Split (1)

train · 816k rows

paragraph_index int64	sec string	p_has_citation int64	cites string	citeids list	pmid int64	cited_id string	sentences string	all_sent_cites list	sent_len int64	sentence_batch_index int64	sent_has_citation float64	qc_fail bool	cited_sentence string	cites_in_sentence list	cln_sentence string	is_cap bool	is_alpha bool	ends_wp bool	cit_qc bool	lgtm bool	__index_level_0__ int64
1	INTRODUCTION	1	11	[ "DDP580C11", "DDP580C12", "DDP580C13", "DDP580C14", "DDP580C15", "DDP580C11", "DDP580C16" ]	20,047,948	pmid-9668348\|pmid-8663398\|pmid-12813057\|pmid-16061944\|pmid-17954913\|pmid-9668348\|pmid-11051765	Although the involvement of saposin C in the degradation of GC is well-established in vitro (11,16), the in vivo mechanisms of its action are not fully understood.	[ "11", "12", "13", "14", "15", "11", "16" ]	163	36,916	0	false	Although the involvement of saposin C in the degradation of GC is well-established in vitro, the in vivo mechanisms of its action are not fully understood.	[ "11,16" ]	Although the involvement of saposin C in the degradation of GC is well-established in vitro, the in vivo mechanisms of its action are not fully understood.	true	true	true	true	true	6,334
2	INTRODUCTION	1	17	[ "DDP580C17", "DDP580C8", "DDP580C18", "DDP580C18", "DDP580C19", "DDP580C20", "DDP580C19", "DDP580C20", "DDP580C14", "DDP580C21" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	Knockout of the gba locus in mice abolishes GCase activity and leads to neonatal death (17).	[ "17", "8", "18", "18", "19", "20", "19", "20", "14", "21" ]	92	36,917	1	false	Knockout of the gba locus in mice abolishes GCase activity and leads to neonatal death.	[ "17" ]	Knockout of the gba locus in mice abolishes GCase activity and leads to neonatal death.	true	true	true	true	true	6,335
2	INTRODUCTION	1	8	[ "DDP580C17", "DDP580C8", "DDP580C18", "DDP580C18", "DDP580C19", "DDP580C20", "DDP580C19", "DDP580C20", "DDP580C14", "DDP580C21" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	In brains of these GCase knockout mice, GS levels are increased by ∼100-fold (8) along with the increases of GC (18).	[ "17", "8", "18", "18", "19", "20", "19", "20", "14", "21" ]	117	36,918	1	false	In brains of these GCase knockout mice, GS levels are increased by ∼100-fold along with the increases of GC.	[ "8", "18" ]	In brains of these GCase knockout mice, GS levels are increased by ∼100-fold along with the increases of GC.	true	true	true	true	true	6,335
2	INTRODUCTION	1	18	[ "DDP580C17", "DDP580C8", "DDP580C18", "DDP580C18", "DDP580C19", "DDP580C20", "DDP580C19", "DDP580C20", "DDP580C14", "DDP580C21" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	Although neuronal loss is not observed, some GC storage in neurons is observed in spinal cord and brain stem (18).	[ "17", "8", "18", "18", "19", "20", "19", "20", "14", "21" ]	114	36,919	1	false	Although neuronal loss is not observed, some GC storage in neurons is observed in spinal cord and brain stem.	[ "18" ]	Although neuronal loss is not observed, some GC storage in neurons is observed in spinal cord and brain stem.	true	true	true	true	true	6,335
2	INTRODUCTION	1	17	[ "DDP580C17", "DDP580C8", "DDP580C18", "DDP580C18", "DDP580C19", "DDP580C20", "DDP580C19", "DDP580C20", "DDP580C14", "DDP580C21" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	Recently, more viable GCase mouse models with acute neuronopathic Gaucher disease have been generated (19,20).	[ "17", "8", "18", "18", "19", "20", "19", "20", "14", "21" ]	110	36,920	0	false	Recently, more viable GCase mouse models with acute neuronopathic Gaucher disease have been generated.	[ "19,20" ]	Recently, more viable GCase mouse models with acute neuronopathic Gaucher disease have been generated.	true	true	true	true	true	6,335
2	INTRODUCTION	1	17	[ "DDP580C17", "DDP580C8", "DDP580C18", "DDP580C18", "DDP580C19", "DDP580C20", "DDP580C19", "DDP580C20", "DDP580C14", "DDP580C21" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	By either rescue of the skin of mice that are null in all other cells or specifically knocking out gba only in neurons, longer lived (2–3 weeks) acute neuronopathic variants were created as mimics of human type 2 Gaucher disease (19,20).	[ "17", "8", "18", "18", "19", "20", "19", "20", "14", "21" ]	237	36,921	0	false	By either rescue of the skin of mice that are null in all other cells or specifically knocking out gba only in neurons, longer lived (2–3 weeks) acute neuronopathic variants were created as mimics of human type 2 Gaucher disease.	[ "19,20" ]	By either rescue of the skin of mice that are null in all other cells or specifically knocking out gba only in neurons, longer lived (2–3 weeks) acute neuronopathic variants were created as mimics of human type 2 Gaucher disease.	true	true	true	true	true	6,335
2	INTRODUCTION	1	17	[ "DDP580C17", "DDP580C8", "DDP580C18", "DDP580C18", "DDP580C19", "DDP580C20", "DDP580C19", "DDP580C20", "DDP580C14", "DDP580C21" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	However, the foreshortened lifespan limits biochemical and neuronopathological studies of the disease progression.	[ "17", "8", "18", "18", "19", "20", "19", "20", "14", "21" ]	114	36,922	0	false	However, the foreshortened lifespan limits biochemical and neuronopathological studies of the disease progression.	[]	However, the foreshortened lifespan limits biochemical and neuronopathological studies of the disease progression.	true	true	true	true	true	6,335
2	INTRODUCTION	1	17	[ "DDP580C17", "DDP580C8", "DDP580C18", "DDP580C18", "DDP580C19", "DDP580C20", "DDP580C19", "DDP580C20", "DDP580C14", "DDP580C21" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	Additional efforts were taken to create Gaucher disease models include knock-ins of point mutations (e.g.	[ "17", "8", "18", "18", "19", "20", "19", "20", "14", "21" ]	105	36,923	0	false	Additional efforts were taken to create Gaucher disease models include knock-ins of point mutations (e.g.	[]	Additional efforts were taken to create Gaucher disease models include knock-ins of point mutations (e.g.	true	true	true	true	true	6,335
2	INTRODUCTION	1	14	[ "DDP580C17", "DDP580C8", "DDP580C18", "DDP580C18", "DDP580C19", "DDP580C20", "DDP580C19", "DDP580C20", "DDP580C14", "DDP580C21" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	V394L, D409H or D409V) with or without combinations with hypomorphic prosaposins (14).	[ "17", "8", "18", "18", "19", "20", "19", "20", "14", "21" ]	86	36,924	1	false	V394L, D409H or D409V) with or without combinations with hypomorphic prosaposins.	[ "14" ]	V394L, D409H or D409V) with or without combinations with hypomorphic prosaposins.	true	true	true	true	true	6,335
2	INTRODUCTION	1	21	[ "DDP580C17", "DDP580C8", "DDP580C18", "DDP580C18", "DDP580C19", "DDP580C20", "DDP580C19", "DDP580C20", "DDP580C14", "DDP580C21" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	The latter models develop storage cells in visceral and GC accumulation in visceral, but have complex GSL accumulations in the CNS due to prosaposin deficiency (21).	[ "17", "8", "18", "18", "19", "20", "19", "20", "14", "21" ]	165	36,925	1	false	The latter models develop storage cells in visceral and GC accumulation in visceral, but have complex GSL accumulations in the CNS due to prosaposin deficiency.	[ "21" ]	The latter models develop storage cells in visceral and GC accumulation in visceral, but have complex GSL accumulations in the CNS due to prosaposin deficiency.	true	true	true	true	true	6,335
2	INTRODUCTION	1	17	[ "DDP580C17", "DDP580C8", "DDP580C18", "DDP580C18", "DDP580C19", "DDP580C20", "DDP580C19", "DDP580C20", "DDP580C14", "DDP580C21" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	A principle impediment to understanding the pathophysiology and therapeutic developments for the CNS variants has been the lack of viable neuronopathic mouse models with sufficient lifespans.	[ "17", "8", "18", "18", "19", "20", "19", "20", "14", "21" ]	191	36,926	0	false	A principle impediment to understanding the pathophysiology and therapeutic developments for the CNS variants has been the lack of viable neuronopathic mouse models with sufficient lifespans.	[]	A principle impediment to understanding the pathophysiology and therapeutic developments for the CNS variants has been the lack of viable neuronopathic mouse models with sufficient lifespans.	true	true	true	true	true	6,335
3	INTRODUCTION	0	null	null	20,047,948	NA	In this study, a new mouse model was generated by cross-breeding of the V394L GCase homozygote into the saposin C null (C−/−) mouse.	null	132	36,927	0	false	null	null	In this study, a new mouse model was generated by cross-breeding of the V394L GCase homozygote into the saposin C null (C−/−) mouse.	true	true	true	true	true	6,336
3	INTRODUCTION	0	null	null	20,047,948	NA	Deficiency of saposin C led to additional reductions of the V394L GCase and increases of GC and GS levels.	null	106	36,928	0	false	null	null	Deficiency of saposin C led to additional reductions of the V394L GCase and increases of GC and GS levels.	true	true	true	true	true	6,336
3	INTRODUCTION	0	null	null	20,047,948	NA	This viable model developed neurological deficits analogous to subacute neuronopathic Gaucher disease.	null	102	36,929	0	false	null	null	This viable model developed neurological deficits analogous to subacute neuronopathic Gaucher disease.	true	true	true	true	true	6,336
0	DISCUSSION	1	26	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	Neuronopathic Gaucher disease variants present with brainstem, cerebellar, thalamic, cerebral cortical and substantia nigra involvement, but the degrees of involvement and affected regions vary among the patients (26–28).	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	221	36,930	0	false	Neuronopathic Gaucher disease variants present with brainstem, cerebellar, thalamic, cerebral cortical and substantia nigra involvement, but the degrees of involvement and affected regions vary among the patients.	[ "26–28" ]	Neuronopathic Gaucher disease variants present with brainstem, cerebellar, thalamic, cerebral cortical and substantia nigra involvement, but the degrees of involvement and affected regions vary among the patients.	true	true	true	true	true	6,337
0	DISCUSSION	1	26	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	The neuropathological involvement has been correlated with the accumulation of GS and GC (6,26) with increased GS mostly associated with the widespread neuron loss in Gaucher disease type 2 (7,29,30).	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	200	36,931	0	false	The neuropathological involvement has been correlated with the accumulation of GS and GC with increased GS mostly associated with the widespread neuron loss in Gaucher disease type 2.	[ "6,26", "7,29,30" ]	The neuropathological involvement has been correlated with the accumulation of GS and GC with increased GS mostly associated with the widespread neuron loss in Gaucher disease type 2.	true	true	true	true	true	6,337
0	DISCUSSION	1	26	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	This neuronal loss is also associated with astrogliosis and microglial nodules (6,27).	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	86	36,932	0	false	This neuronal loss is also associated with astrogliosis and microglial nodules.	[ "6,27" ]	This neuronal loss is also associated with astrogliosis and microglial nodules.	true	true	true	true	true	6,337
0	DISCUSSION	1	31	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	Additionally, GS suppresses neuritogenesis (31).	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	48	36,933	1	false	Additionally, GS suppresses neuritogenesis.	[ "31" ]	Additionally, GS suppresses neuritogenesis.	true	true	true	true	true	6,337
0	DISCUSSION	1	32	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	In vitro GC addition to microsomes from type 1, 2 or 3 Gaucher patients stimulated agonist-induced Ca2+ release and this alteration correlated with the level of GC accumulation (32).	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	182	36,934	1	false	In vitro GC addition to microsomes from type 1, 2 or 3 Gaucher patients stimulated agonist-induced Ca2+ release and this alteration correlated with the level of GC accumulation.	[ "32" ]	In vitro GC addition to microsomes from type 1, 2 or 3 Gaucher patients stimulated agonist-induced Ca2+ release and this alteration correlated with the level of GC accumulation.	true	true	true	true	true	6,337
0	DISCUSSION	1	26	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	GS also directly augments the Ca2+ release in an agonist-independent manner in such microsomes (32,33).	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	103	36,935	0	false	GS also directly augments the Ca2+ release in an agonist-independent manner in such microsomes.	[ "32,33" ]	GS also directly augments the Ca2+ release in an agonist-independent manner in such microsomes.	true	true	true	true	true	6,337
0	DISCUSSION	1	34	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	This Ca2+ release, presumably from endoplasmic reticulum, has been speculated to be responsible for neuron cell death due to GC or GS increases (34).	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	149	36,936	1	false	This Ca2+ release, presumably from endoplasmic reticulum, has been speculated to be responsible for neuron cell death due to GC or GS increases.	[ "34" ]	This Ca2+ release, presumably from endoplasmic reticulum, has been speculated to be responsible for neuron cell death due to GC or GS increases.	true	true	true	true	true	6,337
0	DISCUSSION	1	30	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	Furthermore, hippocampal CA2-4 regions are significantly involved by neuronal injury in neuronopathic Gaucher disease variants (30).	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	132	36,937	1	false	Furthermore, hippocampal CA2-4 regions are significantly involved by neuronal injury in neuronopathic Gaucher disease variants.	[ "30" ]	Furthermore, hippocampal CA2-4 regions are significantly involved by neuronal injury in neuronopathic Gaucher disease variants.	true	true	true	true	true	6,337
0	DISCUSSION	1	26	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	Here, the neuronal deficit in 4L;C* mice was likely caused by excess levels of GS and GC as well as the striking inclusions in axonal and neuronal processes.	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	157	36,938	0	false	Here, the neuronal deficit in 4L;C* mice was likely caused by excess levels of GS and GC as well as the striking inclusions in axonal and neuronal processes.	[]	Here, the neuronal deficit in 4L;C* mice was likely caused by excess levels of GS and GC as well as the striking inclusions in axonal and neuronal processes.	true	true	true	true	true	6,337
0	DISCUSSION	1	26	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	Furthermore, 4L;C* mice showed impaired hippocampal LTP that correlated with substrate accumulation and abnormal neuronal processes.	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	132	36,939	0	false	Furthermore, 4L;C* mice showed impaired hippocampal LTP that correlated with substrate accumulation and abnormal neuronal processes.	[]	Furthermore, 4L;C* mice showed impaired hippocampal LTP that correlated with substrate accumulation and abnormal neuronal processes.	true	true	true	true	true	6,337
0	DISCUSSION	1	26	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	Negative Tunnel assays in 4L;C* CNS tissues indicate that apoptosis was not the cause of neurodegeneration.	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	107	36,940	0	false	Negative Tunnel assays in 4L;C* CNS tissues indicate that apoptosis was not the cause of neurodegeneration.	[]	Negative Tunnel assays in 4L;C* CNS tissues indicate that apoptosis was not the cause of neurodegeneration.	true	true	true	true	true	6,337
0	DISCUSSION	1	25	[ "DDP580C26", "DDP580C28", "DDP580C6", "DDP580C26", "DDP580C7", "DDP580C29", "DDP580C30", "DDP580C6", "DDP580C27", "DDP580C31", "DDP580C32", "DDP580C32", "DDP580C33", "DDP580C34", "DDP580C30", "DDP580C25" ]	20,047,948	NA\|NA\|NA\|pmid-15464415\|pmid-10796875\|NA\|pmid-6524300\|pmid-12208131\|pmid-15464415\|pmid-3364161\|pmid-6524300\|pmid-3752966\|pmid-1718128\|pmid-6524300\|pmid-3752966\|pmid-7097276\|pmid-10926300\|pmid-15234332\|pmid-6524300\|pmid-2286024\|pmid-14678774\|pmid-15649698\|pmid-15649698\|pmid-12709427\|pmid-16970941\|pmid-15234332\|pmid-19398...	The accumulation of p62, an autophagic receptor that mediates autophagic degradation of ubiquitinated proteins (25) and enhanced Lamp2 expression suggest an impairment of protein degradation in the autophagosome and lysosome system that could be the cause of neurodegeneration in this model.	[ "26", "28", "6", "26", "7", "29", "30", "6", "27", "31", "32", "32", "33", "34", "30", "25" ]	291	36,941	1	false	The accumulation of p62, an autophagic receptor that mediates autophagic degradation of ubiquitinated proteins and enhanced Lamp2 expression suggest an impairment of protein degradation in the autophagosome and lysosome system that could be the cause of neurodegeneration in this model.	[ "25" ]	The accumulation of p62, an autophagic receptor that mediates autophagic degradation of ubiquitinated proteins and enhanced Lamp2 expression suggest an impairment of protein degradation in the autophagosome and lysosome system that could be the cause of neurodegeneration in this model.	true	true	true	true	true	6,337
1	DISCUSSION	0	null	null	20,047,948	pmid-9668348\|pmid-8663398\|pmid-12813057\|pmid-16061944\|pmid-17954913\|pmid-9668348\|pmid-11051765	Comparisons of the saposin C−/− mice and the 4L;C* mice provide insights into the function of saposin C and GCase.	null	114	36,942	0	false	null	null	Comparisons of the saposin C−/− mice and the 4L;C* mice provide insights into the function of saposin C and GCase.	true	true	true	true	true	6,338
1	DISCUSSION	0	null	null	20,047,948	pmid-9668348\|pmid-8663398\|pmid-12813057\|pmid-16061944\|pmid-17954913\|pmid-9668348\|pmid-11051765	Importantly, saposin C provides a proteolytic protective effect for GCase within the lysosome and that its presence is required for the full activity of the enzyme.	null	164	36,943	0	false	null	null	Importantly, saposin C provides a proteolytic protective effect for GCase within the lysosome and that its presence is required for the full activity of the enzyme.	true	true	true	true	true	6,338
1	DISCUSSION	0	null	null	20,047,948	pmid-9668348\|pmid-8663398\|pmid-12813057\|pmid-16061944\|pmid-17954913\|pmid-9668348\|pmid-11051765	Here, the singular absence of saposin C led to further decreases in V394L mutant GCase activity as measured in vitro.	null	117	36,944	0	false	null	null	Here, the singular absence of saposin C led to further decreases in V394L mutant GCase activity as measured in vitro.	true	true	true	true	true	6,338
1	DISCUSSION	0	null	null	20,047,948	pmid-9668348\|pmid-8663398\|pmid-12813057\|pmid-16061944\|pmid-17954913\|pmid-9668348\|pmid-11051765	This GCase protein level was also decreased indicating an increased instability or susceptibility of the mutant protein to proteolysis.	null	135	36,945	0	false	null	null	This GCase protein level was also decreased indicating an increased instability or susceptibility of the mutant protein to proteolysis.	true	true	true	true	true	6,338
1	DISCUSSION	0	null	null	20,047,948	pmid-9668348\|pmid-8663398\|pmid-12813057\|pmid-16061944\|pmid-17954913\|pmid-9668348\|pmid-11051765	Because of this decrease in GCase activity from ∼15 to ∼6% of WT levels, a new phenotype emerged with primarily central nervous system disease and with biochemical evidence of GC and GS storage in the viscera.	null	209	36,946	0	false	null	null	Because of this decrease in GCase activity from ∼15 to ∼6% of WT levels, a new phenotype emerged with primarily central nervous system disease and with biochemical evidence of GC and GS storage in the viscera.	true	true	true	true	true	6,338
1	DISCUSSION	0	null	null	20,047,948	pmid-9668348\|pmid-8663398\|pmid-12813057\|pmid-16061944\|pmid-17954913\|pmid-9668348\|pmid-11051765	Furthermore, the reduced V394L GCase activity in the brain was below a threshold to prevent the development of central nervous system disease, since neither the V394L homozygote nor the saposin C−/− mice themselves develop progressive central nervous system disease in the time frame of these studies.	null	301	36,947	0	false	null	null	Furthermore, the reduced V394L GCase activity in the brain was below a threshold to prevent the development of central nervous system disease, since neither the V394L homozygote nor the saposin C−/− mice themselves develop progressive central nervous system disease in the time frame of these studies.	true	true	true	true	true	6,338
2	DISCUSSION	1	31	[ "DDP580C31" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	A curious finding was that the level of GC in the brain had only minor changes, unlike the level of GS that showed major increases.	[ "31" ]	131	36,948	0	false	A curious finding was that the level of GC in the brain had only minor changes, unlike the level of GS that showed major increases.	[]	A curious finding was that the level of GC in the brain had only minor changes, unlike the level of GS that showed major increases.	true	true	true	true	true	6,339
2	DISCUSSION	1	31	[ "DDP580C31" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	GS is known to be highly toxic to cells, particularly neurons (31), and the elevated GS levels led to selective deterioration of the central nervous system in the 4L;C* mice.	[ "31" ]	174	36,949	1	false	GS is known to be highly toxic to cells, particularly neurons, and the elevated GS levels led to selective deterioration of the central nervous system in the 4L;C* mice.	[ "31" ]	GS is known to be highly toxic to cells, particularly neurons, and the elevated GS levels led to selective deterioration of the central nervous system in the 4L;C* mice.	true	true	true	true	true	6,339
2	DISCUSSION	1	31	[ "DDP580C31" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	Although, the levels of GS in visceral tissues, on a fold basis, were similar to or greater than those in the CNS, the visceral organs do not show any major histological abnormalities.	[ "31" ]	184	36,950	0	false	Although, the levels of GS in visceral tissues, on a fold basis, were similar to or greater than those in the CNS, the visceral organs do not show any major histological abnormalities.	[]	Although, the levels of GS in visceral tissues, on a fold basis, were similar to or greater than those in the CNS, the visceral organs do not show any major histological abnormalities.	true	true	true	true	true	6,339
2	DISCUSSION	1	31	[ "DDP580C31" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	The lipid abnormalities were detectable only using MS.	[ "31" ]	54	36,951	0	false	The lipid abnormalities were detectable only using MS.	[]	The lipid abnormalities were detectable only using MS.	true	true	true	true	true	6,339
2	DISCUSSION	1	31	[ "DDP580C31" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	Thus, it appears that the visceral tissues are relatively resistant or insensitive to the toxic effects of GS.	[ "31" ]	110	36,952	0	false	Thus, it appears that the visceral tissues are relatively resistant or insensitive to the toxic effects of GS.	[]	Thus, it appears that the visceral tissues are relatively resistant or insensitive to the toxic effects of GS.	true	true	true	true	true	6,339
2	DISCUSSION	1	31	[ "DDP580C31" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	There is a much greater toxicity to similarly raised levels of GS for CNS cells.	[ "31" ]	80	36,953	0	false	There is a much greater toxicity to similarly raised levels of GS for CNS cells.	[]	There is a much greater toxicity to similarly raised levels of GS for CNS cells.	true	true	true	true	true	6,339
2	DISCUSSION	1	31	[ "DDP580C31" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	This difference in sensitivity may relate to the fact that neurons and glial cells in central nervous system are more vulnerable to GSLs accumulation than the cells in the liver and some other visceral tissues.	[ "31" ]	210	36,954	0	false	This difference in sensitivity may relate to the fact that neurons and glial cells in central nervous system are more vulnerable to GSLs accumulation than the cells in the liver and some other visceral tissues.	[]	This difference in sensitivity may relate to the fact that neurons and glial cells in central nervous system are more vulnerable to GSLs accumulation than the cells in the liver and some other visceral tissues.	true	true	true	true	true	6,339
2	DISCUSSION	1	31	[ "DDP580C31" ]	20,047,948	pmid-1594045\|pmid-12208131\|pmid-7632321\|pmid-7632321\|pmid-17954912\|pmid-18346921\|pmid-17954912\|pmid-18346921\|pmid-16061944\|pmid-12208132\|pmid-14678774	Within the central nervous system, this disease process is also selective with specific involvement of neurons and some cells within the spinal cord while leaving much of the white matter uninvolved.	[ "31" ]	199	36,955	0	false	Within the central nervous system, this disease process is also selective with specific involvement of neurons and some cells within the spinal cord while leaving much of the white matter uninvolved.	[]	Within the central nervous system, this disease process is also selective with specific involvement of neurons and some cells within the spinal cord while leaving much of the white matter uninvolved.	true	true	true	true	true	6,339
3	DISCUSSION	1	23	[ "DDP580C23" ]	20,047,948	NA	It is also clear that saposin C interacts functionally with both WT and mutant GCases.	[ "23" ]	86	36,956	0	false	It is also clear that saposin C interacts functionally with both WT and mutant GCases.	[]	It is also clear that saposin C interacts functionally with both WT and mutant GCases.	true	true	true	true	true	6,340
3	DISCUSSION	1	23	[ "DDP580C23" ]	20,047,948	NA	In both the saposin C−/− mouse with WT or with V394L GCases, the amount of enzyme protein present in the central nervous system is diminished compared with saposin C+/+ animals.	[ "23" ]	177	36,957	0	false	In both the saposin C−/− mouse with WT or with V394L GCases, the amount of enzyme protein present in the central nervous system is diminished compared with saposin C+/+ animals.	[]	In both the saposin C−/− mouse with WT or with V394L GCases, the amount of enzyme protein present in the central nervous system is diminished compared with saposin C+/+ animals.	true	true	true	true	true	6,340
3	DISCUSSION	1	23	[ "DDP580C23" ]	20,047,948	NA	The amount of WT GCase in saposin C−/− mice appears to be sufficient for the maintenance of central nervous system function in a normal state for periods >12 months and that the eventual phenotype is not clearly related to the accumulation of GC or GS within the CNS.	[ "23" ]	267	36,958	0	false	The amount of WT GCase in saposin C−/− mice appears to be sufficient for the maintenance of central nervous system function in a normal state for periods >12 months and that the eventual phenotype is not clearly related to the accumulation of GC or GS within the CNS.	[]	The amount of WT GCase in saposin C−/− mice appears to be sufficient for the maintenance of central nervous system function in a normal state for periods >12 months and that the eventual phenotype is not clearly related to the accumulation of GC or GS within the CNS.	true	true	true	true	true	6,340
3	DISCUSSION	1	23	[ "DDP580C23" ]	20,047,948	NA	Thus, the axonal degeneration and other histological abnormalities seen in the saposin C−/− mouse must relate to other intrinsic functions of saposin C, unrelated to its activity in promoting optimal GCase function (23).	[ "23" ]	220	36,959	1	false	Thus, the axonal degeneration and other histological abnormalities seen in the saposin C−/− mouse must relate to other intrinsic functions of saposin C, unrelated to its activity in promoting optimal GCase function.	[ "23" ]	Thus, the axonal degeneration and other histological abnormalities seen in the saposin C−/− mouse must relate to other intrinsic functions of saposin C, unrelated to its activity in promoting optimal GCase function.	true	true	true	true	true	6,340
3	DISCUSSION	1	23	[ "DDP580C23" ]	20,047,948	NA	In contrast, the additional decrease in V394L activity caused by the absence of saposin C is below a threshold necessary for the protection of the central nervous system from GS toxicity.	[ "23" ]	187	36,960	0	false	In contrast, the additional decrease in V394L activity caused by the absence of saposin C is below a threshold necessary for the protection of the central nervous system from GS toxicity.	[]	In contrast, the additional decrease in V394L activity caused by the absence of saposin C is below a threshold necessary for the protection of the central nervous system from GS toxicity.	true	true	true	true	true	6,340
3	DISCUSSION	1	23	[ "DDP580C23" ]	20,047,948	NA	The early demise of the 4L;C* mice (48 days) compared with the longer lifespan of the saposin C−/− mice (>20 months), suggests that the toxic effects may be attributed to GS.	[ "23" ]	174	36,961	0	false	The early demise of the 4L;C* mice (48 days) compared with the longer lifespan of the saposin C−/− mice (>20 months), suggests that the toxic effects may be attributed to GS.	[]	The early demise of the 4L;C* mice (48 days) compared with the longer lifespan of the saposin C−/− mice, suggests that the toxic effects may be attributed to GS.	true	true	true	true	true	6,340
4	DISCUSSION	1	35	[ "DDP580C35" ]	20,047,948	pmid-3967661	An interesting question is the differential accumulation of GS compared with GC in the brains of 4L;C* mice.	[ "35" ]	108	36,962	0	false	An interesting question is the differential accumulation of GS compared with GC in the brains of 4L;C* mice.	[]	An interesting question is the differential accumulation of GS compared with GC in the brains of 4L;C* mice.	true	true	true	true	true	6,341
4	DISCUSSION	1	35	[ "DDP580C35" ]	20,047,948	pmid-3967661	Possible explanations include either functions related to saposin C or to the mutant enzyme V394L or both.	[ "35" ]	106	36,963	0	false	Possible explanations include either functions related to saposin C or to the mutant enzyme V394L or both.	[]	Possible explanations include either functions related to saposin C or to the mutant enzyme V394L or both.	true	true	true	true	true	6,341
4	DISCUSSION	1	35	[ "DDP580C35" ]	20,047,948	pmid-3967661	Saposin C could affect substrate specificity and enhance the activity of GCase to a greater degree toward the deacylated analog, GS, compared with GC.	[ "35" ]	150	36,964	0	false	Saposin C could affect substrate specificity and enhance the activity of GCase to a greater degree toward the deacylated analog, GS, compared with GC.	[]	Saposin C could affect substrate specificity and enhance the activity of GCase to a greater degree toward the deacylated analog, GS, compared with GC.	true	true	true	true	true	6,341
4	DISCUSSION	1	35	[ "DDP580C35" ]	20,047,948	pmid-3967661	This will be investigated in future studies.	[ "35" ]	44	36,965	0	false	This will be investigated in future studies.	[]	This will be investigated in future studies.	true	true	true	true	true	6,341
4	DISCUSSION	1	35	[ "DDP580C35" ]	20,047,948	pmid-3967661	An alternative explanation is that the V394L has a preference for GS or GC substrates.	[ "35" ]	86	36,966	0	false	An alternative explanation is that the V394L has a preference for GS or GC substrates.	[]	An alternative explanation is that the V394L has a preference for GS or GC substrates.	true	true	true	true	true	6,341
4	DISCUSSION	1	35	[ "DDP580C35" ]	20,047,948	pmid-3967661	GS has an affinity (as measured by Ki) for V394L that is ∼4- to 5-fold decreased compared with WT, and that GC has a normal binding constant for this enzyme (Liou and Grabowski, unpublished data).	[ "35" ]	196	36,967	0	false	GS has an affinity (as measured by Ki) for V394L that is ∼4- to 5-fold decreased compared with WT, and that GC has a normal binding constant for this enzyme (Liou and Grabowski, unpublished data).	[]	GS has an affinity (as measured by Ki) for V394L that is ∼4- to 5-fold decreased compared with WT, and that GC has a normal binding constant for this enzyme (Liou and Grabowski, unpublished data).	true	true	true	true	true	6,341
4	DISCUSSION	1	35	[ "DDP580C35" ]	20,047,948	pmid-3967661	This suggests a potentially pure kinetic effect of a diminished enzymatic activity in which, once below a threshold, GS, because of its poor binding, cannot engage V394L GCase and cannot be hydrolyzed, whereas GC can.	[ "35" ]	217	36,968	0	false	This suggests a potentially pure kinetic effect of a diminished enzymatic activity in which, once below a threshold, GS, because of its poor binding, cannot engage V394L GCase and cannot be hydrolyzed, whereas GC can.	[]	This suggests a potentially pure kinetic effect of a diminished enzymatic activity in which, once below a threshold, GS, because of its poor binding, cannot engage V394L GCase and cannot be hydrolyzed, whereas GC can.	true	true	true	true	true	6,341
4	DISCUSSION	1	35	[ "DDP580C35" ]	20,047,948	pmid-3967661	Vaccaro et al.	[ "35" ]	14	36,969	0	false	Vaccaro et al.	[]	Vaccaro et al.	true	true	true	true	true	6,341
4	DISCUSSION	1	35	[ "DDP580C35" ]	20,047,948	pmid-3967661	(35) showed that the kcat for GS was ∼100-fold less than that for GC using purified WT GCase.	[ "35" ]	93	36,970	1	false	showed that the kcat for GS was ∼100-fold less than that for GC using purified WT GCase.	[ "35" ]	showed that the kcat for GS was ∼100-fold less than that for GC using purified WT GCase.	false	true	true	true	false	6,341
4	DISCUSSION	1	35	[ "DDP580C35" ]	20,047,948	pmid-3967661	If this also applies to the V394L enzyme and the binding constant is diminished, the accumulation of GS could be explained on the basis of a kinetic phenomenon, based on the decreased ability of V394L to cleave the less preferred substrate.	[ "35" ]	240	36,971	0	false	If this also applies to the V394L enzyme and the binding constant is diminished, the accumulation of GS could be explained on the basis of a kinetic phenomenon, based on the decreased ability of V394L to cleave the less preferred substrate.	[]	If this also applies to the V394L enzyme and the binding constant is diminished, the accumulation of GS could be explained on the basis of a kinetic phenomenon, based on the decreased ability of V394L to cleave the less preferred substrate.	true	true	true	true	true	6,341
5	DISCUSSION	0	null	null	20,047,948	null	Finally, the studies here address the question of whether the toxic agent in neuronopathic Gaucher disease is GC or GS.	null	119	36,972	0	false	null	null	Finally, the studies here address the question of whether the toxic agent in neuronopathic Gaucher disease is GC or GS.	true	true	true	true	true	6,342
5	DISCUSSION	0	null	null	20,047,948	null	The 4L;C* mouse accumulates GS to greater relative levels than GC; 4L;C* is nearly a pure GS storage disease that leads to central nervous dysfunction and eventual death.	null	170	36,973	0	false	null	null	The 4L;C* mouse accumulates GS to greater relative levels than GC; 4L;C* is nearly a pure GS storage disease that leads to central nervous dysfunction and eventual death.	true	true	true	true	true	6,342
5	DISCUSSION	0	null	null	20,047,948	null	As a pure GC storage disease of CNS is not available, the question of this lipid's toxicity alone cannot be directly addressed.	null	127	36,974	0	false	null	null	As a pure GC storage disease of CNS is not available, the question of this lipid's toxicity alone cannot be directly addressed.	true	true	true	true	true	6,342
5	DISCUSSION	0	null	null	20,047,948	null	However, the in vitro studies showing toxicity of galactosylsphingosine and GS translate reasonably well to their CNS animal models, i.e.	null	137	36,975	0	false	null	null	However, the in vitro studies showing toxicity of galactosylsphingosine and GS translate reasonably well to their CNS animal models, i.e.	true	true	true	true	true	6,342
5	DISCUSSION	0	null	null	20,047,948	null	the twitcher mouse and the 4L;C* mouse, respectively.	null	53	36,976	0	false	null	null	the twitcher mouse and the 4L;C* mouse, respectively.	false	true	true	true	false	6,342
5	DISCUSSION	0	null	null	20,047,948	null	The in vivo toxicity of GS to neurons remains to be clarified.	null	62	36,977	0	false	null	null	The in vivo toxicity of GS to neurons remains to be clarified.	true	true	true	true	true	6,342
5	DISCUSSION	0	null	null	20,047,948	null	It will be important to address whether a diminution in GS can occur by the use of GC synthase inhibitors, and thereby diminish toxicity of GS.	null	143	36,978	0	false	null	null	It will be important to address whether a diminution in GS can occur by the use of GC synthase inhibitors, and thereby diminish toxicity of GS.	true	true	true	true	true	6,342
5	DISCUSSION	0	null	null	20,047,948	null	If it is true that GC synthase is responsible for all or most of the synthesis of GC and GS, compounds that inhibit this synthase could be therapeutic to the neuropathic forms of Gaucher disease.	null	195	36,979	0	false	null	null	If it is true that GC synthase is responsible for all or most of the synthesis of GC and GS, compounds that inhibit this synthase could be therapeutic to the neuropathic forms of Gaucher disease.	true	true	true	true	true	6,342
0	DISCUSSION	1	7	[ "r7", "r18", "r10", "r12", "r14" ]	19,056,608	pmid-16306382\|pmid-8450063\|pmid-12766130\|pmid-8353919\|pmid-9482439	Our data demonstrate that antecedent hypoglycemia results in a significant decrease in 1) cardiac vagal baroreflex sensitivity and 2) the sympathetic response to both a transient pharmacologically induced hypotensive stress and a graded simulated orthostatic stress using LBNP.	[ "7", "18", "10", "12", "14" ]	277	36,980	0	false	Our data demonstrate that antecedent hypoglycemia results in a significant decrease in 1) cardiac vagal baroreflex sensitivity and 2) the sympathetic response to both a transient pharmacologically induced hypotensive stress and a graded simulated orthostatic stress using LBNP.	[]	Our data demonstrate that antecedent hypoglycemia results in a significant decrease in 1) cardiac vagal baroreflex sensitivity and 2) the sympathetic response to both a transient pharmacologically induced hypotensive stress and a graded simulated orthostatic stress using LBNP.	true	true	true	true	true	6,343
0	DISCUSSION	1	7	[ "r7", "r18", "r10", "r12", "r14" ]	19,056,608	pmid-16306382\|pmid-8450063\|pmid-12766130\|pmid-8353919\|pmid-9482439	It is well established that prior exposure to hypoglycemia attenuates the autonomic nervous system response to subsequent hypoglycemia (7,18).	[ "7", "18", "10", "12", "14" ]	142	36,981	0	false	It is well established that prior exposure to hypoglycemia attenuates the autonomic nervous system response to subsequent hypoglycemia.	[ "7,18" ]	It is well established that prior exposure to hypoglycemia attenuates the autonomic nervous system response to subsequent hypoglycemia.	true	true	true	true	true	6,343
0	DISCUSSION	1	7	[ "r7", "r18", "r10", "r12", "r14" ]	19,056,608	pmid-16306382\|pmid-8450063\|pmid-12766130\|pmid-8353919\|pmid-9482439	The present data, which show that prior hypoglycemia attenuates the autonomic response to specific cardiovascular stresses, extend those findings.	[ "7", "18", "10", "12", "14" ]	146	36,982	0	false	The present data, which show that prior hypoglycemia attenuates the autonomic response to specific cardiovascular stresses, extend those findings.	[]	The present data, which show that prior hypoglycemia attenuates the autonomic response to specific cardiovascular stresses, extend those findings.	true	true	true	true	true	6,343
0	DISCUSSION	1	7	[ "r7", "r18", "r10", "r12", "r14" ]	19,056,608	pmid-16306382\|pmid-8450063\|pmid-12766130\|pmid-8353919\|pmid-9482439	Furthermore, the evidence that antecedent hypoglycemia attenuates cardiovascular autonomic control may have significant clinical implications; impaired autonomic function is associated with and may be a contributor to mortality in diabetes and cardiovascular disease (10,12–14).	[ "7", "18", "10", "12", "14" ]	278	36,983	0	false	Furthermore, the evidence that antecedent hypoglycemia attenuates cardiovascular autonomic control may have significant clinical implications; impaired autonomic function is associated with and may be a contributor to mortality in diabetes and cardiovascular disease.	[ "10,12–14" ]	Furthermore, the evidence that antecedent hypoglycemia attenuates cardiovascular autonomic control may have significant clinical implications; impaired autonomic function is associated with and may be a contributor to mortality in diabetes and cardiovascular disease.	true	true	true	true	true	6,343
1	DISCUSSION	1	7	[ "r7", "r19", "r20", "r21", "r20", "r21" ]	19,056,608	pmid-16306382\|pmid-8194668\|pmid-7962332\|pmid-10615952\|pmid-7962332\|pmid-10615952	It is well established from studies in healthy and diabetic subjects that exposure to recent hypoglycemia reduces the counterregulatory hormone (e.g., epinephrine, glucagon, and adrenocorticotropic hormone) and autonomic nervous system responses to subsequent hypoglycemia.	[ "7", "19", "20", "21", "20", "21" ]	273	36,984	0	false	It is well established from studies in healthy and diabetic subjects that exposure to recent hypoglycemia reduces the counterregulatory hormone (e.g., epinephrine, glucagon, and adrenocorticotropic hormone) and autonomic nervous system responses to subsequent hypoglycemia.	[]	It is well established from studies in healthy and diabetic subjects that exposure to recent hypoglycemia reduces the counterregulatory hormone (e.g., epinephrine, glucagon, and adrenocorticotropic hormone) and autonomic nervous system responses to subsequent hypoglycemia.	true	true	true	true	true	6,344
1	DISCUSSION	1	7	[ "r7", "r19", "r20", "r21", "r20", "r21" ]	19,056,608	pmid-16306382\|pmid-8194668\|pmid-7962332\|pmid-10615952\|pmid-7962332\|pmid-10615952	This hypoglycemia-associated autonomic failure/dysfunction leads to decreased ability to sense hypoglycemia and restore euglycemia (7).	[ "7", "19", "20", "21", "20", "21" ]	135	36,985	1	false	This hypoglycemia-associated autonomic failure/dysfunction leads to decreased ability to sense hypoglycemia and restore euglycemia.	[ "7" ]	This hypoglycemia-associated autonomic failure/dysfunction leads to decreased ability to sense hypoglycemia and restore euglycemia.	true	true	true	true	true	6,344
1	DISCUSSION	1	7	[ "r7", "r19", "r20", "r21", "r20", "r21" ]	19,056,608	pmid-16306382\|pmid-8194668\|pmid-7962332\|pmid-10615952\|pmid-7962332\|pmid-10615952	However, there are conflicting reports as to whether antecedent hypoglycemia impairs the autonomic response to nonhypoglycemic stimuli as well as hypoglycemic stimuli.	[ "7", "19", "20", "21", "20", "21" ]	167	36,986	0	false	However, there are conflicting reports as to whether antecedent hypoglycemia impairs the autonomic response to nonhypoglycemic stimuli as well as hypoglycemic stimuli.	[]	However, there are conflicting reports as to whether antecedent hypoglycemia impairs the autonomic response to nonhypoglycemic stimuli as well as hypoglycemic stimuli.	true	true	true	true	true	6,344
1	DISCUSSION	1	19	[ "r7", "r19", "r20", "r21", "r20", "r21" ]	19,056,608	pmid-16306382\|pmid-8194668\|pmid-7962332\|pmid-10615952\|pmid-7962332\|pmid-10615952	In one study of type 1 diabetic subjects, the epinephrine and norepinephrine responses to exercise and upright posture were intact after antecedent hypoglycemia (19).	[ "7", "19", "20", "21", "20", "21" ]	166	36,987	1	false	In one study of type 1 diabetic subjects, the epinephrine and norepinephrine responses to exercise and upright posture were intact after antecedent hypoglycemia.	[ "19" ]	In one study of type 1 diabetic subjects, the epinephrine and norepinephrine responses to exercise and upright posture were intact after antecedent hypoglycemia.	true	true	true	true	true	6,344
1	DISCUSSION	1	20	[ "r7", "r19", "r20", "r21", "r20", "r21" ]	19,056,608	pmid-16306382\|pmid-8194668\|pmid-7962332\|pmid-10615952\|pmid-7962332\|pmid-10615952	Other studies of type 1 diabetic subjects suggested that the deficit is more generalized (20,21); the epinephrine and norepinephrine responses to a cold pressor test were reduced in well-controlled type 1 diabetic subjects (20), and antecedent hypoglycemia reduced the normal exercise-induced rise in epinephrine, norepi...	[ "7", "19", "20", "21", "20", "21" ]	421	36,988	1	false	Other studies of type 1 diabetic subjects suggested that the deficit is more generalized ; the epinephrine and norepinephrine responses to a cold pressor test were reduced in well-controlled type 1 diabetic subjects, and antecedent hypoglycemia reduced the normal exercise-induced rise in epinephrine, norepinephrine, gl...	[ "20,21", "20", "21" ]	Other studies of type 1 diabetic subjects suggested that the deficit is more generalized ; the epinephrine and norepinephrine responses to a cold pressor test were reduced in well-controlled type 1 diabetic subjects, and antecedent hypoglycemia reduced the normal exercise-induced rise in epinephrine, norepinephrine, gl...	true	true	true	true	true	6,344
1	DISCUSSION	1	7	[ "r7", "r19", "r20", "r21", "r20", "r21" ]	19,056,608	pmid-16306382\|pmid-8194668\|pmid-7962332\|pmid-10615952\|pmid-7962332\|pmid-10615952	Our data are consistent with these latter studies and strongly support the view that the effects of antecedent hypoglycemia on the autonomic nervous system are more generalized and not specific to subsequent hypoglycemic stimuli.	[ "7", "19", "20", "21", "20", "21" ]	229	36,989	0	false	Our data are consistent with these latter studies and strongly support the view that the effects of antecedent hypoglycemia on the autonomic nervous system are more generalized and not specific to subsequent hypoglycemic stimuli.	[]	Our data are consistent with these latter studies and strongly support the view that the effects of antecedent hypoglycemia on the autonomic nervous system are more generalized and not specific to subsequent hypoglycemic stimuli.	true	true	true	true	true	6,344
2	DISCUSSION	1	22	[ "r22" ]	19,056,608	pmid-15161758	Prior studies have shown that during hypoglycemia, there is acquired prolongation of the rate corrected Q-T interval (22).	[ "22" ]	122	36,990	1	false	Prior studies have shown that during hypoglycemia, there is acquired prolongation of the rate corrected Q-T interval.	[ "22" ]	Prior studies have shown that during hypoglycemia, there is acquired prolongation of the rate corrected Q-T interval.	true	true	true	true	true	6,345
2	DISCUSSION	1	22	[ "r22" ]	19,056,608	pmid-15161758	Our findings show that antecedent hypoglycemia leads to impaired control of cardiovascular function, even after euglycemia is restored, and that the effects of antecedent hypoglycemia on autonomic function can last for at least 16 h.	[ "22" ]	233	36,991	0	false	Our findings show that antecedent hypoglycemia leads to impaired control of cardiovascular function, even after euglycemia is restored, and that the effects of antecedent hypoglycemia on autonomic function can last for at least 16 h.	[]	Our findings show that antecedent hypoglycemia leads to impaired control of cardiovascular function, even after euglycemia is restored, and that the effects of antecedent hypoglycemia on autonomic function can last for at least 16 h.	true	true	true	true	true	6,345
2	DISCUSSION	1	22	[ "r22" ]	19,056,608	pmid-15161758	We demonstrated that antecedent hypoglycemia attenuated the sympathoadrenal and muscle sympathetic nerve activity outflow responses to simulated orthostatic stress and transient hypotension.	[ "22" ]	190	36,992	0	false	We demonstrated that antecedent hypoglycemia attenuated the sympathoadrenal and muscle sympathetic nerve activity outflow responses to simulated orthostatic stress and transient hypotension.	[]	We demonstrated that antecedent hypoglycemia attenuated the sympathoadrenal and muscle sympathetic nerve activity outflow responses to simulated orthostatic stress and transient hypotension.	true	true	true	true	true	6,345
2	DISCUSSION	1	22	[ "r22" ]	19,056,608	pmid-15161758	Thus, in the clinical setting, it is possible that recent exposure to hypoglycemia could impair sympathetic nervous system responses to cardiovascular stresses.	[ "22" ]	160	36,993	0	false	Thus, in the clinical setting, it is possible that recent exposure to hypoglycemia could impair sympathetic nervous system responses to cardiovascular stresses.	[]	Thus, in the clinical setting, it is possible that recent exposure to hypoglycemia could impair sympathetic nervous system responses to cardiovascular stresses.	true	true	true	true	true	6,345
3	DISCUSSION	1	12	[ "r12", "r23", "r25", "r13", "r14", "r26" ]	19,056,608	pmid-8353919\|pmid-3812275\|pmid-1872267\|pmid-18068036\|pmid-9482439\|pmid-3168199	Antecedent hypoglycemia also decreased baroreflex sensitivity, which indicates impairment in vagal cardiac modulation.	[ "12", "23", "25", "13", "14", "26" ]	118	36,994	0	false	Antecedent hypoglycemia also decreased baroreflex sensitivity, which indicates impairment in vagal cardiac modulation.	[]	Antecedent hypoglycemia also decreased baroreflex sensitivity, which indicates impairment in vagal cardiac modulation.	true	true	true	true	true	6,346
3	DISCUSSION	1	12	[ "r12", "r23", "r25", "r13", "r14", "r26" ]	19,056,608	pmid-8353919\|pmid-3812275\|pmid-1872267\|pmid-18068036\|pmid-9482439\|pmid-3168199	Decreases in vagal autonomic function may lead to attenuation of vagal protection against sudden arrhythmic death.	[ "12", "23", "25", "13", "14", "26" ]	114	36,995	0	false	Decreases in vagal autonomic function may lead to attenuation of vagal protection against sudden arrhythmic death.	[]	Decreases in vagal autonomic function may lead to attenuation of vagal protection against sudden arrhythmic death.	true	true	true	true	true	6,346
3	DISCUSSION	1	12	[ "r12", "r23", "r25", "r13", "r14", "r26" ]	19,056,608	pmid-8353919\|pmid-3812275\|pmid-1872267\|pmid-18068036\|pmid-9482439\|pmid-3168199	Impaired cardiac vagal control, as determined by reduced heart rate variability, is associated with increased risk of postmyocardial infarction mortality, even after adjusting for clinical, demographic, other Holter features, and ejection fraction (12,23–25).	[ "12", "23", "25", "13", "14", "26" ]	259	36,996	0	false	Impaired cardiac vagal control, as determined by reduced heart rate variability, is associated with increased risk of postmyocardial infarction mortality, even after adjusting for clinical, demographic, other Holter features, and ejection fraction.	[ "12,23–25" ]	Impaired cardiac vagal control, as determined by reduced heart rate variability, is associated with increased risk of postmyocardial infarction mortality, even after adjusting for clinical, demographic, other Holter features, and ejection fraction.	true	true	true	true	true	6,346
3	DISCUSSION	1	26	[ "r12", "r23", "r25", "r13", "r14", "r26" ]	19,056,608	pmid-8353919\|pmid-3812275\|pmid-1872267\|pmid-18068036\|pmid-9482439\|pmid-3168199	In addition, impairment of baroreflex sensitivity has been associated with adverse outcomes in clinical (13,14) and preclinical (26) studies.	[ "12", "23", "25", "13", "14", "26" ]	141	36,997	1	false	In addition, impairment of baroreflex sensitivity has been associated with adverse outcomes in clinical and preclinical studies.	[ "13,14", "26" ]	In addition, impairment of baroreflex sensitivity has been associated with adverse outcomes in clinical and preclinical studies.	true	true	true	true	true	6,346
4	DISCUSSION	1	14	[ "r14", "r13" ]	19,056,608	pmid-9482439\|pmid-18068036	Baroreflex sensitivity, calculated from the measurement of the heart rate–blood pressure relation after an intravenous bolus of phenylephrine, was a significant independent risk predictor of cardiac mortality in the Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) study, an international multicenter pro...	[ "14", "13" ]	394	36,998	1	false	Baroreflex sensitivity, calculated from the measurement of the heart rate–blood pressure relation after an intravenous bolus of phenylephrine, was a significant independent risk predictor of cardiac mortality in the Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) study, an international multicenter pro...	[ "14" ]	Baroreflex sensitivity, calculated from the measurement of the heart rate–blood pressure relation after an intravenous bolus of phenylephrine, was a significant independent risk predictor of cardiac mortality in the Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) study, an international multicenter pro...	true	true	true	true	true	6,347
4	DISCUSSION	1	14	[ "r14", "r13" ]	19,056,608	pmid-9482439\|pmid-18068036	The 2-year mortality for individuals with baroreflex sensitivity <3.1 ms/mmHg was 9%, versus 2% for those with preserved baroreflex sensitivity.	[ "14", "13" ]	144	36,999	0	false	The 2-year mortality for individuals with baroreflex sensitivity <3.1 ms/mmHg was 9%, versus 2% for those with preserved baroreflex sensitivity.	[]	The 2-year mortality for individuals with baroreflex sensitivity <3.1 ms/mmHg was 9%, versus 2% for those with preserved baroreflex sensitivity.	true	true	true	true	true	6,347
4	DISCUSSION	1	13	[ "r14", "r13" ]	19,056,608	pmid-9482439\|pmid-18068036	In a 5-year follow-up study of a subset of 244 patients with ST-segment elevation myocardial infarction and normal ejection fraction, impaired baroreflex sensitivity (<3.1 ms/mmHg) 4–6 weeks after the myocardial infarction identified patients with a relative risk of cardiovascular mortality of 11.4, compared with those...	[ "14", "13" ]	366	37,000	1	false	In a 5-year follow-up study of a subset of 244 patients with ST-segment elevation myocardial infarction and normal ejection fraction, impaired baroreflex sensitivity (<3.1 ms/mmHg) 4–6 weeks after the myocardial infarction identified patients with a relative risk of cardiovascular mortality of 11.4, compared with those...	[ "13" ]	In a 5-year follow-up study of a subset of 244 patients with ST-segment elevation myocardial infarction and normal ejection fraction, impaired baroreflex sensitivity 4–6 weeks after the myocardial infarction identified patients with a relative risk of cardiovascular mortality of 11.4, compared with those without impair...	true	true	true	true	true	6,347
5	DISCUSSION	0	null	null	19,056,608	null	In the current study, baroreflex sensitivity in normal subjects after antecedent hypoglycemia did not reach the level of 3.1 ms/mmHg; however, given the observed reduction that was evident in our studies (6 of 20 subjects had a decrease in baroreflex sensitivity of >5 ms/mmHg, and 3 subjects had a decrease in barorefle...	null	515	37,001	0	false	null	null	In the current study, baroreflex sensitivity in normal subjects after antecedent hypoglycemia did not reach the level of 3.1 ms/mmHg; however, given the observed reduction that was evident in our studies (6 of 20 subjects had a decrease in baroreflex sensitivity of >5 ms/mmHg, and 3 subjects had a decrease in barorefle...	true	true	true	true	true	6,348
5	DISCUSSION	0	null	null	19,056,608	null	Thus, hypoglycemia-induced impairment in baroreflex sensitivity and/or sympathetic nervous system cardiovascular control (as noted above) could have clinical implications, especially in critically ill patients or in patients at high risk for cardiovascular events.	null	264	37,002	0	false	null	null	Thus, hypoglycemia-induced impairment in baroreflex sensitivity and/or sympathetic nervous system cardiovascular control (as noted above) could have clinical implications, especially in critically ill patients or in patients at high risk for cardiovascular events.	true	true	true	true	true	6,348
6	DISCUSSION	0	null	null	19,056,608	null	The high-frequency power of the R-R interval in response to paced breathing, also an index of cardiac vagal control, correlated positively with cardiac vagal baroreflex sensitivity in our study.	null	194	37,003	0	false	null	null	The high-frequency power of the R-R interval in response to paced breathing, also an index of cardiac vagal control, correlated positively with cardiac vagal baroreflex sensitivity in our study.	true	true	true	true	true	6,349
6	DISCUSSION	0	null	null	19,056,608	null	There was a strong tendency toward a reduction in the high-frequency R-R interval power in the posthypoglycemic state, but this did not reach statistical significance.	null	167	37,004	0	false	null	null	There was a strong tendency toward a reduction in the high-frequency R-R interval power in the posthypoglycemic state, but this did not reach statistical significance.	true	true	true	true	true	6,349
6	DISCUSSION	0	null	null	19,056,608	null	Several possible explanations for this finding exist.	null	53	37,005	0	false	null	null	Several possible explanations for this finding exist.	true	true	true	true	true	6,349
6	DISCUSSION	0	null	null	19,056,608	null	These include the following: 1) The provocation for the cardiac vagal baroreflex assessment (transient hypotension) provided a more consistent and potent stimulus than the provocation for respiratory-mediated R-R interval variability (we did not monitor or control the depth of respiration); and 2) there is a differenti...	null	401	37,006	0	false	null	null	These include the following: 1) The provocation for the cardiac vagal baroreflex assessment (transient hypotension) provided a more consistent and potent stimulus than the provocation for respiratory-mediated R-R interval variability (we did not monitor or control the depth of respiration); and 2) there is a differenti...	true	true	true	true	true	6,349
6	DISCUSSION	0	null	null	19,056,608	null	In future studies, both frequency and amplitude of respiration should be monitored.	null	83	37,007	0	false	null	null	In future studies, both frequency and amplitude of respiration should be monitored.	true	true	true	true	true	6,349
7	DISCUSSION	1	10	[ "r10", "r18", "r27", "r28", "r30", "r22" ]	19,056,608	pmid-12766130\|pmid-8450063\|pmid-2147633\|pmid-9133549\|pmid-9802751\|pmid-15161758	The present data may have implications for diabetic subjects particularly those with autonomic neuropathy who may have an increased mortality risk (10).	[ "10", "18", "27", "28", "30", "22" ]	152	37,008	1	false	The present data may have implications for diabetic subjects particularly those with autonomic neuropathy who may have an increased mortality risk.	[ "10" ]	The present data may have implications for diabetic subjects particularly those with autonomic neuropathy who may have an increased mortality risk.	true	true	true	true	true	6,350
7	DISCUSSION	1	10	[ "r10", "r18", "r27", "r28", "r30", "r22" ]	19,056,608	pmid-12766130\|pmid-8450063\|pmid-2147633\|pmid-9133549\|pmid-9802751\|pmid-15161758	Furthermore, it is possible that the consequences of antecedent hypoglycemia on autonomic function may be amplified in diabetic subjects, particularly those with autonomic dysfunction.	[ "10", "18", "27", "28", "30", "22" ]	184	37,009	0	false	Furthermore, it is possible that the consequences of antecedent hypoglycemia on autonomic function may be amplified in diabetic subjects, particularly those with autonomic dysfunction.	[]	Furthermore, it is possible that the consequences of antecedent hypoglycemia on autonomic function may be amplified in diabetic subjects, particularly those with autonomic dysfunction.	true	true	true	true	true	6,350
7	DISCUSSION	1	22	[ "r10", "r18", "r27", "r28", "r30", "r22" ]	19,056,608	pmid-12766130\|pmid-8450063\|pmid-2147633\|pmid-9133549\|pmid-9802751\|pmid-15161758	For example, although the reduced counterregulatory and hormonal response to antecedent hypoglycemia occurs in the absence of diabetic autonomic neuropathy, as measured by standard tests of autonomic function (18,27), several (28–30), although not all (22), studies suggest that the presence of autonomic dysfunction fur...	[ "10", "18", "27", "28", "30", "22" ]	375	37,010	1	false	For example, although the reduced counterregulatory and hormonal response to antecedent hypoglycemia occurs in the absence of diabetic autonomic neuropathy, as measured by standard tests of autonomic function, several, although not all, studies suggest that the presence of autonomic dysfunction further attenuates the a...	[ "18,27", "28–30", "22" ]	For example, although the reduced counterregulatory and hormonal response to antecedent hypoglycemia occurs in the absence of diabetic autonomic neuropathy, as measured by standard tests of autonomic function, several, although not all, studies suggest that the presence of autonomic dysfunction further attenuates the a...	true	true	true	true	true	6,350
8	DISCUSSION	1	8	[ "r8", "r9" ]	19,056,608	pmid-17065355\|pmid-18539917	Other populations in which the consequences of antecedent hypoglycemia on autonomic function may be more apparent are critically ill patients and individuals with diabetes at risk for cardiovascular events.	[ "8", "9" ]	206	37,011	0	false	Other populations in which the consequences of antecedent hypoglycemia on autonomic function may be more apparent are critically ill patients and individuals with diabetes at risk for cardiovascular events.	[]	Other populations in which the consequences of antecedent hypoglycemia on autonomic function may be more apparent are critically ill patients and individuals with diabetes at risk for cardiovascular events.	true	true	true	true	true	6,351
8	DISCUSSION	1	8	[ "r8", "r9" ]	19,056,608	pmid-17065355\|pmid-18539917	There is a significant increase in mortality in critically ill patients who experience hypoglycemia.	[ "8", "9" ]	100	37,012	0	false	There is a significant increase in mortality in critically ill patients who experience hypoglycemia.	[]	There is a significant increase in mortality in critically ill patients who experience hypoglycemia.	true	true	true	true	true	6,351
8	DISCUSSION	1	8	[ "r8", "r9" ]	19,056,608	pmid-17065355\|pmid-18539917	The risk is similar irrespective of whether the critically ill patients received intensive or conventional insulin therapy and is not directly caused by hypoglycemia (8).	[ "8", "9" ]	170	37,013	1	false	The risk is similar irrespective of whether the critically ill patients received intensive or conventional insulin therapy and is not directly caused by hypoglycemia.	[ "8" ]	The risk is similar irrespective of whether the critically ill patients received intensive or conventional insulin therapy and is not directly caused by hypoglycemia.	true	true	true	true	true	6,351
8	DISCUSSION	1	9	[ "r8", "r9" ]	19,056,608	pmid-17065355\|pmid-18539917	Similarly, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which enrolled individuals with diabetes at increased risk of cardiovascular events, intensively lowering blood glucose to a goal glycated hemoglobin (A1C) level of <6.0% increases the risk of death compared with a less intensive treatm...	[ "8", "9" ]	345	37,014	1	false	Similarly, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which enrolled individuals with diabetes at increased risk of cardiovascular events, intensively lowering blood glucose to a goal glycated hemoglobin (A1C) level of <6.0% increases the risk of death compared with a less intensive treatm...	[ "9" ]	Similarly, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which enrolled individuals with diabetes at increased risk of cardiovascular events, intensively lowering blood glucose to a goal glycated hemoglobin (A1C) level of <6.0% increases the risk of death compared with a less intensive treatm...	true	true	true	true	true	6,351
8	DISCUSSION	1	8	[ "r8", "r9" ]	19,056,608	pmid-17065355\|pmid-18539917	The difference does not appear to be directly due to hypoglycemia or the use of a specific drug.	[ "8", "9" ]	96	37,015	0	false	The difference does not appear to be directly due to hypoglycemia or the use of a specific drug.	[]	The difference does not appear to be directly due to hypoglycemia or the use of a specific drug.	true	true	true	true	true	6,351

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