ライフサイエンスコーパス: GPA

1 GPA gives rise to soft communities that provide a differ

2 GPA implants showed massive destruction of the co-implan

3 GPA infestation of Arabidopsis resulted in a transient i

4 GPA is linked to the correlative control exerted by deve

5 GPA spends more time actively feeding from the sieve ele

6 GPA treatment produced a significant increase in mtDNA i

7 GPA-16 function has been analyzed in vivo owing notably

8 GPA-modifying sulfotransferases are promising tools for

9 n- defective let-99(-) mutant zygotes, GOA-1/GPA-16 and NMY-2 act abnormally to oppose centration.

10 In GOA-1/GPA-16-depleted zygotes, NMY-2 aggregate displacement is

11 yosin II NMY-2 and the Galpha proteins GOA-1/GPA-16.

12 lls were further enumerated in NAC (n = 12), GPA (n = 14), SCIT- (n = 10), and SLIT- (n = 8) treated

13 ptors relative to the well-described EBA-175/GPA invasion pathway, we used an ex vivo erythrocyte cul

14 A GPA of 4.0 correlates with the best prognosis, whereas a

15 c cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization.

16 orrelates with the best prognosis, whereas a GPA of 0.0 corresponds with the worst prognosis.

17 The EBA-175/glycophorin A (GPA) and Rh5/basigin ligand-receptor interactions, refer

18 lays a key role by binding to glycophorin A (GPA) on the red cell surface, although the function of t

19 Ter-119) that binds to mouse glycophorin A (GPA) with a variant human single-chain low molecular wei

20 , including GYPA that encodes glycophorin A (GPA), and the up-regulation of members of the HSP70 fami

21 C3 cleavage, onto erythrocyte glycophorin A (GPA).

22 Homodimeric StaL can accommodate GPA substrate in only one of the two active sites becaus

23 and estimate genomic prediction accuracies (GPA) for VS traits.

24 reatine analog beta guanidinopropionic acid (GPA) reduced ATP and PCr levels and increased AMPK mRNA

25 bolic stressor beta-guanidinopropionic acid (GPA), a creatine analogue that reduces ATP levels, activ

26 Activated GPA-12 has the same effect as activated RHO-1, inducing

27 ly blocks increased ACh release by activated GPA-12.

28 as steric constraints that suggest activated GPA-16(it143) is destabilized relative to wild type.

29 Biopsy specimens from patients with active GPA (n = 10) or sinusitis (controls, n = 6) were s.c. co

30 has an important role in antibiosis against GPA.

31 an essential function in antibiosis against GPA.

32 r reveal that PAD4-modulated defense against GPA does not involve EDS1.

33 PAD4-controlled defense against GPA requires neither EDS1 nor SA.

34 sability of EDS1 and SID2 in defense against GPA.

35 mutant plant and attenuated defense against GPA.

36 plays a role in Arabidopsis defense against GPA.

37 which is a key modulator of defenses against GPA.

38 onditioned antibiosis and deterrence against GPA feeding, but S118 was dispensable for deterring GPA

39 tes a phloem-based defense mechanism against GPA.

40 s accompanied by enhanced resistance against GPA in the Arabidopsis constitutive expresser of PR gene

41 Resistance against GPA was also higher in the trehalose hyper-accumulating

42 b monotherapy and/or gastroprotective agent (GPA) cotherapy, and 1,207 (65.8%) received coxibs.

43 gy (PH) domain, followed by two Gly/Pro/Ala (GPA)-rich regions separated by a Src homology 3 (SH3) do

44 ally evaluated in the grass pollen-allergic (GPA) group (n = 28) and nonatopic healthy controls (NAC,

45 Generalized Procrustes Analysis (GPA) demonstrated the consensus between soil, water, for

46 access to the Glaucoma Progression Analysis (GPA) printout.

47 gression on OCT Guided Progression Analysis (GPA) software were drawn from a total of 1271 eyes from

48 Guided progression analysis (GPA) was also compared.

49 A) with HRT and Guided Progression Analysis (GPA) with Cirrus HD-OCT, respectively.

50 (VFI), and the guided progression analysis (GPA).

51 ormed using the Guided Progression Analysis (GPA; Carl-Zeiss Meditec, Inc., Dublin, CA).

52 ated perimetry guided progression analysis, [GPA]) and 21 healthy eyes from the University of Califor

53 Caenorhabditis elegans G proteins ODR-3 and GPA-13.

54 kyrin were present in a complex with C3b and GPA in complement-treated cells.

55 e membranes of complement-treated cells, and GPA was physically associated with the membrane skeleton

56 eement between majority expert consensus and GPA was fair (kappa = 0.52, 95% confidence interval [CI]

57 eement between majority expert consensus and GPA, both before and after access to GPA data, was asses

58 enzyme) to roots restored water content and GPA population size in lox5 plants, thus confirming that

59 5) as progressing compared with VFI, MD, and GPA in suspects (3.8%, 2.7%, 5.6%, and 2.9%, respectivel

60 PR3-ANCA-positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73

61 bditis elegans zygote, GOA-1 (Galpha(o)) and GPA-16 (Galpha(i)) are involved in generating forces tha

62 ed gene expression upon fruit production and GPA, and a drop in chlorophyll levels, suggestive of alt

63 etermination of visual field progression and GPA is fair.

64 RA and GPA may arise from a similar genetic predisposition.

65 The green peach aphid (GPA) (Myzus persicae Sulzer) is an important sap-sucking

66 Green peach aphid (GPA) Myzus persicae (Sulzer) is a phloem-feeding insect

67 er, commonly known as the green peach aphid (GPA), which is an important phloem sap-consuming pest of

68 r), commonly known as the green peach aphid (GPA).

69 ntial for defense against green peach aphid (GPA; Myzus persicae) and the pathogens Pseudomonas syrin

70 Extract of the green peach aphid (GPA; Myzus persicae) triggers responses characteristic o

71 the phloem sap-consuming green peach aphid (GPA; Myzus persicae), an agronomically important insect

72 sponses from a glucose-potentiated arginine (GPA) test, insulin sensitivity from a hyperinsulinemic-e

73 rescences, i.e. global proliferative arrest (GPA) during which all maternal growth ceases upon the pr

74 rocess known as global proliferative arrest (GPA).

75 nts with GM-positive invasive aspergillosis (GPA).

76 published the Graded Prognostic Assessment (GPA), a prognostic index for patients with brain metasta

77 mechanism geometric preferential attachment (GPA), and validate it against the Internet.

78 Over 2 years, the grade point average (GPA) of African Americans was, on average, raised by 0.2

79 ised African Americans' grade-point average (GPA) relative to multiple control groups and halved the

80 isolated fibroblasts was comparable between GPA and controls, GPA samples showed a significant delay

81 The connections between GPA and cosmological models, including inflation, are al

82 breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky perfo

83 We sought to validate the existing breast-GPA in an independent larger cohort and refine it integr

84 The modified breast-GPA incorporates four simple clinical parameters of high

85 We therefore developed the modified breast-GPA integrating a fourth clinical parameter.

86 mances of the breast-GPA and modified breast-GPA were compared using the concordance index.

87 0.85) for the breast-GPA and modified breast-GPA, respectively (P < .001).

88 ed to the development of the modified breast-GPA.

89 The performances of the breast-GPA and modified breast-GPA were compared using the conc

90 d 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P < .001).

91 In multivariable analysis of the breast-GPA and number of brain metastases (> three v </= three)

92 In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P < .001)

93 After validating the breast-GPA, multivariable Cox regression and recursive partitio

94 ected only 31% of locations deteriorating by GPA.

95 d progression by Bayesian slopes, but not by GPA.

96 The median survival times by GPA score and diagnosis were determined.

97 We then determined that DAF, C3b, GPA, and band 3 molecules were laterally immobilized in

98 mation of a membrane skeleton-linked DAF-C3b-GPA-band 3 complex on the erythrocyte surface.

99 d of haematopoietic progenitor cells (CD36(+)GPA(-/low)).

100 This study was designed to compare GPA with other causes of orbital inflammation and to ide

101 the inability of the tps11 mutant to control GPA infestation.

102 sts was comparable between GPA and controls, GPA samples showed a significant delay of apoptosis.

103 ding, but S118 was dispensable for deterring GPA settling and promoting senescence in GPA-infested pl

104 iagnosis, a robust separation into different GPA scores was discerned, implying considerable heteroge

105 is-Specific Graded Prognostic Assessment (DS-GPA) for patients with non-small-cell lung cancer (NSCLC

106 The original DS-GPA was based on 4 factors found in 1833 patients with N

107 patients studied for the creation of the DS-GPA had a median survival of 7 months from the time of i

108 cluded the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations i

109 corporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical

110 The DS-GPA is based on data from patients diagnosed between 198

111 Forty-eight GPA patients and 38 age-matched healthy donors were incl

112 Two separate eliciting GPA-derived fractions trigger induced resistance to GPA

113 ), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features.

114 ines Agency (EMA) system with categories for GPA and MPA; and 3) classification based on ANCA with sp

115 index of suspicion should be maintained for GPA when a patient presents with an orbital mass and sin

116 The median age at presentation for GPA patients was 30 years (mean +/- standard deviation,

117 BAK1 is required for GPA elicitor-mediated induction of reactive oxygen speci

118 fibers and reversal of blunted response for GPA in HD mice.

119 Notably, NK cells from GPA patients expressed markers of recent in vivo activat

120 Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17.

121 presence of CMV in renal biopsy tissue from GPA patients was investigated by immunohistochemistry an

122 releasing motor neurons depends on Galpha12 (GPA-12), which acts via the single C. elegans RGS RhoGEF

123 In addition, graph-GPA also promotes better understanding of genetic mechan

124 propose a novel statistical framework, graph-GPA, to integrate a large number of GWAS datasets for mu

125 Application of graph-GPA to a joint analysis of GWAS datasets for 12 phenotyp

126 datasets for 12 phenotypes shows that graph-GPA improves statistical power to identify risk variants

127 ar components of tissue destruction of human GPA tissue transplanted into immunodeficient mice.

128 and to proteinase 3, a major autoantigen in GPA, and analyzed the effects on NK cell activation.

129 The destruction of nasal cartilage in GPA is mainly mediated by fibroblasts that can be blocke

130 riving the expansion of CD4+CD28- T cells in GPA patients and how this might relate to clinical featu

131 The expansion of CD4+CD28- T cells in GPA patients is associated with CMV infection and leads

132 uggest that, upon inflammatory conditions in GPA, renal MECs may contribute to the recruitment and ac

133 These defects in GPA performance in the lox5 mutant were accompanied by r

134 be applied to prevent severe loss of HCEC in GPA patients.

135 11 function abolished trehalose increases in GPA-infested leaves of the tps11 mutant plant and attenu

136 ression was rapidly induced to high level in GPA-infested plants.

137 ing reactions on the terminal NRPS module in GPA biosynthesis.

138 ing GPA settling and promoting senescence in GPA-infested plants as well as for pathogen resistance.

139 S-box transcription factor FRUITFULL induces GPA by directly repressing genes of the APETALA2 (AP2) c

140 Patients were divided into GPA and non-GPA groups on the basis of their final clini

141 f such a unique demonstration of the limited GPA manifesting as a bilateral ocular involvement and co

142 ain metastases, confirming the original Lung-GPA.

143 idence of longitudinal progression on mGCIPL GPA event analysis were compared with individuals demons

144 and of the effort needed to study and modify GPA-producing strains to prepare new GPAs to address the

145 isms underlying the differences between NAC, GPA, SCIT, and SLIT groups.

146 e for probing the cyclization of non-natural GPA peptides by these powerful biosynthetic enzymes.

147 opomyosin, ICAM-4, GLUT4, Na/K-ATPase, NHE1, GPA, CD47, Duffy, and Kell were reduced.

148 Patients were divided into GPA and non-GPA groups on the basis of their final clinical diagnosi

149 analyzed and compared with those of the non-GPA group.

150 ny destruction (P = 0.048) compared with non-GPA patients.

151 With reference to the HRT TCA and OCT GPA, ONH surface depression occurred before RNFL thinnin

152 emission in localized and generalized ocular GPA.

153 We present an unusual case of GPA manifesting merely as a bilateral ocular involvement

154 In this study, we report two cases of GPA whose corneal ECD decreased significantly after phac

155 By ANCA specificity, categories of GPA, MPA, and kidney-limited disease did not distinguish

156 from presentation to definitive diagnosis of GPA ranged from 3 to 20 months (mean, 12.1 months; media

157 ocular involvement, led to the diagnosis of GPA.

158 olvement, of whom 7 had a final diagnosis of GPA.

159 yte culture system to decrease expression of GPA, GPB, or GPC via lentiviral short hairpin RNA transd

160 ncreased in roots and in petiole exudates of GPA-colonized plants.

161 agnosis may not show the classic features of GPA.

162 A limited form of GPA may be a diagnostic chameleon.

163 year-old male patient with a limited form of GPA who initially presented with bilateral chronic conju

164 be exerted via the selective interaction of GPA-3 with NPR-17 and site-specific SKN-1 binding to the

165 within granulomatous lesions in the lungs of GPA patients.

166 re compared to determine those predictive of GPA, and patients with GPA also had long-term evaluation

167 echanism underpinning the complex process of GPA cyclization and furthermore show the utility of the

168 mutation (G202D) in the switch II region of GPA-16.

169 Access to the results of GPA did not significantly change the level of agreement

170 aims to present a summary of the results of GPA modification obtained with the three major approache

171 perature despite defects in the structure of GPA-16(it143).

172 changes on imaging are highly suggestive of GPA and should prompt a full diagnostic workup.

173 Features highly suggestive of GPA were sinonasal symptoms, sinonasal changes, or paran

174 minogen activator for on-demand targeting of GPA receptors in vivo.

175 ing progressing (by stereophotography and/or GPA) and healthy eyes were 0.778/0.809, 0.639/0.857, and

176 sion (nonprogressed) by stereophotography or GPA.

177 Orbital GPA can be associated with a high morbidity from potenti

178 A diagnosis of orbital GPA and development of systemic GPA were the main outcom

179 However, early diagnosis of orbital GPA may be difficult because anti-neutrophil cytoplasmic

180 Diagnosis of orbital GPA, especially in patients with lacrimal involvement as

181 nd no patient presenting with solely orbital GPA developed later systemic disease over a median follo

182 No patient with solely orbital GPA involvement at presentation developed systemic disea

183 ed systemic disease, suggesting that orbital GPA can remain localized in the long-term.

184 sogenic non-encapsulated DeltaPG0116-PG0120 (GPA) and DeltaPG0109-PG0118 (GPC) mutants of P. gingival

185 rapy, 347 (18.9%) prescribed dual coxib plus GPA cotherapy, 173 (9.4%) prescribed a nonselective NSAI

186 scribed a nonselective NSAID (NS-NSAID) plus GPA cotherapy, and 453 (24.7%) prescribed an NS-NSAID wi

187 ents), and granulomatosis with polyangiitis (GPA) (3 scans, 1 patient).

188 gories for granulomatosis with polyangiitis (GPA) (Wegener's), microscopic polyangiitis (MPA), and ki

189 lvement in granulomatosis with polyangiitis (GPA) commonly accompanies orbital disease, but occasiona

190 Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associ

191 Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibodies (ANCA)-

192 Granulomatosis with polyangiitis (GPA) is an uncommon autoimmune disease involving multipl

193 ps, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGP

194 Granulomatosis with polyangiitis (GPA), previously Wegener's granulomatosis, requires prom

195 s, such as granulomatosis with polyangiitis (GPA).

196 s found in granulomatosis with polyangiitis (GPA, formerly Wegener's) or the development of vasculiti

197 culitides, granulomatosis with polyangiitis (GPA, formerly Wegener's), microscopic polyangiitis (MPA)

198 ulitis and granulomatosis with polyangiitis (GPA, Wegener's granulomatosis).

199 feature of granulomatosis with polyangiitis (GPA; or Wegener's granulomatosis) is the granulomatous i

200 and imaging features most likely to predict GPA and its systemic spread.

201 f earliest longitudinal progression on pRNFL GPA event analysis.

202 loring enzymes, which can be used to produce GPA analogues that could overcome antibiotic resistance.

203 into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology.

204 We detected RBC (GPA(+))-engulfed material in circulating PMos of patient

205 tients with chronically relapsing refractory GPA.

206 Fifty-three patients with refractory GPA (median age 46 years [interquartile range (IQR) 30-6

207 sing on RTX use for patients with refractory GPA and MPA have been reported.

208 study of all patients with chronic relapsing GPA treated with at least 2 courses of RTX between Janua

209 remission in patients with chronic relapsing GPA.

210 ranulomatosis with polyangiitis (Wegener's) (GPA).

211 ranulomatosis with polyangiitis (Wegener's) (GPA).

212 ranulomatosis with polyangiitis (Wegener's) (GPA).

213 granulomatosis with polyangiitis (Wegener's; GPA), microscopic polyangiitis (MPA), and eosinophilic g

214 cells were only expanded in CMV-seropositive GPA patients and controls.

215 In CMV-seropositive GPA patients we observed negative correlations between t

216 e (CYC) for induction of remission in severe GPA and MPA.

217 ive to CYC for remission induction in severe GPA and MPA.

218 is to present the updated diagnosis-specific GPA indices in a single, unified, user-friendly report t

219 s were used to define the diagnosis-specific GPA prognostic indices.

220 s of orbital GPA and development of systemic GPA were the main outcome measures.

221 and 2.9%, respectively), and more eyes than GPA (P = 0.01) in glaucoma (16.0%, 15.3%, 12.0%, and 7.3

222 and 7.3%, respectively), and more eyes than GPA (P = 0.05) in PGON eyes (26.3%, 23.7%, 27.6%, and 14

223 Micrografting experiments demonstrated that GPA performance on foliage is influenced by the LOX5 gen

224 This suggests that GPA represents a form of bud dormancy, and that dominanc

225 The GPA showed progression in 58% of cases in exfoliation, a

226 zing function of ADF3 in defense against the GPA, we show that resistance in adf3 was restored by ove

227 has an important role in defense against the GPA.

228 important regulator of defenses against the GPA.

229 he BR binds to acidic phospholipids, and the GPA region binds to F-actin.

230 f agreement between expert consensus and the GPA result; however, expert consensus did change in 11 o

231 important for enzymatic modifications by the GPA-tailoring enzymes.

232 ion, once they found the sieve elements, the GPA fed for a more prolonged period from sieve elements

233 el was built to incorporate results from the GPA in the prior distribution for the VFI slopes, allowi

234 Furthermore, the GPA population was larger on the mpl1 mutant than the wi

235 llowing intranasal allergen challenge in the GPA group but not in SCIT and SLIT groups.

236 gen induced cT(FH)-cell proliferation in the GPA group but not in the NAC group (P < .05).

237 showed dysregulation of cT(FH) cells in the GPA group compared to NAC, SCIT, and SLIT groups and ind

238 cT(FH) cells were higher in the GPA group compared with the NAC group and were lower in

239 , progression criteria currently used in the GPA have high specificity, but some patients are more li

240 ble, the peptide core of these molecules-the GPA aglycone-remains highly challenging to modify.

241 On average, the specificity of the GPA "likely progression" alert was high-for the entire s

242 ease in fecundity and population size of the GPA and a parallel reduction in callose deposition in th

243 Electrical monitoring of the GPA feeding behavior indicates that the GPA stylets foun

244 35S gene promoter curtailed the size of the GPA population.

245 nsferases modify distinct side chains on the GPA scaffold.

246 The collective data suggest that the GPA and GPB receptors are of greater importance than the

247 the GPA feeding behavior indicates that the GPA stylets found sieve elements faster when feeding on

248 eview and on reevaluation with access to the GPA printout, the level of agreement between majority ex

249 However, it must be considered when the GPA is used in clinical practice where specificity needs

250 likely progression" were determined with the GPA.

251 Their GPA improved, on average, 0.41 points, and their rate of

252 Thus, GPA-3 and SKN-1a are proposed to regulate cross-antagoni

253 sus and GPA, both before and after access to GPA data, was assessed using kappa statistics.

254 to the time of VF deterioration according to GPA or until the last follow-up visit in stable eyes.

255 Seventy eyes (25.5%) worsened according to GPA.

256 erythrocyte, we show that EBA175 binding to GPA leads to an increase in the cytoskeletal tension of

257 A infestation, is required for resistance to GPA in the Arabidopsis accession Columbia.

258 Here, we show that resistance to GPA is unaltered in an eds1 salicylic acid induction def

259 ived fractions trigger induced resistance to GPA that is dependent on the leucine-rich repeat recepto

260 3 is also required for induced resistance to GPA, independently of BAK1 and reactive oxygen species p

261 utant, which exhibits enhanced resistance to GPA.

262 expressed at elevated levels in response to GPA infestation, is required for resistance to GPA in th

263 ere that the role of PAD4 in the response to GPA is conserved in Arabidopsis accessions Wassilewskija

264 onsumption, PGC-1alpha, NRF1 and response to GPA were significantly reduced in myoblasts from HD pati

265 with lacrimal gland involvement secondary to GPA and to compare them with those of other orbital infl

266 The adf3-conferred susceptibility to GPA was overcome by expression of the ADF3 coding sequen

267 jor Arabidopsis phytoalexin that is toxic to GPA.

268 received at least 2 courses of RTX to treat GPA relapses or to maintain remission.

269 structural information in generating unique GPA derivatives.

270 en species, however, strongly decreased upon GPA, a phenomenon that is associated with bud dormancy i

271 , and low mitotic activity in meristems upon GPA, but found that meristems retain their identity and

272 Thus, the upstream GPA-12/RHGF-1 pathway stimulates only a subset of RHO-1

273 es of fields as showing progression than was GPA (P </= 0.002).

274 Twenty-two percent of patients (8/37) with GPA had evidence of systemic involvement at presentation

275 o identify only 32 of the 64 eyes (50%) with GPA progression.

276 PLR criteria led to improved agreement with GPA at the expense of higher false detection rate.

277 teria for PLR led to improved agreement with GPA at the expense of higher false detection rate.

278 The agreement with GPA was significantly better for the Bayesian compared w

279 es (kappa = 0.32 vs. 0.37 for agreement with GPA).

280 of global and pointwise trend analyses with GPA were explored.

281 ty markers was significantly associated with GPA (OR 1.05 per 1-unit increase in genetic risk score,

282 in CTLA4 were significantly associated with GPA in the single-marker meta-analysis (odds ratio [OR]

283 statistically significantly associated with GPA in this study.

284 In cases of disagreement with GPA, the expert consensus classification was usually pro

285 In the first case of 69-year-old male with GPA, the ECD dropped 39.6% (OD) four months after phacoe

286 dition, nasal fibroblasts from patients with GPA (n = 8) and control healthy nasal fibroblasts (n = 5

287 e those predictive of GPA, and patients with GPA also had long-term evaluation for systemic involveme

288 ascertained in a total of 880 patients with GPA and 1,969 control subjects of European descent.

289 A higher proportion of patients with GPA demonstrated sinonasal involvement (P = 0.011) and b

290 risk of malignancy observed in patients with GPA treated with cytotoxic agents and should be avoided

291 inical and imaging features of patients with GPA were analyzed and compared with those of the non-GPA

292 tive of all-cause mortality in patients with GPA, independent of other traditional risk factors for m

293 es were demonstrated in 29% of patients with GPA.

294 time, 64 (9%) had confirmed progression with GPA.

295 Associations of multiple SNPs with GPA were assessed using genetic risk scores based on sus

296 The HD mice treated with GPA had impaired activation of liver PGC-1alpha and deve

297 Treatment with GPA resulted in increased expression of AMPK, PGC-1alpha

298 Treatment with GPA significantly increased expression of PGC-1alpha, NR

299 es, which were exacerbated by treatment with GPA.

300 d 453 (24.7%) prescribed an NS-NSAID without GPA cotherapy.