araag2/HINT huggingface dataset:
Clinical trial NCT00381303 (phase 3, status: completed)
Conditions: hiv, infectious
ICD codes: B20, Z71.7, O98.72, Z21, O98.73, R75, Z11.4, B99.8, B99.9, H20.033, A09, B27.80, B27.81, B27.82
Drugs: darunavir, ritonavir
SMILES: [H][C@@]12CCO[C@]1([H])OC[C@@H]2OC(=O)N[C@@H](CC1=CC=CC=C1)[C@H](O)CN(CC(C)C)S(=O)(=O)C1=CC=C(N)C=C1, CC(C)[C@H](N1CCCNC1=O)C(=O)N[C@H](C[C@H](O)[C@H](CC1=CC=CC=C1)NC(=O)COC1=C(C)C=CC=C1C)CC1=CC=CC=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Documented HIV infection

          -  Plasma HIV-RNA >= 1000 copies/mL

          -  Must be able to comply with protocol requirements

        Exclusion Criteria:

          -  No prior use of PREZISTA (darunavir), TMC125, enfuvirtide, or tipranavir

          -  No currently active AIDS defining illness, Category C conditions according to the
             Center for Disease Control [CDC] Classification System for HIV Infection (1993) with
             the following exceptions, which must be discussed with the Sponsor prior to
             enrollment: stable cutaneous Kaposi's Sarcoma, Wasting syndrome due to HIV infection

          -  Not currently using an investigational drug

          -  Not pregnant or breastfeeding

          -  No Grade 3 or 4 laboratory abnormality as defined by DAIDS (Division of AIDS, National
             Institute of Allergy and Infectious Diseases).
Clinical trial NCT00243646 (phase 3, status: terminated)
Conditions: prostate cancer
ICD codes: C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5
Drugs: lupron, casodex
SMILES: CC(O)(CS(=O)(=O)C1=CC=C(F)C=C1)C(=O)NC1=CC(=C(C=C1)C#N)C(F)(F)F
Reason stopped: 
    poor accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  High risk patients - Two to three of the following: PSA 10-30 ng/mL, Gleason score
             greater than or equal to 6, clinical stage greater than or equal to T2c (2002 ACJJ).

          -  CT of the abdomen and pelvis and bone scan without evidence of metastases.

          -  An enzymatic prostatic acid phosphatase must be obtained prior to randomization.

          -  A serum testosterone must be obtained prior to initiation of androgen deprivation
             therapy.

          -  No prior pelvic external beam radiation therapy for prostate cancer or other
             malignancies.

          -  No prior androgen deprivation therapy.

          -  Minimum 5 year life expectancy.

          -  No other invasive cancer diagnosis other than non-melanoma skin cancer within the last
             5 years.

        Exclusion Criteria:

          -  Exclusion criteria will be limited to patients who do not meet the above eligibility
             criteria.
Clinical trial NCT00650078 (phase 3, status: completed)
Conditions: rheumatoid arthritis
ICD codes: M06.9, M05.9, M06.08, M06.00, M06.011, M06.012, M06.019
Drugs: mr prednisone, placebo
SMILES: [H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Documented history of RA in agreement with ACR criteria

          -  DMARD treatment for RA greater than or equal to 6 months, with a stable dose greater
             than or equal to 6 weeks prior to screening visit

          -  Duration of morning stiffness greater than or equal to 45 minutes

          -  greater than or equal to 4 swollen joints (out of 28)

          -  greater than or equal to 4 tender joints (out of 28)

        Exclusion Criteria:

          -  Suffering from another disease, which requires glucocorticoid treatment during the
             study period

          -  Synovectomy within 4 months prior to study start

          -  Use of glucocorticoids:

               -  Continued use of systemic glucocorticoids within 4 weeks prior to screening visit

               -  Intermittent use of glucocorticoids within 2 weeks prior to screening visit.

               -  Joint injections within 6 weeks prior to screening visit

               -  Topical glucocorticoids must be stopped at screening visit

          -  Use of biologicals such as: tumor necrosis factor α (TNFα) inhibitors and other
             compounds within 5 serum half lives prior to screening visit

          -  Pregnancy or nursing
Clinical trial NCT00295750 (phase 3, status: completed)
Conditions: prostate cancer
ICD codes: C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5
Drugs: degarelix, degarelix, leuprolide 7.5 mg
SMILES: CC(C)C[C@H](NC(=O)[C@@H](CC1=CC=C(NC(N)=O)C=C1)NC(=O)[C@H](CC1=CC=C(NC(=O)[C@@H]2CC(=O)NC(=O)N2)C=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC1=CC=CN=C1)NC(=O)[C@@H](CC1=CC=C(Cl)C=C1)NC(=O)[C@@H](CC1=CC=C2C=CC=CC2=C1)NC(C)=O)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(N)=O, CC(C)C[C@H](NC(=O)[C@@H](CC1=CC=C(NC(N)=O)C=C1)NC(=O)[C@H](CC1=CC=C(NC(=O)[C@@H]2CC(=O)NC(=O)N2)C=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC1=CC=CN=C1)NC(=O)[C@@H](CC1=CC=C(Cl)C=C1)NC(=O)[C@@H](CC1=CC=C2C=CC=CC2=C1)NC(C)=O)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(N)=O, CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O
Eligibility criteria:

        Main Inclusion Criteria:

          -  Patients, aged 18 years or over, with histologically proven prostate cancer of all
             stages in whom endocrine treatment is indicated.

          -  Baseline testosterone >1.5 ng/mL.

          -  Life expectancy of at least 12 months.
Clinical trial NCT01295372 (phase 3, status: completed)
Conditions: schizophrenia
ICD codes: F20.0, F20.1, F20.2, F20.3, F20.5, F20.89, F20.9
Drugs: zicronapine, risperidone
SMILES: CN1CCN(CC1(C)C)[C@@H]1C[C@H](C2=C1C=C(Cl)C=C2)C1=CC=CC=C1, OCCOCCN1CCN(CC1)C1=NC2=CC=CC=C2SC2=CC=CC=C12
Eligibility criteria:

        Inclusion Criteria:

          -  The patient meets the Diagnostic and Statistical Manual of Mental Disorders, 4th
             edition, Text Revision (DSM-IV-TR) criteria for schizophrenia

          -  The patient is a man or woman, ≥18 and ≤65 years old

          -  The patient has a PANSS total score ≥60 and ≤100 (extremes included) at screening and
             baseline

        Exclusion Criteria:

          -  The patient has a current, predominant Axis I psychiatric disorder other than
             schizophrenia as defined in the DSM-IV-TR

          -  The patient has a current diagnosis or a history of substance dependence (except
             nicotine) or substance abuse (except cannabis) according to the DSM-IV-TR criteria ≤6
             months prior to screening

          -  The patient is at significant risk of harming him/herself or others according to the
             investigator's judgement (assisted by the assessment of suicidal ideation and
             behaviour using the C-SSRS)

          -  The patient is resistant to antipsychotic treatment according to the investigator's
             judgement or has been treated with clozapine ≤3 months prior to screening

          -  The patient has experienced an acute exacerbation requiring hospitalisation ≤3 months
             prior to screening or between screening and baseline

          -  The patient has been treated with risperidone or paliperidone ≤6 months prior to
             screening

        Other inclusion and exclusion criteria may apply.
Clinical trial NCT01676987 (phase 3, status: completed)
Conditions: asthma
ICD codes: J45.998, J82.83, J45.909, J45.991, J45.20, J45.30, J45.40
Drugs: fixed combination of budesonide and formoterol, budesonide
SMILES: COC1=CC=C(CC(C)NCC(O)C2=CC(NC=O)=C(O)C=C2)C=C1, COC1=CC=C(CC(C)NCC(O)C2=CC(NC=O)=C(O)C=C2)C=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of uncontrolled asthma

          -  Age ranged from 18 to 77 years

          -  Nonsmokers

        Exclusion Criteria:

          -  Use of oral corticosteroids, anti-leukotrienes, immunoglobulins, beta blockers,
             digitalis, amiodarone, antifungals, antidepressants, monoamine oxidase inhibitors and
             tricyclics during the standardization

          -  Atrial fibrillation, Flutter, severe and complex tachyarrhythmias atrioventricular
             block 1,2 and 3

          -  Diabetes mellitus

          -  Pregnancy

          -  Neuropsychiatric diseases

          -  Pulmonary malformations, tuberculosis, Cystic fibrosis

          -  Immunosuppressive treatment

          -  Hospitalization for asthma or respiratory infection in last 30 days

          -  Severe systemic disease
Clinical trial NCT00219167 (phase 3, status: completed)
Conditions: hypertension
ICD codes: I15.0, I97.3, K76.6, P29.2, G93.2, H40.053, I10
Drugs: aliskiren
SMILES: CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C
Eligibility criteria:

        Inclusion Criteria

          -  Patients with at least 65 years-old

          -  Patients with essential hypertension Exclusion Criteria

          -  Severe hypertension

          -  History or evidence of a secondary form of hypertension

          -  History of Hypertensive encephalopathy or cerebrovascular accident. Other
             protocol-defined inclusion exclusion criteria also apply.
Clinical trial NCT00656136 (phase 3, status: completed)
Conditions: carcinoma, non-small-cell lung
ICD codes: D02.20, D02.21, D02.22
Drugs: placebo, bibw 2992
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, [H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H]
Eligibility criteria:

        Inclusion criteria:

          1. Patients with pathologic confirmation of NSCLC Stage III-B (with pleural effusion) or
             Stage IV adenocarcinoma who have failed at least one but not more than two lines of
             cytotoxic chemotherapy (including adjuvant chemotherapy). One of the chemotherapy
             regimens must have been platinum-based.

          2. Progressive disease following at least 12 weeks of treatment with erlotinib (Tarceva®)
             or gefitinib (Iressa®)

          3. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance Score 0, 1 or 2

          4. Patients with at least one tumor lesion that can accurately be measured by magnetic
             resonance imaging (MRI), or computed tomography (CT) in at least one dimension with
             longest diameter to be recorded as >20 mm using conventional techniques or >10 mm with
             spiral CT scan

          5. Male and female patients age >18 years

          6. Life expectancy of at least three (3) months

          7. Written informed consent that is consistent with ICH-GCP guidelines

        Exclusion criteria:

          1. Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of treatment Day 1

          2. Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance
             non-cancer therapy) or immunotherapy within the past 4 weeks

          3. Active brain metastases

          4. Significant or recent acute gastrointestinal disorders with diarrhea

          5. Patients who have any other life-threatening illness or organ system dysfunction,

          6. Other malignancies diagnosed within the past five (5) years

          7. Radiotherapy within the past 2 weeks prior to treatment

          8. History of clinically significant or uncontrolled cardiac disease

          9. Adequate ANC and platelet count

         10. Adequate liver and kidney function

         11. Patients with any serious active infection including known HIV, active hepatitis B or
             active hepatitis C
Clinical trial NCT03189537 (phase 3, status: completed)
Conditions: influenza, human, acute respiratory infection, common cold, flu, viral infection
ICD codes: J11.81, J11.82, J10.01, J10.81, J10.82, J11.08, J11.2, J06.9, J22, J47.0, J44.0, J00, T48.5X6S, T48.5X3S, T48.5X4S, T48.5X5S, T48.5X6A, T48.5X6D
Drugs: ingavirin (imidazolyl ethanamide pentandioic acid), placebo oral capsule
SMILES: OC(=O)CCCC(=O)NCCC1=CNC=N1, CC1=CC(O)=CC(C)=C1Cl
Eligibility criteria:

        Inclusion Criteria:

          -  Participants who do have continuous contact with ill person (staff members, dormitory,
             family members), laboratory confirmed viral origin, during influenza/other acute viral
             respiratory disease season

          -  First exposure with the ill person who is present with symptoms of flu or acute
             respiratory viral infection (fever, intoxication, catarrhal symptoms) ≤ 48 hours

          -  Signed Informed Contest to participate in the study

          -  Contraception throughout the study

        Exclusion Criteria:

          -  Interferone or interferone inducers intake, or substances with action on immune system
             intake less then 3 months before inclusion

          -  Anti-virals intake, other then investigational drug, throughout the study

          -  Vaccination for Influenza less than 1 year before inclusion

          -  Pregnant or lactating
Clinical trial NCT00611026 (phase 3, status: completed)
Conditions: overactive bladder
ICD codes: N32.81
Drugs: tolterodine er, placebo, fesoterodine
SMILES: CC(C)N(CC[C@H](C1=CC=CC=C1)C1=C(O)C=CC(C)=C1)C(C)C, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CC(C)N(CC[C@H](C1=CC=CC=C1)C1=C(OC(=O)C(C)C)C=CC(CO)=C1)C(C)C
Eligibility criteria:

        Inclusion Criteria:

          -  Adult subjects with overactive bladder symptoms (subject-reported) for greater than or
             equal to 3 months prior to Screening/Enrollment visit.

          -  Reported at least an average of 1 UUI episode per 24 hours in the 3-day bladder diary
             prior to the Randomization/Baseline visit

          -  Mean urinary frequency of greater than or equal to 8 micturitions per 24 hours as
             verified by the 3-day bladder diary prior to randomization/Baseline visit.

        Exclusion Criteria:

          -  Subjects with any condition that would contraindicate their usage of fesoterodine
             including: hypersensitivity to the active substance (fesoterodine fumarate) or to
             peanut or soya or any of the excipients, urinary retention, gastric retention,
             uncontrolled narrow angle glaucoma, myasthenia gravis, severe hepatic impairment
             (Child Pugh C), severe ulcerative colitis, and toxic megacolon.

          -  Subjects with clinically significant hepatic or renal disease or other significant
             unstable diseases.

          -  OAB symptoms caused by neurological conditions, known pathologies of urinary tract,
             etc.

          -  Subjects with previous history of acute urinary retention requiring catheterization,
             or severe voiding difficulties in the judgment of the investigator, prior to baseline.
Clinical trial NCT00236002 (phase 3, status: terminated)
Conditions: osteoporosis
ICD codes: M81.6, Z82.62, Z13.820, M81.8, Z87.310, M81.0, M80.80XS
Drugs: alendronate
SMILES: COC1=CC2=C(C=C1)C=C(C=C2)[C@H](C)C(O)=O
Reason stopped: 
    slow accrual than anticipated.
  
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically/cytologically proven, non-metastatic (M0) adenocarcinoma of the
             prostate.

          -  Life expectancy of > 12 months.

          -  Initiation of treatment with the luteinizing hormone-releasing hormone agonist
             (LHRH-a) Lupron no more than 15 days prior or 30 days following, baseline visit.

          -  Requiring treatment with LHRH agonists for prostate cancer, for a duration of at least
             12 months from baseline.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

          -  Prior to any study-specific procedures, subject (and/or their legally authorized
             representative) has voluntarily signed and dated an informed consent form.

        Exclusion Criteria:

        Bone Metastases Current or previous use with in past 12 months of bisphosphonate. Known
        hypersensitivity to LHRH. Hypocalcaemia. Severe renal impairment, Abnormal liver function,
        Hypothyroidism, Hyperthyroidism, Bilateral hip replacement.

        Use of LHRH or anti-androgen medication within last 12 months. Abnormalities of esophagus
        which delay esophageal emptying. Inability to stand or sit upright for at least 30 minutes.
Clinical trial NCT00424268 (phase 3, status: completed)
Conditions: chronic obstructive pulmonary disease
ICD codes: J44.9, J44.1, J44.0
Drugs: roflumilast, placebo
SMILES: FC(F)OC1=C(OCC2CC2)C=C(C=C1)C(=O)NC1=C(Cl)C=NC=C1Cl, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Main Inclusion Criteria:

          -  History of COPD for at least 12 months prior to baseline visit and chronic productive
             cough for 3 months in each of the 2 years prior to baseline visit

          -  FEV1/FVC ratio (post-bronchodilator) ≤ 70%

          -  FEV1 (post-bronchodilator) between ≥ 40% and ≤ 70% of predicted

          -  Treated with tiotropium for at least 3 months before enrollment

          -  At least 28 puffs of rescue medication during last week prior to randomization

        Main Exclusion Criteria:

          -  COPD exacerbation indicated by a treatment with systemic glucocorticosteroids and/or
             antibiotics not stopped at least 4 weeks prior to baseline visit
Clinical trial NCT01459367 (phase 3, status: completed)
Conditions: erosive esophagitis
ICD codes: B37.81, K20.0, K20.80, K20.81, K20.90, K20.91, K21.9
Drugs: tak-438, tak-438, lansoprazole
SMILES: CNCC1=CN(C(=C1)C1=CC=CC=C1F)S(=O)(=O)C1=CC=CN=C1, CNCC1=CN(C(=C1)C1=CC=CC=C1F)S(=O)(=O)C1=CC=CN=C1, CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1
Eligibility criteria:

        Inclusion Criteria:

          1. At Visit H-1 (start of the treatment period), the participants must have
             endoscopically confirmed erosive esophagitis of Grade A to D, as defined by the LA
             classification grading system, and the target number of participants who are clearly
             Grade C or D is 15% or more of the total participants.

          2. Outpatients (including inpatient for examination)

          3. Participants must have successfully completed the treatment period and have
             endoscopically healed EE at Week 2, 4, or 8 in the treatment period. Endoscopically
             healed EE is defined as those participants who have endoscopically confirmed EE of
             Grade O as defined by the LA classification grading system.

        Exclusion Criteria:

          1. Participants with an esophagus-related complication (eosinophilic esophagitis,
             esophageal varices, scleroderma, viral or fungal infection, esophageal stenosis,
             etc.), a history of radiotherapy or cryotherapy of the esophagus, a caustic or
             physiochemical trauma (esophageal sclerotherapy, etc.). However, participants with
             Schatzki's ring (mucosal tissue ring around inferior esophageal sphincter) or
             Barrett's esophagus are allowed to be included.

          2. Participants who have received surgery or treatment affecting gastroesophageal reflux
             (cardioplasty, dilation of esophageal stenosis [excluding Schatzki's ring], etc.), or
             who have a history of surgery of stomach or duodenum (excluding removal of benign
             polyp under endoscopy)

          3. Participants who have acute upper gastrointestinal bleeding, gastric or duodenal ulcer
             (mucosal defect with white coating) within 30 days prior to Visit H-1 (initiation of
             study drug administration). However, participants with gastric or duodenal erosions
             are allowed to be included.

          4. Participants with a previous or current history of Zollinger-Ellison syndrome, or
             other gastric acid hypersecretion disorder
Clinical trial NCT00661362 (phase 3, status: completed)
Conditions: type 2 diabetes
ICD codes: E11.65, E11.9, E11.21, E11.36, E11.41, E11.42, E11.44
Drugs: saxagliptin, placebo, metformin
SMILES: N[C@H](C(=O)N1[C@H]2C[C@H]2C[C@H]1C#N)C12CC3CC(CC(O)(C3)C1)C2, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CSCC[C@H](N)C(O)=O
Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosed with Type 2 diabetes

          -  Treatment with metformin at a stable dose >1500 mg/day

          -  HbA1c ≥ 7.0% and ≤10.0%

        Exclusion Criteria:

          -  Insulin therapy within one year of enrolment (with the exception of insulin therapy
             during a hospitalization or use in gestational diabetes)

          -  Type 1 diabetes, history of ketoacidosis, or hyperosmolar non-ketonic koma
Clinical trial NCT00038948 (phase 3, status: completed)
Conditions: renal transplantation
ICD codes: N25.0, Q61.4, N23, N26.9, P96.0, Q60.0, Q60.1
Drugs: sirolimus, tacrolimus, cyclosporine a
SMILES: CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2, COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1C(CC2)NC(C)=O, CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C
Eligibility criteria:

        Inclusion Criteria:

          -  Age greater than or equal to 13 years.

          -  Receiving CsA or tacrolimus from the time of transplantation or within 2 weeks
             thereafter

          -  Patients with a functioning allograft and a Nankivell GFR greater than or equal to 20
             mL/min, within 2 weeks before randomization

        Exclusion Criteria:

          -  Biopsy-confirmed acute rejection within 12 weeks before randomization, that was
             determined to require antirejection treatment

          -  Patients in whom kidney-pancreas or other multiple organ transplants have been
             performed
Clinical trial NCT00170963 (phase 3, status: completed)
Conditions: hypertension
ICD codes: I15.0, I97.3, K76.6, P29.2, G93.2, H40.053, I10
Drugs: valsartan/amlodipine
SMILES: CCCCC(=O)N(CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1)[C@@H](C(C)C)C(O)=O
Eligibility criteria:

        Inclusion Criteria:

          -  Patients with uncomplicated, essential hypertension

        Exclusion Criteria:

          -  Severe hypertension

          -  History of stroke, myocardial infarction, heart failure, chest pain, abnormal heart
             rhythm

          -  Liver, kidney, or pancreas disease

          -  Insulin dependent diabetes

          -  Allergy to certain medications used to treat high blood pressure

        Other protocol-defined exclusion criteria may apply.