araag2/HINT huggingface dataset:
Clinical trial NCT00251394 (phase 2, status: completed)
Conditions: non-hodgkin's lymphoma
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: rituxan, 1018 iss
SMILES: [H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C
Eligibility criteria:

        Inclusion Criteria:

          -  18 years of age or older

          -  Pathological evidence of CD20+, B-cell follicular non-Hodgkin's lymphoma

          -  Received at least one previous chemotherapy regimen for lymphoma

          -  Hemoglobin > 8.5 g/dl

          -  WBC > 2,000/mm3

          -  ANC > 1,000/mm3

          -  Platelet count > 75,000/mm3

          -  ECOG performance status of less than or equal to 2

          -  Life expectancy of greater than 4 months

          -  Women and men of childbearing potential must be willing to use highly effective
             methods of birth control for duration of time on the study

        Exclusion Criteria:

          -  Pregnant of lactating women

          -  Treatment with chemotherapy, including systemic steroids, or radiation therapy within
             30 days

          -  Current use of systemic or inhaled steroids

          -  Treatment with radioimmunotherapy, autologous stem cell transplantation, or
             fludarabine within 6 months

          -  Disease progression within 6 months of any previous rituximab therapy

          -  History of allogenic transplantation, including nonmyeloablative transplantation

          -  Unstable angina, symptomatic cardiac arrhythmia or clinical heart failure

          -  Severe pulmonary disease, symptomatic pleural effusions, or clinically significant
             pulmonary symptoms

          -  Active infection requiring systemic antibiotic, antiviral, or antifungal therapy

          -  Clinically apparent CNS lymphoma

          -  Major surgery within 2 weeks

          -  Known human anti-murine antibody (HAMA) or human anti-chimeric antibody (HACA)
             response

          -  Known Hepatitis B surface antigen positive

          -  History of autoimmune disorder

          -  Current therapeutic use of anticoagulants

          -  History of coagulopathy

          -  Known allergy to any of the components of 1018 ISS or Rituxan

          -  Participation in another investigational trial within 30 days

          -  Any clinically significant abnormality in screening blood chemistry, hematology, or
             urinalysis
Clinical trial NCT00298896 (phase 2, status: completed)
Conditions: carcinoma, small cell, small cell lung cancer
ICD codes: C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2
Drugs: sns-595
SMILES: CN[C@H]1CN(C[C@@H]1OC)C1=CC=C2C(=O)C(=CN(C3=NC=CS3)C2=N1)C(O)=O
Eligibility criteria:

        Inclusion Criteria:

          -  Able to understand and willing to sign a written informed consent document

          -  Patients who have recurrent or refractory SCLC requiring second-line chemotherapy who
             previously received first-line chemotherapy

          -  Measurable disease

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2

          -  Brain metastasis may be included if the patient is neurologically stable and has been
             off steroids and anticonvulsants for at least 4 weeks prior to Cycle 1 Day 0

          -  Laboratory values within the normal or reasonable reference range as specified by the
             protocol

        Exclusion Criteria:

          -  Prior exposure to SNS-595

          -  Pregnant or breastfeeding

          -  Women of childbearing potential, or male partners of women of childbearing potential,
             unwilling to use an approved, effective means of contraception according to the
             institution's standards

          -  Other active malignancies or other malignancies within the past 12 months, other than
             non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostatic
             intraepithelial neoplasia

          -  Q-wave myocardial infarction or cerebrovascular accident/transient ischemic attack
             (TIA) within 6 months before the first SNS-595 dose

          -  Thromboembolic event (deep vein thrombosis or pulmonary embolus) within 28 days before
             the first SNS-595 dose

          -  Requires kidney dialysis (hemodialysis or peritoneal)

          -  Prior chemotherapy, investigational agents, or radiation therapy within 28 days before
             Cycle 1 Day 0; however, nitrosoureas, mitomycin C, and therapeutic monoclonal
             antibodies are not permitted for at least 42 days before Cycle 1 Day 0

          -  In patients with toxicities caused by prior cancer therapy, those toxicities must have
             returned to less than or equal to Grade 1, with the exception of alopecia.

          -  Prior pelvic radiation therapy or radiation to greater than 25% of bone marrow
             reserve; radiation to the brain is permitted up to 28 days before the first SNS-595
             dose, as long as the patient does not require treatment with corticosteroids for
             symptom control related to brain metastases.

          -  Any other medical, psychological, or social condition that, in the opinion of the
             Principal Investigator, would contraindicate the patient's participation in the
             clinical trial due to safety or compliance with study procedures
Clinical trial NCT00437892 (phase 2, status: terminated)
Conditions: venous thromboembolism, hypercholesterolemia
ICD codes: O88.22, O88.23, O88.211, O88.212, O88.213, O88.219, E78.01, E78.00, Z83.42
Drugs: atorvastatin, atorvastatin
SMILES: CC(C)C1=C(C(=O)NC2=CC=CC=C2)C(=C(N1CC[C@@H](O)C[C@@H](O)CC(O)=O)C1=CC=C(F)C=C1)C1=CC=CC=C1, CC(C)C1=C(C(=O)NC2=CC=CC=C2)C(=C(N1CC[C@@H](O)C[C@@H](O)CC(O)=O)C1=CC=C(F)C=C1)C1=CC=CC=C1
Reason stopped: 
    competitive trials and slow recruitment rate
  
Eligibility criteria:

        Inclusion Criteria:

          -  Adult patients with a single episode of idiopathic VTE (either DVT or pulmonary
             embolism) who received at least 6 months of adequate treatment with oral
             anticoagulants, for whom treatment withdrawal is planned, and with LDL cholesterol
             levels of equal to or greater than 130 mg/dL.

        Exclusion Criteria:

          -  Age below 18 years,

          -  Pregnancy or puerperium,

          -  Active malignancy,

          -  Need for other anticoagulant treatments (unfractionated heparin, low molecular weight
             heparin),

          -  Presence of transient risk factors for VTE [recent (< 3 months) surgery,

          -  Trauma,

          -  Fractures,

          -  Acute medical disease with immobilization,

          -  Pregnancy or use of oral contraceptives],

          -  Contraindications to statin therapy,

          -  Chronic renal failure (defined by creatinine clearance < 30 mL/min),

          -  Ongoing treatment with statins or fibrates,

          -  Major indication to statin therapy [history of cardiovascular disease, diabetes,
             elevated cardiovascular risk according to the ATP III criteria(19)],

          -  Life expectancy of less than 6 months,

          -  Geographic inaccessibility,

          -  Concomitant enrolment in another clinical trial,

          -  Refused informed consent.
Clinical trial NCT00383331 (phase 2, status: terminated)
Conditions: non-small-cell lung cancer
ICD codes: C78.00, C78.01, C78.02, D14.30, D14.31, D14.32, C34.2
Drugs: pemetrexed, gemcitabine
SMILES: [H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H], [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Reason stopped: 
    trial was stopped early due to low enrollment
  
Eligibility criteria:

        Inclusion Criteria:

          -  histologic or cytologic diagnosis of NSCLC Stage IIIB or IV

          -  no prior systemic chemotherapy for advanced Non-Small Cell Lung Cancer

          -  Prior radiotherapy must be completed at least 4 weeks before study enrollment.

        Exclusion Criteria:

          -  estimated life expectancy of 12 weeks

          -  a serious cardiac condition, such as myocardial infarction within 6 months, angina, or
             heart disease

          -  documented brain metastases unless the patient has completed successful local therapy
             for central nervous system metastases and has been off of corticosteroids for at least
             2 weeks before enrollment

          -  significant weight loss (that is, > 10%) over the previous 6 weeks before study entry.
Clinical trial NCT01254773 (phase 2, status: completed)
Conditions: alzheimer's disease
ICD codes: G30.8, G30.9, G30.0, G30.1
Drugs: experimental bapineuzumab
SMILES: C#CC1=CC=CC(NC2=NC=NC3=CC4=C(OCCOCCOCCO4)C=C23)=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of probable AD

          -  Age from 50 to less than 89

          -  Mini-Mental Status Exam score of 18-26 inclusive

          -  Brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of AD

          -  Stable doses of medications (cholinesterase inhibitors and memantine allowed)

          -  Caregiver able to attend all clinic visits with patient

          -  Amyloid burden on screening PET scan consistent with diagnosis of AD

        Exclusion Criteria:

          -  Significant neurological disease other than AD

          -  Major psychiatric disorder

          -  Significant systemic illness

          -  History of stroke or seizure, autoimmune disease, myocardial infarction within the
             last 2 years

          -  Smoking greater than 20 cigarettes per day

          -  Anticonvulsants, anti-Parkinson's, anticoagulant, or narcotic medications

          -  Prior treatment experimental immunotherapeutics or vaccines for AD

          -  Women of childbearing potential

          -  Presence of pacemakers, CSF shunts, or foreign metal objects in the eyes, skin or body
Clinical trial NCT01573624 (phase 2, status: completed)
Conditions: asthma
ICD codes: J45.998, J82.83, J45.909, J45.991, J45.20, J45.30, J45.40
Drugs: ff/gsk573719, ff/gsk573719, ff/gsk573719, ff/gsk573719, ff/gsk573719, ff, ff/vi
SMILES: OC(C1=CC=CC=C1)(C1=CC=CC=C1)C12CC[N+](CCOCC3=CC=CC=C3)(CC1)CC2, OC(C1=CC=CC=C1)(C1=CC=CC=C1)C12CC[N+](CCOCC3=CC=CC=C3)(CC1)CC2, OC(C1=CC=CC=C1)(C1=CC=CC=C1)C12CC[N+](CCOCC3=CC=CC=C3)(CC1)CC2, OC(C1=CC=CC=C1)(C1=CC=CC=C1)C12CC[N+](CCOCC3=CC=CC=C3)(CC1)CC2, OC(C1=CC=CC=C1)(C1=CC=CC=C1)C12CC[N+](CCOCC3=CC=CC=C3)(CC1)CC2, [H][C@@]12C[C@@H](C)[C@](OC(=O)C3=CC=CO3)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C
Eligibility criteria:

        Inclusion Criteria:

          -  Outpatient

          -  18 years of age or older at Visit 1

          -  Diagnosis of Asthma

          -  Male or eligible Female

          -  Pre-bronchodilator FEV1 of 40-80% of the predicted normal value at Visit 1

          -  Demonstrated reversibility by ≥12% and ≥200mL of FEV1 within 40 minutes following
             albuterol at Visit 1

          -  A need for regular controller therapy (i.e., inhaled corticosteroids alone or in
             combination with a long-acting beta-agonist, or leukotriene modifier etc.,) for a
             minimum of 8 weeks prior to Visit 1.

        Exclusion Criteria:

          -  History of Life threatening asthma

          -  Respiratory infection not resolved

          -  Asthma exacerbation

          -  Concurrent respiratory disease

          -  Current Smokers

          -  Other diseases that are uncontrolled disease or disease state that, in the opinion of
             the investigator, would put the safety of the patient at risk through study
             participation or would confound the interpretation of the efficacy results if the
             condition/disease exacerbated during the study

          -  A positive Hepatitis B surface antigen or positive Hepatitis C antibody and/or HIV

          -  Visual clinical evidence of oropharyngeal candidiasis

          -  Drug or milk protein allergies

          -  Concomitant medications affecting course of asthma

          -  Use of any other investigational medication within 30 days or 5 drug half-lives
             (whichever is longer)

          -  Previous use of GSK573719

          -  Any disease preventing use of anticholinergics

          -  Any condition that impairs compliance with study protocol including visit schedule and
             completion of daily diaries

          -  Any subject with a history of alcohol or substance abuse

          -  Any affiliation with Investigator's site
Clinical trial NCT00259402 (phase 2, status: completed)
Conditions: esophageal neoplasms
ICD codes: K22.2, K22.81, Q39.4, P78.83, I85.00, I85.01, I85.10
Drugs: oxaliplatin + cisplatin + 5-fluorouracil (5-fu)
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Eligibility criteria:

        Inclusion Criteria:

          -  ECOG 0-1

          -  Patients with histologically proven epidermoid carcinoma or adenocarcinoma of
             esophagus or stomach, with unresectable or metastatic disease;

          -  No previous treatment with chemotherapy or radiotherapy

          -  Measurable lesion (uni or bidimensional)

        Exclusion Criteria:

          -  Creatinin clearance <50 mL/min

          -  Total bilirubin >1.5*ULN (Upper Limit of Normal)

          -  AST/ALT > 2.5*ULN

          -  Total White Blood Cell <1.500.000/mL

          -  Platelet count <100.000.000/mL

          -  symptomatic sensitive peripheral neuropathy

          -  pregnant or breast-feeding women

        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.
Clinical trial NCT00308282 (phase 2, status: completed)
Conditions: arthritis, rheumatoid
ICD codes: M06.9, M05.9, M06.08, M06.00, M06.011, M06.012, M06.019
Drugs: ly2127399, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Male or female between the ages of 18 and 75 years

          -  Have given written informed consent approval

          -  Women must not be at risk to become pregnant during study participation

          -  Diagnosis of Rheumatoid Arthritis according to the 1987 revised American Rheumatism
             Association (ARA) criteria for the classification of RA

          -  Serum C-reactive protein (CRP) measurement greater than the upper limit of normal
             (ULN, 0.574 mg/dL), or erythrocyte sedimentation rate (ESR) ≥28 mm/hr

          -  Current, regular use of Methotrexate, at a stable dose

          -  Biologic DMARD naïve, and have had an insufficient response (in the opinion of the
             investigator) to an adequate therapeutic dose of at least 1 oral DMARD

        Exclusion Criteria:

          -  Use of excluded medications (reviewed by study doctor)

          -  Surgical treatment of a joint with 2 months of study enrollment that is to be assessed
             in the study

          -  Are unable to ambulate; that is, confined to bed or wheelchair bound

          -  Have medical findings which, in the opinion of the study doctor, put participant at an
             unacceptable risk for participation in the study

          -  Have had recent or ongoing infection which, in the opinion of the study doctor put
             participant at an unacceptable risk for participation.
Clinical trial NCT00570089 (phase 2, status: completed)
Conditions: myocardial ischemia
ICD codes: I25.6, P29.4
Drugs: ranolazine, placebo
SMILES: COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          1. Women with signs and symptoms of myocardial ischemia (chest pain, abnormal stress
             testing, abnormal noninvasive testing) in the absence of obstructive coronary artery
             disease (epicardial coronary stenosis <50% luminal diameter stenosis).

          2. Women with ≥10% myocardial ischemia by CMR perfusion.

        Exclusion Criteria:

          1. Contraindications to withholding nitrates, beta-blockers, calcium channel agents,
             ACE/ARB agents for 48 hours prior to testing.

          2. Contraindications in CMR including AICD, pacemaker, untreatable claustrophobia or
             known angio-edema.

          3. Contraindications to ranolazine including hepatic insufficiency, prolonged QT, renal
             failure.

          4. Women taking drugs that inhibit CYP3A such as diltiazem, verapamil, ketoconazole,
             macrolides or HIV protease inhibitors.

          5. Women less than 18 years of age.

          6. Women on drugs that prolong the QT interval such as Class Ia or III antiarrhythmic
             agents, erythromycin, certain antipsychotics.

          7. Pregnancy or breast feeding.

          8. Life expectancy less than 6 months.
Clinical trial NCT00003642 (phase 2, status: terminated)
Conditions: bladder cancer
ICD codes: D30.3, C67.5, C67.9, C79.11, C67.0, C67.1, D41.4
Drugs: cisplatin, fluorouracil
SMILES: [H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Reason stopped: 
    low accrual
  
Eligibility criteria:

        DISEASE CHARACTERISTICS: Histologically confirmed unifocal or multifocal transitional cell
        carcinoma of the bladder no greater than 5 cm, with evidence of muscle invasion documented
        by transurethral resection of the bladder (TURB), with no residual visible or palpable
        tumor mass at the end of TURB Stage II or III (T2-T3, N0, M0) No squamous cell or
        adenocarcinoma No evidence of pelvic lymph node involvement by CT scan or MRI No evidence
        of hydronephrosis No evidence of distant metastases No disease in the prostatic urethra

        PATIENT CHARACTERISTICS: Age: Under 76 Performance status: WHO 0-2 Life expectancy: Not
        specified Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 100,000/mm3
        Hemoglobin at least 11 g/dL Hepatic: Not specified Renal: See Disease Characteristics
        Creatinine clearance greater than 50 mL/min Cardiovascular: No progressive ischemic
        cardiopathy Other: No reduced bladder capacity No prior or concurrent malignancy except
        basal cell carcinoma or carcinoma in situ of the cervix treated by hysterectomy

        PRIOR CONCURRENT THERAPY: Biologic therapy: Prior immunotherapy for superficial disease
        allowed No concurrent growth factors Chemotherapy: No prior systemic chemotherapy Prior
        intravesical chemotherapy or intravesical BCG allowed Endocrine therapy: Not specified
        Radiotherapy: No prior pelvic radiotherapy Surgery: No prior surgery for bladder cancer
        except transurethral resection of the bladder
Clinical trial NCT01818921 (phase 2, status: completed)
Conditions: obesity, over-weight, prader-willi syndrome
ICD codes: E66.8, E66.9, E66.1, O99.214, O99.215, O99.210, O99.211, Q87.11
Drugs: zgn-440 sterile diluent, 1.2 mg zgn-440 for injectable suspension, 1.8 mg zgn-440 for injectable suspension
SMILES: CO[C@@H]1[C@@H](CC[C@]2(CO2)[C@H]1[C@@]1(C)O[C@@H]1CC=C(C)C)OC(=O)\C=C\C1=CC=C(OCCN(C)C)C=C1, CO[C@@H]1[C@@H](CC[C@]2(CO2)[C@H]1[C@@]1(C)O[C@@H]1CC=C(C)C)OC(=O)\C=C\C1=CC=C(OCCN(C)C)C=C1, CO[C@@H]1[C@@H](CC[C@]2(CO2)[C@H]1[C@@]1(C)O[C@@H]1CC=C(C)C)OC(=O)\C=C\C1=CC=C(OCCN(C)C)C=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of Prader-Willi Syndrome due to chromosome 15 micro-deletion,
             maternal uniparental disomy, or imprinting defect

          -  BMI ≥25 kg/m2

          -  Type 2 diabetes mellitus is allowed

          -  Subject must agree to stay at the group home or under supervision of the group home or
             site staff (i.e. no home visits) for the duration of the study

          -  Stable body weight during the past 3 months, except for during home visits

        Exclusion Criteria:

          -  Use of weight loss agents in the past 3 months

          -  Type 1 diabetes mellitus

          -  Current or anticipated chronic use of narcotics or opiates
Clinical trial NCT00462332 (phase 2, status: completed)
Conditions: leukemia
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01
Drugs: fludarabine, campath, campath, fludarabine, campath, campath
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, ClCCN(CCCl)P1(=O)NCCCO1
Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of chronic lymphocytic leukemia (CLL)

               -  Advanced or progressive disease with ≥ 2 active clinical signs

        PATIENT CHARACTERISTICS:

          -  Fertile patients must use adequate contraception

          -  No positive Coomb's test with signs of hemolysis

          -  No active infection

          -  No uncontrolled severe disease

          -  No known hypersensitivity or anaphylactic reactions to murine antibodies or proteins

          -  No other malignancies within the past 2 years except for adequately treated
             malignancies

          -  No significant traumatic injury within the past 4 weeks

          -  No coexisting medical or psychological condition that would limit study compliance

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior treatment for CLL

          -  No major surgery within the past 4 weeks

          -  No prior chemotherapy
Clinical trial NCT00371345 (phase 2, status: completed)
Conditions: breast cancer, metastasis
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: dasatinib, dasatinib 100 mg
SMILES: CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1, CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1
Eligibility criteria:

        Inclusion Criteria:

          -  females, 18 or older

          -  recurrent, locally advanced, or metastatic breast cancer with expression of ER/PR
             receptor and/or overexpression of Her2/neu

          -  paraffin-embedded tissue block must be available

          -  measurable disease

          -  prior chemotherapy with an anthracycline and/or a taxane (neoadjuvant, adjuvant, or
             metastatic setting)

          -  0, 1 or 2 chemotherapies in the metastatic setting

          -  adequate organ function

        Exclusion Criteria:

          -  Metastatic disease confined to bone only

          -  Symptomatic central nervous system (CNS) metastasis

          -  Concurrent medical condition which may increase the risk of toxicity

          -  Unable to take oral medication
Clinical trial NCT00205634 (phase 2, status: completed)
Conditions: cystic fibrosis
ICD codes: E84.9, Z14.1, E84.0, E84.11, E84.8, E84.19, P09.4
Drugs: biaxin ( clarithromycin)
SMILES: [H][C@@]1(C[C@@](C)(OC)[C@@H](O)[C@H](C)O1)O[C@H]1[C@H](C)[C@@H](O[C@]2([H])O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@@](C)(C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@](C)(O)[C@@H](CC)OC(=O)[C@@H]1C)OC
Eligibility criteria:

        Inclusion Criteria:

          -  diagnosis of CF

          -  ability to reliably perform spirometry

          -  FEV1 of 30% predicted at the time of screening

        Exclusion Criteria:

          -  Mycobacterium in a sputum culture ever recorded

          -  a respiratory exacerbation requiring IV antibiotics in the 60 days prior

          -  used a investigational drug or device in the 60 days prior

          -  significant (>30ml) of hemoptysis in the past year

          -  require oxygen or have significant liver or renal disease