1.The Multi-targeted Effect of Fascaplysin on the Proliferation and Dedifferentiation of Schwann Cells Inhibits Peripheral Nerve Degeneration by Blocking CDK4/6 and Androgen Receptor
Hyung-Joo CHUNG ; Ja-Eun KIM ; Youngbuhm HUH ; Jin San LEE ; So-Woon KIM ; Kiyong NA ; Jiwon KIM ; Seung Hyeun LEE ; Hiroyuki KONISHI ; Seung Geun YEO ; Dong Keon YON ; Dokyoung KIM ; Junyang JUNG ; Na Young JEONG
Experimental Neurobiology 2024;33(6):266-281
Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.
2.The Multi-targeted Effect of Fascaplysin on the Proliferation and Dedifferentiation of Schwann Cells Inhibits Peripheral Nerve Degeneration by Blocking CDK4/6 and Androgen Receptor
Hyung-Joo CHUNG ; Ja-Eun KIM ; Youngbuhm HUH ; Jin San LEE ; So-Woon KIM ; Kiyong NA ; Jiwon KIM ; Seung Hyeun LEE ; Hiroyuki KONISHI ; Seung Geun YEO ; Dong Keon YON ; Dokyoung KIM ; Junyang JUNG ; Na Young JEONG
Experimental Neurobiology 2024;33(6):266-281
Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.
3.The Multi-targeted Effect of Fascaplysin on the Proliferation and Dedifferentiation of Schwann Cells Inhibits Peripheral Nerve Degeneration by Blocking CDK4/6 and Androgen Receptor
Hyung-Joo CHUNG ; Ja-Eun KIM ; Youngbuhm HUH ; Jin San LEE ; So-Woon KIM ; Kiyong NA ; Jiwon KIM ; Seung Hyeun LEE ; Hiroyuki KONISHI ; Seung Geun YEO ; Dong Keon YON ; Dokyoung KIM ; Junyang JUNG ; Na Young JEONG
Experimental Neurobiology 2024;33(6):266-281
Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.
4.The Multi-targeted Effect of Fascaplysin on the Proliferation and Dedifferentiation of Schwann Cells Inhibits Peripheral Nerve Degeneration by Blocking CDK4/6 and Androgen Receptor
Hyung-Joo CHUNG ; Ja-Eun KIM ; Youngbuhm HUH ; Jin San LEE ; So-Woon KIM ; Kiyong NA ; Jiwon KIM ; Seung Hyeun LEE ; Hiroyuki KONISHI ; Seung Geun YEO ; Dong Keon YON ; Dokyoung KIM ; Junyang JUNG ; Na Young JEONG
Experimental Neurobiology 2024;33(6):266-281
Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.
5.Vessel Wall Changes on Serial High-Resolution MRI and the Use of Cilostazol in Patients With Adult-Onset Moyamoya Disease
Jae Youn KIM ; Hyung Jun KIM ; Eun-Hyeok CHOI ; Kwang Hyun PAN ; Jong-Won CHUNG ; Woo-Keun SEO ; Gyeong-Moon KIM ; Tae Keun JEE ; Je Young YEON ; Jong-Soo KIM ; Seung-Chyul HONG ; Min-Jung SEONG ; Jihoon CHA ; Keon Ha KIM ; Pyoung JEON ; Oh Young BANG
Journal of Clinical Neurology 2022;18(6):610-618
Background:
and Purpose The natural course of adult-onset moyamoya disease (MMD) is unknown, and there is no medical treatment that halts its progression. We hypothesized that progressive shrinkage of large intracranial arteries occurs in adult-onset MMD, and that cilostazol inhibits this process.
Methods:
Serial high-resolution magnetic resonance imaging (HR-MRI) was performed on 66 patients with MMD: 30 patients received cilostazol, 21 received other antiplatelets, and 15 received no antiplatelets or had poor compliance to them. Serial HR-MRI was performed (interval between MRI scans: 29.67±18.02 months, mean±SD), and changes in outer diameter, luminal stenosis, and vascular enhancement were measured. Factors affecting HR-MRI changes were evaluated, including vascular risk factors and the ring finger protein 213 gene variant.
Results:
The progression of stenosis to occlusion, recurrent ischemic stroke, and the development of new stenotic segments were observed in seven, seven, and three patients, respectively. Serial HR-MRI indicated that the degree of stenosis increased with negative remodeling (outer diameter shrinkage). Patients who received cilostazol presented significantly larger outer diameters and lower degrees of stenosis compared with other groups (p=0.005 and p=0.031, respectively). After adjusting for clinical and genetic factors, only cilostazol use was independently associated with negative remodeling (odds ratio=0.29, 95% confidence interval=0.10–0.84, p=0.023). While vascular enhancement was observed in most patients (61 patients), the progression of enhancement or the occurrence of new vascular enhancement was rarely observed on follow-up HR-MRI (6 and 1 patients, respectively).
Conclusions
Adult-onset MMD induces progressive shrinkage of large intracranial arteries, which cilostazol treatment may prevent. Further randomized clinical trials are warranted.
6.Erratum: Correction of Affiliations in the Article “Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study”
Jae Min LEE ; Jung Yoon CHOI ; Kyung Taek HONG ; Hyoung Jin KANG ; Hee Young SHIN ; Hee Jo BAEK ; Hoon KOOK ; Seongkoo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Bin CHO ; Seok-Goo CHO ; Kyung Mi PARK ; Eu Jeen YANG ; Young Tak LIM ; Jin Kyung SUH ; Sung Han KANG ; Hyery KIM ; Kyung-Nam KOH ; Ho Joon IM ; Jong Jin SEO ; Hee Won CHO ; Hee Young JU ; Ji Won LEE ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Kyung Duk PARK ; Jeong Ok HAH ; Min Kyoung KIM ; Jung Woo HAN ; Seung Min HAHN ; Chuhl Joo LYU ; Ye Jee SHIM ; Heung Sik KIM ; Young Rok DO ; Jae Won YOO ; Yeon Jung LIM ; In-Sang JEON ; Hee won CHUEH ; Sung Yong OH ; Hyoung Soo CHOI ; Jun Eun PARK ; Jun Ah LEE ; Hyeon Jin PARK ; Byung-Kiu PARK ; Soon Ki KIM ; Jae Young LIM ; Eun Sil PARK ; Sang Kyu PARK ; Eun Jin CHOI ; Young Bae CHOI ; Jong Hyung YOON ;
Journal of Korean Medical Science 2021;36(4):e37-
7.How Cerebral Vessel Tortuosity Affects Development and Recurrence of Aneurysm: Outer Curvature versus Bifurcation Type
Hyung Jun KIM ; Ha-Na SONG ; Ji-Eun LEE ; Yoon-Chul KIM ; In-Young BAEK ; Ye-Sel KIM ; Jong-Won CHUNG ; Tae Keun JEE ; Je Young YEON ; Oh Young BANG ; Gyeong-Moon KIM ; Keon-Ha KIM ; Jong-Soo KIM ; Seung-Chyul HONG ; Woo-Keun SEO ; Pyeong JEON
Journal of Stroke 2021;23(2):213-222
Background:
and Purpose Previous studies have assessed the relationship between cerebral vessel tortuosity and intracranial aneurysm (IA) based on two-dimensional brain image analysis. We evaluated the relationship between cerebral vessel tortuosity and IA according to the hemodynamic location using three-dimensional (3D) analysis and studied the effect of tortuosity on the recurrence of treated IA.
Methods:
We collected clinical and imaging data from patients with IA and disease-free controls. IAs were categorized into outer curvature and bifurcation types. Computerized analysis of the images provided information on the length of the arterial segment and tortuosity of the cerebral arteries in 3D space.
Results:
Data from 95 patients with IA and 95 controls were analyzed. Regarding parent vessel tortuosity index (TI; P<0.01), average TI (P<0.01), basilar artery (BA; P=0.02), left posterior cerebral artery (P=0.03), both vertebral arteries (VAs; P<0.01), and right internal carotid artery (P<0.01), there was a significant difference only in the outer curvature type compared with the control group. The outer curvature type was analyzed, and the occurrence of an IA was associated with increased TI of the parent vessel, average, BA, right middle cerebral artery, and both VAs in the logistic regression analysis. However, in all aneurysm cases, recanalization of the treated aneurysm was inversely associated with increased TI of the parent vessels.
Conclusions
TIs of intracranial arteries are associated with the occurrence of IA, especially in the outer curvature type. IAs with a high TI in the parent vessel showed good outcomes with endovascular treatment.
8.How Cerebral Vessel Tortuosity Affects Development and Recurrence of Aneurysm: Outer Curvature versus Bifurcation Type
Hyung Jun KIM ; Ha-Na SONG ; Ji-Eun LEE ; Yoon-Chul KIM ; In-Young BAEK ; Ye-Sel KIM ; Jong-Won CHUNG ; Tae Keun JEE ; Je Young YEON ; Oh Young BANG ; Gyeong-Moon KIM ; Keon-Ha KIM ; Jong-Soo KIM ; Seung-Chyul HONG ; Woo-Keun SEO ; Pyeong JEON
Journal of Stroke 2021;23(2):213-222
Background:
and Purpose Previous studies have assessed the relationship between cerebral vessel tortuosity and intracranial aneurysm (IA) based on two-dimensional brain image analysis. We evaluated the relationship between cerebral vessel tortuosity and IA according to the hemodynamic location using three-dimensional (3D) analysis and studied the effect of tortuosity on the recurrence of treated IA.
Methods:
We collected clinical and imaging data from patients with IA and disease-free controls. IAs were categorized into outer curvature and bifurcation types. Computerized analysis of the images provided information on the length of the arterial segment and tortuosity of the cerebral arteries in 3D space.
Results:
Data from 95 patients with IA and 95 controls were analyzed. Regarding parent vessel tortuosity index (TI; P<0.01), average TI (P<0.01), basilar artery (BA; P=0.02), left posterior cerebral artery (P=0.03), both vertebral arteries (VAs; P<0.01), and right internal carotid artery (P<0.01), there was a significant difference only in the outer curvature type compared with the control group. The outer curvature type was analyzed, and the occurrence of an IA was associated with increased TI of the parent vessel, average, BA, right middle cerebral artery, and both VAs in the logistic regression analysis. However, in all aneurysm cases, recanalization of the treated aneurysm was inversely associated with increased TI of the parent vessels.
Conclusions
TIs of intracranial arteries are associated with the occurrence of IA, especially in the outer curvature type. IAs with a high TI in the parent vessel showed good outcomes with endovascular treatment.
9.Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma:a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study
Jae Min LEE ; Jung Yoon CHOI ; Kyung Taek HONG ; Hyoung Jin KANG ; Hee Young SHIN ; Hee Jo BAEK ; Seongkoo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Bin CHO ; Seok-Goo CHO ; Kyung Mi PARK ; Eu Jeen YANG ; Young Tak LIM ; Jin Kyung SUH ; Sung Han KANG ; Hyery KIM ; Kyung-Nam KOH ; Ho Joon IM ; Jong Jin SEO ; Hee Won CHO ; Hee Young JU ; Ji Won LEE ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Kyung Duk PARK ; Jeong Ok HAH ; Min Kyoung KIM ; Jung Woo HAN ; Seung Min HAHN ; Chuhl Joo LYU ; Ye Jee SHIM ; Heung Sik KIM ; Young Rok DO ; Jae Won YOO ; Yeon Jung LIM ; In-Sang JEON ; Hee won CHUEH ; Sung Yong OH ; Hyoung Soo CHOI ; Jun Eun PARK ; Jun Ah LEE ; Hyeon Jin PARK ; Byung-Kiu PARK ; Soon Ki KIM ; Jae Young LIM ; Eun Sil PARK ; Sang Kyu PARK ; Eun Jin CHOI ; Young Bae CHOI ; Jong Hyung YOON ; Hoon KOOK ;
Journal of Korean Medical Science 2020;35(46):e393-
Background:
Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea.
Methods:
We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016.
Results:
A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype.Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, highrisk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level.In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively.
Conclusion
This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.
10.Executive Summary of Stroke Statistics in Korea 2018: A Report from the Epidemiology Research Council of the Korean Stroke Society
Jun Yup KIM ; Kyusik KANG ; Jihoon KANG ; Jaseong KOO ; Dae Hyun KIM ; Beom Joon KIM ; Wook Joo KIM ; Eung Gyu KIM ; Jae Guk KIM ; Jeong Min KIM ; Joon Tae KIM ; Chulho KIM ; Hyun Wook NAH ; Kwang Yeol PARK ; Moo Seok PARK ; Jong Moo PARK ; Jong Ho PARK ; Tai Hwan PARK ; Hong Kyun PARK ; Woo Keun SEO ; Jung Hwa SEO ; Tae Jin SONG ; Seong Hwan AHN ; Mi Sun OH ; Hyung Geun OH ; Sungwook YU ; Keon Joo LEE ; Kyung Bok LEE ; Kijeong LEE ; Sang Hwa LEE ; Soo Joo LEE ; Min Uk JANG ; Jong Won CHUNG ; Yong Jin CHO ; Kang Ho CHOI ; Jay Chol CHOI ; Keun Sik HONG ; Yang Ha HWANG ; Seong Eun KIM ; Ji Sung LEE ; Jimi CHOI ; Min Sun KIM ; Ye Jin KIM ; Jinmi SEOK ; Sujung JANG ; Seokwan HAN ; Hee Won HAN ; Jin Hyuk HONG ; Hyori YUN ; Juneyoung LEE ; Hee Joon BAE
Journal of Stroke 2019;21(1):42-59
Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the “Stroke Statistics in Korea” project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.
Adult
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Aged
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Alcohol Drinking
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Ambulances
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Atrial Fibrillation
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Cerebral Hemorrhage
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Emergency Medical Services
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Emergency Service, Hospital
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Epidemiology
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Female
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Hemorrhage
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Hope
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Humans
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Hypertension
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Incidence
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Korea
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Male
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Mortality
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Prevalence
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Reperfusion
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Risk Factors
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Smoke
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Smoking
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Stroke
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Subarachnoid Hemorrhage
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Writing

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