• Diagnosis of Partial Lipodystrophy.

• Previous treatment with metreleptin.

Eligibility last updated 7/7/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 14 years old. Subjects speaking any language will be offered participation.
• Subjects capable of providing informed consent to the study. For those subjects younger than 18 years old who agree to participate in the study, informed consent will be obtained from patient’s parents/guardian.
• Subjects capable of performing pulmonary function test (PFT) maneuvers, as per pulmonary function test laboratory protocol.
• Patients will be enrolled through the Mayo Clinic Rochester Transgender and Intersex Specialty Care Clinic (TISCC), once patient has decided to undergo hormonal gender-affirming therapies (pubertal blockers, and masculinizing or feminizing hormone therapies).

• Subjects unable to provide consent, or subjects who do not agree to discuss the study with their parents/guardians.
• The presence of contraindications for pulmonary function testing including (these will be reviewed at the time of recruitment and prior to each spirometry associated with the study):
• Recent surgical procedures (< 3 months) that could be affected by lung function testing, including the following categories: Abdominal surgery, Eye surgery, Thoracic surgery, Ear surgery, Brain surgery, Vascular surgery. The presence of previously known respiratory disorders including pulmonary embolism (< 6 months), pleural effusion, pneumothorax, hemoptysis.
• Recent myocardial infarction (< 1 month), new cardiac arrythmia (< 3 months), recent cardiac pacemaker implantation (< 3 months).
• Heart failure symptoms, significant shortness of breath, tachycardia, or angina
• The presence of chronic pulmonary diseases that maybe associated with changes in pulmonary function overtime such as asthma, chronic obstructive pulmonary disease, or interstitial lung diseases.

Eligibility last updated 7/8/22. Questions regarding updates should be directed to the study team contact.

• Subject is 18 years or older at the time of the procedure.
• Pulmonary nodule biopsy attempted/performed using the Ion Endoluminal System and Cios Spin 3D imaging.
• Pulmonary nodule ≤ 2 cm in largest diameter.
• Subject able to understand and adhere to study requirements and provide informed consent.

• Planned lymph node staging performed before nodule biopsy.
• Nodule is a pure ground glass opacity.
• Plan to biopsy multiple nodules.

Eligibility last updated 11/29/22. Questions regarding updates should be directed to the study team contact.

• ≥ 18 years of age. 

• < 18 years of age.

Eligibility last updated 7/12/22. Questions regarding updates should be directed to the study team contact.

• In the Lung Cancer group, any patient of 18 years or older with lung cancer.
• In the control group, any 18 year or older volunteer with no history of Lung Cancer.

• Anyone with a history of lung disease, such as emphysema. Also, anyone with a history of cancer except Lung Cancer in the experimental group.

Eligibility last updated 7/15/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 7/14/22. Questions regarding updates should be directed to the study team contact.

• ≥ 21 years old.
• Diagnosed cervicogenic headache (CGH) or occipital neuralgia (ON) (in accordance with International Classification of Headache Disorders 3 rd edition [ICHD-3] criteria).
• Average occipital head pain score in the last week ≥4 on a scale of 0-10 (BPISF, question #5) at baseline.
• Average pain interference score in the last week ≥4 on a scale of 0-10 (BPISF, question #9) at baseline.
• Able to understand and willing to take part in study and comply with all study requirements.

Additional inclusion criteria (assessed prior to the PNS lead implant procedure): 

• Moderate-severe baseline pain: Average occipital head pain intensity score of ≥4 (determined by calculating the mean “average pain” scores collected consecutively in a 7-day baseline diary, using Question #5 on the BPI-SF; mean score must be ≥4). Individuals are required to complete all 7 days of the baseline diary consecutively to be eligible to participate in the study because an inability to complete the baseline diary suggests an inability or unwillingness to comply with all study requirements.

• Change of prescribed medications affecting pain within the past 4 weeks as indicated from subject-reported medication history.
• Radiofrequency ablation in the affected area within the last six months.
• Botulinum toxin injection in the affected area within the last three months.
• Steroid injection in the affected area within the last six weeks.
• Other confounding therapies including previous destructive ganglionectomy, rhizotomy section or neurectomy procedure affecting C2/C3/occipital distribution
• Beck Depression Inventory (BDI-II) score of > 20.
• Head pain is attributed to cancerous lesion or a headache condition other than CGH or ON, including (but not limited to) episodic or chronic migraine, tensiontype headache, analgesic medication over-use or withdrawal headache, cluster headache, or vascular and non-vascular intracranial disorders.
• Pain is primarily in the distribution of the lesser occipital nerves.
• ID Migraine screener score of ≥ 2.
• Current daily opioid use ≥ 50 MME (morphine milligram equivalents).
• Diabetes mellitus Type 1 or Type 2.
• Compromised immune system based on medical history (i.e., human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS), immunosuppressive therapies such as chemo treatment, radiation, sepsis, active joint or overlying skin infection of the cervical or occipital regions), or other condition that in the opinion of the investigator places the subject at increased risk.
• Implanted electrical stimulation device or metallic implant such as spinal cord stimulator, active cardiac implant (e.g., pacemaker or defibrillator), cochlear implant, cerebrospinal fluid (CSF) shunt, aneurysm clip, or deep brain stimulator.
• Severe traumatic brain injury (TBI) or other central nervous system (CNS) conditions including epilepsy that could be aggravated by the PNS treatment or confound the analysis.
• Allergy to skin-contact materials (stickers, bandages, tape etc.).
• Previous cervical or cranial occipital surgery, such as decompression of the occipital nerve(s), or cervical spine surgery such as laminectomy or fusion at or above the C3 level.
• Participation in any drug or device trial in the past 30 days.
• Any other condition that may interfere with the ability to participate in a clinical trial (e.g., anatomy that may interfere with lead placement or bandaging) as determined by the Investigator.
• Potential secondary gain conflicts of interest (e.g., pending claims or receiving disability).
• .Vulnerable populations (e.g., prisoners, individuals that report to investigators).
• Pregnant (either urine dipstick or serum in females of reproductive potential; to be assessed prior to lead placement procedure).

Eligibility last updated 7/14/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years
• Willing to provide samples at baseline.
• Cirrhosis
  •where Cirrhosis is defined as:
  • At least one liver biopsy within 5 years prior to consent showing either: a) Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis; OR
• If no liver biopsy, the following imaging + laboratory criteria define cirrhosis for the purposes of this protocol:
  • Evidence on imaging, of stiffness, or of varices according to the MOP, AND;
  • Either: FIB-4 > 2.67 OR platelets < 150 (within 180 days prior to consent or during Screening).

• Known and documented prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma.
• Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence.
• Known prior solid organ transplant or bone marrow transplant.
• Current participation in active medication treatment trials at the time of consent for LCN POST.
• Prisoners or individuals with more than 180 days incarceration pending due to difficulty with visits.
• Bariatric surgery in the last 180 days prior to consent.
• Known history of fontan procedure-associated liver disease (FALD).
• Known current medical or psychiatric conditions which, in the opinion of the investigator, would make the participant unsuitable for the study or interfere with or prevent follow-up per protocol.
• Current liver-unrelated end-stage organ failures (Dialysis, stage 3-4 congestive heart failure (CHF), current chronic obstructive pulmonary disease (COPD) on home oxygen, current known active malignancy besides non-melanomatous skin cancer or carcinoma in situ).
• Documented history of acute alcohol-associated hepatitis (according to NIAAA criteria as described in the MOP) in the 180 days prior to consent.
• Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis).
• In patients with primary sclerosing cholangitis (PSC): Current active cholangitis with 90 days prior to consent.
• Documented cardiac cirrhosis.
• Known recent (within the last 365 days) or present hepatic decompensation with ascites/hydrothorax, hepatic encephalopathy or variceal bleeding.
• Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples).
• Current model for end-stage liver disease (MELD) cut off ≥ 15*.
• Current Child-Turcotte-Pugh (CTP) B or C*.
• Current known Hepatitis C Virus (HCV) without sustained virologic response (SVR).
• Current known quantifiable Hepatitis B Virus (HBV) viral DNA on therapy with ongoing adherence on suppressive therapy*.
• In patients with autoimmune hepatitis: serum aspartate aminotransferase (AST) > 2X upper limit of normal (ULN) within 60 days prior to consent or during Screening*.
• In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 60 days prior to consent or during Screening*.

*Indicates an exclusion criterion that may depend on laboratory results and other clinical assessments to be ordered during Screening after confirming the participant is otherwise eligible. If the test was performed as standard-of-care in the 60 days prior to consent, it does not need to be re-done for eligibility.  

Eligibility last updated 7/18/22. Questions regarding updates should be directed to the study team contact.

Healthy Adults

• Healthy participants (≥ 18 years of age) will be recruited from the surrounding community.
• These participants will not have a history of cardiovascular, pulmonary, neurologic, orthopedic, or other diseases affecting the neuromuscular system.
• Additional inclusion criteria include: age, sex, and body mass index matched to the Human Hypertension (HTN) group and those who are able to engage in exercise (i.e., without significant orthopedic limitations or musculoskeletal disorders limiting their ability to exercise).

Patients with Hypertension

•  ≥ 18 years of age.
• Patients with HTN will have a clinical diagnosis of essential HTN and receiving standard pharmacologic therapy for > 3 months.
• In addition to their primary care physician, Dr. Borlaug, M.D. will provide oversight for all participants throughout the study duration. Patients will be tested while receiving optimized standard pharmacologic optimized therapy. All patients will be managed by their primary care physician or cardiologist with additional review by Dr. Borlaug (Co-Investigator) prior to enrollment to ensure inclusion and exclusion criteria have been satisfied and participation in exercise testing is safe. Additional inclusion criteria include no history of cardiovascular (except for HTN), pulmonary, renal, and/or muscular related abnormalities and those who are able to engage in exercise (i.e., without significant orthopedic limitations or musculoskeletal disorders limiting their ability to exercise).

Patients with Heart Failure:

• Patients with HF with reduced ejection fraction and HF with preserved ejection fraction. Patients with HF are expected to have a history of ischemic or idiopathic dilated cardiomyopathy (stable > 6 months with a duration of > 1 year) and New York Heart Association class I-III. Although HF medications may influence multiple physiologic systems, we feel it is important, practical, and safe to study these patients under conditions of optimal care. Concurrent withdrawal of ACE-inhibitor, beta-blocker, digoxin, and/or diuretic therapies would likely be associated with moderate decompensation in a high proportion of patients. All patients will be managed by their primary care physician or cardiologist prior to enrollment to ensure inclusion and exclusion criteria have been satisfied and participation in exercise testing is safe.

• ≥ 18 years of age.
• History of dangerous arrhythmias.
• Body mass index > 35 kg/m^2.
• Current smokers and/or smoking history > 15 pack years.
• Pregnant women (testing will be done by research team if requested).
• Uremia, history of allergy to iodides.
• Impaired renal function.
• Creatinine value greater than or equal to 1.3 mg/dL (via clinical record within the past 6 months).
• Diagnosis of liver disease; or (10) individuals who are not able to engage in exercise.
• For individuals agreeing to undergo dual energy x-ray absorptiometry (DEXA) scanning for measurement of body composition as part of their study visit, additional exclusion criteria apply: recently administered gastrointestinal contrast or radionuclides; severe degenerative changes or fracture deformity in measurement areas; or inability to attain correct position and/or remain motionless for the measurement period.

Eligibility last updated 7/26/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 7/19/22. Questions regarding updates should be directed to the study team contact.

• ≥ 18 years of age. 
• Undergoing Radiofrequency Ablation (RFA) for symptomatic thyroid nodule(s).

• < 18 years of age.
• Decline to participate in research. 

Eligibility last updated 7/20/22. Questions regarding updates should be directed to the study team contact.

• Provide written informed consent.
• Male or female ages 18 or older.
• Evidence of cancer of the colon or rectum that is metastatic to the liver.
  • NOTE:  patients may enroll prior to receiving clinical biopsy results. If they are not confirmed to have adenocarcinoma of the colon or rectum that is metastatic to the liver, they will not be evaluable.
• Treating physician planning to treat CRC liver metastasis with a standard of care therapy.
• Previous adjuvant or neoadjuvant therapies allowed.
• Biopsy may be obtained prior to starting the 2nd cycle of a new standard of care therapy.
• Measurable disease as measured by RECIST 1.1 criteria.
• Life expectancy of ≥ 12 weeks.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2. 
• Adequate coagulation function as evidenced by:
  • Absolute neutrophil count ≥ 1.0 x 10^9/L;
  • Platelets ≥ 50 x 10^9/L;
  • Hemoglobin ≥ 8 g/dL (transfusions are permitted to achieve baseline hemoglobin level);
• ALT/AST (alanine aminotransferase (ALT) / aspartate aminotransferase (AST)) < 2.5 x upper limit of normal (ULN); or
• < 5 x ULN in the presence of liver metastases;
• Total bilirubin < 1.5 x ULN (if total bilirubin ≥ 1.5 x ULN then the subject may participate if the direct bilirubin is ≤ 1.5 x ULN);
• Creatinine clearance > 30 mL/min measured or calculated by Cockcroft-Gault equation or the estimated glomerular filtration rate (GFR) > 30 mL/min/1.73 m^2 using the MDRD;
• INR < 1.5.

• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
• Clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of start of therapy, New York Heart Association Class II, III or IV congestive heart failure, and arrhythmia requiring therapy.
• Presence of significant concurrent, uncontrolled medical condition including but not limited to renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral, active infection, non-healing wound, or psychiatric disease that excludes them from receiving chemotherapy.
• Pregnant or actively breastfeeding women (Pregnant or breastfeeding women are not candidates for chemotherapy).

Eligibility last updated 7/20/22. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/20/22. Questions regarding updates should be directed to the study team contact.

Healthy Volunteer

• Male subjects or female subjects between the ages of 18 and 70 years, inclusive, at Screening.
• Body mass index (BMI) ≥ 25 and <40 kg/m2; and a total body weight ≥50 and ≤150 kg at Screening and Day 1 Pre-dose.
• Suspected or confirmed diagnosis of noncirrhotic NAFLD/NASH with no fibrosis to moderate fibrosis (stages F0-F2) by one of the following:
  • Histologically with liver biopsy within 2 years prior to Screening (documentation with pathology report) [Chalasani 2018]; or
  • Radiologically with ≥5% steatosis measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF), or controlled attenuation parameter (CAP™)and 288 dB/m via FibroScan® assessment, or presence of hepatic steatosis on abdominal ultrasound; and an increase in serum alanine aminotransferase (ALT) > 30 U/L within 1 year prior to Screening; or
  • Clinically with a diagnosis of Metabolic Syndrome (MetS) reflecting the presence of at least 3 of 5 factors/criteria (ie, abdominal obesity, elevated triglycerides, reduced HDL-C, elevated blood pressure, and/or elevated fasting glucose [IFG or type 2 diabetes mellitus]) as defined by the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP ATP III) [Grundy 2005]; and seronegative hepatitis B and C; and fatty liver on imaging within 1 year prior to Screening.
• Subjects who are willing and able to comply with all scheduled visits, clinical research unit (CRU) confinement, dosing plan, laboratory tests, and other study procedures and restrictions detailed in this protocol and listed in the informed consent form/document (ICF).
• Evidence of a personally signed and dated ICF, approved by the IRB, indicating that the subject has been informed of all pertinent aspects of the study, understands, and voluntarily agrees to participate in the study, and authorizes the use of protected health information (PHI) in accordance with national and local subject privacy regulations (ie, HIPAA) prior to the initiation of any study-specific procedure.

• History or presence of cirrhosis by any diagnostic measure (clinical, imaging, histopathology, or laboratory).
• History or presence of other concomitant liver disease as assessed by the Investigator or determined by laboratory findings including, but not limited to the entities listed below:
  • Hepatitis B virus (HBV), defined by presence of hepatitis B surface antigen (HepBsAg) and hepatitis B core antibody (HepBcAb);
  • Hepatitis C virus (HCV), defined by presence of hepatitis C antibody (HCVAb), and HCV RNA (when reflexed based on a positive result for HCVAb);
  • Human Immunodeficiency Virus (HIV) infection, defined as presence of HIV antibody;
  • Alcoholic liver disease;
  • Autoimmune liver disease as defined by compatible liver histology;
  • Primary biliary cholangitis (PBC) as defined by the presence of at least 2 of the following:
    • Biochemical evidence of cholestasis based mainly on alkaline phosphatase (ALP) elevation;
    • Presence of anti-mitochondrial antibody (AMA);
    • Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts.
  • Primary sclerosing cholangitis (PSC);
  • Hemochromatosis or iron overload, defined by presence of 3+ or 4+ stainable iron on liver biopsy;
  • Wilson’s disease, defined by ceruloplasminand < LLN and compatible liver histology;
  • Alpha-1 antitrypsin (A1AT) deficiency, defined by A1AT level < LLN and compatible liver histology;
  • Bile duct obstruction;
  • Suspected or known primary liver cancer (eg, hepatocellular carcinoma) or metastatic cancer involving liver;
  • Prior known drug-induced liver injury (DILI), defined on the basis of typical exposure and history;
  • Any other type of liver disease other than NASH.
• Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities:
  • Serum albumin 1.3 < 3/2 gdL;
  • INR > 1.3;
  • Direct bilirubin >1.3 mg/dL;
  • History of esophageal varices, ascites, or hepatic encephalopathy.
• History of pancreatic disease including acute/chronic pancreatitis, pancreas divisum, annular pancreas or prior history of pancreatic surgery.
• Evidence of portal hypertension (eg, low platelet counts, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly).
• Weight loss ≥ 5% within 6 months prior to Screening.
• Prior or planned (during the study period) bariatric surgery or any other gastrointestinal surgery relative to weight loss (eg, Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, sleeve gastrectomy, duodenal switch with biliopancreatic diversion).
• Uncontrolled diabetes, defined as HbA1c of ≥ 9.5% within 60 days prior to Screening.
• History or presence of a compromised immune system including inherited deficiencies of the immune system; immunosuppressing/immunomodulating drugs including, but not limited to, steroids (corticosteroid, anabolic), antimetabolites, immunoglobulins or cytokine-based therapies within 6 months prior to Day 1 or is expected to receive these agents during study participation; or other conditions causing leukopenia or neutropenia.
• History of malignancy and/or lymphoproliferative disease (suspected disease and/or systemic treatment) or systemic treatment for malignancy (eg, chemotherapy, biologics, vaccines, hormonal treatment, or non-localized radiation therapy) within 5 years prior to Screening with the following exceptions: non-metastatic squamous or basal cell carcinoma of the skin and in-situ cancers (bladder, colon, cervix, or breast) curatively treated at least 1 year prior to Screening visit with no current evidence of disease.
• History of severe allergy or hypersensitivity (eg, anaphylaxis, hepatotoxicity) to a drug or diagnostic imaging agent which required urgent medical treatment (including any component of the IP or other products in the same class), or a history of other allergy that, in the opinion of the Investigator or Sponsor, contraindicates their participation.
• Evidence of poor peripheral venous access that limits phlebotomy, or the inability to have blood drawn.
• Inability to tolerate subcutaneous injection medication(s).
• Clinically significant or unstable cardiovascular disease including, but not limited to the following: unstable angina, myocardial infarction, stroke, or transient ischemic attack within the past 6 months of Screening; ventricular arrhythmia (eg, ventricular tachycardia, ventricular fibrillation or torsades de points) or a family history of long QT syndrome or unexplained death in an otherwise healthy individual between ages of 1 and 30 years; peripheral vascular disease; or other heart conditions (eg, dilated cardiomyopathy with left ventricular ejection fraction < 40% implanted defibrillator or pacemaker, congestive heart failure with New York Association [NYHA] class III or IV, pericarditis, significant pericardial effusion, myocarditis); or other condition that requires the routine use of supplemental oxygen.
• Syncope, palpitations, or unexplained dizziness.
• Previous episodes of seizures or convulsion (lifetime), including absence seizure and febrile convulsion.
• Chronic respiratory disease including chronic obstructive pulmonary disease (COPD), emphysema, cystic fibrosis, pulmonary hypertension, or other chronic condition that requires the routine use of supplemental oxygen.
• Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test at Screening.
• Subjects with a significant Coronavirus disease 2019 (COVID-19) illness within 6 months of enrollment:
  • Diagnosis of COVID-19 pneumonia based on radiological assessment;
  • Diagnosis of COVID-19 with significant findings from pulmonary imaging tests;
  • Diagnosis of COVID-19 requiring hospitalization and/or oxygen supplementation.
• Active infection or use of antibiotic(s) within 28 days prior to Day 1.
• History of any significant bleeding event defined as CTCAE ≥Grade 3 (includes receipt of hematopoietic growth factors, blood, or blood product transfusion) within 3 months prior to Screening; or personal/family history of bleeding disorder (eg, hemophilia, factor deficiencies, disseminated intravascular coagulation).
• Major trauma or surgery including but not limited to operations involving a major organ (eg, the cranium, chest, abdomen, or pelvic cavity) OR requiring a lengthy recovery period (eg, arthroplasty) within 4 weeks prior to Screening; or planned surgery during the study. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 2 weeks before Day 1.
• Subjects currently experiencing any clinically significant or unstable medical condition that might limit their ability to complete the study, to comply with the requirements of the protocol, or interfere with the interpretation of study results which, in the judgment of the Investigator, would make the subject inappropriate for entry into this study, including: dermatologic disease, hematological disease, pulmonary disease, hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease and psychiatric disease.
• History of substance abuse (eg, alcohol, drugs), within 1 year prior to Screening.
• Current or history of significant alcohol consumption exceeding 14 drinks/week for female subjects or 21 drinks/week for male subjects (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within the previous 6 months from Screening; or inability to reliably quantify alcohol intake based on Investigator’s judgment.
• Positive alcohol breath test result or positive urine drug screen at Screening or Day 1 Predose;
  • [NOTE: Subjects who have been medically prescribed benzodiazepines and report the use of these drugs to the Investigator at Screening may be allowed to participate.]
• Subjects with any of the following abnormalities in clinical laboratory tests at Screening or Day 1 Pre-dose, as assessed by the study-specific clinical laboratory and confirmed by a single repeat test, if deemed necessary:
  • Serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) > 5 × Upper Limit of Normal (ULN);
  • Direct Bilirubin > ULN;
    • [NOTE: Subjects with a history of Gilbert syndrome would be eligible for this study provided direct bilirubin level is ≤ULN plus ALT met criteria plus alkaline phosphatase, hemoglobin, and reticulocyte count are ≤ULN.];
  • Platelet count < 150,000/mm^3;
  • International Normalized Ratio (INR) > ULN;
  • Fasting triglycerides ≥ 400 mg/dl 28.
• The presence of abnormal laboratory values (other than those explicitly mentioned in Section 5.2) at Screening or Day 1 Pre-dose considered to be clinically significant by the Investigator (ie, suggestive of underlying disease or increased risk of IP administration). A single repeat measurement/test may be performed to confirm clinical laboratory test(s) abnormalities.
• Supine systolic blood pressure (BP) ≥140 mm Hg and/or diastolic BP ≥ 90 mm Hg after ≥5 minutes of rest at Screening or Day 1 Pre-dose. If needed, the BP may be repeated 2 more times and the average of the 3 BP values will be used to determine the subject’s eligibility.
• Supine systolic BP ≤ 85 mm Hg and/or diastolic BP ≤ 55 mm Hg after ≥ 5 minutes of rest at Screening or Day 1 Pre-dose. If needed, the BP may be repeated 2 more times and the average of the 3 BP values will be used to determine the subject’s eligibility.
• Supine heart rate (HR)/pulse outside the range of 50-100 bpm (not on ECGs) after ≥ 5 minutes of rest at Screening or Day 1 Pre-dose. If needed, the HR may be repeated 2 more times and the average of the 3 HR values will be used to determine the subject’s eligibility.
• Supine 12-lead ECG demonstrating Fridericia method-corrected QT (QTcF) interval >450 msec or a QRS interval >120 msec after ≥10 minutes of rest at Screening or Day 1 Pre-dose. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant’s eligibility.
• Subjects with an estimated glomerular filtration rate (eGFRcr) < 90 mL/min/1.73m2 as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI, 2021) equation, based on serum creatinine and age at Screening or Day 1 Pre-dose.
• Blood donation of approximately 1 pint (500 mL) or more within 56 days prior to Screening, or donation of blood products (eg, plasma, platelets) within 2 weeks prior to Screening; or
  subject is unwilling to forego blood product donation beginning at Screening and for the duration of the study.
• Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential with a positive serum pregnancy result at Screening or positive urine pregnancy result on Day 1 Pre-dose; female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol from the date of signing of informed consent until at least 30 days after the final dose of IP (Section 5.4); female subjects of childbearing potential who are unwilling to refrain from ova donation from start of IP dosing (CRU admission) until at least 30 days after final dose of IP.
• Male subjects who are unwilling or unable to an acceptable method of contraception from the date of Day 1 Pre-dose (baseline) until at least 30 days after the final dose of IP (Section 5.4); male subjects who are unwilling to refrain from sperm donation from the start of IP dosing (CRU admission) until at least 30 days after the final dose of IP.
• Unwilling or unable to comply with the protocol restrictions and lifestyle/activity requirements (Section 5.3) of this protocol.
• Vaccinated or exposed to a live or attenuated vaccine within 2 weeks prior to Screening or anticipated vaccination during the study.
• Participation in another clinical trial (investigational drug, vaccine, medical device, or procedure) within 30 days or 5 half-lives (drug) prior to Day 1 (whichever is longer); planned participation of clinical trial during the study; participation in ≥2 clinical trials within 6 months prior to Screening. Non-interventional follow-up/surveillance for an earlier study will be allowed.
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
• Subjects with known prior participation in a trial involving OA-235i (ie, received at least 1 dose of IP).
• Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Oasis employees, including their family members, directly involved in the conduct of the study.
• Use of the following medications (prescription or over-the-counter [OTC] drugs) or therapies (herbal, homeopathic preparations) within 4 weeks or 5 half-lives (whichever is longer) prior to Day 1 or intention/anticipated use during the study:
  • [NOTE: Subjects who received any of the following medications are eligible if the noted minimum washout criteria are observed and they are not used as concomitant treatments during the study.]
    • Systemic non-steroidal anti-inflammatory drugs (NSAIDs) (chronic use [ie, > 4 days/week]);
    • Coumadin-type anticoagulants (warfarin);
    • Antiarrhythmics, except for beta blockers or calcium channel blockers if used for the management of conditions other than arrhythmias;
    • Anticonvulsants (eg, topiramate);
    • Ezetimibe (Zetia);
    • Fibric acid derivatives (fibrates);
    • Omega-3 fatty acids (fish oil) ;
    • Systemic corticosteroids (inhaled and topical corticosteroids are allowed) (bronchodilator inhalers are allowed);
    • Prescription opioids (eg, hydrocodone [Vicodin®], oxycodone [OxyContin®, Percocet®], oxymorphone [Opana®], morphine [Kadian®, Avinza®], codeine, fentanyl);
    • Medical-grade marijuana, regardless of medical indication;
    • Herbal, nutraceutical, or natural supplement (daily multi-vitamin is allowed)
    • Medications which have been associated with causing/worsening NAFLD/NASH: amiodarone, methotrexate, tetracyclines, tamoxifen, griseofulvin, estrogens at doses greater than those used for hormone replacement (> 2 mg/day), anabolic steroids, valproic acid, nucleoside analogues (except acyclovir), bile acid sequestrants (eg, cholestyramine, colestipol), total parenteral nutrition, and other known hepatotoxins;
    • Medications that may cause pancreatitis: glucagon-like peptide-1 receptor agonists (GLP1 Ras): dulaglutide (Trulicity), exenatide (Byetta), exenatide extended-release (Bydureon), liraglutide (Victoza), lixisenatide (Adlyxin), oral semaglutide (Rybelsus), semaglutide (Ozempic);
    • Certain medications to treat NAFLD/NASH and coexisting conditions such as diabetes, hyperlipidemia, and hypertension will be allowed; however, subjects must be on a stable dose for the noted period of time prior to Day 1:
      • Medications to treat NAFLD/NASH (eg, vitamin E, betaine, s-adenosyl-l-methionine, ursodeoxycholic acid, probiotics, and thiazolidinediones [TZDs]) – subjects must be on a stable dose for at least 6 months prior to Day 1 and still carry a current diagnosis;
      • Anti-diabetic medications (eg, biguanides [metformin], insulin) – subjects must be on a stable dose for at least 12 weeks prior to Day 1; sliding scale of insulin is allowed if the subject's HbA1c remains <9.5%. Subject’s taking other sc drugs (eg, insulin) must be instructed to avoid injections within 20 cm of any given IP injection site for the duration of the trial;
      • HMG-CoA reductase inhibitors (ie, statins) – subjects without a history of cardiovascular disease (CVD) (ie, symptomatic coronary artery disease or ischemic stroke) who are taking a statin for primary prevention are eligible for the trial, but must be discontinued from concomitant statin therapy beginning at least 1 week prior to Day 1 (wash-out) and continuing through 1 week following the final study drug dose; these subjects must also have been on a stable statin dose for at least 8 weeks prior to the wash-out. Note, subjects who have developed CVD and are taking a statin for secondary prevention are ineligible for the trial;
      • Other lipid modifying medications (eg, nicotinic acid/niacin) – subjects must be on a stable dose for at least 8 weeks prior to Day 1.
      • Antihypertensive agents – subjects must be on a stable dose for at least 8 weeks prior to Day 1.
  • Any Investigator questions or concerns regarding the use of treatments, including medications (ie, prescription and OTC drugs) and non-medication therapies (eg, vitamins, nutritional supplements, immunizations) should be discussed with the Oasis Medical Officer/Monitor prior to the subject’s study enrollment and IP administration.

  • Eligibility last updated 7/25/22. Questions regarding updates should be directed to the study team contact.

• Patients self-report as being > 1 year postmenopausal.
• Patients are able to walk without a walking aid.
• Patients own and know how to operate a smart phone or tablet.
• Patients are willing and able to complete the activity monitoring.
• Patients are self-reportedly underactive.

• Patients are < 1 year postmenopausal.
• Patients require a walking aid for daily mobility.
• Patients do not own a smartphone or table, or are unwilling to use such a device for the purposes of the study.
• Patients' primary form of exercise is swimming (the activity monitors are not waterproof).
• Patients are unable or unwilling to complete activity monitoring.
• Patients are unable to provide informed consent independently.

Eligibility last updated 7/22/22. Questions regarding updates should be directed to the study team contact.

• Patients seen in Oncology or surgery with a diagnosis of a solid tumor malignancy,.

• < 18 years of age. 

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.

• 18 to 90 years of age
• Diagnosed with Eosinophilic esophagitis ≥ 15 eosinophils per HPF
• Going through or completed the six-food elimination diet, with milk only or milk plus one additional food identified as a trigger

• Patients with conditions known to be associated with esophageal eosinophilia, including Crohn’s disease, Churg-Strauss, achalasia, and hypereosinophilic syndrome
• Topical swallowed steroids within 8 weeks of study enrollment
• Inability to read due to: Blindness, cognitive dysfunction, or English language illiteracy

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.

1. Patients with cirrhosis admitted to hospital for the treatment of a complication of liver disease (ascites, gastrointestinal bleeding, hepatic encephalopathy, bacterial infections, jaundice, etc.).

1. Age < 18 years old.

2. Pregnancy.

3. Hepatocellular carcinoma outside Milan criteria (i.e., a single lesion < 5 cm or multiple lesions [maximum of three], the largest of which measures ≤ 3 cm).

4. Extrahepatic malignancy other than non-melanoma skin cancer within last 5 years.

5. Previously known severe extrahepatic diseases (e.g., chronic renal failure requiring hemodialysis, severe congestive heart disease [NYHA class ≥ 3]; severe chronic obstructive pulmonary disease [GOLD class ≥ 3], psychiatric disorders).

6. Previous solid organ transplantation.

7. HIV infection with CD4 ≤ 250/µL.

8. Patients who cannot provide prior informed consent and no legal surrogate decision maker.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 8/1/22. Questions regarding updates should be directed to the study team contact.

• Transgender and gender diverse (TGD) identifying patients.
• Patients ≥ 18 years old.
• Patients who are seeking or have sought gender-affirming care or fertility preservation.
• Willingness to provide informed consent and allow recording of the interview.
• Speaks and understand English language proficiently.

• Patients who are not transgender or gender diverse or have not received gender-affirming care or counseling.
• Participants under 18 years old.

Eligibility last updated 8/3/22. Questions regarding updates should be directed to the study team contact.

Study participants taking  the role as circulating clinical personnel and scrub personnel must have the following:

• A high school diploma, or equivalent, minimum level of education.
• Professional working proficiency, or higher, in English.
• Experience working in the OR and trained in aseptic technique.
• The role of circulating clinical personnel can be undertaken by the following people: doctor, surgeon, surgical trainee, surgical technician, or other adequately trained personnel.
• The role of scrub personnel can be undertaken by the following people: surgical technician, surgeon, surgical trainee, or other adequately trained personnel.

Study participants taking the role of the surgeon must have the following:

• A good working knowledge of ENT anatomy.
• Have worked with cadaveric tissue or live patients in the past.

• < 18 years of age. 
• The role of surgeon can be undertaken by the following people: surgeon or surgical trainee. Individuals may take on multiple roles throughout the study, but not during the same test session.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 8/4/22. Questions regarding updates should be directed to the study team contact.

• Infants born via vaginal delivery at Mayo Clinic Rochester.
• Infants must be followed by the Division of Pediatrics with follow-up routine prenatal care to be completed at Baldwin Building.
• 25 infants will be at high risk for development of atopic dermatitis. High risk for development of atopic dermatitis is determined by an immediate family history (parent or sibling) of one of the following: atopic dermatitis, asthma, allergic rhinitis, or food allergy.
• 25 infants will be at low risk for development of atopic dermatitis. Low risk for development of atopic dermatitis is determined by an immediate family history (parent or sibling) without the presence of any of the following medical conditions: atopic dermatitis, asthma, allergic rhinitis, or food allergy.
• No underlying medical conditions at birth including underlying congenital medical conditions.

• Infants born via cesarean section delivery.
• Infants followed by the Division of Family Medicine with routine follow-up prenatal care to be completed outside of Baldwin Building.
• Presence of underlying medical conditions at birth including congenital medical conditions.

Eligibility last updated 9/2/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria:

• Females ≥ 25 and ≤ 60 years of age.
• Appointment at Mayo Clinic Rochester in Gynecology Colposcopy Clinic or ICS (integrated community specialty) Colposcopy Clinic (will always include a speculum exam).
• Appointment at Mayo Clinic Rochester in Gynecology Clinic for indication that will already include a speculum exam (e.g., cervical cancer screening or IUD insertion). 

• Excluded if pregnant.
• Excluded if no cervix (history of total hysterectomy).
• Excluded if moderate to heavy vaginal bleeding on the day of the visit.
• Excluded if reason for visit in Gynecology Clinic is abnormal vaginal discharge.

Eligibility last updated 8/11/22. Questions regarding updates should be directed to the study team contact

• Adult 21 years and older.
• English speaking.
• Able to provide consent.
• Clinically diagnosed stable heart failure with NYHA Class I-III symptoms.

• Patients who are unable to engage in a regularly structured exercise training program.
• History of dangerous arrhythmias.
• BMI > 40 kg/m^2
• Current smokers or smoking history of > 20 pack years
• Pregnant women, implanted pacemaker and/or ICD, cochlear implants, drug infusion pump, or any other implanted metal objects.

Eligibility last updated 8/8/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Childre:

• Ages 3-7.
• Outpatients.
• Any gender, race, or ethnicity.
• Able to provide developmentally appropriate informed assent, and legal guardians able to provide informed consent.
• EBP Severity rated above the clinically significant range (≥120; T-score ≥ 60) (Eyberg Child Behavior Inventory- ECBI; Eyberg & Pincus, 1999).
• Families approached for participation will be asked to commit to complete the treatment:
• At least one primary caregiver and the identified child will have to be able to speak and understand English;
• Must have the ability, technology, and internet access for remote therapy/research visits.   

Inclusion Criteria
•Adults:

• Agree to wear Garmin watch.
• Ages 18-99.
• Any gender, race, ethnicity.
• Able to provide informed consent.
• Able to speak and understand English.
• Has the ability, technology, and internet access for remote therapy/research visits.

Exclusion Criteria
•Children: 

• Formal diagnosis of Severe Intellectual disability, Autistic Spectrum Disorder Level 3, or a psychotic disorder for the child.
• Parents not consenting to the study.
• Parents or child is not able to adhere to the study protocol.
• A Child who is reasonable expected to be unable to tolerate wearing the Garmin device for at least 70% of the time during the day and night 70% of the days during the treatment (12 weeks). This is based on the principal investigator’s discretion.
• Unable to speak and understand English.
• Refusal or withdrawal of consent, inability, or unwillingness to adhere to study procedures.
• Children in foster care.
• Does not have the ability, technology, and/or internet access for remote therapy/research visits.
• Need for more intensive behavioral treatments such as ER visit for behavioral dyscontrol or hospitalization will not be exclusionary or exit criteria.

Exclusion Criteria
•Adults:

• Unable to speak and understand English. 
• Refusal or withdrawal of consent, inability, or unwillingness to adhere to study procedures.

Eligibility last updated  10/19/22. Questions regarding updates should be directed to the study team contact.

• Wrestlers on roster from Rochester Community and Technical College.
• ≥ 18 years of age. 

• Any athlete with a known cardiac condition will be excluded.

Eligibility last updated 8/23/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 and < 70 years.
• Any gender.
• Patients with physician-diagnosed AERD (including a physician diagnosis of bilateral nasal polyposis, and at least one NSAID-induced reaction that caused respiratory symptoms).
• Patients with nasal polyps and no AERD (with and without asthma).
• Patients who require endoscopic sinus surgery (ESS) for treatment of chronic rhinosinusitis and sinonasal polyposis as part of their standard of care treatment.

• Patients under the age of 18 years and above 70 years.
• Patients who are or intend to get pregnant during the course of the study or those who are breastfeeding.
• Patients with mental or legal incapacitation.
• Patients with acute of chronic kidney or liver disease either self-reported or physician-diagnosed.
• Patients with anemia requiring work-up up (hemoglobin < 10 mg/dL).
• Patients with an active peptic ulcer disease.
• Patients with bleeding-disorder or G6PD deficiency.
• Patients with a planned surgical procedure during the 1-year study period.

Eligibility last updated 8/16/22. Questions regarding updates should be directed to the study team contact.

• Primary care clinicians in Rochester/Kasson who complete the pre/posttests, dermoscopy education and conducts skin lesion visits in their practice.  

• Patient refusal for dermoscopy skin lesion photo (skin lesion would then be excluded), dermoscopy image not captured by clinician at visit.

Eligibility last updated 8/18/22. Questions regarding updates should be directed to the study team contact.

• Any autosomal dominant polycystic kidney disease (ADPKD) patient (ages 5-18 years) with confirmed ADPKD (via a combination of imaging, family history, and/or genetic testing), identified from existing and newly identified families for the proposed study.
• Matched controls will be identified as unaffected siblings, unaffected family members of ADPKD subjects, or children recruited from the outpatient primary care clinics.

• ADPKD patients with liver and or kidney transplant.

Eligibility last updated 10/6/22. Questions regarding updates should be directed to the study team contact.