Purpose: There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay. Materials and Methods: Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results. Results: The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations. Conclusion The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

As a technique mainly hiring in forensic investigation field to identify the descents, craniofacial reconstruction (CFR) is also used in archaeology to create the faces from ancient or medieval human remains, when there is little information about his/her appearance. Eung-Cheok Ko (1531–1605) was a writer and scholar in the mid Joseon period. In January of 2019, His mummified body was found at Gumi, Kyeonsangbuk-do, Korea. The remains were anthropologically examined, and archaeological CFR was also requested for this case. This report reveals the case’s facial reconstruction process and his portrait that is drawn based on the 3-dimensional CFR result.

Purpose: High rate of false-positive tests is a major obstacle to use human papillomavirus (HPV) detectionas a diagnostic tool for high-grade squamous intraepithelial lesions or cervical cancer(HSIL+). We investigated whether type-specific viral load or physical state of HPV 16, 18,and 58 are useful biomarkers for HSIL+. Materials and Methods: Type-specific viral loads of E6 and E2 genes in cervical cells from 240, 83, and 79 HPV 16–,18–, and 58–infected women, respectively, were determined using real-time polymerasechain reaction. Viral loads were normalized to cellular DNA (copy/cell). Total and integratedviral loads and physical state were compared between HSIL+ and controls, and diagnosticvalue was determined using receiver operating characteristic analysis. Results: Viral loads of HPV 16, 18, and 58 were significantly different in lesions in the same pathologicgrade. High type-specific total viral loads were significantly associated with HSIL+ (oddsratio [OR], 14.065, 39.472, and 7.103 for HPV 16, 18, and 58, respectively). High integratedviral load was related to HSIL+ in women with HPV 16 (OR, 8.242), and integrated statewas associated with HSIL+ in women with HPV 18 (OR, 9.443). Type-specific total viral loadwas significantly associated with HSIL+ (area under curve, 0.914, 0.937, and 0.971 forHPV 16, 18, and 58, respectively), indicating an excellent performance in detecting HSIL+. Conclusion Type-specific total viral load may be a powerful diagnostic marker for HSIL+ in HPV 16–,18–, and 58–infected HSIL+ lesions. If demonstrated in all other high-risk HPV types, thismethod can lead to a paradigm shift in the strategy of equivocal cytologic abnormalities.

OBJECTIVE: To investigate the real-time cardiovascular response to the progressive overload exercise in different levels of spinal cord injury (SCI), and to find out whether regular exercise has effect on these cardiovascular responses. METHODS: The study enrolled 8 able-bodied individuals in the control group plus 15 SCI subjects who were divided into two groups by their neurological level of injury: high-level SCI group (T6 or above) and low-level SCI group (T7 or below). Also, subjects were divided into exercise group and non-exercise group by usual exercise habits. We instructed the subjects to perform exercises using arm ergometer according to the protocol and checked plethysmograph for the real time assessment of blood pressure, heart rate, and cardiac output. RESULTS: Six subjects were included in high-level SCI group (3 cervical, 3 thoracic injuries), 9 subjects in low-level SCI group (9 thoracic injuries), and 8 able-bodied individuals in control group. During arm ergometer-graded exercise, mean arterial pressure (MAP) was significantly lower in high-level SCI subjects of non-exercise group, compared with high-level SCI subjects of exercise group. In addition, HR was significantly higher in low-level SCI group compared with control group. CONCLUSION: There are significant differences in mean arterial pressure of high-level SCI group according to usual exercise habits. We discovered that even in non-athlete high-level SCI, regular exercise can bring cardiac modulation through blood pressure control.
Arm ; Arterial Pressure ; Blood Pressure ; Cardiac Output ; Cardiovascular Physiological Phenomena ; Exercise ; Exercise Test ; Heart Rate ; Hemodynamics* ; Spinal Cord Injuries* ; Spinal Cord*

OBJECTIVE: To evaluate the cardiopulmonary endurance of subjects with spinal cord injury by measuring the maximal oxygen consumption with varying degrees of spinal cord injury level, age, and regular exercise. METHODS: We instructed the subjects to perform exercises using arm ergometer on healthy adults at 20 years of age or older with spinal cord injury, and their maximal oxygen consumption (VO2max) was measured with a metabolic measurement system. The exercise proceeded stepwise according to the exercise protocol and was stopped when the subject was exhausted or when VO2 reached an equilibriu RESULTS: Among the 40 subjects, there were 10 subjects with cervical cord injury, 27 with thoracic cord injury, and 3 with lumbar cord injury. Twenty-five subjects who were exercised regularly showed statistically higher results of VO2max than those who did not exercise regularly. Subjects with cervical injury showed statistically lower VO2max than the subjects with thoracic or lumbar injury out of the 40 subjects with neurologic injury. In addition, higher age showed a statistically lower VO2max. Lastly, the regularly exercising paraplegic group showed higher VO2max than the non-exercising paraplegic group. CONCLUSION: There are differences in VO2max of subjects with spinal cord injury according to the degree of neurologic injury, age, and whether the subject participates in regular exercise. We found that regular exercise increased the VO2max in individuals with spinal cord injury.
Adult ; Aging ; Arm ; Exercise ; Exercise Test ; Humans ; Male ; Oxygen Consumption ; Spinal Cord Injuries*

OBJECTIVES: Differential diagnosis based on descriptive psychopathology between bipolar and unipolar depression in the clinical setting is a still huge challenge. Projective psychological tests might provide additional clues. This study aimed to find distinct Rorschach test characteristics of bipolar depression in comparison with unipolar depression. METHODS: Medical records and raw data of the Rorschach Inkblot test applied using standardized procedure for the Exner Comprehensive System were retrospectively reviewed for patients with bipolar disorder or unipolar depression. Individual variables of the Rorchach test were compared among three groups, i.e., (hypo) mania (n=59), bipolar depression (n=56) and unipolar depression (n=25). RESULTS: Bipolar depression group, in accordance with (hypo) manic group, showed more color reponses (WSumC), more extroverted and intuitive decision-making (EBright), and higher emotional expression (CF+C) and instability (ebright), compared to unipolar deperssion group. On the contrary, the (hypo) mania group displayed more cognitive errors (Sum6, WSum6) compared to both depression groups. CONCLUSION: This study suggests that Rorchach test might provide valuable markers for differential diagnosis between bipolar and unipolar depression, and that some of those markers could be regarded as trait markers of bipolar disorder.
Bipolar Disorder ; Depression ; Depressive Disorder ; Diagnosis, Differential ; Humans ; Medical Records ; Psychological Tests ; Psychopathology ; Retrospective Studies ; Rorschach Test

The purpose of the present study was to identify the factor structure of neurocognitive tests used on schizophrenia patients by using the confirmative factor analysis, and to assess the factor score differences of schizophrenia patients and healthy controls. Comprehensive neurocognitive tests were administered to stabilized schizophrenia patients (N=114) and healthy controls (N=120). In the results of factor analyses on patients, the multifactorial-6-factor model, which included the speed of processing, working memory, verbal learning and memory, visual learning and memory, attention/vigilance, and reasoning/problem solving as suggested by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), showed the better goodness of fit than any of the other models tested. And assessing the group differences of factor scores, we found the patients performed worse than the controls in all factors, but the result showed meaningful variations of impairments across the cognitive factors. Our study identifies the six major domains with multifactorial structure of cognitive abilities in schizophrenia patients and confirms the distinctive impairment patterns of each cognitive domain. These results may have utility in better understanding the pathology of schizophrenia as well as in genetic studies.
Adolescent ; Adult ; Attention ; Cognition Disorders/etiology ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Memory ; Middle Aged ; Models, Psychological ; Neuropsychological Tests ; Problem Solving ; Schizophrenia/*diagnosis/etiology ; Severity of Illness Index ; Verbal Behavior ; Verbal Learning

OBJECTIVES: Recurrence of mood episodes associated with a specific season has been described in various mood disorders. Seasonal change in mood and behavior as a lifetime trait is also observed in healthy individuals. This study aimed at comparing the lifetime trait of seasonal variations of mood and behavior between bipolar disorder patients and controls as well as investigating associated factors of seasonality. METHODS: Subjects were ninety-four clinically stable patients with bipolar disorder and 188 age- and sex-matched healthy controls. Seasonality of mood and behavior was assessed retrospectively on lifetime basis using Seasonal Pattern Assessment Questionnaire(SPAQ). RESULTS: The patient group showed a higher median global seasonality score(GSS) of SPAQ and a higher rate of seasonal affective disorder(SAD) compared to the control group(p < 0.0001). For subjects showing prominent seasonality, the seasonal symptom profile and seasonal pattern was similar in both patient and control groups. In addition to the diagnosis, female gender was shown to be a predictor of seasonality in the multiple linear regression analysis(p = 0.045). CONCLUSION: This study suggests that lifetime trait of seasonality may be related to the susceptibility of bipolar disorder.
Bipolar Disorder ; Female ; Humans ; Linear Models ; Mood Disorders ; Recurrence ; Retrospective Studies ; Seasons

OBJECTIVES : Whether bipolar II disorder (BP-II) is simply a milder form of bipolar I disorder (BP-I) or a valid diagnostic category that could be separated from BP-I, is an issue still under consideration. Investigations exploring differential clinical and biological features of the two conditions are needed to resolve the controversies. This study aimed to obtain a comprehensive view of differences in clinical course and symptoms characteristics between BP-I and BP-II. METHODS : 44 BP-I and 26 BP-II patients were assessed using the Diagnostic Interview for Genetic Studies (DIGS), Korean version. Demographic data, age at onset, number of (hypo) manic/ depressive episodes, the duration of illness, polarity at onset, seasonality, rapid cycling, atypical depression and symptom profiles of each episode were evaluated. RESULTS : BP-II patients experienced depressive episodes more frequently than BP-I patients after illness onset (U=240.5, p=0.008). More BP-II patients showed seasonality (34.9% vs. 61.5%) and a rapid cycling course (4.5% vs. 18.2%). When comparing symptom profiles of manic/hypomanic episodes, irritable mood, decreased sleep need, inattention, reckless behavior, arrogant/provocative attitude and frequent outbursts of anger were less encountered in BP-II patients. In depressive episodes, leaden paralysis and psychomotor agitation were more frequently observed in BP-II patients. There was no significant difference between the two groups in psychotic symptoms of depressive episode. CONCLUSION : BP-I and BP-II disorders showed differences in clinical courses and symptom profiles. BP-II disorder seems to be less severe than BP-I disorder with regard to the intensity of manic symptoms, but more severe with respect to frequencies of depressive episodes. These results provide additional evidence supporting the distinction of BP-I and BP-II as separate diagnos-tic categories that might have different genetic profiles and/or biological mechanisms.
Anger ; Depression ; Humans ; Irritable Mood ; Paralysis ; Psychomotor Agitation ; Seasons

OBJECTIVES : Whether bipolar II disorder (BP-II) is simply a milder form of bipolar I disorder (BP-I) or a valid diagnostic category that could be separated from BP-I, is an issue still under consideration. Investigations exploring differential clinical and biological features of the two conditions are needed to resolve the controversies. This study aimed to obtain a comprehensive view of differences in clinical course and symptoms characteristics between BP-I and BP-II. METHODS : 44 BP-I and 26 BP-II patients were assessed using the Diagnostic Interview for Genetic Studies (DIGS), Korean version. Demographic data, age at onset, number of (hypo) manic/ depressive episodes, the duration of illness, polarity at onset, seasonality, rapid cycling, atypical depression and symptom profiles of each episode were evaluated. RESULTS : BP-II patients experienced depressive episodes more frequently than BP-I patients after illness onset (U=240.5, p=0.008). More BP-II patients showed seasonality (34.9% vs. 61.5%) and a rapid cycling course (4.5% vs. 18.2%). When comparing symptom profiles of manic/hypomanic episodes, irritable mood, decreased sleep need, inattention, reckless behavior, arrogant/provocative attitude and frequent outbursts of anger were less encountered in BP-II patients. In depressive episodes, leaden paralysis and psychomotor agitation were more frequently observed in BP-II patients. There was no significant difference between the two groups in psychotic symptoms of depressive episode. CONCLUSION : BP-I and BP-II disorders showed differences in clinical courses and symptom profiles. BP-II disorder seems to be less severe than BP-I disorder with regard to the intensity of manic symptoms, but more severe with respect to frequencies of depressive episodes. These results provide additional evidence supporting the distinction of BP-I and BP-II as separate diagnos-tic categories that might have different genetic profiles and/or biological mechanisms.
Anger ; Depression ; Humans ; Irritable Mood ; Paralysis ; Psychomotor Agitation ; Seasons