NATIONAL BOARD OF MEDICAL
EXAMINERS®COMPREHENSIVE BASIC SCIENCE
EXAMINATION (CBSE) & USMLE® STEP 1
EXAMINATION INFORMATION
Total Questions: 200 Multiple-Choice Items
•
Structure: 4 Blocks (50 Questions per Block)
•
• Time Allowed: 4 Hours (60 Minutes per Block)
• Content Blueprint: USMLE Step 1 Content Outline & NBME Item-Writing Manual
GENERAL INSTRUCTIONS
1. This examination consists of clinical vignettes with a single best answer.
2. Choose the one option that most correctly answers the question or completes the
statement.
3. There is no negative marking for incorrect answers; ensure every question is attempted.
4. It is recommended to complete each block sequentially without looking at the answer
keys.
Notice: This document is an original practice simulation designed for educational review and self -assessment
purposes. It is not affiliated with, endorsed by, or copied from the official NBME® or USMLE® organizations .
, 2026/2027 | NEWLY RELEASED
Verified Questions & Answers with Expert Rationales
Guaranteed Pass | Graded A+ | 100% Correct
Q1. A 45-year-old man presents with progressive muscle weakness over the past 6 months. He
reports difficulty climbing stairs and rising from a seated position. Physical examination reveals
proximal muscle weakness and a heliotrope rash on his eyelids. Laboratory studies show
elevated serum creatine kinase. Muscle biopsy reveals perifascicular atrophy and perivascular
inflammatory infiltrates. Which of the following autoantibodies is most likely present in this
patient?
A. Anti-dsDNA
B. Anti-Smith
C. Anti-Jo-1
D. Anti-centromere
Correct Answer: C
Rationale: Correct because the clinical presentation of proximal muscle weakness, heliotrope
rash, and perifascicular atrophy on biopsy is pathognomonic for dermatomyositis.
Pathophysiology of this condition involves complement-mediated microangiopathy causing
ischemic damage to muscle fibers, with anti-Jo-1 being the most common myositis-specific
autoantibody associated with antisynthetase syndrome. The clinical presentation is consistent
with inflammatory myopathy rather than systemic lupus erythematosus (anti-dsDNA, anti-Smith)
or limited scleroderma (anti-centromere).
Q2. A 28-year-old woman presents to the emergency department with severe abdominal pain and
vomiting. She has a history of recurrent episodes of abdominal pain since childhood. Her father
and brother have similar symptoms. Laboratory studies reveal elevated serum lactate and uric
acid. A fasting plasma glucose test shows hypoglycemia. Which of the following enzyme
deficiencies is most likely responsible for this patient's condition?
A. Glucose-6-phosphatase
B. Glycogen phosphorylase
C. Debranching enzyme
D. Branching enzyme
Correct Answer: A
,Rationale: Correct because the combination of fasting hypoglycemia, lactic acidosis,
hyperuricemia, and hepatomegaly in a patient with autosomal recessive inheritance pattern is
diagnostic of von Gierke disease (glycogen storage disease type I). Pathophysiology of this
condition involves defective gluconeogenesis and glycogenolysis due to inability to convert
glucose-6-phosphate to glucose, leading to accumulation of glucose-6-phosphate that shunts into
glycolysis and pentose phosphate pathway. The clinical presentation is consistent with glucose-6-
phosphatase deficiency rather than McArdle disease (glycogen phosphorylase), Cori disease
(debranching enzyme), or Andersen disease (branching enzyme).
Q3. A 6-year-old boy is brought to the pediatrician by his mother due to developmental delay and
seizures. Physical examination reveals a musty odor to the urine and skin, hypopigmentation of
the skin and hair, and microcephaly. Plasma amino acid analysis shows markedly elevated
phenylalanine. Which of the following is the most appropriate dietary management for this
patient?
A. High-protein diet with phenylalanine supplementation
B. Phenylalanine-restricted diet with tyrosine supplementation
C. Low-carbohydrate, high-fat ketogenic diet
D. Gluten-free, casein-free diet
Correct Answer: B
Rationale: Correct because the clinical triad of developmental delay, seizures, and
hypopigmentation with elevated plasma phenylalanine is diagnostic of phenylketonuria (PKU).
Pathophysiology of this condition involves deficiency of phenylalanine hydroxylase, preventing
conversion of phenylalanine to tyrosine and leading to accumulation of toxic metabolites that
impair myelination. The clinical presentation is consistent with classic PKU, which requires
lifelong phenylalanine restriction with tyrosine supplementation to prevent irreversible
neurologic damage.
Q4. A 55-year-old man with a 30-pack-year smoking history presents with hemoptysis, weight
loss, and a new cough. Chest CT reveals a 4 cm spiculated mass in the right upper lobe with
mediastinal lymphadenopathy. Biopsy shows nests of polygonal cells with intercellular bridges
and keratin pearls. Which of the following molecular alterations is most commonly associated
with this histologic subtype?
A. EGFR mutation
B. ALK rearrangement
C. KRAS mutation
D. ROS1 rearrangement
, Correct Answer: C
Rationale: Correct because the histologic features of intercellular bridges and keratin pearls are
diagnostic of squamous cell carcinoma of the lung. Pathophysiology of this condition involves
smoking-related carcinogenesis with frequent alterations in TP53 and KRAS; KRAS mutations
are most common in smoking-associated lung cancers, particularly squamous cell carcinoma and
adenocarcinoma in smokers. The clinical presentation is consistent with centrally located lung
cancer in a heavy smoker, where EGFR and ALK are more characteristic of never-smokers with
adenocarcinoma.
Q5. A 32-year-old woman presents with fatigue, joint pain in her hands and feet, and a malar
rash. Laboratory studies reveal positive ANA, anti-dsDNA antibodies, and low complement
levels. Renal biopsy shows "wire loop" lesions on light microscopy and subendothelial immune
complex deposits on electron microscopy. Which of the following is the most likely diagnosis?
A. Membranous nephropathy
B. Minimal change disease
C. Diffuse proliferative glomerulonephritis
D. Focal segmental glomerulosclerosis
Correct Answer: C
Rationale: Correct because the combination of systemic lupus erythematosus serologies with
wire loop lesions and subendothelial deposits is diagnostic of diffuse proliferative
glomerulonephritis (class IV lupus nephritis). Pathophysiology of this condition involves
immune complex deposition in the subendothelial space activating complement and recruiting
inflammatory cells, leading to proliferative changes and wire loop appearance from thickened
capillary walls. The clinical presentation is consistent with the most aggressive form of lupus
nephritis that requires immunosuppressive therapy.
Q6. A 65-year-old man presents with crushing substernal chest pain radiating to his left arm.
ECG shows ST-segment elevation in leads V1–V4. Emergency cardiac catheterization reveals
100% occlusion of the left anterior descending artery. Which of the following biochemical
markers will rise first following myocardial infarction?
A. Creatine kinase-MB
B. Troponin I
C. Myoglobin
D. LDH
Correct Answer: C
EXAMINERS®COMPREHENSIVE BASIC SCIENCE
EXAMINATION (CBSE) & USMLE® STEP 1
EXAMINATION INFORMATION
Total Questions: 200 Multiple-Choice Items
•
Structure: 4 Blocks (50 Questions per Block)
•
• Time Allowed: 4 Hours (60 Minutes per Block)
• Content Blueprint: USMLE Step 1 Content Outline & NBME Item-Writing Manual
GENERAL INSTRUCTIONS
1. This examination consists of clinical vignettes with a single best answer.
2. Choose the one option that most correctly answers the question or completes the
statement.
3. There is no negative marking for incorrect answers; ensure every question is attempted.
4. It is recommended to complete each block sequentially without looking at the answer
keys.
Notice: This document is an original practice simulation designed for educational review and self -assessment
purposes. It is not affiliated with, endorsed by, or copied from the official NBME® or USMLE® organizations .
, 2026/2027 | NEWLY RELEASED
Verified Questions & Answers with Expert Rationales
Guaranteed Pass | Graded A+ | 100% Correct
Q1. A 45-year-old man presents with progressive muscle weakness over the past 6 months. He
reports difficulty climbing stairs and rising from a seated position. Physical examination reveals
proximal muscle weakness and a heliotrope rash on his eyelids. Laboratory studies show
elevated serum creatine kinase. Muscle biopsy reveals perifascicular atrophy and perivascular
inflammatory infiltrates. Which of the following autoantibodies is most likely present in this
patient?
A. Anti-dsDNA
B. Anti-Smith
C. Anti-Jo-1
D. Anti-centromere
Correct Answer: C
Rationale: Correct because the clinical presentation of proximal muscle weakness, heliotrope
rash, and perifascicular atrophy on biopsy is pathognomonic for dermatomyositis.
Pathophysiology of this condition involves complement-mediated microangiopathy causing
ischemic damage to muscle fibers, with anti-Jo-1 being the most common myositis-specific
autoantibody associated with antisynthetase syndrome. The clinical presentation is consistent
with inflammatory myopathy rather than systemic lupus erythematosus (anti-dsDNA, anti-Smith)
or limited scleroderma (anti-centromere).
Q2. A 28-year-old woman presents to the emergency department with severe abdominal pain and
vomiting. She has a history of recurrent episodes of abdominal pain since childhood. Her father
and brother have similar symptoms. Laboratory studies reveal elevated serum lactate and uric
acid. A fasting plasma glucose test shows hypoglycemia. Which of the following enzyme
deficiencies is most likely responsible for this patient's condition?
A. Glucose-6-phosphatase
B. Glycogen phosphorylase
C. Debranching enzyme
D. Branching enzyme
Correct Answer: A
,Rationale: Correct because the combination of fasting hypoglycemia, lactic acidosis,
hyperuricemia, and hepatomegaly in a patient with autosomal recessive inheritance pattern is
diagnostic of von Gierke disease (glycogen storage disease type I). Pathophysiology of this
condition involves defective gluconeogenesis and glycogenolysis due to inability to convert
glucose-6-phosphate to glucose, leading to accumulation of glucose-6-phosphate that shunts into
glycolysis and pentose phosphate pathway. The clinical presentation is consistent with glucose-6-
phosphatase deficiency rather than McArdle disease (glycogen phosphorylase), Cori disease
(debranching enzyme), or Andersen disease (branching enzyme).
Q3. A 6-year-old boy is brought to the pediatrician by his mother due to developmental delay and
seizures. Physical examination reveals a musty odor to the urine and skin, hypopigmentation of
the skin and hair, and microcephaly. Plasma amino acid analysis shows markedly elevated
phenylalanine. Which of the following is the most appropriate dietary management for this
patient?
A. High-protein diet with phenylalanine supplementation
B. Phenylalanine-restricted diet with tyrosine supplementation
C. Low-carbohydrate, high-fat ketogenic diet
D. Gluten-free, casein-free diet
Correct Answer: B
Rationale: Correct because the clinical triad of developmental delay, seizures, and
hypopigmentation with elevated plasma phenylalanine is diagnostic of phenylketonuria (PKU).
Pathophysiology of this condition involves deficiency of phenylalanine hydroxylase, preventing
conversion of phenylalanine to tyrosine and leading to accumulation of toxic metabolites that
impair myelination. The clinical presentation is consistent with classic PKU, which requires
lifelong phenylalanine restriction with tyrosine supplementation to prevent irreversible
neurologic damage.
Q4. A 55-year-old man with a 30-pack-year smoking history presents with hemoptysis, weight
loss, and a new cough. Chest CT reveals a 4 cm spiculated mass in the right upper lobe with
mediastinal lymphadenopathy. Biopsy shows nests of polygonal cells with intercellular bridges
and keratin pearls. Which of the following molecular alterations is most commonly associated
with this histologic subtype?
A. EGFR mutation
B. ALK rearrangement
C. KRAS mutation
D. ROS1 rearrangement
, Correct Answer: C
Rationale: Correct because the histologic features of intercellular bridges and keratin pearls are
diagnostic of squamous cell carcinoma of the lung. Pathophysiology of this condition involves
smoking-related carcinogenesis with frequent alterations in TP53 and KRAS; KRAS mutations
are most common in smoking-associated lung cancers, particularly squamous cell carcinoma and
adenocarcinoma in smokers. The clinical presentation is consistent with centrally located lung
cancer in a heavy smoker, where EGFR and ALK are more characteristic of never-smokers with
adenocarcinoma.
Q5. A 32-year-old woman presents with fatigue, joint pain in her hands and feet, and a malar
rash. Laboratory studies reveal positive ANA, anti-dsDNA antibodies, and low complement
levels. Renal biopsy shows "wire loop" lesions on light microscopy and subendothelial immune
complex deposits on electron microscopy. Which of the following is the most likely diagnosis?
A. Membranous nephropathy
B. Minimal change disease
C. Diffuse proliferative glomerulonephritis
D. Focal segmental glomerulosclerosis
Correct Answer: C
Rationale: Correct because the combination of systemic lupus erythematosus serologies with
wire loop lesions and subendothelial deposits is diagnostic of diffuse proliferative
glomerulonephritis (class IV lupus nephritis). Pathophysiology of this condition involves
immune complex deposition in the subendothelial space activating complement and recruiting
inflammatory cells, leading to proliferative changes and wire loop appearance from thickened
capillary walls. The clinical presentation is consistent with the most aggressive form of lupus
nephritis that requires immunosuppressive therapy.
Q6. A 65-year-old man presents with crushing substernal chest pain radiating to his left arm.
ECG shows ST-segment elevation in leads V1–V4. Emergency cardiac catheterization reveals
100% occlusion of the left anterior descending artery. Which of the following biochemical
markers will rise first following myocardial infarction?
A. Creatine kinase-MB
B. Troponin I
C. Myoglobin
D. LDH
Correct Answer: C
