ライフサイエンスコーパス: cryptococcal

1 d IL-13) and IL-10 in lung leukocytes and in cryptococcal Ag-pulsed splenocytes, 3) diminished IgE pr

2 central nervous system (CNS) involvement are cryptococcal and coccidioidal, so CSF BG screening can b

3 The clinical significance of low-titer cryptococcal antigen (CrAg) by lateral flow assay is fre

4 antiretroviral therapy, screening serum for cryptococcal antigen (CrAg) combined with adherence supp

5 The cryptococcal antigen (CRAG) lateral flow assay (LFA) had

6 The cryptococcal antigen (CRAG) lateral flow assay (LFA) has

7 Two semiquantitative cryptococcal antigen (CrAg) lateral flow assays (LFAs) h

8 Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptoc

9 Cryptococcal antigen (CrAg) screening and targeted preem

10 Cryptococcal antigen (CrAg) screening and treatment with

11 Retrospective data suggest that cryptococcal antigen (CrAg) screening in patients with l

12 ians with CD4 <150 cells/mL underwent plasma cryptococcal antigen (CRAG) screening.

13 Cryptococcal antigen (CrAg) testing is also changing, wi

14 Higher cryptococcal antigen (CrAg) titers are strongly associat

15 High cryptococcal antigen (CrAg) titers in blood are associat

16 th CD4 T-cell counts </=100 cells/microL for cryptococcal antigen (CrAg) using the CrAg lateral flow

17 ic cryptococcal antigenemia and negative CSF cryptococcal antigen (CrAg) were compared to participant

18 ed from culture to India ink to detection of cryptococcal antigen (CrAg), with the recent development

19 ased validation of the IMMY semiquantitative cryptococcal antigen (CrAgSQ) lateral flow assay (LFA) a

20 x regression; longitudinal patterns in serum cryptococcal antigen (SCrAg) titers and the probability

21 Screening for cryptococcal antigen combined with a short period of adh

22 ity support consisted of screening for serum cryptococcal antigen combined with antifungal therapy fo

23 (95% CI 195 500-340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 60

24 l count <100 cells/microL and negative serum cryptococcal antigen initiating antiretroviral therapy i

25 The cryptococcal antigen lateral flow assay (CrAg LFA) was e

26 Since rapid cryptococcal antigen lateral flow assays (CrAg LFA) may

27 Patient mortality was associated with higher cryptococcal antigen levels, the cerebrospinal fluid (CS

28 staining (Gram and calcofluor white) and CSF cryptococcal antigen or by repeat ME panel testing.

29 andard care group received a home visit or a cryptococcal antigen screen rather than only standard ca

30 therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory

31 nt clinic-based services combined with serum cryptococcal antigen screening.

32 We performed matched laboratory-based serum cryptococcal antigen testing with an enzyme immunoassay

33 S<15 and these patients had lower median CSF cryptococcal antigen titers (P = .042) and CCL2 (P = .00

34 to develop IRS, irrespective of serum or CSF cryptococcal antigen titers and fungemia.

35 aining, acid-fast staining, and lactic acid, cryptococcal antigen, histoplasma antigen, herpes simple

36 cytokine levels were generally similar, and cryptococcal antigen-specific immune stimulation respons

37 d cytokine levels were generally similar and cryptococcal antigen-specific immune stimulation respons

38 ented by screening patients for sub-clinical cryptococcal antigenaemia (CRAG) at antiretroviral-thera

39 Cryptococcal antigenaemia prevalence by country was deri

40 Based on cryptococcal antigenaemia prevalence in each country and

41 We estimated an average global cryptococcal antigenaemia prevalence of 6.0% (95% CI 5.8

42 al mortality was similar between symptomatic cryptococcal antigenemia (32%) and cryptococcal meningit

43 of participants with neurologic-symptomatic cryptococcal antigenemia and negative CSF cryptococcal a

44 Individuals with cryptococcal antigenemia are at high risk of developing

45 n of individuals with neurologic symptomatic cryptococcal antigenemia but negative cerebral spinal fl

46 Eleven participants (5%) had isolated cryptococcal antigenemia with a negative CSF CRAG and cu

47 Cryptococcal antigenemia with meningitis symptoms was th

48 and 4% (54/1201) had neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg.

49 ed, 1,296 were HIV-infected and screened for cryptococcal antigenemia.

50 that defines the fungal-BBB interface during cryptococcal attachment to, and internalization by, the

51 nd p38 MAPK, but not ERK activation, and the cryptococcal capsule blocked this extracellular recognit

52 ributes to the structure and function of the cryptococcal capsule is not known.

53 Cryptococcal capsule size ex vivo is an important contri

54 our understanding of a major polymer of the cryptococcal capsule.

55 ess known as nonlytic exocytosis whereby the cryptococcal cell is released from the macrophage into t

56 observed that melanin is assembled into the cryptococcal cell wall in spherical structures ~200 nm i

57 During pulmonary infection, cryptococcal cells form large polyploid cells that exhib

58 Cryptococcal cells isolated from Anxa2-deficient (Anxa2(

59 Cryptococcal cells that activated their meiotic genes in

60 pathogenesis-a balanced interaction between cryptococcal cells, macrophages, endothelial cells, and

61 the mammalian immune response to respiratory cryptococcal challenge remain poorly defined.

62 neoformans, but ultimately has no effect on cryptococcal control by adaptive immunity.

63 Participants receiving sertraline had faster cryptococcal CSF clearance and a lower incidence of immu

64 .0089) were lower in those who achieved CSF cryptococcal culture negativity compared to those with p

65 dividuals with high CSF lactate >5 mmol/L at cryptococcal diagnosis more likely presented with altere

66 ting antiretroviral therapy (ART) may reduce cryptococcal disease and deaths.

67 g of the importance of antigen detection for cryptococcal disease and invasive aspergillosis, the use

68 e response that may favor the development of cryptococcal disease and the fungal dissemination to the

69 -eight of those patients lacked a history of cryptococcal disease and were the focus of this study.

70 Early cryptococcal disease can be detected via circulating ant

71 w-serum CrAg titers (<=1:10) correlated with cryptococcal disease in a substantial proportion of non-

72 gs suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion

73 compartments with clinical implications for cryptococcal disease outcome, potentially due to their e

74 Cryptococcal disease was an immediate or contributing ca

75 Cryptococcal disease was an important cause of mortality

76 Thorough investigation for cryptococcal disease with LPs and blood cultures, prompt

77 substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa.

78 ntigen (CrAg) is invaluable for establishing cryptococcal disease.

79 timate of global incidence of HIV-associated cryptococcal disease.

80 does not appear to be wholly attributable to cryptococcal disease.

81 immunity places individuals at high risk for cryptococcal disease.

82 linical, radiologic, and laboratory data for cryptococcal disease.

83 lity risk in individuals with HIV-associated cryptococcal disease.

84 performance of CrAg testing in patients with cryptococcal disease.

85 s, prevention, and management of HIV-related cryptococcal disease.

86 ed 79 whose silencing significantly affected cryptococcal engulfment.

87 Cryptococcal epidemiology is shifting toward HIV-negativ

88 d was associated with higher serum titers of cryptococcal glucuronoxylomannan.

89 survival and increased organ burden in mouse cryptococcal granulomas.

90 Human pDCs can also inhibit cryptococcal growth by a mechanism similar to that of mu

91 The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome

92 emental cost-effectiveness ratio (ICER) of 3 cryptococcal induction regimens: (1) amphotericin B deox

93 ean rate of clearance of cerebrospinal fluid cryptococcal infection (EFA).

94 cantly lower rates of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or esophageal cand

95 The prevalence of cryptococcal infection among advanced AIDS patients in t

96 rtant element of antifungal defenses against cryptococcal infection and CNS dissemination.

97 val infection model to assess the process of cryptococcal infection and disease development sequentia

98 We aimed to determine the prevalence of cryptococcal infection and outcomes of those infected am

99 nction of macrophages in normal clearance of cryptococcal infection and the defects present in uncont

100 Screening and pre-emptive treatment for cryptococcal infection combined with a short initial per

101 elation prior to establishing a diagnosis of cryptococcal infection for patients with first-time posi

102 Thus, high-content imaging of cryptococcal infection in vivo demonstrates how very ear

103 response to a fungal pathogen and show that cryptococcal infection triggers iBALT formation.

104 s suggest a role for ANXA2 in the control of cryptococcal infection, macrophage function, and fungal

105 We calculated those at risk for cryptococcal infection, specifically those with CD4 less

106 fungal control during the afferent phase of cryptococcal infection.

107 ungal expansion during the afferent phase of cryptococcal infection.

108 are proposed to contribute to the latency of cryptococcal infection.

109 the deleterious effects of Th2 cells during cryptococcal infection.

110 nts with a CD4 count </=100 cells/microL for cryptococcal infection.

111 en long-term exposure to FTY720 and cases of cryptococcal infection.

112 nd should prompt careful clinical workup for cryptococcal infection.

113 t S1P receptors 1 and 5, in a mouse model of cryptococcal infection.

114 Cryptococcal infections are primarily caused by two rela

115 to play a major role in the pathogenesis of cryptococcal infections, including the enzyme phospholip

116 FA) may expedite treatment of HIV-associated cryptococcal infections, we sought to validate clinic-ba

117 , a receptor not previously evaluated during cryptococcal infections.

118 o such damage, could be valuable in treating cryptococcal infections.

119 d may accelerate treatment of HIV-associated cryptococcal infections.

120 Cryptococcal Kcs1 converts IP6 to PP-IP5/IP7, but the ki

121 se in proliferation and a 2-fold increase in cryptococcal killing within the phagosome.

122 ted the role of Rac in NK cell mediated anti-cryptococcal killing.

123 ates that PD-1 signaling promotes persistent cryptococcal lung infection and identifies this pathway

124 stent infections, as evidenced by studies of cryptococcal lung infection in IL-10-deficient mice.

125 lization of lung DC and Mvarphi in mice with cryptococcal lung infection.

126 ssive fungal disease using a murine model of cryptococcal lung infection.

127 Mitogen- and cryptococcal mannoprotein (CMP)-activated (CD25+CD134+)

128 Responses were assessed following ex vivo cryptococcal mannoprotein stimulation, using 13-color fl

129 ll flexibility as an independent variable in cryptococcal melanin assembly.

130 mptomatic cryptococcal antigenemia (32%) and cryptococcal meningitis (31%; P = .91).

131 lasma CRAG titers >1:640, 96% (27 of 28) had cryptococcal meningitis (cerebrospinal fluid CRAG-positi

132 (25[OH]D) were measured in 150 patients with cryptococcal meningitis (CM) and 150 HIV-infected contro

133 Ocular complications in cryptococcal meningitis (CM) are commonly attributed to

134 ated to raise intracranial pressure (ICP) in cryptococcal meningitis (CM) by mechanical obstruction o

135 Cryptococcal meningitis (CM) causes an estimated 180,000

136 Cryptococcal meningitis (CM) causes high rates of HIV-re

137 y virus (HIV)-infected patients with treated cryptococcal meningitis (CM) commencing combination anti

138 human immunodeficiency virus/AIDS-associated cryptococcal meningitis (CM) frequently experience clini

139 iposomal amphotericin B (L-AmB) regimens for cryptococcal meningitis (CM) in Tanzania and Botswana.

140 Cryptococcal meningitis (CM) is a leading cause of death

141 Cryptococcal meningitis (CM) is a leading cause of HIV-a

142 uman immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is characterized by high fu

143 Cryptococcal meningitis (CM) is one of the most common c

144 study to determine the national incidence of cryptococcal meningitis (CM), and describe characteristi

145 Cryptococcal meningitis (CM)-related mortality may be pr

146 mising as a strategy to reduce the burden of cryptococcal meningitis (CM).

147 patient, who defaulted from care, died from cryptococcal meningitis (CM).

148 One survivor had suffered cryptococcal meningitis 2 years prior.

149 Cryptococcal meningitis accounts for 20 to 25% of acquir

150 nal fluid (CSF) samples for the diagnosis of cryptococcal meningitis against that of existing diagnos

151 201) of participants had confirmed CSF CrAg+ cryptococcal meningitis and 4% (54/1201) had neurologic

152 e in the treatment of fungal infections like cryptococcal meningitis and C. albicans infections.

153 ed adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received

154 body screening in four current patients with cryptococcal meningitis and identified and tested 103 ar

155 to identify and treat those with subclinical cryptococcal meningitis and preemptive fluconazole for t

156 Postmortem cryptococcal meningitis and pulmonary cryptococcosis wer

157 uman studies have shown associations between cryptococcal meningitis and reduced IgM memory B cell le

158 Two others developed cryptococcal meningitis and survived.

159 Cryptococcal meningitis and tuberculosis are both import

160 Cryptococcal meningitis and tuberculosis are both import

161 mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adv

162 uman immunodeficiency virus (HIV)-associated cryptococcal meningitis are poorly defined.

163 Cryptococcal meningitis associated with human immunodefi

164 measured in 44 patients with HIV-associated cryptococcal meningitis at baseline and during follow-up

165 lucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce

166 Cryptococcal meningitis can occur in persons with less-a

167 an Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95

168 In the United States, cryptococcal meningitis causes approximately 3400 hospit

169 individual-level CSF data from 3 sequential cryptococcal meningitis clinical trials conducted during

170 uring human immunodeficiency virus (HIV) and cryptococcal meningitis coinfection are ill defined.

171 ive sertraline in adults with HIV-associated cryptococcal meningitis compared with placebo.

172 a in severely immunocompromised persons with cryptococcal meningitis contributes directly to this mor

173 a in severely immunocompromised persons with cryptococcal meningitis contributes directly to this mor

174 iagnosis prompted screening of patients with cryptococcal meningitis for anticytokine autoantibodies.

175 ly enrolled Ugandans living with HIV who had cryptococcal meningitis from 2010-2012.

176 ectively enrolled HIV-infected Ugandans with cryptococcal meningitis from 2010-2012.

177 trial, we recruited HIV-positive adults with cryptococcal meningitis from two hospitals in Uganda.

178 0 (95% CI 150 600-282 400) incident cases of cryptococcal meningitis globally in 2014.

179 Half of persons with advanced AIDS and cryptococcal meningitis had detectable CMV viremia.

180 No persons with cryptococcal meningitis had negative fingersticks.

181 Cryptococcal meningitis has been described in immunocomp

182 l antigenemia are at high risk of developing cryptococcal meningitis if untreated.

183 the past ten years, standard diagnostics for cryptococcal meningitis in HIV-infected persons have evo

184 reduces the incidence of clinically evident cryptococcal meningitis in individuals living with advan

185 red therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphoteric

186 e high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income

187 r a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda.

188 antibodies are associated with some cases of cryptococcal meningitis in otherwise immunocompetent pat

189 p, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodef

190 l to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is

191 Patients with cryptococcal meningitis in sub-Saharan Africa frequently

192 recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia,

193 Early ART initiation in cryptococcal meningitis increased CSF cellular infiltrat

194 Cryptococcal meningitis is a metric of HIV treatment pro

195 Identifying new antifungals for cryptococcal meningitis is a priority given the inadequa

196 onotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many Afr

197 Cryptococcal meningitis is one of the most common life-t

198 Cryptococcal meningitis is the leading cause of adult me

199 Cryptococcal meningitis is the most common cause of adul

200 Cryptococcal meningitis is the most frequent cause of me

201 on and timing from asymptomatic infection to cryptococcal meningitis is unclear.

202 but negative by the IMMY LFA, none developed cryptococcal meningitis over 3 months of follow-up witho

203 determining disease outcome in HIV-infected cryptococcal meningitis patients infected with Cryptococ

204 In cryptococcal meningitis phase 2 clinical trials, early f

205 ciency virus (HIV)-infected individuals with cryptococcal meningitis places them at risk for Cryptoco

206 Antifungal treatment for cryptococcal meningitis relies on three old, off-patent

207 Cryptococcal meningitis remains a significant cause of d

208 n ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered.

209 Mortality from cryptococcal meningitis remains very high in Africa.

210 r antiretroviral therapy (ART) initiation in cryptococcal meningitis resulted in higher mortality com

211 Altered mental status in cryptococcal meningitis results in poorer survival, but

212 ccus gattii isolated from serial episodes of cryptococcal meningitis that were separated by at least

213 We measured CSF lactate in individuals with cryptococcal meningitis to determine its clinical signif

214 In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) tria

215 Malawi, 236 participants from the Advancing Cryptococcal Meningitis Treatment for Africa trial were

216 addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made

217 One survivor had suffered cryptococcal meningitis two years prior.

218 ng in predicting response in AIDS-associated cryptococcal meningitis using clinical isolates from a r

219 rring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantl

220 Globally, cryptococcal meningitis was responsible for 15% of AIDS-

221 Patients with a first episode of cryptococcal meningitis were enrolled, and their immune

222 duals assessed, 172 HIV-infected adults with cryptococcal meningitis were enrolled.

223 Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% C

224 tibodies in an otherwise healthy female with cryptococcal meningitis who later developed pulmonary al

225 , we recruited HIV-infected individuals with cryptococcal meningitis who presented to Mulago Hospital

226 identified seven HIV-negative patients with cryptococcal meningitis who tested positive for high-tit

227 tive participants, 138 (93%) had evidence of cryptococcal meningitis with a positive CSF CRAG.

228 HIV-infected individuals developing cryptococcal meningitis with CD4 >=100 cells/muL present

229 We review the antifungal drugs used to treat cryptococcal meningitis with respect to clinical effecti

230 meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, mal

231 d to have symptoms, signs, or a diagnosis of cryptococcal meningitis) and those in treatment failure

232 ormans var. grubii is the causative agent of cryptococcal meningitis, a significant source of mortali

233 , none of the three reported adverse events (cryptococcal meningitis, asymptomatic anaemia, and asymp

234 is an important determinant of mortality in cryptococcal meningitis, but its use in aiding clinical

235 With cryptococcal meningitis, lower frequencies of expression

236 uman immunodeficiency virus (HIV)-associated cryptococcal meningitis, screened for the Cryptococcal O

237 s the most attractive treatment strategy for cryptococcal meningitis, though the rising price may be

238 e used to treat patients with HIV-associated cryptococcal meningitis.

239 e in human immunodeficiency virus-associated cryptococcal meningitis.

240 red to participants with confirmed CSF CrAg+ cryptococcal meningitis.

241 an opportunistic pathogen that causes fatal cryptococcal meningitis.

242 of people who are developing and dying from cryptococcal meningitis.

243 , but their use is untested in patients with cryptococcal meningitis.

244 mulating factor (GM-CSF) autoantibodies with cryptococcal meningitis.

245 important contributor to virulence in human cryptococcal meningitis.

246 be considered for point-of-care diagnosis of cryptococcal meningitis.

247 sease severity and outcome in HIV-associated cryptococcal meningitis.

248 rebrospinal fluid samples from patients with cryptococcal meningitis.

249 tosine as first-line induction treatment for cryptococcal meningitis.

250 ws that (1,3)-beta-d-glucan is detectable in cryptococcal meningitis.

251 marker of disease severity and mortality in cryptococcal meningitis.

252 HIV-infected Ugandan adults at diagnosis of cryptococcal meningitis.

253 FA is associated with all-cause mortality in cryptococcal meningitis.

254 on serum and among hospitalized adults with cryptococcal meningitis.

255 e positive among 30 hospitalized adults with cryptococcal meningitis.

256 tococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis.

257 colony-stimulating factor autoantibodies and cryptococcal meningitis; anti-interleukin (IL)-6 autoant

258 Cryptococcal meningoencephalitis (CM) is a major cause o

259 consecutive eligible patients), HIV-negative cryptococcal meningoencephalitis (CM) patients underwent

260 CNS cryptococcal meningoencephalitis in both HIV positive (H

261 Cryptococcal meningoencephalitis is a fungal infection t

262 A murine model of cryptococcal meningoencephalitis was used.

263 ly detection and intervention strategies for cryptococcal meningoencephalitis.

264 We postulate this is early cryptococcal meningoencephalitis.

265 cterize the phenotypic features of different cryptococcal molecular types.

266 p127 therefore advances our understanding of cryptococcal morphological change and may hold significa

267 y flow cytometry in HIV-infected adults with cryptococcal (n = 31) and noncryptococcal (n = 12) menin

268 s, suggesting that Znf2 might interfere with cryptococcal neurotropism upon extrapulmonary disseminat

269 sted no influence of a-alpha interactions on cryptococcal neurotropism, irrespective of the route of

270 The 25-hydroxyvitamin D levels and cryptococcal notifications were analyzed for evidence of

271 ery early in infection and that increases in cryptococcal number are driven by intracellular prolifer

272 ed cryptococcal meningitis, screened for the Cryptococcal Optimal ART Timing (COAT) trial in Uganda a

273 rebrospinal fluid (CSF) and serum during the Cryptococcal Optimal ART Timing (COAT) trial.

274 Despite extensive research on cryptococcal pathogenesis, host genes involved in the in

275 at has been implicated in multiple stages of cryptococcal pathogenesis, including initiation and pers

276 hese findings underscore the contribution of cryptococcal-phagocyte interactions and laccase-dependen

277 What triggers cryptococcal polyploidization and how ploidy reduction i

278 scopy with (15)N-labeled peptide mimetics of cryptococcal polysaccharide antigen (Ag).

279 The cryptococcal polysaccharide capsule is a leading candida

280 addition to the impacts of the life cycle on cryptococcal populations and pathogenesis.

281 g with an inability to control intracellular cryptococcal proliferation, even in the presence of reac

282 lungs but only treatment with FTY720 led to cryptococcal reactivation.

283 Cryptococcal-related mortality is associated with monocy

284 wever, the magnitude of the impact of LPs on cryptococcal-related mortality is unknown.

285 f M2 macrophage markers than those receiving cryptococcal-specific CD4(+) T cells from Il17rb(-/-) mi

286 Il17rb(-/-) mice receiving cryptococcal-specific CD4(+) T cells from wild-type had

287 Cryptococcal-specific CD4(+) T-cell responses were chara

288 Cryptococcal-specific peripheral CD4(+) T-cell responses

289 tential as a tool to differentially identify cryptococcal strains and subtypes.

290 Cryptococcal strains producing larger ex vivo capsules i

291 were also seen to play a role as a niche for cryptococcal survival.

292 The cryptococcal transcript for the extracellular mannoprote

293 host regulators that specifically influence cryptococcal uptake.

294 group significantly and specifically altered cryptococcal uptake; one of them encoded CaMK4, a calciu

295 Thus, our studies define a novel role of the cryptococcal Vad1 protein as a central regulator of cryp

296 occal Vad1 protein as a central regulator of cryptococcal virulence and illustrate that Vad1 promotes

297 rge set of clinical isolates for established cryptococcal virulence traits to evaluate the contributi

298 e is known about the contribution of Plb1 to cryptococcal virulence.

299 nd CNA2580) were not previously described in cryptococcal virulence.

300 Our data identify cryptococcal VPS27 as a required gene for laccase traffi