile level. This association remained significant after adjusting for other cerebral vascular pathologies. T2 [odds ratio (OR): 1.49, 95% confidence interval (CI): 1.03–2.15] and T3 MPV tertile groups (OR: 1.51, 95%CI: 1.04–2.20) had more cerebral WMH lesions compared to T1 MPV tertile group. In addition, the subjects with higher Fazekas scores showed higher MPV level (p=0.020). @*Conclusion@#We found that high MPV level is independently associated with cerebral WMH. This result suggests that platelet activation plays a role in the development of cerebral WMH.
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Tumor microenvironment (TME) is composed of endothelial cells, pericytes, immune cells, cancer-associated fibroblasts (CAFs), cancer stem cells (CSCs), extracellular matrix (ECM) and other components of the complex biological environment. TME interacts with the tumor cells through a large amount of signaling pathways, participates in the process of tumor progression, invasion, and metastasis. Hence, TME has become a potential therapeutic target for cancer treatment, exhibiting excellent therapeutic potential and research value in the field of cancer treatment. Currently, the novel nanotechnology has been widely applied in anticancer therapy, and nanotechnology-mediated drug delivery system is being explored to apply in TME modulation to inhibit tumor progression. Nanotechnology-mediated drug delivery has many advantages over traditional therapeutic modalities, including longer circulation times, improved bioavailability, and reduced toxicity. This review summarized the research of targeted nano-drug delivery based on TME regulation, including regulation strategies based on CSCs, CAFs, immune cells, ECM, tumor vascularization, exosomes, and microbiota. In addition, we summarized the advantages, opportunities, and challenges of TME regulation strategy compared with traditional treatment strategy, which provides a reference for the application of nano-drug delivery system based on TME regulation strategy in tumor precision therapy.
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Purpose@#Team-based learning in medical education facilitates the formation of interpersonal relationships, enhances academic achievement, and establishes future clinical connections. Despite medical schools’ distinct educational environments and curricula, research investigating students’ learning and behavioral characteristics within this context remains limited. This study aimed to investigate the specific characteristics of interpersonal relationship formation among freshmen medical students in team-based learning activities. @*Methods@#Focus group interviews were conducted with 11 students who participated in a team-based class held during the first semester of the premedical year. @*Results@#Medical students passively expressed their thoughts and feelings, such as active sympathy for the team’s opinions and self-censorship of SNS (social networking service) conversations. When performing team activities, students were excessively conscious of others and focused on evenly dividing their work, minimizing their opinions, and fulfilling their share to prevent potential interpersonal conflicts. Interpersonal activities were only superficial, as students intentionally maintained a certain distance from team members or used team activities as an opportunity to accumulate relational capital. @*Conclusion@#The results of this study are expected to provide a useful basis for designing and conducting team activity classes to enhance interpersonal relationship formation.
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Increasing importance of vaccination during coronavirus disease 2019 (COVID-19) pandemic, several vaccines were developed. Messenger RNA (mRNA) vaccines including BNT162b2 (Pfizer, New York, NY, USA; BioNTech, Mainz, Germany), mRNA-1273 (Moderna, Cambridge, MA, USA) have been disclosed side effects such as thrombocytopenia, myocarditis and headache in general. In addition, adverse effects due to autoimmune responses induced by spike glycoproteins of mRNA vaccines are rarely reported such as the Guillain-Barre syndrome, autoimmune encephalitis and so on. Herein, we report a rare case of encephalitis with new-onset refractory status epilepticus after BNT162b2 mRNA COVID-19 vaccination improved with immune therapy.
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The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother.Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.
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Objective:To evaluate the efficacy and safety of of rivaroxaban for different doses in the treatment of isolated distal deep vein thrombosis.Methods:The clinical data of 853 patients of isolated distal deep vein thrombosis attending Nanjing Drum Tower Hospital from Jan 2018 to Dec 2020 was retrospectively analyzed.Results:Thrombotic recurrence rate increased with increasing follow-up in the standard and low dose groups, and it was significantly lower in the standard dose group than in the low dose group (HR=0.44, 95% CI: 0.25-0.78, P=0.005) with most thrombosis occurring within the first year of follow-up. There was no statistical difference between the two groups in terms of major bleeding events (HR=1.70,95%CI 0.56-5.14, P=0.530) and the incidence of clinically relevant non-major bleeding events was significantly higher in the standard dose group than in the low dose group (HR=2.36, 95%CI 1.26-4.44, P=0.020). Subgroup analysis on anticoagulation duration found when anticoagulation duration was longer than 1.5 months, the risk of thrombosis was lower in the standard dose group than the low dose group (1.5-3 months:HR=0.11, 95%CI 0.01-0.87, >3 months: HR=0.19, 95%CI 0.04-0.95), there was an interaction between anticoagulation duration and dose ( P=0.007). Conclusions:Based on the risk of thrombosis recurrence and bleeding events, the standard dose of rivaroxaban (20 mg qd) is recommended for patients with isolated distal deep vein thrombosis, and the anticoagulant duration should be maintained for 1.5 months or more.
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Primary adrenal lymphoma (PAL) is a rare extranodular lymphoma. It is subject to misdiagnosis due to atypical clinical and imaging features. Histopathology is required to establish the diagnosis. Patients often present to the Endocrinology Department upon revelation of adrenal incidentalomas by imaging. PAL is often accompanied by invasion of other tissues and organs, with a high mortality rate and a poor prognosis. In this paper, the clinical features of a patient with primary adrenal lymphoma and intracranial invasion were summarized, and the pathogenesis, clinical manifestations, diagnosis and treatment of this disease were reviewed.
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BACKGROUND/OBJECTIVES@#The diversity of meal provision places has increased in recent years and sodium intake can vary depending on where meals are eaten, particularly in large cities. In this study, an analysis of the recent trends in sodium intake was performed and a comparison of sodium intake level according to meal provision place among citizens of Seoul was performed. @*SUBJECTS/METHODS@#Data from a 24-h recall dietary intake survey from the 2010–2019 Korea National Health and Nutrition Examination Survey (KNHANES) were used in order to determine the trends in sodium intake among citizens of Seoul, aged 3–74 years old. (n = 11,811). The trend of daily sodium intake was presented in absolute amount and proportion compared to the chronic disease risk reduction intake (CDRR) for each selected characteristic. A comparison of sodium intake level according to meal provision place by sex and age groups as a total amount per meal (mg), density per meal (mg/1,000 kcal), and proportion of the daily sodium intake was performed using the 2016–2019 KNHANES. @*RESULTS@#Sodium intake levels showed a downward trend from 2010–2019. The highest level of sodium intake was observed for subjects aged 30–49, and the level for males aged 30–49 was 202.8% higher than the CDRR. Results of the analysis of sodium intake per meal according to meal provision place showed that the highest sodium intake was in the order of restaurant meal (RM) > institutional foodservice (IF) > home meal (HM) > convenience food (CF). A higher sodium density (mg/1,000 kcal) was observed for IF compared with RM in most adults. Adults aged over 50 years old consumed more than half of the daily sodium in HM. @*CONCLUSION@#Significant variation in the level of sodium intake was observed according to sex and age groups, therefore, different approaches and nutrition policies based on meal provision place are needed.
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Aim To systematically evaluate the heat-clearing mechanism of Arnebiae Radix on two mouse models of blood heat syndrome. Methods The drug-forming molecules were screened by comprehensive network pharmacology methods, and the correlation between drug efficacy and related factors and targets was evaluated on the mouse model of short effect blood heat syndrome constructed by 2, 4-dinitrophenol (DNP) and the mouse model of severe blood heat syndrome (heat stroke) constructed by high temperature combined with lipopolysaccharide (LPS). Results A total of 277 shikonin related targets were collected, mainly involving biological processes such as inflammatory reaction, oxidation reaction and coagulation reaction. Shikonin, a representative compound, significantly improved the main syndromes of mice with blood heat syndrome, reduced the levels of inflammatory factors IL-1β, IL-6 and TNF-α in the two models, and reduced the contents of oxidative damage indexes LPO and MDA, and the two showed correlation. The main mechanism was to inhibit the expression of NF-ΚB p65 and up-regulate the expression of Nrf2. Conclusions Shikonin plays a pharmacological role in the prevention and treatment of blood heat syndrome by inhibiting inflammation and improving antioxidant capacity, which provides a pharmacological basis for shikonin in the prevention and treatment of blood heat syndrome.
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Duloxetine and thioctic acid (TA) are standard drugs for treating diabetic neuropathy, a primary complication associated with diabetes. In this study, ultra performance liquid chromatography coupled with tandem mass spectrometry methods was successfully developed and validated for quantifying duloxetine and TA in biological samples. The protein precipitation method was used to extract duloxetine, TA and their internal standards from beagle dog plasma. A Hypersil Gold C18 column (150 × 2.1 mm, 1.9 μm) was used for the experiment. Isocratic elution with 0.1% formic acid in acetonitrile (A) and 0.1% formic acid (B) was used for duloxetine, whereas a gradient elution with 0.03% acetic acid (A) and acetonitrile (B) was used for TA. The validated parameters included linearity, sensitivity, accuracy, precision, selectivity, matrix effect, stability, and recovery under different conditions. The linear ranges of the calibration curves for duloxetine and TA were 5–800 ng/mL and 5–1,000 ng/mL, respectively. An intra- and inter-run precision of ± 15% can be observed in all quality control samples. These methods were successfully used for pharmacokinetics (PKs) studies in beagle dogs to compare PK differences in a fixed-dose combination including duloxetine and TA and co-administration of the 2 drugs.
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Background and Objectives@#Currently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required. @*Methods@#and Results: In our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons. @*Conclusions@#Our study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.
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Purpose@#First-year students can form a preconception based on life experiences before entering college and identifying learners’ existing characteristics can be useful foundation data for curriculum development. This study examines what preconceptions freshman students had about medicine before entering medical school. @*Methods@#A total of 110 first-year students were asked about what preconceptions they had about “medicine”. A total of 1,124 data were used in the content analysis method. @*Results@#The results were extracted into 5, and 12 twelve categories. On the theme of “scientific discipline”, the knowledge students had about general health was based on scant expertise and little evidence. Students perceived medicine as Western and scientific, considering Korean traditional medicine as unscientific. Students believed that “medical practice” should be a “disease treatment” and “patient-centered” approach rather than a “social responsibility”. In “the role of the doctor”, students were concerned about the doctor's being financially stable on the positive side, and about the high-intensity workload on the negative side. In “medical education”, students believed that studying medicine would be “hard and difficult” because of the “importance of memorizing” and “extensive study load”. In “specialty stereotype”, students had biases that were mostly concentrated on “psychiatry” and “surgery” @*Conclusion@#Perception of “medicine” has been revealed to a varied range of themes, but some have been inaccurate or unrealistic. These prejudices and groundless beliefs have a gap with the learning outcomes that students should achieve in the curriculum, and these preconceptions seem to have been influenced by South Korea’s unique cultural context.
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Purpose@#This study examined how students’ academic performance changed after undergoing a transition to online learning during the coronavirus disease 2019 (COVID-19) pandemic, based on the test results of 16 integrated courses conducted in 3 semesters at Hanyang University College of Medicine in Korea. @*Methods@#For the 16 required courses that formed an integrated system-based curriculum running for 3 semesters, the major examinations’ raw scores were collected for each student. Percent-correct scores were used in the subsequent analysis. We used the t-test to compare grades between 2019 and 2020, and the Cohen D was calculated as a measure of effect size. The correlation of scores between courses was calculated using Pearson correlation coefficients. @*Results@#There was a significant decrease in scores in 2020 for 10 courses (62.5%). While most of the integrated system-based curriculum test scores showed strong correlations, with coefficients of 0.6 or higher in both 2019 and 2020, the correlation coefficients were generally higher in 2020. When students were divided into low, middle, and high achievement groups, low-achieving students consistently showed declining test scores in all 3 semesters. @*Conclusion@#Our findings suggest that the transition to online classes due to COVID-19 has led to an overall decline in academic performance. This overall decline, which may occur when the curriculum is centered on recorded lectures, needs to be addressed. Further, medical schools need to consider establishing a support system for the academic development of low-achieving students.
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The emergence of the disease entity of glucocorticoid-responsive systemic immunoglobulin G4 (IgG4)-related pancreatobiliary disease has generated substantial attention among the international gastroenterology society. IgG4-related pancreatobiliary disease includes type 1 autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC). The typical manifestations of IgG4-related pancreatobiliary disease are cholestatic liver dysfunction, obstructive jaundice, and weight loss, although it may present with no clinical symptoms. Since it mimics tumors on imaging, AIP/IgG4-SC may often be misdiagnosed as pancreatic or biliary cancer. The endoscopic armamentarium for the diagnosis of IgG4-related pancreatobiliary disease includes endoscopic ultrasonography, intraductal ultrasonography, endoscopic retrograde cholangiopancreatography, and cholangioscopy. The role of endoscopic tissue acquisition is two-fold in the diagnosis of IgG4-related pancreatobiliary disease: exclusion of cancer and procurement of histopathological proof for diagnosis of AIP/IgG4-SC, which can also be achieved by adding the immunohistochemistry for IgG4. Our review article addresses the role of various endoscopic examinations in diagnosing IgG4-related pancreatobiliary disease, focusing on the differentiation of this condition from pancreatobiliary malingnancies.
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A 70-year-old female was referred for brown-to-gray colored papules and nodules on her lower legs. She had been diagnosed with diffuse large B-cell lymphoma (DLBCL) in her stomach, and myelodysplastic syndrome (MDS) by bone marrow biopsy. Three years after complete remission of DLBCL, she experienced DLBCL recurrence in her small bowel and was hospitalized. MDS had been stationary, but during the treatment of DLBCL, her laboratory findings suggested signs of leukemia. Bone marrow biopsy was done, and acute monoblastic leukemia (AMoL) was diagnosed. After 1 cycle of chemotherapy for AMoL, skin lesions developed, and her skin biopsy showed cutaneous T-cell lymphoma (CTCL). Terminal deoxynucleotidyl transferase staining and CD123 staining were negative, and bone marrow re-biopsy conducted after the skin lesion developed still showed monoblastic proliferation. Whether the CTCL represented with an AMoL lineage switch could not be completely proved due to the absence of molecular or clonal marker evaluations, but the possibility of coexistence of three different malignancies was higher. During treatment, a neutropenic fever developed, and the patient died due to sepsis. We herein report a rare case of CTCL accompanied by AmoL and DLBCL.
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Wolf’s isotopic response refers to the occurrence of a novel skin disease at the site of a preceding treated or untreated skin disease. Although the most common preceding skin disease was found to be herpes zoster (HZ), HZ-related dermatological phenomena are not well known in the literature. We report a case of HZ granulomatous dermatitis in a 77-year-old female with a previous history of hypertension, diabetes mellitus, chronic kidney disease, and HZ. She presented with a 3-month history of a pruritic skin lesion on her right thigh. The location of the lesion was consistent with a previous HZ site. Histopathological examination revealed lympho-histiocytic infiltration in the superficial dermis, forming a granulomatous structure. Based on clinical and histopathological findings, we made a diagnosis of granulomatous dermatitis at a previous HZ site. We assumed that the lesion arose from an isotopic response of Wolf. The patient was treated with topical steroids for 3 months and showed clearance of the lesion and symptom. We suggest that treatment should be based on the individual disease, which in our case was topical steroid.
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Purpose@#This study aims to analyze pre-clerkship medical students’ learning strategies and perceptions in online classes during the coronavirus disease 2019 pandemic. @*Methods@#To develop the survey items, 20 pre-clerkship students were interviewed about their learning experiences in the first semester of 2020. A total of 425 pre-clerkship students have participated in the survey, which comprised four parts (general experience, learning strategies, important features, and overall satisfaction). @*Results@#Before classes began, students generally had “neutral expectations” about online classes (2.90 out of 5). At the end of the semester, overall satisfaction with the curriculum was moderate (3.04 out of 5). Premedical students reported lower scores in “daily study hours” and “regular lifestyle” and higher scores in “experience of playing recorded lectures solely for an attendance check” (p<0.001). In addition, first-year premedical students not only showed significantly lower utilization of learning strategies compared to other grades (p<0.001). @*Conclusion@#Although pre-clerkship students mostly shared similar perceptions and behaviors in their learning regardless of grade level, some characteristics were either more prominent in premedical students on the whole or limited to first-year premedical students.
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Friction melanosis (FM) is an acquired pigmented disease that is caused by recurrent mechanical stress. There is no previous report explaining the presence of tiny brown-colored particles confined to the corneal layer. We describe a case of a rare form of FM of the finger that showed a relatively transient clinical course. A 17-year-old Korean female presented with a 5-month history of an asymptomatic localized hyperpigmented patch on the tip of the right index finger. The dermoscopic examination revealed homogenous globular pattern, which favored pigmentation over hemorrhage. Histopathologically, hyperkeratosis and acanthosis with lymphohistiocytic infiltration of the superficial dermis were noted on hematoxylin and eosin staining; however, there was neither a definite increase in melanophages in the upper dermis nor melanocytic proliferation in the basal layer. Per high-power field, multiple brown-colored tiny particles were scattered in the corneal layer. The particles were not dyed by Fontana-Masson stain, iron stain, and S-100. We questioned the patient about the presence of irritation and found that she had bought new shoes at the time of the onset. She was habituated to placing her fingers in her shoes while wearing them because they were slightly tight. The lesion disappeared spontaneously a week after the cause of friction was eliminated.Altogether, we encountered a rare form of FM that occurred in a rare location with a transient clinical course. Further cases on pigmentation restricted to finger tips might reveal the origin of the particles.
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Objectives@#This study surveyed the quality of psychotherapy training and psychotherapy competencies during residency in Korea. @*Methods@#A questionnaire developed by The Committee of Residency Training of the Korean Neuropsychiatric Association was completed by fourth-year residents of Korean psychiatry (n=120). The questionnaire examined their demographic characteristics, their experience of clinical psychotherapy training, their degree of satisfaction in the quality of psychotherapy training, and self-rated competence regarding the six types of psychotherapies, including supportive psychotherapy, cognitive behavioral therapy, interpersonal psychotherapy, psychoanalytic psychotherapy, group psychotherapy, and family psychotherapy. @*Results@#The degree of satisfaction of the residents with the psychotherapy training was diverse among the types of psychotherapy and contents of training. Across all types of psychotherapies, the satisfaction levels of the quantity and quality of supervision education were low, except for psychoanalytic psychotherapy. Overall, more than 70% of residents were not satisfied with the theoretical education, clinical practice, and supervision education in three types of psychotherapies, including interpersonal psychotherapy, group psychotherapy, and family psychotherapy. A positive correlation was found between the degree of satisfaction with the quality of training experience and self-rated competence of psychotherapy. Specifically, the self-rated competence of psychotherapy was more highly correlated with the experience of clinical cases and supervision than theoretical education @*Conclusion@#This study showed the quantitative and qualitative status of psychotherapy training in Korean psychiatry residency programs, and the satisfaction level of psychotherapy education was low except for psychoanalytic psychotherapy. There is a strong need for the improvement of psychotherapy training programs in Korea.
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Purpose@#This study aims to analyze pre-clerkship medical students’ learning strategies and perceptions in online classes during the coronavirus disease 2019 pandemic. @*Methods@#To develop the survey items, 20 pre-clerkship students were interviewed about their learning experiences in the first semester of 2020. A total of 425 pre-clerkship students have participated in the survey, which comprised four parts (general experience, learning strategies, important features, and overall satisfaction). @*Results@#Before classes began, students generally had “neutral expectations” about online classes (2.90 out of 5). At the end of the semester, overall satisfaction with the curriculum was moderate (3.04 out of 5). Premedical students reported lower scores in “daily study hours” and “regular lifestyle” and higher scores in “experience of playing recorded lectures solely for an attendance check” (p<0.001). In addition, first-year premedical students not only showed significantly lower utilization of learning strategies compared to other grades (p<0.001). @*Conclusion@#Although pre-clerkship students mostly shared similar perceptions and behaviors in their learning regardless of grade level, some characteristics were either more prominent in premedical students on the whole or limited to first-year premedical students.