ライフサイエンスコーパス: undiagnosed

1 nd hypertrophic heart disease and often goes undiagnosed.

2 between groups and that many cases likely go undiagnosed.

3 ogists and may lead to carpal instability if undiagnosed.

4 ow-income and middle-income countries remain undiagnosed.

5 Most subjects with COPD in Canada remain undiagnosed.

6 rimary glaucoma, 196 (72.1%) were previously undiagnosed.

7 s and candidate gene sequencing and remained undiagnosed.

8 h diabetes, 36.4% (95% CI, 30.5%-42.7%) were undiagnosed.

9 Twenty-six patients (48%) died, half undiagnosed.

10 h diabetes, 25.2% (95% CI, 21.1%-29.8%) were undiagnosed.

11 er to one third of all diabetes cases remain undiagnosed.

12 many of these critically ill patients may be undiagnosed.

13 lity of their health and lives, yet often go undiagnosed.

14 Inherited polyneuropathies often go undiagnosed.

15 ficant number of patients remain genetically undiagnosed.

16 d States, and the bulk of those infected are undiagnosed.

17 NVs) in ID, but the majority of cases remain undiagnosed.

18 iduals in the U.S. still remain untested and undiagnosed.

19 be infected with HCV, and more than half are undiagnosed.

20 ted States, and one-third of these cases are undiagnosed.

21 AF may be asymptomatic and therefore undiagnosed.

22 families affected by such conditions remain undiagnosed.

23 by treating STIs that would otherwise remain undiagnosed.

24 lly asymptomatic, symptoms can arise if left undiagnosed.

25 d over a third of participants with HIV were undiagnosed (37.7%; 95% CI 29.8%-46.2%).

26 result, 34.7% of those living with HIV were undiagnosed (95% CI 23.5%-47.9%).

27 any hospital inpatients in South Africa have undiagnosed active and drug-resistant tuberculosis (TB).

28 isk of renal allograft loss in patients with undiagnosed adenine phosphoribosyltransferase deficiency

29 ole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leuk

30 Compared with diagnosed adults, undiagnosed adults have less elevated hemoglobin A1c lev

31 Among undiagnosed adults, 77.0%, 57.9%, 36.0%, and 77.9% met h

32 In contrast, among undiagnosed adults, 84.5% had a usual care provider and

33 cialty care enabled patients with previously undiagnosed advanced disease to be cured.

34 and were classified as "undiagnosed AERD." "Undiagnosed AERD" cases were less likely than "diagnosed

35 " and classify cases as "diagnosed AERD" or "undiagnosed AERD" on the basis of physician-documented A

36 y treating caregiver and were classified as "undiagnosed AERD." "Undiagnosed AERD" cases were less li

37 than 90% of the participants with previously undiagnosed AF accepted initiation of OAC treatment.

38 rdiac monitoring after stroke could identify undiagnosed AF earlier, leading to appropriate oral anti

39 The incidence of previously undiagnosed AF may be substantial in patients with risk

40 a considerable proportion of patients remain undiagnosed after Sanger.

41 A total of 30.0% of eyes with undiagnosed AMD had AMD with large drusen that would hav

42 Undiagnosed AMD was associated with older patient age (o

43 Prevalence of undiagnosed AMD was not different for ophthalmologists a

44 Among eyes with undiagnosed AMD, 32 (10.0%) had hyperpigmentation, 43 (1

45 id-Schiff (PAS) staining and PCR to identify undiagnosed amoebic appendicitis.

46 A total of 355 subjects were undiagnosed and 150 were diagnosed with COPD.

47 lt invasive procedure, patients often remain undiagnosed and inadequately treated.

48 rity of affected individuals probably remain undiagnosed and many do not experience greatly reduced l

49 5% of individuals with celiac disease remain undiagnosed and there is an average delay in diagnosis o

50 one in 40 000 to 300 000, but many cases are undiagnosed and unreported, and awareness among clinicia

51 atients is an unmet need, and there are many undiagnosed and untreated cases of DR.

52 : 1.5-4.3; P = .0012) greater odds of having undiagnosed and untreated glaucoma than non-Hispanic whi

53 Undiagnosed and untreated thiamine deficiencies are ofte

54 NPC is often left undiagnosed and untreated until a late stage of disease.

55 hich may lead to lethal consequences if left undiagnosed and untreated.

56 morbidity and societal burden, it is largely undiagnosed and untreated.

57 of patients with hyperparathyroidism remain undiagnosed and untreated.

58 ldwide, with the majority of cases remaining undiagnosed and untreated.

59 ong those with glaucoma, 78% were previously undiagnosed and untreated.

60 Therefore, MHE patients can remain undiagnosed and untreated.

61 the extent to which mosaicism might explain undiagnosed arrhythmia, we studied 7,500 affected proban

62 ght to evaluate the prevalence of previously undiagnosed arrhythmias in candidates for transcatheter

63 Concussion is frequently undiagnosed as a cause of psychiatric morbidity, especia

64 resent in 42% of the US population, is often undiagnosed as symptoms may not manifest for several yea

65 The prevalence of undiagnosed asthma in AA youth was 8.0% in Detroit and 7

66 gnosed asthma in Detroit, whereas those with undiagnosed asthma in Georgia reported more symptoms.

67 Undiagnosed asthma was defined as multiple respiratory s

68 Individuals with undiagnosed, asymptomatic COPD had an increased risk of

69 or death from all causes in individuals with undiagnosed, asymptomatic COPD.

70 ent ischemic attack (TIA) may be impacted by undiagnosed atrial fibrillation (AF).

71 lve neuropsychiatric manifestations from the undiagnosed autoimmune disease, medical treatment or lif

72 evere psychiatric episodes might suffer from undiagnosed autoimmune encephalitis.

73 icuously absent in a subset of patients with undiagnosed bleeding disorders, and therefore may functi

74 local hospital, the result was classified as undiagnosed C difficile infection.

75 ) were more common in HMT, mostly because of undiagnosed cancer requiring completion thyroidectomy.

76 uld be a marker of cardiovascular disease or undiagnosed cancer.

77 Previously undiagnosed cardiac dysfunction with preserved ejection

78 is expected to wane over time as the pool of undiagnosed cases is depleted, a tool that can help poli

79 e aggressive approaches for detecting as-yet undiagnosed cases obviously require additional resources

80 cessfully identify both known and previously undiagnosed cases of AERD with a high positive predictiv

81 pare the proportion of comorbidities between undiagnosed cases of celiac disease and age- and sex-mat

82 monitoring for pathogens using cfDNA reveals undiagnosed cases of infection, and that certain infecti

83 ed tomography (MDCT) we can further evaluate undiagnosed cases of silent gastric perforations present

84 super-spreaders and predict the existence of undiagnosed cases, potentially leading to early treatmen

85 Mycoplasma genitalium is a frequent undiagnosed cause of NGU in this population with rates o

86 ase of spontaneous perforation in previously undiagnosed CC and review the clinical and pathological

87 on as a potential complication of previously undiagnosed CC may be helpful in the evaluation and mana

88 ality rates in children born to mothers with undiagnosed CD (later CD diagnosis; n = 12,919) and diag

89 ere similar in children born to mothers with undiagnosed CD and in children whose mothers had diagnos

90 Participants with undiagnosed celiac disease (identified by positive resul

91 Undiagnosed celiac disease appeared to be clinically sil

92 is known about the prevalence and burden of undiagnosed celiac disease in individuals younger than a

93 is known about the prevalence and burden of undiagnosed celiac disease in individuals younger than a

94 e determined the prevalence and morbidity of undiagnosed celiac disease in individuals younger than a

95 liac disease, we estimated the prevalence of undiagnosed celiac disease to be 1.1%.

96 ears after testing was 10.8% in persons with undiagnosed celiac disease vs 0.1% in seronegative perso

97 Undiagnosed celiac disease was associated with increased

98 -12 and folate are lower in individuals with undiagnosed celiac disease, and levels of hemoglobin are

99 a, anemia, or fracture) were associated with undiagnosed celiac disease.

100 22 households had no undiagnosed child, and one household refused consent.

101 poised to identify the mutations that cause undiagnosed childhood genetic diseases and those that pr

102 identified between 18% and 42% of previously undiagnosed children in the community.

103 f 27% among 1133 previously investigated yet undiagnosed children with developmental disorders, whils

104 patients with cancer, and many patients have undiagnosed chronic kidney disease (CKD) from underlying

105 ADCY5 should be considered in patients with undiagnosed complex movement disorders even in the absen

106 ic evaluation to rule out the possibility of undiagnosed concurrent systemic lymphoma.

107 Barrett's esophagus (BE) is a commonly undiagnosed condition that predisposes to esophageal ade

108 suspected hereditary xerocytosis (HX) and/or undiagnosed congenital hemolytic anemia.

109 Although patients with undiagnosed COPD experience fewer exacerbations than tho

110 dividuals with asymptomatic and symptomatic, undiagnosed COPD in the general population in Denmark.

111 system burden of exacerbations in those with undiagnosed COPD is considerable.

112 To develop a method for identifying undiagnosed COPD requiring treatment with currently avai

113 classified as having physician-diagnosed or undiagnosed COPD were assessed.

114 lse oximetry as a screening method to detect undiagnosed critical congenital heart defects (CCHD) in

115 en and adults with complex phenotypes remain undiagnosed despite years of searching.

116 and whole exome sequencing on children with undiagnosed developmental disorders and their parents.

117 The tool was applied to 4911 patients with undiagnosed developmental disorders, and 11 events among

118 We used calibrated HbA1c levels to define undiagnosed diabetes (>/=6.5%); prediabetes (5.7% to 6.4

119 22 patients (55%) had either undiagnosed diabetes (fasting glucose >7.0 mmol/L, n=4)

120 To provide national estimates of undiagnosed diabetes by using a confirmatory testing str

121 However, the proportion of undiagnosed diabetes cases decreased, suggesting improve

122 Confirmed undiagnosed diabetes increased during the past 2 decades

123 When a confirmatory definition is used, undiagnosed diabetes is a relatively small fraction of t

124 Establishing the burden of undiagnosed diabetes is critical to monitoring public he

125 The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, > 6.5%) and known

126 additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre-dia

127 ts without known diabetes mellitus, 5.0% had undiagnosed diabetes mellitus and 37.5% had prediabetes.

128 cquired pneumonia, whereas the prevalence of undiagnosed diabetes mellitus and prediabetes in patient

129 The prevalence of undiagnosed diabetes mellitus and prediabetes was estima

130 Patients with undiagnosed diabetes mellitus had a higher 180-day morta

131 s mellitus, and risk factors associated with undiagnosed diabetes mellitus in a large European commun

132 The long-term mortality among patients with undiagnosed diabetes mellitus was high compared to patie

133 Undiagnosed diabetes mellitus was prevalent among commun

134 to determine the prevalence of prediabetes, undiagnosed diabetes mellitus, and risk factors associat

135 gression was used to assess risk factors for undiagnosed diabetes mellitus.

136 erglycemia at admission were associated with undiagnosed diabetes mellitus.

137 ed diabetes increased, but the prevalence of undiagnosed diabetes remained fairly stable, reducing th

138 Undiagnosed diabetes was defined as a fasting plasma glu

139 Confirmed undiagnosed diabetes was defined as elevated levels of f

140 Undiagnosed diabetes was more common in overweight or ob

141 nosed diabetes, 5.2% (95% CI, 4.0%-6.9%) for undiagnosed diabetes, and 38.0% (95% CI, 34.7%-41.3%) fo

142 Undiagnosed diabetes, prediabetes, and glucose control i

143 de, and an estimated 193 million people have undiagnosed diabetes.

144 revalence of total (diagnosed plus confirmed undiagnosed) diabetes increased from 5.5% (9.7 million a

145 ly because of a tremendous ongoing burden of undiagnosed disease.

146 ied children with clinically conspicuous but undiagnosed disease.

147 tes of Health (NIH) Common Fund supports the Undiagnosed Diseases Network (UDN) as an exemplar of thi

148 s of the National Institutes of Health (NIH) undiagnosed diseases program (UDP), and discuss its bene

149 r approach to 129 n-of-one families from the Undiagnosed Diseases Program, nominating 60% of 30 disea

150 these objectives by evaluating patients with undiagnosed diseases, fostering a breadth of expert coll

151 The most common undiagnosed disorders involve a neurologic phenotype.

152 People with undiagnosed disorders related to the presence of vascula

153 being utilized to diagnose individuals with undiagnosed disorders.

154 This study confirms that individuals with undiagnosed DM and prediabetes can be identified in the

155 Higher proportions of patients with undiagnosed DM and prediabetes were observed in the peri

156 f this study is to identify individuals with undiagnosed DM or prediabetes among patients attending a

157 ent, and prognosis, but many patients remain undiagnosed due to suboptimal testing and lack of tests

158 adult community health center patients with undiagnosed dysglycemia and proportionately fewer racial

159 st be considered during the work-up phase of undiagnosed EVD patients presenting to emergency departm

160 s with C difficile infection are potentially undiagnosed every year in 482 European hospitals.

161 After two undiagnosed fatal cases of early disseminated fungal inf

162 In addition, previously undiagnosed fractures were found in 45 patients (50%; 95

163 Undiagnosed fungal infections in these patient populatio

164 ecently emerged as clinical tools to resolve undiagnosed genetic conditions.

165 e of 5,855 individuals recruited for various undiagnosed genetic disorders.

166 Participants with undiagnosed glaucoma (ie, answering no to whether they p

167 studies have assessed ethnic differences in undiagnosed glaucoma among various Asian subgroups.

168 isual field loss in subjects with previously undiagnosed glaucoma identified at the screening.

169 Overall, prevalence of both diagnosed and undiagnosed glaucoma is much higher in minorities and th

170 Prevalence of undiagnosed glaucoma was 2.9%, increasing with age to 6.

171 is, variables associated with higher risk of undiagnosed glaucoma were younger age (odds ratio [OR],

172 ere stage, resulting in a high prevalence of undiagnosed glaucoma worldwide.

173 duce the effect of blindness associated with undiagnosed glaucoma.

174 of, risk factors for, and visual features of undiagnosed glaucoma.

175 opulations with highest burden of previously undiagnosed glaucoma.

176 nal photographs and perimetry; prevalence of undiagnosed glaucoma; and comparison of demographic fact

177 The high mortality in patients with undiagnosed HAE-C1-INH underscores the need to identify

178 is common, seriously impairing, and usually undiagnosed has led to the development of adult ADHD scr

179 y diagnosis could be overcome by the risk of undiagnosed HBP.

180 haracterized the prevalence of diagnosed and undiagnosed HCV in a Midwestern, urban ED.

181 l of 3704 ED patients were estimated to have undiagnosed HCV infection, and screening identified 532

182 ting was effective in identifying previously undiagnosed HCV infections in primary care settings.

183 se (CD) has emerged as a common, but largely undiagnosed health problem.

184 Since sleep apnea is common and frequently undiagnosed, health care providers should be aware of it

185 268 (2%) of 11 570 participants had undiagnosed HIV and reported UAI in the past year were a

186 nvestigate the change in community burden of undiagnosed HIV infection among older children and adole

187 for sharing syringes, and the proportion of undiagnosed HIV infection declined from 84.3% to 15.0% (

188 00-2500 annual infections) nor the number of undiagnosed HIV infections (7370, 95% CrI 6990-7800, in

189 An increasing proportion of undiagnosed HIV infections in MSM in London might have b

190 The main limitation is that prevalence of undiagnosed HIV was defined using a combination of 3 mea

191 es of color tested, proportion of previously undiagnosed HIV-positive youths identified, and rates of

192 ally males of color), identifying previously undiagnosed HIV-positive youths, and linking HIV-negativ

193 d disease, and epidemiologic data to support undiagnosed HS as a common disease are lacking.

194 network recruitment strategy for identifying undiagnosed human immunodeficiency virus (HIV) infection

195 In January 2015, an outbreak of undiagnosed human immunodeficiency virus (HIV) infection

196 ional SBDS-negative SDS cases or molecularly undiagnosed IBMFS cases, we identified 3 independent pat

197 that one-quarter of infections would remain undiagnosed if current CDC birth cohort recommendations

198 Individuals were considered undiagnosed if neither a previous COPD hospital contact,

199 lly actionable genetic disorders that may be undiagnosed in adults.

200 cally actionable genetic conditions possibly undiagnosed in adults.

201 ogeneous, and the molecular etiology remains undiagnosed in the majority of cases.

202 , and despite extensive investigation remain undiagnosed in up to approximately 50% cases.

203 A large percentage (42%) remained undiagnosed, including 12% with normal testing and an is

204 learing of bladder cancer, and for screening undiagnosed individuals who have symptoms of, or are at

205 ung disease have shown that asymptomatic and undiagnosed individuals with ILA have reductions in lung

206 scular parasites in human skin biopsies from undiagnosed individuals.

207 trends in time to diagnosis, incidence, and undiagnosed infection in MSM were interpreted against a

208 en (from 26% to 62%, p<0.0001) suggests that undiagnosed infection might increasingly be recently acq

209 35% (531 of 1505) of HIV-positive MSM had undiagnosed infection, which decreased non-linearly over

210 isk rather than on prevalence, incidence, or undiagnosed infection.

211 Undiagnosed insulin resistance or diabetes were common i

212 nically affected individuals probably remain undiagnosed, largely free from disease-related complicat

213 sk suggests a cholesterol-lowering effect of undiagnosed malignancy.

214 The increase in recent testing in undiagnosed men (from 29% to 67%, p<0.0001) and HIV-nega

215 Undiagnosed men reporting UAI and diagnosed men not excl

216 n ranged from one to three across surveys in undiagnosed men reporting UAI, two to ten in diagnosed m

217 In 2010, we estimate that undiagnosed men, the majority in primary infection, acco

218 hidden epidemic (the number of HIV-infected undiagnosed MSM).

219 r 1000 MSM and there were only 617 (264-858) undiagnosed MSM.

220 diagnosed during their life and 13 (17%) had undiagnosed multidrug-resistant tuberculosis.

221 f disability, the prevalence of symptomatic, undiagnosed NCDs was highest among the lowest 2 wealth q

222 w pathogenic gene variant identification for undiagnosed neurodevelopmental disorders and provided in

223 nd Prevention reports, or investigations for undiagnosed neurologic disease.

224 Clinically undiagnosed neurological disorders are the most frequent

225 lasma genitalium, which also commonly causes undiagnosed NGU, necessitates treatment with macrolides

226 ts met the COPD criteria and 2903 (78%) were undiagnosed, of whom 2052 (71%) were symptomatic.

227 screening of patients whose conditions were undiagnosed on a targeted neuromuscular disease-related

228 ommercially insured children with ASD remain undiagnosed or are being treated only through publicly f

229 tial rise in type 2 diabetes, which is often undiagnosed or poorly controlled.

230 za diagnoses, suggesting influenza is either undiagnosed or undercoded in a substantial proportion of

231 in the contemporary surgical population have undiagnosed OSA.

232 f screening and treatment of subclinical and undiagnosed overt hypothyroidism and hyperthyroidism in

233 ment versus no treatment of screen-detected, undiagnosed overt thyroid dysfunction.

234 asis, suggesting they may identify currently undiagnosed patients and expand our understanding of dis

235 irometry is a cost-effective way to identify undiagnosed patients and has the potential to improve th

236 To review the approach to undiagnosed patients and results of the National Institu

237 Undiagnosed patients available for further testing were

238 nostic efficacy in a paediatric cohort of 30 undiagnosed patients presenting with variable neurometab

239 ns but have not been evaluated in clinically undiagnosed patients to determine validity and generaliz

240 We studied 127 undiagnosed patients with clinical presentation compatib

241 rmline DNA from 20 patients with UFCRC and 5 undiagnosed patients with polyposis.

242 omised placebo-controlled trial, we enrolled undiagnosed patients, aged 18-80 years, with cough, whee

243 reciation of the risk of cerebral abscess in undiagnosed PAVMs is required.

244 ommonly occur in individuals with previously undiagnosed PAVMs.

245 Ds with known mutations and 26 patients with undiagnosed PIDs.

246 ross-sectional data from 2654 US adults with undiagnosed prediabetes who participated in the 2005-201

247 In participants with undiagnosed prediabetes, the use of health claims alone,

248 Active detection of undiagnosed prevalent cases may achieve greater populati

249 d"); and population-based diagnosis of 5% of undiagnosed prevalent cases per year ("active").

250 The prevalence of undiagnosed primary glaucoma varied among ethnic populat

251 The overall prevalence of undiagnosed primary glaucoma was highest among Malays (2

252 dentified a substantial number of previously undiagnosed problems that are more prevalent in an older

253 Determination of whether the donor died from undiagnosed rabies and whether other organ recipients de

254 sis in patients and families with previously undiagnosed rare genetic conditions.

255 ly co-occurs with deafness but often remains undiagnosed, rather than auditory dysfunction that cause

256 We report 2 families with undiagnosed recessive presynaptic congenital myasthenic

257 Reducing the proportion undiagnosed remains the greatest barrier to achieving th

258 (COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk),

259 ot have a left-side angiogram and could have undiagnosed significant coronary artery disease.

260 Previously undiagnosed silent AF was found in 10 (1%) among 848 ind

261 whole-exome sequencing in four probands with undiagnosed skin hyperkeratosis/ichthyosis, we identifie

262 ients with clinically significant AU have an undiagnosed SpA.

263 Number of persons identified with previously undiagnosed spinal or paraspinal infection.

264 k due to the fear that some animals may have undiagnosed subclinical infection, despite uncertainty o

265 Undiagnosed subjects were less symptomatic and functiona

266 th no clear difference between diagnosed and undiagnosed subjects, or between those diagnosed with a

267 s performed on 814 consecutive patients with undiagnosed, suspected genetic conditions at the Univers

268 In this sample of patients with undiagnosed, suspected genetic conditions, trio-CES was

269 INTERPRETATION: Individuals with undiagnosed, symptomatic COPD had an increased risk of e

270 or death from all causes in individuals with undiagnosed, symptomatic COPD.

271 uld consider early referral of children with undiagnosed syndromes to clinical geneticists.

272 f orodental disease and any associated often-undiagnosed systemic disease (e.g., Sjogren syndrome).

273 arrow infection in an elderly Asian man with undiagnosed T cell lymphoma presenting with fever of unk

274 To estimate the prevalence of diagnosed and undiagnosed T2DM among US adolescents, we analyzed a nat

275 Further, undiagnosed T2DM prevalence was 0.12% (95% CI: 0.05, 0.3

276 data are lacking, particularly in regard to undiagnosed T2DM.

277 ause many cases of this disease are probably undiagnosed, this review emphasizes the clinical manifes

278 proportion of total diabetes cases that are undiagnosed to 11% in 2005-2010.

279 mortality; however, interventions to detect undiagnosed tuberculosis in children are underused.

280 screening instruments to detect people with undiagnosed type 2 diabetes among diverse populations ac

281 3.6% and 13.6% of the Danish population have undiagnosed type 2 diabetes mellitus and prediabetes, re

282 creened YAP1 for variants in a cohort of 258 undiagnosed UK patients with developmental eye disorders

283 to treatment leads to most people remaining undiagnosed until later stages of disease when prognosis

284 ho are not diagnosed in infancy often remain undiagnosed until they present with advanced disease.

285 ition that transmission is driven largely by undiagnosed, untreated cases, both in the community and

286 Most patients remain undiagnosed, untreated, and die.

287 of syphilis continues to be a consequence of undiagnosed, untreated, or inadequately treated maternal

288 Previously undiagnosed vascular risk factors were found in 78% of a

289 The potential roles of undiagnosed venous reflux disease and the military physi

290 orrection, $0.5 billion in medical costs for undiagnosed vision loss, and $1.8 billion in other direc

291 ibutable to diagnosed eye-related disorders, undiagnosed vision loss, and medical vision aids using M

292 epresent occult macular injury or previously undiagnosed visual impairment in the affected eye.

293 percentage of total diabetes cases that were undiagnosed was 16.3%; by 2011 to 2014, this estimate ha

294 e-standardized percentage of cases that were undiagnosed was higher among non-Hispanic Asian particip

295 Smoking-associated undiagnosed wheezers also merit recognition.

296 Cluster 4 (19.4%) female-undiagnosed-wheezers had adolescent-onset non-atopic whe

297 f African American adults with T2D to remain undiagnosed when screened with HbA1c.

298 Three of 10 adults with diabetes remain undiagnosed, which may be related to less access to care

299 obstructive pulmonary disease (COPD) remain undiagnosed worldwide.

300 galactose transporter SLC35A2 that define an undiagnosed X-linked congenital disorder of glycosylatio